Sample records for liver histology revealed

  1. Long-term native liver fibrosis in biliary atresia: development of a novel scoring system using histology and standard liver tests.

    PubMed

    Tomita, Hirofumi; Masugi, Yohei; Hoshino, Ken; Fuchimoto, Yasushi; Fujino, Akihiro; Shimojima, Naoki; Ebinuma, Hirotoshi; Saito, Hidetsugu; Sakamoto, Michiie; Kuroda, Tatsuo

    2014-06-01

    Although liver fibrosis is an important predictor of outcomes for biliary atresia (BA), postsurgical native liver histology has not been well reported. Here, we retrospectively evaluated postsurgical native liver histology, and developed and assessed a novel scoring system - the BA liver fibrosis (BALF) score for non-invasively predicting liver fibrosis grades. We identified 259 native liver specimens from 91 BA patients. Of these, 180 specimens, obtained from 62 patients aged ≥1 year at examination, were used to develop the BALF scoring system. The BALF score equation was determined according to the prediction of histological fibrosis grades by multivariate ordered logistic regression analysis. The diagnostic powers of the BALF score and several non-invasive markers were assessed by area under the receiver operating characteristic curve (AUROC) analyses. Natural logarithms of the serum total bilirubin, γ-glutamyltransferase, and albumin levels, and age were selected as significantly independent variables for the BALF score equation. The BALF score had a good diagnostic power (AUROCs=0.86-0.94, p<0.001) and good diagnostic accuracy (79.4-93.3%) for each fibrosis grade. The BALF score revealed a strong correlation with fibrosis grade (r=0.77, p<0.001), and was the preferable non-invasive marker for diagnosing fibrosis grades ⩾F2. In a serial liver histology subgroup analysis, 7/15 patients exhibited liver fibrosis improvement with BALF scores being equivalent to histological fibrosis grades of F0-1. In postsurgical BA patients aged ⩾1year, the BALF score is a potential non-invasive marker of native liver fibrosis. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  2. Shear wave elastography results correlate with liver fibrosis histology and liver function reserve.

    PubMed

    Feng, Yan-Hong; Hu, Xiang-Dong; Zhai, Lin; Liu, Ji-Bin; Qiu, Lan-Yan; Zu, Yuan; Liang, Si; Gui, Yu; Qian, Lin-Xue

    2016-05-07

    To evaluate the correlation of shear wave elastography (SWE) results with liver fibrosis histology and quantitative function reserve. Weekly subcutaneous injection of 60% carbon tetrachloride (1.5 mL/kg) was given to 12 canines for 24 wk to induce experimental liver fibrosis, with olive oil given to 2 control canines. At 24 wk, liver condition was evaluated using clinical biochemistry assays, SWE imaging, lidocaine metabolite monoethylglycine-xylidide (MEGX) test, and histologic fibrosis grading. Clinical biochemistry assays were performed at the institutional central laboratory for routine liver function evaluation. Liver stiffness was measured in triplicate from three different intercostal spaces and expressed as mean liver stiffness modulus (LSM). Plasma concentrations of lidocaine and its metabolite MEGX were determined using high-performance liquid chromatography repeated in duplicate. Liver biopsy samples were fixed in 10% formaldehyde, and liver fibrosis was graded using the modified histological activity index Knodell score (F0-F4). Correlations among histologic grading, LSM, and MEGX measures were analyzed with the Pearson linear correlation coefficient. At 24 wk liver fibrosis histologic grading was as follows: F0, n = 2 (control); F1, n = 0; F2, n = 3; F3, n = 7; and F4, n = 2. SWE LSM was positively correlated with histologic grading (r = 0.835, P < 0.001). Specifically, the F4 group had a significantly higher elastic modulus than the F3, F2, and F0 groups (P = 0.002, P = 0.003, and P = 0.006, respectively), and the F3 group also had a significantly higher modulus than the control F0 group (P = 0.039). LSM was negatively associated with plasma MEGX concentrations at 30 min (r = -0.642; P = 0.013) and 60 min (r = -0.651; P = 0.012), time to ½ of the maximum concentration (r = -0.538; P = 0.047), and the area under the curve (r = -0.636; P = 0.014). Multiple comparisons showed identical differences in these three measures: significantly lower with F4 (P

  3. Diphenyl ditelluride intoxication triggers histological changes in liver, kidney, and lung of mice.

    PubMed

    da Luz, Sônia Cristina Almeida; Daubermann, Melissa Falster; Thomé, Gustavo Roberto; Dos Santos, Matheus Mülling; Ramos, Angelica; Torres Salazar, Gerson; da Rocha, João Batista Teixeira; Barbosa, Nilda Vargas

    2015-01-01

    Tellurium compounds may be cytotoxic to different cells types. Thus, this work evaluated the effect of diphenyl ditelluride ((PhTe)2), an organotellurium commonly used in organic synthesis, on the morphology of liver, kidney, and lung. Adult mice were acutely (a subcutaneous single dose: 250 μmol/kg) or subchronically (one daily subcutaneous dose: 10 or 50 μmol/kg for 7 and 14 days) exposed to (PhTe)2. Afterwards, the histological analyses of liver, kidney, and lungs were performed. Liver histology revealed that the hepatocytes of mice subchronically exposed to (PhTe)2 presented cytoplasmic vacuolization, hydropic degeneration, and hyperchromatic nuclei. Subchronic exposure to 50 μmol/kg (PhTe)2 also caused hepatic necrosis. Microvesicular and macrovesicular steatosis were identified in liver of mice acutely exposed to (PhTe)2. Acute and subchronic intoxication with (PhTe)2 induced changes on epithelial cells of renal tubules, namely, loss of brush border and cytoplasmatic vacuolization. Atrophy and hypertrophy, cast proteinaceous formation, and acute tubular necrosis were also identified in renal tissue. Mice subchronically exposed to 50 μmol/kg (PhTe)2 developed intra-alveolar edema and alveolar wall congestion in some areas of lungs. Acute exposure to (PhTe)2 did not cause histological changes in lungs. Our data show that (PhTe)2 may be considered a histotoxic agent for liver, kidney, and lung.

  4. Correlation between the mechanical and histological properties of liver tissue.

    PubMed

    Yarpuzlu, Berkay; Ayyildiz, Mehmet; Tok, Olgu Enis; Aktas, Ranan Gulhan; Basdogan, Cagatay

    2014-01-01

    In order to gain further insight into the mechanisms of tissue damage during the progression of liver diseases as well as the liver preservation for transplantation, an improved understanding of the relation between the mechanical and histological properties of liver is necessary. We suggest that this relation can only be established truly if the changes in the states of those properties are investigated dynamically as a function of post mortem time. In this regard, we first perform mechanical characterization experiments on three bovine livers to investigate the changes in gross mechanical properties (stiffness, viscosity, and fracture toughness) for the preservation periods of 5, 11, 17, 29, 41 and 53h after harvesting. Then, the histological examination is performed on the samples taken from the same livers to investigate the changes in apoptotic cell count, collagen accumulation, sinusoidal dilatation, and glycogen deposition as a function of the same preservation periods. Finally, the correlation between the mechanical and histological properties is investigated via the Spearman's Rank-Order Correlation method. The results of our study show that stiffness, viscosity, and fracture toughness of bovine liver increase as the preservation period is increased. These macroscopic changes are very strongly correlated with the increase in collagen accumulation and decrease in deposited glycogen level at the microscopic level. Also, we observe that the largest changes in mechanical and histological properties occur after the first 11-17h of preservation. © 2013 Elsevier Ltd. All rights reserved.

  5. Autoimmune acute liver failure: proposed clinical and histological criteria.

    PubMed

    Stravitz, R Todd; Lefkowitch, Jay H; Fontana, Robert J; Gershwin, M Eric; Leung, Patrick S C; Sterling, Richard K; Manns, Michael P; Norman, Gary L; Lee, William M

    2011-02-01

    Identifying autoimmune hepatitis as the etiology of acute liver failure (ALF) is potentially important, because administering corticosteroids might avoid the need for liver transplantation. However, clinical and histological criteria of autoimmune ALF (AI-ALF) have not been defined. Liver sections (biopsies and explants) from a 72-patient subset of the ALF Study Group Registry with indeterminate ALF were reviewed by a pathologist blinded to all clinical data and were diagnosed with probable AI-ALF based on four features suggestive of an autoimmune pathogenesis: distinctive patterns of massive hepatic necrosis (present in 42% of sections), presence of lymphoid follicles (32%), a plasma cell-enriched inflammatory infiltrate (63%), and central perivenulitis (65%). Forty-two sections (58%) were considered probable for AI-ALF; this group demonstrated higher serum globulins (3.7 ± 0.2 g/dL versus 3.0 ± 0.2 g/dL; P = 0.037) and a higher prevalence of antinuclear and/or anti-smooth muscle antibodies (73% versus 48%; P = 0.034) compared to those without histology suggestive of probable AI-ALF. Thirty patients concordant for autoantibodies and probable AI-ALF upon histological analysis were more likely to have the classical autoimmune hepatitis phenotype (female predominance [72% versus 48%; P < 0.05], higher globulins [3.9 ± 0.2 g/dL versus 3.0 ± 0.2 g/dL; P < 0.005], and higher incidence of chronic hepatitis in long-term follow-up [67% versus 17%, P = 0.019]) compared to the population without concordant AI-ALF histology and autoantibodies. Patients with indeterminate ALF often have features of autoimmune disease by histological analysis, serological testing, and clinical recurrence during follow-up. In contrast to classical autoimmune hepatitis, histological features of AI-ALF predominate in the centrilobular zone. Copyright © 2010 American Association for the Study of Liver Diseases.

  6. Growth and liver histology of Channa punctatus exposed to a common biofertilizer.

    PubMed

    Nath, S; Matozzo, V; Bhandari, D; Faggio, C

    2018-01-28

    Mustard oil cake (MOC) is widely used as biofertilizer in the field of agriculture and aquaculture. Channa punctatus was exposed to 0.42 g.L -1 sublethal concentration for 4, 7, 14, 21 and 28 days. Due to such exposure, body growth and histological changes in liver were observed. It was revealed that weight, length and breadth of fish were gradually increased with the days of exposure in compare to control fish, whereas, liver showed an increase in sinusoidal space and lipidosis during early days, followed by a recovery from the stress of MOC on the 28th day.

  7. Hepatic Histological Findings in Suspected Drug-Induced Liver Injury: Systematic Evaluation and Clinical Associations

    PubMed Central

    Kleiner, David E; Chalasani, Naga P; Lee, William M; Fontana, Robert J; Bonkovsky, Herbert L; Watkins, Paul B; Hayashi, Paul H; Davern, Timothy J; Navarro, Victor; Reddy, Rajender; Talwalkar, Jayant A; Stolz, Andrew; Gu, Jiezhun; Barnhart, Huiman; Hoofnagle, Jay H

    2014-01-01

    Drug-induced liver injury (DILI) is considered to be a diagnosis of exclusion. Liver biopsy may contribute to diagnostic accuracy, but the histological features of DILI and their relationship to biochemical parameters and outcomes are not well defined. We have classified the pathological pattern of liver injury and systematically evaluated histological changes in liver biopsies obtained from 249 patients with suspected DILI enrolled in the prospective, observational study conducted by the Drug Induced Liver Injury Network. Histological features were analyzed for their frequency within different clinical phenotypes of liver injury and to identify associations between clinical and laboratory findings and histological features. The most common histological patterns were acute (21%) and chronic hepatitis (14%), acute (9%) and chronic cholestasis (10%), and cholestatic hepatitis (29%). Liver histology from 128 patients presenting with hepatocellular injury had more severe inflammation, necrosis, and apoptosis and more frequently demonstrated lobular disarray, rosette formation, and hemorrhage than those with cholestasis. Conversely, histology of the 73 patients with cholestatic injury more often demonstrated bile plugs and duct paucity. Severe or fatal hepatic injury in 46 patients was associated with higher degrees of necrosis, fibrosis stage, microvesicular steatosis, and ductular reaction among other findings, whereas eosinophils and granulomas were found more often in those with milder injury. Conclusion: We describe an approach for evaluating liver histology in DILI and demonstrate numerous associations between pathological findings and clinical presentations that may serve as a foundation for future studies correlating DILI pathology with its causality and outcome. (Hepatology 2014;59:661–670) PMID:24037963

  8. Coeliac disease and the liver: spectrum of liver histology, serology and treatment response at a tertiary referral centre.

    PubMed

    Majumdar, Kaushik; Sakhuja, Puja; Puri, Amarender Singh; Gaur, Kavita; Haider, Aiman; Gondal, Ranjana

    2018-05-01

    Coeliac disease (CD) is a gluten-sensitive enteropathy diagnosed on the basis of ESPGHAN criteria and clinical response to gluten-free diet (GFD). Histological abnormalities on liver biopsy have been noted in CD but have seldom been described. To assess the histological spectrum of 'coeliac hepatitis' and possibility of reversal of such features after a GFD. Twenty-five patients with concomitant CD and hepatic derangement were analysed for clinical profile, laboratory investigations and duodenal and liver biopsy. A histological comparison of pre- and post-GFD duodenal and liver biopsies was carried out, wherever possible. Fifteen patients presenting with CD subsequently developed abnormal liver function tests; 10 patients presenting with liver disease were found to have tissue positive transglutaminase in 70% and antigliadin antibodies in 60%. Serological markers for autoimmune liver disease (AILD) were positive in eight patients. Liver histology ranged from mild reactive hepatitis, chronic hepatitis, steatosis to cirrhosis. Liver biopsies after a GFD were available in six cases, of which five showed a decrease in steatosis, portal and lobular inflammation and fibrosis score. Coeliac hepatitis could be a distinct entity and the patients may present with either CD or secondary hepatic derangement. Evaluation for the presence of CD is recommended for patients presenting with AILD, unexplained transaminasaemia or anaemia. This is one of the very few studies demonstrating the continuum of liver histological changes in 'coeliac hepatitis'. Trial of a GFD may result in clinicopathological improvement of 'coeliac hepatitis'. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Histological scoring and associated risk factors of non-alcoholic fatty liver disease.

    PubMed

    Majid, N; Ali, Z; Rahman, M R; Akhter, A; Rajib, R C; Ahmad, F; Sharmin, S; Akond, A K; Huq, N

    2013-10-01

    Non alcoholic steatohepatitis is a hepatic disorder with histological features of alcohol induced liver disease that occurs in individual who do not consume significant alcohol. Liver biopsy is an important part of the evaluation in term of both grade & stage. A cross sectional study was carried out in the department of Pathology, Dhaka Medical College, Dhaka & department of Hepatology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from July 2007 to June 2009. Total 55 adult subjects of both sex were included on the basis of predefined inclusion & exclusion criteria in this study to evaluate the histological pattern of non alcoholic fatty liver disease (NAFLD) and its correlation with risk factors. Liver biopsy was done and H & E and Masson's Trichrome stain slides were examined to evaluate the grade and stage of NAFLD. Scoring and semiquantitative assessment of steatosis and NAFLD severity was done according to Kleiner scale known as NAFLD activity score (NAS). The results of Pearson correlation showed only BMI and triglyceride level significantly correlated with NAS score. The results of Spearman's rank correlation showed that BMI, central obesity, triglyceridaemia and age significantly correlated with staging of fibrosis. The results of multiple regression analysis showed that variation of NAS depend on BMI and triglyceride level. The study also revealed that risk factors contributed about 29% risk for the occurrence of non alcoholic steatohepatitis.

  10. Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease.

    PubMed

    Jamali, Raika; Razavizade, Mohsen; Arj, Abbas; Aarabi, Mohammad Hossein

    2016-06-07

    To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease. Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm non-alcoholic liver disease (NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score (NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic (ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis, lobular inflammation and fibrosis. Fifty-four participants aged 37.02 ± 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-α levels were associated independently with steatosis grade of more than 33% [β = 1.08 (95%CI: 1.03-1.14), 1.04 (95%CI: 1.008-1.07), 1.04 (95%CI: 1.004-1.08), P < 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [β = 1.4 (95%CI: 1.09-1.8), 1.07 (95%CI: 1.003-1.15), P < 0.05]. Similarly, higher TNF-α, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [β = 1.06 (95%CI: 1.002-1.12), 19.86 (95%CI: 2.79-141.19), 560.72 (95%CI: 5.98-5255.33), P < 0.05]. Serum IL-8 and TNF-α values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [β = 1.05 (95%CI: 1.01-1.1), 1.13 (95%CI: 1.04-1.22), P < 0.05]. Certain adipokines may

  11. Liver enzymes and histology in obese patients with obstructive sleep apnea.

    PubMed

    Kallwitz, Eric R; Herdegen, James; Madura, James; Jakate, Shriram; Cotler, Scott J

    2007-01-01

    Recent studies have shown an association between obstructive sleep apnea (OSA) and elevated liver enzymes in patients with nonalcoholic fatty liver disease (NAFLD). The aim of the current study was to compare biochemical and histologic findings in patients with NAFLD as a function of OSA status. Subjects consisted of 85 patients who had a sleep study followed by a liver biopsy performed at the time of obesity surgery. The diagnosis of OSA was based on an apnea hypopnea index of >/=15. Demographic and laboratory data were collected retrospectively. Liver biopsies were systematically evaluated for features of NAFLD including degree of steatosis, inflammation, and fibrosis. All but one patient had histologic evidence of NAFLD and 51% of the study population had OSA. A higher proportion of patients with OSA had elevated alanine aminotransferase levels (13/39) compared with those without OSA (3/34) (P=0.01). Only 19% of subjects had fibrosis on liver biopsy and still fewer (5%) had bridging fibrosis or cirrhosis. There was a trend toward a higher prevalence of OSA in patients with evidence of progressive liver disease, as indicated by inflammation plus fibrosis (11/15), compared with those with inflammation alone (22/48) (P=0.06). In obese patients with NAFLD, OSA was associated with elevated alanine aminotransferase levels and a trend toward histologic evidence of progressive liver disease.

  12. Radiosensitivity Differences Between Liver Metastases Based on Primary Histology Suggest Implications for Clinical Outcomes After Stereotactic Body Radiation Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ahmed, Kamran A.; Caudell, Jimmy J.; El-Haddad, Ghassan

    Purpose/Objectives: Evidence from the management of oligometastases with stereotactic body radiation therapy (SBRT) reveals differences in outcomes based on primary histology. We have previously identified a multigene expression index for tumor radiosensitivity (RSI) with validation in multiple independent cohorts. In this study, we assessed RSI in liver metastases and assessed our clinical outcomes after SBRT based on primary histology. Methods and Materials: Patients were identified from our prospective, observational protocol. The previously tested RSI 10 gene assay was run on samples and calculated using the published algorithm. An independent cohort of 33 patients with 38 liver metastases treated with SBRTmore » was used for clinical correlation. Results: A total of 372 unique metastatic liver lesions were identified for inclusion from our prospective, institutional metadata pool. The most common primary histologies for liver metastases were colorectal adenocarcinoma (n=314, 84.4%), breast adenocarcinoma (n=12, 3.2%), and pancreas neuroendocrine (n=11, 3%). There were significant differences in RSI of liver metastases based on histology. The median RSIs for liver metastases in descending order of radioresistance were gastrointestinal stromal tumor (0.57), melanoma (0.53), colorectal neuroendocrine (0.46), pancreas neuroendocrine (0.44), colorectal adenocarcinoma (0.43), breast adenocarcinoma (0.35), lung adenocarcinoma (0.31), pancreas adenocarcinoma (0.27), anal squamous cell cancer (0.22), and small intestine neuroendocrine (0.21) (P<.0001). The 12-month and 24-month Kaplan-Meier rates of local control (LC) for colorectal lesions from the independent clinical cohort were 79% and 59%, compared with 100% for noncolorectal lesions (P=.019), respectively. Conclusions: In this analysis, we found significant differences based on primary histology. This study suggests that primary histology may be an important factor to consider in SBRT radiation dose selection.« less

  13. Magnetic resonance imaging and liver histology as biomarkers of hepatic steatosis in children with nonalcoholic fatty liver disease.

    PubMed

    Schwimmer, Jeffrey B; Middleton, Michael S; Behling, Cynthia; Newton, Kimberly P; Awai, Hannah I; Paiz, Melissa N; Lam, Jessica; Hooker, Jonathan C; Hamilton, Gavin; Fontanesi, John; Sirlin, Claude B

    2015-06-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. In order to advance the field of NAFLD, noninvasive imaging methods for measuring liver fat are needed. Advanced magnetic resonance imaging (MRI) has shown great promise for the quantitative assessment of hepatic steatosis but has not been validated in children. Therefore, this study was designed to evaluate the correlation and diagnostic accuracy of MRI-estimated liver proton density fat fraction (PDFF), a biomarker for hepatic steatosis, compared to histologic steatosis grade in children. The study included 174 children with a mean age of 14.0 years. Liver PDFF estimated by MRI was significantly (P < 0.01) correlated (0.725) with steatosis grade. The correlation of MRI-estimated liver PDFF and steatosis grade was influenced by both sex and fibrosis stage. The correlation was significantly (P < 0.01) stronger in girls (0.86) than in boys (0.70). The correlation was significantly (P < 0.01) weaker in children with stage 2-4 fibrosis (0.61) than children with no fibrosis (0.76) or stage 1 fibrosis (0.78). The diagnostic accuracy of commonly used threshold values to distinguish between no steatosis and mild steatosis ranged from 0.69 to 0.82. The overall accuracy of predicting the histologic steatosis grade from MRI-estimated liver PDFF was 56%. No single threshold had sufficient sensitivity and specificity to be considered diagnostic for an individual child. Advanced magnitude-based MRI can be used to estimate liver PDFF in children, and those PDFF values correlate well with steatosis grade by liver histology. Thus, magnitude-based MRI has the potential for clinical utility in the evaluation of NAFLD, but at this time no single threshold value has sufficient accuracy to be considered diagnostic for an individual child. © 2015 by the American Association for the Study of Liver Diseases.

  14. International trends in liver cancer incidence, overall and by histologic subtype, 1978-2007.

    PubMed

    Petrick, Jessica L; Braunlin, Megan; Laversanne, Mathieu; Valery, Patricia C; Bray, Freddie; McGlynn, Katherine A

    2016-10-01

    Primary liver cancer, the most common histologic types of which are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), is the second leading cause of cancer death worldwide. While rising incidence of liver cancer in low-risk areas and decreasing incidence in some high-risk areas has been reported, trends have not been thoroughly explored by country or by histologic type. We examined liver cancer incidence overall and by histology by calendar time and birth cohort for selected countries between 1978 and 2007. For each successive 5-year period, age-standardized incidence rates were calculated from volumes V-IX of the Cancer Incidence in Five Continents electronic database (CI5plus) and the newly released CI5X (volume X) database. Wide global variations persist in liver cancer incidence. Rates of liver cancer remain highest in Asian countries, specifically Eastern and South-Eastern Asian countries. While rates in most of these high-risk countries have been decreasing in recent years, rates in India and several low-risk countries of Africa, Europe, the Americas, and Oceania have been on the rise. Liver cancer rates by histologic type tend to convey a similar temporal profile. However, in Thailand, France, and Italy, ICC rates have increased while HCC rates have declined. We expect rates in high-risk countries to continue to decrease, as the population seroprevalence of hepatitis B virus (HBV) continues to decline. In low-risk countries, targeted screening and treatment of the hepatitis C virus (HCV), treatment of diabetes and primary prevention of obesity, will be key in reducing future liver cancer incidence. © 2016 UICC.

  15. Magnetic Resonance Imaging and Liver Histology as Biomarkers of Hepatic Steatosis in Children with Nonalcoholic Fatty Liver Disease

    PubMed Central

    Schwimmer, Jeffrey B.; Middleton, Michael S.; Behling, Cynthia; Newton, Kimberly P.; Awai, Hannah I.; Paiz, Melissa N.; Lam, Jessica; Hooker, Jonathan C.; Hamilton, Gavin; Fontanesi, John; Sirlin, Claude B.

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. In order to advance the field of NAFLD, noninvasive imaging methods for measuring liver fat are needed. Advanced magnetic resonance imaging (MRI) has shown great promise for the quantitative assessment of hepatic steatosis but has not been validated in children. Therefore, this study was designed to evaluate the correlation and diagnostic accuracy of MRI-estimated liver proton density fat fraction (PDFF), a biomarker for hepatic steatosis, compared to histologic steatosis grade in children. The study included 174 children with a mean age of 14.0 years. MRI-estimated liver PDFF was significantly (p < 0.01) correlated (0.725) with steatosis grade. Correlation of MRI-estimated liver PDFF and steatosis grade was influenced by both sex and fibrosis stage. The correlation was significantly (p<0.01) stronger in girls (0.86) than in boys (0.70). The correlation was significantly (p<0.01) weaker in children with stage 2–4 fibrosis (0.61) than children with no fibrosis (0.76) or stage 1 fibrosis (0.78). The diagnostic accuracy of commonly used threshold values to distinguish between no steatosis and mild steatosis ranged from 0.69 to 0.82. The overall accuracy of predicting the histologic steatosis grade from MRI-estimated liver PDFF was 56%. No single threshold had sufficient sensitivity and specificity to be considered diagnostic for an individual child. Conclusions Advanced magnitude-based MRI can be used to estimate liver PDFF in children, and those PDFF values correlate well with steatosis grade by liver histology. Thus magnitude-based MRI has the potential for clinical utility in the evaluation of NAFLD, but at this time no single threshold value has sufficient accuracy to be considered diagnostic for an individual child. PMID:25529941

  16. Obstructive sleep apnea and hypoxemia are associated with advanced liver histology in pediatric nonalcoholic fatty liver disease.

    PubMed

    Sundaram, Shikha S; Sokol, Ronald J; Capocelli, Kelley E; Pan, Zhaoxing; Sullivan, Jillian S; Robbins, Kristen; Halbower, Ann C

    2014-04-01

    To determine whether obstructive sleep apnea (OSA) and/or nocturnal hypoxemia are associated with the severity of liver injury in patients with pediatric nonalcoholic fatty liver disease (NAFLD). Obese children aged 10-18 years with liver biopsy-proven NAFLD were enrolled. Demographic, clinical, and laboratory data were collected, polysomnography was performed, and liver histology was scored. Subjects were divided into those with OSA/hypoxemia and those without OSA/hypoxemia for analysis. Of 25 subjects with NAFLD, OSA/hypoxemia was present in 15 (60%) (mean age, 12.8 ± 1.9 years; 68% male; 88% Hispanic; mean body mass index z-score, 2.3 ± 0.3). Subjects with and without OSA/hypoxemia had similar levels of serum aminotransferases, serum lipids, and inflammatory and insulin resistance markers. Although there were no differences between groups in the histological severity of steatosis, inflammation, ballooning degeneration, NAFLD activity score, or histological grade, subjects with OSA/hypoxemia had significantly more severe hepatic fibrosis. Moreover, oxygen saturation nadir during polysomnography was related to hepatic fibrosis stage (r = -0.49; P = .01) and aspartate aminotransferase level (r = 0.42; P < .05). Increasing percentage of time with oxygen saturation ≤90% was related to NAFLD inflammation grade (r = 0.44; P = .03), degree of hepatic steatosis (r = -0.50; P = .01), NAFLD activity score (r = 0.42; P = .04), aspartate aminotransferase level (r = 0.56; P = .004), and alanine aminotransferase level (r = 0.44; P = .03). Moderate OSA/hypoxemia is common in pediatric patients with biopsy-proven NAFLD. OSA and the severity/duration of hypoxemia are associated with biochemical and histological measures of NAFLD severity. Copyright © 2014 Mosby, Inc. All rights reserved.

  17. Donor liver histology--a valuable tool in graft selection.

    PubMed

    Flechtenmacher, Christa; Schirmacher, Peter; Schemmer, Peter

    2015-07-01

    Due to a tremendous organ shortage, livers from donors with extended criteria are increasingly considered for transplantation. Pathologists are more and more requested to evaluate these livers histopathologically using frozen sections at high urgency for acceptability. This article reviews the current knowledge on pre-transplant histology in liver transplantation. Prerequisites and conditions for proper pre-transplant evaluation of donor liver tissue are discussed as well as frozen section evaluation and reporting. Data sources include the relevant medical literature, web sites specialized in organ transplantation, and the authors' experiences in liver transplant centers. Pre-transplant histopathological evaluation is a time-effective, accurate, and reliable tool to assess liver quality from candidate deceased donors. Pre-transplant biopsies are of value in the selection of donor livers for transplantation, especially in case of extended criteria donors, and should be performed more frequently in order to avoid unnecessary loss of organs suitable for transplantation and transplantation of inappropriate organs. Correlation of histopathological findings with clinical conditions is essential and requires excellent communication between pathologists, surgeons, and the other members of the transplant team.

  18. Image-guided radiation therapy for liver tumors: gastrointestinal histology matters.

    PubMed

    Katsoulakis, Evangelia; Riaz, Nadeem; Cannon, Donald M; Goodman, Karyn; Spratt, Daniel E; Lovelock, Michael; Yamada, Yoshiya

    2014-12-01

    To describe the safety and efficacy of single-fraction and hypofractionated image-guided radiotherapy techniques for the treatment of large liver tumors. Forty-six patients, with 50 tumors (10 primary liver tumors, 40 liver metastases) from March 2004 to March 2011 were reviewed. The maximal tumor diameter ranged from 1.2 to 11.3 cm (median, 4.2 cm). Eighty-seven percent of patients received prior systemic chemotherapy. Fifty-nine percent had prior invasive local therapy including surgery, ablation, or embolization. Twenty-five lesions were treated with hypofractionated therapy (24 to 30 Gy in 3 to 5 fractions), whereas 19 received a single fraction (18 or 24 Gy). Local control (LC) was calculated using competing risk analysis. Overall survival was calculated by the Kaplan-Meier method. Median follow-up for all patients was 29.8 months (range, 3 to 46 mo). The median survival was 15.4 months. The 1- and 2-year LC rates were 78% and 75%, respectively. Dose and tumor size had no significant effect on tumor progression. The local progression at 1 and 2 years was 29% and 32% for gastrointestinal (GI) histologies versus 0% for non-GI histologies (P=0.02). Tumor volumes larger than 112 cm correlated with decreased survival (P=0.05). Three patients developed late grade 3 GI stricture or ulceration. Image-guided radiotherapy for liver tumors achieves good rates of LC with minimal toxicity at 1 and 2 years even in patients with large or recurrent disease that has been heavily pretreated. GI histology demonstrated decreased LC rates. Further management strategies should be considered in these patients.

  19. Effects of selective bile duct ligation on liver parenchyma in young animals: histologic and molecular evaluations.

    PubMed

    Tannuri, Ana Cristina A; Coelho, Maria Cecília M; de Oliveira Gonçalves, Josiane; Santos, Maria Mercês; Ferraz da Silva, Luiz Fernando; Bendit, Israel; Tannuri, Uenis

    2012-03-01

    (semiquantitative reverse transcriptase-polymerase chain reaction and real-time polymerase chain reaction, a quantitative method). Histologic analyses revealed the occurrence of ductular proliferation and collagen formation in the portal spaces of both BO and NBO lobes. These phenomena were observed later in NBO than BO. Bile duct density significantly increased 1 week after duct ligation; it decreased after 2 and 3 weeks and then increased again after 4 and 8 weeks in both BO and NBO lobes. The portal space collagen area increased after 2 weeks in both BO and NBO lobes. After 3 weeks, collagen deposition in BO was even higher, and in NBO, the collagen area started decreasing after 2 weeks. Molecular analyses revealed increased expression of the α-SMA gene in both BO and NBO lobes. The semiquantitative and quantitative methods showed concordant results. The ligation of a duct responsible for biliary drainage of the liver lobe promoted alterations in the parenchyma and in the adjacent nonobstructed parenchyma by paracrine and/or endocrine means. This was supported by histologic findings and increased expression of α-SMA, a protein related to hepatic fibrogenesis. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Effects of treatment with sucrose in drinking water on liver histology, lipogenesis and lipogenic gene expression in rats fed high-fiber diet.

    PubMed

    Mašek, Tomislav; Filipović, Natalija; Vuica, Ana; Starčević, Kristina

    2017-01-01

    We studied the influence of sucrose in drinking water on liver histology, fatty acid profile and lipogenic genes expression in rats maintained on high-fiber. The experimental groups were: control group (water) and sucrose group (sucrose solution in drinking water, 30% w/v). Liver histology of sucrose treated rats revealed steatosis and increased number of αSMA immunoreactive cells without the signs of fibrosis. Sucrose treatment increased de novo lipogenesis, lipid peroxidation and MUFA content and decreased PUFA content, C18:2n6 and C20:4n6 content in total phospholipids and phosphatidylethanolamine and C18:2n6 content in cardiolipin. RT-qPCR revealed increase in Δ-9-desaturase and SREBP1c gene expression and decrease in the Δ-5-desaturase and elongase 5 expression. Treatment with sucrose extensively changes fatty acid composition of hepatic lipid and phospholipid classes including cardiolipin, increases oxidative stress and causes pathological changes in liver in rats maintained on high-fiber diet. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Prevalence of histological features of idiopathic noncirrhotic portal hypertension in general population: a retrospective study of incidental liver biopsies.

    PubMed

    Zuo, Chunlai; Chumbalkar, Vaibhav; Ells, Peter F; Bonville, Daniel J; Lee, Hwajeong

    2017-09-01

    Idiopathic noncirrhotic portal hypertension (INCPH) is associated with histologic changes secondary to obliterative portal venopathy without cirrhosis. We studied the prevalence of individual histological features of INCPH in liver biopsies obtained incidentally during unrelated elective procedures and in elective liver biopsies with the diagnosis of fatty liver disease. A total of 53 incidental liver biopsies obtained intraoperatively during unrelated elective procedures and an additional 28 elective biopsies with the diagnosis of fatty liver disease without portal hypertension and cirrhosis were studied. Various histologic features of INCPH were evaluated. Shunt vessel (30%), phlebosclerosis (27%), increased number of portal vessels (19%) and incomplete septa (17%) were common in these liver biopsies after confounding factors such as co-existing fatty liver disease or fibrosis were excluded. At least one feature of INCPH was noted in 90% of the biopsies. Eight (10%) biopsies showed 5-6 features of INCPH. In total, 11 (14%) of 81 patients had risk factors associated with INCPH, including hypercoagulability, autoimmune disease, exposure to drugs, and infections. No patient had portal hypertension at the end of the follow-up. The histologic features of INCPH are seen in incidental liver biopsies and fatty liver disease without portal hypertension. Ten percent of the biopsies show 5-6 features of INCPH without portal hypertension. Interpreting histologic features in the right clinical context is important for proper patient care.

  2. Histology and Glutamine Synthetase Immunoreactivity in Liver Biopsies From Patients With Congestive Heart Failure

    PubMed Central

    Horvath, Bela; Zhu, Lei; Allende, Daniela; Xie, Hao; Guirguis, John; Cruise, Michael; Patil, Deepa T.; O’Shea, Robert; Rivas, John; Yordanka, Reyna; Lan, Nan; Liu, Xiuli

    2017-01-01

    Background Long-standing congestive heart failure can induce a constellation of histopathology changes in the liver that can range from mild sinusoidal dilation to advanced fibrosis and loss of normal perivenular expression of glutamine synthetase (GS). Liver biopsies might be performed to assess the perioperative risk of these patients or to determine the need of synchronous liver transplant. We aimed to assess interobserver agreement in recognizing these liver histologic features in patients undergoing evaluation for heart transplantation and to examine whether immunohistochemistry of GS will aid the diagnosis of cardiac hepatopathy (CH). Methods Hematoxylin-eosin and trichrome-stained slides from 36 liver biopsies from patients undergoing evaluation for heart transplantation were reviewed by four liver pathologists. Histologic features of CH were reviewed and an overall fibrosis (stage) was assessed according to a recently proposed congestive hepatic fibrosis score (CHFS). In addition, 24 liver biopsies with a consensus diagnosis of CH and eight liver biopsies with no significant pathological changes were subjected to immunohistochemistry for GS. The Fleiss’ kappa coefficient (K) analysis was performed to determine the interobserver agreement. Further, histologic features of CH were correlated with the staining pattern of GS. Results Sinusoidal dilation, centrilobular hepatocyte atrophy, centrilobular fibrosis and hemorrhage were the most common findings in this cohort with a substantial-to-fair level of interobserver agreement among four reviewers. The overall agreement on the diagnosis of CH and CHFS was moderate (K = 0.55, 95% confidence interval (CI): 0.32 - 0.73) and fair (K = 0.35, 95% CI: 0.24 - 0.49), respectively. Twelve (of 24, 50%) cases of CH showed loss of the normal perivenular GS staining, while the remaining 12 cases of CH and all eight controls showed retained GS expression. Histologic features of CH (presence of sinusoidal dilation

  3. Genome-Wide Associations Related to Hepatic Histology in Nonalcoholic Fatty Liver Disease in Hispanic Boys.

    PubMed

    Wattacheril, Julia; Lavine, Joel E; Chalasani, Naga P; Guo, Xiuqing; Kwon, Soonil; Schwimmer, Jeffrey; Molleston, Jean P; Loomba, Rohit; Brunt, Elizabeth M; Chen, Yii-Der Ida; Goodarzi, Mark O; Taylor, Kent D; Yates, Katherine P; Tonascia, James; Rotter, Jerome I

    2017-11-01

    To identify genetic loci associated with features of histologic severity of nonalcoholic fatty liver disease in a cohort of Hispanic boys. There were 234 eligible Hispanic boys age 2-17 years with clinical, laboratory, and histologic data enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network included in the analysis of 624 297 single nucleotide polymorphisms (SNPs). After the elimination of 4 outliers and 22 boys with cryptic relatedness, association analyses were performed on 208 DNA samples with corresponding liver histology. Logistic regression analyses were carried out for qualitative traits and linear regression analyses were applied for quantitative traits. The median age and body mass index z-score were 12.0 years (IQR, 11.0-14.0) and 2.4 (IQR, 2.1-2.6), respectively. The nonalcoholic fatty liver disease activity score (scores 1-4 vs 5-8) was associated with SNP rs11166927 on chromosome 8 in the TRAPPC9 region (P = 8.7 -07 ). Fibrosis stage was associated with SNP rs6128907 on chromosome 20, near actin related protein 5 homolog (p = 9.9 -07 ). In comparing our results in Hispanic boys with those of previously reported SNPs in adult nonalcoholic steatohepatitis, 2 of 26 susceptibility loci were associated with nonalcoholic fatty liver disease activity score and 2 were associated with fibrosis stage. In this discovery genome-wide association study, we found significant novel gene effects on histologic traits associated with nonalcoholic fatty liver disease activity score and fibrosis that are distinct from those previously recognized by adult nonalcoholic fatty liver disease genome-wide association studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. A comparison of liver fat content as determined by magnetic resonance imaging-proton density fat fraction and MRS versus liver histology in non-alcoholic fatty liver disease.

    PubMed

    Idilman, Ilkay S; Keskin, Onur; Celik, Azim; Savas, Berna; Elhan, Atilla Halil; Idilman, Ramazan; Karcaaltincaba, Musturay

    2016-03-01

    Many imaging methods have been defined for quantification of hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). However, studies comparing the efficiency of magnetic resonance imaging-proton density fat fraction (MRI-PDFF), magnetic resonance spectroscopy (MRS), and liver histology for quantification of liver fat content are limited. To compare the efficiency of MRI-PDFF and MRS in the quantification of liver fat content in individuals with NAFLD. A total of 19 NAFLD patients underwent MRI-PDFF, MRS, and liver biopsy for quantification of liver fat content. The MR examinations were performed on a 1.5 HDx MRI system. The MRI protocol included T1-independent volumetric multi-echo gradient-echo imaging with T2* correction and spectral fat modeling and MRS with STEAM technique. A close correlation was observed between liver MRI-PDFF- and histology- determined steatosis (r = 0.743, P < 0.001) and between liver MRS- and histology-determined steatosis (r = 0.712, P < 0.001), with no superiority between them (ƶ = 0.19, P = 0.849). For quantification of hepatic steatosis, a high correlation was observed between the two MRI methods (r = 0.986, P < 0.001). MRI-PDFF and MRS accurately differentiated moderate/severe steatosis from mild/no hepatic steatosis (P = 0.007 and 0.013, respectively), with no superiority between them (AUCMRI-PDFF = 0.881 ± 0.0856 versus AUCMRS = 0.857 ± 0.0924, P = 0.461). Both MRI-PDFF and MRS can be used for accurate quantification of hepatic steatosis. © The Foundation Acta Radiologica 2015.

  5. Effect of solution and post-mortem time on mechanical and histological properties of liver during cold preservation.

    PubMed

    Ayyildiz, Mehmet; Aktas, Ranan Gulhan; Basdogan, Cagatay

    2014-01-01

    In liver transplantation, the donor and recipient are in different locations most of the time, and longer preservation periods are inevitable. Hence, the choice of the preservation solution and the duration of the preservation period are critical for the success of the transplant surgery. In this study, we examine the mechanical and histological properties of the bovine liver tissue stored in Lactated Ringer's (control), HTK and UW solutions as a function of preservation period. The mechanical experiments are conducted with a shear rheometer on cylindrical tissue samples extracted from 3 bovine livers and the change in viscoelastic material properties of the bovine liver is characterized using the fractional derivative Kelvin-Voigt Model. Also, the histological examinations are performed on the same liver samples under a light microscope. The results show that the preservation solution and period have a significant effect on the mechanical and histological properties of the liver tissue. The storage and loss shear moduli, the number of the apoptotic cells, the collagen accumulation, and the sinusoidal dilatation increase, and the glycogen deposition decreases as the preservation period is longer. Based on the statistical analyses, we observe that the liver tissue is preserved well in all three solutions for up to 11 h. After then, UW solution provides a better preservation up to 29 h. However, for preservation periods longer than 29 h, HTK is a more effective preservation solution based on the least amount of change in mechanical properties. On the other hand, the highest correlation between the mechanical and histological properties is observed for the liver samples preserved in UW solution.

  6. Histological Spectrum of Idiopathic Noncirrhotic Portal Hypertension in Liver Biopsies From Dialysis Patients.

    PubMed

    Lee, Hwajeong; Ainechi, Sanaz; Singh, Mandeep; Ells, Peter F; Sheehan, Christine E; Lin, Jingmei

    2015-09-01

    Liver biopsy is performed for various indications in dialysis patients. Being a less-common subset, the hepatic pathology in renal dialysis is not well documented. Idiopathic noncirrhotic portal hypertension (INCPH) is a clinical entity associated with unexplained portal hypertension and/or a spectrum of histopathological vascular changes in the liver. After encountering INCPH and vascular changes of INCPH in 2 renal dialysis patients, we sought to further investigate this noteworthy association. A random search for patients on hemodialysis or peritoneal dialysis with liver biopsy was performed. Hematoxylin and eosin, reticulin, trichrome, and CK7 stains were performed on formalin-fixed, paraffin-embedded tissue sections. Histopathological features were reviewed, and the results were correlated with clinical findings. In all, 13 liver biopsies were retrieved. The mean cumulative duration of dialysis was 50 months (range = 17 months to 11 years). All patients had multiple comorbidities. Indications for biopsy were a combination of abnormal liver function tests (6), portal hypertension (4), ascites (3), and possible cirrhosis (3). Two patients with portal hypertension underwent multiple liver biopsies for diagnostic purposes. All (100%) biopsies showed some histological features of INCPH, including narrowed portal venous lumen (9), increased portal vascular channels (8), shunt vessels (3), dilated sinusoids (9), regenerative nodule (5), and features of venous outflow obstruction (3). No cirrhosis was identified. Liver biopsies from patients on dialysis demonstrate histopathological vascular changes of INCPH. Some (31%) patients present with portal hypertension without cirrhosis. The histological changes may be reflective of underlying risk factors for INCPH in this group. © The Author(s) 2015.

  7. Unusual mucoepidermoid carcinoma of the liver misdiagnosed as squamous cell carcinoma by intraoperative histological examination

    PubMed Central

    2014-01-01

    As rare condition, mucoepidermoid carcinoma may occur in liver although its etiology and pathogenesis is still unclear. We report here a case of intrahepatic mucoepidermoid carcinoma misdiagnosed as cholangiocarcinoma and squamous cell carcinoma by preoperative radiologic and intraoperative histological examinations, respectively. A 60-year-old woman presented with a 1-month history of progressive jaundice, epigastric discomfort, and weight loss with slightly increased carbohydrate antigen 19-9 (CA19-9). Computed tomography (CT) showed a large tumor, 8.0 cm in diameter, in the left lobe of the liver. A preliminary diagnosis of a cholangiocarcinoma of the liver was made. In the intraoperative histological examination, a diagnosis of squamous cell carcinoma was made based on predominantly invasive epidermoid cells with abundant keratinization and absence of mucin-producing cell component. However, postoperative histological diagnosis of the lesion was mucoepidermiod carcinoma of liver by thoroughly microscopical inspection and the presence of mucin-producing cells confirmed by Alcian blue staining. Despite surgical excision and chemotherapy, the tumor showed very aggressive malignancy with tumor recurrence. The patient died shortly afterward, surviving 6 months after surgery. Due to its rarity and distinct morphological features, mucoepidermoid carcinoma might be erroneously interpreted as squamous cell carcinoma by those who were not familiar with this condition in unusual locations. Therefore, removal of sufficient tissue from different portions of the lesion is essential for the surgeons and pathologists to make a precise diagnosis in the intraoperative histological examination. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4956311271136060 PMID:24475740

  8. Non-alcoholic fatty liver disease - histological scoring systems: a large cohort single-center, evaluation study.

    PubMed

    Rastogi, Archana; Shasthry, Saggere Muralikrishna; Agarwal, Ayushi; Bihari, Chhagan; Jain, Priyanka; Jindal, Ankur; Sarin, Shiv

    2017-11-01

    Non-alcoholic fatty liver disease (NAFLD) is an increasingly common cause of chronic liver disease. Till date, liver biopsy remains the gold standard for identification and quantification of the wide histological spectra of NAFLD. Histological scorings are very useful and widely applied for the diagnosis and management in clinical trials and follow-up studies of non-alcoholic steatohepatitis (NASH). However, in view of scarce published literature, there is a need to evaluate them in large cohort of NAFLD. This study was aimed to evaluate the two histological scoring systems (NAS-CRN, SAF) in the diagnosis of NAFLD and to assess the role of histological characteristics as injury markers in NAFLD. Retrospective histological study of liver biopsies of 1000 patients diagnosed as NAFLD, between 2010 and 2016, was conducted. Histopathologic evaluation and semiquantiative scoring based on NAS-CRN and SAF algorithm and their correlation with serum aminotransferase and fibrosis were performed. Liver biopsies were classified according to the NAS-CRN scoring, as NAS <3 (not NASH) in 72 (7.2%), NAS 3-4 (borderline NASH) in 310 (31%), and NAS ≥5 (definite NASH) in 618 (61.8%), and SAF classified 117 (11.7%) not NASH and 883 (88.3%) definite NASH. There was excellent concordance for definite NASH and not NASH; however, 88.06% of borderline NASH was classified as NASH by SAF. 76.39% by NAS and 78.63% by SAF algorithm who were diagnosed as not NASH showed the presence of fibrosis; however, higher stages of fibrosis were significantly more prevalent in definite NASH, excluding burnt-out cirrhosis. Serum ALT was significantly associated with increasing stages of fibrosis (p < 0.001) and the three categories (not NASH, borderline NASH, and definite NASH) when classified as with/without fibrosis (p < 0.001). Steatosis of higher grades, more ballooned cells, and more foci of Lobular Inflammation were found in significantly higher proportion of patients with NASH (p < 0

  9. Characterization of CD133+ parenchymal cells in the liver: histology and culture.

    PubMed

    Yoshikawa, Seiichi; Zen, Yoh; Fujii, Takahiko; Sato, Yasunori; Ohta, Tetsuo; Aoyagi, Yutaka; Nakanuma, Yasuni

    2009-10-21

    To reveal the characteristics of CD133(+) cells in the liver. This study examined the histological characteristics of CD133(+) cells in non-neoplastic and neoplastic liver tissues by immunostaining, and also analyzed the biological characteristics of CD133(+) cells derived from human hepatocellular carcinoma (HCC) or cholangiocarcinoma cell lines. Immunostaining revealed constant expression of CD133 in non-neoplastic and neoplastic biliary epithelium, and these cells had the immunophenotype CD133(+)/CK19(+)/HepPar-1(-). A small number of CD133(+)/CK19(-)/HepPar-1(+) cells were also identified in HCC and combined hepatocellular and cholangiocarcinoma. In addition, small ductal structures, resembling the canal of Hering, partly surrounded by hepatocytes were positive for CD133. CD133 expression was observed in three HCC (HuH7, PLC5 and HepG2) and two cholangiocarcinoma cell lines (HuCCT1 and CCKS1). Fluorescence-activated cell sorting (FACS) revealed that CD133(+) and CD133(-) cells derived from HuH7 and HuCCT1 cells similarly produced CD133(+) and CD133(-) cells during subculture. To examine the relationship between CD133(+) cells and the side population (SP) phenotype, FACS was performed using Hoechst 33342 and a monoclonal antibody against CD133. The ratios of CD133(+)/CD133(-) cells were almost identical in the SP and non-SP in HuH7. In addition, four different cellular populations (SP/CD133(+), SP/CD133(-), non-SP/CD133(+), and non-SP/CD133(-)) could similarly produce CD133(+) and CD133(-) cells during subculture. This study revealed that CD133 could be a biliary and progenitor cell marker in vivo. However, CD133 alone is not sufficient to detect tumor-initiating cells in cell lines.

  10. Clinical, biochemical, serological, histological and ultrastructural features of liver disease in drug abusers.

    PubMed Central

    Weller, I V; Cohn, D; Sierralta, A; Mitcheson, M; Ross, M G; Montano, L; Scheuer, P; Thomas, H C

    1984-01-01

    Heroin abusers are frequently found to have abnormal liver function tests and hepatic histology. Hepatitis viruses A, B, and NANB, other drugs or drug contaminants and excessive alcohol consumption are factors thought to contribute. One hundred and sixteen heroin abusers attending a London treatment centre were studied. Sixty two (53%) had a raised aspartate transaminase. This was not explained by current infection with hepatitis A and B, cytomegalo or Epstein-Barr viruses, excessive alcohol consumption (greater than 80 g/day) or concomitant drug taking. Abnormal liver function tests were as frequent in those with markers of current or past HBV infection as those without and there was evidence that both HBV infection and the cause of the abnormal liver function tests were acquired in the first few years of intravenous drug abuse. Liver biopsies from eight patients showed chronic hepatitis with a mild lobular and portal inflammatory infiltrate, fatty change and prominent sinusoidal cells. Electron microscopy showed cytoplasmic trilaminar tubular structures and dense fused membranes in dilated endoplasmic reticulum. These clinical, biochemical, serological, and histological features would suggest a major role for NANB virus infection in the aetiology of hepatitis in heroin abusers. Images Fig. 2 Fig. 3 Fig. 4 PMID:6423458

  11. Metabolic and histological implications of intrahepatic triglyceride content in nonalcoholic fatty liver disease.

    PubMed

    Bril, Fernando; Barb, Diana; Portillo-Sanchez, Paola; Biernacki, Diane; Lomonaco, Romina; Suman, Amitabh; Weber, Michelle H; Budd, Jeffrey T; Lupi, Maria E; Cusi, Kenneth

    2017-04-01

    The cut-off point of intrahepatic triglyceride (IHTG) content to define nonalcoholic fatty liver disease (NAFLD) by proton magnetic resonance spectroscopy ( 1 H-MRS) was established based on the 95th percentile in a group of healthy individuals (i.e., ≥5.56%). Whether this threshold correlates with metabolic and histological changes and whether a further accumulation of IHTG is associated with worsening of these parameters has not been properly assessed in a large cohort of patients. In this cross-sectional study, 352 subjects were carefully characterized with the following studies: liver 1 H-MRS; euglycemic insulin clamp with measurement of glucose turnover; oral glucose tolerance test; and a liver biopsy. Hepatic insulin sensitivity (suppression of endogenous glucose production by insulin) was affected early on after IHTG content was ∼1.5% and remained uniformly impaired (∼40%-45%), regardless of further IHTG accumulation. Skeletal muscle insulin sensitivity showed a gradual impairment at low degrees of IHTG accumulation, but remained unchanged after IHTG content reached the ∼6 ± 2% threshold. A similar pattern was observed for metabolic changes typically associated with NAFLD, such as hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C). In contrast, adipose tissue insulin sensitivity (suppression of free fatty acids by insulin) showed a continuous worsening across the spectrum of IHTG accumulation in NAFLD (r = -0.38; P < 0.001). Histological severity of liver disease (inflammation, ballooning, and fibrosis) was not associated with the amount of IHTG content. IHTG accumulation is strongly associated with adipose tissue insulin resistance (IR), supporting the current theory of lipotoxicity as a driver of IHTG accumulation. Once IHTG accumulation reaches ∼6 ± 2%, skeletal muscle IR, hypertriglyceridemia, and low HDL-C become fully established. Histological activity appears to have an early threshold and is not significantly

  12. Caffeine intake decreases oxidative stress and inflammatory biomarkers in experimental liver diseases induced by thioacetamide: Biochemical and histological study.

    PubMed

    Amer, Mona G; Mazen, Nehad F; Mohamed, Ahmed M

    2017-03-01

    Liver disease remains a significant global health problem. Increased caffeine consumption has been associated with a lower prevalence of chronic liver disease. This study aimed to investigate the modifying effects of caffeine on liver injury induced by thioacetamide (TAA) administration in male rats and the possible underlying mechanisms. Forty adult male rats were equally classified into four groups: control group, received only tap water; caffeine-treated group, received caffeine (37.5 mg/kg per day); TAA-treated group, received intraperitoneal (i.p.) TAA (200 mg/kg b.w.) twice a week; and caffeine + TAA-treated group, received combined TAA and caffeine in the same previous doses. After eight weeks of treatment, blood samples were collected for biochemical analysis and liver specimens were prepared for histological and immunohistochemical studies and for assessment of oxidative stress. TAA induced liver toxicity with elevated liver enzymes and histological alterations, fatty changes, apoptosis, and fibrosis evidenced by increased immunohistochemical reaction to matrix metalloproteinase-9 (MMP-9) and collagen type IV in hepatocytes. Also, the levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in serum were significantly elevated. Co-treatment with caffeine and TAA restored normal liver structure and function. Caffeine provided an anti-fibrogenic, anti-inflammatory, and antioxidant effect that was associated with recovery of hepatic histological and functional alterations from TAA-induced hepatotoxicity.

  13. A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy.

    PubMed

    Wada, Keisuke; Kobayashi, Hironori; Moriyama, Aisa; Haneda, Yasuhiro; Mushimoto, Yuichi; Hasegawa, Yuki; Onigata, Kazumichi; Kumori, Koji; Ishikawa, Noriyoshi; Maruyama, Riruke; Sogo, Tsuyoshi; Murphy, Lynne; Taketani, Takeshi

    2017-01-01

    Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic posterior lobe, and the patient was diagnosed with congenital CPHD based on decreased secretion of cortisol and GH by the pituitary anterior lobe load test. D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We subsequently began replacement with levothyroxine (L-T 4 ) and GH, and liver histology showed normal interlobular bile ducts at 8 mo old. This is the first case report of proven histological improvement after hormone replacement therapy. This suggested that pituitary-mediated hormones, especially cortisol, might be involved in the development of the bile ducts.

  14. A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy

    PubMed Central

    Wada, Keisuke; Kobayashi, Hironori; Moriyama, Aisa; Haneda, Yasuhiro; Mushimoto, Yuichi; Hasegawa, Yuki; Onigata, Kazumichi; Kumori, Koji; Ishikawa, Noriyoshi; Maruyama, Riruke; Sogo, Tsuyoshi; Murphy, Lynne; Taketani, Takeshi

    2017-01-01

    Abstract. Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic posterior lobe, and the patient was diagnosed with congenital CPHD based on decreased secretion of cortisol and GH by the pituitary anterior lobe load test. D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We subsequently began replacement with levothyroxine (L-T4) and GH, and liver histology showed normal interlobular bile ducts at 8 mo old. This is the first case report of proven histological improvement after hormone replacement therapy. This suggested that pituitary-mediated hormones, especially cortisol, might be involved in the development of the bile ducts. PMID:29026274

  15. Correlation between liver histology and novel magnetic resonance imaging in adult patients with non-alcoholic fatty liver disease - MRI accurately quantifies hepatic steatosis in NAFLD.

    PubMed

    Permutt, Z; Le, T-A; Peterson, M R; Seki, E; Brenner, D A; Sirlin, C; Loomba, R

    2012-07-01

    Conventional magnetic resonance imaging (MRI) techniques that measure hepatic steatosis are limited by T1 bias, T(2)* decay and multi-frequency signal-interference effects of protons in fat. Newer MR techniques such as the proton density-fat fraction (PDFF) that correct for these factors have not been specifically compared to liver biopsy in adult patients with non-alcoholic fatty liver disease (NAFLD). To examine the association between MRI-determined PDFF and histology-determined steatosis grade, and their association with fibrosis. A total of 51 adult patients with biopsy-confirmed NAFLD underwent metabolic-biochemical profiling, MRI-determined PDFF measurement of hepatic steatosis and liver biopsy assessment according to NASH-CRN histological scoring system. The average MRI-determined PDFF increased significantly with increasing histology-determined steatosis grade: 8.9% at grade-1, 16.3% at grade-2, and 25.0% at grade-3 with P ≤ 0.0001 (correlation: r(2) = 0.56, P < 0.0001). Patients with stage-4 fibrosis, when compared with patients with stage 0-3 fibrosis, had significantly lower hepatic steatosis by both MRI-determined PDFF (7.6% vs. 17.8%, P < 0.005) and histology-determined steatosis grade (1.4 vs. 2.2, P < 0.05). NAFLD patients with grade 1 steatosis were more likely to have characteristics of advanced liver disease including higher average AST:ALT (0.87 vs. 0.60, P < 0.02), GGT (140 vs. 67, P < 0.01), and INR (1.06 vs. 0.99, P < 0.01), higher stage of fibrosis and hepatocellular ballooning. MRI-determined proton density-fat fraction correlates with histology-determined steatosis grade in adults with NAFLD. Steatosis is non-linearly related to fibrosis progression. In patients with NAFLD, a low amount of hepatic steatosis on imaging does not necessarily indicate mild disease. © 2012 Blackwell Publishing Ltd.

  16. [Prediction of histological liver damage in asymptomatic alcoholic patients by means of clinical and laboratory data].

    PubMed

    Iturriaga, H; Hirsch, S; Bunout, D; Díaz, M; Kelly, M; Silva, G; de la Maza, M P; Petermann, M; Ugarte, G

    1993-04-01

    Looking for a noninvasive method to predict liver histologic alterations in alcoholic patients without clinical signs of liver failure, we studied 187 chronic alcoholics recently abstinent, divided in 2 series. In the model series (n = 94) several clinical variables and results of common laboratory tests were confronted to the findings of liver biopsies. These were classified in 3 groups: 1. Normal liver; 2. Moderate alterations; 3. Marked alterations, including alcoholic hepatitis and cirrhosis. Multivariate methods used were logistic regression analysis and a classification and regression tree (CART). Both methods entered gamma-glutamyltransferase (GGT), aspartate-aminotransferase (AST), weight and age as significant and independent variables. Univariate analysis with GGT and AST at different cutoffs were also performed. To predict the presence of any kind of damage (Groups 2 and 3), CART and AST > 30 IU showed the higher sensitivity, specificity and correct prediction, both in the model and validation series. For prediction of marked liver damage, a score based on logistic regression and GGT > 110 IU had the higher efficiencies. It is concluded that GGT and AST are good markers of alcoholic liver damage and that, using sample cutoffs, histologic diagnosis can be correctly predicted in 80% of recently abstinent asymptomatic alcoholics.

  17. Comparison of magnetic resonance spectroscopy, proton density fat fraction and histological analysis in the quantification of liver steatosis in children and adolescents

    PubMed Central

    Di Martino, Michele; Pacifico, Lucia; Bezzi, Mario; Di Miscio, Rossella; Sacconi, Beatrice; Chiesa, Claudio; Catalano, Carlo

    2016-01-01

    AIM To establish a threshold value for liver fat content between healthy children and those with non-alcoholic fatty liver disease (NAFLD) by using magnetic resonance imaging (MRI), with liver biopsy serving as a reference standard. METHODS The study was approved by the local ethics committee, and written informed consent was obtained from all participants and their legal guardians before the study began. Twenty-seven children with NAFLD underwent liver biopsy to assess the presence of nonalcoholic steatohepatitis. The assessment of liver fat fraction was performed using MRI, with a high field magnet and 2D gradient-echo and multiple-echo T1-weighted sequence with low flip angle and single-voxel point-resolved ¹H MR-Spectroscopy (¹H-MRS), corrected for T1 and T2* decays. Receiver operating characteristic curve analysis was used to determine the best cut-off value. Lin coefficient test was used to evaluate the correlation between histology, MRS and MRI-PDFF. A Mann-Whitney U-test and multivariate analysis were performed to analyze the continuous variables. RESULTS According to MRS, the threshold value between healthy children and those with NAFLD is 6%; using MRI-PDFF, a cut-off value of 3.5% is suggested. The Lin analysis revealed a good fit between the histology and MRS as well as MRI-PDFF. CONCLUSION MRS is an accurate and precise method for detecting NAFLD in children. PMID:27818597

  18. Early histological and functional effects of chronic copper exposure in rat liver.

    PubMed

    Cisternas, Felipe A; Tapia, Gladys; Arredondo, Miguel; Cartier-Ugarte, Denise; Romanque, Pamela; Sierralta, Walter D; Vial, María T; Videla, Luis A; Araya, Magdalena

    2005-10-01

    Cu is an essential trace element capable of producing toxic effects in animals and man when ingested acutely or chronically in excess. Although chronic Cu exposure is increasingly recognized as a public health issue, its early effects remain largely unknown. We approached the significance of a moderate chronic Cu load in young rats to correlate early hepatic histopathological changes with functional alterations of liver cells. For this purpose, supplementation with 1,200 ppm of Cu in rat food for 16 weeks was chosen. In these conditions, Cu load elicited a significant decrease in growth curves. There were mild light microscopy alterations in Cu-treated rats, although increasing intracellular Cu storage was correlated with longer Cu exposure both by histological and biochemical measurements. Ultrastructural alterations included lysosomal inclusions as well as mitochondrial and nuclear changes. Liver perfusion studies revealed higher rates of basal O(2) consumption and colloidal carbon-induced O(2) uptake in Cu-treated rats, with enhanced carbon-induced O(2)/carbon uptake ratios and NF-kappaB DNA binding activity. These changes were time-dependent and returned to control values after 12 or 16 weeks. It is concluded that subchronic Cu loading in young rats induces early hepatic morphological changes, with enhancement in Küpffer cell-dependent respiratory burst activity and NF-kappaB DNA binding, cellular responses that may prevent or alleviate the hepatotoxicity of the metal.

  19. Low-dose steroids associated with milder histological changes after pediatric liver transplantation.

    PubMed

    Kosola, Silja; Lampela, Hanna; Jalanko, Hannu; Mäkisalo, Heikki; Lohi, Jouko; Arola, Johanna; Pakarinen, Mikko P

    2013-02-01

    Controversy remains about the role of protocol liver biopsy for symptom-free recipients and about the long-term use of low-dose steroids after pediatric liver transplantation (LT). We conducted a national cross-sectional study of pediatric recipients who underwent LT between 1987 and 2007. Liver biopsy samples were taken from 54 patients (82% of survivors) after a median posttransplant follow-up of 11 years, and they were reviewed by 2 pathologists blinded to the clinical data. Biopsy samples from 18 patients (33%) showed nearly normal histology with no inflammation, fibrosis, or steatosis. Portal inflammation was detected in 14 samples (26%), showed no correlation with anti-nuclear antibodies, and was less frequent in the 35 patients whose immunosuppression included steroids (14% versus 47% of patients not using steroids, P = 0.008). Fibrosis was present in 21 biopsy samples (39%). According to the Metavir classification, 16 were stage 1, 3 were stage 2, and 2 were stage 3. The fibrosis stage correlated negatively with serum prealbumin levels (r = -0.364, P = 0.007) and positively with chronic cholestasis (cytokeratin 7 staining; r = 0.529, P < 0.001) and portal inflammation (r = 0.350, P = 0.01). Microvesicular steatosis was found in 23 biopsy samples (43% of patients in 5%-80% of hepatocytes), and it correlated with the body mass index (r = 0.458, P < 0.001) but not with steroid use. The age of the allograft (donor age plus follow-up time) correlated with higher serum gamma-glutamyltransferase (r = 0.472, P < 0.001) and conjugated bilirubin levels (r = 0.420, P = 0.002) as well as chronic cholestasis (r = 0.299, P = 0.03). The biopsy findings led to treatment changes in 10 patients (19%), whereas only 1 complication (subcapsular hematoma) was encountered. In conclusion, continuing low-dose steroids indefinitely after pediatric LT may have a positive effect on the long-term histological state of the liver graft. Allograft aging may lead to chronic cholestasis and

  20. Histologic analysis of rabbit liver cancer treated by bulk ultrasound ablation

    NASA Astrophysics Data System (ADS)

    Karunakaran, Chandra Priya; Rudich, Steven M.; Alqadah, Amel; Burgess, Mark T.; Narmoneva, Daria A.; Mast, T. Douglas

    2012-10-01

    VX2 rabbit liver cancer, treated in vivo using bulk ultrasound ablation by miniaturized image-ablate arrays, was histologically analyzed using TTC vital stain and DAPI nucleic acid stain. VX2 cells were implanted into rabbit liver lobes and allowed to grow for 11-21 days. Liver lobes containing solid VX2 tumors were then treated with 4.8 MHz, 22.5-38.5 W/cm2 in situ intensity, unfocused ultrasound for exposure times of 20-120 s. After animal sacrifice, thermal lesions were bisected along the imaging/treatment plane, one face stained with TTC, and the other with DAPI. Levels of TTC uptake (no uptake, partial uptake, and complete uptake) in liver parenchyma corresponded to three discrete regions of tan, pink and red color. By processing images of DAPI-stained parenchymal tissue from these three regions, cellular damage was quantified. A viability index parameter incorporating the size and shape of DAPI-stained nuclei correlated significantly with levels of TTC uptake, and thus with local tissue viability. For ablation of normal liver, viability indices for parenchymal regions of no TTC uptake and partial TTC uptake were significantly different from those for viable tissue. For ablation of VX2 tumor, differences in viability index between regions of no TTC uptake and complete TTC uptake were smaller, but significant overall.

  1. Histologically-Proven Efficacy of Bland Embolization in a Patient with Net Liver Metastasis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Monfardini, Lorenzo, E-mail: lorenzo.monfardini@poliambulanza.it, E-mail: lorenzo.monfardini@ieo.it; Varano, Gianluca Maria; Foà, Riccardo

    2016-06-15

    We present a case of 57-year-old patient with three liver metastases from a primary neuroendocrine duodenal tumor, who underwent bland embolization with excellent response to therapy, followed by surgical resection. The purpose of our case report is to describe the histological characteristics of tumoral response to therapy after bland embolization focusing on intralesional necrosis and microsphere distribution.

  2. Obstructive Sleep Apnea Is Associated with Nonalcoholic Steatohepatitis and Advanced Liver Histology.

    PubMed

    Corey, Kathleen E; Misdraji, Joseph; Gelrud, Lou; King, Lindsay Y; Zheng, Hui; Malhotra, Atul; Chung, Raymond T

    2015-08-01

    Nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) are growing in prevalence in the USA. Existing data on the relationship between OSA and NAFLD are conflicting and limited by the use of various histologic definitions of nonalcoholic steatohepatitis (NASH). Using a robust definition of NASH in a large, well-characterized cohort, we sought to evaluate whether OSA was associated with NASH and advanced fibrosis. Two hundred and thirteen subjects undergoing weight loss surgery were queried for OSA and then underwent liver biopsy. NASH was defined, as recommended by the American Association for the Study of Liver Disease, by the presence of all of the following: >5 % macrovesicular steatosis, lobular inflammation, and hepatocyte ballooning. NAFLD activity score (NAS) was also determined for each subject. Subjects with OSA had significantly higher alanine and aspartate aminotransferase levels than subjects without OSA (ALT 54.1 vs. 37.7 U/L, P = 0.0007; AST 31.7 vs. 20.5 U/L, P = 0.0007). OSA was associated with the presence of NASH, and this remained significant after adjusting for age, gender, race, and diabetes mellitus (P = 0.03 OR 2.01; 95 %, 1.05-3.87). Steatosis grade, lobular inflammation grade, NAS score, and fibrosis stage were all significantly associated with the presence of OSA and remained so after adjustment. OSA is associated with elevated aminotransferase levels, the presence of NASH, and advanced NASH histology. Further studies are needed to evaluate the impact of OSA treatment on NASH.

  3. Obstructive Sleep Apnea is associated with Nonalcoholic Steatohepatitis and Advanced Liver Histology

    PubMed Central

    Corey, Kathleen E; Misdraji, Joseph; Gelrud, Lou; King, Lindsay Y.; Zheng, Hui; Malhotra, Atul; Chung, Raymond T

    2015-01-01

    Background and Aims Nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) are growing in prevalence in the United States. Existing data on the relationship between OSA and NAFLD is conflicting and limited by the use of various histologic definitions of nonalcoholic steatohepatitis (NASH). Using a robust definition of NASH in a large, well-characterized cohort we sought to evaluate whether OSA was associated with NASH and advanced fibrosis. Methods Two hundred thirteen subjects undergoing weight loss surgery were queried for OSA and then underwent liver biopsy. NASH was defined, as recommended by the American Association for the Study of Liver Disease, by the presence of all of the following: >5% macrovesicular steatosis, lobular inflammation and hepatocyte ballooning. NAFLD activity score (NAS) was also determined for each subject. Results Subjects with OSA had significantly higher alanine and aspartate aminotransferase levels than subjects without OSA (ALT 54.1 U/L vs. 37.7 U/L, P=0.0007; AST 31.7 U/L vs. 20.5 U/L, P=0.0007). OSA was associated with the presence of NASH and this remained significant after adjusting for age, gender, race, and diabetes mellitus (P =0.03 OR, 2.01; 95%, 1.05-3.87). Steatosis grade, lobular inflammation grade, NAS score and fibrosis stage were all significantly associated with the presence of OSA and remained so after adjustment. Conclusions OSA is associated with elevated aminotransferase levels, the presence of NASH and advanced NASH histology. Further studies are needed to evaluate the impact of OSA treatment on NASH. PMID:25840922

  4. Comparison of acoustic radiation force impulse imaging (ARFI) to liver biopsy histologic scores in the evaluation of chronic liver disease: A pilot study.

    PubMed

    Haque, Mazhar; Robinson, Charlotte; Owen, David; Yoshida, Eric M; Harris, Alison

    2010-01-01

    Acoustic Radiation Force Impulse Imaging (ARFI) is a novel non invasive technique studying the localized mechanical properties of tissue by utilising short, high intensity acoustic pulses (shear wave pulses) to assess the mechanical response (tissue displacement), providing a measure of tissue elasticity. The aim of this study is to investigate the feasibility of ARFI imaging as a non-invasive method for the assessment of liver fibrosis compared to liver biopsy scores. A prospective blind comparison study of ARFI elastography (Virtual Touch Imaging., ACUSON S2000 Ultrasound Unit, Siemens, Mountain View CA) in a consecutive series of patients who underwent liver biopsy for assessment of fibrosis in chronic liver disease. ARFI shear-wave propagation velocity was measured in meters per second. Mean ARFI velocities were compared with both Batts-Ludwig (F0 to F4) and Modified Ishak scores (F0 to F4) for fibrosis in liver biopsy findings. Twenty-one patients with chronic liver disease (Hepatitis C (HCV) =16, Hepatitis B (HBV) = 1, both HCV and HBV = 1 Alcoholic liver disease (ALD) = 1, others = 2) underwent ARFI and liver biopsy on the same day. The Spearman correlation coefficients between the median values of the ARFI measurements and the histological fibrosis stage of the Modified Ishak score and Batts-Lud- (3) wig score were both highly significant (p < 0.01) with rho = 0.69 and rho = 0.72 respectively. The median ARFI (total 180 replications; minimum 5, maximum 10 measurements per patients) velocities for our study population range from 0.92 to 4.17 m/sec. Areas under the receiver operating characteristic curve for the accuracy of ARFI imaging was 1.00 and 0.35, for the diagnosis of moderate fibrosis (histologic fibrosis stage, F (3) 2) and 0.85 and 0.85 respectively for Ishak and Batts-Ludwig score, for the diagnosis of cirrhosis. ARFI imaging has a strong correlation with the fibrosis stage of both Batts-Ludwig and shak score in chronic liver disease. It

  5. Diwu Yanggan capsule improving liver histological response for patients with HBeAg-negative chronic hepatitis B: a randomized controlled clinical trial.

    PubMed

    Li, Hanmin; Ye, Zhihua; Gao, Xiang; Zhang, Lisheng; Yao, Xin; Gu, Jianxun; Lu, Dingbo; Wan, Ming; Xiao, Lin; Cai, Wangxi; Yan, Xuesheng; Zhao, Binbin; Wu, Yu; Zhang, Jinrong

    2018-01-01

    The number of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) has shown a significant upward trend in recent years. However, antiviral drugs are not very effective. Regulation of liver regeneration by traditional Chinese medicine is an important way to improve clinical efficacy. This randomized controlled trial assessed the efficacy and safety of DWYG in patients with HBeAg-negative CHB. Overall, 130 subjects were randomized to (A) DWYG 1.2 g three times daily (n = 44), (B) entecavir 0.5 mg/day (n = 43) in combination with DWYG or (C) entecavir 0.5 mg/day (n = 43). The liver histological response rate was assessed as the primary efficacy endpoint. The results showed that the liver histological response rate in the combination treatment group was significantly higher than that in the group with entecavir (71.43% versus 22.22%; P = 0.036) after 48 weeks of treatment. And the pathological progression rate of liver in the group with DWYG was significantly lower than that of the entecavir group during 228 weeks of follow-up (0% versus 60.00%; P = 0.019). No significant adverse events occurred during the study. In conclusion, treating HBeAg-negative CHB with DWYG is safe and effective to improve liver histological response.

  6. Simultaneous evaluation of lymphocyte subpopulations in the liver and in peripheral blood mononuclear cells of HCV-infected patients: relationship with histological lesions

    PubMed Central

    PERNOLLET, M; JOUVIN-MARCHE, E; LEROY, V; VIGAN, I; ZARSKI, J -P; MARCHE, P N

    2002-01-01

    Intrahepatic lymphocytes are believed to be involved in the immunopathogenesis of hepatitis C virus (HCV) infection and the evolution of HCV-induced hepatitis. In the present study, we examined the three main intrahepatic lymphocyte subsets, namely CD3+CD56− conventional T lymphocytes, CD3+CD56+ natural T (NT) lymphocytes and CD3−CD56+ natural killer (NK) lymphocytes in HCV-infected patients. The proportion of each lymphocyte subset was evaluated both in liver biopsies and in samples of peripheral blood lymphocytes (PBL) by flow cytometry in 21 patients with histologically proven chronic hepatitis C. Simultaneously, alanine aminotransferase (ALT) levels, viral load and histological lesions were assessed. Neither NT nor NK populations correlated with any biochemical, viral or histological parameters. Furthermore, Vα24+ NT lymphocytes showed no preferential enrichment in the liver of HCV-infected patients. Regarding conventional T lymphocytes, a highly significant linear correlation was found between intrahepatic CD3+CD56− T lymphocytes and the Knodell score, a numerical score for assessing histological activity and fibrosis (r = 0·715, P < 0·0001) and more specifically with the periportal necrosis parameter, which is the main lesion of chronic hepatitis C. In addition, analysis of the peripheral compartment revealed a high correlation between values of CD3+CD56− lymphocytes and both Knodell score (r = 0·624, P = 0·003) and serum ALT levels and again with periportal necrosis. The strong correlation between the proportion of peripheral CD3+CD56− conventional T lymphocytes and the severity of hepatic lesions leads us to propose that evaluation of this accessible peripheral population could be used as an indicator test for the severity of histological lesions in chronic hepatitis C. Abbreviations: PMID:12452844

  7. [Histology of gill, liver and kidney in juvenile fish Colossoma macropomum exposed to three temperatures].

    PubMed

    Rojas, Luz-Marina; Mata, Claunis; Oliveros, Aridays; Salazar-Lugo, Raquel

    2013-06-01

    Abstract: Histology of gill, liver and kidney in juvenile fish Colossoma macropomum exposed to three temperatures. Water temperature is an important factor that affects growth and antioxidant enzyme activities in fish, and when adverse, it may trigger diseases in fish populations. C. macropomum is a freshwater neotropical fish widely distributed in South America and abundant in river basins as the Amazon and Orinoco. It is highly used for intensive aquaculture development and is a very important product for the local riverside economy in Venezuela. The purpose of our study was to examine the water temperature effect on gills, liver and kidneys of juvenile fishes of C macropomum. Eighteen juveniles with biometrical index of 17.87 +/- 7.88 cm and 87.69 +/- 34.23 g were respectively exposed to three culture temperatures (T18, T29 and T35 degrees C) during a period of 21 days. Histological analyses on gills, liver and kidney were made according to standard methodologies. Our results showed that these tissues exhibited normal citoarchitecture at T29. On the contrary, T18-gills displayed brachiallipid droplets inside brachial epithelium; and disorganization in the brachial tissue was observed at T35. Furthermore, we observed two kinds of hepatocytes (dark and light) on T180 degrees C-liver. The T35-liver samples showed cytoplasmatic granulation and damages in cytoplasmatic membrane. Kidney samples from T18 observed alterations in the cellular distribution of the hematopoietic tissue; while, at T35, the most important feature observed was the disorganization of the glomerular structure. We concluded that T18 and T35 are respectively critical and severe temperatures to C. macropomum; besides, the most sensible tissues to changes induced by temperature in this species were the liver and gills.

  8. Influence of type 2 diabetes mellitus on liver histology among morbidly obese individuals. A cross-sectional study.

    PubMed

    Cazzo, Everton; Jimenez, Laísa Simakawa; Gallo, Fábio de Felice; Pareja, José Carlos; Chaim, Elinton Adami

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) has become a public health concern. It encompasses a wide spectrum of histological abnormalities and has close relationships with insulin resistance and type 2 diabetes mellitus (T2DM). This study sought to compare the histological alterations observed in morbidly obese individuals with and without T2DM who underwent Roux-en-Y gastric bypass. Cross-sectional study in a tertiary-level public hospital. This was a cross-sectional study on 197 individuals who underwent gastric bypass surgery between 2011 and 2013. NAFLD was assessed through liver biopsies. T2DM was diagnosed through the International Diabetes Federation criteria. Non-diabetics presented significantly more biopsies without any histological abnormalities, regarding steatosis (42.6% versus 25.5%; P = 0.0400), fibrosis (60.6% versus 36.2%; P = 0.0042) and steatohepatitis (27.3% versus 12.8%; P = 0.0495), while diabetics presented significantly higher frequency of moderate forms of steatosis (36.2% versus 20%; P = 0.0307) and fibrosis (23.4% versus 4%; P = 0.0002). T2DM was associated with more advanced forms of NAFLD within the population studied. NAFLD has previously been correlated with severe forms of heart disease. Screening for and early detecting of NAFLD in high-risk populations are important for avoiding further development of severe forms and the need for liver transplantation.

  9. Liver fat deposition and mitochondrial dysfunction in morbid obesity: An approach combining metabolomics with liver imaging and histology.

    PubMed

    Calvo, Nahum; Beltrán-Debón, Raúl; Rodríguez-Gallego, Esther; Hernández-Aguilera, Anna; Guirro, Maria; Mariné-Casadó, Roger; Millá, Lidón; Alegret, Josep M; Sabench, Fàtima; del Castillo, Daniel; Vinaixa, María; Rodríguez, Miguel Àngel; Correig, Xavier; García-Álvarez, Roberto; Menendez, Javier A; Camps, Jordi; Joven, Jorge

    2015-06-28

    To explore the usefulness of magnetic resonance imaging (MRI) and spectroscopy (MRS) for assessment of non-alcoholic fat liver disease (NAFLD) as compared with liver histological and metabolomics findings. Patients undergoing bariatric surgery following procedures involved in laparoscopic sleeve gastrectomy were recruited as a model of obesity-induced NAFLD in an observational, prospective, single-site, cross-sectional study with a pre-set duration of 1 year. Relevant data were obtained prospectively and surrogates for inflammation, oxidative stress and lipid and glucose metabolism were obtained through standard laboratory measurements. To provide reliable data from MRI and MRS, novel procedures were designed to limit sampling variability and other sources of error using a 1.5T Signa HDx scanner and protocols acquired from the 3D or 2D Fat SAT FIESTA prescription manager. We used our previously described (1)H NMR-based metabolomics assays. Data were obtained immediately before surgery and after a 12-mo period including histology of the liver and measurement of metabolites. Values from (1)H NMR spectra obtained after surgery were omitted due to technical limitations. MRI data showed excellent correlation with the concentration of liver triglycerides, other hepatic lipid components and the histological assessment, which excluded the presence of non-alcoholic steatohepatitis (NASH). MRI was sufficient to follow up NAFLD in obese patients undergoing bariatric surgery and data suggest usefulness in other clinical situations. The information provided by MRS replicated that obtained by MRI using the -CH3 peak (0.9 ppm), the -CH2- peak (1.3 ppm, mostly triglyceride) and the -CH=CH- peak (2.2 ppm). No patient depicted NASH. After surgery all patients significantly decreased their body weight and steatosis was virtually absent even in patients with previous severe disease. Improvement was also observed in the serum concentrations of selected variables. The most relevant

  10. Effect of Aqueous Extract of Psidium Guajava Leaves on Liver Enzymes, Histological Integrity and Hematological Indices in Rats

    PubMed Central

    Uboh, Friday E.; Okon, Iniobong E.; Ekong, Moses B.

    2010-01-01

    Background Serum alanine aminotransferase (ALT), aspartate aminotransferase(AST), alkaline phosphatase (ALP), albumin and total protein levels, as well as the tissue histological assay are known to be useful in assessing the functional integrity of the liver. Also, assessment of red and white blood cells count, hematocrit and hemoglobin concentrations is useful in determining the effect of some chemical substances on hemotopoietic system. In recent times, reports from medicinal plants research indicate that extracts from some plants are both hepatotoxic and hematotoxic, while others on the other hand are reported to be hepatoprotective and hematopoietic in action. This study considers the effects of aqueous extract of Psidium guajava (P. guajava) leaves on the histology and biochemical indices of liver function as well as hematological indices in rats. Methods In this study, phytochemical screening of the aqueous extract of P. guajava leaves was carried out. Also, male and female rats were administered with 200 mg/kg body weight oral daily doses of aqueous extract of P. guajava leaves for a period of 30 days. At the end of the administration period, the rats were anaesthesized with chloroform vapors and dissected for the collection of blood and liver tissues which were used for the hematopoietic and liver functions investigations. Results Preliminary phytochemical analysis of the plant leaves showed the presence of alkaloids, flavonoids, glycosides, polyphenols, reducing compounds, saponins and tannins. Liver function tests revealed that the serum ALT, AST and ALP, as well as the concentrations of total protein and albumin in male and female rats were not significantly (P > 0.05) affected by the oral administration of the extract. Histopathological study also did not show any adverse alteration in the morphological architecture of the liver tissues in both sexes of the animal model. However, red blood cell counts, hemotocrit and hemoglobin concentrations increased

  11. Effect of Aqueous Extract of Psidium Guajava Leaves on Liver Enzymes, Histological Integrity and Hematological Indices in Rats.

    PubMed

    Uboh, Friday E; Okon, Iniobong E; Ekong, Moses B

    2010-02-01

    Serum alanine aminotransferase (ALT), aspartate aminotransferase(AST), alkaline phosphatase (ALP), albumin and total protein levels, as well as the tissue histological assay are known to be useful in assessing the functional integrity of the liver. Also, assessment of red and white blood cells count, hematocrit and hemoglobin concentrations is useful in determining the effect of some chemical substances on hemotopoietic system. In recent times, reports from medicinal plants research indicate that extracts from some plants are both hepatotoxic and hematotoxic, while others on the other hand are reported to be hepatoprotective and hematopoietic in action. This study considers the effects of aqueous extract of Psidium guajava (P. guajava) leaves on the histology and biochemical indices of liver function as well as hematological indices in rats. In this study, phytochemical screening of the aqueous extract of P. guajava leaves was carried out. Also, male and female rats were administered with 200 mg/kg body weight oral daily doses of aqueous extract of P. guajava leaves for a period of 30 days. At the end of the administration period, the rats were anaesthesized with chloroform vapors and dissected for the collection of blood and liver tissues which were used for the hematopoietic and liver functions investigations. Preliminary phytochemical analysis of the plant leaves showed the presence of alkaloids, flavonoids, glycosides, polyphenols, reducing compounds, saponins and tannins. Liver function tests revealed that the serum ALT, AST and ALP, as well as the concentrations of total protein and albumin in male and female rats were not significantly (P > 0.05) affected by the oral administration of the extract. Histopathological study also did not show any adverse alteration in the morphological architecture of the liver tissues in both sexes of the animal model. However, red blood cell counts, hemotocrit and hemoglobin concentrations increased significantly (P < 0.05) on

  12. Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric-Onset Intestinal Failure.

    PubMed

    Korpela, Katri; Mutanen, Annika; Salonen, Anne; Savilahti, Erkki; de Vos, Willem M; Pakarinen, Mikko P

    2017-02-01

    Intestinal failure (IF)-associated liver disease (IFALD) is the major cause of mortality in IF. The link between intestinal microbiota and IFALD is unclear. We compared intestinal microbiota of patients with IF (n = 23) with healthy controls (n = 58) using culture-independent phylogenetic microarray analysis. The microbiota was related to histological liver injury, fecal markers of intestinal inflammation, matrix metalloproteinase 9 and calprotectin, and disease characteristics. Overabundance of Lactobacilli, Proteobacteria, and Actinobacteria was observed in IF, whereas bacteria related to Clostridium clusters III, IV, and XIVa along with overall diversity and richness were reduced. Patients were segregated into 3 subgroups based on dominating bacteria: Clostridium cluster XIVa, Proteobacteria, and bacteria related to Lactobacillus plantarum. In addition to liver steatosis and fibrosis, Proteobacteria were associated with prolonged current parenteral nutrition (PN) as well as liver and intestinal inflammation. Lactobacilli were related to advanced steatosis and fibrosis mostly after weaning off PN without associated inflammation. In multivariate permutational analysis of variance, liver steatosis, bowel length, PN calories, and antibiotic treatment best explained the microbiota variation among patients with IF. Intestinal microbiota composition was associated with liver steatosis in IF and better predicted steatosis than duration of PN or length of the remaining intestine. Our results may be explained by a model in which steatosis is initiated during PN in response to proinflammatory lipopolysaccharides produced by Proteobacteria and progresses after weaning off PN, as the L plantarum group Lactobacilli becomes dominant and affects lipid metabolism by altering bile acid signaling.

  13. B cell-activating factor is associated with the histological severity of nonalcoholic fatty liver disease.

    PubMed

    Miyake, Teruki; Abe, Masanori; Tokumoto, Yoshio; Hirooka, Masashi; Furukawa, Shinya; Kumagi, Teru; Hamada, Maho; Kawasaki, Keitarou; Tada, Fujimasa; Ueda, Teruhisa; Hiasa, Yoichi; Matsuura, Bunzo; Onji, Morikazu

    2013-06-01

    B cell-activating factor (BAFF) is expressed in adipocytes and affects lipogenesis and insulin sensitivity. In addition, the BAFF receptor is expressed in visceral adipose tissue and liver. The aim of this study was to analyze serum BAFF levels in patients with nonalcoholic steatohepatitis (NASH) and simple steatosis (SS) and to compare their respective clinical and histological findings. A total of 96 patients with nonalcoholic fatty liver disease (20 with SS and 76 with NASH) were enrolled and their serum BAFF levels were analyzed. Comprehensive blood chemistry analysis and histological examination of liver samples were also conducted. Serum BAFF levels were higher in patients with NASH than in those with SS (p = 0.016). NASH patients with ballooning hepatocytes and advanced fibrosis had higher levels of BAFF in sera (p = 0.016 and p = 0.006, respectively). In addition, the prevalence of NASH increased significantly as the serum BAFF level increased (p = 0.004). Higher serum BAFF levels were found to be an independent risk factor for development of NASH (OR 1.003, 95% CI 1.0003-1.006; p = 0.047). Nonalcoholic steatohepatitis patients had higher levels of serum BAFF than patients with SS, and higher levels were associated with the presence of hepatocyte ballooning and advanced fibrosis. The serum BAFF level may be a useful tool for distinguishing NASH from SS.

  14. Watchful waiting with periodic liver biopsy versus immediate empirical therapy for histologically mild chronic hepatitis C. A cost-effectiveness analysis.

    PubMed

    Wong, J B; Koff, R S

    2000-11-07

    Not all patients with histologically mild chronic hepatitis C progress to cirrhosis. To compare no antiviral treatment, periodic liver biopsy with subsequent antiviral treatment for moderate hepatitis or cirrhosis, and immediate antiviral therapy. Cost-effectiveness analysis. Clinical trial data and published studies. Hepatitis C virus-infected patients with histologically mild hepatitis. Lifetime. Societal. Immediate combination antiviral treatment or biopsy every 3 years plus combination antiviral therapy for moderate hepatitis or cirrhosis. Life expectancy, quality-adjusted life expectancy, and costs. Over 20 years, biopsy every 3 years with treatment of moderate hepatitis would avoid treatment in 50% of the cohort and would result in an 18% likelihood of cirrhosis compared with 16% for immediate treatment and 27% for no antiviral therapy. Immediate antiviral treatment should increase life expectancy by 1.0 quality-adjusted life-year compared with biopsy management. Over an average lifetime, biopsy management would lead to six liver biopsies costing $6200; immediate antiviral treatment would cost $5100 less than biopsy management because of savings related to biopsy and prevention of future hepatitis C-related morbidity. Immediate therapy was cost-effective compared with biopsy management and had a cost-effectiveness ratio of $7000 compared with no antiviral therapy. When age, sex, genotype, and estimates of histologic progression or compliance with follow-up are varied, immediate therapy should result in an increase of at least 0. 8 quality-adjusted life-year compared with biopsy management. For histologically mild chronic hepatitis C, initial combination treatment compared with periodic liver biopsy should reduce the future risk for cirrhosis, prolong life, and be cost-effective.

  15. Interferon-free regimens improve portal hypertension and histological necroinflammation in HIV/HCV patients with advanced liver disease.

    PubMed

    Schwabl, P; Mandorfer, M; Steiner, S; Scheiner, B; Chromy, D; Herac, M; Bucsics, T; Hayden, H; Grabmeier-Pfistershammer, K; Ferlitsch, A; Oberhuber, G; Trauner, M; Peck-Radosavljevic, M; Reiberger, T

    2017-01-01

    HIV/HCV co-infected patients show accelerated fibrosis progression and higher risk for complications of portal hypertension (PHT). To assess the effects of interferon-free therapy on portal pressure, liver histology and plasma biomarkers in HIV/HCV-coinfected patients with PHT. Twenty-two patients with paired hepatic venous pressure gradient (HVPG) measurements prior and after successful treatment (SVR) with interferon-free regimens were included. Liver stiffness was assessed by transient elastography and biopsies were scored according to METAVIR. Plasma biomarkers were determined by ELISA. Overall, HVPG decreased from 10.7 ± 4.1 mmHg at baseline to 7.4 ± 4.2 mmHg after HCV treatment (Δ:-3.3 ± 2.7 mmHg; p < 0.001). In patients with clinically significant PHT (HVPG≥10 mmHg, n = 11), HVPG decreased from 14.1 ± 2.9 to 10.4 ± 3.9 mmHg (Δ:-3.7 ± 3.3 mmHg; p = 0.004) and a haemodynamic response (HVPG decrease ≥10%) was observed in 73%. In 64% of patients with subclinical PHT (HVPG 6-9 mmHg, n = 11), portal pressure normalised at SVR. Mean liver stiffness decreased from 20.8 kPa to 11.5 kPa (Δ:-8.8 ± 7.4 kPa; p < 0.001). Fifty percent (7/14) of patients with cirrhosis were re-classified as METAVIR ≤F3 and all patients with decompensated cirrhosis improved their Child-Pugh stage. After successful HCV treatment, 39% still had persistent histological necroinflammatory activity (METAVIR A1), which correlated with less HVPG response and more steatosis. While most biomarkers improved with SVR, METAVIR A1 patients had significantly higher plasma levels of fibrogenic (PDGF, TGF-β) and angiogenic (VEGF, Angiopoietin1) biomarkers. Interferon-free therapy reduces PHT and halts histological necroinflammatory activity in the majority of HIV/HCV-coinfected patients after SVR, which may lead to re-compensation of liver function in cirrhosis. Biomarkers could identify patients with persisting hepatic necroinflammation. © 2016 John Wiley & Sons Ltd.

  16. Long-term Effects on the Histology and Function of Livers and Spleens in Rats after 33% Toploading of PEG-PLA-nano Artificial Red Blood Cells

    PubMed Central

    Liu, Zun Chang; Chang, Thomas M.S.

    2012-01-01

    This study is to investigate the long-term effects of nanodimension PEG-PLA artificial red blood cells containing hemoglobin and red blood cell enzymes on the liver and spleen after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: Nano artificial red blood cells in Ringer lactate, Ringer lactate, stroma-free hemoglobin, polyhemoglobin, and autologous rat whole blood. Blood samples were taken before infusions and on days 1, 7, and 21 after infusions for analysis. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not have any significant adverse effects on alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine kinase, amylase and creatine kinase. On the other hand, stroma-free hemoglobin induced significant adverse effects on liver as shown by elevation in alanine aminotransferase and aspartate aminotransferase throughout the 21 days. On day 21 after infusions rats were sacrificed and livers and spleens were excised for histological examination. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not cause any abnormalities in the microscopic histology of the livers and spleens. In the stroma-free hemoglobin group the livers showed accumulation of hemoglobin in central veins and sinusoids, and hepatic steatosis. In conclusion, injected nano artificial red blood cells can be efficiently metabolized and removed by the reticuloendothelial system, and do not have any biochemical or histological adverse effects on the livers or the spleens. PMID:19043818

  17. Transcriptomics, metabolomics and histology indicate that high-carbohydrate diet negatively affects the liver health of blunt snout bream (Megalobrama amblycephala).

    PubMed

    Prisingkorn, Wassana; Prathomya, Panita; Jakovlić, Ivan; Liu, Han; Zhao, Yu-Hua; Wang, Wei-Min

    2017-11-09

    Global trend of the introduction of high levels of relatively cheap carbohydrates to reduce the amount of costly protein in the aquatic animal feed production has affected the aquaculture of an economically important cyprinid fish, blunt snout bream (Megalobrama amblycephala). This dietary shift has resulted in increased prevalence of metabolic disorders, often causing economic losses. High dietary intake of carbohydrates, associated with obesity, is one of the major causes of non-alcoholic fatty liver disease (NAFLD) in humans. We have conducted an eight-week feeding trial to better understand how a high-carbohydrate diet (HCBD) affects the liver health in this fish. Hepatosomatic index and lipid content were significantly (P < 0.05) higher in the HCBD group. Histology results also suggested pathological changes in the livers of HCBD group, with excessive lipid accumulation and indication of liver damage. Metabolomics and serum biochemistry analyses showed that a number of metabolites indicative of liver damage were increased in the HCBD group. This group also exhibited low levels of betaine, which is a metabolite crucial for maintaining the healthy liver functions. Transcriptomic and qPCR analyses indicated that HCBD had a strong impact on the expression of a large number of genes associated with the NAFLD and insulin signalling pathways, which may lead to the development of insulin resistance in hepatocytes, pathological liver changes, and eventually the NAFLD. Transcriptomics, metabolomics and histology results all indicate early symptoms of liver damage. However whether these would actually lead to the development of NAFLD after a longer period of time, remains inconclusive. Additionally, a very high number of upregulated genes in the HCBD group associated with several neurodegenerative diseases is a strong indication of neurodegenerative changes caused by the high-carbohydrate diet in blunt snout bream. This suggests that fish might present a good model to

  18. Clinical significance of liver histology on outcomes in biliary atresia.

    PubMed

    Webb, Nicholas L; Jiwane, Ashish; Ooi, Chee Y; Nightinghale, Scott; Adams, Susan E; Krishnan, Usha

    2017-03-01

    Biliary atresia (BA) literature has focussed on the relationship between age at Kasai procedure (KP) and post-KP outcomes. This study primarily examines post-KP outcomes including, 6-month normalisation of bilirubin, 5-year native liver survival (NLS), development of portal hypertension (PHT) and incidence of ascending cholangitis at a single tertiary paediatric centre in Australia. The study also evaluated prognostic factors which may influence these aforementioned outcomes. Retrospective chart review of all BA cases between 1999 and 2014. Age at KP, liver biopsy results, use of ursodeoxycholic acid or prophylactic antibiotics and occurrence of PHT and ascending cholangitis post-KP were recorded and related to the primary post-KP outcome measures. BA was diagnosed in 29 patients. Twenty-four of 29 patients underwent KP. Median age at KP was 68 days (29-104). Fourteen of 24 (58.3%) had bridging fibrosis and 5 of 24 (20.8%) had cirrhosis at time of KP. Median follow-up was 8.4 years (2.08-15.58 years). Bilirubin normalisation within 6 months occurred in 7 of 24 (29.2%) patients and 5-year NLS was 45.8% (11/24). Fourteen of 24 (58.3%) had PHT and 18 of 24 (75%) patients had ascending cholangitis post-KP. Absence of bridging fibrosis in liver histology at KP was the only factor to be significantly associated with improved 5-year NLS. None of the other variables examined had a significant association with either 5-year NLS or bilirubin normalisation by 6 months. Five-year NLS in this series was 45.8%. Absence of bridging fibrosis at time of KP was the only factor significantly associated with improved 5-year NLS. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  19. A primary tumor of mixed histological type is a novel poor prognostic factor for patients undergoing resection of liver metastasis from gastric cancer.

    PubMed

    Ikari, Naoki; Taniguchi, Kiyoaki; Serizawa, Akiko; Yamada, Takuji; Yamamoto, Masakazu; Furukawa, Toru

    2017-05-01

    Surgical resection can be an option for the treatment of metastatic liver tumors originating from gastric cancer; however, its prognostic impact is controversial. The aim of this study was to identify prognostic factors in patients with surgical resection of liver metastasis from gastric cancer. We retrospectively analyzed the clinicopathological features of 38 consecutive patients undergoing hepatectomy for metastatic tumors from gastric cancer in our institution between 1990 and 2014. The median overall survival of the patients was 28 months. The 5-year survival rate was 33.9%. Primary tumors of a mixed histological type, and residual tumors during the course of treatment were identified as significant independent poor prognostic factors. Histological evaluation of primary tumors may aid to identify patients suitable for undergoing surgical resection of liver metastasis from gastric cancer. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  20. MR diffusion histology and micro-tractography reveal mesoscale features of the human cerebellum.

    PubMed

    Dell'Acqua, Flavio; Bodi, Istvan; Slater, David; Catani, Marco; Modo, Michel

    2013-12-01

    After 140 years from the discovery of Golgi's black reaction, the study of connectivity of the cerebellum remains a fascinating yet challenging task. Current histological techniques provide powerful methods for unravelling local axonal architecture, but the relatively low volume of data that can be acquired in a reasonable amount of time limits their application to small samples. State-of-the-art in vivo magnetic resonance imaging (MRI) methods, such as diffusion tractography techniques, can reveal trajectories of the major white matter pathways, but their correspondence with underlying anatomy is yet to be established. Hence, a significant gap exists between these two approaches as neither of them can adequately describe the three-dimensional complexity of fibre architecture at the level of the mesoscale (from a few millimetres to micrometres). In this study, we report the application of MR diffusion histology and micro-tractography methods to reveal the combined cytoarchitectural organisation and connectivity of the human cerebellum at a resolution of 100-μm (2 nl/voxel volume). Results show that the diffusion characteristics for each layer of the cerebellar cortex correctly reflect the known cellular composition and its architectural pattern. Micro-tractography also reveals details of the axonal connectivity of individual cerebellar folia and the intra-cortical organisation of the different cerebellar layers. The direct correspondence between MR diffusion histology and micro-tractography with immunohistochemistry indicates that these approaches have the potential to complement traditional histology techniques by providing a non-destructive, quantitative and three-dimensional description of the microstructural organisation of the healthy and pathological tissue.

  1. Digital histology quantification of intra-hepatic fat in patients undergoing liver resection.

    PubMed

    Parkin, E; O'Reilly, D A; Plumb, A A; Manoharan, P; Rao, M; Coe, P; Frystyk, J; Ammori, B; de Liguori Carino, N; Deshpande, R; Sherlock, D J; Renehan, A G

    2015-08-01

    High intra-hepatic fat (IHF) content is associated with insulin resistance, visceral adiposity, and increased morbidity and mortality following liver resection. However, in clinical practice, IHF is assessed indirectly by pre-operative imaging [for example, chemical-shift magnetic resonance (CS-MR)]. We used the opportunity in patients undergoing liver resection to quantify IHF by digital histology (D-IHF) and relate this to CT-derived anthropometrics, insulin-related serum biomarkers, and IHF estimated by CS-MR. A reproducible method for quantification of D-IHF using 7 histology slides (inter- and intra-rater concordance: 0.97 and 0.98) was developed. In 35 patients undergoing resection for colorectal cancer metastases, we measured: CT-derived subcutaneous and visceral adipose tissue volumes, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), fasting serum adiponectin, leptin and fetuin-A. We estimated relative IHF using CS-MR and developed prediction models for IHF using a factor-clustered approach. The multivariate linear regression models showed that D-IHF was best predicted by HOMA-IR (Beta coefficient(per doubling): 2.410, 95% CI: 1.093, 5.313) and adiponectin (β(per doubling): 0.197, 95% CI: 0.058, 0.667), but not by anthropometrics. MR-derived IHF correlated with D-IHF (rho: 0.626; p = 0.0001), but levels of agreement deviated in upper range values (CS-MR over-estimated IHF: regression versus zero, p = 0.009); this could be adjusted for by a correction factor (CF: 0.7816). Our findings show IHF is associated with measures of insulin resistance, but not measures of visceral adiposity. CS-MR over-estimated IHF in the upper range. Larger studies are indicated to test whether a correction of imaging-derived IHF estimates is valid. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Subcellular distribution of trace elements and liver histology of landlocked Arctic char (Salvelinus alpinus) sampled along a mercury contamination gradient.

    PubMed

    Barst, Benjamin D; Rosabal, Maikel; Campbell, Peter G C; Muir, Derek G C; Wang, Xioawa; Köck, Günter; Drevnick, Paul E

    2016-05-01

    We sampled landlocked Arctic char (Salvelinus alpinus) from four lakes (Small, 9-Mile, North, Amituk) in the Canadian High Arctic that span a gradient of mercury contamination. Metals (Hg, Se, Tl, and Fe) were measured in char tissues to determine their relationships with health indices (relative condition factor and hepatosomatic index), stable nitrogen isotope ratios, and liver histology. A subcellular partitioning procedure was employed to determine how metals were distributed between potentially sensitive and detoxified compartments of Arctic char livers from a low- and high-mercury lake (Small Lake and Amituk Lake, respectively). Differences in health indices and metal concentrations among char populations were likely related to differences in feeding ecology. Concentrations of Hg, Se, and Tl were highest in the livers of Amituk char, whereas concentrations of Fe were highest in Small and 9-Mile char. At the subcellular level we found that although Amituk char had higher concentrations of Tl in whole liver than Small Lake char, they maintained a greater proportion of this metal in detoxified fractions, suggesting an attempt at detoxification. Mercury was found mainly in potentially sensitive fractions of both Small and Amituk Lake char, indicating that Arctic char are not effectively detoxifying this metal. Histological changes in char livers, mainly in the form of melano-macrophage aggregates and hepatic fibrosis, could be linked to the concentrations and subcellular distributions of essential or non-essential metals. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Diffusion-weighted and T2-weighted MR imaging for colorectal liver metastases detection in a rat model at 7 T: a comparative study using histological examination as reference.

    PubMed

    Wagner, Mathilde; Maggiori, Léon; Ronot, Maxime; Paradis, Valérie; Vilgrain, Valérie; Panis, Yves; Van Beers, Bernard E

    2013-08-01

    To compare diffusion-weighted (DW) and T2-weighted MR imaging in detecting colorectal liver metastases in a rat model, using histological examination as a reference method. Eighteen rats had four liver injections of colon cancer cells. MR examinations at 7 T included FSE-T2-weighted imaging and SE-DW MR imaging (b = 0, 20 and 150 s/mm(2)) and were analysed by two independent readers. Histological examination was performed on 0.4-mm slices. McNemar's test was used to compare the sensitivities and the Wilcoxon matched pairs test to compare the average number of false-positives per rat. One hundred and sixty-six liver metastases were identified on histological examination. The sensitivity in detecting liver metastases was significantly higher on DW MR than on T2-weighted images (99/166 (60 %) (reader 1) and 92/166 (55 %) (reader 2) versus 77/166 (46 %), P ≤ 0.001), without an increase in false-positives per rat (P = 0.773/P = 0.850). After stratification according to metastasis diameter, DW MR imaging had a significantly higher sensitivity than T2-weighted imaging only for metastases with a diameter (0.6-1.2 mm) similar to that of the spatial resolution of MR imaging in the current study. This MR study with histological correlations shows the higher sensitivity of DW relative to T2-weighted imaging at 7 T for detecting liver metastases, especially small ones. • Diffusion weighted (DW) sequences are increasingly used in magnetic resonance imaging (MRI). • DW has higher sensitivity for liver metastases than T2-weighted imaging at 7 T. • This increase in sensitivity is especially marked for small liver metastasis detection. • This higher sensitivity is confirmed in an animal model with histological correlation. • DW imaging has the potential for earlier diagnosis of small liver metastases.

  4. Stereological Analysis of Liver Biopsy Histology Sections as a Reference Standard for Validating Non-Invasive Liver Fat Fraction Measurements by MRI

    PubMed Central

    St. Pierre, Tim G.; House, Michael J.; Bangma, Sander J.; Pang, Wenjie; Bathgate, Andrew; Gan, Eng K.; Ayonrinde, Oyekoya T.; Bhathal, Prithi S.; Clouston, Andrew; Olynyk, John K.; Adams, Leon A.

    2016-01-01

    Background and Aims Validation of non-invasive methods of liver fat quantification requires a reference standard. However, using standard histopathology assessment of liver biopsies is problematical because of poor repeatability. We aimed to assess a stereological method of measuring volumetric liver fat fraction (VLFF) in liver biopsies and to use the method to validate a magnetic resonance imaging method for measurement of VLFF. Methods VLFFs were measured in 59 subjects (1) by three independent analysts using a stereological point counting technique combined with the Delesse principle on liver biopsy histological sections and (2) by three independent analysts using the HepaFat-Scan® technique on magnetic resonance images of the liver. Bland Altman statistics and intraclass correlation (IC) were used to assess the repeatability of each method and the bias between the methods of liver fat fraction measurement. Results Inter-analyst repeatability coefficients for the stereology and HepaFat-Scan® methods were 8.2 (95% CI 7.7–8.8)% and 2.4 (95% CI 2.2–2.5)% VLFF respectively. IC coefficients were 0.86 (95% CI 0.69–0.93) and 0.990 (95% CI 0.985–0.994) respectively. Small biases (≤3.4%) were observable between two pairs of analysts using stereology while no significant biases were observable between any of the three pairs of analysts using HepaFat-Scan®. A bias of 1.4±0.5% VLFF was observed between the HepaFat-Scan® method and the stereological method. Conclusions Repeatability of the stereological method is superior to the previously reported performance of assessment of hepatic steatosis by histopathologists and is a suitable reference standard for validating non-invasive methods of measurement of VLFF. PMID:27501242

  5. Quantitative intrahepatic HBV cccDNA correlates with histological liver inflammation in chronic hepatitis B virus infection.

    PubMed

    Liang, Ling-Bo; Zhu, Xia; Yan, Li-Bo; Du, Ling-Yao; Liu, Cong; Liao, Juan; Tang, Hong

    2016-11-01

    The aim of this study was to determine the role of baseline hepatitis B virus (HBV) forming covalently closed circular DNA (HBV cccDNA) in liver inflammation in patients infected with HBV with serum alanine aminotransferase (ALT) levels under two times the upper limit of normal (2×ULN). After liver biopsy and serum virological and biochemical marker screening, patients diagnosed with chronic HBV infection with serum ALT levels under 2×ULN and histological liver inflammation of less than grade G2 were prospectively recruited into this study. Recruitment took place between March 2009 and November 2010 at the Center of Infectious Disease, Sichuan University. Patient virological and biochemical markers, as well as markers of liver inflammation, were monitored. A total of 102 patients were recruited and 68 met the inclusion criteria; the median follow-up was 4.1 years (range 3.9-5.2 years). During follow-up, 41 patients (60.3%) exhibited signs of inflammation. Baseline HBV cccDNA >1 copy/cell (odds ratio 9.43, p=0.049) and liver inflammation grade ≥G1 (odds ratio 5.77, p=0.046) were both independent predictors of liver inflammation. A higher baseline intrahepatic HBV cccDNA level may increase the risk of liver inflammation. Further investigations will be required to validate HBV cccDNA as an intrahepatic virological marker of patients who require extended outpatient management. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Clinico-biochemical correlation to histological findings in alcoholic liver disease: a single centre study from eastern India.

    PubMed

    Ray, Sayantan; Khanra, Dibbendhu; Sonthalia, Nikhil; Kundu, Supratip; Biswas, Kaushik; Talukdar, Arunansu; Saha, Manjari; Bera, Himel

    2014-10-01

    Alcoholism is a health problem not only in developed countries but also in developing countries. Cirrhosis due to alcohol is a common cause of death among individuals abusing alcohol. A better knowledge of the spectrum of alcoholic liver diseases, its clinical, biochemical and histopathological features could result in early detection and prevention of alcoholic liver diseases before it's catastrophic and life threatening effects. A total of 200 patients with alcoholic liver diseases were studied with respect to alcohol consumption, clinical features, biochemical and histopathological changes. The clinical features, biochemical parameters, and histopathology of liver including Ishak's modified histological activity index (HAI) were correlated with the amount and duration of alcohol consumed. Majority of the patients were in the age group of 40-49 years and all the cases were males. Majority consumed alcohol of about 75-90 grams per day for a duration of 10-12 years. Anorexia and jaundice were the most common symptom and clinical finding respectively. Hyperbilirubinemia and hypoalbuminemia were the most common abnormalities observed in liver function tests. Advanced HAI stages with features of cirrhosis were most frequent histo-pathological finding noted in this study. Clinico-biochemical profile was significantly correlated with degree of alcohol ingestion as well as with liver histopathology. The wide prevalence of alcoholic liver disease including cirrhosis among Indian males was noted with significantly lower quantity and duration of alcohol ingestion. The severity of liver damage is directly proportional to the quantity and duration of alcohol consumed. Clinical features and biochemical changes may forecast the liver histopathology among the patients of alcoholic liver disease.

  7. Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease.

    PubMed

    Kowdley, Kris V; Belt, Patricia; Wilson, Laura A; Yeh, Matthew M; Neuschwander-Tetri, Brent A; Chalasani, Naga; Sanyal, Arun J; Nelson, James E

    2012-01-01

    Serum ferritin (SF) levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) because of systemic inflammation, increased iron stores, or both. The aim of this study was to examine the relationship between elevated SF and NAFLD severity. Demographic, clinical, histologic, laboratory, and anthropometric data were analyzed in 628 adult patients with NAFLD (age, ≥ 18 years) with biopsy-proven NAFLD and an SF measurement within 6 months of their liver biopsy. A threshold SF >1.5 × upper limit of normal (ULN) (i.e., >300 ng/mL in women and >450 ng/mL in men) was significantly associated with male sex, elevated serum alanine aminotransferase, aspartate aminotransferase, iron, transferrin-iron saturation, iron stain grade, and decreased platelets (P < 0.01). Histologic features of NAFLD were more severe among patients with SF >1.5 × ULN, including steatosis, fibrosis, hepatocellular ballooning, and diagnosis of NASH (P < 0.026). On multiple regression analysis, SF >1.5 × ULN was independently associated with advanced hepatic fibrosis (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.05-2.62; P = 0.028) and increased NAFLD Activity Score (NAS) (OR, 1.99; 95% CI, 1.06-3.75; P = 0.033). A SF >1.5 × ULN is associated with hepatic iron deposition, a diagnosis of NASH, and worsened histologic activity and is an independent predictor of advanced hepatic fibrosis among patients with NAFLD. Furthermore, elevated SF is independently associated with higher NAS, even among patients without hepatic iron deposition. We conclude that SF is useful to identify NAFLD patients at risk for NASH and advanced fibrosis. Copyright © 2011 American Association for the Study of Liver Diseases.

  8. Automated image analysis method for detecting and quantifying macrovesicular steatosis in hematoxylin and eosin-stained histology images of human livers.

    PubMed

    Nativ, Nir I; Chen, Alvin I; Yarmush, Gabriel; Henry, Scot D; Lefkowitch, Jay H; Klein, Kenneth M; Maguire, Timothy J; Schloss, Rene; Guarrera, James V; Berthiaume, Francois; Yarmush, Martin L

    2014-02-01

    Large-droplet macrovesicular steatosis (ld-MaS) in more than 30% of liver graft hepatocytes is a major risk factor for liver transplantation. An accurate assessment of the ld-MaS percentage is crucial for determining liver graft transplantability, which is currently based on pathologists' evaluations of hematoxylin and eosin (H&E)-stained liver histology specimens, with the predominant criteria being the relative size of the lipid droplets (LDs) and their propensity to displace a hepatocyte's nucleus to the cell periphery. Automated image analysis systems aimed at objectively and reproducibly quantifying ld-MaS do not accurately differentiate large LDs from small-droplet macrovesicular steatosis and do not take into account LD-mediated nuclear displacement; this leads to a poor correlation with pathologists' assessments. Here we present an improved image analysis method that incorporates nuclear displacement as a key image feature for segmenting and classifying ld-MaS from H&E-stained liver histology slides. 52,000 LDs in 54 digital images from 9 patients were analyzed, and the performance of the proposed method was compared against the performance of current image analysis methods and the ld-MaS percentage evaluations of 2 trained pathologists from different centers. We show that combining nuclear displacement and LD size information significantly improves the separation between large and small macrovesicular LDs (specificity = 93.7%, sensitivity = 99.3%) and the correlation with pathologists' ld-MaS percentage assessments (linear regression coefficient of determination = 0.97). This performance vastly exceeds that of other automated image analyzers, which typically underestimate or overestimate pathologists' ld-MaS scores. This work demonstrates the potential of automated ld-MaS analysis in monitoring the steatotic state of livers. The image analysis principles demonstrated here may help to standardize ld-MaS scores among centers and ultimately help

  9. Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach.

    PubMed

    Alkafafy, Mohamed El-Sayed; Ibrahim, Zein Shaban; Ahmed, Mohamed Mohamed; El-Shazly, Samir Ahmed

    2015-06-01

    The current work was undertaken to settle the debate about the toxicity of artificial sweeteners (AS), particularly aspartame and saccharin. Twenty-five, 7-week-old male Wistar albino rats with an average body weight of 101 ± 4.8 g were divided into a control group and four experimental groups (n = 5 rats). The first and second experimental groups received daily doses equivalent to the acceptable daily intake (ADI) of aspartame (250 mg/Kg BW) and four-fold ADI of aspartame (1000 mg/Kg BW). The third and fourth experimental groups received daily doses equivalent to ADI of saccharin (25 mg/Kg BW) and four-fold ADI of saccharin (100 mg/Kg BW). The experimental groups received the corresponding sweetener dissolved in water by oral route for 8 weeks. The activities of enzymes relevant to liver functions and antioxidants were measured in the blood plasma. Histological studies were used for the evaluation of the changes in the hepatic tissues. The gene expression levels of the key oncogene (h-Ras) and the tumor suppressor gene (P27) were also evaluated. In addition to a significant reduction in the body weight, the AS-treated groups displayed elevated enzymes activities, lowered antioxidants values, and histological changes reflecting the hepatotoxic effect of aspartame and saccharin. Moreover, the overexpression of the key oncogene (h-Ras) and the downregulation of the tumor suppressor gene (P27) in all treated rat groups may indicate a potential risk of liver carcinogenesis, particularly on long-term exposure. © The Author(s) 2015.

  10. Alcoholic Liver Disease: A Mouse Model Reveals Protection by Lactobacillus fermentum

    PubMed Central

    Barone, Rosario; Rappa, Francesca; Macaluso, Filippo; Caruso Bavisotto, Celeste; Sangiorgi, Claudia; Di Paola, Gaia; Tomasello, Giovanni; Di Felice, Valentina; Marcianò, Vito; Farina, Felicia; Zummo, Giovanni; Conway de Macario, Everly; J.L. Macario, Alberto; Cocchi, Massimo; Cappello, MD, Francesco; Marino Gammazza, Antonella

    2016-01-01

    Objectives: Alcoholism is one of the most devastating diseases with high incidence, but knowledge of its pathology and treatment is still plagued with gaps mostly because of the inherent limitations of research with patients. We developed an animal model for studying liver histopathology, Hsp (heat-shock protein)-chaperones involvement, and response to treatment. Methods: The system was standardized using mice to which ethanol was orally administered alone or in combination with Lactobacillus fermentum following a precise schedule over time and applying, at predetermined intervals, a battery of techniques (histology, immunohistochemistry, western blotting, real-time PCR, immunoprecipitation, 3-nitrotyrosine labeling) to assess liver pathology (e.g., steatosis, fibrosis), and Hsp60 and iNOS (inducible form of nitric oxide synthase) gene expression and protein levels, and post-translational modifications. Results: Typical ethanol-induced liver pathology occurred and the effect of the probiotic could be reliably monitored. Steatosis score, iNOS levels, and nitrated proteins (e.g., Hsp60) decreased after probiotic intake. Conclusions: We describe a mouse model useful for studying liver disease induced by chronic ethanol intake and for testing pertinent therapeutic agents, e.g., probiotics. We tested L. fermentum, which reduced considerably ethanol-induced tissue damage and deleterious post-translational modifications of the chaperone Hsp60. The model is available to test other agents and probiotics with therapeutic potential in alcoholic liver disease. PMID:26795070

  11. There were no differences in serum HBV DNA level between HBeAg-positive and HBeAg-negative chronic hepatitis B with same liver histological necroinflammation grade but differences among grades 1, 2, 3 and 4 apportioned by the same hepatic parenchyma cell volume.

    PubMed

    Ke, W-M; Xie, S-B; Li, X-J; Zhang, S-Q; Lai, J; Ye, Y-N; Gao, Z-L; Chen, P-J

    2011-09-01

    Hepatitis B virus (HBV) DNA levels and liver histological necroinflammation grades are correlated with the antiviral efficacy. It is necessary to clarify the relationship between HBV replication levels apportioned by the same hepatic parenchyma cell volume and severity of liver histological necroinflammation grades in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative chronic hepatitis B. The serum HBV DNA levels apportioned by the same hepatic parenchyma cell volume were compared between HBeAg-positive and HBeAg-negative chronic hepatitis B as well as among liver histological necroinflammation grades 1, 2, 3 and 4, respectively. There were no differences in the serum HBV DNA levels between HBeAg-positive and HBeAg-negative chronic hepatitis B as well as among liver histological necroinflammation grades 1, 2, 3 and 4. However, there were differences in the serum HBV DNA levels apportioned by the same hepatic parenchyma cell volume among liver histological necroinflammation grades 1, 2, 3 and 4 in both HBeAg-positive and HBeAg-negative chronic hepatitis B, respectively. There were no differences in HBV DNA levels with the same liver histological necroinflammation grade activated by HBV wild-type and variant strains. After the differences in hepatic parenchyma cell volume for HBV replication of the same liver histological necroinflammation grade accompanied by different hepatic fibrosis stages were adjusted, the serum HBV DNA level apportioned by the same hepatic parenchyma cell volume was correlated with the severity of liver histological necroinflammation grade. © 2011 Blackwell Publishing Ltd.

  12. Mechanisms of fibrosis in acute liver failure.

    PubMed

    He, Yingli; Jin, Li; Wang, Jing; Yan, Zhi; Chen, Tianyan; Zhao, Yingren

    2015-07-01

    Acute liver failure (ALF) is a condition with high mortality and morbidity. Fibrosis in chronic liver disease was extensively researched, whereas fibrosis and underlying mechanism in acute liver failure remains unclear. Hepatitis B virus related ALF patients were recruited to investigate if there was ongoing fibrosis by liver histology and liver stiffness measurement(LSM) analysis as well as fibrosis markers assay. Sera HMGB1 were kinetically detected in progression and remission stage of ALF. Hepatic stellate cell(HSC) activation by HMGB1 was explored by testing mRNA and protein level of α-SMA and collagen 1a1 by using qPCR and western blot. Autophagy induction by HMGB1 was explored by LC3-II conversion, autophagy flux and fluorescence. Firstly, ongoing fibrosis in progression stage of ALF was confirmed by histological analysis, LS measurement as well as fibrosis markers detection. HSC activation and autophagy induction in explanted liver tissue also revealed. Next, kinetic monitoring sera HMGB1 revealed elevated HMGB1 in progression stage of ALF vs HBsAg carrier, and drop back to base level in remission stage. Thirdly, rHMGB1 dose dependently activated HSCs, as indicated by increased mRNA and proteins level in α-SMA and collagen 1a1. Moreover, autophagy was induced in HSC treated with rHMGB1, as illustrated by increased LC3 lipidation, elevated autophagy flux and GFP-LC3 puncta. Acute liver failure is accompanied by ongoing fibrosis, HSC activation and autophagy induction. Increased HMGB1 activates HSC via autophagy induction. Those findings integrate HMGB1, HSCs activation, autophagy into a common framework that underlies the fibrosis in ALF. © 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.

  13. Volumetric laser endomicroscopy in the biliary and pancreatic ducts: a feasibility study with histological correlation.

    PubMed

    Corral, Juan E; Mousa, Omar Y; Krishna, Murli; Levink, Iris J M; Pursell, Khela R; Afsh, Mohammad; Kröner, Paul T; Harnois, Denise M; Wolfsen, Herbert C; Wallace, Michael B; Lukens, Frank J

    2018-06-18

     Volumetric laser endomicroscopy (VLE) provides circumferential images 3 mm into the biliary and pancreatic ducts. We aimed to correlate VLE images with the normal and abnormal microstructure of these ducts. Samples from patients undergoing hepatic or pancreatic resection were evaluated. VLE images were collected using a low-profile VLE catheter inserted manually into the biliary and pancreatic ducts ex vivo. Histological correlation was assessed by two unblinded investigators.  25 patients (20 liver and 5 pancreatic samples) and 111 images were analyzed. VLE revealed three histological layers: epithelium, connective tissue, and parenchyma. It identified distinctive patterns for primary sclerosing cholangitis (PSC), pancreatic cysts, neuroendocrine tumor, and adenocarcinoma adjacent to the pancreatic duct or ampulla. VLE failed to identify dysplasia in a dominant stricture and inflammatory infiltrates in PSC. Reflectivity measurements of the liver parenchyma diagnosed liver cirrhosis with high sensitivity.  VLE can identify histological changes in the biliary and pancreatic ducts allowing real-time diagnosis. Further studies are needed to measure the accuracy of VLE in a larger sample and to validate our findings in vivo. © Georg Thieme Verlag KG Stuttgart · New York.

  14. IGF-1 modulates gene expression of proteins involved in inflammation, cytoskeleton, and liver architecture.

    PubMed

    Lara-Diaz, V J; Castilla-Cortazar, I; Martín-Estal, I; García-Magariño, M; Aguirre, G A; Puche, J E; de la Garza, R G; Morales, L A; Muñoz, U

    2017-05-01

    Even though the liver synthesizes most of circulating IGF-1, it lacks its receptor under physiological conditions. However, according to previous studies, a damaged liver expresses the receptor. For this reason, herein, we examine hepatic histology and expression of genes encoding proteins of the cytoskeleton, extracellular matrix, and cell-cell molecules and inflammation-related proteins. A partial IGF-1 deficiency murine model was used to investigate IGF-1's effects on liver by comparing wild-type controls, heterozygous igf1 +/- , and heterozygous mice treated with IGF-1 for 10 days. Histology, microarray for mRNA gene expression, RT-qPCR, and lipid peroxidation were assessed. Microarray analyses revealed significant underexpression of igf1 in heterozygous mice compared to control mice, restoring normal liver expression after treatment, which then normalized its circulating levels. IGF-1 receptor mRNA was overexpressed in Hz mice liver, while treated mice displayed a similar expression to that of the controls. Heterozygous mice showed overexpression of several genes encoding proteins related to inflammatory and acute-phase proteins and underexpression or overexpression of genes which coded for extracellular matrix, cytoskeleton, and cell junction components. Histology revealed an altered hepatic architecture. In addition, liver oxidative damage was found increased in the heterozygous group. The mere IGF-1 partial deficiency is associated with relevant alterations of the hepatic architecture and expression of genes involved in cytoskeleton, hepatocyte polarity, cell junctions, and extracellular matrix proteins. Moreover, it induces hepatic expression of the IGF-1 receptor and elevated acute-phase and inflammation mediators, which all resulted in liver oxidative damage.

  15. Histological long-term outcomes from acute antibody-mediated rejection following ABO-compatible liver transplantation.

    PubMed

    Del Bello, Arnaud; Danjoux, Marie; Congy-Jolivet, Nicolas; Lavayssière, Laurence; Esposito, Laure; Muscari, Fabrice; Kamar, Nassim

    2017-04-01

    Acute antibody-mediated rejection (aAMR) is an unusual complication after orthotopic ABO-compatible liver transplantation. To date, the clinical and histological long-term outcomes after aAMR are not well known. Herein, we describe nine cases of aAMR that occurred in our liver-transplant center between 2008 and 2016, with an initial and reevaluation liver biopsy available for reexamination. Two patients presented with aAMR at 10.5 (10, 11) days post-transplantation, caused by preformed donor-specific antibodies. Seven other recipients developed de novo donor-specific antibodies and aAMR at 11.2 (3-24) months post-transplantation. Eight of the nine patients received a B-cell targeting agent (rituximab, with or without plasma exchange), associated with polyclonal antibodies (three patients) or intravenous immunoglobulins (three patients). At the last follow up (i.e. 21 [4-90] months post-aAMR), seven patients were alive, including two patients with normal liver tests. Grafts' survival was 66%. A liver biopsy performed at 11.5 (5-48.5) months after the first biopsy showed no significant improvement in aAMR score (from 2 ± 1.3 to 1.6 ± 1.5, P = 0.6), a significant improvement in chronic AMR score (from 37 ± 9 to 25 ± 8, P = 0.003) and an increase in the Metavir score (1.2 ± 0.6 to 2.1 ± 0.9, P = 0.03). In this study, a B-cell-depleting agent seemed to improve the prognosis of aAMR in selected cases, but several patients kept active lesions antibody-mediated rejection. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  16. miR-122 negatively correlates with liver fibrosis as detected by histology and FibroScan

    PubMed Central

    Halász, Tünde; Horváth, Gábor; Pár, Gabriella; Werling, Klára; Kiss, András; Schaff, Zsuzsa; Lendvai, Gábor

    2015-01-01

    AIM: To investigate whether expression of selected miRNAs obtained from fibrotic liver biopsies correlate with fibrosis stage. METHODS: Altogether, 52 patients were enrolled in the study representing various etiologic backgrounds of fibrosis: 24 cases with chronic hepatitis infections (types B, C), 19 with autoimmune liver diseases (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, overlapping syndrome cases), and 9 of mixed etiology (alcoholic and nonalcoholic steatosis, cryptogenic cases). Severity of fibrosis was determined by both histologic staging using the METAVIR scoring system and noninvasive transient elastography. Following RNA isolation, expression levels of miR-21, miR-122, miR-214, miR-221, miR-222, and miR-224 were determined using TaqMan MicroRNA Assays applying miR-140 as the reference. Selection of miRNAs was based on their characteristic up- or downregulation observed in hepatocellular carcinoma. Relative expression of miRNAs was correlated with fibrosis stage and liver stiffness (LS) value measured by transient elastography, as well as with serum alanine aminotransferase (ALT) level. RESULTS: The expression of individual miRNAs showed deregulated patterns in stages F1-F4 as compared with stage F0, but only the reduced level of miR-122 in stage F4 was statistically significant (P < 0.04). When analyzing miRNA expression in relation to fibrosis, levels of miR-122 and miR-221 showed negative correlations with fibrosis stage, and miR-122 was found to correlate negatively and miR-224 positively with LS values (all P < 0.05). ALT levels displayed a positive correlation with miR-21 (P < 0.04). Negative correlations were observed in the fibrosis samples of mixed etiology between miR-122 and fibrosis stage and LS values (P < 0.05), and in the samples of chronic viral hepatitis, between miR-221 and fibrosis stage (P < 0.01), whereas miR-21 showed positive correlation with ALT values in the samples of autoimmune liver

  17. miR-122 negatively correlates with liver fibrosis as detected by histology and FibroScan.

    PubMed

    Halász, Tünde; Horváth, Gábor; Pár, Gabriella; Werling, Klára; Kiss, András; Schaff, Zsuzsa; Lendvai, Gábor

    2015-07-07

    To investigate whether expression of selected miRNAs obtained from fibrotic liver biopsies correlate with fibrosis stage. Altogether, 52 patients were enrolled in the study representing various etiologic backgrounds of fibrosis: 24 cases with chronic hepatitis infections (types B, C), 19 with autoimmune liver diseases (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, overlapping syndrome cases), and 9 of mixed etiology (alcoholic and nonalcoholic steatosis, cryptogenic cases). Severity of fibrosis was determined by both histologic staging using the METAVIR scoring system and noninvasive transient elastography. Following RNA isolation, expression levels of miR-21, miR-122, miR-214, miR-221, miR-222, and miR-224 were determined using TaqMan MicroRNA Assays applying miR-140 as the reference. Selection of miRNAs was based on their characteristic up- or downregulation observed in hepatocellular carcinoma. Relative expression of miRNAs was correlated with fibrosis stage and liver stiffness (LS) value measured by transient elastography, as well as with serum alanine aminotransferase (ALT) level. The expression of individual miRNAs showed deregulated patterns in stages F1-F4 as compared with stage F0, but only the reduced level of miR-122 in stage F4 was statistically significant (P < 0.04). When analyzing miRNA expression in relation to fibrosis, levels of miR-122 and miR-221 showed negative correlations with fibrosis stage, and miR-122 was found to correlate negatively and miR-224 positively with LS values (all P < 0.05). ALT levels displayed a positive correlation with miR-21 (P < 0.04). Negative correlations were observed in the fibrosis samples of mixed etiology between miR-122 and fibrosis stage and LS values (P < 0.05), and in the samples of chronic viral hepatitis, between miR-221 and fibrosis stage (P < 0.01), whereas miR-21 showed positive correlation with ALT values in the samples of autoimmune liver diseases (P < 0.03). The

  18. Mesenchymal stem cells: In vivo therapeutic application ameliorates carbon tetrachloride induced liver fibrosis in rats.

    PubMed

    Raafat, Nermin; Abdel Aal, Sara M; Abdo, Fadia K; El Ghonaimy, Nabila M

    2015-11-01

    Egypt has the highest prevalence of hepatitis C virus in the world with infection rate up to 60%, for which liver fibrosis or hepatic carcinoma is the final outcome. Stem cell therapy provides a new hope for hepatic repair instead of traditional treatment, liver transplantation, as it is safer, gives long term engraftment and avoid expensive immunosuppressive drugs and unexpected hazardous effects. This work aimed at determining the therapeutic potential of mesenchymal stem cells (MSC) in hepatic repair as a new line of therapy for liver fibrosis. 33 female albino rats were divided into three groups: Group I: 10 rats injected subcutaneously with olive oil, Group II: 13 rats injected with carbon tetrachloride (CCl4) and Group III: 10 rats injected with CCl4 then bone marrow derived MSC from male rats. Blood and liver tissue samples were taken from all rats for biochemical and histological study. Liver functions for group II rats showed significant deterioration in response to CCl4 in addition to significant histological changes in liver lobules and portal areas. Those parameters tend to be normal in MSC-treated group. Group III rats revealed normalized liver function and histological picture. Meanwhile, most of the pathological lesions were still detected in rats of second group. Undifferentiated MSCs have the ability to ameliorate CCl4 induced liver injury in albino rats in terms of liver functions and histological features. So, stem cell therapy can be considered clinically to offer a hope for patients suffering from liver fibrosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Association of nonalcoholic fatty liver disease and liver cancer

    PubMed Central

    Schulz, Perla Oliveira; Ferreira, Fabio Gonçalves; Nascimento, Maria de Fátima Araújo; Vieira, Andrea; Ribeiro, Mauricio Alves; David, André Ibrahim; Szutan, Luiz Arnaldo

    2015-01-01

    AIM: To investigate the association between nonalcoholic fatty liver disease (NAFLD) and liver cancer, and NAFLD prevalence in different liver tumors. METHODS: This is a retrospective study of the clinical, laboratory and histological data of 120 patients diagnosed with primary or secondary hepatic neoplasms and treated at a tertiary center where they underwent hepatic resection and/or liver transplantation, with subsequent evaluation of the explant or liver biopsy. The following criteria were used to exclude patients from the study: a history of alcohol abuse, hepatitis B or C infection, no tumor detected in the liver tissue examined by histological analysis, and the presence of chronic autoimmune hepatitis, hemochromatosis, Wilson’s disease, or hepatoblastoma. The occurrence of NAFLD and the association with its known risk factors were studied. The risk factors considered were diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, body mass index, dyslipidemia, and arterial hypertension. Presence of reticulin fibers in the hepatic neoplasms was assessed by histological analysis using slide-mounted specimens stained with either hematoxylin and eosin or Masson’s trichrome and silver impregnation. Analysis of tumor-free liver parenchyma was carried out to determine the association between NAFLD and its histological grade. RESULTS: No difference was found in the association of NAFLD with the general population (34.2% and 30.0% respectively, 95%CI: 25.8-43.4). Evaluation by cancer type showed that NAFLD was more prevalent in patients with liver metastasis of colorectal cancer than in patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma (OR = 3.99, 95%CI: 1.78-8.94, P < 0.001 vs OR = 0.60, 95%CI: 0.18-2.01, P = 0.406 and OR = 0.70, 95%CI: 0.18-2.80, P = 0.613, respectively). There was a higher prevalence of liver fibrosis in patients with hepatocellular carcinoma (OR = 3.50, 95%CI: 1.06-11.57, P = 0.032). Evaluation of the

  20. Primary perivascular epithelioid cell tumour (PEComa) of the liver.

    PubMed

    Cheung, Tan To; Trendell-Smith, Nigel; Poon, Ronnie T P

    2013-07-10

    We present a case of a 53-year-old woman with abdominal discomfort for 6 months. The liver was enlarged. Contrast CT scan of the abdomen revealed a 10 cm hypervascular tumour at the right lobe of the liver. Right hepatectomy with complete excision of the tumour was achieved. Histological and immunohistochemical findings were consistent with perivascular epithelioid cell tumour. She is regularly followed up with contrast CT assessment. There is no tumour recurrence 12 months after the operation.

  1. Cytotoxic effect of aspartame (diet sweet) on the histological and genetic structures of female albino rats and their offspring.

    PubMed

    Abd Elfatah, Azza A M; Ghaly, Inas S; Hanafy, Safaa M

    2012-10-01

    The present study evaluated the effect of aspartame intake on the histological and genetic structures of mother albino rats and their offspring. Sixty adult female albino rats and 180 of their offspring were equally divided into two groups (control and treated), each group divided into three subgroups. Each subgroup consisted of 10 pregnant rats and 30 of their offspring. The experimental design divided into three periods: (1) the gestation period (subgroup one), (2) the gestation period and three weeks after delivery (subgroup two) and (3) animals in the third subgroup treated as subgroup two then left till the end of the ninth week after delivery. Each pregnant rat in the treated subgroups was given a single daily dose of 1 mL aspartame solution (50.4 mg) by gastric gavage throughout the time intervals of experimental design. At the end of each experimental period for control and treated subgroups, the liver of half of both control and treated groups were subjected for histological study while the liver and bone marrow of the other halves were subjected for cytogenetic studies. Body weight of both groups were recorded individually twice weekly in the morning before offering the diet. The results revealed that the rats and their offspring in the subgroups of control animals showed increases in body weight, normal histological sections, low chromosomal aberration and low DNA fragmentation. The treated animals in the three subgroups rats and their offspring revealed decreases in body weight, high histological lesions, increases in the chromosomal aberration and DNA fragmentation compared with control groups. In conclusion, the consumption of aspartame leads to histopathological lesions in the liver and alterations of the genetic system in the liver and bone marrow of mother albino rats and their offspring. These toxicological changes were directly proportional to the duration of its administration and improved after its withdrawal.

  2. Relationships between Genetic Variations of PNPLA3, TM6SF2 and Histological Features of Nonalcoholic Fatty Liver Disease in Japan.

    PubMed

    Akuta, Norio; Kawamura, Yusuke; Arase, Yasuji; Suzuki, Fumitaka; Sezaki, Hitomi; Hosaka, Tetsuya; Kobayashi, Masahiro; Kobayashi, Mariko; Saitoh, Satoshi; Suzuki, Yoshiyuki; Ikeda, Kenji; Kumada, Hiromitsu

    2016-05-23

    It is important to determine the noninvasive parameters of histological features in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the value of genetic variations as surrogate markers of histological features. The parameters that affected the histological features of NAFLD were investigated in 211 Japanese patients with biopsy-proven NAFLD. The relationships between genetic variations in PNPLA3 rs738409 or TM6SF2 rs58542926 and histological features were analyzed. Furthermore, the impact of genetic variations that affected the pathological criteria for the diagnosis of nonalcoholic steatohepatitis (NASH) (Matteoni classification and NAFLD activity score) was evaluated. The fibrosis stage of PNPLA3 GG was significantly more progressive than that of CG by multiple comparisons. Multivariate analysis identified PNPLA3 genotypes as predictors of fibrosis of stage 2 or more, but the impact tended to decrease at stage 3 or greater. There were no significant differences among the histological features of the three genotypes of TM6SF2. PNPLA3 genotypes partly affected the definition of NASH by the NAFLD activity score, but TM6SF2 genotypes did not affect the definition of NASH. In Japanese patients with biopsy-proven NAFLD, PNPLA3 genotypes may partly affect histological features, including stage of fibrosis, but the TM6SF2 genotype does not affect histological features.

  3. Effects of varying dietary carbohydrate levels on growth performance, body composition and liver histology of Malaysian mahseer fingerlings (Tor tambroides).

    PubMed

    Ishak, Sairatul Dahlianis; Kamarudin, Mohd Salleh; Ramezani-Fard, Ehsan; Saad, Che Roos; Yusof, Yus Aniza

    2016-07-01

    We investigated the effects of four iso-nitrogenous (40% crude protein) and iso-caloric (17.6 kJ g(-1)) diets with different dietary carbohydrate levels (15%, 20%, 25% and 30%) on the growth performance, feed utilization efficiency, body composition and liver histology of Malaysian mahseer (Tor tambroides) fingerlings in a 10-week feeding trial. Fish (initial weight of 0.8?0.1 g; initial total length 4.2?0.1 cm) were fed twice daily at 4% body mass. Dietary carbohydrate level had significant effects (P<0.05) on weight gain, SGR (specific growth rate), FCR (feed conversion rate), PER (protein efficiency rate), survival percentage and all nutrient retention values (PRV, LRV, CRV, ERV). Protein, carbohydrate and gross energy composition of the fish body were also significantly differed (P<0.05) among treatments. Liver histology showed mild hepatic steatosis and hypertrophy for fishes receiving a higher dietary carbohydrate inclusion. In general, treatments with 20% and 25% dietary carbohydrate levels produced better growth results compared to the rest of the treatments. Using a second-order polynomial regression analysis model, the optimal dietary carbohydrate level of 23.4% was estimated for mahseer fingerlings. ?

  4. Childhood Liver Cancer Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Childhood liver cancer has two major histologic subgroups: hepatoblastoma and hepatocellular carcinoma. Less common histologies are undifferentiated embryonal sarcoma of the liver, infantile choriocarcinoma, and vascular liver tumors. Get detailed information about newly diagnosed and recurrent childhood liver cancers including tumor biology, presentation, prognosis, staging, and treatment in this summary for clinicians.

  5. Primary perivascular epithelioid cell tumour (PEComa) of the liver

    PubMed Central

    Cheung, Tan To; Trendell-Smith, Nigel; Poon, Ronnie T P

    2013-01-01

    We present a case of a 53-year-old woman with abdominal discomfort for 6 months. The liver was enlarged. Contrast CT scan of the abdomen revealed a 10 cm hypervascular tumour at the right lobe of the liver. Right hepatectomy with complete excision of the tumour was achieved. Histological and immunohistochemical findings were consistent with perivascular epithelioid cell tumour. She is regularly followed up with contrast CT assessment. There is no tumour recurrence 12 months after the operation. PMID:23845671

  6. [Histological and biochemical studies on the postnatal development of the guinea pig liver (author's transl)].

    PubMed

    Matthiesen, T h; Sallmann, H P; Heimann, W; Kunstýr, I

    1976-01-01

    In newborn guinea pigs the structural development of the liver was studied with emphasis on changes in the lipid content as related to biochemical parameters. The livers of 149 guinea pigs (strain PIRBRIGHT) up to an age of 21 days were examined. The mothers were grouped in cages and kept as usual (room temperature 22 degrees C, air humidity 60-70%, natural light-dark rhythm and commercial standard diet ad libitum, sawdust and straw as bedding). Pregnant animals were placed in individual cages being left there together with their offspring until weaning or sacrification. In this period additional uptake of solid diet was allowed to the guinea pigs. The animals were bleeded to death in anesthesia (by head stroke). For histological examination tissue samples from the Lobes sinister lateralis were fixed in Barker's formol or absolute alcohol. The following staining reactions were applied (paraffin embedding or frozen sections): haemalum-eosin stain; PAS-reaction; Sudan III; Sudan black; Best's carmine (for details on the techniques see ROMEIS 1968). In biochemical analysis the total lipids of the liver were determined by the isolation methods reported by FOLCH et al.(1957). Moreover, in modification of the analytical procedures earlier described (SALLMANN 1972 a, b) several fractions of the liver total lipids could be isolated. By dialysis against a rubber membrane a dialysable lipid component (hydrocarbons, triglycerides, incomplete glycerides, cholesterol and free lipid acids) was isolated from the phosphatide fractions. Further separation of the "dialysable" lipids on Florisil columns yielded purified glyceride fractions. The total lipids as well as all components isolated from these were determined gravimetrically after removal of the solvents concerned. In biochemical analysis the livers of fetuses 10-12 days ante partum and of young animals up to 53 days were included. Results (see also table 1): The relative liver weight--related to the body weight reduced for

  7. Character and temporal evolution of apoptosis in acetaminophen-induced acute liver failure*.

    PubMed

    Possamai, Lucia A; McPhail, Mark J W; Quaglia, Alberto; Zingarelli, Valentina; Abeles, R Daniel; Tidswell, Robert; Puthucheary, Zudin; Rawal, Jakirty; Karvellas, Constantine J; Leslie, Elaine M; Hughes, Robin D; Ma, Yun; Jassem, Wayel; Shawcross, Debbie L; Bernal, William; Dharwan, Anil; Heaton, Nigel D; Thursz, Mark; Wendon, Julia A; Mitry, Ragai R; Antoniades, Charalambos G

    2013-11-01

    To evaluate the role of hepatocellular and extrahepatic apoptosis during the evolution of acetaminophen-induced acute liver failure. A prospective observational study in two tertiary liver transplant units. Eighty-eight patients with acetaminophen-induced acute liver failure were recruited. Control groups included patients with nonacetaminophen-induced acute liver failure (n = 13), nonhepatic multiple organ failure (n = 28), chronic liver disease (n = 19), and healthy controls (n = 11). Total and caspase-cleaved cytokeratin-18 (M65 and M30) measured at admission and sequentially on days 3, 7, and 10 following admission. Levels were also determined from hepatic vein, portal vein, and systemic arterial blood in seven patients undergoing transplantation. Protein arrays of liver homogenates from patients with acetaminophen-induced acute liver failure were assessed for apoptosis-associated proteins, and histological assessment of liver tissue was performed. Admission M30 levels were significantly elevated in acetaminophen-induced acute liver failure and non-acetaminophen induced acute liver failure patients compared with multiple organ failure, chronic liver disease, and healthy controls. Admission M30 levels correlated with outcome with area under receiver operating characteristic of 0.755 (0.639-0.885, p < 0.001). Peak levels in patients with acute liver failure were seen at admission then fell significantly but did not normalize over 10 days. A negative gradient of M30 from the portal to hepatic vein was demonstrated in patients with acetaminophen-induced acute liver failure (p = 0.042) at the time of liver transplant. Analysis of protein array data demonstrated lower apoptosis-associated protein and higher catalase concentrations in acetaminophen-induced acute liver failure compared with controls (p < 0.05). Explant histological analysis revealed evidence of cellular proliferation with an absence of histological evidence of apoptosis. Hepatocellular apoptosis occurs

  8. Electrochemical lesions in the rat liver support its potential for treatment of liver tumors.

    PubMed

    Wemyss-Holden, S A; Robertson, G S; Dennison, A R; de la M Hall, P; Fothergill, J C; Jones, B; Maddern, G J

    2000-09-01

    An effective therapy is needed for patients with surgically unresectable liver tumors who have very limited life expectancy. One possible treatment is electrochemical tumor necrosis. This study investigated the natural history of electrochemical lesions in the normal rat liver. A direct current generator, connected to platinum electrodes, was used to create controlled areas of liver necrosis. Animals were sacrificed 2 days, 2 weeks, 2 months, and 6 months after treatment and the macroscopic and histological appearance of the necrotic lesions was followed. No animal died as a result of electrolysis; postoperatively, all gained weight normally. Liver enzymes were significantly (P < 0.001) elevated after treatment, but returned to normal after a week. Two days after electrolysis, histology confirmed an ellipsoidal area of coagulative necrosis at the site of the electrode tip and commonly a segment of peripheral necrosis. After 2 weeks there was histological evidence of healing. By 6 months, very little necrotic tissue remained within a small fibrous scar. Electrolysis is a safe method for creating defined areas of liver necrosis that heal well with no associated mortality. This study supports the potential of electrolysis for treating patients with unresectable liver tumors. Copyright 2000 Academic Press.

  9. Clinicopathologic, gross necropsy, and histologic findings after intramuscular injection of carprofen in a pigeon (Columba livia) model.

    PubMed

    Zollinger, Tawina J; Hoover, John P; Payton, Mark E; Schiller, Chris A

    2011-09-01

    To evaluate the pathologic effects of carprofen in a pigeon model (Columba livia), 52 young adult pigeons were used in a randomized control study design. Sixteen pigeons were randomly assigned to 1 of 3 treatment groups and received carprofen by intramuscular injection at dosages of either 2, 5, or 10 mg/kg once daily for 7 days. Four pigeons served as saline-injected controls. Four pigeons from each group and 1 control pigeon were randomly selected on days 2, 4, 6, and 8 to obtain blood samples and then were euthanatized and submitted for necropsy. Histologic lesions in pectoral muscle, liver, kidney, and digestive tract tissue samples were ranked in severity as 0, normal/not present; 1, minimal; 2, mild; 3, mild to moderate; 4, moderate; 5, moderate to marked; and 6, marked pathologic changes. Two-way analysis of variance (day x dose) and pairwise t tests revealed significant (P < or = .05) mild decreases in total protein and glucose concentrations and marked increases in aspartate aminotransferase and alanine aminotransferase enzyme activities after carprofen treatments. Gross lesions in carprofen-treated pigeons were pale injection sites (23/48 [47.9%]), mottled yellow livers (9/48 [18.8%]), and congestion of small intestines (7/48 [14.6%]). Liver, kidney, and muscle injection sites had significantly increased (P < or = .05) severity of histologic lesions. In pigeons, intramuscular administration of carprofen is associated with increased aspartate aminotransferase and alanine aminotransferase enzyme concentrations, gross lesions in muscle injection sites and liver, and histologic lesions in liver and muscle.

  10. Chronic Liver Diseases in Children: Clinical Profile and Histology.

    PubMed

    Dhole, Sachin Devidas; Kher, Archana S; Ghildiyal, Radha G; Tambse, Manjusha P

    2015-07-01

    The main aim of the study is to study the clinical profile of disorders of the liver and hepatobiliary system in paediatric patients and to correlate the histopathology findings of liver biopsy in chronic liver disease. Another aim being to assess the prognosis and to know the outcome and the effects of treatment in chronic liver diseases in paediatric age group. It was a prospective study, included the clinical profile of Chronic Liver Diseases (CLD) in children and the histopathological correlation. A total of 55 children were thoroughly investigated by doing relevant investigations and liver biopsy. A male predominance (60%) was noted with maximum incidence in the age group of 6-12 years. The incidence of CLD was 1.1% of total admissions. The most common presenting complaint was jaundice and abdominal distension. Hepatic encephalopathy was noted in 29% patients. Hepatomegaly was seen in 63% patients and spleenomegaly was seen in 60% patients. The incidence of cirrhosis on liver biopsy was 42% (23cases) in CLD patients. The most common diagnosis on histopathology was Wilson's disease (22%), followed by hepatitis and autoimmune hepatitis. The predominant spectrum of CLD was metabolic liver disease and also the predominant cause of death. As the incidence of CLD is quite low, a very high index of suspicion is required for its diagnosis. Some uncommon causes of CLD in children were seen in our study like neutral lipid storage disease, α1-Antitrypsin deficiency disease, lupus hepatitis, Alagille syndrome and Budd-Chiari syndrome. A patient of CLD with jaundice and hepatomegaly should be treated aggressively as those are the poor prognostic indicators of the disease. Hepatic encephalopathy and cirrhosis are also associated with poor outcome in patients with CLD. Liver biopsy histopathology by an expert and its correlation with laboratory investigations plays an important role in the diagnosis of CLD. The major cause of deaths in patients with CLD is due to end stage

  11. Circulating microRNA signature in non-alcoholic fatty liver disease: from serum non-coding RNAs to liver histology and disease pathogenesis.

    PubMed

    Pirola, Carlos J; Fernández Gianotti, Tomas; Castaño, Gustavo O; Mallardi, Pablo; San Martino, Julio; Mora Gonzalez Lopez Ledesma, María; Flichman, Diego; Mirshahi, Faridodin; Sanyal, Arun J; Sookoian, Silvia

    2015-05-01

    We used a screening strategy of global serum microRNA (miRNA) profiling, followed by a second stage of independent replication and exploration of liver expression of selected miRNAs to study: (1) the circulating miRNA signature associated with non-alcoholic fatty liver disease (NAFLD) progression and predictive power, (2) the role of miRNAs in disease biology and (3) the association between circulating miRNAs and features of the metabolic syndrome. The study used a case-control design and included patients with NAFLD proven through biopsy and healthy controls. Among 84 circulating miRNAs analysed, miR-122, miR-192, miR-19a and miR-19b, miR-125b, and miR-375 were upregulated >2-fold (p<0.05) either in simple steatosis (SS) or non-alcoholic steatohepatitis (NASH). The most dramatic and significant fold changes were observed in the serum levels of miR-122 (7.2-fold change in NASH vs controls and 3.1-fold change in NASH vs SS) and miR-192 (4.4-fold change in NASH vs controls); these results were replicated in the validation set. The majority of serum miR-122 circulate in argonaute2-free forms. Circulating miR-19a/b and miR-125b were correlated with biomarkers of atherosclerosis. Liver miR-122 expression was 10-fold (p<0.03) downregulated in NASH compared with SS and was preferentially expressed at the edge of lipid-laden hepatocytes. In vitro exploration showed that overexpression of miR-122 enhances alanine aminotransferase activity. miR-122 plays a role of physiological significance in the biology of NAFLD; circulating miRNAs mirror the histological and molecular events occurring in the liver. NAFLD has a distinguishing circulating miRNA profile associated with a global dysmetabolic disease state and cardiovascular risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  12. Acute liver damage and ecstasy ingestion.

    PubMed Central

    Ellis, A J; Wendon, J A; Portmann, B; Williams, R

    1996-01-01

    Eight cases of ecstasy related acute liver damage referred to a specialised liver unit are described. Two patients presented after collapse within six hours of ecstasy ingestion with hyperthermia, hypotension, fitting, and subsequently disseminated intravascular coagulation with rhabdomyolysis together with biochemical evidence of severe hepatic damage. One patient recovered and the other with evidence of hyperacute liver failure was transplanted but subsequently died, histological examination showing widespread microvesicular fatty change. Four patients presented with acute liver failure without hyperthermia. All four fulfilled criteria for transplantation, one died before a donor organ became available, and two died within one month post-transplantation of overwhelming sepsis. Histological examination showed submassive lobular collapse. Two patients presented with abdominal pain and jaundice and recovered over a period of three weeks; histological examination showed a lobular hepatitis with cholestasis. Patients developing jaundice or with evidence of hepatic failure particularly encephalopathy and prolongation of the international normalised ratio, or both, whether or not preceded by hyperthermia, should be referred to a specialised liver unit as liver transplantation probably provides the only chance of recovery. Images Figure 1 Figure 2 Figure 3 PMID:8675102

  13. Non-invasive assessment of the liver using imaging

    NASA Astrophysics Data System (ADS)

    Thorling Thompson, Camilla; Wang, Haolu; Liu, Xin; Liang, Xiaowen; Crawford, Darrell H.; Roberts, Michael S.

    2016-12-01

    Chronic liver disease causes 2,000 deaths in Australia per year and early diagnosis is crucial to avoid progression to cirrhosis and end stage liver disease. There is no ideal method to evaluate liver function. Blood tests and liver biopsies provide spot examinations and are unable to track changes in function quickly. Therefore better techniques are needed. Non-invasive imaging has the potential to extract increased information over a large sampling area, continuously tracking dynamic changes in liver function. This project aimed to study the ability of three imaging techniques, multiphoton and fluorescence lifetime imaging microscopy, infrared thermography and photoacoustic imaging, in measuring liver function. Collagen deposition was obvious in multiphoton and fluorescence lifetime imaging in fibrosis and cirrhosis and comparable to conventional histology. Infrared thermography revealed a significantly increased liver temperature in hepatocellular carcinoma. In addition, multiphoton and fluorescence lifetime imaging and photoacoustic imaging could both track uptake and excretion of indocyanine green in rat liver. These results prove that non-invasive imaging can extract crucial information about the liver continuously over time and has the potential to be translated into clinic in the assessment of liver disease.

  14. Mechanotransduction-modulated fibrotic microniches reveal the contribution of angiogenesis in liver fibrosis

    NASA Astrophysics Data System (ADS)

    Liu, Longwei; You, Zhifeng; Yu, Hongsheng; Zhou, Lyu; Zhao, Hui; Yan, Xiaojun; Li, Dulei; Wang, Bingjie; Zhu, Lu; Xu, Yuzhou; Xia, Tie; Shi, Yan; Huang, Chenyu; Hou, Wei; Du, Yanan

    2017-12-01

    The role of pathological angiogenesis on liver fibrogenesis is still unknown. Here, we developed fibrotic microniches (FμNs) that recapitulate the interaction of liver sinusoid endothelial cells (LSECs) and hepatic stellate cells (HSCs). We investigated how the mechanical properties of their substrates affect the formation of capillary-like structures and how they relate to the progression of angiogenesis during liver fibrosis. Differences in cell response in the FμNs were synonymous of the early and late stages of liver fibrosis. The stiffness of the early-stage FμNs was significantly elevated due to condensation of collagen fibrils induced by angiogenesis, and led to activation of HSCs by LSECs. We utilized these FμNs to understand the response to anti-angiogenic drugs, and it was evident that these drugs were effective only for early-stage liver fibrosis in vitro and in an in vivo mouse model of liver fibrosis. Late-stage liver fibrosis was not reversed following treatment with anti-angiogenic drugs but rather with inhibitors of collagen condensation. Our work reveals stage-specific angiogenesis-induced liver fibrogenesis via a previously unrevealed mechanotransduction mechanism which may offer precise intervention strategies targeting stage-specific disease progression.

  15. Epoxy composite dusts with and without carbon nanotubes cause similar pulmonary responses, but differences in liver histology in mice following pulmonary deposition.

    PubMed

    Saber, Anne Thoustrup; Mortensen, Alicja; Szarek, Józef; Koponen, Ismo Kalevi; Levin, Marcus; Jacobsen, Nicklas Raun; Pozzebon, Maria Elena; Mucelli, Stefano Pozzi; Rickerby, David George; Kling, Kirsten; Atluri, Rambabu; Madsen, Anne Mette; Jackson, Petra; Kyjovska, Zdenka Orabi; Vogel, Ulla; Jensen, Keld Alstrup; Wallin, Håkan

    2016-06-29

    The toxicity of dusts from mechanical abrasion of multi-walled carbon nanotube (CNT) epoxy nanocomposites is unknown. We compared the toxic effects of dusts generated by sanding of epoxy composites with and without CNT. The used CNT type was included for comparison. Mice received a single intratracheal instillation of 18, 54 and 162 μg of CNT or 54, 162 and 486 μg of the sanding dust from epoxy composite with and without CNT. DNA damage in lung and liver, lung inflammation and liver histology were evaluated 1, 3 and 28 days after intratracheal instillation. Furthermore, the mRNA expression of interleukin 6 and heme oxygenase 1 was measured in the lungs and serum amyloid A1 in the liver. Printex 90 carbon black was included as a reference particle. Pulmonary exposure to CNT and all dusts obtained by sanding epoxy composite boards resulted in recruitment of inflammatory cells into lung lumen: On day 1 after instillation these cells were primarily neutrophils but on day 3, eosinophils contributed significantly to the cell population. There were still increased numbers of neutrophils 28 days after intratracheal instillation of the highest dose of the epoxy dusts. Both CNT and epoxy dusts induced DNA damage in lung tissue up to 3 days after intratracheal instillation but not in liver tissue. There was no additive effect of adding CNT to epoxy resins for any of the pulmonary endpoints. In livers of mice instilled with CNT and epoxy dust with CNTs inflammatory and necrotic histological changes were observed, however, not in mice instilled with epoxy dust without CNT. Pulmonary deposition of epoxy dusts with and without CNT induced inflammation and DNA damage in lung tissue. There was no additive effect of adding CNT to epoxies for any of the pulmonary endpoints. However, hepatic inflammatory and necrotic histopathological changes were seen in mice instilled with sanding dust from CNT-containing epoxy but not in mice instilled with reference epoxy.

  16. MR elastography of the liver at 3.0 T in diagnosing liver fibrosis grades; preliminary clinical experience.

    PubMed

    Yoshimitsu, Kengo; Mitsufuji, Toshimichi; Shinagawa, Yoshinobu; Fujimitsu, Ritsuko; Morita, Ayako; Urakawa, Hiroshi; Hayashi, Hiroyuki; Takano, Koichi

    2016-03-01

    To clarify the usefulness of 3.0-T MR elastography (MRE) in diagnosing the histological grades of liver fibrosis using preliminary clinical data. Between November 2012 and March 2014, MRE was applied to all patients who underwent liver MR study at a 3.0-T clinical unit. Among them, those who had pathological evaluation of liver tissue within 3 months from MR examinations were retrospectively recruited, and the liver stiffness measured by MRE was correlated with histological results. Institutional review board approved this study, waiving informed consent. There were 70 patients who met the inclusion criteria. Liver stiffness showed significant correlation with the pathological grades of liver fibrosis (rho = 0.89, p < 0.0001, Spearman's rank correlation). Areas under the receiver operating characteristic curve were 0.93, 0.95, 0.99 and 0.95 for fibrosis score greater than or equal to F1, F2, F3 and F4, with cut-off values of 3.13, 3.85, 4.28 and 5.38 kPa, respectively. Multivariate analysis suggested that grades of necroinflammation also affected liver stiffness, but to a significantly lesser degree as compared to fibrosis. 3.0-T clinical MRE was suggested to be sufficiently useful in assessing the grades of liver fibrosis. MR elastography may help clinicians assess patients with chronic liver diseases. Usefulness of 3.0-T MR elastography has rarely been reported. Measured liver stiffness correlated well with the histological grades of liver fibrosis. Measured liver stiffness was also affected by necroinflammation, but to a lesser degree. 3.0-T MRE could be a non-invasive alternative to liver biopsy.

  17. Prognostic value of clinical variables and liver histology for development of fibrosis and cirrhosis in autoimmune hepatitis.

    PubMed

    Puustinen, Lauri; Boyd, Sonja; Mustonen, Harri; Arkkila, Perttu; Arola, Johanna; Färkkilä, Martti

    2017-03-01

    In autoimmune hepatitis, data on the prognostic value of baseline liver biopsy and the sequential histology is controversial. Our aim was to evaluate the prognostic value of clinical variables and biopsy at the time of diagnosis and during the disease course. All 98 patients in our hospital during 1995-2012 were included. Sequential biopsies were available in 66 patients. Analyses based on clinical and histological variables were performed to find parameters predicting the progression of fibrosis, and development of cirrhosis. At the time of diagnosis, 7% were cirrhotic. Fibrosis progressed in 28 (42%) patients, remained stable in 26 (39%) and resolved in 12 (18%) patients. Findings which predicted fibrosis progression, were baseline total inflammation (odds ratio 1.7, 95% CI 1.01-2.8), cumulative total inflammation (1.8, 95% CI 1.01-3.2, rosette formation (2.8, 95% CI 1.1-7.1), absence of pericholangitis (0.4, 95% CI 0.1-1.0) and necrosis (1.4, 95% CI 1.0-2.0). Risk factors for the development of cirrhosis were cholestasis (4.6, 95% CI 1.2-16.9), interphase inflammation (3.4, 95% CI 1.1-10.4), and necrosis (3.3, 95% CI 1.2-9.7). In a cumulative model, cumulative total inflammation (4.5, 95% CI 1.4-15.0), necrosis (6.7, 95% CI 1.3-34.6), or cumulative immunoglobulin G load (61.8, 95% CI 2.0-1954.3) were risk factors. None of the patients with histological pericholangitis or granulomas developed cirrhosis. The histology provides prognostic information regarding progression of fibrosis or the development of cirrhosis. The total cumulative inflammatory activity predicts the progression of fibrosis, whereas baseline fibrosis, interphase inflammation, cholestasis, necrosis, as well as the cumulative total inflammation and cumulative immunoglobulin G, are risk factors for cirrhosis.

  18. A liver-metastatic model of human primary gastric lymphoma in nude mice orthotopically constructed by using histologically intact patient specimens.

    PubMed

    Yang, Bo; Tuo, Shuai; Tuo, Chao-Wei; Zhang, Ning; Liu, Qiu-Zhen

    2010-06-01

    In recent years, incidence and mortality of lymphoma are markedly increasing worldwide. However, the pathogenesis and mechanism of invasion and metastasis for lymphoma are not yet fully clarified. It is mainly due to the lack of ideal animal models, which can precisely simulate the invasion and metastasis of lymphoma in the human body. So, it is very necessary to establish a highly metastatic nude mouse model of human lymphoma. This study developed a liver-metastatic model of primary gastric lymphoma in nude mice by using orthotopic surgical implantation of histologically intact patient specimens into the corresponding organs of the recipient small animals. A histologically intact fragment of liver metastasis derived from a surgical specimen of a patient with primary gastric lymphoma was implanted into the submucosa of the stomach in nude mice. Tumorigenicity, invasion, metastasis, morphologic characteristics (via light microscopy, electron microscopy, and immunohistochemistry), karyotype analysis, and DNA content of the orthotopically transplanted tumors were studied. An orthotopic liver metastatic model of human primary gastric lymphoma in nude mice (termed HGBL-0304) was successfully established. The histopathology of the transplanted tumors showed primary gastric diffuse large B-cell lymphoma. CD19, CD20, CD22, and CD79alpha were positive, but CD3 and CD7 were negative. The serum level of lactate dehydrogenase (LDH) was elevated [(1010.56+/-200.85) U/L]. The number of chromosomes ranged from 75 to 89. The DNA index (DI) was 1.45+/-0.25 (that is, heteroploid). So far, the HGBL-0304 model has been passed on for 45 generations of nude mice. A total of 263 nude mice were used for the transplantation. Both the growth and resuscitation rates of liquid nitrogen cryopreservation of the transplanted tumors were 100%. The transplanted tumors autonomically invasively grew and damaged a whole layer in the stomach of nude mice. The metastasis rates of liver, spleen, lymph

  19. Liver Histology During Mipomersen Therapy for Severe Hypercholesterolemia

    PubMed Central

    Hashemi, Nikroo; Odze, Robert D.; McGowan, Mary P.; Santos, Raul D.; Stroes, Erik S.G.; Cohen, David E.

    2014-01-01

    Background Mipomersen is an antisense oligonucleotide that inhibits apolipoprotein (apo) B synthesis and lowers plasma low density lipoprotein (LDL) cholesterol even in the absence of LDL receptor function, presumably due to the inhibition of hepatic production of triglyceride-rich very low density lipoprotein (VLDL) particles. By virtue of this mechanism, mipomersen therapy commonly results in the development of hepatic steatosis. Because this is frequently accompanied by alanine aminotransferase (ALT) elevations, concern has arisen that mipomersen could promote the development of steatohepatitis, which could in turn lead to fibrosis and cirrhosis over time. Objective The objective of this study was to assess the liver biopsy findings in patients treated with mipomersen. Methods We describe 7 patients who underwent liver biopsy during the mipomersen clinical development programs. Liver biopsies were reviewed by a single, blinded pathologist. Results The histopathological features were characterized by simple steatosis, without significant inflammation or fibrosis. Conclusion These findings suggest that hepatic steatosis due to mipomersen is distinct from non-alcoholic steatohepatitis. PMID:25499943

  20. Liver histology during Mipomersen therapy for severe hypercholesterolemia.

    PubMed

    Hashemi, Nikroo; Odze, Robert D; McGowan, Mary P; Santos, Raul D; Stroes, Erik S G; Cohen, David E

    2014-01-01

    Mipomersen is an antisense oligonucleotide that inhibits apolipoprotein B synthesis and lowers plasma low-density lipoprotein cholesterol even in the absence of low-density lipoprotein receptor function, presumably from inhibition of hepatic production of triglyceride-rich very low-density lipoprotein particles. By virtue of this mechanism, mipomersen therapy commonly results in the development of hepatic steatosis. Because this is frequently accompanied by alanine aminotransferase elevations, concern has arisen that mipomersen could promote the development of steatohepatitis, which could in turn lead to fibrosis and cirrhosis over time. The objective of this study was to assess the liver biopsy findings in patients treated with mipomersen. We describe 7 patients who underwent liver biopsy during the mipomersen clinical development programs. Liver biopsies were reviewed by a single, blinded pathologist. The histopathological features were characterized by simple steatosis, without significant inflammation or fibrosis. These findings suggest that hepatic steatosis resulting from mipomersen is distinct from nonalcoholic steatohepatitis. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  1. Effect of lead nitrate on the liver of the cichlid fish (Oreochromis niloticus): a light microscope study.

    PubMed

    Khidr, Bothaina M; Mekkawy, Imam A A; Harabawy, Ahmed S A; Ohaida, Abdel Salam M I

    2012-09-15

    The adverse impacts of heavy metals on fish liver were evident with great variability among organs and species. The present study deals with the histological changes of the hepatocytes of the Nile tilapia, Oreochromis niloticus, following exposure to 2.5, 5, 10 ppm of lead nitrate for 1, 2, 3, 4 weeks. The present results revealed that lead nitrate exerts some histological effects on the hepatic tissue after exposure to the first concentration in the form of dilatation and congestion of the blood vessels, vacuolation of hepatic cells, proliferation of connective tissue and hepatic necrosis. Leucocyte aggregation-mostly lymphatic in nature-was seen infiltrating hepatic tissue. These alterations became more pronounced in liver of fishes exposed to second concentrations indicating more progressive signs of necrosis. The presence of eosinophilic oedematous areas surrounding some blood vessels was also observed. Finally, at the third concentration, in addition to the above alterations, melanomacrophages, which store lipofuscin at the site of necrosis, were observed. These histological results imply that the fish liver may serve as a target organ for the toxicity of sublethal concentrations of lead nitrate.

  2. Pathologic Criteria to Estimate the State of the Liver in Potential Donors.

    PubMed

    Shaimardanova, Caliya; Fedotovskikh, Galina; Savchuk, Aleksandr; Doszhan, Ainura; Smagulova, Aigerim; Gaipov, Abduzhappar

    2015-11-01

    The pathologic evaluation of the liver is one of the most important issues in liver transplants. We evaluated the histopathological condition of livers in potential donors. After liver biopsy, 37 potential donor livers were histologically studied. Liver tissue was stained by hematoxylin and eosin as well as Masson Trichrome. The results of the study showed the morphologic criteria used to estimate the state of the liver in potential donors is not only steatosis and fibrosis, but other important histologic criteria, such as proteinosis, necrosis of hepatocytes, endotheliitis of central veins, inflammatory infiltration, endarteritis in portal tracts and phlebitis in portal tracts, proliferation of the bile ducts, and cholestasis. Results of the study showed that the morphologic criteria to estimate the state of the liver in potential donors includes not only steatosis and fibrosis, but other important histologic criteria as well.

  3. Clinicopathological features of liver injury in patients with type 2 diabetes mellitus and comparative study of histologically proven nonalcoholic fatty liver diseases with or without type 2 diabetes mellitus.

    PubMed

    Shima, Toshihide; Uto, Hirofumi; Ueki, Kohjiro; Takamura, Toshinari; Kohgo, Yutaka; Kawata, Sumio; Yasui, Kohichiroh; Park, Hyohun; Nakamura, Naoto; Nakatou, Tatsuaki; Tanaka, Nobuyoshi; Umemura, Atsushi; Mizuno, Masayuki; Tanaka, Junko; Okanoue, Takeshi

    2013-04-01

    The Japan Society of Diabetes Mellitus reported that the leading cause of death in patients with diabetes mellitus (DM) was chronic liver disease; however, there are limited studies investigating the cause of liver injury in these patients. Our study aimed to clarify the clinicopathological features of liver injury and the characteristics of nonalcoholic fatty liver disease (NAFLD) in DM patients. In total, 5,642 DM patients and 365 histologically proven NAFLD patients were enrolled. Clinical and laboratory parameters and liver biopsy results were, respectively, recorded and analyzed for the two sets of patients. Positivity rates for Hepatitis B surface antigens (HBsAg) and anti-hepatitis C virus antibodies (anti-HCV Ab) were 1.7 and 5.1 %, respectively. The proportion of drinkers consuming 20-59 g and ≥60 g alcohol daily was 14.9 and 4.3 %, respectively. The percentage of DM patients with elevated serum alanine aminotransferase (ALT) levels (≥31 IU/L) was 28.6 %. Alcohol consumption had no significant effect on serum ALT levels. Seventy-two percent of HBsAg-positive patients were serum hepatitis B virus (HBV)-DNA negative, whereas 10 % exhibited high levels of the same (>4.0 log copies/ml). Thirty-eight percent of anti-HCV Ab-positive patients were serum HCV-RNA negative. Among the NAFLD patients, the frequencies of NASH and advanced stage NASH were significantly higher in male DM patients than in male patients without DM. Although HBsAg- and anti-HCV Ab-positivity rates were high in our Japanese DM patients, a majority of liver injuries could be associated with NAFLD/nonalcoholic steatohepatitis.

  4. Drug-Eluting Beads Loaded With Doxorubicin (DEBDOX) Chemoembolisation Before Liver Transplantation for Hepatocellular Carcinoma: An Imaging/Histologic Correlation Study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pauwels, Xavier, E-mail: xpauwels@hotmail.com; Azahaf, Mustapha, E-mail: mustapha.azahaf@chru-lille.fr; Lassailly, Guillaume, E-mail: guillaume.lassailly@chru-lille.fr

    Purpose Most transplant centers use chemoembolisation as locoregional bridge therapy for hepatocellular carcinoma (HCC) before liver transplantation (LT). Chemoembolisation using beads loaded with doxorubicin (DEBDOX) is a promising technique that enables delivery of a large quantity of drugs against HCC. We sought to assess the imaging–histologic correlation after DEBDOX chemoembolisation.Materials and Methods All consecutive patients who had undergone DEBDOX chemoembolisation before receiving liver graft for HCC were included. Tumour response was evaluated according to Response Evaluation Criteria in Solid Tumours (RECIST) and modified RECIST (mRECIST) criteria. The result of final imaging made before LT was correlated with histological data to predict tumourmore » necrosis.ResultsTwenty-eight patients underwent 43 DEBDOX procedures for 45 HCC. Therapy had a significant effect as shown by a decrease in the mean size of the largest nodule (p = 0.02) and the sum of viable part of tumour sizes according to mRECIST criteria (p < 0.001). An objective response using mRECIST criteria was significantly correlated with mean tumour necrosis ≥90 % (p = 0.03). A complete response using mRECIST criteria enabled accurate prediction of complete tumour necrosis (p = 0.01). Correlations using RECIST criteria were not significant.ConclusionOur data confirm the potential benefit of DEBDOX chemoembolisation as bridge therapy before LT, and they provide a rational basis for new studies focusing on recurrence-free survival after LT. Radiologic evaluation according to mRECIST criteria enables accurate prediction of tumour necrosis, whereas RECIST criteria do not.« less

  5. Non-invasive oxidative stress markers for liver fibrosis development in the evolution of toxic hepatitis.

    PubMed

    Clichici, Simona; Catoi, C; Mocan, T; Filip, A; Login, C; Nagy, A; Daicoviciu, D; Decea, N; Gherman, C; Moldovan, R; Muresan, Adriana

    2011-06-01

    Oxidative stress is related to the liver fibrosis, anticipating the hepatic stellate cells' (HSC) activation. Our aim was to correlate oxidative stress markers with the histological liver alterations in order to identify predictive, noninvasive parameters of fibrosis progression in the evolution of toxic hepatitis.CCl4 in sunflower oil was administered to rats intragastrically, twice a week. After 2, 3, 4 and 8 weeks of treatment, plasma levels of malondialdehyde (MDA), protein carbonyls (PC), hydrogen donor capacity (HD), sulfhydryl groups (SH), and glutathione (GSH) were measured and histological examination of the liver slides was performed. Dynamics of histological disorders was assessed by The Knodell score. Significant elevation of inflammation grade was obtained after the second week of the experiment only (p=0.001), while fibrosis started to become significant (p=0.001) after 1 month of CCl4 administration. Between plasma MDA and liver fibrosis development a good correlation was obtained (r=0.877, p=0.05). Correlation between PC dynamics and liver alterations was marginally significant for inflammation grade (r=0.756, p=0.138). HD evolution revealed a marginally inverse correlation with inflammation grade (r=-0.794, p=0.108). No correlations could be established for other parameters with either inflammation grade or fibrosis stage.Our study shows that MDA elevation offers the best prediction potential for fibrosis, while marginal prediction fiability could be attributed to high levels of plasma PC and low levels of HD.

  6. Propylthiouracil-Induced Acute Liver Failure: Role of Liver Transplantation

    PubMed Central

    Carrion, Andres F.; Czul, Frank; Arosemena, Leopoldo R.; Selvaggi, Gennaro; Garcia, Monica T.; Tekin, Akin; Tzakis, Andreas G.; Martin, Paul; Ghanta, Ravi K.

    2010-01-01

    Propylthiouracil- (PTU-) induced hepatotoxicity is rare but potentially lethal with a spectrum of liver injury ranging from asymptomatic elevation of transaminases to fulminant hepatic failure and death. We describe two cases of acute hepatic failure due to PTU that required liver transplantation. Differences in the clinical presentation, histological characteristics, and posttransplant management are described as well as alternative therapeutic options. Frequent monitoring for PTU-induced hepatic dysfunction is strongly advised because timely discontinuation of this drug and implementation of noninvasive therapeutic interventions may prevent progression to liver failure or even death. PMID:21234410

  7. Histological versus clinical cirrhosis in chronic hepatitis C: does race/ethnicity really matter?

    PubMed

    Kohla, Mohamed; Iwata, Shunpei; Ea, Roth; Keyhan, Sanaz; Taylor, Robert; Yu, Mimi C; Groshen, Susan; Bonacini, Maurizio

    2012-03-01

    Liver fibrosis progression in hepatitis C virus (HCV) infection has been in part associated with race/ethnicity. Little is known of the frequency of clinical cirrhosis in Asian patients in the US. To compare histological and clinical features of chronic hepatitis C (CHC) in a multiethnic cohort of patients. Retrospective query of an electronic medical registry for CHC patients evaluated from 1999 to 2005. Histological cirrhosis was defined as advanced METAVIR fibrosis score at biopsy. Clinical cirrhosis was defined as any of: varices, ascites, or splenomegaly. Liver cirrhosis was defined as either histological or clinical cirrhosis. Chi-square tests, t tests, and logistic regression method were used for data analysis. Six hundred and ninety-two patients were categorized into four racial-ethnic groups: 292 Caucasian (C), 145 Hispanic (H), 121 African American (AA), and 134 Asian (As) patients. Median age of AA (54 years) and As (53) was higher than C (52), or H (50) (p < 0.05). H patients had a higher percentage of alcohol abuse (60%) than AA and C (42-44%) and As (14%; p < 0.0001). Body mass index (BMI) was significantly lower in Asians compared to all other groups (p < 0.0001). Features of the metabolic syndrome were common, ranging from 28% in As to 72% in H patients. Liver cirrhosis was found in 53% H, 35% C, 29% As, and 19% AA. In multivariable analysis, only alcohol abuse, BMI, diabetes mellitus (DM), and age were significantly associated with liver cirrhosis. There was a trend for AA to have less cirrhosis, either histological or clinical (p = 0.08). Using only histology, liver cirrhosis was significantly underestimated. In our cohort, severity of CHC was not clearly affected by race when alcohol use and features of the metabolic syndrome were taken into consideration. However, there was a trend for African Americans to have lower cirrhosis rates.

  8. Failure to obtain an autoimmune response following cryosurgery to the normal rat liver.

    PubMed Central

    Townell, N H; Tsantoulas, D; Holborow, E J; Hobbs, K E

    1980-01-01

    Smooth muscle antibody (SMA) and anti-liver-specific lipoprotein (anti-LSP) responses were investigated following five different freeze thaw regimes to the normal rat liver. The livers were examined histologically for evidence of autoimmune liver disease. No SMA or anti-LSP was found in any animal and on histological examination the unfrozen part of all livers was normal. It is concluded that cryosurgical damage to the liver is unlikely to provoke an autoimmune response. PMID:7460392

  9. 1H-Nuclear Magnetic Resonance-Based Plasma Metabolic Profiling of Dairy Cows with Fatty Liver

    PubMed Central

    Xu, Chuang; Sun, Ling-wei; Xia, Cheng; Zhang, Hong-you; Zheng, Jia-san; Wang, Jun-song

    2016-01-01

    Fatty liver is a common metabolic disorder of dairy cows during the transition period. Historically, the diagnosis of fatty liver has involved liver biopsy, biochemical or histological examination of liver specimens, and ultrasonographic imaging of the liver. However, more convenient and noninvasive methods would be beneficial for the diagnosis of fatty liver in dairy cows. The plasma metabolic profiles of dairy cows with fatty liver and normal (control) cows were investigated to identify new biomarkers using 1H nuclear magnetic resonance. Compared with the control group, the primary differences in the fatty liver group included increases in β-hydroxybutyric acid, acetone, glycine, valine, trimethylamine-N-oxide, citrulline, and isobutyrate, and decreases in alanine, asparagine, glucose, γ-aminobutyric acid glycerol, and creatinine. This analysis revealed a global profile of endogenous metabolites, which may present potential biomarkers for the diagnosis of fatty liver in dairy cows. PMID:26732447

  10. Donation after cardiac death liver transplantation: Graft quality evaluation based on pretransplant liver biopsy.

    PubMed

    Xia, Weiliang; Ke, Qinghong; Wang, Ye; Feng, Xiaowen; Guo, Haijun; Wang, Weilin; Zhang, Min; Shen, Yan; Wu, Jian; Xu, Xiao; Yan, Sheng; Zheng, Shusen

    2015-06-01

    Donation after cardiac death (DCD) liver grafts are associated with inferior clinical outcomes and high discard rates because of poor graft quality. We investigated the predictive value of DCD liver biopsy for the pretransplant graft quality evaluation. DCD liver transplants that took place between October 2010 and April 2014 were included (n = 127). Histological features of graft biopsy samples were analyzed to assess risk factors for graft survival. Macrovesicular steatosis ≥ 20% [hazard ratio (HR) = 2.973; P = 0.045] and sinusoidal neutrophilic infiltrate (HR = 6.969; P = 0.005) were confirmed as independent risk factors for graft survival; hepatocellular swelling, vacuolation, and necrosis failed to show prognostic value. Additionally, a donor serum total bilirubin level ≥ 34.2 μmol/L was also associated with a lower probability of graft survival. Our analysis indicates that macrovesicular steatosis ≥ 20% and sinusoidal neutrophilic infiltrate are novel and useful histological markers for DCD liver grafts with unacceptable quality. This finding can be used by transplant surgeons to improve DCD liver acceptance protocols. © 2015 American Association for the Study of Liver Diseases.

  11. Spatial Systems Lipidomics Reveals Nonalcoholic Fatty Liver Disease Heterogeneity

    PubMed Central

    2018-01-01

    Hepatocellular lipid accumulation characterizes nonalcoholic fatty liver disease (NAFLD). However, the types of lipids associated with disease progression are debated, as is the impact of their localization. Traditional lipidomics analysis using liver homogenates or plasma dilutes and averages lipid concentrations, and does not provide spatial information about lipid distribution. We aimed to characterize the distribution of specific lipid species related to NAFLD severity by performing label-free molecular analysis by mass spectrometry imaging (MSI). Fresh frozen liver biopsies from obese subjects undergoing bariatric surgery (n = 23) with various degrees of NAFLD were cryosectioned and analyzed by matrix-assisted laser desorption/ionization (MALDI)-MSI. Molecular identification was verified by tandem MS. Tissue sections were histopathologically stained, annotated according to the Kleiner classification, and coregistered with the MSI data set. Lipid pathway analysis was performed and linked to local proteome networks. Spatially resolved lipid profiles showed pronounced differences between nonsteatotic and steatotic tissues. Lipid identification and network analyses revealed phosphatidylinositols and arachidonic acid metabolism in nonsteatotic regions, whereas low–density lipoprotein (LDL) and very low–density lipoprotein (VLDL) metabolism was associated with steatotic tissue. Supervised and unsupervised discriminant analysis using lipid based classifiers outperformed simulated analysis of liver tissue homogenates in predicting steatosis severity. We conclude that lipid composition of steatotic and nonsteatotic tissue is highly distinct, implying that spatial context is important for understanding the mechanisms of lipid accumulation in NAFLD. MSI combined with principal component–linear discriminant analysis linking lipid and protein pathways represents a novel tool enabling detailed, comprehensive studies of the heterogeneity of NAFLD. PMID:29570976

  12. The protective effect of hydroalcoholic extract of Ginger (Zingiber officinale Rosc.) against iron-induced functional and histological damages in rat liver and kidney

    PubMed Central

    Gholampour, Firouzeh; Behzadi Ghiasabadi, Fatemeh; Owji, Seyed Mohammad; Vatanparast, Jaafar

    2017-01-01

    Objective: Iron overload in the body is related with toxic effects and threatens the health. The aim of this study was to evaluate the protective role of hydroalcoholic extract of ginger (Zingiber officinale) against ferrous sulfate-induced hepatic and renal functional disorders and histological damages in rats. Materials and Methods: The rats were divided into four groups (n=7): Sham, Sham + G.E (ginger extract, 400 mg/kg/day for 14 days), FS (ferrous sulfate, 30 mg/kg/day for 14 days), FS+G.E (ferrous sulfate, 30 mg/kg/day for 14 days; ginger extract, 400 mg/kg/day for 11 days from the fourth day of ferrous sulfate injection). After 24 hr, blood, urine and tissue samples were collected. Results: Compared with Sham and Sham + G.E groups, administration of ferrous sulfate resulted in liver and kidney dysfunction as evidenced by significantly higher levels of serum hepatic markers and bilirubin, and lower levels of serum albumin, total protein, triglyceride, cholesterol and glucose, as well as lower creatinine clearance and higher fractional excretion of sodium (p<0.001). This was accompanied by increased malondialdehyde levels and histological damages (p<0.001). In the FS + G.E, ginger extract significantly (p<0.01) reversed the levels of serum hepatic markers, renal functional markers and lipid peroxidation marker. Furthermore, it restored the levels of serum total protein, albumin, glucose, triglycerides and cholesterol and decreased bilirubin concentration in the blood. All these changes were corroborated by histological observations of liver and kidney. Conclusion: In conclusion, ginger extract appears to exert protective effects against ferrous sulfate-induced hepatic and renal toxicity by reducing lipid peroxidation and chelating iron. PMID:29299437

  13. The protective effect of hydroalcoholic extract of Ginger (Zingiber officinale Rosc.) against iron-induced functional and histological damages in rat liver and kidney.

    PubMed

    Gholampour, Firouzeh; Behzadi Ghiasabadi, Fatemeh; Owji, Seyed Mohammad; Vatanparast, Jaafar

    2017-01-01

    Iron overload in the body is related with toxic effects and threatens the health. The aim of this study was to evaluate the protective role of hydroalcoholic extract of ginger ( Zingiber officinale ) against ferrous sulfate-induced hepatic and renal functional disorders and histological damages in rats. The rats were divided into four groups (n=7): Sham, Sham + G.E (ginger extract, 400 mg/kg/day for 14 days), FS (ferrous sulfate, 30 mg/kg/day for 14 days), FS+G.E (ferrous sulfate, 30 mg/kg/day for 14 days; ginger extract, 400 mg/kg/day for 11 days from the fourth day of ferrous sulfate injection). After 24 hr, blood, urine and tissue samples were collected. Compared with Sham and Sham + G.E groups, administration of ferrous sulfate resulted in liver and kidney dysfunction as evidenced by significantly higher levels of serum hepatic markers and bilirubin, and lower levels of serum albumin, total protein, triglyceride, cholesterol and glucose, as well as lower creatinine clearance and higher fractional excretion of sodium (p<0.001). This was accompanied by increased malondialdehyde levels and histological damages (p<0.001). In the FS + G.E, ginger extract significantly (p<0.01) reversed the levels of serum hepatic markers, renal functional markers and lipid peroxidation marker. Furthermore, it restored the levels of serum total protein, albumin, glucose, triglycerides and cholesterol and decreased bilirubin concentration in the blood. All these changes were corroborated by histological observations of liver and kidney. In conclusion, ginger extract appears to exert protective effects against ferrous sulfate-induced hepatic and renal toxicity by reducing lipid peroxidation and chelating iron.

  14. Markers of activated inflammatory cells correlate with severity of liver damage in children with nonalcoholic fatty liver disease.

    PubMed

    De Vito, Rita; Alisi, Anna; Masotti, Andrea; Ceccarelli, Sara; Panera, Nadia; Citti, Arianna; Salata, Michele; Valenti, Luca; Feldstein, Ariel E; Nobili, Valerio

    2012-07-01

    Concomitantly to the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become the leading cause of liver disease in children. NAFLD encompasses a spectrum of histological damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), with possible progression to cirrhosis. There is growing evidence that the immune system plays a pivotal role in the initiation and progression to NASH but the cellular nature of the hepatic inflammation is still unknown. The present study includes 34 children with biopsy-proven NAFLD. Liver damage was evaluated by the NAFLD activity score (NAS), and the inflammatory infiltrate was characterized by immunohistochemistry for CD45, CD3 and CD163 which are markers of leukocytes, T cells and activated Kupffer cells/macrophages, respectively. Our results have shown that CD45+ (P<0.0001) and CD163+ (P<0.0001) cells were markedly increased in children with severe histological activity (NAS≥5) compared to children with lower activity (NAS<5), whereas CD3+ cells were significantly lower (P<0.01) in children with severe histological activity. There was a significant association between the numbers of CD45+, CD3+ and CD163+ cells, regarding both the portal tract and liver lobule, and the severity of steatosis, ballooning and fibrosis (P<0.01). These data suggest that the severity and composition of the inflammatory infiltrate correlate with steatosis and the severity of disease in children with NAFLD. Moreover, a decrease in CD3+ cells may be involved in the pathogenesis of liver damage. Future studies should evaluate whether it can predict the progression of liver disease independently of established histological scores.

  15. M1 macrophage infiltrations and histological changes in the liver after portal vein embolization using fibrinogen and OK432 in the rat.

    PubMed

    Sato, Tetsu; Marubashi, Shigeru; Kenjo, Akira; Tsuchiya, Takao; Kimura, Takashi; Sato, Naoya; Watanabe, Junichiro; Tasaki, Kazuhiro; Hashimoto, Yuko; Wada, Ikuo; Gotoh, Mitsukazu

    2016-05-01

    The mechanism of anti-tumor effect of transarterial Immuno-Embolization (TIE) using OK-432 has not been well elucidated. In this study, we aimed to investigate the tissue injury and immune response after portal venous embolization (PVE) with/without OK-432. Embolic materials (L group: lipiodol, LF group: lipiodol+fibrinogen, LO group: lipiodol+OK-432, LFO group: lipiodol+fibrinogen+OK-432) were administered via the right portal vein in Wistar rats. The histological findings in LFO group demonstrated liver damage with severe architectural changes. The concentrations of CD68(+) cells were observed in a time-dependent manner; it was significantly increased in the LO group on day 1 and in the LFO group on day 3. CD68(+)CD163(-) macrophages significantly increased in the LFO group on day 7 (P<0.05). In conclusion, PVE with fibrinogen and OK-432 markedly increased the CD68(+)CD163(-) infiltrating macrophages around the peri-portal area in the liver. This novel technique could be applied as immune-enhanced chemo-embolization of liver tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Neonatal liver failure and Leigh syndrome possibly due to CoQ-responsive OXPHOS deficiency.

    PubMed

    Leshinsky-Silver, E; Levine, A; Nissenkorn, A; Barash, V; Perach, M; Buzhaker, E; Shahmurov, M; Polak-Charcon, S; Lev, D; Lerman-Sagie, T

    2003-08-01

    CoQ transfers electrons from complexes I and II of the mitochondrial respiratory chain to complex III. There are very few reports on human CoQ deficiency. The clinical presentation is usually characterized by: epilepsy, muscle weakness, ataxia, cerebellar atrophy, migraine, myogloblinuria and developmental delay. We describe a patient who presented with neonatal liver and pancreatic insufficiency, tyrosinemia and hyperammonemia and later developed sensorineural hearing loss and Leigh syndrome. Liver biopsy revealed markedly reduced complex I+III and II+III. Addition of CoQ to the liver homogenate restored the activities, suggesting CoQ depletion. Histological staining showed prominent bridging; septal fibrosis and widening of portal spaces with prominent mixed inflammatory infiltrate, associated with interface hepatitis, bile duct proliferation with numerous bile plugs. Electron microscopy revealed a large number of mitochondria, which were altered in shape and size, widened and disordered intercristal spaces. This may be the first case of Leigh syndrome with liver and pancreas insufficiency, possibly caused by CoQ responsive oxphos deficiency.

  17. The Natural Course of Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Calzadilla Bertot, Luis; Adams, Leon Anton

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM). NAFLD exhibits a histological spectrum, ranging from “bland steatosis” to the more aggressive necro-inflammatory form, non-alcoholic steatohepatitis (NASH) which may accumulate fibrosis to result in cirrhosis. Emerging data suggests fibrosis, rather than NASH per se, to be the most important histological predictor of liver and non-liver related death. Nevertheless, only a small proportion of individuals develop cirrhosis, however the large proportion of the population affected by NAFLD has led to predictions that NAFLD will become a leading cause of end stage liver disease, hepatocellular carcinoma (HCC), and indication for liver transplantation. HCC may arise in non-cirrhotic liver in the setting of NAFLD and is associated with the presence of the metabolic syndrome (MetS) and male gender. The MetS and its components also play a key role in the histological progression of NAFLD, however other genetic and environmental factors may also influence the natural history. The importance of NAFLD in terms of overall survival extends beyond the liver where cardiovascular disease and malignancy represents additional important causes of death. PMID:27213358

  18. CITED1 Expression in Liver Development and Hepatoblastoma12

    PubMed Central

    Murphy, Andrew J; de Caestecker, Christian; Pierce, Janene; Boyle, Scott C; Ayers, Gregory D; Zhao, Zhiguo; Libes, Jaime M; Correa, Hernan; Walter, Teagan; Huppert, Stacey S; Perantoni, Alan O; de Caestecker, Mark P; Lovvorn, Harold N

    2012-01-01

    Hepatoblastoma, the most common pediatric liver cancer, consists of epithelial mixed embryonal/fetal (EMEF) and pure fetal histologic subtypes, with the latter exhibiting a more favorable prognosis. Few embryonal histology markers that yield insight into the biologic basis for this prognostic discrepancy exist. CBP/P-300 interacting transactivator 1 (CITED1), a transcriptional co-activator, is expressed in the self-renewing nephron progenitor population of the developing kidney and broadly in its malignant analog, Wilms tumor (WT). In this current study, CITED1 expression is detected in mouse embryonic liver initially on post-coitum day 10.5 (e10.5), begins to taper by e14.5, and is undetectable in e18.5 and adult livers. CITED1 expression is detected in regenerating murine hepatocytes following liver injury by partial hepatectomy and 3,5-diethoxycarbonyl-1,4-dihydrocollidine. Importantly, while CITED1 is undetectable in normal human adult livers, 36 of 41 (87.8%) hepatoblastoma specimens express CITED1, where it is enriched in EMEF specimens compared to specimens of pure fetal histology. CITED1 overexpression in Hep293TT human hepatoblastoma cells induces cellular proliferation and upregulates the Wnt inhibitors Kringle containing transmembrane protein 1 (KREMEN1) and CXXC finger protein 4 (CXXC4). CITED1 mRNA expression correlates with expression of CXXC4 and KREMEN1 in clinical hepatoblastoma specimens. These data show that CITED1 is expressed during a defined time course of liver development and is no longer expressed in the adult liver but is upregulated in regenerating hepatocytes following liver injury. Moreover, as in WT, this embryonic marker is reexpressed in hepatoblastoma and correlates with embryonal histology. These findings identify CITED1 as a novel marker of hepatic progenitor cells that is re-expressed following liver injury and in embryonic liver tumors. PMID:23308048

  19. Structural and ultrastructural study of rat liver influenced by electromagnetic radiation.

    PubMed

    Holovská, K; Almášiová, V; Cigánková, V; Beňová, K; Račeková, E; Martončíková, M

    2015-01-01

    Mobile communication systems are undoubtedly an environmental source of electromagnetic radiation (EMR). There is an increasing concern regarding the interactions of EMR with the humans. The aim of this study was to examine the effects of EMR on Wistar rat liver. Mature rats were exposed to electromagnetic field of frequency 2.45 GHz and mean power density of 2.8 mW/cm2 for 3 h/d for 3 wk. Samples of the liver were obtained 3 h after the last irradiation and processed histologically for light and transmission electron microscopy. Data demonstrated the presence of moderate hyperemia, dilatation of liver sinusoids, and small inflammatory foci in the center of liver lobules. Structure of hepatocytes was not altered and all described changes were classified as moderate. Electron microscopy of hepatocytes revealed vesicles of different sizes and shapes, lipid droplets, and proliferation of smooth endoplasmic reticulum. Occasionally necrotizing hepatocytes were observed. Our observations demonstrate that EMR exposure produced adverse effects on rat liver.

  20. Fatal methanol poisoning: features of liver histopathology.

    PubMed

    Akhgari, Maryam; Panahianpour, Mohammad Hadi; Bazmi, Elham; Etemadi-Aleagha, Afshar; Mahdavi, Amirhosein; Nazari, Saeed Hashemi

    2013-03-01

    Methanol poisoning has become a considerable problem in Iran. Liver can show some features of poisoning after methanol ingestion. Therefore, our concern was to examine liver tissue histopathology in fatal methanol poisoning cases in Iranian population. In this study, 44 cases of fatal methanol poisoning were identified in a year. The histological changes of the liver were reviewed. The most striking features of liver damage by light microscopy were micro-vesicular steatosis, macro-vesicular steatosis, focal hepatocyte necrosis, mild intra-hepatocyte bile stasis, feathery degeneration and hydropic degeneration. Blood and vitreous humor methanol concentrations were examined to confirm the proposed history of methanol poisoning. The majority of cases were men (86.36%). In conclusion, methanol poisoning can cause histological changes in liver tissues. Most importantly in cases with mean blood and vitreous humor methanol levels greater than 127 ± 38.9 mg/dL more than one pathologic features were detected.

  1. Effect of diffusion time on liver DWI: an experimental study of normal and fibrotic livers.

    PubMed

    Zhou, Iris Y; Gao, Darwin S; Chow, April M; Fan, Shujuan; Cheung, Matthew M; Ling, Changchun; Liu, Xiaobing; Cao, Peng; Guo, Hua; Man, Kwan; Wu, Ed X

    2014-11-01

    To investigate whether diffusion time (Δ) affects the diffusion measurements in liver and their sensitivity in detecting fibrosis. Liver fibrosis was induced in Sprague-Dawley rats (n = 12) by carbon tetrachloride (CCl(4)) injections. Diffusion-weighted MRI was performed longitudinally during 8-week CCl(4) administration at 7 Tesla (T) using single-shot stimulated-echo EPI with five b-values (0 to 1000 s/mm(2)) and three Δs. Apparent diffusion coefficient (ADC) and true diffusion coefficient (D(true)) were calculated by using all five b-values and large b-values, respectively. ADC and D(true) decreased with Δ for both normal and fibrotic liver at each time point. ADC and D(true) also generally decreased with the time after CCl(4) insult. The reductions in D(true) between 2-week and 4-week CCl(4) insult were larger than the ADC reductions at all Δs. At each time point, D(true) measured with long Δ (200 ms) detected the largest changes among the 3 Δs examined. Histology revealed gradual collagen deposition and presence of intracellular fat vacuoles after CCl(4) insult. Our results demonstrated the Δ dependent diffusion measurements, indicating restricted diffusion in both normal and fibrotic liver. D(true) measured with long Δ acted as a more sensitive index of the pathological alterations in liver microstructure during fibrogenesis. Copyright © 2013 Wiley Periodicals, Inc.

  2. A Pilot Comparative Study of Quantitative Ultrasound, Conventional Ultrasound, and MRI for Predicting Histology-Determined Steatosis Grade in Adult Nonalcoholic Fatty Liver Disease

    PubMed Central

    Paige, Jeremy S.; Bernstein, Gregory S.; Heba, Elhamy; Costa, Eduardo A. C.; Fereirra, Marilia; Wolfson, Tanya; Gamst, Anthony C.; Valasek, Mark A.; Lin, Grace Y.; Han, Aiguo; Erdman, John W.; O’Brien, William D.; Andre, Michael P.; Loomba, Rohit; Sirlin, Claude B.

    2017-01-01

    OBJECTIVE The purpose of this study is to explore the diagnostic performance of two investigational quantitative ultrasound (QUS) parameters, attenuation coefficient and backscatter coefficient, in comparison with conventional ultrasound (CUS) and MRI-estimated proton density fat fraction (PDFF) for predicting histology-confirmed steatosis grade in adults with nonalcoholic fatty liver disease (NAFLD). SUBJECTS AND METHODS In this prospectively designed pilot study, 61 adults with histology-confirmed NAFLD were enrolled from September 2012 to February 2014. Subjects underwent QUS, CUS, and MRI examinations within 100 days of clinical-care liver biopsy. QUS parameters (attenuation coefficient and backscatter coefficient) were estimated using a reference phantom technique by two analysts independently. Three-point ordinal CUS scores intended to predict steatosis grade (1, 2, or 3) were generated independently by two radiologists on the basis of QUS features. PDFF was estimated using an advanced chemical shift–based MRI technique. Using histologic examination as the reference standard, ROC analysis was performed. Optimal attenuation coefficient, backscatter coefficient, and PDFF cutoff thresholds were identified, and the accuracy of attenuation coefficient, backscatter coefficient, PDFF, and CUS to predict steatosis grade was determined. Interobserver agreement for attenuation coefficient, backscatter coefficient, and CUS was analyzed. RESULTS CUS had 51.7% grading accuracy. The raw and cross-validated steatosis grading accuracies were 61.7% and 55.0%, respectively, for attenuation coefficient, 68.3% and 68.3% for backscatter coefficient, and 76.7% and 71.3% for MRI-estimated PDFF. Interobserver agreements were 53.3% for CUS (κ = 0.61), 90.0% for attenuation coefficient (κ = 0.87), and 71.7% for backscatter coefficient (κ = 0.82) (p < 0.0001 for all). CONCLUSION Preliminary observations suggest that QUS parameters may be more accurate and provide higher

  3. A Pilot Comparative Study of Quantitative Ultrasound, Conventional Ultrasound, and MRI for Predicting Histology-Determined Steatosis Grade in Adult Nonalcoholic Fatty Liver Disease.

    PubMed

    Paige, Jeremy S; Bernstein, Gregory S; Heba, Elhamy; Costa, Eduardo A C; Fereirra, Marilia; Wolfson, Tanya; Gamst, Anthony C; Valasek, Mark A; Lin, Grace Y; Han, Aiguo; Erdman, John W; O'Brien, William D; Andre, Michael P; Loomba, Rohit; Sirlin, Claude B

    2017-05-01

    The purpose of this study is to explore the diagnostic performance of two investigational quantitative ultrasound (QUS) parameters, attenuation coefficient and backscatter coefficient, in comparison with conventional ultrasound (CUS) and MRI-estimated proton density fat fraction (PDFF) for predicting histology-confirmed steatosis grade in adults with nonalcoholic fatty liver disease (NAFLD). In this prospectively designed pilot study, 61 adults with histology-confirmed NAFLD were enrolled from September 2012 to February 2014. Subjects underwent QUS, CUS, and MRI examinations within 100 days of clinical-care liver biopsy. QUS parameters (attenuation coefficient and backscatter coefficient) were estimated using a reference phantom technique by two analysts independently. Three-point ordinal CUS scores intended to predict steatosis grade (1, 2, or 3) were generated independently by two radiologists on the basis of QUS features. PDFF was estimated using an advanced chemical shift-based MRI technique. Using histologic examination as the reference standard, ROC analysis was performed. Optimal attenuation coefficient, backscatter coefficient, and PDFF cutoff thresholds were identified, and the accuracy of attenuation coefficient, backscatter coefficient, PDFF, and CUS to predict steatosis grade was determined. Interobserver agreement for attenuation coefficient, backscatter coefficient, and CUS was analyzed. CUS had 51.7% grading accuracy. The raw and cross-validated steatosis grading accuracies were 61.7% and 55.0%, respectively, for attenuation coefficient, 68.3% and 68.3% for backscatter coefficient, and 76.7% and 71.3% for MRI-estimated PDFF. Interobserver agreements were 53.3% for CUS (κ = 0.61), 90.0% for attenuation coefficient (κ = 0.87), and 71.7% for backscatter coefficient (κ = 0.82) (p < 0.0001 for all). Preliminary observations suggest that QUS parameters may be more accurate and provide higher interobserver agreement than CUS for predicting hepatic

  4. A histological atlas of the tissues and organs of neotenic and metamorphosed axolotl.

    PubMed

    Demircan, Turan; İlhan, Ayşe Elif; Aytürk, Nilüfer; Yıldırım, Berna; Öztürk, Gürkan; Keskin, İlknur

    2016-09-01

    Axolotl (Ambystoma Mexicanum) has been emerging as a promising model in stem cell and regeneration researches due to its exceptional regenerative capacity. Although it represents lifelong lasting neoteny, induction to metamorphosis with thyroid hormones (THs) treatment advances the utilization of Axolotl in various studies. It has been reported that amphibians undergo anatomical and histological remodeling during metamorphosis and this transformation is crucial for adaptation to terrestrial conditions. However, there is no comprehensive histological investigation regarding the morphological alterations of Axolotl organs and tissues throughout the metamorphosis. Here, we reveal the histological differences or resemblances between the neotenic and metamorphic axolotl tissues. In order to examine structural features and cellular organization of Axolotl organs, we performed Hematoxylin & Eosin, Luxol-Fast blue, Masson's trichrome, Alcian blue, Orcein and Weigart's staining. Stained samples from brain, gallbladder, heart, intestine, liver, lung, muscle, skin, spleen, stomach, tail, tongue and vessel were analyzed under the light microscope. Our findings contribute to the validation of the link between newly acquired functions and structural changes of tissues and organs as observed in tail, skin, gallbladder and spleen. We believe that this descriptive work provides new insights for a better histological understanding of both neotenic and metamorphic Axolotl tissues. Copyright © 2016 Elsevier GmbH. All rights reserved.

  5. Toxicity of Doxorubicin on Pig Liver After Chemoembolization with Doxorubicin-loaded Microspheres: A Pilot DNA-microarrays and Histology Study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Verret, Valentin, E-mail: valentin.verret@archimmed.com; Namur, Julien; Ghegediban, Saieda Homayra

    The potential mechanisms accounting for the hepatotoxicity of doxorubicin-loaded microspheres in chemoembolization were examined by combining histology and DNA-microarray techniques.The left hepatic arteries of two pigs were embolized with 1 mL of doxorubicin-loaded (25 mg; (DoxMS)) or non-loaded (BlandMS) microspheres. The histopathological effects of the embolization were analyzed at 1 week. RNAs extracted from both the embolized and control liver areas were hybridized onto Agilent porcine microarrays. Genes showing significantly different expression (p < 0.01; fold-change > 2) between two groups were classified by biological process. At 1 week after embolization, DoxMS caused arterial and parenchymal necrosis in 51 andmore » 38 % of embolized vessels, respectively. By contrast, BlandMS did not cause any tissue damage. Up-regulated genes following embolization with DoxMS (vs. BlandMS, n = 353) were mainly involved in cell death, apoptosis, and metabolism of doxorubicin. Down-regulated genes (n = 120) were mainly related to hepatic functions, including enzymes of lipid and carbohydrate metabolisms. Up-regulated genes included genes related to cell proliferation (growth factors and transcription factors), tissue remodeling (MMPs and several collagen types), inflammatory reaction (interleukins and chemokines), and angiogenesis (angiogenic factors and HIF1a pathway), all of which play an important role in liver healing and regeneration. DoxMS caused lesions to the liver, provoked cell death, and disturbed liver metabolism. An inflammatory repair process with cell proliferation, tissue remodeling, and angiogenesis was rapidly initiated during the first week after chemoembolization. This pilot study provides a comprehensive method to compare different types of DoxMS in healthy animals or tumor models.« less

  6. The absence of obstructive sleep apnea may protect against non-alcoholic fatty liver in patients undergoing bariatric surgery.

    PubMed

    Corey, Kathleen E; Misdraji, Joseph; Zheng, Hui; Malecki, Kyle M; Kneeman, Jacob; Gelrud, Louis; Chung, Raymond T

    2013-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide and its progressive form, steatohepatitis, will be the leading indication for liver transplant by 2020. While risk factors for steatohepatitis have been identified, little work has been performed to identify factors protective against NAFLD development. This study sought to identify factors predictive of normal liver histology in a bariatric cohort. Patients undergoing weight loss surgery with liver biopsies at the time of surgery were included. Patients with other causes of chronic liver disease were excluded. One hundred fifty-nine patients were included. Forty-nine patients had normal liver histology and 110 patients had NAFLD. Several previously identified factors associated with normal liver histology were found. Black race was the strongest predictor of the absence of NAFLD with an odds ratio (OR) of 6.8, 95% confidence interval (CI) 2.4-18.9. Low HOMA-IR was also associated with normal histology (OR 1.4, 95% CI 1.03-1.9). In contrast, low HDL was associated with a decreased chance of normal histology (OR 0.38, 95% CI 0.05-0.83). Interestingly, a novel protective factor, the absence of obstructive sleep apnea (OSA) was strongly associated with normal histology (OR 5.6, 95% CI 2.0-16.1). In multivariate regression controlling for BMI, black race, absence of OSA, low HOMA-IR and low ALT independently predicted normal liver histology with an area under the ROC curve of 0.85. Our study confirmed several factors associated with normal liver histology, including black race and identified a novel factor, absence of OSA. Further evaluation of these factors will allow for improved understanding of the pathogenesis of NAFLD.

  7. The protective effect of pentoxifylline versus silymarin on the pancreas through increasing adenosine by CD39 in a rat model of liver cirrhosis: Pharmacological, biochemical and histological study.

    PubMed

    Mohamed, Doaa I; Nabih, Enas S; El-Waseef, Dalia A A; El-Kharashi, Omnyah A; Abd El Samad, Abeer A

    2018-04-20

    Impaired glucose homoeostasis due to insulin resistance and decrease sensitivity of pancreatic β-cells is a feature of liver disease and results into hepatogenous diabetes. Decrease expression of CD39 was linked to inflammation and occurrence of diabetes. Therefore, we performed this study to explore the protective effect of pentoxifylline (PTX) and silymarin administration on the β-cells of the pancreas in a rat model of thioacetamide induced liver cirrhosis. Biochemical, histological and immunohistochemistry studies of the liver and pancreas were performed and provided an evidence on the protective effect of PTX to pancreatic β-cells compared to silymarin. Also, silymarin induced a significant improvement of liver cirrhosis compared to PTX. In conclusion, the potential protective effect of PTX against β-cells deterioration could be attributed to increasing pancreatic CD39 expression and the subsequent increase of adenosine. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Association between macroscopic appearance of liver lesions and liver histology in dogs with splenic hemangiosarcoma: 79 cases (2004-2009).

    PubMed

    Clendaniel, Daphne C; Sivacolundhu, Ramesh K; Sorenmo, Karin U; Donovan, Taryn A; Turner, Avenelle; Arteaga, Theresa; Bergman, Philip J

    2014-01-01

    Medical records for 79 dogs with confirmed splenic hemangiosarcoma (HSA) following splenectomy were reviewed for information regarding either the presence or absence of macroscopic liver lesions and the histopathological characteristics of the liver. Only 29 of 58 dogs (50%) with grossly abnormal livers had HSA metastasis. No dogs with grossly normal livers had metastasis detected on liver pathology. Gross lesions in the liver such as multiple nodules, dark-colored nodules, and active bleeding nodules were highly associated with malignancy. For the dogs in this study, performing biopsy in a grossly normal liver was a low-yield procedure in dogs with splenic HSA.

  9. Non-alcoholic Fatty Liver Disease (NAFLD)--A Review.

    PubMed

    Karim, M F; Al-Mahtab, M; Rahman, S; Debnath, C R

    2015-10-01

    Non-alcoholic fatty liver disease (NAFLD) is an emerging problem in Hepatology clinics. It is closely related to the increased frequency of overweight or obesity. It has recognised association with metabolic syndrome. Central obesity, diabetes mellitus, dyslipidemia are commonest risk factors. Association with hepatitis C genotype 3 is also recognised. NAFLD is an important cause of cyptogenic cirrhosis of liver. It affects all populations and all age groups. Most patients with NAFLD are asymptomatic or vague upper abdominal pain. Liver function tests are mostly normal or mild elevation of aminotranferases. Histological features almost identical to those of alcohol-induced liver damage and can range from mild steatosis to cirrhosis. Two hit hypothesis is prevailing theory for the development of NAFLD. Diagnosis is usually made by imaging tools like ultrasonogram which reveal a bright liver while liver biopsy is gold standard for diagnosis as well as differentiating simple fatty liver and non-alcoholic steatohepatitis (NASH). Prognosis is variable. Simple hepatic steatosis generally has a benign long-term prognosis. However, one to two third of NASH progress to fibrosis or cirrhosis and may have a similar prognosis as cirrhosis from other liver diseases. Treatment is mostly control of underlying disorders and dietary advice, exercise, insulin sensitizers, antioxidants, or cytoprotective agents. The prevalence of NAFLD is increasing. So it needs more research to address this problem.

  10. Fish gut-liver immunity during homeostasis or inflammation revealed by integrative transcriptome and proteome studies

    NASA Astrophysics Data System (ADS)

    Wu, Nan; Song, Yu-Long; Wang, Bei; Zhang, Xiang-Yang; Zhang, Xu-Jie; Wang, Ya-Li; Cheng, Ying-Yin; Chen, Dan-Dan; Xia, Xiao-Qin; Lu, Yi-Shan; Zhang, Yong-An

    2016-11-01

    The gut-associated lymphoid tissue, connected with liver via bile and blood, constructs a local immune environment of both defense and tolerance. The gut-liver immunity has been well-studied in mammals, yet in fish remains largely unknown, even though enteritis as well as liver and gallbladder syndrome emerged as a limitation in aquaculture. In this study, we performed integrative bioinformatic analysis for both transcriptomic (gut and liver) and proteomic (intestinal mucus and bile) data, in both healthy and infected tilapias. We found more categories of immune transcripts in gut than liver, as well as more adaptive immune in gut meanwhile more innate in liver. Interestingly reduced differential immune transcripts between gut and liver upon inflammation were also revealed. In addition, more immune proteins in bile than intestinal mucus were identified. And bile probably providing immune effectors to intestinal mucus upon inflammation was deduced. Specifically, many key immune transcripts in gut or liver as well as key immune proteins in mucus or bile were demonstrated. Accordingly, we proposed a hypothesized profile of fish gut-liver immunity, during either homeostasis or inflammation. Current data suggested that fish gut and liver may collaborate immunologically while keep homeostasis using own strategies, including potential unique mechanisms.

  11. Fialuridine induces acute liver failure in chimeric TK-NOG mice: a model for detecting hepatic drug toxicity prior to human testing.

    PubMed

    Xu, Dan; Nishimura, Toshi; Nishimura, Sachiko; Zhang, Haili; Zheng, Ming; Guo, Ying-Ying; Masek, Marylin; Michie, Sara A; Glenn, Jeffrey; Peltz, Gary

    2014-04-01

    Seven of 15 clinical trial participants treated with a nucleoside analogue (fialuridine [FIAU]) developed acute liver failure. Five treated participants died, and two required a liver transplant. Preclinical toxicology studies in mice, rats, dogs, and primates did not provide any indication that FIAU would be hepatotoxic in humans. Therefore, we investigated whether FIAU-induced liver toxicity could be detected in chimeric TK-NOG mice with humanized livers. Control and chimeric TK-NOG mice with humanized livers were treated orally with FIAU 400, 100, 25, or 2.5 mg/kg/d. The response to drug treatment was evaluated by measuring plasma lactate and liver enzymes, by assessing liver histology, and by electron microscopy. After treatment with FIAU 400 mg/kg/d for 4 d, chimeric mice developed clinical and serologic evidence of liver failure and lactic acidosis. Analysis of liver tissue revealed steatosis in regions with human, but not mouse, hepatocytes. Electron micrographs revealed lipid and mitochondrial abnormalities in the human hepatocytes in FIAU-treated chimeric mice. Dose-dependent liver toxicity was detected in chimeric mice treated with FIAU 100, 25, or 2.5 mg/kg/d for 14 d. Liver toxicity did not develop in control mice that were treated with the same FIAU doses for 14 d. In contrast, treatment with another nucleotide analogue (sofosbuvir 440 or 44 mg/kg/d po) for 14 d, which did not cause liver toxicity in human trial participants, did not cause liver toxicity in mice with humanized livers. FIAU-induced liver toxicity could be readily detected using chimeric TK-NOG mice with humanized livers, even when the mice were treated with a FIAU dose that was only 10-fold above the dose used in human participants. The clinical features, laboratory abnormalities, liver histology, and ultra-structural changes observed in FIAU-treated chimeric mice mirrored those of FIAU-treated human participants. The use of chimeric mice in preclinical toxicology studies could improve

  12. Rapidly progressing malignant insulinoma presented with multiple liver metastases: a case report.

    PubMed

    Erdogan, Askin; Askin, Erdogan; Kose, Fatih; Fatih, Kose; Akkaya, Hampar; Hampar, Akkaya; Bascil Tutuncu, Neslihan; Tutuncu, Neslihan Bascil; Ozyilkan, Ozgur; Ozgur, Ozyilkan

    2010-12-01

    A 51-year-old female was admitted to emergency unit with sudden loss of consciousness. Her blood glucose level from fingertip was 33 mg/dl, and insulin level was 55 (normal range, 4-17 IU). Abdominal ultrasonography revealed pancreatic mass with diffuse liver metastases. Biopsy of liver metastases showed differentiated neuroendocrine carcinoma. Diazoxide and chemotherapy stabilized her glucose level for more than 4 months. However, the disease showed progression, and death occurred 8 months later. In conclusion, this case may suggest that biologic behavior may differ from histological behavior in insulinoma and platin-based systemic chemotherapy may provide some benefit in patients those who had diazoxide- and octreotide-resistant tumors.

  13. Histological Changes in Autoimmune Hepatitis with Graves' Disease: A Child Case Report.

    PubMed

    Yamada, Mamiko; Shibata, Hironori; Masugi, Yohei; Ishi, Tomohiro; Kameyama, Kaori; Ebinuma, Hirotoshi; Hasegawa, Tomonobu

    2017-08-15

    We herein report a child case of autoimmune hepatitis (AIH) accompanied with Graves' disease. Elevated aminotransferase levels were found in a 12-year-old Japanese girl with Graves' disease. In her first liver biopsy, necrosis and inflammation was limited to the centrilobular area, while the second biopsy showed different findings. Namely, portal injury newly appeared, including interface hepatitis, which represents the histological characteristics of AIH. As the histological findings at the onset of AIH do not always show typical findings, a re-biopsy is considered to be important in individuals suspected to have AIH. AIH should be included in the differential diagnosis of liver dysfunction in Graves' disease, even in children.

  14. Comparison of Elastography, Serum Marker Scores, and Histology for the Assessment of Liver Fibrosis in Hepatitis B Virus (HBV)-Infected Patients in Burkina Faso

    PubMed Central

    Bonnard, Philippe; Sombié, Roger; Lescure, Francois-Xavier; Bougouma, Alain; Guiard-Schmid, Jean Baptiste; Poynard, Thierry; Calès, Paul; Housset, Chantal; Callard, Patrice; Pendeven, Catherine Le; Drabo, Joseph; Carrat, Fabrice; Pialoux, Gilles

    2010-01-01

    Liver fibrosis (LF) must be assessed before talking treatment decisions in hepatitis B. In Burkina Faso, liver biopsy (LB) remains the “gold standard” method for this purpose. Access to treatment might be simpler if reliable alternative techniques for LF evaluation were available. The hepatitis B virus (HBV)-infected patients who underwent LB was invited to have liver stiffness measurement (Fibroscan) and serum marker assays. Fifty-nine patients were enrolled. The performance of each technique for distinguishing F0F1 from F2F3F4 was compared. The area under receiver operating characteristic (AUROC) curves was 0.61, 0.71, 0.79, 0.82, and 0.87 for the aspartate transaminase to platelet ratio index (APRI), Fib-4, Fibrotest, Fibrometre, and Fibroscan. Elastometric thresholds were identified for significant fibrosis and cirrhosis. Combined use of Fibroscan and a serum marker could avoid 80% of biopsies. This study shows that the results of alternative methods concord with those of histology in HBV-infected patients in Burkina Faso. These alternative techniques could help physicians to identify patients requiring treatment. PMID:20207872

  15. Evaluation of Fish Health Status and Histopathology in Gills and Liver Due to Metal Contaminated Sediments Exposure.

    PubMed

    Jabeen, Ghazala; Manzoor, Farkhanda; Javid, Arshad; Azmat, Hamda; Arshad, Mateen; Fatima, Shafaq

    2018-04-01

    Health status of freshwater fish, Cirrhina mrigala was studied by qualitative and quantitative histopathological analysis, alterations in frequency/prevalence percentages (%) and histological alteration indices (HAI) in response to metal contaminated sediments of the River Ravi aquatic ecosystem. Histo-structures of gill and liver samples of fish were analyzed and comparison between the degree of damage of the alterations in fish organs was performed after exposure to metal contaminated sediments for 7, 14 and 28 days under semi-static water renewal bioassays. Histopathological studies revealed marked histological alterations in the gills and liver of exposed fish as compared to normal tissue structure observed in control fish. The frequency and prevalence percentages observed in 28-day exposed fish were significantly higher as compared to 7- and 14-day exposed fish. The order of frequency and prevalence percentage for gills and liver of exposed fish was as: 28-day > 14-day > 7-day. The highest prevalence percentages recorded were 83 and 80% as focal area of necrosis in gill and liver, respectively, after 28-day exposure. The lowest prevalence percentage observed in 7-day exposed Cirrhina mrigala was dilation of sinusoids (17%).

  16. Urinary proteomic profiling reveals diclofenac-induced renal injury and hepatic regeneration in mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Swelm, Rachel P.L. van; Laarakkers, Coby M.M.; Pertijs, Jeanne C.L.M.

    Diclofenac (DF) is a widely used non-steroidal anti-inflammatory drug for the treatment of rheumatic disorders, but is often associated with liver injury. We applied urinary proteomic profiling using MALDI-TOF MS to identify biomarkers for DF-induced hepatotoxicity in mice. Female CH3/HeOUJIco mice were treated with 75 mg/kg bw DF by oral gavage and 24 h urine was collected. Proteins identified in urine of DF-treated mice included epidermal growth factor, transthyretin, kallikrein, clusterin, fatty acid binding protein 1 and urokinase, which are related to liver regeneration but also to kidney injury. Both organs showed enhanced levels of oxidative stress (TBARS, p histology and increased Kim1 and Il-6 mRNA expression levels (p < 0.001 and p < 0.01). Liver histology and plasma ALT levels in DF-treated mice were not different from control, but mRNA expression of Stat3 (p < 0.001) and protein expression of PCNA (p < 0.05) were increased, indicating liver regeneration. In conclusion, urinary proteome analysis revealed that DF treatment in mice induced kidney and liver injury. Within 24 h, however, the liver was able to recover by activating tissue regeneration processes. Hence, the proteins found in urine of DF-treated mice represent kidney damage rather than hepatic injury. - Highlights: • The urinary proteome shows biological processes involved in adverse drug reactions. • Urine proteins of DF-treated mice relate to kidney injury rather than liver injury. • Liver regeneration, not liver injury, is apparent 24h after oral DF administration. • Pretreatment with LPS does not enhance DF-induced liver injury in mice.« less

  17. Automated quantitative histology reveals vascular morphodynamics during Arabidopsis hypocotyl secondary growth.

    PubMed

    Sankar, Martial; Nieminen, Kaisa; Ragni, Laura; Xenarios, Ioannis; Hardtke, Christian S

    2014-02-11

    Among various advantages, their small size makes model organisms preferred subjects of investigation. Yet, even in model systems detailed analysis of numerous developmental processes at cellular level is severely hampered by their scale. For instance, secondary growth of Arabidopsis hypocotyls creates a radial pattern of highly specialized tissues that comprises several thousand cells starting from a few dozen. This dynamic process is difficult to follow because of its scale and because it can only be investigated invasively, precluding comprehensive understanding of the cell proliferation, differentiation, and patterning events involved. To overcome such limitation, we established an automated quantitative histology approach. We acquired hypocotyl cross-sections from tiled high-resolution images and extracted their information content using custom high-throughput image processing and segmentation. Coupled with automated cell type recognition through machine learning, we could establish a cellular resolution atlas that reveals vascular morphodynamics during secondary growth, for example equidistant phloem pole formation. DOI: http://dx.doi.org/10.7554/eLife.01567.001.

  18. Automated quantitative histology reveals vascular morphodynamics during Arabidopsis hypocotyl secondary growth

    PubMed Central

    Sankar, Martial; Nieminen, Kaisa; Ragni, Laura; Xenarios, Ioannis; Hardtke, Christian S

    2014-01-01

    Among various advantages, their small size makes model organisms preferred subjects of investigation. Yet, even in model systems detailed analysis of numerous developmental processes at cellular level is severely hampered by their scale. For instance, secondary growth of Arabidopsis hypocotyls creates a radial pattern of highly specialized tissues that comprises several thousand cells starting from a few dozen. This dynamic process is difficult to follow because of its scale and because it can only be investigated invasively, precluding comprehensive understanding of the cell proliferation, differentiation, and patterning events involved. To overcome such limitation, we established an automated quantitative histology approach. We acquired hypocotyl cross-sections from tiled high-resolution images and extracted their information content using custom high-throughput image processing and segmentation. Coupled with automated cell type recognition through machine learning, we could establish a cellular resolution atlas that reveals vascular morphodynamics during secondary growth, for example equidistant phloem pole formation. DOI: http://dx.doi.org/10.7554/eLife.01567.001 PMID:24520159

  19. Diagnostic criteria for selenium toxicosis in aquatic birds: histologic lesions

    USGS Publications Warehouse

    Green, D.E.; Albers, P.H.

    1997-01-01

    Chronic selenium toxicosis was induced in 1-year-old male mallard ducks (Anas platyrhynchos) by feeding selenium, as seleno-DL-methionine, in amounts of 0, 10, 20, 40, and 80 parts per million (ppm) to five groups of 21 ducks each for 16 wk during March to July 1988. All mallards in the 80 ppm group, three in the 40 ppm group, and one in the 20 ppm group died. Histologic lesions in mallards that died of selenosis were hepatocellular vacuolar degeneration progressing to centrolobular and panlobular necrosis, nephrosis, apoptosis of pancreatic exocrine cells, hypermaturity and avascularity of contour feathers of the head with atrophy of feather follicles, lymphocytic necrosis and atrophy of lymphoid organs (spleen, gut-associated lymphoid tissue, and lumbar lymph nodes), and severe atrophy and degeneration of fat. Histologic lesions in surviving mallards in the 40 ppm group, which had tissue residues of selenium comparable to mallards that died, were fewer and much milder than mallards that died; lesions consisted of atrophy of lymphoid tissue, hyalinogranular swelling of hepatocytes, atrophy of seminiferous tubules, and senescence of feathers. No significant histologic lesions were detected in euthanized mallards in the 0, 10 and 20 ppm groups. Based on tissue residues and histologic findings, primarily in the liver, there was a threshold of selenium accumulation above which pathophysiologic changes were rapid and fatal. Pathognomonic histologic lesions of fatal and nonfatal selenosis were not detected. Criteria for diagnosis of fatal selenosis in aquatic birds include consistent histologic lesions in the liver, kidneys, and organs of the immune system. Although histologic changes were present in cases of chronic non-fatal selenosis, these were inconsistent. Consistent features of fatal and non-fatal chronic selenosis were marked weight loss and elevated concentrations of selenium in organs.

  20. Systematic review with meta-analysis: the significance of histological disease severity in lean patients with nonalcoholic fatty liver disease.

    PubMed

    Sookoian, S; Pirola, C J

    2018-01-01

    Current evidence suggests that lean and obese patients with nonalcoholic fatty liver disease (NAFLD) share an altered metabolic and cardiovascular profile. However, there is an incomplete understanding of the natural history of "lean-NAFLD." Indeed, an unanswered question is whether lean (BMI ≤ 25 Kg/m 2 ) NAFLD-patients are protected from severe histological outcomes. To perform a meta-analysis with the goal of providing a quantitative estimation of the magnitude of fibrosis, as well as histological features associated with the disease severity, in lean versus overweight/obese-NAFLD patients. Through a systematic search up to July 2017, we identified eight studies that compared histological outcomes in lean (n = 493) versus overweight/obese (n = 2209) patients. Relative to lean-NAFLD, overweight/obese-NAFLD patients showed significantly (P = .032) higher fibrosis scores; the observed difference in means between the two groups, which is the absolute difference between the mean value of fibrosis score [0-4] ± standard error, was 0.28 ± 0.13. The risk of having nonalcoholic steatohepatitis-NASH (OR 0.58 95% CI 0.34-0.97) was significantly lower in lean-NAFLD (n = 322) than in overweight/obese-NAFLD (n = 1357), P = .04. Relative to lean-NAFLD, overweight/obese-NAFLD patients also have significantly greater NAFLD activity (difference in means ± SE: 0.58 ± 0.16, P = .0004) and steatosis (difference in means ± SE: 0.23 ± 0.07, P = .002) scores. Lean-NAFLD patients tend to show less severe histological features as compared to overweight/obese-NAFLD patients. Subsequent longitudinal assessment is needed to understand the clinical impact of these findings; however, the significant ~ 25% increment of mean fibrosis score in overweight/obese patients suggests that obesity could predict a worse long-term prognosis. © 2017 John Wiley & Sons Ltd.

  1. Assessing inflammatory liver injury in an acute CCl4 model using dynamic 3D metabolic imaging of hyperpolarized [1-(13)C]pyruvate.

    PubMed

    Josan, Sonal; Billingsley, Kelvin; Orduna, Juan; Park, Jae Mo; Luong, Richard; Yu, Liqing; Hurd, Ralph; Pfefferbaum, Adolf; Spielman, Daniel; Mayer, Dirk

    2015-12-01

    To facilitate diagnosis and staging of liver disease, sensitive and non-invasive methods for the measurement of liver metabolism are needed. This study used hyperpolarized (13)C-pyruvate to assess metabolic parameters in a CCl4 model of liver damage in rats. Dynamic 3D (13)C chemical shift imaging data from a volume covering kidney and liver were acquired from 8 control and 10 CCl4-treated rats. At 12 time points at 5 s temporal resolution, we quantified the signal intensities and established time courses for pyruvate, alanine, and lactate. These measurements were compared with standard liver histology and an alanine transaminase (ALT) enzyme assay using liver tissue from the same animals. All CCl4-treated but none of the control animals showed histological liver damage and elevated ALT enzyme levels. In agreement with these results, metabolic imaging revealed an increased alanine/pyruvate ratio in liver of CCl4-treated rats, which is indicative of elevated ALT activity. Similarly, lactate/pyruvate ratios were higher in CCl4-treated compared with control animals, demonstrating the presence of inflammation. No significant differences in metabolite ratios were observed in kidney or vasculature. Thus this work shows that metabolic imaging using (13)C-pyruvate can be a successful tool to non-invasively assess liver damage in vivo. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Comparative Circadian Metabolomics Reveal Differential Effects of Nutritional Challenge in the Serum and Liver.

    PubMed

    Abbondante, Serena; Eckel-Mahan, Kristin L; Ceglia, Nicholas J; Baldi, Pierre; Sassone-Corsi, Paolo

    2016-02-05

    Diagnosis and therapeutic interventions in pathological conditions rely upon clinical monitoring of key metabolites in the serum. Recent studies show that a wide range of metabolic pathways are controlled by circadian rhythms whose oscillation is affected by nutritional challenges, underscoring the importance of assessing a temporal window for clinical testing and thereby questioning the accuracy of the reading of critical pathological markers in circulation. We have been interested in studying the communication between peripheral tissues under metabolic homeostasis perturbation. Here we present a comparative circadian metabolomic analysis on serum and liver in mice under high fat diet. Our data reveal that the nutritional challenge induces a loss of serum metabolite rhythmicity compared with liver, indicating a circadian misalignment between the tissues analyzed. Importantly, our results show that the levels of serum metabolites do not reflect the circadian liver metabolic signature or the effect of nutritional challenge. This notion reveals the possibility that misleading reads of metabolites in circulation may result in misdiagnosis and improper treatments. Our findings also demonstrate a tissue-specific and time-dependent disruption of metabolic homeostasis in response to altered nutrition. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Genistein modifies liver fibrosis and improves liver function by inducing uPA expression and proteolytic activity in CCl4-treated rats.

    PubMed

    Salas, Alfonso Leija; Montezuma, Tania Díaz; Fariña, German Garrido; Reyes-Esparza, Jorge; Rodríguez-Fragoso, Lourdes

    2008-01-01

    To evaluate the effect of genistein on the fibrosis and matrix degradation caused by experimentally induced fibrosis in rats. Hepatic fibrosis was brought about by chronic administration of carbon tetrachloride to rats. To evaluate the effect of genistein on liver fibrosis and function, total collagen content and proteolytic activity in the liver were quantified. Urokinase-type plasminogen activator (uPA) expression during experimental fibrosis was localized by immunohistochemistry. Histopathological changes were evaluated using light and electron microscopy. Animals with fibrosis and treated with genistein showed an important reduction (73%) in hepatic collagen content as well as an improvement in liver function (p < 0.001). Genistein increased the capacity of the liver to degrade type I collagen and Matrigel (3.1- and 3.7-fold, respectively; p < 0.001) in animals with liver fibrosis. Genistein increased the number of uPA-immunoreactive cells. The increase in the uPA expression correlated with an increase in proteolytic activity. Histological analysis revealed a reduction in the number of fiber septa in pericentral and perisinusoidal areas. Transmission electron micrographs of livers from animals with fibrosis and treated with genistein showed a reduction in the number of hepatic stellate cells activated and a smaller number of collagen fibers. Genistein is able to improve the liver after injury and fibrosis induced by chronic administration of carbon tetrachloride. This finding suggests that genistein has antifibrogenic potential and could therefore be useful for treating chronic liver disease. (c) 2008 S. Karger AG, Basel.

  4. The Effect of Geraniol on Liver Regeneration Αfter Hepatectomy in Rats

    PubMed Central

    CANBEK, MEDIHA; UYANOGLU, MUSTAFA; CANBEK, SELCUK; CEYHAN, EMRE; OZEN, AHMET; DURMUS, BASAK; TURGAK, OZGE

    2017-01-01

    Geraniol is a monoterpenoid alcohol that has a hepatoprotective effect. We investigated the regenerative effects of geraniol in rats after a 70% partial hepatectomy (PH). Using Wistar albino rats, nine groups were created: Group I was the control group, while the remaining groups received a single intraperitoneal dose of saline, Silymarin, or geraniol after PH. A 70% PH was performed on all groups except for groups II and III. Blood serum samples were obtained for alanine amino transferase (ALT) analysis. Then liver tissues were harvested for histological and real-time polymerase chain reaction (PCR) analyses. Tumor necrosis factor-α (TNFα) and interleukin 6 (IL6) gene expression were examined 24 and 48 h after PH. ALT levels were found to be statistically significantly increased in all PH-treated groups. TNFα and IL6 gene expression levels were elevated in geraniol-treated groups. Histological evaluation revealed a hepatoprotective effect for geraniol-treated groups. Our results suggest that geraniol plays a significant role during liver regeneration, which involves the elevated expression of TNFα and IL6 48 h after PH. PMID:28358702

  5. Fibroblast growth factor (Fgf) signaling pathway regulates liver homeostasis in zebrafish.

    PubMed

    Tsai, Su-Mei; Liu, Da-Wei; Wang, Wen-Pin

    2013-04-01

    In mammals, fibroblast growth factor (FGF) signaling controls liver specification and regulates the metabolism of lipids, cholesterol, and bile acids. FGF signaling also promotes hepatocyte proliferation, and helps detoxify hepatotoxin during liver regeneration after partial hepatectomy. However, the function of Fgf in zebrafish liver is not yet well understood, specifically for postnatal homeostasis. The current study analyzed the expression of fgf receptors (fgfrs) in the liver of zebrafish. We then investigated the function of Fgf signaling in the zebrafish liver by expressing a dominant-negative Fgf receptor in hepatocytes (lfabp:dnfgfr1-egfp, lf:dnfr). Histological analysis showed that our genetic intervention resulted in a small liver size with defected medial expansion of developing livers in transgenic (Tg) larvae. Morphologically, the liver lobe of lf:dnfr adult fish was shorter than that of control. Ballooning degeneration of hepatocytes was observed in fish as young as 3 months. Further examination revealed the development of hepatic steatosis and cholestasis. In adult Tg fish, we unexpectedly observed increased liver-to-body-weight ratios, with higher percentages of proliferating hepatocytes. Considering all these findings, we concluded that as in mammals, in adult zebrafish the metabolism of lipid and bile acids in the liver are regulated by Fgf signaling. Disruption of the Fgf signal-mediated metabolism might indirectly affect hepatocyte proliferation.

  6. Developmental palaeontology of Reptilia as revealed by histological studies.

    PubMed

    Scheyer, Torsten M; Klein, Nicole; Sander, P Martin

    2010-06-01

    Among the fossilized ontogenetic series known for tetrapods, only more basal groups like temnospondyl amphibians have been used extensively in developmental studies, whereas reptilian and synapsid data have been largely neglected so far. However, before such ontogenetic series can be subject to study, the relative age and affiliation of putative specimens within a series has to be verified. Bone histology has a long-standing tradition as being a source of palaeobiological and growth history data in fossil amniotes and indeed, the analysis of bone microstructures still remains the most important and most reliable tool for determining the absolute ontogenetic age of fossil vertebrates. It is also the only direct way to reconstruct life histories and growth strategies for extinct animals. Herein the record of bone histology among Reptilia and its application to elucidate and expand fossilized ontogenies as a source of developmental data are reviewed. (c) 2009 Elsevier Ltd. All rights reserved.

  7. Liver precancerous lesions and hepatocellular carcinoma: the histology report.

    PubMed

    Roncalli, Massimo; Terracciano, Luigi; Di Tommaso, Luca; David, Ezio; Colombo, Massimo

    2011-03-01

    The current ability to increase the survival of patients with hepatocellular carcinoma (HCC) relies upon the surveillance of cirrhotic patients. Surveillance allows HCC precursors (dysplastic nodules) and malignant tumors to be recognized at an earlier stage making cure possible. Radiology plays a major role in HCC diagnosis because HCC is characterized by neoarterial vascularisation with a typical imaging pattern. Current international guidelines have restricted the use of the liver biopsy to the characterization of hepatocellular nodules which remain diagnostically equivocal after imaging. Thus pathologists are today facing very challenging and often well differentiated lesions, leading to difficulties in distinguishing high grade dysplasia and well differentiated HCC. In this scenario novel concepts obtained through international consensus have been proposed with emphasis on HCC of small size (up to 2 cm) which includes 2 distinct types, the early and progressed HCC. In this paper we will report the main histopathological criteria of a biopsy which allow the differentiation of HCC precursors (dysplastic nodules) from well differentiated HCC with attention to the role and weight of both classical histopathological criteria and novel immunocytochemical markers. The second part of the paper is devoted to the histopathology report of HCC on surgical specimens including explanted livers and on the differential diagnosis between HCC and liver metastasis. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd.. All rights reserved.

  8. PNPLA3 variant and portal/periportal histological pattern in patients with biopsy-proven non-alcoholic fatty liver disease: a possible role for oxidative stress.

    PubMed

    Carpino, Guido; Pastori, Daniele; Baratta, Francesco; Overi, Diletta; Labbadia, Giancarlo; Polimeni, Licia; Di Costanzo, Alessia; Pannitteri, Gaetano; Carnevale, Roberto; Del Ben, Maria; Arca, Marcello; Violi, Francesco; Angelico, Francesco; Gaudio, Eugenio

    2017-11-17

    Pathogenesis of non-alcoholic fatty liver disease (NAFLD) is influenced by predisposing genetic variations, dysmetabolism, systemic oxidative stress, and local cellular and molecular cross-talks. Patatin-like phospholipase domain containing 3 (PNPLA3) gene I148M variant is a known determinant of NAFLD. Aims were to evaluate whether PNPLA3 I148M variant was associated with a specific histological pattern, hepatic stem/progenitor cell (HpSC) niche activation and serum oxidative stress markers. Liver biopsies were obtained from 54 NAFLD patients. The activation of HpSC compartment was evaluated by the extension of ductular reaction (DR); hepatic stellate cells, myofibroblasts (MFs), and macrophages were evaluated by immunohistochemistry. Systemic oxidative stress was assessed measuring serum levels of soluble NOX2-derived peptide (sNOX2-dp) and 8-isoprostaglandin F 2α (8-iso-PGF 2α ). PNPLA3 carriers showed higher steatosis, portal inflammation and HpSC niche activation compared to wild-type patients. DR was correlated with NAFLD activity score (NAS) and fibrosis score. Serum 8-iso-PGF 2α were significantly higher in I148M carriers compared to non-carriers and were correlated with DR and portal inflammation. sNox2-dp was correlated with NAS and with HpSC niche activation. In conclusion, NAFLD patients carrying PNPLA3 I148M are characterized by a prominent activation of HpSC niche which is associated with a more aggressive histological pattern (portal fibrogenesis) and increased oxidative stress.

  9. Anaplastic transformation of an atypical intraventricular meningioma with metastases to the liver: case report.

    PubMed

    Garcia-Conde, M; Roldan-Delgado, H; Martel-Barth-Hansen, D; Manzano-Sanz, C

    2009-12-01

    Malignant intraventricular meningiomas are very rare. To the best of our knowledge, only eleven cases have been reported thus far. Seven of them developed cerebrospinal fluid (CSF) metastases. We present herein the first case of a malignant intraventricular meningioma with extraneural metastases. We report a 44 year-old-man with a history of progressive headache and disorientation. Magnetic resonance imaging (MRI) revealed a 5-cm homogeneously-enhancing mass in the right trigone. The lesion was totally resected via a parietooccipital transcortical approach. Histological examination demonstrated an atypical meningioma. Thereafter, the tumor recurred twice. At first recurrence, the tumor was completely removed again and external radiotherapy was administered. At surgery at second recurrence, the tumor was more aggressive, invading the brain parenchyma. Histological examination showed anaplastic meningioma. The patient was readmitted to hospital with fever and pain in right hypochondrium. Abdominal ultrasound examination disclosed multiple hypoechoic liver lesions. Biopsy was consistent with liver metastases of a malignant meningioma. The patient died of acute liver failure seven months after initial diagnosis. Malignant intraventricular meningiomas are prone to recur and develop metastases, mainly through the CSF. Nevertheless, our case shows that extraneural metastases are also possible. Therefore, when systemic deterioration occurs in a patient with a malignant intraventricular meningioma, metastases to extraneural organs such as the liver must be ruled out.

  10. Solitary Fibrous Tumor in the Round Ligament of the Liver: A Fortunate Intraoperative Discovery

    PubMed Central

    Beyer, Laura; Delpero, Jean-Robert; Chetaille, Bruno; Sarran, Anthony; Perrot, Delphine; Moureau-Zabotto, Laurence; Guiramand, Jérôme; Bertucci, François

    2012-01-01

    Solitary fibrous tumors (SFTs) are mesenchymal neoplasms of fibroblastic origin, most commonly found in the pleura. Numerous extrathoracic locations have been reported during the last 2 decades. Herein, we report the first case of an SFT in the round ligament of the liver. A 46-year-old Caucasian man presented with a 12-month history of abdominal pain. An ultrasonography-guided microbiopsy first revealed a desmoid tumor. After failure of first- and second-line medical treatments (celecoxib and tamoxifen, then imatinib), histological reexamination was suspicious for a low-grade sarcoma. MRI was also suspicious for a malignant process. Hence, surgery was decided. Laparotomy found a huge and well-limited tumor that, unexpectedly, was appended to the round ligament of the liver and free from any other intra-abdominal contact. The tumor was easily removed. Excision was monobloc and macroscopically complete. Histological analysis diagnosed an SFT arising from the round ligament of the liver. No adjuvant treatment was given. Ten months after surgery, the patient is alive without any signs or symptoms of relapse. This is the first report of SFT arising from the round ligament of the liver. It illustrates the difficulty in diagnosing such tumors. Whilst diagnosis of SFT is rare, it should be kept in mind to allow early diagnosis and complete surgical resection, which provide the best chance for recovery. PMID:22666211

  11. Solitary fibrous tumor in the round ligament of the liver: a fortunate intraoperative discovery.

    PubMed

    Beyer, Laura; Delpero, Jean-Robert; Chetaille, Bruno; Sarran, Anthony; Perrot, Delphine; Moureau-Zabotto, Laurence; Guiramand, Jérôme; Bertucci, François

    2012-01-01

    Solitary fibrous tumors (SFTs) are mesenchymal neoplasms of fibroblastic origin, most commonly found in the pleura. Numerous extrathoracic locations have been reported during the last 2 decades. Herein, we report the first case of an SFT in the round ligament of the liver. A 46-year-old Caucasian man presented with a 12-month history of abdominal pain. An ultrasonography-guided microbiopsy first revealed a desmoid tumor. After failure of first- and second-line medical treatments (celecoxib and tamoxifen, then imatinib), histological reexamination was suspicious for a low-grade sarcoma. MRI was also suspicious for a malignant process. Hence, surgery was decided. Laparotomy found a huge and well-limited tumor that, unexpectedly, was appended to the round ligament of the liver and free from any other intra-abdominal contact. The tumor was easily removed. Excision was monobloc and macroscopically complete. Histological analysis diagnosed an SFT arising from the round ligament of the liver. No adjuvant treatment was given. Ten months after surgery, the patient is alive without any signs or symptoms of relapse. This is the first report of SFT arising from the round ligament of the liver. It illustrates the difficulty in diagnosing such tumors. Whilst diagnosis of SFT is rare, it should be kept in mind to allow early diagnosis and complete surgical resection, which provide the best chance for recovery.

  12. Effect of Increased Intra-abdominal Pressure on Liver Histology and Hemodynamics: An Experimental Study

    PubMed Central

    ANTONIOU, EFSTATHIOS A; KAIRI, EVI; MARGONIS, GEORGIOS A; ANDREATOS, NIKOLAOS; SASAKI, KAZUNARI; DAMASKOS, CHRISTOS; GARMPIS, NIKOLAOS; SAMAHA, MARIO; ARGYRA, ERIPHYLI; POLYMENEAS, GEORGE; WEISS, MATTHEW J; PAWLIK, TIMOTHY M; VOROS, DIONYSIOS; KOURAKLIS, GREGORY

    2018-01-01

    Background: While reduction of portal venous (PV) blood flow has been described in animal models of intra-abdominal hypertension, reports on compensatory changes in hepatic arterial (HA) flow, known as the hepatic arterial buffer response are controversial. Materials and Methods: Pneumoperitoneum with helium was induced in 13 piglets. Hemodynamic measurements and pathological assessment were conducted at baseline and during the three subsequent phases: Phase A: 45 minutes with a stable intra-abdominal pressure of 25 mmHg; phase B: 45 minutes with a stable intra-abdominal pressure of 40 mmHg; and phase C during which the abdomen was re-explored and reperfusion of the liver was allowed to take place. Results: Phase B pressure was significantly greater than phase A pressure in both the PV and the inferior vena cava, demonstrating a positive association between escalating intra-abdominal hypertension and the pressure in these two vessels (all p<0.001). In contrast, HA pressure was comparable between baseline and phase A, while it tended to decrease in phase B. Regarding histology, the most notable abnormality was the presence of inflammatory infiltrates and hepatocyte necrosis. Conclusion: Helium-insufflation increased PV pressure with a partial compensatory decrease of HA pressure. Nonetheless, findings consistent with hepatic ischemia were observed on pathology. PMID:29275303

  13. Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in Japanese patients with non-alcoholic fatty liver disease.

    PubMed

    Kato, Ken-Ichiro; Takeshita, Yumie; Misu, Hirofumi; Zen, Yoh; Kaneko, Shuichi; Takamura, Toshinari

    2015-03-01

    To examine the association between liver histological features and organ-specific insulin resistance indices calculated from 75-g oral glucose tolerance test data in patients with non-alcoholic fatty liver disease. Liver biopsy specimens were obtained from 72 patients with non-alcoholic fatty liver disease, and were scored for steatosis, grade and stage. Hepatic and skeletal muscle insulin resistance indices (hepatic insulin resistance index and Matsuda index, respectively) were calculated from 75-g oral glucose tolerance test data, and metabolic clearance rate was measured using the euglycemic hyperinsulinemic clamp method. The degree of hepatic steatosis, and grade and stage of non-alcoholic steatohepatitis were significantly correlated with Matsuda index (steatosis r = -0.45, P < 0.001; grade r = -0.54, P < 0.001; stage r = -0.37, P < 0.01), but not with hepatic insulin resistance index. Multiple regression analyses adjusted for age, sex, body mass index and each histological score showed that the degree of hepatic steatosis (coefficient = -0.22, P < 0.05) and grade (coefficient = -0.40, P < 0.01) were associated with Matsuda index, whereas the association between stage and Matsuda index (coefficient = -0.07, P = 0.593) was no longer significant. A similar trend was observed for the association between steatosis and metabolic clearance rate (coefficient = -0.62, P = 0.059). Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in patients with non-alcoholic fatty liver disease, suggesting a central role of fatty liver in the development of peripheral insulin resistance and the existence of a network between the liver and skeletal muscle.

  14. Influence of large intrahepatic blood vessels on the gross and histological characteristics of lesions produced by radiofrequency ablation in a pig liver model.

    PubMed

    Tamaki, Katsuyoshi; Shimizu, Ichiro; Oshio, Atsuo; Fukuno, Hiroshi; Inoue, Hiroshi; Tsutsui, Akemi; Shibata, Hiroshi; Sano, Nobuya; Ito, Susumu

    2004-12-01

    To determine whether the presence of large intrahepatic blood vessels (>/=3 mm) affect radiofrequency (RF)-induced coagulation necrosis, the gross and histological characteristics of RF-ablated areas proximal to or around vessels were examined in normal pig livers. An RF ablation treatment using a two-stepwise extension technique produced 12 lesions: six contained vessels (Group A), and the other six were localized around vessels (Group B). Gross examination revealed that the longest and shortest diameters of the ablated lesions were significantly larger in Group B than in Group A. In Group A, patent vessels contiguous to the lesion were present in a tongue-shaped area, whereas the lesions in Group B were spherical. Staining with nicotinamide adenine dinucleotide diaphorase was negative within the ablated area; but, if vessels were present in the ablated area, the cells around the vessels in an opposite direction to the ablation were stained blue. Roll-off can be achieved with 100% cellular destruction within a lesion that does not contain large vessels. The ablated area was decreased in lesions that contained large vessels, suggesting that the presence of large vessels in the ablated area further increases the cooling effect and may require repeated RF ablation treatment to achieve complete coagulation necrosis.

  15. Mechanics of fresh, frozen-thawed and heated porcine liver tissue.

    PubMed

    Wex, Cora; Stoll, Anke; Fröhlich, Marlen; Arndt, Susann; Lippert, Hans

    2014-06-01

    For a better understanding of the effects of thermally altered soft tissue, the biothermomechanics of these tissues need to be studied. Without the knowledge of the underlying physical processes and the parameters that can be controlled clinically, thermal treatment of cancerous hepatic tissue or the preservation of liver grafts are based primarily on trial and error. Thus, this study is concerned with the investigation of the influence of temperature on the rheological properties and the histological properties of porcine liver. Heating previously cooled porcine liver tissue above 40 °C leads to significant, irreversible stiffness changes observed in the amplitude sweep. The increase of the complex shear module of healthy porcine liver from room temperature to 70 °C is approximately 9-fold. Comparing the temperatures -20 °C and 20 °C, no significant difference of the mechanical properties was observed. Furthermore, there is a strong relation between the mechanical and histological properties of the porcine liver. Temperatures above 40 °C destroy the collagen matrix within the liver tissue. This results in the alteration of the biomechanical properties. The time-temperature superposition principle is applied to generate temperature-dependent shift factors that can be described by a two-part exponential function model with an inflection temperature of 45 °C. Tumor ablation techniques such as heating or freezing have a significant influence on the histology of liver tissue. However, only for temperatures above body temperature an influence on the mechanical properties of hepatic tissues was noticeable. Freezing up to -20 °C did not affect the liver mechanics.

  16. Dendrobium huoshanense polysaccharide prevents ethanol-induced liver injury in mice by metabolomic analysis.

    PubMed

    Wang, Xiao-Yu; Luo, Jian-Ping; Chen, Rui; Zha, Xue-Qiang; Pan, Li-Hua

    2015-01-01

    The prevalence of alcohol consumption has increased in modern dietary life and alcoholic liver injury can follow. Dendrobium huoshanense polysaccharide (DHP) is a homogeneous polysaccharide isolated from Dendrobium huoshanense, which possesses hepatoprotection function. In this study, we investigated the metabolic profiles of serum and liver tissues extracts from control, ethanol-treated and DHP\\ethanol-treated mice using a UHPLC/LTQ Orbitrap XL MS-based metabolomics approach. Our results indicated that DHP alleviated early steatosis and inflammation in liver histology and the metabolomic analysis of serum and hepatic tissue revealed that first, ethanol treatment mainly altered phosphatidylcholines (PCs) including PC (13:0) and phosphocholine, arachidonic acid metabolites including 20-ethyl PGF2α and amino acids including L-Proline; Second, DHP supplementation ameliorated the altered metabolic levels particularly involved in phosphocholine and L-Proline. These data suggested that DHP might restore the perturbed metabolism pathways by ethanol exposure to prevent the progression of alcoholic liver injury. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Liver-specific deletion of prohibitin 1 results in spontaneous liver injury, fibrosis, and hepatocellular carcinoma in mice.

    PubMed

    Ko, Kwang Suk; Tomasi, Maria Lauda; Iglesias-Ara, Ainhoa; French, Barbara A; French, Samuel W; Ramani, Komal; Lozano, Juan José; Oh, Pilsoo; He, Lina; Stiles, Bangyan L; Li, Tony W H; Yang, Heping; Martínez-Chantar, M Luz; Mato, José M; Lu, Shelly C

    2010-12-01

    Prohibitin 1 (PHB1) is a highly conserved, ubiquitously expressed protein that participates in diverse processes including mitochondrial chaperone, growth and apoptosis. The role of PHB1 in vivo is unclear and whether it is a tumor suppressor is controversial. Mice lacking methionine adenosyltransferase 1A (MAT1A) have reduced PHB1 expression, impaired mitochondrial function, and spontaneously develop hepatocellular carcinoma (HCC). To see if reduced PHB1 expression contributes to the Mat1a knockout (KO) phenotype, we generated liver-specific Phb1 KO mice. Expression was determined at the messenger RNA and protein levels. PHB1 expression in cells was varied by small interfering RNA or overexpression. At 3 weeks, KO mice exhibit biochemical and histologic liver injury. Immunohistochemistry revealed apoptosis, proliferation, oxidative stress, fibrosis, bile duct epithelial metaplasia, hepatocyte dysplasia, and increased staining for stem cell and preneoplastic markers. Mitochondria are swollen and many have no discernible cristae. Differential gene expression revealed that genes associated with proliferation, malignant transformation, and liver fibrosis are highly up-regulated. From 20 weeks on, KO mice have multiple liver nodules and from 35 to 46 weeks, 38% have multifocal HCC. PHB1 protein levels were higher in normal human hepatocytes compared to human HCC cell lines Huh-7 and HepG2. Knockdown of PHB1 in murine nontransformed AML12 cells (normal mouse hepatocyte cell line) raised cyclin D1 expression, increased E2F transcription factor binding to cyclin D1 promoter, and proliferation. The opposite occurred with PHB1 overexpression. Knockdown or overexpression of PHB1 in Huh-7 cells did not affect proliferation significantly or sensitize cells to sorafenib-induced apoptosis. Hepatocyte-specific PHB1 deficiency results in marked liver injury, oxidative stress, and fibrosis with development of HCC by 8 months. These results support PHB1 as a tumor suppressor in

  18. Genetic Polymorphism of Cytochrome P450 4F2, Vitamin E Level and Histological Response in Adults and Children with Nonalcoholic Fatty Liver Disease Who Participated in PIVENS and TONIC Clinical Trials

    PubMed Central

    Athinarayanan, Shaminie; Wei, Rongrong; Zhang, Min; Bai, Shaochun; Traber, Maret G.; Yates, Katherine; Cummings, Oscar W.; Molleston, Jean; Liu, Wanqing; Chalasani, Naga

    2014-01-01

    Vitamin E improved liver histology in children and adults with NAFLD who participated in TONIC and PIVENS clinical trials, but with significant inter-individual variability in its efficacy. Cytochrome P450 4F2 (CYP4F2) is the major enzyme metabolizing Vit E, with two common genetic variants (V433M, rs2108622 and W12G, rs3093105) found to alter its activity. We investigated the relationship between CYP4F2 genotypes, α-tocopherol levels and histological improvement in these two trials. V433M and W12G variants were genotyped in TONIC (n = 155) and PIVENS (n = 213) DNA samples. The relationships between CYP4F2 genotypes, plasma α-tocopherol levels at baseline and weeks 48 (w48) and 96 (w96) and histological end points (overall improvement in liver histology and resolution of NASH) were investigated. As a result, the V433M genotype was significantly associated with baseline plasma α-tocopherol in the TONIC trial (p = 0.004), but not in PIVENS. Among those receiving Vit E treatment, CYP4F2 V433M genotype was associated with significantly decreased plasma α-tocopherol levels at w48 (p = 0.003 for PIVENS and p = 0.026 for TONIC) but not at w96. The w96 α-tocopherol level was significantly associated with resolution of NASH (p = 0.006) and overall histology improvement (p = 0.021)in the PIVENS, but not in the TONIC trial. There was no significant association between CYP4F2 genotypes and histological end points in either trial. Our study suggested the a moderate role of CYP4F2 polymorphisms in affecting the pharmacokinetics of Vit E as a therapeutic agent. In addition, there may be age-dependent relationship between CYP4F2 genetic variability and Vit E pharmacokinetics in NAFLD. PMID:24759732

  19. Lack of clinical and histological progression of chronic hepatitis C in individuals with true persistently normal ALT: the result of a 17-year follow-up.

    PubMed

    Nunnari, G; Pinzone, M R; Cacopardo, B

    2013-04-01

    Thirty to 40% of patients with chronic hepatitis C have persistently normal alanine aminotransferase (PNALT). Even though traditionally considered as healthy people, most PNALT carriers actually have some degree of clinical progression and histological liver damage. We evaluated the clinical and histological outcome of a 17-year follow-up on a cohort of patients with chronic HCV infection and PNALT. Between 1994 and 2011, 70 PNALTs and 55 Hyper-alanine aminotransferase (ALT) subjects underwent a clinical, biochemical, virological and histological follow-up. At the end of the follow-up, all patients were alive. In the PNALT group, none of the patients developed hepatic decompensation, while 14.5% of Hyper-ALTs were diagnosed as affected by decompensated cirrhosis. No significant variation of the Metavir grading and staging scores was observed among PNALTs by comparing pre- and post-follow-up liver specimens. On the contrary, a significant increase in both Metavir grading and staging scores was noticed within the Hyper-ALT group. Finally, the analysis of IL28B single-nucleotide polymorphism rs12979860 revealed no difference between Hyper-ALTs and PNALTs in terms of frequency of C/C genotype. In conclusion, progression of chronic hepatitis C among PNALTs is slow or even absent, because at the end of the 17-year follow-up histological and clinical parameters had not worsened significantly. © 2012 Blackwell Publishing Ltd.

  20. Induction of Three-Dimensional Growth of Human Liver Cells in Simulated Microgravity

    NASA Technical Reports Server (NTRS)

    Pellis, Neal R.; Khaoustov, V. I.; Yoffe, B.; Murry, D. J.; Soriano, H. E.; Risin, D.; Dawson, David L. (Technical Monitor)

    1999-01-01

    We previously reported that a NASA-developed bioreactor that simulates microgravity environment and creates the unique environment of low shear force and high-mass transfer is conducive for maintaining long term 3-D cell cultures of functional hepatocytes (60 days). However, significant further expansion of liver mass, or the remodeling of liver in vitro was jeopardized by the appearance of apoptotic zones in the center of large cell aggregates. To optimize oxygenation and nutritional uptake within growing cellular aggregates we cultured primary human liver cells (HLC) in a bioreactor in the presence or absence of microcarriers and biodegradable scaffolds. Also, to promote angiogenesis, HLC were cultured with or without microvascular endothelial cells. HLC were harvested from human livers by collagenase perfusion. While microcarriers did not affect cell growth, HLC cultured with biodegradable scaffolds made from polyglycolic acid (PGA) formed aggregates up to 3 cm in length. Culturing cells with PGA scaffolds increased the efficiency of cell self-assembly and the formation of larger cell aggregates. Based on histological evaluation it appears that the degree of apoptotic cells was diminished as compared to cultures without scaffolds. Histology of HLC with PGA-scaffolds revealed cell distribution between the fibers of the scaffolds, and cell-cell and cell-fiber interactions. Analyses of HLC spheroids revealed tissue-like structures comprised of hepatocytes, biliary epithelial cells and/or progenitor liver cells that were arranged as bile duct-like structures along nascent vascular sprouts. Electron microscopy revealed groups of cohesive hepatocytes and bile canaliculi with multiple microvilli and tight cellular junctions. Hepatocytes were further organized into tight clusters surrounded by complex stromal structures and reticulin fibers. Also, we observed higher levels of albumin mRNA expression when hepatocytes were co-cultured with endothelial cells. To evaluate

  1. Histological Evaluation of Selected Organs of the Eurasian Beavers (Castor fiber) Inhabiting Poland.

    PubMed

    Dolka, I; Giżejewska, A; Giżejewski, Z; Kluciński, W; Kołodziejska, J

    2015-10-01

    There is a general scarcity of data on the histological structure of major organs in the Eurasian beaver (Castor fiber). This study presents the histological characteristics of beaver organs such as the liver, spleen, cardiac muscle, lungs and kidneys. Tissue samples were collected from 21 beavers and analysed. Selected samples of tail tissue were additionally examined. Tissue samples were placed in neutral buffered formalin and embedded in paraffin. 4-μm-thick sections were stained with haematoxylin and eosin, and other staining techniques were also used. Scant amounts of inter-lobular connective tissue were found in the liver. Ion or copper deposition was not observed, but scattered cytoplasmic glycogen deposits were present in hepatocytes. Our results suggest that beavers have defensive rather than storage spleens. Interestingly, the presence of melanin in splenic red pulp was noted. The histological structure of the examined organs closely resembled that of other rodent species. According to our knowledge, this is the first study evaluating the histological structure of beaver organs. Nevertheless, precise characterization of the evaluated organs requires further work with the involvement of accurate and reliable techniques, such as molecular biology or electron microscopy methods. © 2014 Blackwell Verlag GmbH.

  2. The Effect of Geraniol on Liver Regeneration After Hepatectomy in Rats.

    PubMed

    Canbek, Mediha; Uyanoglu, Mustafa; Canbek, Selcuk; Ceyhan, Emre; Ozen, Ahmet; Durmus, Basak; Turgak, Ozge

    2017-01-01

    Geraniol is a monoterpenoid alcohol that has a hepatoprotective effect. We investigated the regenerative effects of geraniol in rats after a 70% partial hepatectomy (PH). Using Wistar albino rats, nine groups were created: Group I was the control group, while the remaining groups received a single intraperitoneal dose of saline, Silymarin, or geraniol after PH. A 70% PH was performed on all groups except for groups II and III. Blood serum samples were obtained for alanine amino transferase (ALT) analysis. Then liver tissues were harvested for histological and real-time polymerase chain reaction (PCR) analyses. Tumor necrosis factor-α (TNFα) and interleukin 6 (IL6) gene expression were examined 24 and 48 h after PH. ALT levels were found to be statistically significantly increased in all PH-treated groups. TNFα and IL6 gene expression levels were elevated in geraniol-treated groups. Histological evaluation revealed a hepatoprotective effect for geraniol-treated groups. Our results suggest that geraniol plays a significant role during liver regeneration, which involves the elevated expression of TNFα and IL6 48 h after PH. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Quantitative MR Imaging of Hepatic Steatosis: Validation in Ex Vivo Human Livers

    PubMed Central

    Bannas, Peter; Kramer, Harald; Hernando, Diego; Agni, Rashmi; Cunningham, Ashley M.; Mandal, Rakesh; Motosugi, Utaroh; Sharma, Samir D.; del Rio, Alejandro Munoz; Fernandez, Luis; Reeder, Scott B.

    2015-01-01

    Emerging magnetic resonance imaging (MRI) biomarkers of hepatic steatosis have demonstrated tremendous promise for accurate quantification of hepatic triglyceride concentration. These methods quantify the “proton density fat-fraction” (PDFF), which reflects the concentration of triglycerides in tissue. Previous in vivo studies have compared MRI-PDFF with histologic steatosis grading for assessment of hepatic steatosis. However, the correlation of MRI-PDFF with the underlying hepatic triglyceride content remained unknown. The aim of this ex vivo study was to validate the accuracy of MRI-PDFF as an imaging biomarker of hepatic steatosis. Using ex vivo human livers, we compared MRI-PDFF with magnetic resonance spectroscopy-PDFF (MRS-PDFF), biochemical triglyceride extraction and histology as three independent reference standards. A secondary aim was to compare the precision of MRI-PDFF relative to biopsy for the quantification of hepatic steatosis. MRI-PDFF was prospectively performed at 1.5T in 13 explanted human livers. We performed co-localized paired evaluation of liver fat content in all nine Couinaud segments using single-voxel MRS-PDFF (n=117), tissue wedges for biochemical triglyceride extraction (n=117), and five core biopsies performed in each segment for histologic grading (n=585). Accuracy of MRI-PDFF was assessed through linear regression with MRS-PDFF, triglyceride extraction and histology. Intra-observer agreement, inter-observer agreement and repeatability of MRI-PDFF and histologic grading were assessed through Bland-Altman analyses. MRI-PDFF showed an excellent correlation with MRS-PDFF (r=0.984; CI: 0.978–0.989) and strong correlation with histology (r=0.850; CI: 0.791–0.894) and triglyceride extraction (r=0.871; CI: 0.818–0.909). Intra-observer agreement, inter-observer agreement and repeatability showed a significantly smaller variance for MRI-PDFF than for histologic steatosis grading (all p<0.001). Conclusion MRI-PDFF is an accurate

  4. Spinal Cord Injury Causes Chronic Liver Pathology in Rats

    PubMed Central

    Sauerbeck, Andrew D.; Laws, J. Lukas; Bandaru, Veera V.R.; Popovich, Phillip G.; Haughey, Norman J.

    2015-01-01

    Abstract Traumatic spinal cord injury (SCI) causes major disruption to peripheral organ innervation and regulation. Relatively little work has investigated these post-SCI systemic changes, however, despite considerable evidence that multiple organ system dysfunction contributes to chronic impairments in health. Because metabolic dysfunction is common after SCI and the liver is a pivotal site for metabolic homeostasis, we sought to determine if liver pathology occurs as a result of SCI in a rat spinal contusion model. Histologic evidence showed excess lipid accumulation in the liver for at least 21 days post-injury after cervical or midthoracic SCI. Lipidomic analysis revealed an acute increase in hepatic ceramides as well as chronically elevated lactosylceramide. Post-SCI hepatic changes also included increased proinflammatory gene expression, including interleukin (IL)-1α, IL-1β, chemokine ligand-2, and tumor necrosis factor-α mRNA. These were coincident with increased CD68+ macrophages in the liver through 21 days post-injury. Serum alanine transaminase, used clinically to detect liver damage, was significantly increased at 21 days post-injury, suggesting that early metabolic and inflammatory damage preceded overt liver pathology. Surprisingly, liver inflammation was even detected after lumbar SCI. Collectively, these results suggest that SCI produces chronic liver injury with symptoms strikingly similar to those of nonalcoholic steatohepatitis (fatty liver disease). These clinically significant hepatic changes after SCI are known to contribute to systemic inflammation, cardiovascular disease, and metabolic syndrome, all of which are more prevalent in persons with SCI. Targeting acute and prolonged hepatic pathology may improve recovery and reduce long-term complications after SCI. PMID:25036371

  5. Quantification of Liver Fat with Magnetic Resonance Imaging

    PubMed Central

    Reeder, Scott B.; Sirlin, Claude

    2010-01-01

    Intracellular fat accumulation is common feature of liver disease. Intracellular fat (steatosis) is the histological hallmark of non-alcoholic fatty liver disease (NAFLD) but also may occur with alcohol abuse, viral hepatitis, HIV and genetic lipodystrophies, and chemotherapy. This article reviews emerging magnetic resonance imaging techniques that attempt to quantify liver fat. The content provides an overview of fatty liver disease and diseases where fat is an important disease feature. Also discussed is the current use and limitation of non-targeted biopsy in diffuse liver disease, and why quantitative non-invasive biomarkers of liver fat would be beneficial. PMID:21094444

  6. Role of docosahexaenoic acid treatment in improving liver histology in pediatric nonalcoholic fatty liver disease.

    PubMed

    Nobili, Valerio; Carpino, Guido; Alisi, Anna; De Vito, Rita; Franchitto, Antonio; Alpini, Gianfranco; Onori, Paolo; Gaudio, Eugenio

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most important causes of liver-related morbidity and mortality in children. Recently, we have reported the effects of docosahexaenoic acid (DHA), the major dietary long-chain polyunsaturated fatty acids, in children with NAFLD. DHA exerts a potent anti-inflammatory activity through the G protein-coupled receptor (GPR)120. Our aim was to investigate in pediatric NAFLD the mechanisms underlying the effects of DHA administration on histo-pathological aspects, GPR120 expression, hepatic progenitor cell activation and macrophage pool. 20 children with untreated NAFLD were included. Children were treated with DHA for 18 months. Liver biopsies before and after the treatment were analyzed. Hepatic progenitor cell activation, macrophage pool and GPR120 expression were evaluated and correlated with clinical and histo-pathological parameters. GPR120 was expressed by hepatocytes, liver macrophages, and hepatic progenitor cells. After DHA treatment, the following modifications were present: i) the improvement of histo-pathological parameters such as NAFLD activity score, ballooning, and steatosis; ii) the reduction of hepatic progenitor cell activation in correlation with histo-pathological parameters; iii) the reduction of the number of inflammatory macrophages; iv) the increase of GPR120 expression in hepatocytes; v) the reduction of serine-311-phosphorylated nuclear factor kappa B (NF-κB) nuclear translocation in hepatocytes and macrophages in correlation with serum inflammatory cytokines. DHA could modulate hepatic progenitor cell activation, hepatocyte survival and macrophage polarization through the interaction with GPR120 and NF-κB repression. In this scenario, the modulation of GPR120 exploits a novel crucial role in the regulation of the cell-to-cell cross-talk that drives inflammatory response, hepatic progenitor cell activation and hepatocyte survival.

  7. Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease

    PubMed Central

    Lombardi, Rosa; Buzzetti, Elena; Roccarina, Davide; Tsochatzis, Emmanuel A

    2015-01-01

    Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current “gold standard” for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence. PMID:26494961

  8. Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease.

    PubMed

    Lombardi, Rosa; Buzzetti, Elena; Roccarina, Davide; Tsochatzis, Emmanuel A

    2015-10-21

    Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current "gold standard" for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence.

  9. Destructive granuloma derived from a liver cyst: A case report

    PubMed Central

    Kawashita, Yujo; Kamohara, Yukio; Furui, Junichiro; Fujita, Fumihiko; Miyamoto, Shungo; Takatsuki, Mitsuhisa; Abe, Kuniko; Hayashi, Tomayoshi; Ohno, Yasuharu; Kanematsu, Takashi

    2006-01-01

    We herein report the case of an idiopathic liver cystic mass which aggressively infiltrated the thoraco-abdominal wall. A 74-year-old woman who had a huge cystic lesion in her right hepatic lobe was transferred to our hospital for further examinations. Imaging studies revealed a simple liver cyst, and the cytological findings of intracystic fluid were negative. She was followed up periodically by computed tomography (CT) scans. Seven years later, she complained of a prominence and dull pain in her right thoraco-abdominal region. CT revealed an enlargement of the cystic lesion and infiltration into the intercostal subcutaneous tissue. We suspected the development of a malignancy inside the liver cyst such as cystadenocarcinoma, and she therefore underwent surgery. A tumor extirpation was performed, including the chest wall, from the 7th to the 10th rib, as well as a right hepatic lobectomy. Pathologically, the lesion consisted of severe inflammatory change with epithelioid cell granuloma and bone destruction without any malignant neoplasm. No specific pathogens were evident based on further histological and molecular examinations. Therefore the lesion was diagnosed to be a destructive granuloma associated with a long-standing hepatic cyst. Since undergoing surgery, the patient has been doing well without any signs of recurrence. PMID:16586558

  10. High frequency of X chromosome abnormalities in women with short stature and elevated liver enzymes.

    PubMed

    Roulot, Dominique; Malan, Valérie; Ziol, Marianne; Linglart, Agnès; Bourcier, Valérie; Beaugrand, Michel; Benzacken, Brigitte

    2014-08-01

    Paucisymptomatic forms of Turner's syndrome (TS), in which short stature is the predominant clinical abnormality, remain underdiagnosed. Abnormal liver tests are extremely frequent in adult TS patients reflecting various types of hepatic lesions. The objective of the study was to investigate whether unexplained elevated liver enzymes in women with short stature could reveal X chromosome abnormalities of undiagnosed TS. Thirty-one consecutive short stature women displaying elevated liver enzymes and no previous diagnosis of TS were compared with 31 age-matched controls in a prospective study. Liver biopsy was performed in 26 patients. Systematic karyotype analysis and fluorescence in situ hybridization. X chromosome abnormalities were found in 27 patients and one control (87.0% vs 3.2%, P < .0001), including a 45,X/46,XX mosaicism in 24 patients and isochromosome of the long arm in three. Liver histological analysis showed architectural changes in 17 patients with nodular regenerative hyperplasia in 12. Biliary lesions were present in 13 patients and liver steatosis in 20. X chromosome abnormalities indicative of cryptic TS are extremely frequent in short-stature women with unexplained elevated liver enzymes. In short-stature women, abnormal liver tests should lead to systematic karyotype analysis.

  11. Association of caffeine intake and histological features of chronic hepatitis C.

    PubMed

    Costentin, Charlotte E; Roudot-Thoraval, Françoise; Zafrani, Elie-Serge; Medkour, Fatiha; Pawlotsky, Jean-Michel; Mallat, Ariane; Hézode, Christophe

    2011-06-01

    The severity of chronic hepatitis C (CHC) is modulated by host and environmental factors. Several reports suggest that caffeine intake exerts hepatoprotective effects in patients with chronic liver disease. The aim of this study was to evaluate the impact of caffeine consumption on activity grade and fibrosis stage in patients with CHC. A total of 238 treatment-naïve patients with histologically-proven CHC were included in the study. Demographic, epidemiological, environmental, virological, and metabolic data were collected, including daily consumption of alcohol, cannabis, tobacco, and caffeine during the six months preceding liver biopsy. Daily caffeine consumption was estimated as the sum of mean intakes of caffeinated coffee, tea, and caffeine-containing sodas. Histological activity grade and fibrosis stage were scored according to Metavir. Patients (154 men, 84 women, mean age: 45±11 years) were categorized according to caffeine consumption quartiles: group 1 (<225 mg/day, n=59), group 2 (225-407 mg/day, n=57), group 3 (408-678 mg/day, n=62), and group 4 (>678 mg/day, n=60). There was a significant inverse relationship between activity grade and daily caffeine consumption: activity grade>A2 was present in 78%, 61%, 52%, and 48% of patients in group 1, 2, 3, and 4, respectively (p<0.001). By multivariate analysis, daily caffeine consumption greater than 408 mg/day was associated with a lesser risk of activity grade>A2 (OR=0.32 (0.12-0.85). Caffeine intake showed no relation with fibrosis stage. Caffeine consumption greater than 408 mg/day (3 cups or more) is associated with reduced histological activity in patients with CHC. These findings support potential hepatoprotective properties of caffeine in chronic liver diseases. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  12. Lower levels of insulin-like growth factor-1 standard deviation score are associated with histological severity of non-alcoholic fatty liver disease.

    PubMed

    Sumida, Yoshio; Yonei, Yoshikazu; Tanaka, Saiyu; Mori, Kojiroh; Kanemasa, Kazuyuki; Imai, Shunsuke; Taketani, Hiroyoshi; Hara, Tasuku; Seko, Yuya; Ishiba, Hiroshi; Okajima, Akira; Yamaguchi, Kanji; Moriguchi, Michihisa; Mitsuyoshi, Hironori; Yasui, Kohichiroh; Minami, Masahito; Itoh, Yoshito

    2015-07-01

    Growth hormone (GH) deficiency may be associated with histological progression of non-alcoholic fatty liver disease (NAFLD) which includes non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Insulin-like growth factor 1 (IGF-1) is mainly produced by hepatocytes and its secretion is stimulated by GH. Our aim was to determine whether more histologically advanced NAFLD is associated with low circulating levels of IGF-1 in Japanese patients. Serum samples were obtained in 199 Japanese patients with biopsy-proven NAFLD and in 2911 sex- and age-matched healthy people undergoing health checkups. The serum levels of IGF-1 were measured using a commercially available immunoradiometric assay. The standard deviation scores (SDS) of IGF-1 according to age and sex were also calculated in NAFLD patients. The serum IGF-1 levels in NAFLD patients were significantly lower (median, 112 ng/mL) compared with the control population (median, 121 ng/mL, P < 0.0001). IGF-1 SDS less than -2.0 SD from median were found in 11.6% of 199 patients. NASH patients exhibited significantly lower levels of IGF-1 SDS (n = 130; median, -0.7) compared with NAFL patients (n = 69; median, -0.3; P = 0.026). The IGF-1 SDS values decreased significantly with increasing lobular inflammation (P < 0.001) and fibrosis (P < 0.001). In multiple regressions, the association between the IGF-1 SDS values and the severity of NAFLD persisted after adjusting for age, sex and insulin resistance. Low levels of circulating IGF-1 may have a role in the development of advanced NAFLD, independent of insulin resistance. Supplementation with GH/IGF-1 may be a candidate for the treatment of NASH. © 2014 The Japan Society of Hepatology.

  13. HISTOLOGIC, IMMUNOHISTOCHEMICAL, AND ELECTRON MICROSCOPIC CHARACTERIZATION OF A MALIGNANT IRIDOPHOROMA IN A DWARF BEARDED DRAGON (POGONA HENRYLAWSONI).

    PubMed

    de Brot, Simone; Sydler, Titus; Nufer, Lisbeth; Ruetten, Maja

    2015-09-01

    A dwarf bearded dragon (Pogona henrylawsoni) was presented with a white subcutaneous mandibular mass and multiple nodules in the oral mucosa, heart, liver, kidney, intestine, and visceral fat. Histologically, the tumor consisted of densely packed spindle-shaped cells with brow intracytoplasmic pigment that exhibited white-blue birefringence with polarized light. Immunohistochemical staining was negative for S-100 and weakly positive with melan A. Electron microscopic examination revealed cytoplasmic irregular and oblong empty spaces, laminated and often arranged into short stacks, compatible with reflecting platelet profiles typically seen in iridophores. However, in unstained ultrathin sections, electron-dense crystalline material was present, which filled the empty spaces described for stained sections before. Based on histology, immunohistochemistry, and biologic behavior, a malignant iridophoroma was diagnosed. To the authors' knowledge, iridophoromas in lizards have rarely been characterized by using electronic microscopy. Moreover, this is the first description of an iridophoroma in a dwarf bearded dragon.

  14. Effect of Increased Intra-abdominal Pressure on Liver Histology and Hemodynamics: An Experimental Study.

    PubMed

    Antoniou, Efstathios A; Kairi, Evi; Margonis, Georgios A; Andreatos, Nikolaos; Sasaki, Kazunari; Damaskos, Christos; Garmpis, Nikolaos; Samaha, Mario; Argyra, Eriphyli; Polymeneas, George; Weiss, Matthew J; Pawlik, Timothy M; Voros, Dionysios; Kouraklis, Gregory

    2018-01-01

    While reduction of portal venous (PV) blood flow has been described in animal models of intra-abdominal hypertension, reports on compensatory changes in hepatic arterial (HA) flow, known as the hepatic arterial buffer response are controversial. Pneumoperitoneum with helium was induced in 13 piglets. Hemodynamic measurements and pathological assessment were conducted at baseline and during the three subsequent phases: Phase A: 45 minutes with a stable intra-abdominal pressure of 25 mmHg; phase B: 45 minutes with a stable intra-abdominal pressure of 40 mmHg; and phase C during which the abdomen was re-explored and reperfusion of the liver was allowed to take place. Phase B pressure was significantly greater than phase A pressure in both the PV and the inferior vena cava, demonstrating a positive association between escalating intra-abdominal hypertension and the pressure in these two vessels (all p<0.001). In contrast, HA pressure was comparable between baseline and phase A, while it tended to decrease in phase B. Regarding histology, the most notable abnormality was the presence of inflammatory infiltrates and hepatocyte necrosis. Helium-insufflation increased PV pressure with a partial compensatory decrease of HA pressure. Nonetheless, findings consistent with hepatic ischemia were observed on pathology. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  15. Molecular and histological study on the effects of non-thermal irreversible electroporation on the liver.

    PubMed

    Zhang, Yanfang; Lyu, Chenang; Liu, Yu; Lv, Yanpeng; Chang, Tammy T; Rubinsky, Boris

    2018-06-07

    Non-thermal irreversible electroporation (NTIRE) is a biophysical phenomenon in which certain electric fields delivered across the cell membrane in tissue, cause cell death, without affecting the extracellular matrix. "Minimally invasive regenerative surgery" is a new medical modality for treatment of end-stage organ or tissue failure in which exogenous cells are implanted in a decellularized niche in tissue, formed by the delivery of NTIRE electric fields across a targeted volume of tissue. We anticipate that the success of the procedure will depend on the time of implantation relative to the application of NTIRE. This study was performed to elucidate the histological and molecular events that occur within 24 h after NTIRE, in the context of optimal criteria for the time of implantation. To this end, we examined the histology of NTIRE treated rat liver with H&E, Masson trichrome and TUNEL staining. Western blot was used to examine pro and cleaved caspase-3 (marker for apoptosis), pro and cleaved caspase-1 and gasdermin D (markers for pyroptosis), and RIP3 and MLKL (markers for necroptosis). The key findings are that, complete hepatocytes disintegration within an intact extracellular matrix is seen at 6 h and, new hepatocytes are seen in the treated region at 24 h, after NTIRE. There is no evidence of apoptotic cell death from NTIRE, contrary to commonly made claims in the NTIRE literature. However, molecular pathways of pyroptosis and necroptosis, programed necrosis associated with inflammation, are activated at 6 h after NTIRE and are not evident at 24 h after NTIRE. These are fundamental new findings of basic value to the field of NTIRE in all its applications. Taken together the results suggest the hypothesis that an optimal time for implantation is about 24 h after NTIRE. Future studies in which exogenous cells are implanted at different times after NTIRE are required to examine this hypothesis. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. A Study of the Modulating Action of Quercetin on Biochemical and Histological Alterations Induced by Lead Exposure in the Liver and Kidney of Rats.

    PubMed

    Mohammed, Ghena M.; Sedky, Azza; Elsawy, Hany

    2017-06-30

    Lead is a highly toxic metal and a very potent poison. Lead poisoning is a serious condition but can be treated. Quercetin is a flavonoid with many beneficial uses. The aim of the present study was to investigate the possible modulating action of quercetin as a model of an antioxidant against the toxic effects of lead acetate on liver and kidneys of rats. Rats were randomly divided into four groups: (i) saline group (control); (ii) lead group received i.p. lead acetate (20 mg/kg b.w.); (iii) quercetin group received i.p. quercetin (50 mg/kg b.w.); (iv) lead and quercetin group received i.p. lead acetate (20 mg/kg b.w.) followed by i.p. quercetin (50 mg/kg b.w.) for 4 weeks. The lead concentrations were determined in the liver and kidney tissues. Liver marker enzymes, bilirubin, albumin, total protein, creatinine, uric acid and urea, were assessed in the serum and light microscopic studies were performed. The results showed that lead acetate administration was associated with an increase in serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, total bilirubin, creatinine, uric acid, urea levels. Lead accumulation in kidneys and liver tissues was also found, but were associated with decrease in albumin and total protein in comparison with the respective mean values of the control. Lead acetate caused numerous histological alterations in the liver, including chronic inflammation, bilary hyperplasia, edema, congestion, Kupffer cells hyperplasia and hemosiderosis, and in the kidney, including tubular dilation, atrophy of glomerular tuft, widening of urinary space and mild fibroblast. In contrary, administration of lead acetate along with quercetin partially restored the studied parameters to normal values and improved structure of liver and kidney with significant decreases in the severity of histopathological changes when compared with the lead acetate group. In conclusion, treatment with quercetin may provide a

  17. Accuracy of ultrasound in the detection of liver fibrosis in chronic viral hepatitis.

    PubMed

    D'Onofrio, Mirko; Martone, Enrico; Brunelli, Silvia; Faccioli, Niccolò; Zamboni, Giulia; Zagni, Irene; Fattovich, Giovanna; Pozzi Mucelli, Roberto

    2005-10-01

    To assess the accuracy of ultrasonography (US) in the identification and grading of hepatic fibrosis in patients afflicted with chronic viral liver disease, compared to histological examination as a gold standard. We prospectively studied 105 patients (32 F, 73 M) affected by chronic viral liver disease in 36 months. Patients were studied with B-mode US and then underwent US-guided liver biopsy. All the patients were studied with conventional US with a Sequoia 512, 6.0 (Acuson, Mountain View CA, USA). We evaluated the following US parameters: liver margins, parenchymal echotexture, portal vein caliber and spleen diameter. The four B-mode US parameters were used for the US grading (from 0 to 4). Scheuer's grading (from 0 to 4) was used for the histological score. Grades 3 and 4 were considered as positive for fibrosis. Sensitivity, specificity, positive and negative predictive values and accuracy were calculated in the case of absence, positivity of one or all the US parameters. The correlation between US and histological scores was evaluated with Spearman's test. At histology seventy-seven patients (73%) had absent grade 0 (1 patient; 1%), low-moderate grade 1 (35 patients; 33%) or grade 2 (41 patients; 39%) liver fibrosis. Twenty-eight patients (27%) had severe grade 3 (16 patients; 15%) or grade 4 (12 patients; 11%) fibrosis. In the case of absence of US parameters sensitivity was 32%, specificity 32%, positive predictive value 15%, negative predictive value 57% and accuracy 32%. In the case of positivity of at least one of the US parameters the values were 68%, 68%, 43%, 84% and 69%. In the case of presence of all the US signs the results were 25%, 100%, 100%, 79% and 80%. None of the 77 patients with a healthy liver or with low-grade fibrosis was positive for all the US parameters. All the patients positive for all of the ultrasonographic parameters had high-grade fibrosis or cirrhosis at liver biopsy. Correlation between B-mode and histological scores was not

  18. Photoacoustic physio-chemical analysis of liver conditions in animal and human subjects

    NASA Astrophysics Data System (ADS)

    Wang, Xueding; Xu, Guan; Tian, Chao; Wan, Shanshan; Welling, Theodore H.; Lok, Anna S. F.; Rubin, Jonathan M.

    2016-03-01

    Non-alcoholic fatty liver disease (NAFLD) is a common liver disease affecting 30% of the population in the United States. Biopsy is the gold standard for diagnosing NAFLD. Liver histology assesses the amount of fat, and determines type and extent of cell injury, inflammation and fibrosis. However, liver biopsy is invasive and is limited by sampling error. Current radiological diagnostic modalities can evaluate the 'physical' morphology in liver by quantifying the backscattered US signals, but cannot interrogate the 'histochemical' components forming these backscatterers. For example, ultrasound (US) imaging can detect the presence of fat but cannot differentiate steatosis alone from steatohepatitis. Our previous study of photoacoustic physiochemical analysis (PAPCA) has demonstrated that this method can characterize the histological changes in livers during the progression of NAFLD in animal models. In this study, we will further validate PAPCA with human livers. Ex vivo human liver samples with steatosis, fibrosis and cirrhosis will be scanned using optical illumination at wavelengths of 680-1700 nm and compared to histology results. In vivo study on human subjects with confirmed steatosis is planned using our PA-ultrasound (US) parallel imaging system based on Verasonic US imaging flatform with an L7-4 probe. 10 mJ/cm2 per pulse optical energy at 755 nm will be delivered to the skin surface, which is under the safety limit of American National Standard Institute. Preliminary study with ex vivo human tissue has demonstrated the potential of the proposed approach in differentiating human liver conditions.

  19. Antioxidant vitamins in the context of nonalcoholic fatty liver disease in obese children and adolescents

    PubMed Central

    Ued, Fábio da Veiga; Weffort, Virgínia Resende S.

    2013-01-01

    OBJECTIVE: To review the literature on the importance of antioxidant vitamins, analyzed in the context of dietary intake, its plasma levels, and its current use as a supplementation treatment in obese children and adolescents with nonalcoholic fatty liver disease. DATA SOURCES: The articles were identified in Lilacs, Ibecs, SciELO, PubMed/Medline, and Scopus databases. To conduct the survey, the "fatty liver" descriptor was associated to the following words: "children", "antioxidants" and "vitamins". The search was limited to articles written in Portuguese, Spanish and English, with publication date until December, 2012. DATA SYNTHESIS: Six studies were selected. The survey revealed a low dietary intake and low antioxidant vitamins serum levels in this population. The changes in lifestyle, with adequate dietary intake of vitamins, and the increase in physical activity were associated with a significant improvement in liver histology and in laboratory tests. Vitamin supplementation also improved the disease progression markers, as the alanine aminotransferase serum levels and the histological characteristics of lobular inflammation and hepatocellular damage. However, these improvements were not statistically significant in all studies. CONCLUSIONS: There is insufficient evidence to recommend or to refute antioxidant supplementation in patients with simple steatosis or steatohepatitis. The changes in lifestyle seem to be, at the present time, the more advisable therapy. PMID:24473959

  20. Prolonged feeding with guanidinoacetate, a methyl group consumer, exacerbates ethanol-induced liver injury.

    PubMed

    Osna, Natalia A; Feng, Dan; Ganesan, Murali; Maillacheruvu, Priya F; Orlicky, David J; French, Samuel W; Tuma, Dean J; Kharbanda, Kusum K

    2016-10-14

    To investigate the hypothesis that exposure to guanidinoacetate (GAA, a potent methyl-group consumer) either alone or combined with ethanol intake for a prolonged period of time would cause more advanced liver pathology thus identifying methylation defects as the initiator and stimulator for progressive liver damage. Adult male Wistar rats were fed the control or ethanol Lieber DeCarli diet in the absence or presence of GAA supplementation. At the end of 6 wk of the feeding regimen, various biochemical and histological analyses were conducted. Contrary to our expectations, we observed that GAA treatment alone resulted in a histologically normal liver without evidence of hepatosteatosis despite persistence of some abnormal biochemical parameters. This protection could result from the generation of creatine from the ingested GAA. Ethanol treatment for 6 wk exhibited changes in liver methionine metabolism and persistence of histological and biochemical defects as reported before. Further, when the rats were fed the GAA-supplemented ethanol diet, similar histological and biochemical changes as observed after 2 wk of combined treatment, including inflammation, macro- and micro-vesicular steatosis and a marked decrease in the methylation index were noted. In addition, rats on the combined treatment exhibited increased liver toxicity and even early fibrotic changes in a subset of animals in this group. The worsening liver pathology could be related to the profound reduction in the hepatic methylation index, an increased accumulation of GAA and the inability of creatine generated to exert its hepato-protective effects in the setting of ethanol. To conclude, prolonged exposure to a methyl consumer superimposed on chronic ethanol consumption causes persistent and pronounced liver damage.

  1. Prolonged feeding with guanidinoacetate, a methyl group consumer, exacerbates ethanol-induced liver injury

    PubMed Central

    Osna, Natalia A; Feng, Dan; Ganesan, Murali; Maillacheruvu, Priya F; Orlicky, David J; French, Samuel W; Tuma, Dean J; Kharbanda, Kusum K

    2016-01-01

    AIM To investigate the hypothesis that exposure to guanidinoacetate (GAA, a potent methyl-group consumer) either alone or combined with ethanol intake for a prolonged period of time would cause more advanced liver pathology thus identifying methylation defects as the initiator and stimulator for progressive liver damage. METHODS Adult male Wistar rats were fed the control or ethanol Lieber DeCarli diet in the absence or presence of GAA supplementation. At the end of 6 wk of the feeding regimen, various biochemical and histological analyses were conducted. RESULTS Contrary to our expectations, we observed that GAA treatment alone resulted in a histologically normal liver without evidence of hepatosteatosis despite persistence of some abnormal biochemical parameters. This protection could result from the generation of creatine from the ingested GAA. Ethanol treatment for 6 wk exhibited changes in liver methionine metabolism and persistence of histological and biochemical defects as reported before. Further, when the rats were fed the GAA-supplemented ethanol diet, similar histological and biochemical changes as observed after 2 wk of combined treatment, including inflammation, macro- and micro-vesicular steatosis and a marked decrease in the methylation index were noted. In addition, rats on the combined treatment exhibited increased liver toxicity and even early fibrotic changes in a subset of animals in this group. The worsening liver pathology could be related to the profound reduction in the hepatic methylation index, an increased accumulation of GAA and the inability of creatine generated to exert its hepato-protective effects in the setting of ethanol. CONCLUSION To conclude, prolonged exposure to a methyl consumer superimposed on chronic ethanol consumption causes persistent and pronounced liver damage. PMID:27784962

  2. Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors.

    PubMed

    De Martin, Eleonora; Michot, Jean-Marie; Papouin, Barbara; Champiat, Stéphane; Mateus, Christine; Lambotte, Olivier; Roche, Bruno; Antonini, Teresa Maria; Coilly, Audrey; Laghouati, Salim; Robert, Caroline; Marabelle, Aurélien; Guettier, Catherine; Samuel, Didier

    2018-06-01

    Immunotherapy for metastatic cancer can be complicated by the onset of hepatic immune-related adverse events (IRAEs). This study compared hepatic IRAEs associated with anti-programmed cell death protein 1 (PD-1)/PD ligand 1 (PD-L1) and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) monoclonal antibodies (mAbs). Among 536 patients treated with anti-PD-1/PD-L1 or CTLA-4 immunotherapies, 19 (3.5%) were referred to the liver unit for grade ≥3 hepatitis. Of these patients, nine had received anti-PD-1/PD-L1 and seven had received anti-CTLA-4 mAbs, in monotherapy or in combination with anti-PD-1. Liver investigations were undertaken in these 16 patients, including viral assays, autoimmune tests and liver biopsy, histological review, and immunostaining of liver specimens. In the 16 patients included in this study, median age was 63 (range 33-84) years, and nine (56%) were female. Time between therapy initiation and hepatitis was five (range, 1-49) weeks and median number of immunotherapy injections was two (range, 1-36). No patients developed hepatic failure. Histology related to anti-CTLA-4 mAbs demonstrated granulomatous hepatitis including fibrin ring granulomas and central vein endotheliitis. Histology related to anti-PD-1/PD-L1 mAbs was characterised by lobular hepatitis. The management of hepatic IRAEs was tailored according to the severity of both the biology and histology of liver injury: six patients improved spontaneously; seven received oral corticosteroids at 0.5-1 mg/kg/day; two were maintained on 0.2 mg/kg/day corticosteroids; and one patient required pulses and 2.5 mg/kg/day of corticosteroids, and the addition of a second immunosuppressive drug. In three patients, immunotherapy was reintroduced without recurrence of liver dysfunction. Acute hepatitis resulting from immunotherapy for metastatic cancer is rare (3.5%) and, in most cases, not severe. Histological assessment can distinguish between anti-PD-1/PD-L1 and anti-CTLA-4 mAb toxicity. The

  3. L-arginine reduces liver and biliary tract damage after liver transplantation from non-heart-beating donor pigs.

    PubMed

    Valero, R; García-Valdecasas, J C; Net, M; Beltran, J; Ordi, J; González, F X; López-Boado, M A; Almenara, R; Taurá, P; Elena, M; Capdevila, L; Manyalich, M; Visa, J

    2000-09-15

    To evaluate whether L-arginine reduces liver and biliary tract damage after transplantation from non heart-beating donor pigs. Twenty-five animals received an allograft from non-heart-beating donors. After 40 min of cardiac arrest, normothermic recirculation was run for 30 min. The animals were randomly treated with L-arginine (400 mg x kg(-1) during normothermic recirculation) or saline (control group). Then, the animals were cooled and their livers were transplanted after 6 hr of cold ischemia. The animals were killed on the 5th day, liver damage was assessed on wedged liver biopsies by a semiquantitative analysis and by morphometric analysis of the necrotic areas, and biliary tract damage by histological examination of the explanted liver. Seventeen animals survived the study period. The histological parameters assessed (sinusoidal congestion and dilatation, sinusoidal infiltration by polymorphonuclear cells and lymphocytes, endothelitis, dissociation of liver cell plates, and centrilobular necrosis) were significantly worse in the control group. The necrotic area affected 15.9 +/- 14.5% of the liver biopsies in the control group and 3.7 +/- 3.1% in the L-arginine group (P<0.05). Six of eight animal in the control group and only one of eight survivors in the L-arginine group developed ischemic cholangitis (P<0.01). L-Arginine administration was associated with higher portal blood flow (676.9 +/- 149.46 vs. 475.2 +/- 205.6 ml x min x m(-2); P<0.05), higher hepatic hialuronic acid extraction at normothermic recirculation (38.8 +/- 53.7% vs. -4.2 +/- 18.2%; P<0.05) and after reperfusion (28.6 +/- 55.5% vs. -10.9 +/- 15.5%; P<0.05) and lower levels of alpha-glutation-S-transferase at reperfusion (1325 +/- 1098% respect to baseline vs. 6488 +/- 5612%; P<0.02). L-Arginine administration during liver procurement from non heart beating donors prevents liver and biliary tract damage.

  4. A comparison of classical histology to anatomy revealed by hard x-rays

    NASA Astrophysics Data System (ADS)

    Richter, Claus-Peter; Tan, Xiaodong; Young, Hunter; Stock, Stuart; Robinson, Alan; Byskosh, Orest; Zheng, Jing; Soriano, Carmen; Xiao, Xianghui; Whitlon, Donna

    2016-10-01

    Many diseases trigger morphological changes in affected tissue. Today, classical histology is still the "gold standard" used to study and describe those changes. Classical histology, however, is time consuming and requires chemical tissue manipulations that can result in significant tissue distortions. It is sometimes difficult to separate tissue-processing artifacts from changes caused by the disease process. We show that synchrotron X-ray phase-contrast micro-computed tomography (micro-CT) can be used to examine non-embedded, hydrated tissue at a resolution comparable to that obtained with classical histology. The data analysis from stacks of reconstructed micro-CT images is more flexible and faster than when using the classical, physically embedded sections that are by necessity fixed in a particular orientation. We show that in a three-dimensional (3D) structure with meticulous structural details such as the cochlea and the kidney, micro-CT is more flexible, faster and more convenient for morphological studies and disease diagnoses.

  5. Autoimmune hepatitis, one disease with many faces: Etiopathogenetic, clinico-laboratory and histological characteristics

    PubMed Central

    Gatselis, Nikolaos K; Zachou, Kalliopi; Koukoulis, George K; Dalekos, George N

    2015-01-01

    Autoimmune hepatitis (AIH) is an unresolving progressive liver disease of unknown etiology characterized by hypergammaglobulinemia, autoantibodies detection and interface hepatitis. Due to the absence of specific diagnostic markers and the large heterogeneity of its clinical, laboratory and histological features, AIH diagnosis may be potentially difficult. Therefore, in this in-depth review we summarize the substantial progress on etiopathogenesis, clinical, serological and histological phenotypes of AIH. AIH has a global distribution affecting any age, both sexes and all ethnic groups. Clinical manifestations vary from asymptomatic to severe or rarely fulminant hepatitis. Hypergammaglobulinemia with selective elevation of IgG is found in most cases. Autoimmune attack is perpetuated, possibly via molecular mimicry, and favored by the impaired control of T-regulatory cells. Histology (interface hepatitis, emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic, are still the hallmark for a timely diagnosis. AIH remains a major diagnostic challenge. AIH should be considered in every case in the absence of viral, metabolic, genetic and toxic etiology of chronic or acute hepatitis. Laboratory personnel, hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient. PMID:25574080

  6. Symbiotic formulation in experimentally induced liver fibrosis in rats: intestinal microbiota as a key point to treat liver damage?

    PubMed

    D'Argenio, Giuseppe; Cariello, Rita; Tuccillo, Concetta; Mazzone, Giovanna; Federico, Alessandro; Funaro, Annalisa; De Magistris, Laura; Grossi, Enzo; Callegari, Maria L; Chirico, Marilena; Caporaso, Nicola; Romano, Marco; Morelli, Lorenzo; Loguercio, Carmela

    2013-05-01

    Evidence indicates that intestinal microbiota may participate in both the induction and the progression of liver damage. The aim of our research was the detection and evaluation of the effects of chronic treatment with a symbiotic formulation on CCl4 -induced rat liver fibrosis. CCl4 significantly increased gastric permeability in respect to basal values, and the treatment with symbiotic significantly decreased it. CCl4 per se induced a decrease in intestinal permeability. This effect was also seen in fibrotic rats treated with symbiotic and was still evident when normal rats were treated with symbiotic alone (P < 0.001 in all cases). Circulating levels of pro-inflammatory cytokine TNF-α were significantly increased in rats with liver fibrosis as compared with normal rats, while symbiotic treatment normalized the plasma levels of TNF-α and significantly enhanced anti-inflammatory cytokine IL 10. TNF-α, TGF-β, TLR4, TLR2, iNOS and α-SMA mRNA expression in the liver were up-regulated in rats with CCl4 -induced liver fibrosis and down-regulated by symbiotic treatment. Moreover, IL-10 and eNOS mRNA levels were increased in the CCL4 (+) symbiotic group. Symbiotic treatment of fibrotic rats normalized serum ALT, AST and improved histology and liver collagen deposition. DGGE analysis of faecal samples revealed that CCl4 administration and symbiotic treatment either alone or in combination produced modifications in faecal profiles vs controls. Our results provide evidence that in CCl4 -induced liver fibrosis, significant changes in gastro-intestinal permeability and in faecal flora occur. Treatment with a specific symbiotic formulation significantly affects these changes, leading to improvement in both liver inflammation and fibrosis. © 2013 John Wiley & Sons A/S.

  7. [The clinicopathological analysis of 88 patients with abnormal liver function test of unknown etiology].

    PubMed

    Pang, Shu-zhen; Ou, Xiao-juan; Shi, Xiao-yan; Wang, Tai-ling; Duan, Wei-jia; Jia, Ji-dong

    2011-01-01

    To evaluate the clinical and histological features of patients with abnormal liver tests of unknown etiology, and then to investigate the diagnosis and differential diagnosis. Patients with abnormal liver function test hospitalized and had liver biopsies during 2008 - 2009 constituted this retrospective study cohort. After excluding those patients diagnosed with hepatotropic viral hepatitis, space occupying lesions of the liver, alcoholic liver disease and obstruction of bile duct caused by stone or malignancy and AMA/AMA-M(2) positive of primary biliary cirrhosis (PBC), the clinical and histological characteristics were evaluated. Out of the 180 patients who underwent liver biopsy, 88 patients were included in the present analysis. The final diagnosis involved 15 categories of diseases, with drug-induced liver injury (DILI) [34.09% (30/88)], autoimmune liver diseases [22.73% (20/88)], and nonalcoholic fatty liver disease (NAFLD) [12.50% (11/88)] being the most common causes, following by genetic and other rare diseases. DILI, autoimmune liver disease and NAFLD were the most common causes of abnormal liver tests in these non-viral liver diseases. Some rare diseases such as hereditary metabolic liver disease also represent a considerable proportion in patients with abnormal liver function test.

  8. Targeting nuclear receptors for the treatment of fatty liver disease.

    PubMed

    Tanaka, Naoki; Aoyama, Toshifumi; Kimura, Shioko; Gonzalez, Frank J

    2017-11-01

    Ligand-activated nuclear receptors, including peroxisome proliferator-activated receptor alpha (PPARα), pregnane X receptor, and constitutive androstane receptor, were first identified as key regulators of the responses against chemical toxicants. However, numerous studies using mouse disease models and human samples have revealed critical roles for these receptors and others, such as PPARβ/δ, PPARγ, farnesoid X receptor (FXR), and liver X receptor (LXR), in maintaining nutrient/energy homeostasis in part through modulation of the gut-liver-adipose axis. Recently, disorders associated with disrupted nutrient/energy homeostasis, e.g., obesity, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD), are increasing worldwide. Notably, in NAFLD, a progressive subtype exists, designated as non-alcoholic steatohepatitis (NASH) that is characterized by typical histological features resembling alcoholic steatohepatitis (ASH), and NASH/ASH are recognized as major causes of hepatitis virus-unrelated liver cirrhosis and hepatocellular carcinoma. Since hepatic steatosis is basically caused by an imbalance between fat/energy influx and utilization, abnormal signaling of these nuclear receptors contribute to the pathogenesis of fatty liver disease. Standard therapeutic interventions have not been fully established for fatty liver disease, but some new agents that activate or inhibit nuclear receptor signaling have shown promise as possible therapeutic targets. In this review, we summarize recent findings on the roles of nuclear receptors in fatty liver disease and discuss future perspectives to develop promising pharmacological strategies targeting nuclear receptors for NAFLD/NASH. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. PET/CT with 18F Fluorocholine as an Imaging Biomarker for Chronic Liver Disease: A Preliminary Radiopathologic Correspondence Study in Patients with Liver Cancer.

    PubMed

    Kwee, Sandi A; Wong, Linda; Chan, Owen T M; Kalathil, Sumodh; Tsai, Naoky

    2018-04-01

    Purpose To determine the relationship between hepatic uptake at preoperative fluorine 18 ( 18 F) fluorocholine combined positron emission tomography (PET) and computed tomography (CT) and the histopathologic features of chronic liver disease in patients with Child-Pugh class A or B disease who are undergoing hepatic resection for liver cancer. Materials and Methods Forty-eight patients with resectable liver tumors underwent preoperative 18 F fluorocholine PET/CT. Mean liver standardized uptake value (SUV mean ) measurements were obtained from PET images, while histologic indexes of inflammation and fibrosis were applied to nontumor liver tissue from resection specimens. Effects of histopathologic features on liver SUV mean were examined with analysis of variance. Results Liver SUV mean ranged from 4.3 to 11.6, correlating significantly with Knodell histologic activity index (ρ = -0.81, P < .001) and several clinical indexes of liver disease severity. Liver SUV mean also differed significantly across groups stratified by necroinflammatory severity and Metavir fibrosis stage (P < . 001). The area under the receiver operating characteristic curve for 18 F fluorocholine PET/CT detecting Metavir fibrosis stage F1 or higher was 0.89 ± 0.05, with an odds-ratio of 3.03 (95% confidence interval: 1.59, 5.88) and sensitivity and specificity of 82% and 93%, respectively. Conclusion Correlations found in patients undergoing hepatic resection for liver cancer between liver 18 F fluorocholine uptake and histopathologic indexes of liver fibrosis and inflammation support the use of 18 F fluorocholine PET/CT as a potential imaging biomarker for chronic liver disease. © RSNA, 2018.

  10. Digital liver biopsy: Bio-imaging of fatty liver for translational and clinical research

    PubMed Central

    Mancini, Marcello; Summers, Paul; Faita, Francesco; Brunetto, Maurizia R; Callea, Francesco; De Nicola, Andrea; Di Lascio, Nicole; Farinati, Fabio; Gastaldelli, Amalia; Gridelli, Bruno; Mirabelli, Peppino; Neri, Emanuele; Salvadori, Piero A; Rebelos, Eleni; Tiribelli, Claudio; Valenti, Luca; Salvatore, Marco; Bonino, Ferruccio

    2018-01-01

    The rapidly growing field of functional, molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a “digital biopsy” for in vivo study of liver pathophysiology. To foster the application of bio-imaging in clinical and translational research, there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver. It can be hoped that the combination of digital, liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies, diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer. A group of experts of different disciplines (Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver, Institute for Biostructures and Bio-imaging of the National Research Council and Bio-banking and Biomolecular Resources Research Infrastructure) discussed criteria, methods and guidelines for facilitating the requisite application of data collection. This manuscript provides a multi-Author review of the issue with special focus on fatty liver. PMID:29527259

  11. Digital liver biopsy: Bio-imaging of fatty liver for translational and clinical research.

    PubMed

    Mancini, Marcello; Summers, Paul; Faita, Francesco; Brunetto, Maurizia R; Callea, Francesco; De Nicola, Andrea; Di Lascio, Nicole; Farinati, Fabio; Gastaldelli, Amalia; Gridelli, Bruno; Mirabelli, Peppino; Neri, Emanuele; Salvadori, Piero A; Rebelos, Eleni; Tiribelli, Claudio; Valenti, Luca; Salvatore, Marco; Bonino, Ferruccio

    2018-02-27

    The rapidly growing field of functional, molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a "digital biopsy" for in vivo study of liver pathophysiology. To foster the application of bio-imaging in clinical and translational research, there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver. It can be hoped that the combination of digital, liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies, diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer. A group of experts of different disciplines (Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver, Institute for Biostructures and Bio-imaging of the National Research Council and Bio-banking and Biomolecular Resources Research Infrastructure) discussed criteria, methods and guidelines for facilitating the requisite application of data collection. This manuscript provides a multi-Author review of the issue with special focus on fatty liver.

  12. Prognostic Value of Non-Invasive Fibrosis and Steatosis Tools, Hepatic Venous Pressure Gradient (HVPG) and Histology in Nonalcoholic Steatohepatitis.

    PubMed

    Sebastiani, Giada; Alshaalan, Rasha; Wong, Philip; Rubino, Maria; Salman, Ayat; Metrakos, Peter; Deschenes, Marc; Ghali, Peter

    2015-01-01

    Non-invasive diagnostic methods for liver fibrosis predict clinical outcomes in viral hepatitis and nonalcoholic fatty liver disease (NAFLD). We specifically evaluated prognostic value of non-invasive fibrosis methods in nonalcoholic steatohepatitis (NASH) against hepatic venous pressure gradient (HVPG) and liver histology. This was a retrospective cohort study of 148 consecutive patients who met the following criteria: transjugular liver biopsy with HVPG measurement; biopsy-proven NASH; absence of decompensation; AST-to-Platelets Ratio Index (APRI), fibrosis-4 (FIB-4), NAFLD fibrosis score, ultrasound, hepatic steatosis index and Xenon-133 scan available within 6 months from biopsy; a minimum follow-up of 1 year. Outcomes were defined by death, liver transplantation, cirrhosis complications. Kaplan-Meier and Cox regression analyses were employed to estimate incidence and predictors of outcomes, respectively. Prognostic value was expressed as area under the curve (AUC). During a median follow-up of 5 years (interquartile range 3-8), 16.2% developed outcomes, including 7.4% who died or underwent liver transplantation. After adjustment for age, sex, diabetes, the following fibrosis tools predicted outcomes: HVPG >10mmHg (HR=9.60; 95% confidence interval [CI] 3.07-30.12), histologic fibrosis F3-F4 (HR=3.14; 1.41-6.95), APRI >1.5 (HR=5.02; 1.6-15.7), FIB-4 >3.25 (HR=6.33; 1.98-20.2), NAFLD fibrosis score >0.676 (HR=11.9; 3.79-37.4). Prognostic value was as follows: histologic fibrosis stage, AUC=0.85 (95% CI 0.76-0.93); HVPG, AUC=0.81 (0.70-0.91); APRI, AUC=0.89 (0.82-0.96); FIB-4, AUC=0.89 (0.83-0.95); NAFLD fibrosis score, AUC=0.79 (0.69-0.91). Neither histologic steatosis nor non-invasive steatosis methods predicted outcomes (AUC<0.50). Non-invasive methods for liver fibrosis predict outcomes of patients with NASH. They could be used for serial monitoring, risk stratification and targeted interventions.

  13. Coconut water vinegar ameliorates recovery of acetaminophen induced liver damage in mice.

    PubMed

    Mohamad, Nurul Elyani; Yeap, Swee Keong; Beh, Boon-Kee; Ky, Huynh; Lim, Kian Lam; Ho, Wan Yong; Sharifuddin, Shaiful Adzni; Long, Kamariah; Alitheen, Noorjahan Banu

    2018-06-25

    Coconut water has been commonly consumed as a beverage for its multiple health benefits while vinegar has been used as common seasoning and a traditional Chinese medicine. The present study investigates the potential of coconut water vinegar in promoting recovery on acetaminophen induced liver damage. Mice were injected with 250 mg/kg body weight acetaminophen for 7 days and were treated with distilled water (untreated), Silybin (positive control) and coconut water vinegar (0.08 mL/kg and 2 mL/kg body weight). Level of oxidation stress and inflammation among treated and untreated mice were compared. Untreated mice oral administrated with acetaminophen were observed with elevation of serum liver profiles, liver histological changes, high level of cytochrome P450 2E1, reduced level of liver antioxidant and increased level of inflammatory related markers indicating liver damage. On the other hand, acetaminophen challenged mice treated with 14 days of coconut water vinegar were recorded with reduction of serum liver profiles, improved liver histology, restored liver antioxidant, reduction of liver inflammation and decreased level of liver cytochrome P450 2E1 in dosage dependent level. Coconut water vinegar has helped to attenuate acetaminophen-induced liver damage by restoring antioxidant activity and suppression of inflammation.

  14. The protective effect of 1alpha, 25-dihydroxyvitamin d3 and metformin on liver in type 2 diabetic rats.

    PubMed

    Elattar, Samah; Estaphan, Suzanne; Mohamed, Enas A; Elzainy, Ahmed; Naguib, Mary

    2017-10-01

    There is an accumulating evidence suggesting an immunomodulatory role of 1α,25(OH) 2 D3. Altered 1α,25(OH) 2 D3 level may play a role in the development of T2DM and contribute to the pathogenesis of liver diseases. Our study was designed to study and compare the effect of metformin and 1α,25(OH) 2 D3 supplementation on liver injury in type 2 diabetic rat. Sixty male Albino rats were divided into 5 groups; group 1: control rats. the remaining rats were fed high fat diet for 2 weeks and injected with streptozotocin (35mg/kg BW, i.p.) to induce T2DM and were divided into: group 2: untreated diabetic rats, group 3: diabetic rats treated by metformin (100mg/kgBW/d, orally), group 4: diabetic rats supplemented by 1α,25(OH) 2 D3 (0.5μg/kg BW, i.p.) 3 times weekly and group 5: supplemented by both 1α,25(OH) 2 D3 and metformin. Eight weeks later, serum glucose and insulin levels were measured, HOMA IR was calculated, lipid profile, Ca2+, ALT and AST were estimated. Liver specimens were taken to investigate PPAR-α (regulator of lipid metabolism), NF-κB p65, caspase 3 and PCNA (proliferating cell nuclear antigen) and for histological examination. The liver enzymes were elevated in the diabetic rats and the histological results revealed an injurious effect of diabetes on the liver. 1α,25(OH) 2 D3, metformin and both drugs treatment significantly improved liver enzymes as compared to the untreated rats. The improvement was associated with a significant improvement in the glycemic control, lipid profile and serum Ca2+ with a significant reduction in NF-κB p65 and caspase 3 and increased PPAR-α, and PCNA expression as compared to the untreated group. 1α,25(OH) 2 D3 induced a slightly better effect as compared to metformin. Both agents together had a synergistic action and almost completely protected the liver. Histological results confirmed the biochemical findings. Our results showed a protective effect of 1α,25(OH) 2 D3 and metformin on liver in diabetic rats as

  15. Liver metabolomics study reveals protective function of Phyllanthus urinaria against CCl4-induced liver injury.

    PubMed

    Guo, Qing; Zhang, Qian-Qian; Chen, Jia-Qing; Zhang, Wei; Qiu, Hong-Cong; Zhang, Zun-Jian; Liu, Bu-Ming; Xu, Feng-Guo

    2017-07-01

    Phyllanthus Urinaria L. (PUL) is a traditional Chinese medicine used to treat hepatic and renal disorders. However, the mechanism of its hepatoprotective action is not fully understood. In the present study, blood biochemical indexes and liver histopathological changes were used to estimate the extent of hepatic injury. GC/MS and LC/MS-based untargeted metabolomics were used in combination to characterize the potential biomarkers associated with the protective activity of PUL against CCl 4 -induced liver injury in rats. PUL treatment could reverse the increase in ALT, AST and ALP induced by CCl 4 and attenuate the pathological changes in rat liver. Significant changes in liver metabolic profiling were observed in PUL-treated group compared with liver injury model group. Seventeen biomarkers related to the hepatoprotective effects of PUL against CCl 4 -induced liver injury were screened out using nonparametric test and Pearson's correlation analysis (OPLS-DA). The results suggested that the potential hepatoprotective effects of PUL in attenuating CCl 4 -induced hepatotoxicity could be partially attributed to regulating L-carnitine, taurocholic acid, and amino acids metabolism, which may become promising targets for treatment of liver toxicity. In conclusion, this study provides new insights into the mechanism of the hepatoprotection of Phyllanthus Urinaria. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  16. Chronic DON exposure and acute LPS challenge: effects on porcine liver morphology and function.

    PubMed

    Renner, Lydia; Kahlert, Stefan; Tesch, Tanja; Bannert, Erik; Frahm, Jana; Barta-Böszörményi, Anikó; Kluess, Jeannette; Kersten, Susanne; Schönfeld, Peter; Rothkötter, Hermann-Josef; Dänicke, Sven

    2017-08-01

    The aim of the present study was to examine the role of chronic deoxynivalenol (DON) exposition on the liver morphology and function in combination with pre- and post-hepatic lipopolysaccharide (LPS) stress in young pigs fed for 4 weeks with a DON-contaminated diet (4.59 mg/kg feed). At the end of the experiment, LPS (7.5 μg/kg BW) was administered for 1 h pre-hepatically (Vena portae hepatis) or post-hepatically (Vena jugularis). Liver morphology was macroscopically checked and showed haemorrhage in all LPS groups, significantly higher relative liver weights, accompanied by marked oedema in the gallbladder wall. Histological changes were judged by a modified histology activity index (HAI). Liver HAI score was significantly increased in all LPS groups compared to placebo, primarily due to neutrophil infiltration and haemorrhage. DON feed alone was without effect on the liver HAI. Liver function was characterized by (i) hepatic biochemical markers, (ii) mitochondrial respiration and (iii) Ca 2+ accumulation capacity of isolated mitochondria. Clinical chemical parameters characterizing liver function were initially (<3 h) slightly influenced by LPS. After 3 h, bilirubin and alkaline phosphatase were increased significantly, in DON-fed, jugular-infused LPS group. Respiration and Ca 2+ accumulation capacity of isolated liver mitochondria was not impaired by chronic DON exposure, acute LPS challenge or combined treatments. DON-contaminated feed did not change macroscopy and histology of the liver, but modified the function under LPS stress. The different function was not linked to modifications of liver mitochondria.

  17. Plugged percutaneous biopsy of the liver in living-donor liver transplantation recipients suspected to have graft rejection.

    PubMed

    Kim, Sung Jung; Won, Je Hwan; Kim, Young Bae; Wang, Hee-Jung; Kim, Bong-Wan; Kim, Haeryoung; Kim, Jinoo

    2017-07-01

    Background Percutaneous biopsy is a widely-accepted technique for acquiring histologic samples of the liver. When there is concern for bleeding, plugged percutaneous biopsy (PPB) may be performed, which involves embolization of the biopsy tract. Purpose To evaluate the efficacy and safety of PPB of the liver in patients suspected to have graft rejection after living-donor liver transplantation (LDLT). Material and Methods During January 2007 and December 2013, 51 patients who underwent PPB of the liver under the suspicion of post-LDLT graft rejection were retrospectively analyzed. A total of 73 biopsies were performed. Biopsy was performed with a 17-gauge core needle and 18-gauge cutting needle. The needle tract was embolized using gelatin sponge (n = 44) or N-butyl cyanoacrylate (NBCA) (n = 29). The specimens were reviewed to determine their adequacy for histologic diagnosis. We reviewed all medical records after PPB. Results Specimens were successfully acquired in all procedures (100%). They were adequate for diagnosis in 70 cases (95.9%) and inadequate in three (1.3%). Average of 9.8 complete portal tracts was counted per specimen. One minor complication (1.4%) occurred where the patient had transient fever after the procedure. Conclusion PPB is easy and safe to perform in LDLT recipients and provides high diagnostic yield.

  18. [Prolyl hydroxylase activity in liver specimens in chronic liver diseases (author's transl)].

    PubMed

    Langness, U; Clausnitzer, H; Verspohl, M; Grasedyck, K

    1978-08-25

    100 patients were laparoscopied, liver tissue specimens taken from atypically altered areas. Prolyl hydroxylase was determined in the specimen, in parallel tissue was examined by light microscope. 8 groups of patients could be differentiated: Patients 1. with active, 2, with inactive cirrhosis, 3. with fatty infiltrations, 4. with fatty infiltration and mesenchymal reaction, 5. with aggressive, 6. with persistent, 7. with reactive hepatitis, 8. patients without histological changes. In the case of connective tissue increase in the liver prolyl hydroxylase activities were statistically significant above normal. In addition, there was a statistically significant difference between the enzyme activities of each group. A correlation could be found between prolyl hydroxylase activity and morphologically estimated connective tissue formation, but not the serum enzyme activities usually determined in liver diseases. Therefore, could be concluded that prolyl hydroxylase activity is an index of actual collagen biosynthesis in chronic liver diseases.

  19. Quantification of liver fibrosis via second harmonic imaging of the Glisson's capsule from liver surface.

    PubMed

    Xu, Shuoyu; Kang, Chiang Huen; Gou, Xiaoli; Peng, Qiwen; Yan, Jie; Zhuo, Shuangmu; Cheng, Chee Leong; He, Yuting; Kang, Yuzhan; Xia, Wuzheng; So, Peter T C; Welsch, Roy; Rajapakse, Jagath C; Yu, Hanry

    2016-04-01

    Liver surface is covered by a collagenous layer called the Glisson's capsule. The structure of the Glisson's capsule is barely seen in the biopsy samples for histology assessment, thus the changes of the collagen network from the Glisson's capsule during the liver disease progression are not well studied. In this report, we investigated whether non-linear optical imaging of the Glisson's capsule at liver surface would yield sufficient information to allow quantitative staging of liver fibrosis. In contrast to conventional tissue sections whereby tissues are cut perpendicular to the liver surface and interior information from the liver biopsy samples were used, we have established a capsule index based on significant parameters extracted from the second harmonic generation (SHG) microscopy images of capsule collagen from anterior surface of rat livers. Thioacetamide (TAA) induced liver fibrosis animal models was used in this study. The capsule index is capable of differentiating different fibrosis stages, with area under receiver operating characteristics curve (AUC) up to 0.91, making it possible to quantitatively stage liver fibrosis via liver surface imaging potentially with endomicroscopy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Nondestructive Methods for Monitoring Cell Removal During Rat Liver Decellularization.

    PubMed

    Geerts, Sharon; Ozer, Sinan; Jaramillo, Maria; Yarmush, Martin L; Uygun, Basak E

    2016-07-01

    Whole liver engineering holds the promise to create transplantable liver grafts that may serve as substitutes for donor organs, addressing the donor shortage in liver transplantation. While decellularization and recellularization of livers in animal models have been successfully achieved, scale up to human livers has been slow. There are a number of donor human livers that are discarded because they are not found suitable for transplantation, but are available for engineering liver grafts. These livers are rejected due to a variety of reasons, which in turn may affect the decellularization outcome. Hence, a one-size-fit-for all decellularization protocol may not result in scaffolds with consistent matrix quality, subsequently influencing downstream recellularization and transplantation outcomes. There is a need for a noninvasive monitoring method to evaluate the extent of cell removal, while ensuring preservation of matrix components during decellularization. In this study, we decellularized rat livers using a protocol previously established by our group, and we monitored decellularization through traditional destructive techniques, including evaluation of DNA, collagen, and glycosaminoglycan (GAG) content in decellularized scaffolds, as well as histology. In addition, we used computed tomography and perfusate analysis as alternative nondestructive decellularization monitoring methods. We found that DNA removal correlates well with the Hounsfield unit of the liver, and perfusate analysis revealed that significant amount of GAG is removed during perfusion with 0.1% sodium dodecyl sulfate. This allowed for optimization of our decellularization protocol leading to scaffolds that have significantly higher GAG content, while maintaining appropriate removal of cellular contents. The significance of this is the creation of a nondestructive monitoring strategy that can be used for optimization of decellularization protocols for individual human livers available for liver

  1. Nondestructive Methods for Monitoring Cell Removal During Rat Liver Decellularization

    PubMed Central

    Geerts, Sharon; Ozer, Sinan; Jaramillo, Maria; Yarmush, Martin L.

    2016-01-01

    Whole liver engineering holds the promise to create transplantable liver grafts that may serve as substitutes for donor organs, addressing the donor shortage in liver transplantation. While decellularization and recellularization of livers in animal models have been successfully achieved, scale up to human livers has been slow. There are a number of donor human livers that are discarded because they are not found suitable for transplantation, but are available for engineering liver grafts. These livers are rejected due to a variety of reasons, which in turn may affect the decellularization outcome. Hence, a one-size-fit-for all decellularization protocol may not result in scaffolds with consistent matrix quality, subsequently influencing downstream recellularization and transplantation outcomes. There is a need for a noninvasive monitoring method to evaluate the extent of cell removal, while ensuring preservation of matrix components during decellularization. In this study, we decellularized rat livers using a protocol previously established by our group, and we monitored decellularization through traditional destructive techniques, including evaluation of DNA, collagen, and glycosaminoglycan (GAG) content in decellularized scaffolds, as well as histology. In addition, we used computed tomography and perfusate analysis as alternative nondestructive decellularization monitoring methods. We found that DNA removal correlates well with the Hounsfield unit of the liver, and perfusate analysis revealed that significant amount of GAG is removed during perfusion with 0.1% sodium dodecyl sulfate. This allowed for optimization of our decellularization protocol leading to scaffolds that have significantly higher GAG content, while maintaining appropriate removal of cellular contents. The significance of this is the creation of a nondestructive monitoring strategy that can be used for optimization of decellularization protocols for individual human livers available for liver

  2. Doxorubicin coupled to lactosaminated albumin: Effects on rats with liver fibrosis and cirrhosis.

    PubMed

    Di Stefano, G; Fiume, L; Domenicali, M; Busi, C; Chieco, P; Kratz, F; Lanza, M; Mattioli, A; Pariali, M; Bernardi, M

    2006-06-01

    The conjugate of doxorubicin with lactosaminated human albumin has the potential of increasing the doxorubicin efficacy in the treatment of hepatocellular carcinomas expressing the asialoglycoprotein receptor. However, coupled doxorubicin also accumulates in the liver, which might damage hepatocytes. To verify whether coupled doxorubicin impairs liver function in rats with liver fibrosis and cirrhosis. Coupled doxorubicin was administered using the same schedule which exerted an antineoplastic effect on rat hepatocellular carcinomas (4-weekly injections of doxorubicin at 1 microg/g). Liver fibrosis/cirrhosis was produced by carbon tetrachloride (CCl4) poisoning. Liver samples were studied histologically. Serum parameters of liver function and viability were determined. In normal rats, administration of coupled doxorubicin neither caused microscopic changes of hepatocytes nor modified serum liver parameters. In rats with fibrosis/cirrhosis, although a selective doxorubicin accumulation within the liver followed coupled doxorubicin administration, the drug did not have a detrimental effect on the histology of the liver and, among serum liver tests, only alanine aminotransferase and aspartate aminotransferase levels were moderately modified. Coupled doxorubicin can be administered to rats with liver fibrosis/cirrhosis without inducing a severe liver damage. If further studies will confirm the efficacy and safety of this compound, coupled doxorubicin therapy may open a new perspective in the treatment of hepatocellular carcinoma.

  3. Chemical shift magnetic resonance imaging is helpful in detecting hepatic steatosis but not fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).

    PubMed

    Kalra, Naveen; Duseja, Ajay; Das, Ashim; Dhiman, Radha Krishan; Virmani, Vivek; Chawla, Yogesh; Singh, Paramjee; Khandelwal, Niranjan

    2009-01-01

    Imaging modalities have a role in the diagnosis of patients with nonalcoholic fatty liver disease. Aim of the present study was to evaluate the role of chemical shift magnetic resonance imaging in assessing hepatic steatosis and fibrosis in patients with nonalcoholic fatty liver disease. Chemical shift magnetic resonance imaging was done in 10 biopsy proven patients (7 females, mean age 41 +/- 9.2 years) with nonalcoholic fatty liver disease. Objective measurements of signal intensity (SI) were done and a ratio was calculated (SI out-of- phase liver/ SI out-of- phase kidney)/ (SI in- phase liver/ SI in-phase kidney). A lower ratio indicated a higher signal drop and hence higher fat content. The ratio was correlated with hepatic steatosis on histology (< 33% and > 33%). Patients were classified as having histological NASH or no NASH and MRI was assessed in diagnosing hepatic fibrosis as seen on liver histology. Six patients had > 33% hepatic steatosis on histology. Five patients (50%) had evidence of histological NASH. MRI was not helpful in differentiating patients with and without histological NASH. One patient amongst NASH patients did not have fibrosis, one had stage 1, 2 had stage 2 and one had stage 4 fibrosis. SI ratio ranged between 0.35-0.69 in 6 patients with steatosis > 33% and was in the range of 0.69-1.20 in four patients with steatosis < 33% on histology. Fibrotic changes seen in 4 patients on biopsy were not detected on MRI. Chemical shift MRI provides objective data on fat infiltration in patients with NAFLD without giving information about hepatic fibrosis.

  4. Single-Pass Percutaneous Liver Biopsy for Diffuse Liver Disease Using an Automated Device: Experience in 154 Procedures

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rivera-Sanfeliz, Gerant, E-mail: gerantrivera@ucsd.edu; Kinney, Thomas B.; Rose, Steven C.

    2005-06-15

    Purpose: To describe our experience with ultrasound (US)-guided percutaneous liver biopsies using the INRAD 18G Express core needle biopsy system.Methods: One hundred and fifty-four consecutive percutaneous core liver biopsy procedures were performed in 153 men in a single institution over 37 months. The medical charts, pathology reports, and radiology files were retrospectively reviewed. The number of needle passes, type of guidance, change in hematocrit level, and adequacy of specimens for histologic analysis were evaluated.Results: All biopsies were performed for histologic staging of chronic liver diseases. The majority of patients had hepatitis C (134/153, 90.2%). All patients were discharged to homemore » after 4 hr of postprocedural observation. In 145 of 154 (94%) biopsies, a single needle pass was sufficient for diagnosis. US guidance was utilized in all but one of the procedures (153/154, 99.4%). The mean hematocrit decrease was 1.2% (44.1-42.9%). Pain requiring narcotic analgesia, the most frequent complication, occurred in 28 of 154 procedures (18.2%). No major complications occurred. The specimens were diagnostic in 152 of 154 procedures (98.7%).Conclusions: Single-pass percutaneous US-guided liver biopsy with the INRAD 18G Express core needle biopsy system is safe and provides definitive pathologic diagnosis of chronic liver disease. It can be performed on an outpatient basis. Routine post-biopsy monitoring of hematocrit level in stable, asymptomatic patients is probably not warranted.« less

  5. New method for assessing liver fibrosis based on acoustic radiation force impulse: a special reference to the difference between right and left liver.

    PubMed

    Toshima, Takeo; Shirabe, Ken; Takeishi, Kazuki; Motomura, Takashi; Mano, Youhei; Uchiyama, Hideaki; Yoshizumi, Tomoharu; Soejima, Yuji; Taketomi, Akinobu; Maehara, Yoshihiko

    2011-05-01

    Virtual touch tissue quantification (VTTQ) based on acoustic radiation force impulse (ARFI) imaging has been developed as a noninvasive bedside method for the assessment of liver stiffness. In this study, we examined the diagnostic performance of ARFI imaging in 103 patients, focusing on the difference in VTTQ values between the right and left liver lobes. We evaluated VTTQ values of the right and left lobes in 79 patients with chronic liver disease who underwent histological examination of liver fibrosis and in 24 healthy volunteers. The diagnostic accuracy of VTTQ was compared with several serum markers, including hyaluronic acid, type 4 collagen, and aspartate transaminase to platelet ratio index. The VTTQ values (meters per second) in the right and left lobes were 1.61 ± 0.51 and 1.90 ± 0.68, respectively, and the difference was statistically significant (P < 0.0001). The VTTQ values in both liver lobes were correlated significantly with histological fibrosis grades (P < 0.001). The standard deviations of the VTTQ values in the right lobe were significantly lower than those in the left lobe (P < 0.001). The area under the receiver-operating characteristic curve for the diagnosis of fibrosis (F ≥ 3) using VTTQ values in both liver lobes was superior to serum markers, especially in the right lobe. VTTQ is an accurate and reliable tool for the assessment of liver fibrosis. VTTQ of the right lobe was more accurate for diagnosing liver fibrosis than in the left lobe.

  6. Liver metastasis of meningeal hemangiopericytoma: a study of 5 cases

    PubMed Central

    Lo, Regina C.; Suriawinata, Arief A.; Rubin, Brian P.

    2016-01-01

    Mesenchymal tumors in the liver, whether primary or metastatic, are rare. Meningeal hemangiopericytoma (HPC) is characteristically associated with delayed metastasis and the liver is one of the most common sites. Despite its consistent histological features, a pathological diagnosis of HPC in the liver is sometimes not straightforward due to its rarity and usually remote medical history of the primary meningeal tumor. In this report, the clinicopathological features of 5 cases of metastatic HPC to the liver were reviewed and described. PMID:27044772

  7. Contribution of Transjugular Liver Biopsy in Patients with the Clinical Presentation of Acute Liver Failure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miraglia, Roberto, E-mail: rmiraglia@ismett.edu; Luca, Angelo; Gruttadauria, Salvatore

    2006-12-15

    Purpose. Acute liver failure (ALF) treated with conservative therapy has a poor prognosis, although individual survival varies greatly. In these patients, the eligibility for liver transplantation must be quickly decided. The aim of this study was to assess the role of transjugular liver biopsy (TJLB) in the management of patients with the clinical presentation of ALF. Methods. Seventeen patients with the clinical presentation of ALF were referred to our institution during a 52 month period. A TJLB was performed using the Cook Quick-Core needle biopsy. Clinical data, procedural complications, and histologic findings were evaluated. Results. Causes of ALF were virusmore » hepatitis B infection in 7 patients, drug toxicity in 4, mushroom in 1, Wilson's disease in 1, and unknown origin in 4. TJLB was technically successful in all patients without procedure-related complications. Tissue specimens were satisfactory for diagnosis in all cases. In 14 of 17 patients the initial clinical diagnosis was confirmed by TJLB; in 3 patients the initial diagnosis was altered by the presence of unknown cirrhosis. Seven patients with necrosis <60% were successfully treated with medical therapy; 6 patients with submassive or massive necrosis ({>=}85%) were treated with liver transplantation. Four patients died, 3 had cirrhosis, and 1 had submassive necrosis. There was a strict statistical correlation (r = 0.972, p < 0.0001) between the amount of necrosis at the frozen section examination and the necrosis found at routine histologic examination. The average time for TJLB and frozen section examination was 80 min. Conclusion. In patients with the clinical presentation of ALF, submassive or massive liver necrosis and cirrhosis are predictors of poor prognosis. TLJB using an automated device and frozen section examination can be a quick and effective tool in clinical decision-making, especially in deciding patient selection and the best timing for liver transplantation.« less

  8. Changes of FibroScan, APRI, and FIB-4 in chronic hepatitis B patients with significant liver histological changes receiving 3-year entecavir therapy.

    PubMed

    Li, Qiang; Chen, Liang; Zhou, Yu

    2018-05-01

    Noninvasive fibrosis tests have been used widely for evaluation of liver fibrosis in patients with chronic hepatitis B (CHB). We aimed to investigate the influence of antiviral treatment on FibroScan, APRI, and FIB-4 in CHB patients with significant liver histological changes (SLHC) defined as inflammatory grade ≥ A2 and/or fibrosis stage ≥ F2. A total of 104 CHB patients with SLHC at the baseline were included. FibroScan, APRI, and FIB-4 values were compared before and after 3-year entecavir (ETV) treatment. Liver stiffness measurement values decreased significantly after 3-year ETV treatment in cirrhosis group (from 13.6 to 9.6 kPa, p = 0.018), significant fibrosis group (from 8.4 to 5.8 kPa, p = 0.001), and mild fibrosis group (from 5.5 to 4 kPa, p < 0.001). APRI decreased significantly after 3-year ETV treatment in patients with cirrhosis (from 0.80 to 0.25, p < 0.001), patients with significant fibrosis (from 0.54 to 0.24, p < 0.001), and those with mild fibrosis (from 0.35 to 0.23, p < 0.001). FIB-4 decreased significantly after 3-year ETV treatment in patients with cirrhosis (from 1.27 to 0.81, p = 0.007) and significant fibrosis (from 1.12 to 0.78, p < 0.001), while did not decrease significantly in patients with mild fibrosis (from 0.90 to 0.80, p = 0.389). FibroScan, APRI, and FIB-4 values decreased significantly after 3-year ETV treatment in CHB patients, which indicates that these noninvasive fibrosis tests might be useful for monitoring regression of liver fibrosis and assessing treatment efficacy during long-term ETV treatment.

  9. Effects of gallic acid on delta - aminolevulinic dehydratase activity and in the biochemical, histological and oxidative stress parameters in the liver and kidney of diabetic rats.

    PubMed

    de Oliveira, Lizielle Souza; Thomé, Gustavo Roberto; Lopes, Thauan Faccin; Reichert, Karine Paula; de Oliveira, Juliana Sorraila; da Silva Pereira, Aline; Baldissareli, Jucimara; da Costa Krewer, Cristina; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa; Spanevello, Roselia Maria

    2016-12-01

    Diabetes mellitus (DM) is characterised by hyperglycaemia associated with the increase of oxidative stress. Gallic acid has potent antioxidant properties. The aim of this study was to evaluate the effect of gallic acid on the biochemical, histological and oxidative stress parameters in the liver and kidney of diabetic rats. Male rats were divided in groups: control, gallic acid, diabetic and diabetic plus gallic acid. DM was induced in the animals by intraperitoneal injection of streptozotocin (65mg/kg). Gallic acid (30mg/kg) was administered orally for 21days. Our results showed an increase in reactive species levels and lipid peroxidation, and a decrease in activity of the enzymes superoxide dismutase and delta-aminolevulinic acid dehydratase in the liver and kidney of the diabetic animals (P<0.05). Gallic acid treatment showed protective effects in these parameters evaluated, and also prevented a decrease in the activity of catalase and glutathione S-transferase, and vitamin C levels in the liver of diabetic rats. In addition, gallic acid reduced the number of nuclei and increased the area of the core in hepatic tissue, and increased the glomerular area in renal tissue. These results indicate that gallic acid can protect against oxidative stress-induced damage in the diabetic state. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Autoimmune paediatric liver disease

    PubMed Central

    Mieli-Vergani, Giorgina; Vergani, Diego

    2008-01-01

    Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a

  11. Autoimmune paediatric liver disease.

    PubMed

    Mieli-Vergani, Giorgina; Vergani, Diego

    2008-06-07

    Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a

  12. [Transfection of hBcl-2 gene protects the liver against ischemia/reperfusion injury in rats during liver transplantation].

    PubMed

    Liu, Ji-tong; Liu, Jing-shi; Jiang, Jin-yu; Zhou, Li-xue; Liang, Gang; Li, Yan-chun

    2010-12-01

    To study the effect of hBcl-2 gene transfer on rat liver against ischemia-reperfusion injury, and explore the feasibility of this approach to reduce ischemia-reperfusion injury in liver transplantation. We constructed the replication-deficient recombinant adenoviruses Adv-EGFP and Adv-Bcl-2 and transfected them into 293 cells and packaged into adenovirus particles for amplification and purification. The empty plasmid vector virus was constructed similarly. Male SD rats were randomized into Adv-Bcl-2-transfected group, Adv-EGFP-transfected group, ischemia-reperfusion group, and sham-operated group, and liver allograft transplantation model was established by sleeve method. In the transfected groups, the recombinant viruses were administered by perfusion through the portal vein, and the ischemia-reperfusion and sham-operated groups received no treatment. Real-time quantitative PCR and Western blotting were used to detect the mRNA and protein expressions of bcl-2 in the liver tissue of each group, and at 0, 60 and 180 min after reperfusion, serum AST, LDH, and MDA levels were measured. Histological changes of the liver cells were evaluated by HE staining. Bcl-2 mRNA and protein expressions in Adv-Bcl-2-transfected group, as compared with those in Adv-EGFP-transfected group and control group, were significantly increased (P<0.01); the serum levels of AST, LDH and MDA in Adv-Bcl-2-transfected group were significantly lower than those of Adv-EGFP-transfected group and ischemia-reperfusion group (P<0.05 or 0.01). Compared with the sham-operated group, Adv-Bcl-2 treatment group showed lessened edema and vacuolar degeneration of the liver cells without patches or spots of necrosis. In ischemia-reperfusion and Adv-EGFP group, HE staining revealed hepatic lobular destruction and extensive liver cell swelling, enlargement, vacuolar degeneration, edema and occasional focal necrosis. Adv-Bcl-2 transfection can induce the expression of bcl-2 gene to reduce ischemia

  13. Recurrent viral liver disease (hepatitis B and C) after liver transplantation.

    PubMed

    Olivera-Martínez, Marco Antonio; Gallegos-Orozco, Juan F

    2007-08-01

    Hepatitis C represents more than 35% of liver transplant candidates worldwide. Meanwhile, hepatitis B continues to be an important cause of end-stage liver disease and hepatocellular carcinoma in Asia and Africa. Recurrent viral liver disease is a significant event after liver transplantation and continues to be one of the main causes of graft dysfunction and loss in the middle and long-term follow-up. Mechanisms of liver reinfection and disease recurrence vary between these two viruses and pre-emptive as well as the therapeutic approaches are different. Hepatitis B patients can be managed with immune globulin immediately after liver transplant and various agents such as nucleotide and nucleoside analogues can be associated. As a result, disease recurrence has been delayed or prevented in these patients. Individuals transplanted for hepatitis C are known to have universal reinfection and a high rate of disease recurrence has been reported in the literature. Strategies to treat hepatitis C recurrence are limited to the use of pegylated interferon and ribavirin when disease is demonstrated histologically and biochemically, although other strategies have been described with limited or no success. We herein review the mechanisms of disease recurrence and the current as well as the future therapeutic approaches to prevent and to treat these diseases.

  14. Liver histopathology in the cane toad, Rhinella marina (Amphibia: Bufonidae), induced by Ortleppascaris sp. larvae (Nematoda: Ascarididae).

    PubMed

    Silva, Jefferson P E; da Silva, Djane C B; Melo, Francisco T V; Giese, Elane G; Furtado, Adriano P; Santos, Jeannie N

    2013-04-01

    Exposure to parasites is considered to be an important factor in the development of many diseases and histopathologies which are the result of the parasite-host interaction. The present study evaluated the impact of natural infection by larvae of Ortleppascaris sp. (Nematoda: Ascaridida) in the liver of the cane toad Rhinella marina (Linnaeus, 1758). Larvae were encysted in nodules delimited by collagenous fibers and fibroblasts or freely within the hepatic parenchyma, provoking a clear response from the host. The histological examination of the liver revealed viable larvae in a number of different developmental stages, as well as cysts filled with amorphous material and cell residues and surrounded by dense fibrotic tissue. The infection of the liver by these larvae induces a significant increase in the area occupied by melanomacrophages and a reduction or deficit in the vascularization of the liver, hypertrophy of the hepatocytes, vacuolar bodies, and cytoplasmatic granules. Focal concentrations of inflammatory infiltrates were observed enclosing the unencapsulated early-stage larvae. These results indicate that infection by Ortleppascaris sp. induces severe physiological problems and histopathological lesions in the liver of R. marina .

  15. Nationwide population-based study reveals increased malignancy risk in taiwanese liver transplant recipients.

    PubMed

    Tsai, Yung Fong; Chen, Hsiu Pin; Liu, Fu Chao; Liu, Shih Hao; Chen, Chun Yu; Cheng, Chih Wen; Lin, Jr-Rung

    2016-12-13

    Post-transplant malignancy is a major cause of late mortality for liver transplant recipients (LTRs). This nationwide population-based cohort study investigated the cancer type, incidence, and risk factors associated with post-transplant malignancies in 2938 Taiwanese LTRs who underwent transplantation between 1998 and 2012. Data from the National Health Insurance Research Database were extracted on the basis of the International Classification of Disease, Ninth Revision, Clinical Modification codes. Among these patients, 284 post-transplant malignancies were diagnosed. These included 99 de novo malignancies among 98 patients, yielding a standardized incidence ratio of 2.17 (95% CI, 1.76 to 2.64) compared to the general population. The most common malignancies were infection related liver cancer (19.39%), oropharyngeal cancer (19.39%), non-Hodgkin's lymphoma (9.18%), and esophageal cancer (5.10%), as well as non-infection-related prostate cancer (6.12%). Patients with recurrent malignancies had the highest mortality. Furthermore, 186 recurrent malignancies relapsed, and the commonly affected organs were the liver (83.33%), lung (4.84%), bone and bone marrow (4.30%), and intrahepatic bile ducts (2.69%). Old age, the male sex, liver cirrhosis, hepatitis B, peptic ulcer, diabetes mellitus, and pre-existing cancer were all risk factors associated with post-transplant malignancies. Recipients with biliary atresia or urea cycle metabolism disorders were protected from post-transplant malignancies. Our data revealed a significantly increased risk of malignancies in Taiwanese LTRs and suggest implementation of a careful malignancy-surveillance program and immunosuppression-minimizing strategy for high-risk patients.

  16. Histological improvement of non-alcoholic steatohepatitis with a prebiotic: a pilot clinical trial.

    PubMed

    Bomhof, Marc R; Parnell, Jill A; Ramay, Hena R; Crotty, Pam; Rioux, Kevin P; Probert, Chris S; Jayakumar, Saumya; Raman, Maitreyi; Reimer, Raylene A

    2018-05-19

    In obesity and diabetes the liver is highly susceptible to abnormal uptake and storage of fat. In certain individuals hepatic steatosis predisposes to the development of non-alcoholic steatohepatitis (NASH), a disease marked by hepatic inflammation and fibrosis. Although the precise pathophysiology of NASH is unknown, it is believed that the gut microbiota-liver axis influences the development of this disease. With few treatment strategies available for NASH, exploration of gut microbiota-targeted interventions is warranted. We investigated the therapeutic potential of a prebiotic supplement to improve histological parameters of NASH. In a placebo-controlled, randomized pilot trial, 14 individuals with liver-biopsy-confirmed NASH [non-alcoholic fatty liver activity score (NAS) ≥ 5] were randomized to receive oligofructose (8 g/day for 12 weeks followed by 16 g/day for 24 weeks) or isocaloric placebo for 9 months. The primary outcome measure was the change in liver biopsy NAS score and the secondary outcomes included changes in body weight, body composition, glucose tolerance, inflammatory markers, and gut microbiota. Independent of weight loss, oligofructose improved liver steatosis relative to placebo and improved overall NAS score (P = 0.016). Bifidobacterium was enhanced by oligofructose, whereas bacteria within Clostridium cluster XI and I were reduced with oligofructose (P < 0.05). There were no adverse side effects that deterred individuals from consuming oligofructose for treatment of this disease. Independent of other lifestyle changes, prebiotic supplementation reduced histologically-confirmed steatosis in patients with NASH. Larger follow-up studies are warranted. This trial was registered at Clinicaltrials.com as NCT03184376.

  17. Autoimmune liver disease in children.

    PubMed

    Mieli-Vergani, G; Vergani, D

    2003-03-01

    Autoimmune liver disorders are characterised by an inflammatory liver histology, circulating non-organ specific autoantibodies and increased levels of immunoglobulin G (IgG) in the absence of a known aetiology. They respond to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Liver disorders with a likely autoimmune pathogenesis include autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC). Two types of AIH are recognised according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1-positive patients tend to present more acutely, at a younger age, and commonly have immunoglobulin A (IgA) deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological and histological presentation of ASC is often indistinguishable from that of AIH. In both, there are high IgG, non-organ specific autoantibodies and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalisation of biochemical parameters and decreased inflammatory activity on follow-up liver biopsies. However, the cholangiopathy can progress and there may be an evolution from AIH to ASC over the years, despite treatment. Whether the juvenile autoimmune form of sclerosing cholangitis and AIH are 2 distinct entities, or different aspects of the same condition, remains to be elucidated.

  18. Liver BCATm transgenic mouse model reveals the important role of the liver in maintaining BCAA homeostasis.

    PubMed

    Ananieva, Elitsa A; Van Horn, Cynthia G; Jones, Meghan R; Hutson, Susan M

    2017-02-01

    Unlike other amino acids, the branched-chain amino acids (BCAAs) largely bypass first-pass liver degradation due to a lack of hepatocyte expression of the mitochondrial branched-chain aminotransferase (BCATm). This sets up interorgan shuttling of BCAAs and liver-skeletal muscle cooperation in BCAA catabolism. To explore whether complete liver catabolism of BCAAs may impact BCAA shuttling in peripheral tissues, the BCATm gene was stably introduced into mouse liver. Two transgenic mouse lines with low and high hepatocyte expression of the BCATm transgene (LivTg-LE and LivTg-HE) were created and used to measure liver and plasma amino acid concentrations and determine whether the first two BCAA enzymatic steps in liver, skeletal muscle, heart and kidney were impacted. Expression of the hepatic BCATm transgene lowered the concentrations of hepatic BCAAs while enhancing the concentrations of some nonessential amino acids. Extrahepatic BCAA metabolic enzymes and plasma amino acids were largely unaffected, and no growth rate or body composition differences were observed in the transgenic animals as compared to wild-type mice. Feeding the transgenic animals a high-fat diet did not reverse the effect of the BCATm transgene on the hepatic BCAA catabolism, nor did the high-fat diet cause elevation in plasma BCAAs. However, the high-fat-diet-fed BCATm transgenic animals experienced attenuation in the mammalian target of rapamycin (mTOR) pathway in the liver and had impaired blood glucose tolerance. These results suggest that complete liver BCAA metabolism influences the regulation of glucose utilization during diet-induced obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Liver BCATm transgenic mouse model reveals the important role of the liver in maintaining BCAA homeostasis

    PubMed Central

    Ananieva, Elitsa A.; Van Horn, Cynthia G.; Jones, Meghan R.; Hutson, Susan M.

    2016-01-01

    Unlike other amino acids, the branched chain amino acids (BCAAs) largely bypass first pass liver degradation due to a lack of hepatocyte expression of the mitochondrial branched chain aminotransferase (BCATm). This sets up interorgan shuttling of BCAAs and liver-skeletal muscle cooperation in BCAA catabolism. To explore whether complete liver catabolism of BCAAs may impact BCAA shuttling in peripheral tissues, the BCATm gene was stably introduced into mouse liver. Two transgenic mouse lines with low and high hepatocyte expression of the BCATm transgene (LivTg-LE and LivTg-HE) were created and used to measure liver and plasma amino acid concentrations and determine whether the first two BCAA enzymatic steps in liver, skeletal muscle, heart, and kidney were impacted. Expression of the hepatic BCATm transgene lowered the concentrations of hepatic BCAAs while enhancing the concentrations of some nonessential amino acids. Extrahepatic BCAA metabolic enzymes and plasma amino acids were largely unaffected and no growth rate or body composition differences were observed in the transgenic animals as compared to wild type (WT) mice. Feeding the transgenic animals a high fat diet did not reverse the effect of the BCATm transgene on the hepatic BCAA catabolism nor did the high fat diet cause elevation in plasma BCAAs. However, the high fat diet fed BCATm transgenic animals experienced attenuation in the mammalian target of rapamycin (mTOR) pathway in the liver and had impaired blood glucose tolerance. These results suggest that complete liver BCAA metabolism influences the regulation of glucose utilization during diet-induced obesity. PMID:27886623

  20. Non-invasive evaluation of liver stiffness after splenectomy in rabbits with CCl4-induced liver fibrosis.

    PubMed

    Wang, Ming-Jun; Ling, Wen-Wu; Wang, Hong; Meng, Ling-Wei; Cai, He; Peng, Bing

    2016-12-14

    To investigate the diagnostic performance of liver stiffness measurement (LSM) by elastography point quantification (ElastPQ) in animal models and determine the longitudinal changes in liver stiffness by ElastPQ after splenectomy at different stages of fibrosis. Liver stiffness was measured in sixty-eight rabbits with CCl 4 -induced liver fibrosis at different stages and eight healthy control rabbits by ElastPQ. Liver biopsies and blood samples were obtained at scheduled time points to assess liver function and degree of fibrosis. Thirty-one rabbits with complete data that underwent splenectomy at different stages of liver fibrosis were then included for dynamic monitoring of changes in liver stiffness by ElastPQ and liver function according to blood tests. LSM by ElastPQ was significantly correlated with histologic fibrosis stage ( r = 0.85, P < 0.001). The optimal cutoff values by ElastPQ were 11.27, 14.89, and 18.21 kPa for predicting minimal fibrosis, moderate fibrosis, and cirrhosis, respectively. Longitudinal monitoring of the changes in liver stiffness by ElastPQ showed that early splenectomy (especially F1) may delay liver fibrosis progression. ElastPQ is an available, convenient, objective and non-invasive technique for assessing liver stiffness in rabbits with CCl 4 -induced liver fibrosis. In addition, liver stiffness measurements using ElastPQ can dynamically monitor the changes in liver stiffness in rabbit models, and in patients, after splenectomy.

  1. Successful resection of metachronous para-aortic, Virchow lymph node and liver metastatic recurrence of rectal cancer.

    PubMed

    Takeshita, Nobuyoshi; Fukunaga, Toru; Kimura, Masayuki; Sugamoto, Yuji; Tasaki, Kentaro; Hoshino, Isamu; Ota, Takumi; Maruyama, Tetsuro; Tamachi, Tomohide; Hosokawa, Takashi; Asai, Yo; Matsubara, Hisahiro

    2015-11-28

    A 66-year-old female presented with the main complaint of defecation trouble and abdominal distention. With diagnosis of rectal cancer, cSS, cN0, cH0, cP0, cM0 cStage II, Hartmann's operation with D3 lymph node dissection was performed and a para-aortic lymph node and a disseminated node near the primary tumor were resected. Histological examination showed moderately differentiated adenocarcinoma, pSS, pN3, pH0, pP1, pM1 (para-aortic lymph node, dissemination) fStage IV. After the operation, the patient received chemotherapy with FOLFIRI regimen. After 12 cycles of FOLFIRI regimen, computed tomography (CT) detected an 11 mm of liver metastasis in the postero-inferior segment of right hepatic lobe. With diagnosis of liver metastatic recurrence, we performed partial hepatectomy. Histological examination revealed moderately differentiated adenocarcinoma as a metastatic rectal cancer with cut end microscopically positive. After the second operation, the patient received chemotherapy with TS1 alone for 2 years. Ten months after the break, CT detected a 20 mm of para-aortic lymph node metastasis and a 10 mm of lymph node metastasis at the hepato-duodenal ligament. With diagnosis of lymph node metastatic recurrences, we performed lymph node dissection. Histological examination revealed moderately differentiated adenocarcinoma as metastatic rectal cancer in para-aortic and hepato-duodenal ligament areas. After the third operation, we started chemotherapy with modified FOLFOX6 regimen. After 2 cycles of modified FOLFOX6 regimen, due to the onset of neutropenia and liver dysfunction, we switched to capecitabine alone and continued it for 6 mo and then stopped. Eleven months after the break, CT detected two swelling 12 mm of lymph nodes at the left supraclavicular region. With diagnosis of Virchow lymph node metastatic recurrence, we started chemotherapy with capecitabine plus bevacizumab regimen. Due to the onset of neutropenia and hand foot syndrome (Grade 3), we managed to

  2. Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial.

    PubMed

    Loguercio, Carmela; Andreone, Pietro; Brisc, Ciprian; Brisc, Michaela Cristina; Bugianesi, Elisabetta; Chiaramonte, Maria; Cursaro, Carmela; Danila, Mirela; de Sio, Ilario; Floreani, Annarosa; Freni, Maria Antonietta; Grieco, Antonio; Groppo, Marzia; Lazzari, Roberta; Lobello, Salvatore; Lorefice, Elisabetta; Margotti, Marzia; Miele, Luca; Milani, Stefano; Okolicsanyi, Lajos; Palasciano, Giuseppe; Portincasa, Piero; Saltarelli, Patrizia; Smedile, Antonina; Somalvico, Francesco; Spadaro, Aldo; Sporea, Ioan; Sorrentino, Paolo; Vecchione, Raffaela; Tuccillo, Concetta; Del Vecchio Blanco, Camillo; Federico, Alessandro

    2012-05-01

    The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight. These findings warrant further investigation. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Magnetic Resonance Imaging Quantification of Liver Iron

    PubMed Central

    Sirlin, Claude B.; Reeder, Scott B.

    2011-01-01

    Iron overload is the histological hallmark of genetic hemochromatosis and transfusional hemosiderosis but also may occur in chronic hepatopathies. This article provides an overview of iron deposition and diseases where liver iron overload is clinically relevant. Next, this article reviews why quantitative non-invasive biomarkers of liver iron would be beneficial. Finally, we describe current state of the art methods for quantifying iron with MRI and review remaining challenges and unsolved problems, PMID:21094445

  4. Accurate assessment of liver steatosis in animal models using a high throughput Raman fiber optic probe.

    PubMed

    Hewitt, Kevin C; Ghassemi Rad, Javad; McGregor, Hanna C; Brouwers, Erin; Sapp, Heidi; Short, Michael A; Fashir, Samia B; Zeng, Haishan; Alwayn, Ian P

    2015-10-07

    Due to the shortage of healthy donor organs, steatotic livers are commonly used for transplantation, placing patients at higher risk for graft dysfunction and lower survival rates. Raman Spectroscopy is a technique which has shown the ability to rapidly detect the vibration state of C-H bonds in triglycerides. The aim of this study is to determine whether conventional Raman spectroscopy can reliably detect and quantify fat in an animal model of liver steatosis. Mice and rats fed a methionine and choline-deficient (MCD) and control diets were sacrificed on one, two, three and four weeks' time points. A confocal Raman microscope, a commercial Raman (iRaman) fiber optic probe and a highly sensitive Raman fiber optic probe system, the latter utilizing a 785 nm excitation laser, were used to detect changes in the Raman spectra of steatotic mouse livers. Thin layer chromatography was used to assess the triglyceride content of liver specimens, and sections were scored blindly for fat content using histological examination. Principal component analysis (PCA) of Raman spectra was used to extract the principal components responsible for spectroscopic differences with MCD week (time on MCD diet). Confocal Raman microscopy revealed the presence of saturated fats in mice liver sections. A commercially available handheld Raman spectroscopy probe could not distinguish the presence of fat in the liver whereas our specially designed, high throughput Raman system could clearly distinguish lobe-specific changes in fat content. In the left lobe in particular, the Raman PC scores exhibited a significant correlation (R(2) = 0.96) with the gold standard, blinded scoring by histological examination. The specially designed, high throughput Raman system can be used for clinical purposes. Its application to the field of transplantation would enable surgeons to determine the hepatic fat content of the donor's liver in the field prior to proceeding with organ retrieval. Next steps include

  5. Micro-RNA Profiling in Human Serum Reveals Compartment-Specific Roles of miR-571 and miR-652 in Liver Cirrhosis

    PubMed Central

    Roderburg, Christoph; Mollnow, Tobias; Bongaerts, Brenda; Elfimova, Natalia; Vargas Cardenas, David; Berger, Katharina; Zimmermann, Henning; Koch, Alexander; Vucur, Mihael; Luedde, Mark; Hellerbrand, Claus; Odenthal, Margarete; Trautwein, Christian; Tacke, Frank; Luedde, Tom

    2012-01-01

    Background and Aims Micro-RNAs (miRNAs) have recently emerged as crucial modulators of molecular processes involved in chronic liver diseases. The few miRNAs with previously proposed roles in liver cirrhosis were identified in screening approaches on liver parenchyma, mostly in rodent models. Therefore, in the present study we performed a systematic screening approach in order to identify miRNAs with altered levels in the serum of patients with chronic liver disease and liver cirrhosis. Methods We performed a systematic, array-based miRNA expression analysis on serum samples from patients with liver cirrhosis. In functional experiments we evaluated the relationship between alterations of miRNA serum levels and their role in distinct cellular compartments involved in hepatic cirrhosis. Results The array analysis and the subsequent confirmation by qPCR in a larger patient cohort identified significant alterations in serum levels of miR-513-3p, miR-571 and miR-652, three previously uncharacterized miRNAs, in patients with alcoholic or hepatitis C induced liver cirrhosis. Of these, miR-571 serum levels closely correlated with disease stages, thus revealing potential as a novel biomarker for hepatic cirrhosis. Further analysis revealed that up-regulation of miR-571 in serum reflected a concordant regulation in cirrhotic liver tissue. In isolated primary human liver cells, miR-571 was up-regulated in human hepatocytes and hepatic stellate cells in response to the pro-fibrogenic cytokine TGF-β. In contrast, alterations in serum levels of miR-652 were stage-independent, reflecting a concordant down-regulation of this miRNA in circulating monocytes of patients with liver cirrhosis, which was inducible by proinflammatory stimuli like bacterial lipopolysaccharide. Conclusion Alterations of miR571 and miR-652 serum levels in patients with chronic liver disease reflect their putative roles in the mediation of fibrogenic and inflammatory processes in distinct cellular

  6. Subnormothermic ex vivo liver perfusion reduces endothelial cell and bile duct injury after donation after cardiac death pig liver transplantation.

    PubMed

    Knaak, Jan M; Spetzler, Vinzent N; Goldaracena, Nicolas; Boehnert, Markus U; Bazerbachi, Fateh; Louis, Kristine S; Adeyi, Oyedele A; Minkovich, Leonid; Yip, Paul M; Keshavjee, Shaf; Levy, Gary A; Grant, David R; Selzner, Nazia; Selzner, Markus

    2014-11-01

    An ischemic-type biliary stricture (ITBS) is a common feature after liver transplantation using donation after cardiac death (DCD) grafts. We compared sequential subnormothermic ex vivo liver perfusion (SNEVLP; 33°C) with cold storage (CS) for the prevention of ITBS in DCD liver grafts in pig liver transplantation (n = 5 for each group). Liver grafts were stored for 10 hours at 4°C (CS) or preserved with combined 7-hour CS and 3-hour SNEVLP. Parameters of hepatocyte [aspartate aminotransferase (AST), international normalized ratio (INR), factor V, and caspase 3 immunohistochemistry], endothelial cell (EC; CD31 immunohistochemistry and hyaluronic acid), and biliary injury and function [alkaline phosphatase (ALP), total bilirubin, and bile lactate dehydrogenase (LDH)] were determined. Long-term survival (7 days) after transplantation was similar between the SNEVLP and CS groups (60% versus 40%, P = 0.13). No difference was observed between SNEVLP- and CS-treated animals with respect to the peak of serum INR, factor V, or AST levels within 24 hours. CD31 staining 8 hours after transplantation demonstrated intact EC lining in SNEVLP-treated livers (7.3 × 10(-4) ± 2.6 × 10(-4) cells/μm(2)) but not in CS-treated livers (3.7 × 10(-4) ± 1.3 × 10(-4) cells/μm(2) , P = 0.03). Posttransplant SNEVLP animals had decreased serum ALP and serum bilirubin levels in comparison with CS animals. In addition, LDH in bile fluid was lower in SNEVLP pigs versus CS pigs (14 ± 10 versus 60 ± 18 μmol/L, P = 0.02). Bile duct histology revealed severe bile duct necrosis in 3 of 5 animals in the CS group but none in the SNEVLP group (P = 0.03). Sequential SNEVLP preservation of DCD grafts reduces bile duct and EC injury after liver transplantation. © 2014 American Association for the Study of Liver Diseases.

  7. Ischemia-reperfusion injury in rat fatty liver: role of nutritional status.

    PubMed

    Caraceni, P; Nardo, B; Domenicali, M; Turi, P; Vici, M; Simoncini, M; De Maria, N; Trevisani, F; Van Thiel, D H; Derenzini, M; Cavallari, A; Bernardi, M

    1999-04-01

    Fatty livers are more sensitive to the deleterious effects of ischemia-reperfusion than normal livers. Nutritional status greatly modulates this injury in normal livers, but its role in the specific setting of fatty liver is unknown. This study aimed to determine the effect of nutritional status on warm ischemia-reperfusion injury in rat fatty livers. Fed and fasted rats with normal or fatty liver induced by a choline deficient diet underwent 1 hour of lobar ischemia and reperfusion. Rat survival was determined for 7 days. Serum transaminases, liver histology and cell ultrastructure were assessed before and after ischemia, and at 30 minutes, 2 hours, 8 hours, and 24 hours after reperfusion. Survival was also determined in fatty fasted rats supplemented with glucose before surgery. The preischemic hepatic glycogen was measured in all groups. Whereas survival was similar in fasted and fed rats with normal liver (90% vs. 100%), fasting dramatically reduced survival in rats with fatty liver (14% vs. 64%, P <.01). Accordingly, fasting and fatty degeneration had a synergistic effect in exacerbating liver injury. Mitochondrial damage was a predominant feature of ultrastructural hepatocyte injury in fasted fatty livers. Glucose supplementation partially prevented the fasting-induced depletion of glycogen and improved the 7-day rat survival to 45%. These data indicate that rat fatty livers exposed to normothermic ischemia-reperfusion injury are much more sensitive to fasting than histologically normal livers. Because glucose supplementation improves both the hepatic glycogen stores and the rat survival, a nutritional repletion procedure may be part of a treatment strategy aimed to prevent ischemia-reperfusion injury in fatty livers.

  8. Histological Image Feature Mining Reveals Emergent Diagnostic Properties for Renal Cancer

    PubMed Central

    Kothari, Sonal; Phan, John H.; Young, Andrew N.; Wang, May D.

    2016-01-01

    Computer-aided histological image classification systems are important for making objective and timely cancer diagnostic decisions. These systems use combinations of image features that quantify a variety of image properties. Because researchers tend to validate their diagnostic systems on specific cancer endpoints, it is difficult to predict which image features will perform well given a new cancer endpoint. In this paper, we define a comprehensive set of common image features (consisting of 12 distinct feature subsets) that quantify a variety of image properties. We use a data-mining approach to determine which feature subsets and image properties emerge as part of an “optimal” diagnostic model when applied to specific cancer endpoints. Our goal is to assess the performance of such comprehensive image feature sets for application to a wide variety of diagnostic problems. We perform this study on 12 endpoints including 6 renal tumor subtype endpoints and 6 renal cancer grade endpoints. Keywords-histology, image mining, computer-aided diagnosis PMID:28163980

  9. A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population.

    PubMed

    Verrijken, A; Beckers, S; Francque, S; Hilden, H; Caron, S; Zegers, D; Ruppert, M; Hubens, G; Van Marck, E; Michielsen, P; Staels, B; Taskinen, M-R; Van Hul, W; Van Gaal, L

    2013-10-01

    Mechanisms explaining the relationship in non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance are poorly understood. A genetic basis has been suggested. We studied the association between the genes patatin-like phospholipase domain-containing protein 3 (PNPLA3) and apolipoprotein C3 (APOC3) and metabolic and histological parameters of NAFLD in obese patients. Overweight and obese patients underwent a metabolic and liver assessment. If NAFLD was suspected, liver biopsy was proposed. APOC3 variant rs2854117 and PNPLA3 variant rs738409 were genotyped. Four hundred seventy patients were included (61.1% had liver biopsy). The percentage of patients with non-alcoholic steatohepatitis (NASH) was significantly different according to the PNPLA3 variant. After adjustment for age and body mass index, the PNPLA3 variant was associated with alanine aminotransferase (P < 0.001) and aspartate aminotransferase (P < 0.001). The PNPLA3 variant was associated with more severe features of steatohepatitis: steatosis (P < 0.001), lobular inflammation (P < 0.001), and ballooning (P = 0.002), but not with liver fibrosis, anthropometry, or insulin resistance. No significant difference in liver histology, anthropometric, or metabolic parameters was found between carriers and non-carriers of the APOC3 variant. PNPLA3 polymorphism rs738409 was associated with NASH and the severity of necroinflammatory changes independently of metabolic factors. No association between APOC3 gene variant rs2854117 and histological or metabolic parameters of NAFLD was found. Copyright © 2013 The Obesity Society.

  10. Liver and spleen stiffness and their ratio assessed by real-time two dimensional-shear wave elastography in patients with liver fibrosis and cirrhosis due to chronic viral hepatitis.

    PubMed

    Grgurevic, Ivica; Puljiz, Zeljko; Brnic, Darko; Bokun, Tomislav; Heinzl, Renata; Lukic, Anita; Luksic, Boris; Kujundzic, Milan; Brkljacic, Boris

    2015-11-01

    To investigate the performance of real-time 2D shear wave elastography (RT 2D-SWE) for non-invasive staging of liver disease in patients with chronic viral hepatitis (CVH). Naive CVH patients underwent liver (LS) and spleen stiffness (SS) measurements by an intercostal approach. Patients with ALT >3× upper limit of normal, cholestasis as revealed by dilated intrahepatic biliary tree, and liver congestion were excluded. Results were expressed in kPa and compared to histological stage (Ishak) of liver fibrosis (LF). Patients with decompensated liver cirrhosis (LC) were diagnosed using standard clinical, ultrasound, and endoscopic criteria. Of 123 patients, LS was successfully measured in 79.7% and SS in 53.7%. LS accurately differentiated between liver disease stages, with cut-off values of 8.1 (AUC 0.991) for F ≥ 3, 10.8 kPa (AUC 0.954) for F ≥ 5, and 27 kPa (AUC 0.961) for decompensated LC. SS was significantly different between non-cirrhotic stages (F0-4) and LC (cut-off 24 kPa; AUC 0.821). While both LS and SS increased with liver disease progression, the difference between them decreased, as reflected by the stiffness ratio index. RT 2D-SWE can accurately differentiate between the stages of LF, and can distinguish LF from LC and compensated from decompensated LC. • RT 2D-SWE is an accurate method for assessment of liver fibrosis. • RT 2D-SWE is applicable in 80% of patients with chronic viral hepatitis. • RT 2D-SWE accurately differentiates compensated from decompensated liver cirrhosis. • Both liver and spleen stiffness increase with progression of liver fibrosis. • In cirrhosis, the difference between liver and spleen stiffness decreases.

  11. Nonlinear optical microscopy: use of second harmonic generation and two-photon microscopy for automated quantitative liver fibrosis studies.

    PubMed

    Sun, Wanxin; Chang, Shi; Tai, Dean C S; Tan, Nancy; Xiao, Guangfa; Tang, Huihuan; Yu, Hanry

    2008-01-01

    Liver fibrosis is associated with an abnormal increase in an extracellular matrix in chronic liver diseases. Quantitative characterization of fibrillar collagen in intact tissue is essential for both fibrosis studies and clinical applications. Commonly used methods, histological staining followed by either semiquantitative or computerized image analysis, have limited sensitivity, accuracy, and operator-dependent variations. The fibrillar collagen in sinusoids of normal livers could be observed through second-harmonic generation (SHG) microscopy. The two-photon excited fluorescence (TPEF) images, recorded simultaneously with SHG, clearly revealed the hepatocyte morphology. We have systematically optimized the parameters for the quantitative SHG/TPEF imaging of liver tissue and developed fully automated image analysis algorithms to extract the information of collagen changes and cell necrosis. Subtle changes in the distribution and amount of collagen and cell morphology are quantitatively characterized in SHG/TPEF images. By comparing to traditional staining, such as Masson's trichrome and Sirius red, SHG/TPEF is a sensitive quantitative tool for automated collagen characterization in liver tissue. Our system allows for enhanced detection and quantification of sinusoidal collagen fibers in fibrosis research and clinical diagnostics.

  12. Liver fibrosis markers of nonalcoholic steatohepatitis

    PubMed Central

    Enomoto, Hirayuki; Bando, Yukihiro; Nakamura, Hideji; Nishiguchi, Shuhei; Koga, Masafumi

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver injury. NAFLD includes a wide range of clinical conditions from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and liver cirrhosis. The histological findings of NASH indicate hepatic steatosis and inflammation with characteristic hepatocyte injury (e.g., ballooning degeneration), as is observed in the patients with alcoholic liver disease. NASH is considered to be a potentially health-threatening disease that can progress to cirrhosis. A liver biopsy remains the most reliable diagnostic method to appropriately diagnose NASH, evaluate the severity of liver fibrosis, and determine the prognosis and optimal treatment. However, this invasive technique is associated with several limitations in routine use, and a number of biomarkers have been developed in order to predict the degree of liver fibrosis. In the present article, we review the current status of noninvasive biomarkers available to estimate liver fibrosis in the patients with NASH. We also discuss our recent findings on the use of the glycated albumin-to-glycated hemoglobin ratio, which is a new index that correlates to various chronic liver diseases, including NASH. PMID:26139988

  13. Liver fibrosis markers of nonalcoholic steatohepatitis.

    PubMed

    Enomoto, Hirayuki; Bando, Yukihiro; Nakamura, Hideji; Nishiguchi, Shuhei; Koga, Masafumi

    2015-06-28

    Nonalcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver injury. NAFLD includes a wide range of clinical conditions from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and liver cirrhosis. The histological findings of NASH indicate hepatic steatosis and inflammation with characteristic hepatocyte injury (e.g., ballooning degeneration), as is observed in the patients with alcoholic liver disease. NASH is considered to be a potentially health-threatening disease that can progress to cirrhosis. A liver biopsy remains the most reliable diagnostic method to appropriately diagnose NASH, evaluate the severity of liver fibrosis, and determine the prognosis and optimal treatment. However, this invasive technique is associated with several limitations in routine use, and a number of biomarkers have been developed in order to predict the degree of liver fibrosis. In the present article, we review the current status of noninvasive biomarkers available to estimate liver fibrosis in the patients with NASH. We also discuss our recent findings on the use of the glycated albumin-to-glycated hemoglobin ratio, which is a new index that correlates to various chronic liver diseases, including NASH.

  14. Chronic viral hepatitis: the histology report.

    PubMed

    Guido, Maria; Mangia, Alessandra; Faa, Gavino

    2011-03-01

    In chronic viral hepatitis, the role of liver biopsy as a diagnostic test has seen a decline, paralleled by its increasing importance for prognostic purposes. Nowadays, the main indication for liver biopsy in chronic viral hepatitis is to assess the severity of the disease, in terms of both necro-inflammation (grade) and fibrosis (stage), which is important for prognosis and therapeutic management. Several scoring systems have been proposed for grading and staging chronic viral hepatitis and there is no a general consensus on the best system to be used in the daily practice. All scoring systems have their drawbacks and all may be affected by sampling and observer variability. Whatever the system used, a histological score is a reductive approach since damage in chronic viral hepatitis is a complex biological process. Thus, scoring systems are not intended to replace the detailed, descriptive, pathology report. In fact, lesions other than those scored for grading and staging may have clinical relevance and should be assessed and reported. This paper aims to provide a systematic approach to the interpretation of liver biopsies obtained in cases of chronic viral hepatitis, with the hope of helping general pathologists in their diagnostic practice. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd.. All rights reserved.

  15. Betanin attenuates carbon tetrachloride (CCl4)-induced liver injury in common carp (Cyprinus carpio L.).

    PubMed

    Han, Junyan; Gao, Cheng; Yang, Shaobin; Wang, Jun; Tan, Dehong

    2014-06-01

    This study investigates the protective effect of betanin against liver injury induced by carbon tetrachloride (CCl4) in common carp (Cyprinus carpio L.). The fish were treated with 1, 2, and 4 % betanin in fodder throughout the experiment. After 20 days of treatment, the fish were intraperitoneally injected with 20 % (v/v in peanut oil) CCl4 at a volume of 0.5 mL/kg body weight. The fish were killed 3 days after CCl4 intoxication, and then, histological and biochemical assays were performed. Results showed that CCl4-induced liver CYP2E1 activity, oxidative stress, and injury, as indicated by the depleted glycogen storage, increased serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) activities and liver histological damage. Compared with the CCl4 control group, the betanin-treated groups exhibited reduced CYP2E1 activity, decreased malondialdehyde level, increased liver antioxidative capacity (increased glutathione level and superoxide dismutase and catalase activities), increased liver glycogen storage, and reduced serum AST/ALT activities, with significant differences in the 2 and 4 % groups (p < 0.05). Histological assay further confirmed the protective effect of betanin. In conclusion, betanin attenuates CCl4-induced liver damage in common carp. Moreover, the inhibition of CYP2E1 activity and oxidative stress may have significant roles in the protective effect of betanin.

  16. Glucomannan or Glucomannan Plus Spirulina-Enriched Squid-Surimi Diets Reduce Histological Damage to Liver and Heart in Zucker fa/fa Rats Fed a Cholesterol-Enriched and Non-Cholesterol-Enriched Atherogenic Diet.

    PubMed

    Vázquez-Velasco, Miguel; González-Torres, Laura; García-Fernández, Rosa A; Méndez, María Teresa; Bastida, Sara; Benedí, Juana; González-Muñoz, María José; Sánchez-Muniz, Francisco J

    2017-06-01

    Glucomannan-enriched squid surimi improves cholesterolemia and liver antioxidant status. The effect of squid surimi enriched with glucomannan or glucomannan plus spirulina on liver and heart structures and cell damage markers was tested in fa/fa rats fed highly saturated-hyper-energetic diets. Animals were fed 70% AIN-93M rodent diet plus six versions of 30% squid surimi for 7 weeks: control (C), glucomannan (G), and glucomannan plus spirulina (GS). The cholesterol-control (HC), cholesterol-glucomannan (HG), and cholesterol-glucomannan plus spirulina (HGS) groups were given similar diets that were enriched with 2% cholesterol and 0.4% cholic acid. G and GS diets versus C diet significantly inhibited weight gain and lowered plasma alanine aminotransferase and aspartate aminotransferase, liver steatosis, lipogranulomas, and total inflammation and alteration scores. The hypercholesterolemic agent significantly increased the harmful effects of the C diet. Liver weight, the hepatosomatic index, all damage markers, and total histological scoring rose for HC versus C (at least P < .05). The addition of glucomannan (HG vs. HC) improved these biomarkers, and non-additional effects from spirulina were observed except for the total liver alteration score. In conclusion, glucomannan and glucomannan plus spirulina blocked the highly saturated-hyper-energetic diet negative effects both with and without added cholesterol. Results suggest the usefulness of including these functional ingredients in fish products.

  17. Non-invasive evaluation of liver stiffness after splenectomy in rabbits with CCl4-induced liver fibrosis

    PubMed Central

    Wang, Ming-Jun; Ling, Wen-Wu; Wang, Hong; Meng, Ling-Wei; Cai, He; Peng, Bing

    2016-01-01

    AIM To investigate the diagnostic performance of liver stiffness measurement (LSM) by elastography point quantification (ElastPQ) in animal models and determine the longitudinal changes in liver stiffness by ElastPQ after splenectomy at different stages of fibrosis. METHODS Liver stiffness was measured in sixty-eight rabbits with CCl4-induced liver fibrosis at different stages and eight healthy control rabbits by ElastPQ. Liver biopsies and blood samples were obtained at scheduled time points to assess liver function and degree of fibrosis. Thirty-one rabbits with complete data that underwent splenectomy at different stages of liver fibrosis were then included for dynamic monitoring of changes in liver stiffness by ElastPQ and liver function according to blood tests. RESULTS LSM by ElastPQ was significantly correlated with histologic fibrosis stage (r = 0.85, P < 0.001). The optimal cutoff values by ElastPQ were 11.27, 14.89, and 18.21 kPa for predicting minimal fibrosis, moderate fibrosis, and cirrhosis, respectively. Longitudinal monitoring of the changes in liver stiffness by ElastPQ showed that early splenectomy (especially F1) may delay liver fibrosis progression. CONCLUSION ElastPQ is an available, convenient, objective and non-invasive technique for assessing liver stiffness in rabbits with CCl4-induced liver fibrosis. In addition, liver stiffness measurements using ElastPQ can dynamically monitor the changes in liver stiffness in rabbit models, and in patients, after splenectomy. PMID:28028365

  18. Liver protein profiles in insulin receptor-knockout mice reveal novel molecules involved in the diabetes pathophysiology.

    PubMed

    Capuani, Barbara; Della-Morte, David; Donadel, Giulia; Caratelli, Sara; Bova, Luca; Pastore, Donatella; De Canio, Michele; D'Aguanno, Simona; Coppola, Andrea; Pacifici, Francesca; Arriga, Roberto; Bellia, Alfonso; Ferrelli, Francesca; Tesauro, Manfredi; Federici, Massimo; Neri, Anna; Bernardini, Sergio; Sbraccia, Paolo; Di Daniele, Nicola; Sconocchia, Giuseppe; Orlandi, Augusto; Urbani, Andrea; Lauro, Davide

    2015-05-01

    Liver has a principal role in glucose regulation and lipids homeostasis. It is under a complex control by substrates such as hormones, nutrients, and neuronal impulses. Insulin promotes glycogen synthesis, lipogenesis, and lipoprotein synthesis and inhibits gluconeogenesis, glycogenolysis, and VLDL secretion by modifying the expression and enzymatic activity of specific molecules. To understand the pathophysiological mechanisms leading to metabolic liver disease, we analyzed liver protein patterns expressed in a mouse model of diabetes by proteomic approaches. We used insulin receptor-knockout (IR(-/-)) and heterozygous (IR(+/-)) mice as a murine model of liver metabolic dysfunction associated with diabetic ketoacidosis and insulin resistance. We evaluated liver fatty acid levels by microscopic examination and protein expression profiles by orthogonal experimental strategies using protein 2-DE MALDI-TOF/TOF and peptic nLC-MS/MS shotgun profiling. Identified proteins were then loaded into Ingenuity Pathways Analysis to find possible molecular networks. Twenty-eight proteins identified by 2-DE analysis and 24 identified by nLC-MS/MS shotgun were differentially expressed among the three genotypes. Bioinformatic analysis revealed a central role of high-mobility group box 1/2 and huntigtin never reported before in association with metabolic and related liver disease. A different modulation of these proteins in both blood and hepatic tissue further suggests their role in these processes. These results provide new insight into pathophysiology of insulin resistance and hepatic steatosis and could be useful in identifying novel biomarkers to predict risk for diabetes and its complications. Copyright © 2015 the American Physiological Society.

  19. Reactive hyperemia index (RHI) and cognitive performance indexes are associated with histologic markers of liver disease in subjects with non-alcoholic fatty liver disease (NAFLD): a case control study.

    PubMed

    Tuttolomondo, Antonino; Petta, Salvatore; Casuccio, Alessandra; Maida, Carlo; Corte, Vittoriano Della; Daidone, Mario; Di Raimondo, Domenico; Pecoraro, Rosaria; Fonte, Roberto; Cirrincione, Anna; Zafonte, Rita; Cabibi, Daniela; Cammà, Calogero; Di Marco, Vito; Licata, Anna; Magliozzo, Franco; Marchesini, Giulio; Merlino, Giovanni; Craxì, Antonio; Pinto, Antonio

    2018-02-16

    No study evaluated vascular health markers in subjects with non-alcoholic fatty liver disease (NAFLD) through a combined analysis of reactive hyperemia peripheral arterial tonometry (RH-PAT) and arterial stiffness indexes. We aimed to assess whether NAFLD and its histological severity are associated with impairment of arterial stiffness and RH-PAT indexes in a mixed cohort of patients with biopsy-proven NAFLD. The Kleiner classification was used to grade NAFLD grade. Pulse wave velocity (PWV) and augmentation index (Aix) were used as markers of arterial stiffness, whereas endothelial function was assessed using reactive hyperemia index (RHI). The mini-mental state examination (MMSE) was administered to test cognitive performance. 80 consecutive patients with biopsy-proven NAFLD and 83 controls without fatty liver disease. NAFLD subjects showed significantly lower mean RHI, higher mean arterial stiffness indexes and lower mean MMSE score. Multivariable analysis after correction for BMI, dyslipidaemia, hypertension, sex, diabetes, age and cardiovascular disease showed that BMI, diastolic blood pressure and RHI are significantly associated to NAFLD. Simple linear regression analysis showed among non-alcoholic steatohepatitis (NASH) subjects a significant negative relationship between ballooning grade and MMSE and a significant positive association between Kleiner steatosis grade and augmentation index. Future research will be addressed to evaluate the relationship between inflammatory markers and arterial stiffness and endothelial function indexes in NAFLD subjects. These study will evaluate association between cardiovascular event incidence and arterial stiffness, endothelial and cognitive markers, and they will address the beneficial effects of cardiovascular drugs such as statins and ACE inhibitors on these surrogate markers in NAFLD subjects.

  20. Liver histopathology in Baltic eelpout (Zoarces viviparus) - A baseline study for use in marine environmental monitoring.

    PubMed

    Fricke, Nicolai F; Stentiford, Grant D; Feist, Stephen W; Lang, Thomas

    2012-12-01

    The use of liver histopathology in various fish species as a biomarker in marine monitoring programmes to assess the biological effect of exposure to anthropogenic contaminants is well established. However, although the eelpout (Zoarces viviparus) has repeatedly been recommended as an appropriate bioindicator for monitoring purposes in the Baltic Sea, information on histopathological liver alterations of this species is scarce. In order to obtain an overview, a total of 1070 eelpout, collected in the period between spring 2001 and winter 2010 from 34 sampling sites distributed over large parts of the Baltic Sea, were histologically analyzed. Liver lesions were recorded and classified according to established liver lesion categories. A high prevalence of non-specific and early toxicopathic non-neoplastic hepatic lesions was recorded. In contrast, pre-neoplastic lesions were observed only in rare cases and neoplastic changes were absent. A comparison with published data on other fish species revealed that the observed alterations may indicate effects of environmental stressors including contaminants. The results of the present study, thus, support the application of eelpout liver histopathology in environmental monitoring. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Extracellular Vesicles from Human Liver Stem Cells Reduce Injury in an Ex Vivo Normothermic Hypoxic Rat Liver Perfusion Model.

    PubMed

    Rigo, Federica; De Stefano, Nicola; Navarro-Tableros, Victor; David, Ezio; Rizza, Giorgia; Catalano, Giorgia; Gilbo, Nicholas; Maione, Francesca; Gonella, Federica; Roggio, Dorotea; Martini, Silvia; Patrono, Damiano; Salizzoni, Mauro; Camussi, Giovanni; Romagnoli, Renato

    2018-05-01

    The gold standard for organ preservation before transplantation is static cold storage, which is unable to fully protect suboptimal livers from ischemia/reperfusion injury. An emerging alternative is normothermic machine perfusion (NMP), which permits organ reconditioning. Here, we aimed to explore the feasibility of a pharmacological intervention on isolated rat livers by using a combination of NMP and human liver stem cells-derived extracellular vesicles (HLSC-EV). We established an ex vivo murine model of NMP capable to maintain liver function despite an ongoing hypoxic injury induced by hemodilution. Livers were perfused for 4 hours without (control group, n = 10) or with HLSC-EV (treated group, n = 9). Bile production was quantified; perfusate samples were collected hourly to measure metabolic (pH, pO2, pCO2) and cytolysis parameters (AST, alanine aminotransferase, lactate dehydrogenase). At the end of perfusion, we assessed HLSC-EV engraftment by immunofluorescence, tissue injury by histology, apoptosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, tissue hypoxia-inducible factor 1-α, and transforming growth factor-beta 1 RNA expression by quantitative reverse transcription-polymerase chain reaction. During hypoxic NMP, livers were able to maintain homeostasis and produce bile. In the treated group, AST (P = 0.018) and lactate dehydrogenase (P = 0.032) levels were significantly lower than those of the control group at 3 hours of perfusion, and AST levels persisted lower at 4 hours (P = 0.003). By the end of NMP, HLSC-EV had been uptaken by hepatocytes, and EV treatment significantly reduced histological damage (P = 0.030), apoptosis (P = 0.049), and RNA overexpression of hypoxia-inducible factor 1-α (P < 0.0001) and transforming growth factor-beta 1 (P = 0.014). HLSC-EV treatment, even in a short-duration model, was feasible and effectively reduced liver injury during hypoxic NMP.

  2. Case report: primary acinar cell carcinoma of the liver treated with multimodality therapy

    PubMed Central

    Basturk, Olca; Shia, Jinru; Klimstra, David S.; Alago, William; D’Angelica, Michael I.; Abou-Alfa, Ghassan K.; O’Reilly, Eileen M.; Lowery, Maeve A.

    2017-01-01

    We describe a case of primary acinar cell carcinoma (ACC) originating in the liver in a 54-year-old female, diagnosed following persistent abnormal elevated liver function. Imaging revealed two masses, one dominant lesion in the right hepatic lobe and another in segment IVA. A right hepatectomy was performed to remove the larger lesion, while the mass in segment IVA was unresectable due to its proximity to the left hepatic vein. Immunohistochemical staining showed positivity for trypsin and chymotrypsin. Postoperatively the patient underwent hepatic arterial embolization of the other unresectable lesion followed by FOLFOX chemotherapy. At 20 months from diagnosis the patient is currently under observation with a decreasing necrotic mass and no other disease evident. Based on histology, immunohistochemistry and radiological findings a diagnosis of primary ACC of the liver was made. Genomic assessment of somatic mutations within the patient’s tumor was also performed through next generation sequencing and findings were consistent with an acinar malignancy. This case highlights a rare tumor subtype treated with a combination of therapeutic modalities through a multidisciplinary approach. PMID:29184698

  3. Steatotic livers are susceptible to normothermic ischemia-reperfusion injury from mitochondrial Complex-I dysfunction

    PubMed Central

    Chu, Michael JJ; Premkumar, Rakesh; Hickey, Anthony JR; Jiang, Yannan; Delahunt, Brett; Phillips, Anthony RJ; Bartlett, Adam SJR

    2016-01-01

    AIM: To assess the effects of ischemic preconditioning (IPC, 10-min ischemia/10-min reperfusion) on steatotic liver mitochondrial function after normothermic ischemia-reperfusion injury (IRI). METHODS: Sixty male Sprague-Dawley rats were fed 8-wk with either control chow or high-fat/high-sucrose diet inducing > 60% mixed steatosis. Three groups (n = 10/group) for each dietary state were tested: (1) the IRI group underwent 60 min partial hepatic ischemia and 4 h reperfusion; (2) the IPC group underwent IPC prior to same standard IRI; and (3) sham underwent the same surgery without IRI or IPC. Hepatic mitochondrial function was analyzed by oxygraphs. Mitochondrial Complex-I, Complex-II enzyme activity, serum alanine aminotransferase (ALT), and histological injury were measured. RESULTS: Steatotic-IRI livers had a greater increase in ALT (2476 ± 166 vs 1457 ± 103 IU/L, P < 0.01) and histological injury following IRI compared to the lean liver group. Steatotic-IRI demonstrated lower Complex-I activity at baseline [78.4 ± 2.5 vs 116.4 ± 6.0 nmol/(min.mg protein), P < 0.001] and following IRI [28.0 ± 6.2 vs 104.3 ± 12.6 nmol/(min.mg protein), P < 0.001]. Steatotic-IRI also demonstrated impaired Complex-I function post-IRI compared to the lean liver IRI group. Complex-II activity was unaffected by hepatic steatosis or IRI. Lean liver mitochondrial function was unchanged following IRI. IPC normalized ALT and histological injury in steatotic livers but had no effect on overall steatotic liver mitochondrial function or individual mitochondrial complex enzyme activities. CONCLUSION: Warm IRI impairs steatotic liver Complex-I activity and function. The protective effects of IPC in steatotic livers may not be mediated through mitochondria. PMID:27217699

  4. Interactome of E. piscicida and grouper liver proteins reveals strategies of bacterial infection and host immune response.

    PubMed

    Li, Hui; Zhu, Qing-Feng; Peng, Xuan-Xian; Peng, Bo

    2017-01-03

    The occurrence of infectious diseases is related to heterogeneous protein interactions between a host and a microbe. Therefore, elucidating the host-pathogen interplay is essential. We previously revealed the protein interactome between Edwardsiella piscicida and fish gill cells, and the present study identified the protein interactome between E. piscicida and E. drummondhayi liver cells. E. drummondhayi liver cells and bacterial pull-down approaches were used to identify E. piscicida outer membrane proteins that bind to liver cells and fish liver cell proteins that interact with bacterial cells, respectively. Eight bacterial proteins and 11 fish proteins were characterized. Heterogeneous protein-protein interactions between these bacterial cells and fish liver cells were investigated through far-Western blotting and co-immunoprecipitation. A network was constructed based on 42 heterogeneous protein-protein interactions between seven bacterial proteins and 10 fish proteins. A comparison of the new interactome with the previously reported interactome showed that four bacterial proteins overlapped, whereas all of the identified fish proteins were new, suggesting a difference between bacterial tricks for evading host immunity and the host strategy for combating bacterial infection. Furthermore, these bacterial proteins were found to regulate the expression of host innate immune-related proteins. These findings indicate that the interactome contributes to bacterial infection and host immunity.

  5. Histologic characterization of canine dilated cardiomyopathy.

    PubMed

    Tidholm, A; Jönsson, L

    2005-01-01

    Dilated cardiomyopathy (DCM), characterized by chamber dilatation and myocardial systolic and diastolic dysfunction, is one of the most common heart diseases in dogs. The clinical diagnosis is based on findings on echocardiographic and Doppler examinations, with the active exclusion of other acquired or congenital heart diseases. However, the echocardiographic criteria for the diagnosis of DCM are not wholly specific for the disease, and histologic examination may be necessary for final diagnosis. Review of reports on histologic findings in dogs with clinically diagnosed DCM reveals two histologically distinct forms of DCM: 1) cardiomyopathy of Boxers and Doberman Pinschers, corresponding to the "fatty infiltration-degenerative" type and 2) the form seen in many giant, large-, and medium-sized breeds, including some Boxers and Doberman Pinschers, classified as the "attenuated wavy fiber" type of DCM. The histologic changes of the attenuated wavy fiber type of DCM may precede clinical and echocardiographic signs of heart disease, thus indicating an early stage of DCM.

  6. Hepatoprotective effects of Vaccinium arctostaphylos against CCl4-induced acute liver injury in rats.

    PubMed

    Ravan, Alireza Pouyandeh; Bahmani, Mahdi; Ghasemi Basir, Hamid Reza; Salehi, Iraj; Oshaghi, Ebrahim Abbasi

    2017-09-26

    This study was carried out to evaluate the antioxidant and hepatoprotective effects of Vaccinium arctostaphylos (V.a) methanolic extract on carbon tetrachloride (CCl4)-induced acute liver injury in Wistar rats. Total phenolic and total flavonoid contents as well as antioxidant activity of V.a were determined. Extracts of V.a at doses of 200 and 400 mg/kg were administered by oral gavage to rats once per day for 7 days and then were given an intraperitoneal injection of 1 mL/kg CCl4 (1:1 in olive oil) for 3 consecutive days. Serum biochemical markers of liver injury, oxidative markers, as well as hydroxyproline (HP) content and histopathology of liver were evaluated. The obtained results showed that V.a had strong antioxidant activity. Treatment of rats with V.a blocked the CCl4-induced elevation of serum markers of liver function and enhanced albumin and total protein levels. The level of hepatic HP content was also reduced by the administration of V.a treatment. Histological examination of the liver section revealed that V.a prevented the occurrence of pathological changes in CCl4-treated rats. These findings suggested that V.a may be useful in the treatment and prevention of hepatic injury induced by CCl4.

  7. Molecular profiling of subclinical inflammatory lesions in long-term surviving adult liver transplant recipients.

    PubMed

    Londoño, María-Carlota; Souza, Lara Neves; Lozano, Juan-José; Miquel, Rosa; Abraldes, Juan G; Llovet, Laura-Patricia; Quaglia, Alberto; Rimola, Antoni; Navasa, Miquel; Sánchez-Fueyo, Alberto

    2018-04-28

    Subclinical inflammatory changes are commonly described in long-term transplant recipients undergoing protocol liver biopsies. The pathogenesis of these lesions remains unclear. The aim of this study was to identify the key molecular pathways driving progressive subclinical inflammatory liver allograft damage. All liver recipients followed at Hospital Clínic Barcelona who were >10 years post-transplant were screened for participation in the study. Patients with recurrence of underlying liver disease, biliary or vascular complications, chronic rejection, and abnormal liver function tests were excluded. Sixty-seven patients agreed to participate and underwent blood and serological tests, transient elastography and a liver biopsy. Transcriptome profiling was performed on RNA extracted from 49 out of the 67 biopsies employing a whole genome next generation sequencing platform. Patients were followed for a median of 6.8 years following the index liver biopsy. Median time since transplantation to liver biopsy was 13 years (10-22). The most frequently observed histological abnormality was portal inflammation with different degrees of fibrosis, present in 45 biopsies (67%). Two modules of 102 and 425 co-expressed genes were significantly correlated with portal inflammation, interface hepatitis and portal fibrosis. These modules were enriched in molecular pathways known to be associated with T cell mediated rejection. Liver allografts showing the highest expression levels for the two modules recapitulated the transcriptional profile of biopsies with clinically apparent rejection and developed progressive damage over time, as assessed by non-invasive markers of fibrosis. A large proportion of adult liver transplant recipients who survive long-term exhibit subclinical histological abnormalities. The transcriptomic profile of these patients' liver tissue closely resembles that of T cell mediated rejection and may result in progressive allograft damage. A large

  8. An experimental research on chronic intermittent hypoxia leading to liver injury.

    PubMed

    Feng, Shu-zhi; Tian, Jian-li; Zhang, Qiang; Wang, Hui; Sun, Ning; Zhang, Yun; Chen, Bao-yuan

    2011-09-01

    Sleep apnea-hypopnea syndrome and its chronic intermittent hypoxia component may cause multi-system-targeted injury. The latest finding shows that liver is one of the injured organs. The purpose of the study is to observe the dynamic process of the influence that chronic intermittent hypoxia plays on rat liver enzyme, hepatic histology, and ultrastructure based on lipid disorders. A total of 72 male Wistar rats were randomly divided into three groups. The control group was fed with a regular chow diet, the high fat group with a high fat diet, and the high fat plus intermittent hypoxia group with a high fat diet with a 7-h/day intermittent hypoxia treatment. Changes were observed in rat liver enzyme, hepatic histology, and ultrastructure of the three groups on the third, sixth, and ninth weeks, respectively. The liver paraffin sections were detected with myeloperoxidase. The liver function and structure of the control group were found to be normal; the liver enzyme level of the high fat group was significantly higher than that of the control group on the sixth and ninth weeks; and the liver enzyme level of the high fat plus intermittent hypoxia group was significantly higher than that of the control group and the high fat group on the third, sixth, and ninth weeks (all P < 0.01). Observed by a light microscope and a transmission electron microscope, the high fat group and the high fat plus intermittent hypoxia group were all characterized by nonalcoholic fatty liver disease: the high fat group was characterized by simple fatty liver on the third and sixth weeks and by steatohepatitis on the ninth week; the damage of the high fat plus intermittent hypoxia group was significantly more severe than that of the high fat group in all the monitoring points, characterized by steatohepatitis on the sixth week and by obvious liver fibrosis on the ninth week; the myeloperoxidase level of the high fat plus intermittent hypoxia group was significantly higher than that of the

  9. Perioperative liver and spleen elastography in patients without chronic liver disease.

    PubMed

    Eriksson, Sam; Borsiin, Hanna; Öberg, Carl-Fredrik; Brange, Hannes; Mijovic, Zoran; Sturesson, Christian

    2018-02-27

    To investigate changes in hepatic and splenic stiffness in patients without chronic liver disease during liver resection for hepatic tumors. Patients scheduled for liver resection for hepatic tumors were considered for enrollment. Tissue stiffness measurements on liver and spleen were conducted before and two days after liver resection using point shear-wave elastography. Histological analysis of the resected liver specimen was conducted in all patients and patients with marked liver fibrosis were excluded from further study analysis. Patients were divided into groups depending on size of resection and whether they had received preoperative chemotherapy or not. The relation between tissue stiffness and postoperative biochemistry was investigated. Results are presented as median (interquartile range). 35 patients were included. The liver stiffness increased in patients undergoing a major resection from 1.41 (1.24-1.63) m/s to 2.20 (1.72-2.44) m/s ( P = 0.001). No change in liver stiffness in patients undergoing a minor resection was found [1.31 (1.15-1.52) m/s vs 1.37 (1.12-1.77) m/s, P = 0.438]. A major resection resulted in a 16% (7%-33%) increase in spleen stiffness, more ( P = 0.047) than after a minor resection [2 (-1-13) %]. Patients who underwent preoperative chemotherapy ( n = 20) did not differ from others in preoperative right liver lobe [1.31 (1.16-1.50) vs 1.38 (1.12-1.56) m/s, P = 0.569] or spleen [2.79 (2.33-3.11) vs 2.71 (2.37-2.86) m/s, P = 0.515] stiffness. Remnant liver stiffness on the second postoperative day did not show strong correlations with maximum postoperative increase in bilirubin ( R 2 = 0.154, Pearson's r = 0.392, P = 0.032) and international normalized ratio ( R 2 = 0.285, Pearson's r = 0.534, P = 0.003). Liver and spleen stiffness increase after a major liver resection for hepatic tumors in patients without chronic liver disease.

  10. Perioperative liver and spleen elastography in patients without chronic liver disease

    PubMed Central

    Eriksson, Sam; Borsiin, Hanna; Öberg, Carl-Fredrik; Brange, Hannes; Mijovic, Zoran; Sturesson, Christian

    2018-01-01

    AIM To investigate changes in hepatic and splenic stiffness in patients without chronic liver disease during liver resection for hepatic tumors. METHODS Patients scheduled for liver resection for hepatic tumors were considered for enrollment. Tissue stiffness measurements on liver and spleen were conducted before and two days after liver resection using point shear-wave elastography. Histological analysis of the resected liver specimen was conducted in all patients and patients with marked liver fibrosis were excluded from further study analysis. Patients were divided into groups depending on size of resection and whether they had received preoperative chemotherapy or not. The relation between tissue stiffness and postoperative biochemistry was investigated. RESULTS Results are presented as median (interquartile range). 35 patients were included. The liver stiffness increased in patients undergoing a major resection from 1.41 (1.24-1.63) m/s to 2.20 (1.72-2.44) m/s (P = 0.001). No change in liver stiffness in patients undergoing a minor resection was found [1.31 (1.15-1.52) m/s vs 1.37 (1.12-1.77) m/s, P = 0.438]. A major resection resulted in a 16% (7%-33%) increase in spleen stiffness, more (P = 0.047) than after a minor resection [2 (-1-13) %]. Patients who underwent preoperative chemotherapy (n = 20) did not differ from others in preoperative right liver lobe [1.31 (1.16-1.50) vs 1.38 (1.12-1.56) m/s, P = 0.569] or spleen [2.79 (2.33-3.11) vs 2.71 (2.37-2.86) m/s, P = 0.515] stiffness. Remnant liver stiffness on the second postoperative day did not show strong correlations with maximum postoperative increase in bilirubin (R2 = 0.154, Pearson’s r = 0.392, P = 0.032) and international normalized ratio (R2 = 0.285, Pearson’s r = 0.534, P = 0.003). CONCLUSION Liver and spleen stiffness increase after a major liver resection for hepatic tumors in patients without chronic liver disease. PMID:29492187

  11. Histologic and apoptotic changes induced by titanium dioxide nanoparticles in the livers of rats

    PubMed Central

    Alarifi, Saud; Ali, Daoud; Al-Doaiss, Amin A; Ali, Bahy A; Ahmed, Mukhtar; Al-Khedhairy, Abdulaziz A

    2013-01-01

    Titanium dioxide (TiO2) nanoparticles are among the top five nanoparticles used in consumer products, paints, and pharmaceutical preparations. Given that exposure to such nanoparticles is mainly via the skin and inhalation, the present study was conducted in male Wistar albino rats (Rattus norvegicus). Our aim was to investigate the effect of TiO2 nanoparticles on hepatic tissue in an attempt to understand their toxicity and the potential effect of their therapeutic and diagnostic use. To investigate the effects of TiO2 nanoparticles on liver tissue, 30 healthy male Wistar albino rats were exposed to TiO2 nanoparticles at doses of 63 mg, 126 mg, and 252 mg per animal for 24 and 48 hours. Serum glutamate oxaloacetate transaminase and alkaline phosphatase activity was altered. Changes in hepatocytes can be summarized as hydropic degeneration, cloudy swelling, fatty degeneration, portal and lobular infiltration by chronic inflammatory cells, and congested dilated central veins. The histologic alterations observed might be an indication of hepatocyte injury due to the toxicity of TiO2 nanoparticles, resulting in an inability to deal with accumulated residues from the metabolic and structural disturbances caused by these nanoparticles. The appearance of cytoplasmic degeneration and destruction of nuclei in hepatocytes suggests that TiO2 nanoparticles interact with proteins and enzymes in hepatic tissue, interfering with antioxidant defense mechanisms and leading to generation of reactive oxygen species which, in turn, may induce stress in hepatocytes, promoting atrophy, apoptosis, and necrosis. More immunohistochemical and ultrastructural investigations are needed in relation to TiO2 nanoparticles and their potential effects when used as therapeutic and diagnostic tools. PMID:24143098

  12. The relationship between liver histology and noninvasive markers in primary biliary cirrhosis.

    PubMed

    Olmez, Sehmus; Sayar, Suleyman; Avcioglu, Ufuk; Tenlik, İlyas; Ozaslan, Ersan; Koseoglu, Hasan T; Altiparmak, Emin

    2016-07-01

    Primary biliary cirrhosis (PBC) is a disease that affects liver with various severity and progression rates. It is important to diagnose advanced stage of the disease to lower liver-related morbidity and mortality. Since liver biopsy is an invasive method, liver biopsy tends to be replaced by noninvasive methods. In this study, we aim to show the role of aminotransferase to platelet ratio index (APRI) and fibrosis index on the basis of the four factors (FIB-4) scores, laboratory values, and their effectiveness in predicting advanced disease. PBC patients diagnosed pathologically at Numune Education and Research Hospital were included in the study between the years 1995 and 2013. Patients were grouped according to their fibrosis level: group 1 (early stage) included 18 patients with F1 and F2 fibrosis and group 2 (advanced stage) included 22 patients with F3 and F4 fibrosis. APRI and FIB-4 scores, routine laboratory values, and their proportions were compared. The effectiveness of parameters showing advanced stage was further compared. There were statistically significant differences in APRI, FIB-4 scores, and aspartate aminotransferase (AST) levels between the groups with early and advanced stages of disease. Receiver operating curve analysis was used to determine APRI, FIB-4 and AST levels. The most effective parameters for diagnosing an advanced stage were APRI, AST levels, and FIB-4 scores, respectively. In conclusion, APRI and FIB-4 scores can be calculated simply and easily by routine laboratory tests at low cost and also these scores may be a predictor of advanced stage of the disease in PBC. These tests may be reproducible and may be used to monitor disease progression.

  13. Harmonic curved shears system prevent of bile leakage after liver resection in a pig model.

    PubMed

    Shimoda, Mitsugi; Iwasaki, Yoshimi; Kubota, Keiichi

    2014-01-01

    We evaluated the efficacy of TachoComb (TC) collagen fleece and Harmonic Focus (HF) shears in a pig liver resection model. Pigs were divided into 3 groups of 7, in which vessels were tied with silk and TC was applied to the cut surfaces (Silk+TC group), sealed and sheared with HF and TC (HF+TC group), or sealed using HF alone (HF-TC group). After 1 month, we conducted a histologic evaluation and recorded the incidence of bile leakage with infected collections at the liver cut surface. Six pigs were evaluated in each group. In the Silk+TC group, 4 of the 6 pigs had infected collections at the cut surface. Histologically, the silk had remained under the fibrotic tissue, which contained remnants of TC fragments. In the HF+TC group, 5 of the 6 pigs also had infected collections, and histologically, TC had remained in the hard fibrotic tissues. In the HF-TC group, none of the 6 pigs had infected collections, and the histologic findings were normal. Use of the HF alone may be an effective method for preventing bile leakage in infected collections after liver resection.

  14. The action of aminoguanidine on the liver of trained diabetic rats

    PubMed Central

    2013-01-01

    Background This study evaluated the effect of aminoguanidine on liver of diabetic rats subject to physical exercises using histological and histochemical techniques. Methods The rats used in this study were divided into five groups: sedentary control, sedentary diabetic, trained diabetic, sedentary diabetic and treated with aminoguanidine, trained diabetic and treated with aminoguanidine. Results The results showed no effect of aminoguanidine on the liver tissue, although there was improvement with exercise training showing cytological, morpho-histological and histochemical alterations in liver cells of animals from groups trained diabetic and/or treated diabetic compared to those individuals in the sedentary control and sedentary diabetic. These changes included: hepatocytes hypertrophy, presence and distribution of polysaccharides in the hepatocytes cytoplasm and, especially, congestion of the liver blood vessels. Conclusion Our results suggest that aminoguanidine is not hepatotoxic, when used at dosage of 1 g/L for the treatment of diabetes complications, and confirmed that the practice of moderate physical exercise assuaged the damage caused by diabetes without the use of insulin. PMID:23837632

  15. Evaluation of the 13C-octanoate breath test as a surrogate marker of liver damage in animal models.

    PubMed

    Shalev, Tamar; Aeed, Hussein; Sorin, Vladimir; Shahmurov, Mark; Didkovsky, Elena; Ilan, Yaron; Avni, Yona; Shirin, Haim

    2010-06-01

    Octanoate (also known as sodium octanoate), a medium-chain fatty acid metabolized in the liver, is a potential substrate for non-invasive breath testing of hepatic mitochondrial beta-oxidation. We evaluated the 13C-octanoate breath test (OBT) for assessing injury in acute hepatitis and two rat models of liver cirrhosis, first testing octanoate absorption (per os or intraperitoneally (i.p.)) in normal rats. We then induced acute hepatitis with thioacetamide (300 mg/kg/i.p., 24-h intervals). Liver injury end points were serum aminotransferase levels and 13C-OBT (24 and 48 h following initial injection). Thioacetamide (200 mg/kg/i.p., twice per week, 12 weeks) was used to induce liver cirrhosis. OBT and liver histological assessment were performed every 4 weeks. Bile duct ligation (BDL) was used to induce cholestatic liver injury. We completed breath tests with 13C-OBT and 13C-methacetin (MBID), liver biochemistry, and liver histology in BDL and sham-operated rats (baseline, 6, 14, 20 days post-BDL). Octanoate absorbs well by either route. Peak amplitudes and cumulative percentage dose recovered at 30 and 60 min (CPDR30/60), but not peak time, correlated with acute hepatitis. Fibrosis stage 3 at week 8 significantly correlated with each OBT parameter. Cholestatic liver injury (serum bilirubin, ALP, gamma-GT, liver histology) was associated with significant suppression of the maximal peak values and CPDR30/60, respectively (P<0.05),using MBID but not 13C-octanoate. OBT is sensitive for potentially evaluating liver function in rat models of acute hepatitis and thioacetamide-induced liver cirrhosis but not in cholestatic liver injury. The MBID test may be better for evaluation of cholestatic liver disease in this model.

  16. Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance.

    PubMed

    Stål, Per

    2015-10-21

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis (stage F3) and cirrhosis (stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers (e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques (transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD.

  17. Biological effects of two successive shock waves focused on liver tissues and melanoma cells.

    PubMed

    Benes, J; Sunka, P; Králová, J; Kaspar, J; Poucková, P

    2007-01-01

    A new generator of two successive shock waves focused to a common focal point has been developed. Cylindrical pressure waves created by multichannel electrical discharges on two cylindrical composite anodes are focused by a metallic parabolic reflector - cathode, and near the focus they are transformed to strong shock waves. Schlieren photos of the focal region have demonstrated that mutual interaction of the two waves results in generation of a large number of secondary short-wavelength shocks. Interaction of the focused shockwaves with liver tissues and cancer cell suspensions was investigated. Localized injury of rabbit liver induced by the shock waves was demonstrated by magnetic resonance imaging. Histological analysis of liver samples taken from the injured region revealed that the transition between the injured and the healthy tissues is sharp. Suspension of melanoma B16 cells was exposed and the number of the surviving cells rapidly decreased with increasing number of shocks and only 8 % of cells survived 350 shocks. Photographs of cells demonstrate that even small number of shocks results in perforation of cell membranes.

  18. Impact of PNPLA3 variants on liver histology of 168 patients with HIV infection and chronic hepatitis C.

    PubMed

    Sagnelli, C; Merli, M; Uberti-Foppa, C; Hasson, H; Cirillo, G; Grandone, A; Salpietro, S; Minichini, C; Del Giudice, E M; Lazzarin, A; Sagnelli, E; Coppola, N

    2016-04-01

    This study analysed the impact of PNPLA3 variants on liver histology of 168 HIV/hepatitis C virus (HCV)-coinfected patients who were naïve for HCV treatment. A athologist unaware of the patients' condition graded liver fibrosis and necroinflammation (Ishak) and steatosis (Kleiner). Patients were tested for PNPLA3 variants and genotyped for the PNPLA3 rs738409 C to G variant underlying the I148M substitution. All were hepatitis B surface antigen negative and stated no alcohol abuse. The mean age was 40.6 (37.6-44.1) years, 72.6% were males, 42% had HCV genotype 3, 38.9% HCV genotype 1 and 79.2% were receiving highly active antiretroviral therapy. The 79 patients with the PNPLA3 p.148I/M or M/M variants more frequently showed severe steatosis (score 3-4) than the 89 with PNPLA3 p.148I/I (43% vs. 24.7%, p 0.001), whereas no difference was observed in the degree of necroinflammation or fibrosis. Compared with 112 patients with lower scores, 56 with severe steatosis showed higher body mass index (p 0.03), higher rate of HCV genotype 3 (55.6% vs. 35.2%, p 0.01), PNPLA3 p.148I/M or M/M (60.7% vs. 39.3%, p 0.01) and lower CD4(+) cells/mm(3) (514.00 (390.5-673.0) vs. 500.00 (399.0-627.0); p 0.002). At multivariate analysis, body mass index (p 0.01), HCV genotype 3 (p 0.006), CD4(+) cell count (p 0.005) and PNPLA3 p.148I/M or M/M variants (p 0.01) were found to be independent predictors of severe liver steatosis. The PNPLA3 p.148 I/M or M/M variants and CD4(+) cell count were the only independent predictors of severe steatosis in patients with HCV non-3 genotypes. This is the first study to show that among HIV/HCV-coinfected patients the PNPLA3 p.148I/M or M/M variant have substantially less impact on steatosis for those with HCV genotype 3 than non-genotype 3. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  19. Controlled Attenuation Parameter and Liver Stiffness Measurements for Steatosis Assessment in the Liver Transplant of Brain Dead Donors.

    PubMed

    Mancia, Claire; Loustaud-Ratti, Véronique; Carrier, Paul; Naudet, Florian; Bellissant, Eric; Labrousse, François; Pichon, Nicolas

    2015-08-01

    One of the main selection criteria of the quality of a liver graft is the degree of steatosis, which will determine the success of the transplantation. The aim of this study was to evaluate the ability of FibroScan and its related methods Controlled Attenuation Parameter and Liver Stiffness to assess objectively steatosis and fibrosis in livers from brain-dead donors to be potentially used for transplantation. Over a period of 10 months, 23 consecutive brain dead donors screened for liver procurement underwent a FibroScan and a liver biopsy. The different predictive models of liver retrievability using liver biopsy as the gold standard have led to the following area under receiver operating characteristic curve: 76.6% (95% confidence intervals [95% CIs], 48.2%-100%) when based solely on controlled attenuation parameter, 75.0% (95% CIs, 34.3%-100%) when based solely on liver stiffness, and 96.7% (95% CIs, 88.7%-100%) when based on combined indices. Our study suggests that a preoperative selection of brain-dead donors based on a combination of both Controlled Attenuation Parameter and Liver Stiffness obtained with FibroScan could result in a good preoperative prediction of the histological status and degree of steatosis of a potential liver graft.

  20. Diagnosis of liver involvement in early syphilis. A critical review.

    PubMed

    Veeravahu, M

    1985-01-01

    The diagnosis of liver involvement in early syphilis has always posed problems because of its rarity and the difficulty of excluding coincidental liver disease caused by a multitude of pathogens. Case reports deal predominantly with jaundiced homosexual men in whom syphilis is discovered later, and the prospective studies of patients with early syphilis disclose only mild biochemical abnormalities in liver function test results. There is no single characteristic feature attributable to early syphilitic hepatitis. Even liver histologic findings are variable. At least in those patients who have jaundice, there is a likelihood of coincidental viral hepatitis. Therefore, the evidence to implicate Treponema pallidum as a liver pathogen in early syphilis is not convincing.

  1. Histological change and heat shock protein 70 expression in different tissues of Japanese flounder Paralichthys olivaceus in response to elevated temperature

    NASA Astrophysics Data System (ADS)

    Liu, Yifan; Ma, Daoyuan; Xiao, Zhizhong; Xu, Shihong; Wang, Yanfeng; Wang, Yufu; Xiao, Yongshuang; Song, Zongcheng; Teng, Zhaojun; Liu, Qinghua; Li, Jun

    2015-01-01

    High temperature influences the homeostasis of fish. We investigated the effects of elevated temperature on tissues of Japanese flounder ( Paralichthys olivaceus) by analyzing the histology and heat shock protein 70 ( hsp70) expression of fish reared in warm conditions. In this study, temperature was increased at 1±0.5°C/day starting at 24±0.5°C, and was kept at that temperature for 5 days before the next rise. After raising temperature at the rate up to 32±0.5°C, tissue samples from midgut, spleen, stomach, liver, muscle, gill, heart, trunk kidney and brain were collected for histological analysis and mRNA assay. Almost all the tissues showed changes in morphological structure and hsp70 level at 32±0.5°C. Histological assessment of the tissues indicated that the gill had the most serious damage, including highly severe epithelial lifting and edema, curved tips and hyperemia at the ending of the lamellars, desquamation and necrosis. The next most severe damage was found in liver and kidney. The hsp70 levels in all the tissues first increased and then decreased. The gut, stomach, muscle, heart, and brain had the highest expressions in 6 h, whereas the spleen, liver, gill and kidney had the highest expressions in 2 h. Therefore, tissues with the most significant lesions (especially gill and liver) responded much earlier (2 h) in hsp70 expression than other tissues, and these tissues demonstrated the most marked histological disruption and elevated mRNA levels, making them ideal candidates for further studies on the thermal physiology of this species.

  2. Evaluation of liver fibrosis: "Something old, something new…".

    PubMed

    Almpanis, Zannis; Demonakou, Maria; Tiniakos, Dina

    2016-01-01

    Hepatic fibrogenesis may gradually result to cirrhosis due to the accumulation of extracellular matrix components as a response to liver injury. Thus, therapeutic decisions in chronic liver disease, regardless of the cause, should first and foremost be guided by an accurate quantification of hepatic fibrosis. Detection and assessment of the extent of hepatic fibrosis represent a challenge in modern Hepatology. Although traditional histological staging systems remain the "best standard", they are not able to quantify liver fibrosis as a dynamic process and may not accurately substage cirrhosis. This review aims to compare the currently used non-invasive methods of measuring liver fibrosis and provide an update in current tissue-based digital techniques developed for this purpose, that may prove of value in daily clinical practice.

  3. Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment (II). The treatment of nonalcoholic fatty liver disease.

    PubMed

    Brea, Ángel; Pintó, Xavier; Ascaso, Juan F; Blasco, Mariano; Díaz, Ángel; González-Santos, Pedro; Hernández-Mijares, Antonio; Mantilla, Teresa; Millán, Jesús; Pedro-Botet, Juan

    Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of histologically similar to those induced by alcohol consumption in people with very little or no liver damage same. The importance of NAFLD is its high prevalence in our Western societies, from the point of view liver in its progressive evolution from steatosis to steatohepatitis, cirrhosis and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with accelerated atherosclerosis and cardiovascular events, the leading cause of morbidity and mortality. This updated January 2016 revision consists of two parts. In this second part, the treatment of NAFLD and its influence on cardiovascular disease and drugs used in the control of cardiovascular risk factors showing a beneficial effect on the liver disease will be reviewed. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Noninvasive markers of liver fibrosis: on-treatment changes of serum markers predict the outcome of antifibrotic therapy.

    PubMed

    Tanwar, Sudeep; Trembling, Paul M; Hogan, Brian J; Srivastava, Ankur; Parkes, Julie; Harris, Scott; Grant, Paul; Nastouli, Eleni; Ocker, Mathias; Wehr, Klaus; Herold, Christoph; Neureiter, Daniel; Schuppan, Detlef; Rosenberg, William M

    2017-03-01

    The utility of noninvasive serum markers to longitudinally monitor liver fibrosis is not established. A total of 70 patients with chronic hepatitis C who had previously failed antiviral therapy were randomized to receive pegylated interferon with or without silymarin for 24 months. Enhanced Liver Fibrosis (ELF) tests (hyularonic acid, terminal peptide of procollagen III, tissue inhibitor of matrix metaloproteinase-1) were performed on patient sera obtained before, during and at the end of the study (0, 12, 24 months) and liver histology obtained before and at the end of the study. At 24 months, absolute changes in Ishak fibrosis stage and ELF ranged from -4 to +4 and from -2.41 to +2.68, respectively. Absolute changes in ELF at 12 months were significantly associated with changes in both ELF and histology at 24 months. A model combining both baseline ELF and change of ELF at 12 months could predict the 24-month ELF (R=0.609, P<1×10), a decrease in ELF at 24 months [area under the curve (AUC): 0.80-0.85] and an increase in ELF at 24 months (AUC: 0.81-0.85). Furthermore, a model combining both baseline histologic stage and ELF together with the change of ELF at 12 months could predict 24-month histology (R=0.601, P<1×10, AUC: 0.88-0.92), histologic fibrosis regression (AUC: 0.81-0.84) and progression (AUC: 0.86-0.91). Our observations suggest that a change in the serum marker ELF predicts changes in liver fibrosis over a longer period. These data support the use of ELF as a surrogate marker of liver fibrosis evolution in monitoring antifibrotic treatments, thus permitting 'response-guided' therapy by the early identification of patients who will benefit from prolonged treatment.

  5. The effects of dexpanthenol in streptozotocin-induced diabetic rats: histological, histochemical and immunological evidences.

    PubMed

    Gulle, K; Ceri, N G; Akpolat, M; Arasli, M; Demirci, B

    2014-10-01

    This study was designed to investigate the effects of Dexpanthenol (Dxp) on liver and pancreas histology and cytokine levels in streptozotocine (STZ)-induced diabetic rats. Twenty-four Wistar albino male rats were divided into four groups: control, Dxp, STZ-induced diabetic (STZ) and diabetic treatment with Dexpanthenol (STZ-Dxp) groups. Experimental diabetes was induced by single dose STZ (50 mg/kg) intraperitoneally (i.p.). After administration of STZ, the STZ-Dxp group began to receive a 300 mg/kg/day i.p. dose of Dxp for 6 weeks. Liver and pancreas tissues of the control group were in normal morphology. Liver tissue of STZ group showed vacuolisation of hepatocytes in the liver parenchyma with enlargement of sinusoidal spaces and increasing amounts of connective tissue in the portal area. Pancreatic section of STZ group displayed β-cells with of cytoplasmic mass, reduction of islet size, and atrophy. The STZ-Dxp group that received Dxp treatment exhibit partially normal hepatic parenchyma. Histochemical examinations revealed that the diabetes-induced glycogen depletion markedly improved with the Dxp treatment (p⟨0.001). The severity of degenerative alteration was lessened by Dxp supplementation in the STZ-Dxp group. Induction of STZ presented a significant increase both in interleukin-1α (IL-1α) (p=0.033) and monocyte chemotactic protein-1 (MCP-1) (p=0.011) levels, when compared with the control rats. DXP-treated diabetic rats' IL-1α and MCP-1 levels were similar to control value. This evidence suggests that Dxp is effective in reducing STZ-induced, diabetic-related complications and may be beneficial for the treatment of diabetic patients.

  6. Liver pathology in Malawian children with fatal encephalopathy

    PubMed Central

    Whitten, Richard; Milner, Danny A.; Yeh, Matthew M.; Kamiza, Steve; Molyneux, Malcolm E.; Taylor, Terrie E.

    2010-01-01

    A common clinical presentation of Plasmodium falciparum is parasitemia complicated by an encephalopathy for which other explanations cannot be found, termed cerebral malaria—an important cause of death in young children in endemic areas. Our objective was to study hepatic histopathology in Malawian children with fatal encephalopathy, with and without P falciparum parasitaemia, in order to assess the contributions of severe malaria. We report autopsy results from a series of 87 Malawian children who died between 1996 and 2008. Among 75 cases with P falciparum parasitaemia, 51 had intracerebral sequestered parasites, while 24 without sequestered parasites had other causes of death revealed by autopsy including 4 patients with clinicopathological findings which may represent Reye’s Syndrome. Hepatic histology in parasitaemic cases revealed very limited sequestration of parasites in hepatic sinusoids, even in cases with extensive sequestration elsewhere, but increased numbers of hemozoin-laden Kupffer cells were invariably present with a strong association with histological evidence of cerebral malaria by quantitative analysis. Of 12 patients who were consistently aparasitaemic during their fatal illness, 5 had clinicopathological findings which may represent Reye’s Syndrome. Hepatic sequestration of parasitized erythrocytes is not a feature of fatal malaria in Malawian children, and there is no structural damage in the liver. Reye’s syndrome may be an important cause of fatal encephalopathy in children in Malawi with and without peripheral parasitemia and warrants close scrutiny of aspirin use in malaria endemic areas. PMID:21396681

  7. Microscale 3D Liver Bioreactor for In Vitro Hepatotoxicity Testing under Perfusion Conditions.

    PubMed

    Freyer, Nora; Greuel, Selina; Knöspel, Fanny; Gerstmann, Florian; Storch, Lisa; Damm, Georg; Seehofer, Daniel; Foster Harris, Jennifer; Iyer, Rashi; Schubert, Frank; Zeilinger, Katrin

    2018-03-15

    The accurate prediction of hepatotoxicity demands validated human in vitro models that can close the gap between preclinical animal studies and clinical trials. In this study we investigated the response of primary human liver cells to toxic drug exposure in a perfused microscale 3D liver bioreactor. The cellularized bioreactors were treated with 5, 10, or 30 mM acetaminophen (APAP) used as a reference substance. Lactate production significantly decreased upon treatment with 30 mM APAP ( p < 0.05) and ammonia release significantly increased in bioreactors treated with 10 or 30 mM APAP ( p < 0.0001), indicating APAP-induced dose-dependent toxicity. The release of prostaglandin E2 showed a significant increase at 30 mM APAP ( p < 0.05), suggesting an inflammatory reaction towards enhanced cellular stress. The expression of genes involved in drug metabolism, antioxidant reactions, urea synthesis, and apoptosis was differentially influenced by APAP exposure. Histological examinations revealed that primary human liver cells in untreated control bioreactors were reorganized in tissue-like cell aggregates. These aggregates were partly disintegrated upon APAP treatment, lacking expression of hepatocyte-specific proteins and transporters. In conclusion, our results validate the suitability of the microscale 3D liver bioreactor to detect hepatotoxic effects of drugs in vitro under perfusion conditions.

  8. Microscale 3D Liver Bioreactor for In Vitro Hepatotoxicity Testing under Perfusion Conditions

    PubMed Central

    Freyer, Nora; Greuel, Selina; Knöspel, Fanny; Gerstmann, Florian; Storch, Lisa; Damm, Georg; Seehofer, Daniel; Foster Harris, Jennifer; Iyer, Rashi; Schubert, Frank; Zeilinger, Katrin

    2018-01-01

    The accurate prediction of hepatotoxicity demands validated human in vitro models that can close the gap between preclinical animal studies and clinical trials. In this study we investigated the response of primary human liver cells to toxic drug exposure in a perfused microscale 3D liver bioreactor. The cellularized bioreactors were treated with 5, 10, or 30 mM acetaminophen (APAP) used as a reference substance. Lactate production significantly decreased upon treatment with 30 mM APAP (p < 0.05) and ammonia release significantly increased in bioreactors treated with 10 or 30 mM APAP (p < 0.0001), indicating APAP-induced dose-dependent toxicity. The release of prostaglandin E2 showed a significant increase at 30 mM APAP (p < 0.05), suggesting an inflammatory reaction towards enhanced cellular stress. The expression of genes involved in drug metabolism, antioxidant reactions, urea synthesis, and apoptosis was differentially influenced by APAP exposure. Histological examinations revealed that primary human liver cells in untreated control bioreactors were reorganized in tissue-like cell aggregates. These aggregates were partly disintegrated upon APAP treatment, lacking expression of hepatocyte-specific proteins and transporters. In conclusion, our results validate the suitability of the microscale 3D liver bioreactor to detect hepatotoxic effects of drugs in vitro under perfusion conditions. PMID:29543727

  9. Imaging-guided and nonimaging-guided fine needle aspiration of liver lesions: experience with 406 patients.

    PubMed

    Edoute, Y; Tibon-Fisher, O; Ben-Haim, S A; Malberger, E

    1991-12-01

    The aim of the present study was to determine the diagnostic accuracy of different modes of fine needle aspiration (FNA) of liver lesions. A total of 492 FNAs were performed on 406 patients in order to confirm or to rule out focal or multifocal neoplastic disease: 29% under ultrasound (US) guidance, 3% with computed tomographic (CT) guidance, 67% preoperatively, and 1% intraoperatively without imaging guidance. Based on histologic, cytologic, and clinical findings, final diagnoses were reached in 387 patients, of whom 264 had malignant liver disease and 123 had benign liver disease. Of 321 aspirations performed in patients with malignant liver disease, the cytologic findings suggested malignancy in 225 (70.1%), suspected malignancy in 25 (7.8%), and did not reveal malignancy in 71 aspirations (22.1%). Among the 123 patients with benign liver disease, the cytologic findings were reported as benign in all but two patients, who had false-positive cytologic findings. The overall sensitivity, specificity, positive, and negative predictive values for cytologic findings were 85.6, 98.4, 99.1, and 76.1%, respectively. The overall diagnostic accuracy was 89.7%. In one patient, fatal intraperitoneal bleeding due to chronic intravascular coagulation complicated the FNA procedure. We conclude that imaging-guided FNA as well as nonguided FNA for cytologic diagnosis of liver lesions are highly accurate and only rarely may be associated with a fatal complication.

  10. Does the phycotoxin Okadaic acid cause oxidative stress damages and histological alterations to seabream (Sparus aurata)?

    PubMed

    Souid, Ghada; Souayed, Nouha; Haouas, Zohra; Maaroufi, Khira

    2018-03-15

    Okadaic Acid (OA) is a marine toxin responsible for DSP (Diarrheic Shellfish Poisoning) in humans produced by dinoflagellate. The genotoxic and cytotoxic effects of OA have been well reported in mammalian experimental animals and in vitro cultured cells. However, there are no available investigations regarding the involvement of the oxidative stress pathways in OA toxicity, especially on aquatic animals such as fish. In this context, we aimed in the present work to demonstrate whether OA (7.5 μg/ml) induces oxidative stress and histopathological damages in the fish species Sparus aurata under short term exposure (2 h, 4 h and 24 h). To this end, we have assessed lipid peroxidation and anti-oxidative stress response in liver tissue, and finally ultrastructural changes were investigated in hepatic and gills tissues. Our results clearly showed that OA induced significant enhancement in all tested parameters in a time dependent manner and seems to be a strong inducer of oxidative stress in aquatic animals. The data of the present study indicate also that histology is a successful tool to reveal OA impact on liver and gill tissues of Sparus aurata since the animal showed vascular dilation and hepatocellular membrane disintegration in liver and hypertrophy in secondary lamellae and necrotic aspect in the primary lamellae in gill tissue. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Post-dive ultrasound detection of gas in the liver of rats and scuba divers.

    PubMed

    L'abbate, Antonio; Marabotti, Claudio; Kusmic, Claudia; Pagliazzo, Antonino; Navari, Alessandro; Positano, Vincenzo; Palermo, Mario; Benassi, Antonio; Bedini, Remo

    2011-09-01

    In a previous study, we obtained histologic documentation of liver gas embolism in the rat model of rapid decompression. The aim of the study was to assess in the same model occurrence and time course of liver embolism using 2-D ultrasound imaging, and to explore by this means putative liver gas embolism in recreational scuba divers. Following 42 min compression at 7 ATA breathing air and 12 min decompression, eight surviving female rats were anesthetized and the liver imaged by ultrasound at 20 min intervals up to 120 min. A significant enhancement of echo signal was recorded from 60 to 120 min as compared to earlier post-decompression times. Enzymatic markers of liver damage (AST, ALT, and GGT) increased significantly at 24 h upon decompression. Twelve healthy experienced divers were studied basally and at 15-min intervals up to 60 min following a 30-min scuba dive at 30 msw depth. At 30 min upon surfacing echo images showed significant signal enhancement that progressed and reached plateau at 45 and 60 min. Total bilirubin at 24 h increased significantly (p = 0.02) with respect to basal values although within the reference range. In conclusion, 2-D ultrasound liver imaging allowed detection of gas embolism in the rat and defined the time course of gas accumulation. Its application to scuba divers revealed liver gas accumulation in all subjects in the absence of clear-cut evidence of liver damage or of any symptom. The clinical significance of our findings remains to be investigated.

  12. High regenerative capacity of the liver and irreversible injury of male reproductive system in carbon tetrachloride-induced liver fibrosis rat model.

    PubMed

    Bubnov, Rostyslav V; Drahulian, Maria V; Buchek, Polina V; Gulko, Tamara P

    2018-03-01

    Liver fibrosis (LF) is a chronic disease, associated with many collateral diseases including reproductive dysfunction. Although the normal liver has a large regenerative capacity the complications of LF could be severe and irreversible. Hormone and sex-related issues of LF development and interactions with male reproductive have not been finally studied. The aim was to study the reproductive function of male rats in experimental CCl 4 -induced liver fibrosis rat model, and the capability for restoration of both the liver and male reproduction system. Studies were conducted on 20 3-month old Wistar male rats. The experimental animals were injected with freshly prepared 50% olive oil solution of carbohydrate tetrachloride (CCl 4 ). On the 8th week after injection we noted the manifestations of liver fibrosis. The rats were left to self-healing of the liver for 8 weeks. All male rats underwent ultrasound and biopsy of the liver and testes on the 8th and 16th weeks. The male rats were mated with healthy females before CCl 4 injection, after modeling LF on the 8th week, and after self-healing of the liver. Pregnancy was monitored on ultrasound. On the 8th week of experiment we observed ultrasound manifestation of advanced liver fibrosis, including hepatosplenomegaly, portal hypertension. Ultrasound exam of the rat testes showed testicular degeneration, hydrocele, fibrosis, scarring, petrifications, size reduction, and restriction of testicular descent; testes size decreased from 1.24 ± 0.62 ml to 0.61 ± 0.13, p  < 0.01. Liver histology showed granular dystrophy of hepatocytes, necrotic areas, lipid inclusions in parenchyma. Rats with liver fibrosis demonstrated severe injury of the reproductive system and altering of fertility: the offspring of male rats with advanced LF was 4.71 ± 0.53 born alive vs 9.55 ± 0.47 born from mating with healthy males, p  < 0.001. Eight weeks after last CCl 4 injection, we revealed signs of liver regeneration, significant

  13. A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver.

    PubMed

    Im, Hwi-Jin; Kim, Hyeong-Geug; Lee, Jin-Seok; Kim, Hyo-Seon; Cho, Jung-Hyo; Jo, Il-Joo; Park, Sung-Joo; Son, Chang-Gue

    2016-04-01

    Liver metastasis is the main cause of death from colorectal cancer. Alcohol consumption impacts liver function and is suggested to be an independent risk factor for liver metastasis of colorectal cancer, but no experimental evidence supporting this hypothesis has been demonstrated to date. In this study, we investigated the effect of alcohol intake on liver metastasis. We examined colon cancer cell spread from the spleen in mice provided with water (control group), alcohol for 4 weeks before tumor injection (prealcohol), alcohol for 3 weeks after tumor injection (postalcohol), or alcohol throughout the 7-week study (alcohol). Alcohol intake significantly increased hepatic metastatic burden in the prealcohol (2.4-fold, P < 0.001), postalcohol (2.0-fold, P < 0.01), and alcohol groups (2.2-fold, P < 0.001). A fluorescence-based metastasis tracking assay also confirmed an alcohol-induced increase in the abundance of tumor cells in the liver (2.5-fold, P < 0.001). Investigation of the host microenvironment revealed an alcohol-induced inflammatory response marked by elevated TNFα, IL1β, IL6, and IFNγ protein levels, as well as increased expression of intercellular molecule-1 (ICAM1) in hepatic tissues after 4 weeks of alcohol consumption. Moreover, the peripheral blood of mice provided with alcohol for 4 weeks exhibited reduced natural killer and CD8(+) T-cell counts. Collectively, our findings suggest that chronic alcohol consumption accelerates liver metastasis of colorectal cancer cells through alterations to the liver microenvironment and inactivation of immune surveillance. Cancer Res; 76(7); 1698-704. ©2016 AACR. ©2016 American Association for Cancer Research.

  14. Histology Atlas of the Developing Mouse Hepatobiliary System with Emphasis on Embryonic Days 9.5-18.5

    PubMed Central

    Crawford, Laura Wilding; Foley, Julie F.; Elmore, Susan A.

    2012-01-01

    Animal model phenotyping, in utero exposure toxiciy studies, and investigation into causes of embryonic, fetal, or perinatal deaths have required pathologists to recognize and diagnose developmental disorders in spontaneous and engineered mouse models of disease. In mammals, the liver is the main site of hematopoiesis during fetal development, has endocrine and exocrine functions important for maintaining homeostasis in fetal and adult life; and performs other functions including waste detoxification, production and removal of glucose, glycogen storage, triglyceride and fatty acid processing, and serum protein production. Due to its role in many critical functions, alterations in the size, morphology, or function(s) of the liver often lead to embryonic lethality. Many publications and websites describe individual aspects of hepatobiliary development at defined stages. However, no single resource provides a detailed histological evaluation of H&E-stained sections of the developing murine liver and biliary systems using high-magnification and high-resolution color images. The work herein provides a histology atlas of hepatobiliary development between embryonic days 9.5-18.5. Although the focus of this work is normal hepatobiliary development, common defects in liver development are also described as a reference for pathologists who may be asked to phenotype mice with congenital, inherited, or treatment-related hepatobiliary defects. PMID:20805319

  15. Approach to the patient with abnormal liver tests.

    PubMed

    Mahl, T C

    1998-01-01

    Patients with abnormal liver blood tests are frequently encountered by primary care practitioners. An understanding of the cellular implications of these abnormalities is helpful in determining the etiology of liver injury. Elevated serum aminotransferases suggest injury of hepatocytes. Elevations in alkaline phosphatase suggest injury to any part of the biliary tree. Neither of these enzymes measures liver function. Serum bilirubin and albumin levels, as well as prothrombin time, do measure function and can be used in conjunction with the physical examination and the specific etiology of the patient's disorder to determine a patient's prognosis. Many diverse disorders result in similar biochemical patterns of liver injury. The history, physical examination, and use of specific disease markers (hepatitis serology, autoimmune markers, and so forth) help to narrow the differential diagnosis. The definitive diagnosis of all liver diseases usually rests on histology: the liver biopsy is the gold standard. With the advent of treatments for liver disease, identifying and accurately diagnosing patients with liver disorders will result in improved quality of life and survival.

  16. Sleep apnea hypopnea syndrome and liver injury.

    PubMed

    Tian, Jian-li; Zhang, Yun; Chen, Bao-yuan

    2010-01-05

    A general review was made of studies involving: (1) the relationship between sleep apnea hypopnea syndrome/sleep apnea style intermittent hypoxia and liver injury and (2) the mechanism that causes the liver injury. The data used in this review were mainly from Medline and PubMed published in English from 1993 to February 2009. The search term was "sleep apnea hypopnea syndrome". (1) Clinical and laboratory evidence that sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia leads to liver injury; (2) the mechanism that causes the liver injury. The effect of sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia on the liver function is characterized by serum aminotransferase elevation. The liver histological injury includes hepatic steatosis, hepatocyte ballooning, lobular inflammation, lobular necrosis, and liver fibrosis. Sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia can cause insulin resistance and oxidative stress. Sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia can lead to chronic liver injury, which, in most cases, is shown as nonalcoholic fatty liver disease. Insulin resistance and oxidative stress caused by sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia play an important role in the mechanism of chronic liver disease development.

  17. Application of a quantitative histological health index for Antarctic rock cod (Trematomus bernacchii) from Davis Station, East Antarctica.

    PubMed

    Corbett, Patricia A; King, Catherine K; Mondon, Julie A

    2015-08-01

    A quantitative Histological Health Index (HHI) was applied to Antarctic rock cod (Trematomus bernacchii) using gill, liver, spleen, kidney and gonad to assess the impact of wastewater effluent from Davis Station, East Antarctica. A total of 120 fish were collected from 6 sites in the Prydz Bay region of East Antarctica at varying distances from the wastewater outfall. The HHI revealed a greater severity of alteration in fish at the wastewater outfall, which decreased stepwise with distance. Gill and liver displayed the greatest severity of alteration in fish occurring in close proximity to the wastewater outfall, showing severe and pronounced alteration respectively. Findings of the HHI add to a growing weight of evidence indicating that the current level of wastewater treatment at Davis Station is insufficient to prevent impact to the surrounding environment. The HHI for T. bernacchii developed in this study is recommended as a useful risk assessment tool for assessing in situ, sub-lethal impacts from station-derived contamination in coastal regions throughout Antarctica. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: The liver disease of our age?

    PubMed Central

    Firneisz, Gábor

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients. PMID:25083080

  19. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age?

    PubMed

    Firneisz, Gábor

    2014-07-21

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.

  20. [Histomorphology of the liver by damage with phenolisatine-containing laxatives (Recurrent chronic cholangiohepatitis)].

    PubMed

    Lüders, C J; Riske, W E; Henning, H; Vogel, H M

    1975-01-01

    In the case of 36 female patients who were anamnestically known to have taken laxatives, semiquantitative histological investigations with laparoscopically obtained liver needle biopsies were effected after the exposition with preparations containing phenolisatine. The time gap until exposition was 12 to 24 h (16 cases), 48 h (8 cases), 72 to 96 h (4 cases) and 7 to 14 days (4 cases). The histological result after the exposition is an acute cholangiolitis of the allergic-hyperergic type with edema and a dense eosinophile infiltration of the portal fields with destruction of the epithelium of preformed bile ducts and portally proliferated ductles. In addition, the parenchyma of the liver shows a pleomorphism of the cells in form and colour with a cellular edema and with disseminated acidophilic necroses and necrobioses of the individual cells as well as with little reactive proliferation of the Kupffer's cell. After a period of 8 days the acute process has more or less subsided. Also, in the majority of cases there are histological signs of an aggressive chronic hepatitis of type IIa, partially in the active stage with piece-meal necroses and partially stabilized or in the process of healing. A transition to the picture of hepatitic cirrhosis is possible. In serious cases the picture of a chronic non-purulent destructive cholangitis can be simulated by the hepatocellular and canalicular damage. Thirty-one bioptic pre-examinations from the same results, whereby the acute cholangiolitical exacerbation can be attributed to an exposition of the patients themselves. The clinical picture of the phenolisatine damage in its entirety is induced by medication and is described as a recurrent chronic cholangiohepatitis. Similarities exist between the liver damages caused by chlorpromazine and arsphenamine. When medication is discontinued, the morphologic substrate recedes leaving behind an inactive fibrosis or cirrhosis. The formal and known causal pathogenetic connections are

  1. Phlebotomy improves histology in chronic hepatitis C males with mild iron overload

    PubMed Central

    Sartori, Massimo; Andorno, Silvano; Rossini, Angelo; Boldorini, Renzo; Bozzola, Cristina; Carmagnola, Stefania; Piano, Mario Del; Albano, Emanuele

    2010-01-01

    AIM: To investigate the usefulness of mild iron depletion and the factors predictive for histological improvement following phlebotomy in Caucasians with chronic hepatitis C (CHC). METHODS: We investigated 28 CHC Caucasians with persistently elevated serum aminotransferase levels and non responders to, or unsuitable for, antiviral therapy who underwent mild iron depletion (ferritin ≤ 70 ng/mL) by long-term phlebotomy. Histological improvement, as defined by at least one point reduction in the staging score or, in case of unchanged stage, as at least two points reduction in the grading score (Knodell), was evaluated in two subsequent liver biopsies (before and at the end of phlebotomy, 48 ± 16 mo apart). RESULTS: Phlebotomy showed an excellent safety profile. Histological improvement occurred in 12/28 phlebotomized patients. Only males responded to phlebotomy. At univariate logistic analysis alcohol intake (P = 0.034), high histological grading (P = 0.01) and high hepatic iron concentration (HIC) (P = 0.04) before treatment were associated with histological improvement. Multivariate logistic analysis showed that in males high HIC was the only predictor of histological improvement following phlebotomy (OR = 1.41, 95% CI: 1.03-1.94, P = 0.031). Accordingly, 12 out of 17 (70%) patients with HIC ≥ 20 μmol/g showed histological improvements at the second biopsy. CONCLUSION: Male CHC Caucasian non-responders to antiviral therapy with low-grade iron overload can benefit from mild iron depletion by long-term phlebotomy. PMID:20128028

  2. Chronic hepatitis in the English springer spaniel: clinical presentation, histological description and outcome.

    PubMed

    Bexfield, N H; Andres-Abdo, C; Scase, T J; Constantino-Casas, F; Watson, P J

    2011-10-15

    Medical records and liver histology of 68 English springer spaniels (ESS) with a histological diagnosis of CH were reviewed retrospectively. PCR was performed on liver tissue for canine adenovirus-1 (CAV-1), canine parvovirus, canine herpesvirus and pathogenic Leptospira species. Follow-up information was obtained to calculate survival times. Median age at presentation was three years seven months (range, seven months to eight years five months) and there were 48 female and 20 male dogs. Clinical signs were non-specific and five dogs were asymptomatic. All dogs had an increase in serum activity of one or more hepatobiliary enzymes. Histopathology demonstrated hepatocyte necrosis and apoptosis with varying amounts of fibrosis. A predominantly lymphoplasmacytic infiltrate throughout the hepatic parenchyma was found in all 68 dogs, but 45 of these dogs also had a neutrophilic component to the inflammatory infiltrate. There was no significant copper accumulation and no aetiological agent was identified by PCR. The median survival time was 189 days (range, 1 to 1211 days), 38 dogs died within three months and 12 dogs survived more than a year following diagnosis.

  3. Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance

    PubMed Central

    Stål, Per

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis (stage F3) and cirrhosis (stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers (e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques (transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD. PMID:26494963

  4. Non invasive evaluation of liver fibrosis in paediatric patients with nonalcoholic steatohepatitis.

    PubMed

    Iacobellis, Angelo; Marcellini, Matilde; Andriulli, Angelo; Perri, Francesco; Leandro, Gioacchino; Devito, Rita; Nobili, Valerio

    2006-12-28

    To identify the independent predictors of hepatic fibrosis in 69 children with nonalcoholic steatohepatitis (NASH) due to nonalcoholic fatty liver disease (NAFLD). All patients with clinically suspected NASH underwent liver biopsy as a confirmatory test. The following clinical and biochemical variables at baseline were examined as likely predictors of fibrosis at histology: age, body mass index (BMI), systolic blood pressure (SBP), dyastolic blood pressure (DBP), fasting glucose, fasting insulin, homeostatic model assessment for insulin resistence (HOMA-IR), cholesterol, tryglicerides, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT ratio, gamma glutamil transferase (GT), platelet count, prothrombin time (PT). At histology 28 (40.6%) patients had no fibrosis and 41 (59.4%) had mild to bridging fibrosis. At multivariate analysis, BMI > 26.3 was the only independent predictor of fibrosis (OR = 5.85, 95% CI = 1.6-21). BMI helps identify children with NASH who might have fibrotic deposition in the liver.

  5. Thermal fixation of swine liver tissue after magnetic resonance-guided high-intensity focused ultrasound ablation.

    PubMed

    Courivaud, Frédéric; Kazaryan, Airazat M; Lund, Alice; Orszagh, Vivian C; Svindland, Aud; Marangos, Irina Pavlik; Halvorsen, Per Steinar; Jebsen, Peter; Fosse, Erik; Hol, Per Kristian; Edwin, Bjørn

    2014-07-01

    The aim of this study was to investigate experimental conditions for efficient and controlled in vivo liver tissue ablation by magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU) in a swine model, with the ultimate goal of improving clinical treatment outcome. Histological changes were examined both acutely (four animals) and 1 wk after treatment (five animals). Effects of acoustic power and multiple sonication cycles were investigated. There was good correlation between target size and observed ablation size by thermal dose calculation, post-procedural MR imaging and histopathology, when temperature at the focal point was kept below 90°C. Structural histopathology investigations revealed tissue thermal fixation in ablated regions. In the presence of cavitation, mechanical tissue destruction occurred, resulting in an ablation larger than the target. Complete extra-corporeal MR-guided HIFU ablation in the liver is feasible using high acoustic power. Nearby large vessels were preserved, which makes MR-guided HIFU promising for the ablation of liver tumors adjacent to large veins. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  6. Transient elastography for the assessment of chronic liver disease: Ready for the clinic?

    PubMed Central

    Cobbold, JFL; Morin, S; Taylor-Robinson, SD

    2007-01-01

    Transient elastography is a recently developed non-invasive technique for the assessment of hepatic fibrosis. The technique has been subject to rigorous evaluation in a number of studies in patients with chronic liver disease of varying aetiology. Transient elastography has been compared with histological assessment of percutaneous liver biopsy, with high sensitivity and specificity for the diagnosis of cirrhosis, and has also been used to assess pre-cirrhotic disease. However, the cut-off values between different histological stages vary substantially in different studies, patient groups and aetiology of liver disease. More recent studies have examined the possible place of transient elastography in clinical practice, including risk stratification for the development of complications of cirrhosis. This review describes the technique of transient elastography and discusses the interpretation of recent studies, emphasizing its applicability in the clinical setting. PMID:17828808

  7. Integrated analysis of microRNA and gene expression profiles reveals a functional regulatory module associated with liver fibrosis.

    PubMed

    Chen, Wei; Zhao, Wenshan; Yang, Aiting; Xu, Anjian; Wang, Huan; Cong, Min; Liu, Tianhui; Wang, Ping; You, Hong

    2017-12-15

    Liver fibrosis, characterized with the excessive accumulation of extracellular matrix (ECM) proteins, represents the final common pathway of chronic liver inflammation. Ever-increasing evidence indicates microRNAs (miRNAs) dysregulation has important implications in the different stages of liver fibrosis. However, our knowledge of miRNA-gene regulation details pertaining to such disease remains unclear. The publicly available Gene Expression Omnibus (GEO) datasets of patients suffered from cirrhosis were extracted for integrated analysis. Differentially expressed miRNAs (DEMs) and genes (DEGs) were identified using GEO2R web tool. Putative target gene prediction of DEMs was carried out using the intersection of five major algorithms: DIANA-microT, TargetScan, miRanda, PICTAR5 and miRWalk. Functional miRNA-gene regulatory network (FMGRN) was constructed based on the computational target predictions at the sequence level and the inverse expression relationships between DEMs and DEGs. DAVID web server was selected to perform KEGG pathway enrichment analysis. Functional miRNA-gene regulatory module was generated based on the biological interpretation. Internal connections among genes in liver fibrosis-related module were determined using String database. MiRNA-gene regulatory modules related to liver fibrosis were experimentally verified in recombinant human TGFβ1 stimulated and specific miRNA inhibitor treated LX-2 cells. We totally identified 85 and 923 dysregulated miRNAs and genes in liver cirrhosis biopsy samples compared to their normal controls. All evident miRNA-gene pairs were identified and assembled into FMGRN which consisted of 990 regulations between 51 miRNAs and 275 genes, forming two big sub-networks that were defined as down-network and up-network, respectively. KEGG pathway enrichment analysis revealed that up-network was prominently involved in several KEGG pathways, in which "Focal adhesion", "PI3K-Akt signaling pathway" and "ECM

  8. Pattern of distant extrahepatic metastases in primary liver cancer: a SEER based study.

    PubMed

    Wu, Wenrui; He, Xingkang; Andayani, Dewi; Yang, Liya; Ye, Jianzhong; Li, Yating; Chen, Yanfei; Li, Lanjuan

    2017-01-01

    Background and Aims : Primary liver cancer remains still the common cause of cancer-related deaths globally and the prognosis for patients with extrahepatic metastasis is poor. The aim of our study was to assess extrahepatic metastatic pattern of different histological subtypes and evaluate prognostic effects of extrahepatic metastasis in patients with advanced disease. Methods: Based on the Surveillance, Epidemiology and End Results (SEER) database, eligible patients diagnosed with primary liver cancer was identified between 2010 to 2012. We adopted Chi-square test to compared metastasis distribution among different histological types. We compared survival difference of patients with different extrahepatic metastasises by Kaplan-Meier analysis. Cox proportional hazard models were performed to identify other prognostic factors of overall survival. Results: We finally identified 8677 patients who were diagnosed with primary liver cancer from 2010 to 2012 and 1775 patients were in distant metastasis stages. Intrahepatic cholangiocarcinoma was more invasive and had a higher percentage of metastasis compared with hepatocellular carcinoma. Lung was the most common metastasis and brain was the least common site for both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Extrahepatic metastasis could consider as an independent prognostic factor for patients with liver cancer. Patients with brain metastasis had the worst prognosis, compared with other metastasis in overall survival (OS) and cancer-specific survival (CSS) analysis. Conclusions: Different histological subtypes of liver cancer had different metastasis patterns. There were profound differences in risk of mortality among distant extrahepatic metastatic sites. Results from our studies would provide some information for follow-up strategies and future studies.

  9. Study of curcumin on microvasculature characteristic in diabetic rat's liver as revealed by vascular corrosion cast/scanning electron microscope (SEM) technique.

    PubMed

    Khimmaktong, Wipapan; Petpiboolthai, Hattaya; Panyarachun, Busaba; Anupunpisit, Vipavee

    2012-05-01

    To investigate the effect of curcumin on the structural change ofmicrovasculature in STZ-induced diabetic rat' liver. Diabetic rats were induced by streptozotocin (60 mg/kg BW). Male rats were divided into thre groups, control (C), diabetic (DM) and diabetic rats treated with curcumin (DMC) (200 mg/kg BW). After 8 weeks o experiments, blood vessels of rat's liver were studied under conventional light microscope (LM) and vascular corrosion cas technique with scanning electron microscope (SEM). LM observation demonstrated that there were pathology and destruction of liver tissues and microvasculature in diabetic animals. The sinusoids around central veins were dilated and filled with red blood cells. There was an accumulation of lipid droplets in the cytoplasm of hepatocytes and hepatocyte nuclei showed pathological sign of pyknosis. Moreover, the inflammation change of liver tissues revealed the infiltration of lymphocytes and increasing of collagen deposition in the area of portal triad. In curcumin-treated rats, the distinguished recovery of liver tissues showed regained normal pattern of central veins, sinusoids, hepatocytes and portal triad, when compared with liver tissues of control group. By using vascular corrosion casting with SEM, the liver blood vessels of DM group revealed higher and expanded sizes, compared with control group; proximal parts of portal veins (C = 577.75 +/- 126.23, DM = 892 +/- 35.79, DMC = 469.5 +/- 8553 microm), distal parts of portal veins (C = 76.72 +/- 1.48, DM = 200 +/- 31.05, DMC = 76.38 +/- 2.98 microm) and venules (C = 27.03 +/- 0.55, DM = 45.15 +/- 5.03, DMC = 28.38 +/- 3.67 microm) and corresponding to increased blood volumes compared with control group; proximal parts of portal veins (C = 20.8 +/- 1.28, DM = 62.2 +/- 3.39, DMC = 14.9 +/- 0.67 microm3), distal parts of portal veins (C = 0.46 +/- 0.03, DM = 3.81 +/- 0.18, DMC = 0.41 +/- 0.05 microm3) and venules (C = 0.05 +/- 0.05, DM = 0.24 +/- 0.013, DMC = 0.05 +/- 0

  10. Radiocolloid liver imaging in tuberculous hepatitis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Essop, A.R.; Posen, J.A.; Savitch, I.

    1984-02-01

    Twenty of 22 patients with tuberculous hepatitis had abnormal Tc-99m tin colloid liver scans. However, in the majority of the patients the changes were mild and nonspecific. The most frequent scintigraphic picture was a decreased uptake of the radiocolloid by the liver, with shunting to the spleen and bone marrow. The decreased hepatic uptake was usually mildly heterogeneous, but it was sometimes homogeneous, and in five patients obvious defects were present. The liver was enlarged in six patients and the spleen in six patients. Increased extrahepatic uptake of the radiocolloid was the only abnormality in five patients. The severity ofmore » the scintigraphic changes did not correlate with the following histologic findings: number of granulomas, degree of associated fibrosis, degree of hepatocyte swelling, or extent of fatty change.« less

  11. Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vila, Laia; Rebollo, Alba; Adalsteisson, Gunnar S.

    Consumption of beverages that contain fructose favors the increasing prevalence of metabolic syndrome alterations in humans, including non-alcoholic fatty liver disease (NAFLD). Although the only effective treatment for NAFLD is caloric restriction and weight loss, existing data show that atorvastatin, a hydroxymethyl-glutaryl-CoA reductase inhibitor, can be used safely in patients with NAFLD and improves hepatic histology. To gain further insight into the molecular mechanisms of atorvastatin's therapeutic effect on NAFLD, we used an experimental model that mimics human consumption of fructose-sweetened beverages. Control, fructose (10% w/v solution) and fructose + atorvastatin (30 mg/kg/day) Sprague-Dawley rats were sacrificed after 14 days.more » Plasma and liver tissue samples were obtained to determine plasma analytes, liver histology, and the expression of liver proteins that are related to fatty acid synthesis and catabolism, and inflammatory processes. Fructose supplementation induced hypertriglyceridemia and hyperleptinemia, hepatic steatosis and necroinflammation, increased the expression of genes related to fatty acid synthesis and decreased fatty acid {beta}-oxidation activity. Atorvastatin treatment completely abolished histological signs of necroinflammation, reducing the hepatic expression of metallothionein-1 and nuclear factor kappa B binding. Furthermore, atorvastatin reduced plasma (x 0.74) and liver triglyceride (x 0.62) concentrations, decreased the liver expression of carbohydrate response element binding protein transcription factor (x0.45) and its target genes, and increased the hepatic activity of the fatty acid {beta}-oxidation system (x 1.15). These effects may be related to the fact that atorvastatin decreased the expression of fructokinase (x 0.6) in livers of fructose-supplemented rats, reducing the metabolic burden on the liver that is imposed by continuous fructose ingestion. - Graphical Abstract: Display Omitted Research Highlights

  12. The Use of an Acellular Oxygen Carrier in a Human Liver Model of Normothermic Machine Perfusion.

    PubMed

    Laing, Richard W; Bhogal, Ricky H; Wallace, Lorraine; Boteon, Yuri; Neil, Desley A H; Smith, Amanda; Stephenson, Barney T F; Schlegel, Andrea; Hübscher, Stefan G; Mirza, Darius F; Afford, Simon C; Mergental, Hynek

    2017-11-01

    Normothermic machine perfusion of the liver (NMP-L) is a novel technique that preserves liver grafts under near-physiological conditions while maintaining their normal metabolic activity. This process requires an adequate oxygen supply, typically delivered by packed red blood cells (RBC). We present the first experience using an acellular hemoglobin-based oxygen carrier (HBOC) Hemopure in a human model of NMP-L. Five discarded high-risk human livers were perfused with HBOC-based perfusion fluid and matched to 5 RBC-perfused livers. Perfusion parameters, oxygen extraction, metabolic activity, and histological features were compared during 6 hours of NMP-L. The cytotoxicity of Hemopure was also tested on human hepatic primary cell line cultures using an in vitro model of ischemia reperfusion injury. The vascular flow parameters and the perfusate lactate clearance were similar in both groups. The HBOC-perfused livers extracted more oxygen than those perfused with RBCs (O2 extraction ratio 13.75 vs 9.43 % ×10 per gram of tissue, P = 0.001). In vitro exposure to Hemopure did not alter intracellular levels of reactive oxygen species, and there was no increase in apoptosis or necrosis observed in any of the tested cell lines. Histological findings were comparable between groups. There was no evidence of histological damage caused by Hemopure. Hemopure can be used as an alternative oxygen carrier to packed red cells in NMP-L perfusion fluid.

  13. Chronic CCl4 intoxication causes liver and bone damage similar to the human pathology of hepatic osteodystrophy: a mouse model to analyse the liver-bone axis.

    PubMed

    Nussler, Andreas K; Wildemann, Britt; Freude, Thomas; Litzka, Christian; Soldo, Petra; Friess, Helmut; Hammad, Seddik; Hengstler, Jan G; Braun, Karl F; Trak-Smayra, Viviane; Godoy, Patricio; Ehnert, Sabrina

    2014-04-01

    Patients with chronic liver diseases frequently exhibit decreased bone mineral densities (BMD), which is defined as hepatic osteodystrophy (HOD). HOD is a multifactorial disease whose regulatory mechanisms are barely understood. Thus, an early diagnosis and therapy is hardly possible. Therefore, the aim of our study consisted in characterizing a mouse model reflecting the human pathomechanism. Serum samples were collected from patients with chronic liver diseases and 12-week old C57Bl6/N mice after 6-week treatment with carbon tetrachloride (CCl4). Repetitive injections of CCl4 induced liver damage in mice, resembling liver fibrosis in patients, as assessed by serum analysis and histological staining. Although CCl4 did not affect primary osteoblast cultures, μCT analysis revealed significantly decreased BMD, bone volume, trabecular number and thickness in CCl4-treated mice. In both HOD patients and CCl4-treated mice, an altered vitamin D metabolism with decreased CYP27A1, CYP2R1, vitamin D-binding protein GC and increased 7-dehydrocholesterol reductase hepatic gene expression, results in decreased 25-OH vitamin D serum levels. Moreover, both groups exhibit excessively high active transforming growth factor-beta (TGF-β) serum levels, inhibiting osteoblast function in vitro. Summarizing, our mouse model presents possible mediators of HOD, e.g. altered vitamin D metabolism and increased active TGF-β. Liver damage and significant changes in bone structure and mineralization are already visible by μCT analysis after 6 weeks of CCl4 treatment. This fast response and easy transferability makes it an ideal model to investigate specific gene functions in HOD.

  14. HCV genotype 3 and squamous cell carcinoma antigen (SCCA)-IgM are independently associated with histological features of NASH in HCV-infected patients.

    PubMed

    Martini, A; Fattovich, G; Guido, M; Bugianesi, E; Biasiolo, A; Ieluzzi, D; Gallotta, A; Fassina, G; Merkel, C; Gatta, A; Negro, F; Pontisso, P

    2015-10-01

    Nonalcoholic steatohepatitis (NASH) enhances the risk of progressive liver disease. In chronic hepatitis C (CHC), liver steatosis is frequent, especially in genotype 3, but its clinical significance is debated. As squamous cell carcinoma antigen (SCCA)-IgM has been associated with advanced liver disease and risk of tumour development, we evaluated its occurrence in CHC and the possible relation with NASH at liver biopsy. Using a validated ELISA, serum SCCA-IgM was measured in 91 patients with CHC at the time of liver biopsy performed before antiviral treatment, at the end of treatment and 6 months thereafter, and in 93 HCV-negative patients with histological diagnosis of nonalcoholic fatty liver disease, as controls. SCCA-IgM was detected in 33% of CHC patients and in 4% of controls. This biomarker was found more elevated in CHC patients with histological NASH, and at multivariate analysis, SCCA-IgM and HCV genotype 3 were independently associated with NASH [OR (95% CI): 6.94 (1.21-40) and 27.02 (4.44-166.6)]. As predictors of NASH, HCV genotype 3 and SCCA-IgM had a specificity and a sensitivity of 97% and 44%, and of 95% and 27%, respectively. PPV and NPV were 80% and 86% for HCV genotype 3 vs 73% and 72% for SCCA-IgM. In patients with sustained virologic response to therapy, SCCA-IgM levels decreased significantly, while these remained unchanged in nonresponders. In conclusion, SCCA-IgM is detectable in one-third of patients with CHC and significantly correlates with histological NASH. © 2015 John Wiley & Sons Ltd.

  15. Immunohistochemical study of macrophage migration inhibitory factor in rat liver fibrosis induced by thioacetamide.

    PubMed

    Hori, Y; Sato, S; Yamate, J; Kurasaki, M; Nishihira, J; Hosokawa, T; Fujita, H; Saito, T

    2003-01-01

    Macrophage migration inhibitory factor (MIF) is a molecule known to regulate macrophage accumulation at sites of inflammation. To elucidate the role of MIF in progression of liver fibrosis, the immunohistochemical localization of MIF and macrophages in the liver were examined. Male Wistar rats received thioacetamide (TA) injections (200 mg/kg, i.p.) for 1 or 6 weeks. In biochemical and histological tests, it was confirmed that liver fibrosis was induced. In immunohistochemical analyses, the expression of MIF protein was seen in hepatocytes in the areas extending out from the central veins to the portal tracts. In particular, at 6 weeks, immunoreactivity was detected in degenerated hepatocytes adjacent to the fibrotic areas but hardly observed in the fibrotic areas. On the other hand, a number of exudate macrophages stained by antibody ED1 were seen in the areas from the central veins to the portal tracts at 1 week and in the fibrotic areas at 6 weeks. Macrophages also showed a significant increase in number as compared with controls. These results revealed that there was a close relationship between the appearance of MIF expression and ED1-positive exudate macrophages in degenerated hepatocytes during the progression of TA-induced liver fibrosis.

  16. Evaluation of the bioactive extract of actinomyces isolated from the Egyptian environment against aflatoxin B1-induce cytotoxicity, genotoxicity and oxidative stress in the liver of rats.

    PubMed

    El-Nekeety, Aziza A; Salman, Asmaa S; Hathout, Amal S; Sabry, Bassem A; Abdel-Aziem, Sekena H; Hassan, Nabila S; Abdel-Wahhab, Mosaad A

    2017-07-01

    This study aimed to determine the bioactive compounds of actinomyces (ACT) isolated from the Egyptian environment (D-EGY) and to evaluate their protective activity against AFB 1 in female Sprague-Dawley rats. Six groups of animals were treated orally for 3 weeks included: C, the control group, T1, AFB 1 -treated group (80 μg/kg b.w), T2 and T3, the groups received ACT extract at low (25 mg/kg b.w) or high (50 mg/kg b.w) doses, T4 and T5, the groups received AFB 1 plus the low or high dose of ACT extract. Blood, bone marrow and tissue samples were collected for different analyses and histological examination. The results revealed the identification of 40 components, representing 99.98%. Treatment with AFB 1 disturbs liver function parameters, oxidative stress markers, antioxidant gene expressions, DNA fragmentation and induced severe histological changes. ACT extract at the low or high doses did not induce significant changes in all the tested parameters or histological picture of the liver. Moreover, ACT extract succeeded to induce a significant protection against the toxicity of AFB 1 . It could be concluded that the bioactive compounds in ACT are promise candidate for the development of food additive or drugs for the protection and treatment of liver disorders in the endemic area. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Activity of essential phospholipids (EPL) from soybean in liver diseases.

    PubMed

    Gundermann, Karl-Josef; Kuenker, Ann; Kuntz, Erwin; Droździk, Marek

    2011-01-01

    Essential phospholipids (EPL) contain a highly purified extract of polyenylphosphatidylcholine (PPC) molecules from soybean. The main active ingredient is 1,2-dilinoleoylphosphatidylcholine (DLPC), which differentiates it from other phospholipids, lecithins, or extracts from other sources. Although EPLis widely used in liver diseases of various origins, its mode of action and pharmacological and clinical evidence of its efficacy have not yet been concisely reviewed. This paper critically summarizes experimental and clinical results. With regard to in-vitro and animal tests, EPL influenced membrane-dependent cellular functions and showed anti-oxidant, anti-inflammatory, anti-fibrotic, apoptosis-modulating, regenerative, membrane-repairing and -protective, cell-signaling and receptor-influencing, as well as lipid-regulating effects in intoxication models with chemicals or drugs. Clinical studies, primarily from European and Asian countries, have shown improvement in subjective symptoms; clinical, biochemical and imaging findings; and histology in liver indications such as fatty liver of different origin, drug hepatotoxicity, and adjuvant in chronic viral hepatitis and hepatic coma. The available studies characterize EPL as evidence-based medicine, although further long-term controlled clinical trials are required to precisely determine its benefit for alleviating symptoms, improving well-being, inducing histological changes and slowing the progression of liver disease. EPL-related relevant side effects were not observed.

  18. Morphometric investigations on the portal tracts of the liver, the differentiation of variable progression in chronic persistent hepatitis.

    PubMed

    Volmer, J; Lüders, C J

    1981-01-01

    Morphometric investigations were carried out on the portal tracts of the liver in different forms of chronic hepatitis. The investigation groups each contained 25 liver biopsies, which were subdivided into cases with normal liver, a subsiding acute virus hepatitis, three different forms of chronic persistent hepatitis (CPH) and chronic aggressive hepatitis type IIa (CAH IIa). Determinations of the volume and surface of the portal tracts and their components enabled three forms of COH (type Ia, Ib, Ic) to be characterised. Preliminary clinical and semiquantitative histological investigations were correlated with a significant difference in the histological characteristics and prognosis. HBsAg-positive and HBsAg-negative cases showed no significant morphologically detectable differences in all grups investigated. Morphometry is suitable for investigation of pathological changes in liver tissue, especially the portal tracts.

  19. Levosimendan: a cardiovascular drug to prevent liver ischemia-reperfusion injury?

    PubMed

    Onody, Peter; Stangl, Rita; Fulop, Andras; Rosero, Oliver; Garbaisz, David; Turoczi, Zsolt; Lotz, Gabor; Rakonczay, Zoltan; Balla, Zsolt; Hegedus, Viktor; Harsanyi, Laszlo; Szijarto, Attila

    2013-01-01

    Temporary occlusion of the hepatoduodenal ligament leads to an ischemic-reperfusion (IR) injury in the liver. Levosimendan is a new positive inotropic drug, which induces preconditioning-like adaptive mechanisms due to opening of mitochondrial KATP channels. The aim of this study was to examine possible protective effects of levosimendan in a rat model of hepatic IR injury. Levosimendan was administered to male Wistar rats 1 hour (early pretreatment) or 24 hours (late pretreatment) before induction of 60-minute segmental liver ischemia. Microcirculation of the liver was monitored by laser Doppler flowmeter. After 24 hours of reperfusion, liver and blood samples were taken for histology, immuno- and enzyme-histochemistry (TUNEL; PARP; NADH-TR) as well as for laboratory tests. Furthermore, liver antioxidant status was assessed and HSP72 expression was measured. In both groups pretreated with levosimendan, significantly better hepatic microcirculation was observed compared to respective IR control groups. Similarly, histological damage was also reduced after levosimendan administration. This observation was supported by significantly lower activities of serum ALT (p early = 0.02; p late = 0.005), AST (p early = 0.02; p late = 0.004) and less DNA damage by TUNEL test (p early = 0.05; p late = 0.034) and PAR positivity (p early = 0.02; p late = 0.04). Levosimendan pretreatment resulted in significant improvement of liver redox homeostasis. Further, significantly better mitochondrial function was detected in animals receiving late pretreatment. Finally, HSP72 expression was increased by IR injury, but it was not affected by levosimendan pretreatment. Levosimendan pretreatment can be hepatoprotective and it could be useful before extensive liver resection.

  20. Levosimendan: A Cardiovascular Drug to Prevent Liver Ischemia-Reperfusion Injury?

    PubMed Central

    Fulop, Andras; Rosero, Oliver; Garbaisz, David; Turoczi, Zsolt; Lotz, Gabor; Rakonczay, Zoltan; Balla, Zsolt; Hegedus, Viktor; Harsanyi, Laszlo; Szijarto, Attila

    2013-01-01

    Introduction Temporary occlusion of the hepatoduodenal ligament leads to an ischemic-reperfusion (IR) injury in the liver. Levosimendan is a new positive inotropic drug, which induces preconditioning-like adaptive mechanisms due to opening of mitochondrial KATP channels. The aim of this study was to examine possible protective effects of levosimendan in a rat model of hepatic IR injury. Material and Methods Levosimendan was administered to male Wistar rats 1 hour (early pretreatment) or 24 hours (late pretreatment) before induction of 60-minute segmental liver ischemia. Microcirculation of the liver was monitored by laser Doppler flowmeter. After 24 hours of reperfusion, liver and blood samples were taken for histology, immuno- and enzyme-histochemistry (TUNEL; PARP; NADH-TR) as well as for laboratory tests. Furthermore, liver antioxidant status was assessed and HSP72 expression was measured. Results In both groups pretreated with levosimendan, significantly better hepatic microcirculation was observed compared to respective IR control groups. Similarly, histological damage was also reduced after levosimendan administration. This observation was supported by significantly lower activities of serum ALT (pearly = 0.02; plate = 0.005), AST (pearly = 0.02; plate = 0.004) and less DNA damage by TUNEL test (pearly = 0.05; plate = 0.034) and PAR positivity (pearly = 0.02; plate = 0.04). Levosimendan pretreatment resulted in significant improvement of liver redox homeostasis. Further, significantly better mitochondrial function was detected in animals receiving late pretreatment. Finally, HSP72 expression was increased by IR injury, but it was not affected by levosimendan pretreatment. Conclusion Levosimendan pretreatment can be hepatoprotective and it could be useful before extensive liver resection. PMID:24040056

  1. Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease.

    PubMed

    Pereira, Evelyn Nunes Goulart da Silva; Silvares, Raquel Rangel; Flores, Edgar Eduardo Ilaquita; Rodrigues, Karine Lino; Ramos, Isalira Peroba; da Silva, Igor José; Machado, Marcelo Pelajo; Miranda, Rosiane Aparecida; Pazos-Moura, Carmen Cabanelas; Gonçalves-de-Albuquerque, Cassiano F; Faria-Neto, Hugo Caire de Castro; Tibiriça, Eduardo; Daliry, Anissa

    2017-01-01

    This study aimed to investigate the pathophysiology of hepatic microcirculatory dysfunction in non-alcoholic fatty liver disease (NAFLD). In Wistar rats, NAFLD model was induced by 20 weeks of high-fat diet (HFD) feeding. Rolling and adhesion of leukocytes and tissue perfusion in hepatic microcirculation were examined using in vivo microscopic and laser speckle contrast imaging (LSCI), respectively. Oxidative stress and inflamatory parameters were analysed by TBARs, catalase enzyme activity, RT-PCR and ELISA. The participation of advanced glycation end-products (AGE) and its receptor RAGE was evaluated by the measurement of gene and protein expression of RAGE by RT-PCR and Western-blot, respectively and by liver and serum quantification of fluorescent AGEs. Wistar rats fed high-fat diet (HFD) showed increase in epididymal and abdominal fat content, systolic arterial blood pressure, fasting blood glucose levels, hepatic triglycerides and cholesterol, and impairment of glucose and insulin metabolisms. Liver histology confirmed the presence of steatosis and ultrasound analysis revealed increased liver size and parenchymal echogenicity in HFD-fed rats. HFD causes significant increases in leukocyte rolling and adhesion on hepatic microcirculation and decrease in liver microvascular blood flow. Liver tissue presented increase in oxidative stress and inflammtion. At 20 weeks, there was a significantly increase in AGE content in the liver and serum of HFD-fed rats and an increase in RAGE gene expression in the liver. The increase in liver AGE levels and microcirculatory disturbances could play a role in the pathogenesis of liver injury and are key components of NAFLD.

  2. Gas embolization of the liver in a rat model of rapid decompression.

    PubMed

    L'Abbate, Antonio; Kusmic, Claudia; Matteucci, Marco; Pelosi, Gualtiero; Navari, Alessandro; Pagliazzo, Antonino; Longobardi, Pasquale; Bedini, Remo

    2010-08-01

    Occurrence of liver gas embolism after rapid decompression was assessed in 31 female rats that were decompressed in 12 min after 42 min of compression at 7 ATA (protocol A). Sixteen rats died after decompression (group I). Of the surviving rats, seven were killed at 3 h (group II), and eight at 24 h (group III). In group I, bubbles were visible in the right heart, aortic arch, liver, and mesenteric veins and on the intestinal surface. Histology showed perilobular microcavities in sinusoids, interstitial spaces, and hepatocytes. In group II, liver gas was visible in two rats. Perilobular vacuolization and significant plasma aminotransferase increase were present. In group III, liver edema was evident at gross examination in all cases. Histology showed perilobular cell swelling, vacuolization, or hydropic degeneration. Compared with basal, enzymatic markers of liver damage increased significantly. An additional 14 rats were decompressed twice (protocol B). Overall mortality was 93%. In addition to diffuse hydropic degeneration, centrilobular necrosis was frequently observed after the second decompression. Additionally, 10 rats were exposed to three decompression sessions (protocol C) with doubled decompression time. Their mortality rate decreased to 20%, but enzymatic markers still increased in surviving rats compared with predecompression, and perilobular cell swelling and vacuolization were present in five rats. Study challenges were 1) liver is not part of the pathophysiology of decompression in the existing paradigm, and 2) although significant cellular necrosis was observed in few animals, zonal or diffuse hepatocellular damage associated with liver dysfunction was frequently demonstrated. Liver participation in human decompression sickness should be looked for and clinically evaluated.

  3. Diffusion-weighted MRI in intrahepatic bile duct adenoma arising from the cirrhotic liver.

    PubMed

    An, Chansik; Park, Sumi; Choi, Yoon Jung

    2013-01-01

    A 64-year-old male patient with liver cirrhosis underwent a CT study for hepatocellular carcinoma surveillance, which demonstrated a 1.4-cm hypervascular subcapsular tumor in the liver. On gadoxetic acid-enhanced MRI, the tumor showed brisk arterial enhancement and persistent hyperenhancement in the portal phase, but hypointensity in the hepatobiliary phase. On diffusion-weighted MRI, the tumor showed an apparent diffusion coefficient twofold greater than that of the background liver parenchyma, which suggested that the lesion was benign. The histologic diagnosis was intrahepatic bile duct adenoma with alcoholic liver cirrhosis.

  4. Transcatheter intra-arterial infusion of doxorubicin loaded porous magnetic nano-clusters with iodinated oil for the treatment of liver cancer.

    PubMed

    Jeon, Min Jeong; Gordon, Andrew C; Larson, Andrew C; Chung, Jin Wook; Kim, Young Il; Kim, Dong-Hyun

    2016-05-01

    A promising strategy for liver cancer treatment is to deliver chemotherapeutic agents with multifunctional carriers into the tumor tissue via intra-arterial (IA) transcatheter infusion. These carriers should release drugs within the target tissue for prolonged periods and permit intra-procedural multi-modal imaging of selective tumor delivery. This targeted transcatheter delivery approach is enabled via the arterial blood supply to liver tumors and utilized in current clinical practice which is called chemoembolization or radioembolization. During our study, we developed Doxorubicin (Dox) loaded porous magnetic nano-clusters (Dox-pMNCs). The porous structure and carboxylic groups on the MNCs achieved high-drug loading efficiency and sustained drug release, along with magnetic properties resulting in high MRI T2-weighted image contrast. Dox-pMNC within iodinated oil, Dox-pMNCs, and Dox within iodinated oil were infused via hepatic arteries to target liver tumors in a rabbit model. MRI and histological evaluations revealed that the long-term drug release and retention of Dox-pMNCs within iodinated oil induced significantly enhanced liver cancer cell death. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Non invasive evaluation of liver fibrosis in paediatric patients with nonalcoholic steatohepatitis

    PubMed Central

    Iacobellis, Angelo; Marcellini, Matilde; Andriulli, Angelo; Perri, Francesco; Leandro, Gioacchino; Devito, Rita; Nobili, Valerio

    2006-01-01

    AIM: To identify the independent predictors of hepatic fibrosis in 69 children with nonalcoholic steatohepatitis (NASH) due to nonalcoholic fatty liver disease (NAFLD). METHODS: All patients with clinically suspected NASH underwent liver biopsy as a confirmatory test. The following clinical and biochemical variables at baseline were examined as likely predictors of fibrosis at histology: age, body mass index (BMI), systolic blood pressure (SBP), dyastolic blood pressure (DBP), fasting glucose, fasting insulin, homeostatic model assessment for insulin resistence (HOMA-IR), cholesterol, tryglicerides, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT ratio, gamma glutamil transferase (GT), platelet count, prothrombin time (PT). RESULTS: At histology 28 (40.6%) patients had no fibrosis and 41 (59.4%) had mild to bridging fibrosis. At multivariate analysis, BMI > 26.3 was the only independent predictor of fibrosis (OR = 5.85, 95% CI = 1.6-21). CONCLUSION: BMI helps identify children with NASH who might have fibrotic deposition in the liver. PMID:17203527

  6. Immunohistochemical and scanning electron microscopic comparison of the collagen network constructions between pig, goat and chicken livers.

    PubMed

    Nishimura, Shotaro; Sagara, Ayano; Oshima, Ichiro; Ono, Yoshitaka; Iwamoto, Hisao; Okano, Kaoru; Miyachi, Hideyuki; Tabata, Shoji

    2009-08-01

    The distribution and three-dimensional architecture of collagen fibers were compared between pig, goat and chicken livers. Immunohistochemical staining revealed that collagen type I was identified in the interlobular connective tissue region and intralobular areas in pigs and goats. Type III collagen was also identified in the interlobular connective tissue region and intralobular sinusoidal walls. In the chicken liver, only the circumference region of the vessels was immunostained with collagen type I and III antibodies and the interlobular connective tissue wall could not be distinguished clearly. In the intralobular region, collagen type I antibody immunoreacted around the hepatic cells but collagen type III antibody immunoreacted weakly. In the NaOH macerated specimen, well-developed collagen bundles formed the prominent interlobular walls in pigs. In contrast, the wall in the goat liver comprised a thin layer of the bundles. In the chicken liver, there were no notable collagen septa between lobules. The intralobular collagen construction was quite different between the animals, indicating a fragile collagen fibril networks in pigs, a robust framework in goats and dense fabric-like septa in chickens. These results indicate that the distinct collagen frameworks may contribute to the histological strength of the livers in each of the animal species.

  7. Metabolomics Reveals Aryl Hydrocarbon Receptor Activation Induces Liver and Mammary Gland Metabolic Dysfunction in Lactating Mice.

    PubMed

    Belton, Kerry R; Tian, Yuan; Zhang, Limin; Anitha, Mallappa; Smith, Philip B; Perdew, Gary H; Patterson, Andrew D

    2018-04-06

    The liver and the mammary gland have complementary metabolic roles during lactation. Substrates synthesized by the liver are released into the circulation and are taken up by the mammary gland for milk production. The aryl hydrocarbon receptor (AHR) has been identified as a lactation regulator in mice, and its activation has been associated with myriad morphological, molecular, and functional defects such as stunted gland development, decreased milk production, and changes in gene expression. In this study, we identified adverse metabolic changes in the lactation network (mammary, liver, and serum) associated with AHR activation using 1 H nuclear magnetic resonance (NMR)-based metabolomics. Pregnant mice expressing Ahr d (low affinity) or Ahr b (high affinity) were fed diets containing beta naphthoflavone (BNF), a potent AHR agonist. Mammary, serum, and liver metabolomics analysis identified significant changes in lipid and TCA cycle intermediates in the Ahr b mice. We observed decreased amino acid and glucose levels in the mammary gland extracts of Ahr b mice fed BNF. The serum of BNF fed Ahr b mice had significant changes in LDL/VLDL (increased) and HDL, PC, and GPC (decreased). Quantitative PCR analysis revealed ∼50% reduction in the expression of key lactogenesis mammary genes including whey acid protein, α-lactalbumin, and β-casein. We also observed morphologic and developmental disruptions in the mammary gland that are consistent with previous reports. Our observations support that AHR activity contributes to metabolism regulation in the lactation network.

  8. A histology-based fish health assessment of the tigerfish, Hydrocynus vittatus from a DDT-affected area

    NASA Astrophysics Data System (ADS)

    McHugh, K. J.; Smit, N. J.; Van Vuren, J. H. J.; Van Dyk, J. C.; Bervoets, L.; Covaci, A.; Wepener, V.

    The Pongolapoort Dam (PPD) in the Phongola River, Kwa-Zulu Natal, South Africa and the surrounding area are classified as intermediate to low risk malaria areas and are continually being treated with DDT for malaria vector control. DDT is known as an endocrine disrupting chemical posing estrogenic and anti-androgenic properties and therefore might impact on the health of the 18 freshwater fish species found within this system. Of these species the tigerfish, Hydrocynus vittatus, is targeted by both recreational and local subsistence fishermen and was recently included in the South African threatened or protected species list. Their protected status and importance as a food source therefore emphasises the need for their health status elucidation. Previous research on H. vittatus in the Phongola floodplain highlighted DDT biomagnification in this species. Recent data show that the sum of the DDT levels in February 2009 (5403.9 ng/g lipid) and July 2009 (5537.4 ng/g lipid) is still comparable to the high levels found 30 years earlier. The aim of the current study was thus to determine the health status of H. vittatus in relation to DDT exposure by means of a histology-based fish health assessment protocol. Tigerfish were collected in February 2009 ( n = 30) and July 2009 ( n = 15) and gill, kidney and liver tissue were subjected to histological analyses. Mean Index values showed that the Kidney Index ( IK), Gill Index ( IG) and Fish Index ( IFISH) were higher in fish from the February survey while the Liver Index was higher in those collected during July. Liver alterations identified included intercellular oedema, granular degeneration, vacuolation, nuclear pleomorphism and lymphocyte infiltration. Kidney alterations included dilation of the glomerulus capillaries, vacuolation and hyaline droplet degeneration. Gill alterations identified included telangiectasia and hyperplasia of the secondary lamella, congestion, and rupture of pillar cells. Although histological

  9. Impaired branched-chain amino acid metabolism may underlie the nonalcoholic fatty liver disease-like pathology of neonatal testosterone-treated female rats.

    PubMed

    Anzai, Álvaro; Marcondes, Rodrigo R; Gonçalves, Thiago H; Carvalho, Kátia C; Simões, Manuel J; Garcia, Natália; Soares, José M; Padmanabhan, Vasantha; Baracat, Edmund C; da Silva, Ismael D C G; Maciel, Gustavo A R

    2017-10-13

    Polycystic ovary syndrome (PCOS) is frequently associated with non-alcoholic fatty liver disease (NAFLD), but the mechanisms involved in the development of NAFLD in PCOS are not well known. We investigated histological changes and metabolomic profile in the liver of rat models of PCOS phenotype induced by testosterone or estradiol. Two-day old female rats received sc injections of 1.25 mg testosterone propionate (Testos; n = 10), 0.5 mg estradiol benzoate (E2; n = 10), or vehicle (control group, CNT; n = 10). Animals were euthanized at 90-94 d of age and the liver was harvested for histological and metabolomic analyses. Findings showed only Testos group exhibited fatty liver morphology and higher levels of ketogenic and branched-chain amino acids (BCAA). Enrichment analysis showed effects of testosterone on BCAA degradation pathway and mitochondrial enzymes related to BCAA metabolism. Testos group also had a decreased liver fatty acid elongase 2 (ELOVL2) activity. E2 group had reduced lipid and acylcarnitine metabolites in the liver. Both groups had increased organic cation transporters (SLC22A4 and SLC16A9) activity. These findings indicate that neonatal testosterone treatment, but not estradiol, produces histological changes in female rat liver that mimic NAFLD with testosterone-treated rats showing impaired BCAA metabolism and dysfunctions in ELOVL2, SLC22A4 and SLC16A9 activity.

  10. Effect of Boron Neutron Capture Therapy (BNCT) on Normal Liver Regeneration: Towards a Novel Therapy for Liver Metastases

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jorge E. Cardoso; Elisa M. Heber; David W. Nigg

    2007-10-01

    The “TAORMINA project” developed a new method for Boron Neutron Capture Therapy (BNCT) of human multifocal unresectable liver metastases based on whole liver ex-situ BNCT mediated by boronophenylalanine (BPA), followed by whole liver autograft. This technique involved a high risk, prolonged anhepatic phase. The Roffo Institute liver surgeons (JEC) herein propose a novel technique to pursue ex-situ liver BNCT studies with a drastically lower surgical risk for the patient. The technique would involve, sequentially, ex-situ BNCT of left liver segments II and III, partial liver autograft, and induction of partial atrophy of the untreated right liver. The working hypothesis ismore » that the atrophy of the right, untreated, diseased liver would stimulate regeneration of the left, treated, “cured” liver to yield a healthy liver mass, allowing for the resection of the remaining portion of diseased liver. This technique does not involve an anhepatic phase and would thus pose a drastically lower surgical risk to the patient but requires sine qua non that BNCT should not impair the regenerative capacity of normal hepatocytes. The aim of the present study was to assess the effect of therapeutic doses of BNCT mediated by BPA, GB-10 (Na2 10B10H10) or (GB- 10 + BPA) on normal liver regeneration in the Wistar rat employing partial hepatectomy as a regenerative stimulus. BNCT did not cause alterations in the outcome of normal liver regeneration, regenerated liver function or histology. We provide proof of principle to support the development of a novel, promising BNCT technique for the treatment of liver metastases.« less

  11. Review article: Non-alcoholic fatty liver disease in morbidly obese patients and the effect of bariatric surgery.

    PubMed

    De Ridder, R J J; Schoon, E J; Smulders, J F; van Hout, G C M; Stockbrügger, R W; Koek, G H

    2007-12-01

    Morbid obesity is strongly associated with non-alcoholic fatty liver disease. The effects of bariatric surgery on liver tests an histological abnormalities after weight loss are controversial. To review the literature on the prevalence of non-alcoholic fatty liver disease in patients with morbid obesity with respect to laboratory and histopathological parameters and the effect of weight loss on these parameters after bariatric surgery. Standard liver tests do not seem to be a sensitive tool for the assessment and follow-up of non-alcoholic fatty liver disease in obesity. In nearly all patients with morbid obesity, histological abnormalities reflecting non-alcoholic fatty liver disease are present. Bariatric surgery in these patients will decrease the grade of steatosis. However, there are some concerns about the effect of bariatric surgery on hepatic inflammation and fibrosis. In particular, older follow-up studies reported negative results as opposed to more recent studies, which also showed improvement in hepatic inflammation and fibrosis. Unfortunately, most studies had limitations because of the selection of patients. Despite limitations in many studies, bariatric surgery seems to be a promising treatment in patients with obesity presenting with non-alcoholic fatty liver disease.

  12. Role of autoimmunity in nonviral chronic liver disease.

    PubMed

    Amarapurkar, D N; Amarapurkar, A D

    2000-11-01

    To evaluate the prevalence and clinical profile of autoimmune hepatitis (AIH) in patients with chronic liver disease. Four hundred and thirty five consecutive patient with chronic liver disease seen in our department from January 1997 to December 1998 were studied with detailed history and clinical examination. All the patients underwent liver function tests, ultrasonography, isotope liver scanning, viral markers, autoimmune markers ANA, ASMA, LKM1 and AMA (by immunofluorescence technique) and liver histology whenever permissible. Appropriate work up for Wilson's disease was done whenever suspected clinically. Diagnosis of autoimmune hepatitis was made by the composite scoring system by international autoimmune hepatitis group. Twenty out of the 435 patients met the criteria of definite autoimmune hepatitis and seven patient had probable autoimmune hepatitis. Forty out of 408 patients showed markers of autoimmunity positive but did not qualify diagnosis of AIH on composite scores. Demographic profile of 27 patients with autoimmune hepatitis was as follows; male:female ratio 1:8, mean age 39.8 +/- 13 years (Range 4-65 years); mode of presentation as cirrhosis 11/27 (40.7%), chronic hepatitis 12/27 (44.4%) and acute hepatitis 4/27 (14.8%). Elevated serum bilirubin levels were seen in 12 (44.4%) patients while mean serum aminotransferases levels were 249 +/- 343 and 262 +/- 418 respectively. Other disease associations seen were as follows: diabetes in 4 (14.8%), rheumatoid arthritis in 3 (11%), hypothyroidism in 2 (7.4%) and ulcerative colitis in 1 (3.7%). The pattern of autoimmune markers was ANA +ve 23/27 (85%) (+ve titres of ANA > 1:80 in adults and 1:20 in children), ASMA +ve in 16/27 (59.2%) (+ve titres of ASMA > 1:40) and LKM1 in 3 patients. AMA in tires less than 1:80 was found in 3 patients. Liver histology changes seen were lymphoplasmacytic infiltrates (100%), bridging necrosis (93%), liver cell rossetting (80%) and fibrosis with or without cirrhosis (50

  13. Global Transcriptional Response of Human Liver Cells to Ethanol Stress of Different Strength Reveals Hormetic Behavior.

    PubMed

    Schmidt-Heck, Wolfgang; Wönne, Eva C; Hiller, Thomas; Menzel, Uwe; Koczan, Dirk; Damm, Georg; Seehofer, Daniel; Knöspel, Fanny; Freyer, Nora; Guthke, Reinhard; Dooley, Steven; Zeilinger, Katrin

    2017-05-01

    The liver is the major site for alcohol metabolism in the body and therefore the primary target organ for ethanol (EtOH)-induced toxicity. In this study, we investigated the in vitro response of human liver cells to different EtOH concentrations in a perfused bioartificial liver device that mimics the complex architecture of the natural organ. Primary human liver cells were cultured in the bioartificial liver device and treated for 24 hours with medium containing 150 mM (low), 300 mM (medium), or 600 mM (high) EtOH, while a control culture was kept untreated. Gene expression patterns for each EtOH concentration were monitored using Affymetrix Human Gene 1.0 ST Gene chips. Scaled expression profiles of differentially expressed genes (DEGs) were clustered using Fuzzy c-means algorithm. In addition, functional classification methods, KEGG pathway mapping and also a machine learning approach (Random Forest) were utilized. A number of 966 (150 mM EtOH), 1,334 (300 mM EtOH), or 4,132 (600 mM EtOH) genes were found to be differentially expressed. Dose-response relationships of the identified clusters of co-expressed genes showed a monotonic, threshold, or nonmonotonic (hormetic) behavior. Functional classification of DEGs revealed that low or medium EtOH concentrations operate adaptation processes, while alterations observed for the high EtOH concentration reflect the response to cellular damage. The genes displaying a hormetic response were functionally characterized by overrepresented "cellular ketone metabolism" and "carboxylic acid metabolism." Altered expression of the genes BAHD1 and H3F3B was identified as sufficient to classify the samples according to the applied EtOH doses. Different pathways of metabolic and epigenetic regulation are affected by EtOH exposition and partly undergo hormetic regulation in the bioartificial liver device. Gene expression changes observed at high EtOH concentrations reflect in some aspects the situation of alcoholic hepatitis

  14. HEPATOBLASTOMAS IN THE MUMMICHOG, FUNDULUS HETEROCLITUS (L.), FROM A CREOSOTE-CONTAMINATED ENVIRONMENT: A HISTOLOGIC, ULTRASTRUCTURAL AND IMMUNOHISTOCHEMICAL STUDY

    EPA Science Inventory

    A detailed histologic and ultrastructural description of two cases of hepatoblastoma, a primitive liver cell neoplasm, is provided from mummichog, Fundulus heteroclitus(L.), inhabiting a creosote-contaminated site in the Elizabeth River, Virginia, USA. Both neoplasms were multifo...

  15. Contrast-enhanced ultrasonography for the evaluation of liver fibrosis after biliary obstruction.

    PubMed

    Shin, Hyun Joo; Chang, Eun Young; Lee, Hye Sun; Hong, Jung Hwa; Park, Gyuri; Kim, Hyun Gi; Kim, Myung-Joon; Lee, Mi-Jung

    2015-03-07

    To investigate perfusion change in contrast-enhanced ultrasonography (CEUS) to evaluate liver fibrosis based on biliary obstruction using an animal model. New Zealand white rabbits (3-4 kg) underwent bile duct ligation to form a biliary obstruction model. We performed liver CEUS and laboratory tests on the day before the operation (day 0) and every 7 postoperative days until the rabbits were sacrificed. After CEUS, signal intensity of liver parenchyma with a time-intensity curve was analyzed. Perfusion parameters were automatically calculated from region-of-interests, including peak signal intensity, mean transit time, area under the curve and time to peak. Histological grades of liver fibrosis were assessed according to the Metavir score system immediately after sacrifice. Generalized estimating equations were used to analyze the association between liver fibrosis grades and perfusion parameters for statistical analysis. The perfusion parameters were measured on the last day and the difference between day 0 and the last day were evaluated. From the nine rabbits, histological grades of liver fibrosis were grade 1 in one rabbit, grade 2 and 3 in three rabbits each, and grade 4 in two rabbits. Among the four CEUS parameters, only the peak signal intensity measured on the last day demonstrated a significant association with liver fibrosis grades (OR = 1.392, 95%CI: 1.114-1.741, P = 0.004). The difference in peak signal intensity between day 0 and the last day also demonstrated an association with liver fibrosis (OR = 1.191, 95%CI: 0.999-1.419, P = 0.051). The other parameters tested, including mean transit time, area under the curve, and time to peak, showed no significant correlation with liver fibrosis grades. This animal study demonstrates that CEUS can be used to evaluate liver fibrosis from biliary obstruction using peak signal intensity as a parameter.

  16. Liver involvement in Langerhans' cell histiocytosis. Case report.

    PubMed

    Dina, Ion; Copaescu, Catalin; Herlea, Vlad; Wrba, Fritz; Iacobescu, Claudia

    2006-03-01

    Langerhans'cell histiocytosis (Histiocytosis X) is a rare disease of unknown cause characterized by oligoclonal proliferation of Langerhans cells. It occurs mostly in children and young adults and involves one or more body systems such as bone, hypothalamus, posterior pituitary gland, lymph nodes, liver or various soft tissues. The diagnosis is always made by a histological approach. We report a case of Langerhans'cell histiocytosis in a young patient with clinical signs of diabetes insipidus and hepatic involvement in whom the immunohistochemical analysis of the liver tissue led to the definitive diagnosis.

  17. Visualizing liver anatomy, physiology and pharmacology using multiphoton microscopy.

    PubMed

    Wang, Haolu; Liang, Xiaowen; Gravot, Germain; Thorling, Camilla A; Crawford, Darrell H G; Xu, Zhi Ping; Liu, Xin; Roberts, Michael S

    2017-01-01

    Multiphoton microscopy (MPM) has become increasingly popular and widely used in both basic and clinical liver studies over the past few years. This technology provides insights into deep live tissues with less photobleaching and phototoxicity, which helps us to better understand the cellular morphology, microenvironment, immune responses and spatiotemporal dynamics of drugs and therapeutic cells in the healthy and diseased liver. This review summarizes the principles, opportunities, applications and limitations of MPM in hepatology. A key emphasis is on the use of fluorescence lifetime imaging (FLIM) to add additional quantification and specificity to the detection of endogenous fluorescent species in the liver as well as exogenous molecules and nanoparticles that are applied to the liver in vivo. We anticipate that in the near future MPM-FLIM will advance our understanding of the cellular and molecular mechanisms of liver diseases, and will be evaluated from bench to bedside, leading to real-time histology of human liver diseases. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Comparison between high-frequency ultrasonography and histological assessment reveals weak correlation for measurements of scar tissue thickness.

    PubMed

    Agabalyan, Natacha A; Su, Samuel; Sinha, Sarthak; Gabriel, Vincent

    2017-05-01

    Current methods for evaluating scar tissue volume following burns have shortcomings. The Vancouver Burn Scar scale is subjective, leading to a high variability in assessment. Although histological assessment via punch biopsy can discriminate between the different layers of skin, such an approach is invasive, inefficient, and detrimental to patient experience and wound healing. This study investigates the accuracy of high-frequency ultrasonography, a non-invasive alternative to histology, for measuring dermal and epidermal thickness in scar tissue. Scar thicknesses of 10 patients following burns were assessed using a 2-D high-frequency ultrasound probe. The scars were then biopsied using a circular 4mm punch biopsy for histological assessment. Dermal, epidermal, and total thickness of the scar tissue was measured using ultrasound and histology, and correlations between the two measurements were calculated. There was not a strong correlation between ultrasound measurement and histological analysis for epidermal, dermal, and total thickness (Spearman's rank correlation of -0.1223, -0.6242, and -0.6242) of scar tissue. Measurements of scar thickness using high-frequency ultrasonography did not recapitulate the in vivo dermal, epidermal and total thickness. Based on these findings, strategies for further optimization of 2-D ultrasonography is discussed before clinical and research use. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  19. The Use of an Acellular Oxygen Carrier in a Human Liver Model of Normothermic Machine Perfusion

    PubMed Central

    Wallace, Lorraine; Boteon, Yuri; Neil, Desley AH; Smith, Amanda; Stephenson, Barney TF; Schlegel, Andrea; Hübscher, Stefan G; Mirza, Darius F

    2017-01-01

    Background Normothermic machine perfusion of the liver (NMP-L) is a novel technique that preserves liver grafts under near-physiological conditions whilst maintaining their normal metabolic activity. This process requires an adequate oxygen supply, typically delivered by packed red blood cells (RBC). We present the first experience using an acellular hemoglobin-based oxygen carrier (HBOC) Hemopure in a human model of NMP-L. Methods Five discarded high-risk human livers were perfused with HBOC-based perfusion fluid and matched to 5 RBC-perfused livers. Perfusion parameters, oxygen extraction, metabolic activity and histological features were compared during 6 hours of NMP-L. The cytotoxicity of Hemopure was also tested on human hepatic primary cell line cultures using an in vitro model of ischemia reperfusion injury. Results The vascular flow parameters and the perfusate lactate clearance were similar in both groups. The HBOC-perfused livers extracted more oxygen than those perfused with RBCs (O2ER 13.75 vs 9.43 % x105 per gram of tissue, p=0.001). In vitro exposure to Hemopure did not alter intracellular levels of reactive oxygen species and there was no increase in apoptosis or necrosis observed in any of the tested cell lines. Histological findings were comparable between groups. There was no evidence of histological damage caused by Hemopure. Conclusion Hemopure can be used as an alternative oxygen carrier to packed red cells in NMP-L perfusion fluid. PMID:28520579

  20. Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK

    PubMed Central

    Panisello-Roselló, Arnau; Verde, Eva; Flores, Marta; Folch-Puy, Emma; Rolo, Anabela; Palmeira, Carlos; Hotter, Georgina; Adam, René; Roselló-Catafau, Joan

    2018-01-01

    Institute Goeorges Lopez 1 (IGL-1) and Histidine-Tryptophan-Ketoglutarate (HTK) preservation solutions are regularly used in clinical for liver transplantation besides University of Wisconsin (UW) solution and Celsior. Several clinical trials and experimental works have been carried out comparing all the solutions, however the comparative IGL-1 and HTK appraisals are poor; especially when they deal with the underlying protection mechanisms of the fatty liver graft during cold storage. Fatty livers from male obese Zücker rats were conserved for 24 h at 4 °C in IGL-1 or HTK preservation solutions. After organ recovery and rinsing of fatty liver grafts with Ringer Lactate solution, we measured the changes in mechanistic target of rapamycin (mTOR) signaling activation, liver autophagy markers (Beclin-1, Beclin-2, LC3B and ATG7) and apoptotic markers (caspase 3, caspase 9 and TUNEL). These determinations were correlated with the prevention of liver injury (aspartate and alanine aminostransferase (AST/ALT), histology) and mitochondrial damage (glutamate dehydrogenase (GLDH) and confocal microscopy findings). Liver grafts preserved in IGL-1 solution showed a marked reduction on p-TOR/mTOR ratio when compared to HTK. This was concomitant with significant increased cyto-protective autophagy and prevention of liver apoptosis, including inflammatory cytokines such as HMGB1. Together, our results revealed that IGL-1 preservation solution better protected fatty liver grafts against cold ischemia damage than HTK solution. IGL-1 protection was associated with a reduced liver damage, higher induced autophagy and decreased apoptosis. All these effects would contribute to limit the subsequent extension of reperfusion injury after graft revascularization in liver transplantation procedures. PMID:29364854

  1. Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment. (I). Nonalcoholic fatty liver disease and its association with cardiovascular disease.

    PubMed

    Brea, Ángel; Pintó, Xavier; Ascaso, Juan F; Blasco, Mariano; Díaz, Ángel; González-Santos, Pedro; Hernández Mijares, Antonio; Mantilla, Teresa; Millán, Jesús; Pedro-Botet, Juan

    Non-alcoholic fatty liver disease (NAFLD) comprises a series of histologically lesions similar to those induced by alcohol consumption in people with very little or no liver damage. The importance of NAFLD is its high prevalence in the Western world and, from the point of view of the liver, in its gradual progression from steatosis to steatohepatitis, cirrhosis, and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with acceleration of arteriosclerosis and events related to it, being the main cause of its morbidity and mortality. This review, updated to January 2016, consists of two parts, with the first part analysing the association of NAFLD with cardiovascular disease. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Male 11β-HSD1 Knockout Mice Fed Trans-Fats and Fructose Are Not Protected From Metabolic Syndrome or Nonalcoholic Fatty Liver Disease.

    PubMed

    Larner, Dean P; Morgan, Stuart A; Gathercole, Laura L; Doig, Craig L; Guest, Phil; Weston, Christopher; Hazeldine, Jon; Tomlinson, Jeremy W; Stewart, Paul M; Lavery, Gareth G

    2016-09-01

    Nonalcoholic fatty liver disease (NAFLD) defines a spectrum of conditions from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis and is regarded as the hepatic manifestation of the metabolic syndrome. Glucocorticoids can promote steatosis by stimulating lipolysis within adipose tissue, free fatty acid delivery to liver and hepatic de novo lipogenesis. Glucocorticoids can be reactivated in liver through 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme activity. Inhibition of 11β-HSD1 has been suggested as a potential treatment for NAFLD. To test this, male mice with global (11β-HSD1 knockout [KO]) and liver-specific (LKO) 11β-HSD1 loss of function were fed the American Lifestyle Induced Obesity Syndrome (ALIOS) diet, known to recapitulate the spectrum of NAFLD, and metabolic and liver phenotypes assessed. Body weight, muscle and adipose tissue masses, and parameters of glucose homeostasis showed that 11β-HSD1KO and LKO mice were not protected from systemic metabolic disease. Evaluation of hepatic histology, triglyceride content, and blinded NAFLD activity score assessment indicated that levels of steatosis were similar between 11β-HSD1KO, LKO, and control mice. Unexpectedly, histological analysis revealed significantly increased levels of immune foci present in livers of 11β-HSD1KO but not LKO or control mice, suggestive of a transition to NASH. This was endorsed by elevated hepatic expression of key immune cell and inflammatory markers. These data indicate that 11β-HSD1-deficient mice are not protected from metabolic disease or hepatosteatosis in the face of a NAFLD-inducing diet. However, global deficiency of 11β-HSD1 did increase markers of hepatic inflammation and suggests a critical role for 11β-HSD1 in restraining the transition to NASH.

  3. Bacterial microflora of normal and telangiectatic livers in cattle.

    PubMed

    Stotland, E I; Edwards, J F; Roussel, A J; Simpson, R B

    2001-07-01

    To identify potential bacterial pathogens in normal and telangiectatic livers of mature cattle at slaughter and to identify consumer risk associated with hepatic telangiectasia. 50 normal livers and 50 severely telangiectatic livers. Normal and telangiectatic livers were collected at slaughter for aerobic and anaerobic bacterial culture. Isolates were identified, and patterns of isolation were analyzed. Histologic examination of all livers was performed. Human pathogens isolated from normal and telangiectatic livers included Escherichia coli O157:H7 and group-D streptococci. Most livers in both groups contained bacteria in low numbers; however, more normal livers yielded negative culture results. More group-D streptococci were isolated from the right lobes of telangiectatic livers than from the left lobes, and more gram-negative anaerobic bacteria were isolated from left lobes of telangiectatic livers than from right lobes. All telangiectatic lesions were free of fibrosis, active necrotizing processes, and inflammation. The USDA regulation condemning telangiectatic livers is justified insofar as these livers contain more bacteria than normal livers do; however, normal livers contain similar species of microflora. Development of telangiectasia could not be linked to an infectious process. The finding of E coli O157:H7 in bovine livers suggests that information regarding bacterial content of other offal and muscle may identify sources of this and other potential foodborne pathogens and assist in establishing critical control points for the meat industry.

  4. Evaluation of neoadjuvant chemotherapy effects on liver parenchyma in resected pediatric malignancies.

    PubMed

    Scuderi, Maria Grazia; Magro, Gaetano; Di Cataldo, Andrea; Pesce, Antonino; Scalora, Luisa; Vecchio, Giada Maria; Portale, Rosanna; Di Benedetto, Vincenzo; Puleo, Stefano

    2013-08-01

    Neoadjuvant chemotherapy for colorectal liver metastases in adults is responsible for chemotherapy-associated liver injury (CALI), characterized by steatosis, steatohepatitis, and sinusoidal obstruction syndrome. These alterations cause delayed operation to reduce the risk of hemorrhage, portal hypertension, and hepatic failure. Children with hepatic malignancies usually receive neoadjuvant chemotherapy prior to surgery. The aim of this study was to evaluate retrospectively whether the CALI occurs in this pediatric population. This study evaluated patients referred since 1996 for hepatic malignancies who received hepatectomy after chemotherapy. Liver resection material was reviewed, in order to investigate the presence of morphological changes compatible with the CALI in the peritumoral hepatic tissue. Twelve patients were recruited. All patients satisfied the inclusion criteria except one who did not receive neoadjuvant chemotherapy. Eleven children underwent surgery 1 month after the last chemotherapy cycle. All are alive disease-free. Histological examination of specimen revealed only mild changes such as diffuse swelling of hepatocytes and focal, mild portal inflammation. Severe hepatic changes such as steatosis, necrosis, or fibrosis were not identified. CALI-related morphological changes were not found in our patients. The absence of the CALI could be attributed to the younger age of patients (possible different response to stress) and/or to the different chemotherapy schedules compared to those in use for adults patients.

  5. Obstructive sleep apnea is associated with fatty liver and abnormal liver enzymes: a meta-analysis.

    PubMed

    Sookoian, Silvia; Pirola, Carlos J

    2013-11-01

    Obstructive sleep apnea (OSA) is associated with the cluster of clinical conditions that comprise the metabolic syndrome, including nonalcoholic fatty liver disease (NAFLD). Our primary purpose was to estimate the effect of OSA on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Our secondary purpose was to investigate the potential influence of OSA on histological severity of NAFLD to explore whether chronic intermittent hypoxia is associated with inflammation and fibrosis. Our literature search identified 11 studies, from which we extracted information about numbers of control subjects and OSA patients, and ALT, AST, and NAFLD. From a total of 668 OSA patients and 404 controls, we found that the standardized difference in mean values of ALT and AST levels in patients with OSA was significantly different from that in the controls. Meta-regression showed that the association was independent of body mass index and type 2 diabetes. Fatty liver was associated with OSA in five studies with 400 subjects. OSA was significantly associated with liver fibrosis in 208 subjects, but not with lobular inflammation. Routine assessment of liver enzymes and liver damage should be implemented in OSA patients because they have an increase of 13.3% of ALT and 4.4% of AST levels, and a 2.6-fold higher risk of liver fibrosis when they have NAFLD, which is 2.6 times more frequent in OSA patients.

  6. Counteracting effects on free radicals and histological alterations induced by a fraction with casearins.

    PubMed

    Araújo, Éverton José Ferreira de; De Oliveira, Guilherme Antônio Lopes; de Sousa, Lívia Queiroz; Bolzani, Vanderlan da Silva; Cavalheiro, Alberto José; Tome, Adriana da Rocha; Peron, Ana Paula; dos Santos, André Gonzaga; Citó, Antonia Maria das Graças Lopes; Pessoa, Cláudia; de Freitas, Rivelilson Mendes; Ferreira, Paulo Michel Pinheiro

    2015-09-01

    Casearia sylvestris Swartz is a medicinal plant widely distributed in Brazil. It has anti-inflammatory, antiulcer and antitumor activities and is popularly used to treat snakebites, wounds, diarrhea, flu and chest colds. Its leaves are rich in oxygenated tricyclic cis-clerodane diterpenes, particulary casearins. Herein, we evaluated the antioxidant activities of a fraction with casearins (FC) isolated from C. sylvestris and histological changes on the central nervous system and livers of Mus musculus mice. Firstly, in vitro studies (0.9, 1.8, 3.6, 5.4 and 7.2 μg/mL) revealed EC50 values of 3.7, 6.4 and 0.16 µg/mL for nitrite, hydroxyl radical and TBARS levels, respectively. Secondly, FC (2.5, 5, 10 and 25 mg/kg/day) was intraperitoneally administered to Swiss mice for 7 consecutive days. Nitrite levels in the hippocampus (26.2, 27.3, 30.2 and 26.6 µM) and striatum (26.3, 25.4, 34.3 and 27.5 µM) increased in all treated animals (P < 0.05). Lower doses dropped reduced glutathione, catalase and TBARS levels in the hippocampus and striatum. With the exception of this reduction in TBARS formation, FC displayed only in vitro antioxidant activity. Animals exhibited histological alterations suggestive of neurotoxicity and hepatotoxicity, indicating the need for precaution regarding the consumption of medicinal formulations based on Casearia sylvestris.

  7. Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines.

    PubMed

    Zong, L; Yu, Q H; Du, Y X; Deng, X M

    2014-02-01

    Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis.

  8. Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines

    PubMed Central

    Zong, L.; Yu, Q.H.; Du, Y.X.; Deng, X.M.

    2014-01-01

    Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis. PMID:24554039

  9. Analysis of the histologic features in the differential diagnosis of intrahepatic neonatal cholestasis

    PubMed Central

    Bellomo-Brandao, Maria Angela; Escanhoela, Cecilia AF; Meirelles, Luciana R; Porta, Gilda; Hessel, Gabriel

    2009-01-01

    AIM: To compare the histologic features of the liver in intrahepatic neonatal cholestasis (IHNC) with infectious, genetic-endocrine-metabolic, and idiopathic etiologies. METHODS: Liver biopsies from 86 infants with IHNC were evaluated. The inclusion criteria consisted of jaundice beginning at 3 mo of age and a hepatic biopsy during the 1st year of life. The following histologic features were evaluated: cholestasis, eosinophilia, giant cells, erythropoiesis, siderosis, portal fibrosis, and the presence of a septum. RESULTS: Based on the diagnosis, patients were classified into three groups: group 1 (infectious; n = 18), group 2 (genetic-endocrine-metabolic; n = 18), and group 3 (idiopathic; n = 50). There were no significant differences with respect to the following variables: cholestasis, eosinophilia, giant cells, siderosis, portal fibrosis, and presence of a septum. A significant difference was observed with respect to erythropoiesis, which was more severe in group 1 (Fisher’s exact test, P = 0.016). CONCLUSION: A significant difference was observed in IHNC of infectious etiology, in which erythropoiesis was more severe than that in genetic-endocrine-metabolic and idiopathic etiologies, whereas there were no significant differences among cholestasis, eosinophilia, giant cells, siderosis, portal fibrosis, and the presence of a septum. PMID:19152454

  10. Spontaneous and induced tolerance for liver transplant recipients.

    PubMed

    Feng, Sandy

    2016-02-01

    Transformative medical and surgical advances have remarkably improved short-term survival after liver transplantation. There is, however, pervasive concern that the cumulative toxicities of modern immunosuppression regimens severely compromise both quality and quantity of life for liver transplant recipients. The inherently tolerogenic nature of the liver offers the tantalizing opportunity to change the current paradigm of nonspecific and lifelong immunosuppression. Safe minimization or discontinuation of immunosuppression without damage to the liver allograft is an attractive strategy to improve long-term survival after liver transplantation. Recent prospective, multicenter clinical trials have demonstrated that immunosuppression can be safely withdrawn from selected liver transplant recipients with preservation of allograft histology. These successes have spurred multiple avenues of investigation to identify peripheral blood and/or tissue biomarkers and delineate mechanisms of tolerance. Concomitant advances in the ability to expand regulatory T cells in the laboratory have spawned clinical trials to facilitate immunosuppression minimization and/or discontinuation. This review will delineate the unique liver immunobiology that has driven the recent clinical trials to unmask spontaneous tolerance or induce tolerance for liver transplant recipients. The emerging results of these trials over the next 5 years hold promise to reduce the burden of lifelong immunosuppression and thereby optimize the long-term health of liver transplant recipients.

  11. Liver and kidney toxicity induced by Afzal smokeless tobacco product in Oman.

    PubMed

    Al-Mukhaini, Nawal; Ba-Omar, Taher; Eltayeb, Elsadig; Al-Shihi, Aisha; Al-Riyami, Nafila; Al-Belushi, Jamila; Al-Adawi, Kawthar

    2017-04-01

    Afzal, the common smokeless tobacco product (STP) in Oman, is believed to contain toxins that may impair the function of some organs such as liver and kidney. An aqueous extract from Afzal was added to drinking water to be administrated orally to Wistar albino rats (n=72) young and adult from both genders weighing between 60-80g and 150-240g respectively for 8 weeks. Animals were divided into three groups: control (distilled water instead of Afzal extract), low-dose (3mgnicotine/kgbodyweight/day) and high-dose (6mgnicotine/kgbodyweight/day). The animals were euthanized and their blood, liver and kidney were collected for biochemical and histopathological investigations. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed for the liver function, while blood urea nitrogen (BUN) and creatinine (CRT) were assayed for the kidney function. The results showed a significant increase in the ALT, AST, BUN and CRT levels (P<0.05) in both Afzal-treated groups (low and high doses) compared with the control. Histopathological findings revealed the initial but seem to be serious degenerative alterations of periportal fibrosis in liver and edematous and calcified changes in renal glomerulus among Afzal-treated groups. Additionally, the weight gain of the Afzal-treated groups was lower than the control group. Our findings show that the exposure of Wistar rats to the Afzal extract has the potentials of causing decreased weight gain and dose-dependent functional and structural damage to the biochemical and histological profiles of liver and kidney as well as serious biochemical effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Aragonès, Gemma; Auguet, Teresa; Armengol, Sandra; Berlanga, Alba; Guiu-Jurado, Esther; Aguilar, Carmen; Martínez, Salomé; Sabench, Fátima; Porras, José Antonio; Ruiz, Maikel Daniel; Hernández, Mercé; Sirvent, Joan Josep; Del Castillo, Daniel; Richart, Cristóbal

    2016-01-01

    Recent reports suggest a role for the Patatin-like phospholipase domain-containing protein 3 (PNPLA3) in the pathology of non-alcoholic fatty liver disease (NAFLD). Lipid deposition in the liver seems to be a critical process in the pathogenesis of NAFLD. The aim of the present work was to evaluate the association between the liver PNPLA3 expression, key genes of lipid metabolism, and the presence of NAFLD in morbidly obese women. We used real-time polymerase chain reaction (PCR) analysis to analyze the hepatic expression of PNPLA3 and lipid metabolism-related genes in 55 morbidly obese subjects with normal liver histology (NL, n = 18), simple steatosis (SS, n = 20), and non-alcoholic steatohepatitis (NASH, n = 17). Liver biopsies were collected during bariatric surgery. We observed that liver PNPLA3 expression was increased in NAFLD than in NL. It was also upregulated in SS than in NL. Interestingly, we found that the expression of PNPLA3 was significantly higher in severe than mild SS group. In addition, the expression of the transcription factors LXRα, PPARα, and SREBP2 was positively correlated with PNPLA3 liver expression. Regarding rs738409 polymorphism, GG genotype was positive correlated with the presence of NASH. In conclusion, our results show that PNPLA3 could be related to lipid accumulation in liver, mainly in the development and progression of simple steatosis. PMID:27128907

  13. PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease.

    PubMed

    Aragonès, Gemma; Auguet, Teresa; Armengol, Sandra; Berlanga, Alba; Guiu-Jurado, Esther; Aguilar, Carmen; Martínez, Salomé; Sabench, Fátima; Porras, José Antonio; Ruiz, Maikel Daniel; Hernández, Mercé; Sirvent, Joan Josep; Del Castillo, Daniel; Richart, Cristóbal

    2016-04-27

    Recent reports suggest a role for the Patatin-like phospholipase domain-containing protein 3 (PNPLA3) in the pathology of non-alcoholic fatty liver disease (NAFLD). Lipid deposition in the liver seems to be a critical process in the pathogenesis of NAFLD. The aim of the present work was to evaluate the association between the liver PNPLA3 expression, key genes of lipid metabolism, and the presence of NAFLD in morbidly obese women. We used real-time polymerase chain reaction (PCR) analysis to analyze the hepatic expression of PNPLA3 and lipid metabolism-related genes in 55 morbidly obese subjects with normal liver histology (NL, n = 18), simple steatosis (SS, n = 20), and non-alcoholic steatohepatitis (NASH, n = 17). Liver biopsies were collected during bariatric surgery. We observed that liver PNPLA3 expression was increased in NAFLD than in NL. It was also upregulated in SS than in NL. Interestingly, we found that the expression of PNPLA3 was significantly higher in severe than mild SS group. In addition, the expression of the transcription factors LXRα, PPARα, and SREBP2 was positively correlated with PNPLA3 liver expression. Regarding rs738409 polymorphism, GG genotype was positive correlated with the presence of NASH. In conclusion, our results show that PNPLA3 could be related to lipid accumulation in liver, mainly in the development and progression of simple steatosis.

  14. Simultaneous quantification of hepatic MRI-PDFF and R2* in a rabbit model with nonalcoholic fatty liver disease.

    PubMed

    Wang, Xiaomin; Zhang, Xiaojing; Ma, Lin; Li, Shengli

    2018-06-20

    Quantification of hepatic fat and iron content is important for early detection and monitoring of nonalcoholic fatty liver disease (NAFLD) patients. This study evaluated quantification efficiency of hepatic proton density fat fraction (PDFF) by MRI using NAFLD rabbits. R2* was also measured to investigate whether it correlates with fat levels in NAFLD. NAFLD rabbit model was successfully established by high fat and cholesterol diet. Rabbits underwent MRI examination for fat and iron analyses, compared with liver histological findings. MR examinations were performed on a 3.0T MR system using multi-echo 3D gradient recalled echo (GRE) sequence. MRI-PDFF showed significant differences between different steatosis grades with medians of 3.72% (normal), 5.43% (mild), 9.11% (moderate) and 11.17% (severe), whereas this was not observed in R2*. Close correlation between MRI-PDFF and histological steatosis was observed (r=0.78, P=0.000). Hepatic iron deposit was not found in any rabbits. There was no correlation between R2* and either liver MRI-PDFF or histological steatosis. MR measuring MRI-PDFF and R2* simultaneously provides promising quantification of steatosis and iron. Rabbit NAFLD model confirmed accuracy of MRI-PDFF for liver fat quantification. R2* measurement and relationship between fat and iron of NAFLD liver need further experimental investigation.

  15. Non-alcoholic fatty liver disease: A poorly known pandemic.

    PubMed

    Augustin, Salvador; Graupera, Isabel; Caballeria, Juan

    2017-12-20

    Non-alcoholic fatty liver disease (NAFLD) consists of an excessive depositing of fat in the liver, which can end up by causing inflammation, fibrosis and also cirrhosis with the corresponding complications including liver cancer. NAFLD has become the most common liver disease worldwide. The incidence has increased in parallel with the obesity, diabetes and metabolic syndrome epidemic, thus resulting in becoming one of the main indications for liver transplant. The diagnosis has principally been through histology but with the development of non-invasive methods, these have helped in simplifying the management of these patients in clinical practice. The only therapeutic strategies currently available are focused on weight loss (lifestyle changes or bariatric surgery). There is still no approved pharmacological option for the treatment of NAFLD, however there are a number of molecular studies in advanced stages of development. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  16. Somatotropic Axis Dysfunction in Non-Alcoholic Fatty Liver Disease: Beneficial Hepatic and Systemic Effects of Hormone Supplementation

    PubMed Central

    Cabrera, Daniel; Solís, Nancy; San Martín, Diego; Cofré, Catalina; Pizarro, Margarita; Abrigo, Johanna; Campos, Fabián; Irigoyen, Betzabé; Carrasco-Avino, Gonzalo; Bezares, Katiuska; Riquelme, Valentina; Riquelme, Arnoldo; Arrese, Marco; Barrera, Francisco

    2018-01-01

    Background: Somatotropic axis dysfunction associated with non-alcoholic fatty liver disease (NAFLD) has potential multisystemic detrimental effects. Here, we analysed the effects of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) supplementation on liver histology, adipokine profile and muscle function in an NAFLD model. Methods: C57BL/6 mice were fed with a high fat diet (HFD) for 12 weeks and were separated into three groups treated for 4 weeks with: (1) High fat diet (HFD) (n = 10); (2) HFD + GH 9 μg/g/d (n = 10); (3) HFD + IGF-1 0.02 µg/g/d (n = 9). A control group fed a chow diet was included (n = 6). Liver histology, liver triglycerides content, serum alanine aminotransferase (ALT) activity, adiponectin and leptin serum levels, in vivo muscle strength, tetanic force and muscle fibre cross-sectional area (CSA) were measured. Results: HFD + GH and HFD + IGF-1 groups showed significantly lower ALT activity compared to HFD (p < 0.01). Liver triglyceride content in HFD + GH was decreased compared to HFD (p < 0.01). Histologic steatosis score was increased in HFD and HFD + GH group (p < 0.01), whereas HFD + IGF-1 presented no difference compared to the chow group (p = 0.3). HFD + GH group presented lower serum leptin and adiponectin levels compared to HFD. GH and IGF-1 supplementation therapy reverted HFD-induced reduction in muscle strength and CSA (sarcopenia). Conclusions: GH and IGF-1 supplementation induced significant improvement in liver steatosis, aminotransferases and sarcopenia in a diet-induced NAFLD model. PMID:29724029

  17. Ultrasound imaging in an experimental model of fatty liver disease and cirrhosis in rats

    PubMed Central

    2010-01-01

    Background Domestic dogs and cats are very well known to develop chronic hepatic diseases, including hepatic lipidosis and cirrhosis. Ultrasonographic examination is extensively used to detect them. However, there are still few reports on the use of the ultrasound B-mode scan in correlation with histological findings to evaluate diffuse hepatic changes in rodents, which represent the most important animal group used in experimental models of liver diseases. The purpose of this study was to determine the reliability of ultrasound findings in the assessment of fatty liver disease and cirrhosis when compared to histological results in Wistar rats by following up a murine model of chronic hepatic disease. Results Forty Wistar rats (30 treated, 10 controls) were included. Liver injury was induced by dual exposure to CCl4 and ethanol for 4, 8 and 15 weeks. Liver echogenicity, its correlation to the right renal cortex echogenicity, measurement of portal vein diameter (PVD) and the presence of ascites were evaluated and compared to histological findings of hepatic steatosis and cirrhosis. Liver echogenicity correlated to hepatic steatosis when it was greater or equal to the right renal cortex echogenicity, with a sensitivity of 90%, specificity of 100%, positive and negative predictive values of 100% and 76.9% respectively, and accuracy of 92.5%. Findings of heterogeneous liver echogenicity and irregular surface correlated to liver cirrhosis with a sensitivity of 70.6%, specificity of 100%, positive and negative predictive values of 100% and 82.1% respectively, and accuracy of 87.5%. PVD was significantly increased in both steatotic and cirrhotic rats; however, the later had greater diameters. PVD cut-off point separating steatosis from cirrhosis was 2.1 mm (sensitivity of 100% and specificity of 90.5%). One third of cirrhotic rats presented with ascites. Conclusion The use of ultrasound imaging in the follow-up of murine diffuse liver disease models is feasible and

  18. In vivo bioluminescence imaging reveals copper deficiency in a murine model of nonalcoholic fatty liver disease

    PubMed Central

    Heffern, Marie C.; Park, Hyo Min; Au-Yeung, Ho Yu; Van de Bittner, Genevieve C.; Ackerman, Cheri M.; Stahl, Andreas; Chang, Christopher J.

    2016-01-01

    Copper is a required metal nutrient for life, but global or local alterations in its homeostasis are linked to diseases spanning genetic and metabolic disorders to cancer and neurodegeneration. Technologies that enable longitudinal in vivo monitoring of dynamic copper pools can help meet the need to study the complex interplay between copper status, health, and disease in the same living organism over time. Here, we present the synthesis, characterization, and in vivo imaging applications of Copper-Caged Luciferin-1 (CCL-1), a bioluminescent reporter for tissue-specific copper visualization in living animals. CCL-1 uses a selective copper(I)-dependent oxidative cleavage reaction to release d-luciferin for subsequent bioluminescent reaction with firefly luciferase. The probe can detect physiological changes in labile Cu+ levels in live cells and mice under situations of copper deficiency or overload. Application of CCL-1 to mice with liver-specific luciferase expression in a diet-induced model of nonalcoholic fatty liver disease reveals onset of hepatic copper deficiency and altered expression levels of central copper trafficking proteins that accompany symptoms of glucose intolerance and weight gain. The data connect copper dysregulation to metabolic liver disease and provide a starting point for expanding the toolbox of reactivity-based chemical reporters for cell- and tissue-specific in vivo imaging. PMID:27911810

  19. Rapid and high-resolution imaging of human liver specimens by full-field optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Zhu, Yue; Gao, Wanrong; Zhou, Yuan; Guo, Yingcheng; Guo, Feng; He, Yong

    2015-11-01

    We report rapid and high-resolution tomographic en face imaging of human liver specimens by full-field optical coherence tomography (FF-OCT). First, the arrangement of the FF-OCT system was described and the performance of the system was measured. The measured axial and lateral resolutions of the system are 0.8 and 0.9 μm, respectively. The system has a sensitivity of ˜60 dB and can achieve an imaging rate of 7 fps and a penetration depth of ˜80 μm. The histological structures of normal liver can be seen clearly in the en face tomographic images, including central veins, cords of hepatocytes separated by sinusoidal spaces, and portal area (portal vein, the hepatic arteriole, and the bile duct). A wide variety of histological subtypes of hepatocellular carcinoma was observed in en face tomographic images, revealing notable cancerous features, including the nuclear atypia (enlarged convoluted nuclei), the polygonal tumor cells with obvious resemblance to hepatocytes with enlarged nuclei. In addition, thicker fibrous bands, which make the cytoplasmic plump vesicular nuclei indistinct, were also seen in the images. Finally, comparison between the portal vein in a normal specimen versus that seen in the rare type of cholangiocarcinoma was made. The results show that the cholangiocarcinoma presents with a blurred pattern of portal vein in the lateral direction and an aggregated distribution in the axial direction; the surrounding sinusoidal spaces and nuclei of cholangiocarcinoma are absent. The findings in this work may be used as additional signs of liver cancer or cholangiocarcinoma, demonstrating capacity of FF-OCT device for early cancer diagnosis and many other tumor-related studies in biopsy.

  20. Chronic intermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver.

    PubMed

    Savransky, Vladimir; Bevans, Shannon; Nanayakkara, Ashika; Li, Jianguo; Smith, Philip L; Torbenson, Michael S; Polotsky, Vsevolod Y

    2007-10-01

    Obstructive sleep apnea (OSA) causes chronic intermittent hypoxia (CIH) during sleep. OSA is associated with nonalcoholic steatohepatitis (NASH) in obese individuals and may contribute to progression of nonalcoholic fatty liver disease from steatosis to NASH. The purpose of this study was to examine whether CIH induces inflammatory changes in the liver in mice with diet-induced hepatic steatosis. C57BL/6J mice (n = 8) on a high-fat, high-cholesterol diet were exposed to CIH for 6 mo and were compared with mice on the same diet exposed to intermittent air (control; n = 8). CIH caused liver injury with an increase in serum ALT (461 +/- 58 U/l vs. 103 +/- 16 U/l in the control group; P < 0.01) and AST (637 +/- 37 U/l vs. 175 +/- 13 U/l in the control group; P < 0.001), whereas alkaline phosphatase and total bilirubin levels were unchanged. Histology revealed hepatic steatosis in both groups, with mild accentuation of fat staining in the zone 3 hepatocytes in mice exposed to CIH. Animals exposed to CIH exhibited lobular inflammation and fibrosis in the liver, which were not evident in control mice. CIH caused significant increases in lipid peroxidation in serum and liver tissue; significant increases in hepatic levels of myeloperoxidase and proinflammatory cytokines IL-1beta, IL-6, and CXC chemokine MIP-2; a trend toward an increase in TNF-alpha; and an increase in alpha1(I)-collagen mRNA. We conclude that CIH induces lipid peroxidation and inflammation in the livers of mice on a high-fat, high-cholesterol diet.

  1. Berberis vulgaris L. effects on oxidative stress and liver injury in lead-intoxicated mice.

    PubMed

    Laamech, Jawhar; El-Hilaly, Jaouad; Fetoui, Hamadi; Chtourou, Yassine; Gouitaa, Hanane; Tahraoui, Adel; Lyoussi, Badiaa

    2017-03-01

    Background Berberis vulgaris L. (BV), commonly known as "Aghriss" in Moroccan pharmacopoeia, is used to cure liver disorders and other diseases. The present study aimed to investigate the protective effect of BV aqueous extract against lead-induced toxicity in mice liver. Methods Sixty IOPS mice were divided into six groups and were treated as follows: group 1 (normal control) received double distilled water; group 2 (toxic control) received lead acetate (5 mg/kg body weight/day) in double distilled water for 40 days; groups 3-6 received BV aqueous extract at doses of 25, 50, 100 and 150 mg/kg body weight , respectively, once daily for 30 days from 11 day after beginning of lead acetate exposure to the end of the experiment. Results Toxic control group showed a significant alteration of serum alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), total cholesterol (TC), total bilirubin (TB), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH). Histological assessment of lead-intoxicated mice liver revealed alterations in hepatocytes and focal necrosis. BV treatment significantly prevented lead accumulation, increased ALT, AST, TC, and TB, inhibited lipid peroxidation and protein carbonyls(PCO) formation. Additionally, BV extract normalized the antioxidant enzymes (CAT, SOD and GPx), GSH and architecture of liver tissues. Conclusions BV aqueous extract exerts significant hepatoprotective effects against lead-induced oxidative stress and liver dysfunction. The BV effect may be mediated through the enhancement of antioxidant status, lead-chelating abilities and free radicals quenching.

  2. l-Methionine and silymarin: A comparison of prophylactic protective capabilities in acetaminophen-induced injuries of the liver, kidney and cerebral cortex.

    PubMed

    Onaolapo, Olakunle J; Adekola, Moses A; Azeez, Taiwo O; Salami, Karimat; Onaolapo, Adejoke Y

    2017-01-01

    We compared the relative protective abilities of silymarin and l-methionine pre-treatment in acetaminophen overdose injuries of the liver, kidney and cerebral cortex by assessing behaviours, antioxidant status, tissue histological changes and biochemical parameters of hepatic/renal function. Rats were divided into six groups of ten each; animals in five of these groups were pre-treated with oral distilled water, silymarin (25mg/kg) or l-methionine (2.5, 5 and 10mg/kg body weight) for 14days; and then administered intraperitoneal (i.p.) acetaminophen at 800mg/kg/day for 3days. Rats in the sixth group (normal control) received distilled water orally for 14days and then i.p. for 3days. Neurobehavioural tests were conducted 7days after last i.p treatment, and animals sacrificed on the 8th day. Plasma was assayed for biochemical markers of liver/kidney function; while sections of the liver, kidney and cerebral cortex were either homogenised for assay of antioxidant status or processed for histology. Acetaminophen overdose resulted in locomotor retardation, excessive self-grooming, working-memory impairment, anxiety, derangement of liver/kidney biochemistry, antioxidant imbalance, and histological changes in the liver, kidney and cerebral cortex. Administration of silymarin or increasing doses of l-methionine counteracted the behavioural changes, reversed biochemical indices of liver/kidney injury, and improved antioxidant activity. Silymarin and l-methionine also conferred variable degrees of tissue protection, on histology. Either silymarin or l-methionine can protect vulnerable tissues from acetaminophen overdose injury; however, each offers variable protection to different tissues. This study highlights an obstacle to seeking the 'ideal' protective agent against acetaminophen overdose. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Grape Leucoanthocyanidin Protects Liver Tissue in Albino Rabbits with Nonalcoholic Hepatic Steatosis.

    PubMed

    Franklin, Reginaldo; Bispo, Rodrigo Freitas Monte; Sousa-Rodrigues, Célio Fernando; Pires, Lucas Alves Sarmento; Fonseca, Albino; Babinski, Marcio Antonio

    2018-06-18

    Nonalcoholic fatty liver disease (NAFLD) is a common ailment. It is usually found in association with diabetes or obesity. There are no approved drugs to treat this condition. The study of flavonoid consumption has increased over the decades due to their antioxidative properties, although the literature is scarce when it comes to their effects in liver tissue. The purpose of this study was to evaluate the role of leucoanthocyanidin in nonalcoholic hepatic steatosis. Thirty male albino rabbits were divided in 3 groups. Group 1 had a regular commercial diet. The second group had a regular diet and 10 mL of egg yolk and 1.5 g of pure cholesterol. The rabbits of the third group were on the same regimen as the second, but were also treated with grape leucoanthocyanidin (50 mg/kg/day) for 100 days. On the last day of the experiment, the animals were euthanized, and the livers excised and fixated in a 10% formalin solution. Afterwards, fragments of each liver were removed and histologically processed and analyzed. The stereological evaluation showed that leucoanthocyanidin reduced NAFLD in comparison with the nontreated group. This was also observed in the histological analysis of the liver tissue, as the treated group had less foci of fatty tissue. Leucoanthocyanidin may therefore be a promising substance to treat NAFLD, although further studies are needed. © 2018 S. Karger AG, Basel.

  4. Alpha-lipoic acid treatment of acetaminophen-induced rat liver damage.

    PubMed

    Mahmoud, Y I; Mahmoud, A A; Nassar, G

    2015-01-01

    Acetaminophen (paracetamol) is a well-tolerated analgesic and antipyretic drug when used at therapeutic doses. Overdoses, however, cause oxidative stress, which leads to acute liver failure. Alpha lipoic acid is an antioxidant that has proven effective for ameliorating many pathological conditions caused by oxidative stress. We evaluated the effect of alpha lipoic acid on the histological and histochemical alterations of liver caused by an acute overdose of acetaminophen in rats. Livers of acetaminophen-intoxicated rats were congested and showed centrilobular necrosis, vacuolar degeneration and inflammatory cell infiltration. Necrotic hepatocytes lost most of their carbohydrates, lipids and structural proteins. Liver sections from rats pre-treated with lipoic acid showed fewer pathological changes; the hepatocytes appeared moderately vacuolated with moderate staining of carbohydrates and proteins. Nevertheless, alpha lipoic acid at the dose we used did not protect the liver fully from acetaminophen-induced acute toxicity.

  5. Optical analysis of cirrhotic liver by near infrared time resolved spectroscopy

    NASA Astrophysics Data System (ADS)

    Nishio, Toshihiro; Kitai, Toshiyuki; Miwa, Mitsuharu; Takahashi, Rei; Yamaoka, Yoshio

    1999-10-01

    The severity of liver cirrhosis was related with the optical properties of liver tissue. Various grades of liver cirrhosis were produced in rats by intraperitoneal injection of thioacetamide (TAA) for different periods: 4 weeks, 8 weeks, 12 weeks, and 16 weeks. Optical properties of the liver, absorption, coefficient ((mu) a) and scattering coefficient (microsecond(s) '), were measured by near-infrared time- resolved spectroscopy. Histological examination confirmed cirrhotic changes in the liver, which were more severe in rats with TAA administration for longer periods. The (mu) a increased in 4- and 8-week rats, and then decreased in 12- and 16-week rats. The (mu) a of blood-free liver decreased as liver cirrhosis progressed. The hemoglobin content in the liver calculated from the (mu) a values increased in 4- and 8-week rats and decreased in 12- and 16-week rats. The microsecond(s) ' decreased in the cirrhotic liver, probably reflecting the decrease in the mitochondria content. It was shown that (mu) a and microsecond(s) ' determination is useful to assess the severity of liver cirrhosis.

  6. Cross-sectional and longitudinal evaluation of liver volume and total liver fat burden in adults with nonalcoholic steatohepatitis

    PubMed Central

    Tang, An; Chen, Joshua; Le, Thuy-Anh; Changchien, Christopher; Hamilton, Gavin; Middleton, Michael S.; Loomba, Rohit; Sirlin, Claude B.

    2014-01-01

    Purpose To explore the cross-sectional and longitudinal relationships between fractional liver fat content, liver volume, and total liver fat burden. Methods In 43 adults with non-alcoholic steatohepatitis participating in a clinical trial, liver volume was estimated by segmentation of magnitude-based low-flip-angle multiecho GRE images. The liver mean proton density fat fraction (PDFF) was calculated. The total liver fat index (TLFI) was estimated as the product of liver mean PDFF and liver volume. Linear regression analyses were performed. Results Cross-sectional analyses revealed statistically significant relationships between TLFI and liver mean PDFF (R2 = 0.740 baseline/0.791 follow-up, P < 0.001 baseline/P < 0.001 follow-up), and between TLFI and liver volume (R2 = 0.352/0.452, P < 0.001/< 0.001). Longitudinal analyses revealed statistically significant relationships between liver volume change and liver mean PDFF change (R2 = 0.556, P < 0.001), between TLFI change and liver mean PDFF change (R2 = 0.920, P < 0.001), and between TLFI change and liver volume change (R2 = 0.735, P < 0.001). Conclusion Liver segmentation in combination with MRI-based PDFF estimation may be used to monitor liver volume, liver mean PDFF, and TLFI in a clinical trial. PMID:25015398

  7. Insulin resistance in clinical and experimental alcoholic liver disease

    PubMed Central

    Carr, Rotonya M.; Correnti, Jason

    2015-01-01

    Alcoholic liver disease (ALD) is the number one cause of liver failure worldwide; its management costs billions of health care dollars annually. Since the advent of the obesity epidemic, insulin resistance and diabetes have become common clinical findings in patients with ALD; and the development of insulin resistance predicts the progression from simple steatosis to cirrhosis in ALD patients. Both clinical and experimental data implicate the impairment of several mediators of insulin signaling in ALD, and experimental data suggest that insulin-sensitizing therapies improve liver histology. This review explores the contribution of impaired insulin signaling in ALD and summarizes the current understanding of the synergistic relationship between alcohol and nutrient excess in promoting hepatic inflammation and disease. PMID:25998863

  8. Evaluation of liver function using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid enhanced magnetic resonance imaging based on a three-dimensional volumetric analysis system.

    PubMed

    Kudo, Masashi; Gotohda, Naoto; Sugimoto, Motokazu; Kobayashi, Tatsushi; Kojima, Motohiro; Takahashi, Shinichiro; Konishi, Masaru; Hayashi, Ryuichi

    2018-06-02

    Magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (EOB-MRI) is a diagnostic modality for liver tumors. Three-dimensional (3D) volumetric analysis systems using EOB-MRI data are used to simulate liver anatomy for surgery. This study was conducted to investigate clinical utility of a 3D volumetric analysis system on EOB-MRI to evaluate liver function. Between August 2014 and December 2015, 181 patients underwent laboratory and radiological exams as standardized preoperative evaluation for liver surgery. The liver-spleen contrast-enhanced ratio (LSR) was measured by a semi-automated 3D volumetric analysis system on EOB-MRI. First, the inter-evaluator variability of the calculated LSR was evaluated. Additionally, a subset of liver surgical specimens was evaluated histologically by using immunohistochemical staining. Finally, the correlations between the LSR and grading systems of liver function, laboratory data, or histological findings were analyzed. The inter-evaluator correlation coefficient of the measured LSR was 0.986. The mean LSR was significantly correlated with the Child-Pugh score (p = 0.014) and the ALBI score (p < 0.001). Significant correlations were also observed between the LSR and indocyanine green retention rate at 15 min (r = - 0.601, p < 0.001), between the LSR and liver fibrosis stage (r = - 0.556, p < 0.001), and between the LSR and liver steatosis grade (r = - 0.396, p < 0.001). The LSR calculated by a 3D volumetric analysis system on EOB-MRI was highly reproducible and was shown to be correlated with liver function parameters and liver histology. These data suggest that this imaging modality can be a reliable tool to evaluate liver function.

  9. Effect of fibrin glue occlusion of the hepatobiliary tract on thioacetamide-induced liver failure.

    PubMed

    Schmandra, T C; Bauer, H; Petrowsky, H; Herrmann, G; Encke, A; Hanisch, E

    2001-07-01

    Expression and activation of hepatocyte growth factor (HGF) is stimulated by a complex system of interacting proteins, with thrombin playing an initial role in this process. The impact of temporary occlusion of the hepatobiliary tract with fibrin glue (major component thrombin) on the HGF system in acute and chronic liver damage in a rat model was investigated. Chronic liver damage was induced in 40 rats by daily intraperitoneal application of thioacetamide (100 mg/kg) for 14 days. After 7 days half of them received an injection of 0.2 mL fibrin glue into the hepatobiliary system. Daily intraperitoneal administration of thioacetamide continued for 7 consecutive days. The rats were then sacrificed for blood and tissue analysis. Acute liver failure was induced in 12 rats by intraperitoneal administration of a lethal dose of thioacetamide (500 mg/kg per day for 3 days) after an injection with 0.2 mL fibrin glue into their hepatobiliary tract. Survival rates and histological outcome were investigated and compared with control animals. Fibrin glue occluded rats showed significantly lower liver enzyme activities and serum levels of bilirubin, creatinine and urea nitrogen. Immunohistochemistry revealed a significant increase in c-met-, HGFalpha- and especially HGFbeta-positive cells. Rats subjected to a lethal dose of thioacetamide survived when fibrin glue was applied 24 hours prior to the toxic challenge. These animals showed normal liver structure and no clinical abnormalities. Fibrin glue occlusion of the hepatobiliary tract induces therapeutic and prophylactic effects on chronic and acute liver failure by stimulating the HGF system. Therefore, fibrin glue occlusion might be useful in treating toxic liver failure.

  10. Electrolytic ablation as an adjunct to liver resection: Safety and efficacy in patients.

    PubMed

    Wemyss-Holden, Simon A; Berry, David P; Robertson, Gavin S M; Dennison, Ashley R; De La M Hall, Pauline; Maddern, Guy J

    2002-08-01

    Electrolytic ablation is a relatively new method for the local destruction of colorectal liver metastases. Experimental work in animal models has shown this method to be safe and efficacious. However, before proceeding to clinical trials it was necessary to confirm these findings in a pilot study of five patients. Five patients with colorectal liver metastases were studied prospectively. Each patient underwent a potentially curative liver resection. One of the metastases to be removed was treated using electrolysis before resection. Each patient was monitored closely during and after electrolysis to determine any morbidity associated with the treatment. Once resected, the metastases were examined histologically for completeness of ablation. All patients tolerated the electrolysis well; there were no deaths or complications related to the treatment. Histological examination of the resected metastases which had been treated electrolytically showed complete tissue destruction with no viable malignant cells remaining at the site of treatment. This pilot study of electrolytic ablation of liver metastases in five patients showed the treatment to be well tolerated and safe. Additionally, it demonstrated total destruction of the malignant tissue at the site of electrolysis. Based on these encouraging results, clinical trials can now begin.

  11. Fate of Entamoeba histolytica during establishment of amoebic liver abscess analyzed by quantitative radioimaging and histology.

    PubMed

    Rigothier, Marie-Christine; Khun, Hout; Tavares, Paulo; Cardona, Ana; Huerre, Michel; Guillén, Nancy

    2002-06-01

    The protozoan parasite Entamoeba histolytica is the causative agent of amoebiasis, a human disease characterized by dysentery and liver abscess. The physiopathology of hepatic lesions can be satisfactorily reproduced in the hamster animal model by the administration of trophozoites through the portal vein route. Hamsters were infected with radioactively labeled amoebas for analysis of liver abscess establishment and progression. The radioimaging of material from parasite origin and quantification of the number inflammation foci, with or without amoebas, described here provides the first detailed assessment of trophozoite survival and death during liver infection by E. histolytica. The massive death of trophozoites observed in the first hours postinfection correlates with the presence of a majority of inflammatory foci without parasites. A critical point for success of infection is reached after 12 h when the lowest number of trophozoites is observed. The process then enters a commitment phase during which parasites multiply and the size of the infection foci increases fast. The liver shows extensive areas of dead hepatocytes that are surrounded by a peripheral layer of parasites facing inflammatory cells leading to acute inflammation. Our results show that the host response promotes massive parasite death but also suggest also that this is a major contributor to the establishment of inflammation during development of liver abscess.

  12. Fate of Entamoeba histolytica during Establishment of Amoebic Liver Abscess Analyzed by Quantitative Radioimaging and Histology

    PubMed Central

    Rigothier, Marie-Christine; Khun, Hout; Tavares, Paulo; Cardona, Ana; Huerre, Michel; Guillén, Nancy

    2002-01-01

    The protozoan parasite Entamoeba histolytica is the causative agent of amoebiasis, a human disease characterized by dysentery and liver abscess. The physiopathology of hepatic lesions can be satisfactorily reproduced in the hamster animal model by the administration of trophozoites through the portal vein route. Hamsters were infected with radioactively labeled amoebas for analysis of liver abscess establishment and progression. The radioimaging of material from parasite origin and quantification of the number inflammation foci, with or without amoebas, described here provides the first detailed assessment of trophozoite survival and death during liver infection by E. histolytica. The massive death of trophozoites observed in the first hours postinfection correlates with the presence of a majority of inflammatory foci without parasites. A critical point for success of infection is reached after 12 h when the lowest number of trophozoites is observed. The process then enters a commitment phase during which parasites multiply and the size of the infection foci increases fast. The liver shows extensive areas of dead hepatocytes that are surrounded by a peripheral layer of parasites facing inflammatory cells leading to acute inflammation. Our results show that the host response promotes massive parasite death but also suggest also that this is a major contributor to the establishment of inflammation during development of liver abscess. PMID:12011016

  13. Stability, Visibility, and Histologic Analysis of a New Implanted Fiducial for Use as a Kilovoltage Radiographic or Radioactive Marker for Patient Positioning and Monitoring in Radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Neustadter, David, E-mail: david.n@navotek.co; Tune, Michal; Zaretsky, Asaph

    Purpose: To analyze the stability, visibility, and histology of a novel implantable soft-tissue marker (nonradioactive and radioactive) implanted in dog prostate and rabbit liver. Methods and Materials: A total of 34 nonradioactive and 35 radioactive markers were implanted in 1 dog and 16 rabbits. Stability was assessed by measuring intermarker distance (IMD) variation relative to IMDs at implantation. The IMDs were measured weekly for 4 months in the dog and biweekly for 2-4 weeks in the rabbits. Ultrasound and X-ray imaging were performed on all subjects. Computed tomography and MRI were performed on the dog. Histologic analysis was performed onmore » the rabbits after 2 or 4 months. Results: A total of 139 measurements had a mean ({+-} SD) absolute IMD variation of 1.1 {+-} 1.1 mm. These IMD variations are consistent with those reported in the literature as due to random organ deformation. The markers were visible, identifiable, and induced minimal or no image artifacts in all tested imaging modalities. Histologic analysis revealed that all pathologic changes were highly localized and not expected to be clinically significant. Conclusions: The markers were stable from the time of implantation. The markers were found to be compatible with all common medical imaging modalities. The markers caused no significant histologic effects. With respect to marker stability, visibility, and histologic analysis these implanted fiducials are appropriate for soft-tissue target positioning in radiotherapy.« less

  14. Sleeping Beauty Transposon Vectors in Liver-directed Gene Delivery of LDLR and VLDLR for Gene Therapy of Familial Hypercholesterolemia

    PubMed Central

    Turunen, Tytteli A K; Kurkipuro, Jere; Heikura, Tommi; Vuorio, Taina; Hytönen, Elisa; Izsvák, Zsuzsanna; Ylä-Herttuala, Seppo

    2016-01-01

    Plasmid-based Sleeping Beauty (SB) transposon vectors were developed and used to deliver genes for low-density lipoprotein and very-low-density lipoprotein receptors (LDLR and VLDLR, respectively) or lacZ reporter into liver of an LDLR-deficient mouse model of familial hypercholesterolemia (FH). SB transposase, SB100x, was used to integrate the therapeutic transposons into mice livers for evaluating the feasibility of the vectors in reducing high blood cholesterol and the progression of atherosclerosis. Hydrodynamic gene delivery of transposon-VLDLR into the livers of the mice resulted in initial 17–19% reductions in plasma cholesterol, and at the later time points, in a significant stabilization of the cholesterol level for the 6.5-month duration of the study compared to the control mice. Transposon-LDLR-treated animals also demonstrated a trend of stabilization in the cholesterol levels in the long term. Vector-treated mice had slightly less lipid accumulation in the liver and reduced aortic atherosclerosis. Clinical chemistry and histological analyses revealed normal liver function and morphology comparable to that of the controls during the follow-up with no safety issues regarding the vector type, transgenes, or the gene transfer method. The study demonstrates the safety and potential benefits of the SB transposon vectors in the treatment of FH. PMID:26670130

  15. Chronic administration of Angelica sinensis polysaccharide effectively improves fatty liver and glucose homeostasis in high-fat diet-fed mice.

    PubMed

    Wang, Kaiping; Cao, Peng; Wang, Hanxiang; Tang, Zhuohong; Wang, Na; Wang, Jinglin; Zhang, Yu

    2016-05-18

    This study aimed to investigate the therapeutic effects of Angelica sinensis polysaccharide (ASP), an active component derived from a water extract of Angelica sinensis, in high-fat diet (HFD)-fed BALB/c mice. The potential mechanisms underlying the activity of this compound were also considered. Specifically, serum and hepatic biochemical parameters were evaluated, and key proteins involved in the lipid/glucose metabolism were analyzed. Long-term feeding with a HFD induced severe fatty liver and hyperglycemia. Histological examination clearly showed that ASP reduced lipid accumulation in the liver and attenuated hepatic steatosis in HFD-fed mice. In addition, ASP markedly alleviated serum and liver lipid disorders and fatty liver via the upregulation of PPARγ expression and the activation of adiponectin-SIRT1-AMPK signaling. Furthermore, ASP also significantly relieved severe oxidative stress, demonstrating that ASP might attenuate nonalcoholic fatty liver disease via a "two-hit" mechanism. In addition, ASP reduced blood glucose levels and ameliorated insulin resistance via the regulation of related metabolic enzymes and by activating the PI3K/Akt pathway in HFD-fed mice. Our findings revealed that ASP might be used as an alternative dietary supplement or health care product to ameliorate metabolic syndrome in populations that consistently consume HFDs.

  16. [Parasitological examinations of the hydatoid cysts of liver].

    PubMed

    Cielecka, D; Gierczak, A; Michałowicz, B; Grytner-Ziecina, B

    2001-01-01

    Liver cysts taken from 9 patients, operated on in the Medical Academy Clinic in 2000, have been examined. Cyst layers, their thickness and content have been analysed. We have searched for the cestoid scolexes and rostellar hooks. In 6 patients Echinococcus granulosus larvae have been found. In 4 cases there have been protoscolexes discovered, however with some signs of degeneration of the larva. In one case dead larva has been diagnosed on the basis of the presence of single hooks and in one patient one larva alive with unchanged structures has been revealed. Profound parasitological examination is a good supplement to the examination of the histopathological slides, especially in the case of degenerating larvae, when the tissues of the parasite lose their contact with the connective tissue layer of the host. Separated layer fragments, as well as protoscolexes and rostellar hooks need not be exposed to histological cutting.

  17. Functional pitch of a liver: fatty liver disease diagnosis with photoacoustic spectrum analysis

    NASA Astrophysics Data System (ADS)

    Xu, Guan; Meng, Zhuoxian; Lin, Jiandie; Carson, Paul; Wang, Xueding

    2014-03-01

    To provide more information for classification and assessment of biological tissues, photoacoustic spectrum analysis (PASA) moves beyond the quantification of the intensities of the photoacoustic (PA) signals by the use of the frequency-domain power distribution, namely power spectrum, of broadband PA signals. The method of PASA quantifies the linear-fit to the power spectrum of the PA signals from a biological tissue with 3 parameters, including intercept, midband-fit and slope. Intercept and midband-fit reflect the total optical absorption of the tissues whereas slope reflects the heterogeneity of the tissue structure. Taking advantage of the optical absorption contrasts contributed by lipid and blood at 1200 and 532 nm, respectively and the heterogeneous tissue microstructure in fatty liver due to the lipid infiltration, we investigate the capability of PASA in identifying histological changes of fatty livers in mouse model. 6 and 9 pairs of normal and fatty liver tissues from rat models were examined by ex vivo experiment with a conventional rotational PA measurement system. One pair of rat models with normal and fatty livers was examined non-invasively and in situ with our recently developed ultrasound and PA parallel imaging system. The results support our hypotheses that the spectrum analysis of PA signals can provide quantitative measures of the differences between the normal and fatty liver tissues and that part of the PA power spectrum can suffice for characterization of microstructures in biological tissues. Experimental results also indicate that the vibrational absorption peak of lipid at 1200nm could facilitate fatty liver diagnosis.

  18. Temporary Arterial Embolization of Liver Parenchyma with Degradable Starch Microspheres (EmboCept{sup ®}S) in a Swine Model

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pieper, Claus C., E-mail: claus.christian.pieper@ukb.uni-bonn.de; Meyer, Carsten, E-mail: Carsten.Meyer@ukb.uni-bonn.de; Vollmar, Brigitte, E-mail: brigitte.vollmar@med.uni-rostock.de

    BackgroundThis study aimed to evaluate the embolic properties, time to reperfusion, and histologic changes in temporary embolization of liver tissue with degradable starch microspheres (DSM) in a swine model.MethodsIn four adult minipigs, DSMs were injected into the right or left hepatic artery on the lobar level until complete stasis of the blood flow was detectable angiographically. The time required to complete angiographically determined reperfusion was noted. The animals were killed 3 h after complete reperfusion, and samples were taken from the liver. Histologic examinations of the embolized liver parenchyma and untreated tissue were performed.ResultsHepatic arterial embolization using DSMs was technically successfulmore » in all cases, with complete blood flow stasis shown by control angiography. A single vial of DSMs (450 mg/7.5 ml) was sufficient to embolize a whole liver lobe in all cases. Angiography showed complete reconstitution of hepatic arterial perfusion after a mean time to reperfusion of 32 ± 6.1 min (range, 26–39 min). Hematoxylin and eosin staining showed no histologically detectable differences between untreated tissue and parenchyma embolized with DSMs except for mild sinusoidal congestion in one case. Indirect in situ DNA nick end labeling staining (TUNEL) showed only single positive hepatocytes, indicating apoptosis.ConclusionTemporary embolization of the hepatic artery using DSMs is feasible with complete reperfusion after 30 min in pigs. Even after complete arterial blood flow stasis, no extensive tissue damage to the embolized liver parenchyma was observed at histologic examinations in this short-term study.« less

  19. Bendiocarb induced histopathological and biochemical alterations in rat liver and preventive role of vitamins C and E.

    PubMed

    Apaydin, Fatma Gökçe; Baş, Hatice; Kalender, Suna; Kalender, Yusuf

    2017-01-01

    In this study, biochemical changes and histological structure of rat liver after bendiocarb administration and possible preventive effects of vitamins C and E were studied. The animals were given with bendiocarb, vitamin C and vitamin E, daily 0,8mg/kg of body weight (bw), 100mg/kg-bw and 100mg/kg-bw for 28days, respectively. Lipid peroxidation, antioxidant enzyme activities, histological alterations and antioxidant capacity assays of liver and also liver function tests and lipid profile were measured. Bendiocarb treatment decreased the antioxidant enzyme activities, FRAP and TEAC values and increased malondialdehyde levels compared to control. Also, there were statistically significant alterations in liver function tests, lipid profile parameters and histopathological changes in bendiocarb treated groups. Vitamins C and E showed protective effects against examining parameters. According to results we can say that co-treatment of vitamin C and vitamin E may be more effective than use of them alone. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Pathology and biopsy assessment of non-alcoholic fatty liver disease.

    PubMed

    Straub, Beate Katharina; Schirmacher, Peter

    2010-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases in Western industrialized countries with dramatically rising incidence. The diagnosis of NAFLD requires the existence of steatosis in the absence of significant alcohol consumption. In cases of relevant inflammation pathogenetically linked to steatosis, it is termed non-alcoholic steatohepatitis (NASH). While pure steatosis represents a relatively harmless and rapidly reversible condition without a significant tendency to progression, NASH carries a significant morbidity and progression risk. Noninvasive methods neither reliably establish the diagnosis nor define the extent of disease in NASH, making histopathology the diagnostic gold standard. Since current therapeutic options in NASH are limited, indication for biopsy is made in the clinical context, predominantly in unclear clinical constellations, prior to invasive measures, for follow-up purposes and in the context of clinical studies. Histological hallmarks of NASH are steatosis, hepatocellular ballooning (with and without Mallory-Denk bodies), necroinflammation, and progressing disease a characteristic with perisinusoidal fibrosis. For semiquantitative assessment of necroinflammation (grading) and fibrosis (staging), a score has recently been implemented. Although histology does not reliably distinguish alcoholic steatohepatitis/alcoholic fatty liver disease from NASH/NAFLD, it may give valuable hints. NASH has a tendency for more steatosis, the so-called glycogenated nuclei, and less necroinflammatory activity. Future development of biopsy diagnosis will be coupled to the development of differential systemic therapeutic approaches. Especially in the context of clinical studies, detailed histological evaluation should be considered for the detection of predictive parameters. Copyright 2010 S. Karger AG, Basel.

  1. Distribution of Ca, Fe, Cu and Zn in primary colorectal cancer and secondary colorectal liver metastases

    NASA Astrophysics Data System (ADS)

    Al-Ebraheem, A.; Mersov, A.; Gurusamy, K.; Farquharson, M. J.

    2010-07-01

    A microbeam synchrotron X-ray fluorescence (μSRXRF) technique has been used to determine the localization and the relative concentrations of Zn, Cu, Fe and Ca in primary colorectal cancer and secondary colorectal liver metastases. 24 colon and 23 liver samples were examined, all of which were formalin fixed tissues arranged as microarrays of 1.0 mm diameter and 10 μm thickness. The distribution of these metals was compared with light transmission images of adjacent sections that were H and E stained to reveal the location of the cancer cells. Histological details were provided for each sample which enable concentrations of all elements in different tissue types to be compared. In the case of liver, significant differences have been found for all elements when comparing tumour, normal, necrotic, fibrotic, and blood vessel tissues (Kruskal Wallis Test, P<0.0001). The concentrations of all elements have also been found to be significantly different among tumour, necrotic, fibrotic, and mucin tissues in the colon samples (Kruskal Wallis Test, P<0.0001). The concentrations of all elements have been compared between primary colorectal samples and colorectal liver metastases. Concentration of Zn, Cu, Fe and Ca are higher in all types of liver tissues compared to those in the colon tissues. Comparing liver tumour and colon tumour samples, significant differences have been found for all elements (Mann Whitney, P<0.0001). For necrotic tissues, significant increase has been found for Zn, Ca, Cu and Fe (Mann Whitney, P<0.0001 for Fe and Zn, 0.014 for Ca, and 0.001 for Cu). The liver fibrotic levels of Zn, Ca, Cu and Fe were higher than the fibrotic colon areas (independent T test, P=0.007 for Zn and Mann Whitney test P<0.0001 for Cu, Fe and Ca). For the blood vessel tissue, the analysis revealed that the difference was only significant for Fe ( P=0.009) from independent T test.

  2. CHARACTERISTICS OF RAT LIVER EXPOSED TO NANOPARTICLES OF LEAD COMPOUNDS.

    PubMed

    Omelchuk, S; Aleksijchuk, V; Sokurenko, L; Blagaia, A; Prudchenko, S

    2016-12-01

    In recent times, the lead becomes great importance in environmental pollution, including its nanoparticles. In the literature, there is little data on the changes in the liver after the exposure with lead nanoparticles. The purpose of this study was the identification and determination of macroscopic, microscopic, and biochemical changes of the structural elements of the rat's liver exposed to the action of lead compounds. The study was carried out on 60 male Wistar rats. The first and second groups of animals were intraperitoneally injected with colloidal solution of nanoparticles of Lead Sulfide size of 10 nm and 30 nm, and the third group was intraperitoneally injected with a solution of nitrate lead. Macroscopic, histological, histochemical, biochemical methods and gas chromatography were used to identify the changes of fatty acids metabolism. The experiment has found that body weights of animals in all tested groups were decreased after 6 weeks of lead nanoparticles injection, while relative liver weight was increased. Levels of total lipids and cholesterol, total protein and albumin in the blood serum in study groups have decreased, and the level of triglycerides and glucose have increased. Moderate dystrophic changes were observed in the histological examinations of the liver, and this was confirmed by morphometric and densitometric parameters. Changes of fatty acid composition of lipids of the liver exposed to nanoparticles were the result of increasing arachidonic fatty acid content and reduction of the stearic fatty acid content. Thus, it has been proven by the experiment that the effect of lead nanoparticles depends on their size.

  3. Prevention of CCl4-induced liver damage by ginger, garlic and vitamin E.

    PubMed

    Patrick-Iwuanyanwu, K C; Wegwu, M O; Ayalogu, E O

    2007-02-15

    The hepatoprotective effects of garlic (Allium sativum), ginger (Zingiber officinale) and vitamin E pre-treatment against carbon tetrachloride (CCl4)-induced liver damage in male wistar albino rats were investigated. Carbon tetrachloride (0.5 mL kg(-1) body weight) was administered after 28 days of feeding animals with diets containing ginger, garlic, vitamin E and various mixtures of ginger and garlic. Serum alanine amino transferase, aspartate amino transferase and alkaline phosphatase levels, 24 h after CCl4 administration, decreased significantly (p < or = 0.05) in rats pre-treated with garlic, ginger, vitamin E and various mixtures of garlic and ginger than in CCl4-treated rats only. Lipid peroxidation expressed by serum malondialdehyde (MDA) concentration was assayed to assess the extent of liver damage by CCl4; including the extent of hepatoprotection by garlic, ginger and vitamin E. MDA concentration was significantly decreased (p < or = 0.05) in rats pretreated with garlic, ginger, vitamin E and various mixtures of garlic and ginger than in rats administered CCl4-alone. Histological examination of the liver revealed severe infiltration of inflammatory cells in rats treated with CCl4 alone. However, the observed alteration in the normal architecture of the hepatic cells decreased remarkably in pre-treated rats.

  4. Interobserver Variability in Histologic Evaluation of Liver Fibrosis Using Categorical and Quantitative Scores.

    PubMed

    Pavlides, Michael; Birks, Jacqueline; Fryer, Eve; Delaney, David; Sarania, Nikita; Banerjee, Rajarshi; Neubauer, Stefan; Barnes, Eleanor; Fleming, Kenneth A; Wang, Lai Mun

    2017-04-01

    The aim of the study was to investigate the interobserver agreement for categorical and quantitative scores of liver fibrosis. Sixty-five consecutive biopsy specimens from patients with mixed liver disease etiologies were assessed by three pathologists using the Ishak and nonalcoholic steatohepatitis Clinical Research Network (NASH CRN) scoring systems, and the fibrosis area (collagen proportionate area [CPA]) was estimated by visual inspection (visual-CPA). A subset of 20 biopsy specimens was analyzed using digital imaging analysis (DIA) for the measurement of CPA (DIA-CPA). The bivariate weighted κ between any two pathologists ranged from 0.57 to 0.67 for Ishak staging and from 0.47 to 0.57 for the NASH CRN staging. Bland-Altman analysis showed poor agreement between all possible pathologist pairings for visual-CPA but good agreement between all pathologist pairings for DIA-CPA. There was good agreement between the two pathologists who assessed biopsy specimens by visual-CPA and DIA-CPA. The intraclass correlation coefficient, which is equivalent to the κ statistic for continuous variables, was 0.78 for visual-CPA and 0.97 for DIA-CPA. These results suggest that DIA-CPA is the most robust method for assessing liver fibrosis followed by visual-CPA. Categorical scores perform less well than both the quantitative CPA scores assessed here. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  5. Three-dimensional visualization of the microvasculature of bile duct ligation-induced liver fibrosis in rats by x-ray phase-contrast imaging computed tomography

    NASA Astrophysics Data System (ADS)

    Xuan, Ruijiao; Zhao, Xinyan; Hu, Doudou; Jian, Jianbo; Wang, Tailing; Hu, Chunhong

    2015-07-01

    X-ray phase-contrast imaging (PCI) can substantially enhance contrast, and is particularly useful in differentiating biological soft tissues with small density differences. Combined with computed tomography (CT), PCI-CT enables the acquisition of accurate microstructures inside biological samples. In this study, liver microvasculature was visualized without contrast agents in vitro with PCI-CT using liver fibrosis samples induced by bile duct ligation (BDL) in rats. The histological section examination confirmed the correspondence of CT images with the microvascular morphology of the samples. By means of the PCI-CT and three-dimensional (3D) visualization technique, 3D microvascular structures in samples from different stages of liver fibrosis were clearly revealed. Different types of blood vessels, including portal veins and hepatic veins, in addition to ductular proliferation and bile ducts, could be distinguished with good sensitivity, excellent specificity and excellent accuracy. The study showed that PCI-CT could assess the morphological changes in liver microvasculature that result from fibrosis and allow characterization of the anatomical and pathological features of the microvasculature. With further development of PCI-CT technique, it may become a novel noninvasive imaging technique for the auxiliary analysis of liver fibrosis.

  6. T1-weighted dual-echo MRI for fat quantification in pediatric nonalcoholic fatty liver disease.

    PubMed

    Pacifico, Lucia; Martino, Michele Di; Catalano, Carlo; Panebianco, Valeria; Bezzi, Mario; Anania, Caterina; Chiesa, Claudio

    2011-07-07

    To determine in obese children with nonalcoholic fatty liver disease (NAFLD) the accuracy of magnetic resonance imaging (MRI) in assessing liver fat concentration. A case-control study was performed. Cases were 25 obese children with biopsy-proven NAFLD. Controls were 25 obese children matched for age and gender, without NAFLD at ultrasonography and with normal levels of aminotransferases and insulin. Hepatic fat fraction (HFF) by MRI was obtained using a modification of the Dixon method. HFF ranged from 2% to 44% [mean, 19.0% (95% CI, 15.1-27.4)] in children with NAFLD, while in the controls this value ranged from 0.08% to 4.69% [2.0% (1.3-2.5), P < 0.0001]. HFF was highly correlated with histological steatosis (r = 0.883, P < 0.0001) in the NAFLD children. According to the histological grade of steatosis, the mean HFF was 8.7% (95% CI, 6.0-11.6) for mild, 21.6% (15.3-27.0) for moderate, and 39.7% (34.4-45.0) for severe fatty liver infiltration. With a cutoff of 4.85%, HFF had a sensitivity of 95.8% for the diagnosis of histological steatosis ≥ 5%. All control children had HFF lower than 4.85%; thus, the specificity was 100%. After 12 mo, children with weight loss displayed a significant decrease in HFF. MRI is an accurate methodology for liver fat quantification in pediatric NAFLD.

  7. Hepatic injury due to combined choline-deprivation and thioacetamide administration: an experimental approach to liver diseases.

    PubMed

    Al-Humadi, Hussam; Theocharis, Stamatios; Dontas, Ismene; Stolakis, Vasileios; Zarros, Apostolos; Kyriakaki, Argyro; Al-Saigh, Rafal; Liapi, Charis

    2012-12-01

    The induction of prolonged choline-deprivation (CD) in rats receiving thioacetamide (TAA) is an experimental approach of mild hepatotoxicity that could resemble commonly presented cases in clinical practice (in which states of malnutrition and/or alcoholism are complicated by the development of other liver-associated diseases). The present study aimed to investigate the time-dependent effects of a 30-, a 60- and a 90-day dietary CD and/or TAA administration on the adult rat liver histopathology and the serum markers of hepatic functional integrity. Rats were divided into four main groups: (a) control, (b) CD, (c) TAA and (d) CD + TAA. Dietary CD was provoked through the administration of choline-deficient diet, while TAA administration was performed ad libitum through the drinking water (300 mg/l of drinking water). Histological examination of the CD + TAA liver sections revealed micro- and macro-vesicular steatosis with degeneration and primary fibrosis at day 30, to extensive steatosis and fibrosis at day 90. Steatosis was mostly of the macrovesicular type, involving all zones of the lobule, while inflammatory infiltrate consisted of foci of acute and chronic inflammatory cells randomly distributed in the lobule. These changes were accompanied by gradually increasing mitotic activity, as well as by a constantly high alpha-smooth muscle actin immunohistochemical staining. The determination of hepatocellular injury markers such as the serum enzyme levels' of alanine aminotransferase and aspartate aminotransferase demonstrated a decrease at day 30 (they returned to control levels at days 60 and 90). However, the determination of those serum enzymes used for the assessment of cholestatic liver injury (gamma-glutamyltransferase, alkaline phosphatase) revealed a constant (time-independent) statistically-significant increase versus control values. Long-term combined dietary CD and TAA administration could be a more realistic experimental approach to human liver diseases

  8. Evaluation of liver fibrosis: “Something old, something new…”

    PubMed Central

    Almpanis, Zannis; Demonakou, Maria; Tiniakos, Dina

    2016-01-01

    Hepatic fibrogenesis may gradually result to cirrhosis due to the accumulation of extracellular matrix components as a response to liver injury. Thus, therapeutic decisions in chronic liver disease, regardless of the cause, should first and foremost be guided by an accurate quantification of hepatic fibrosis. Detection and assessment of the extent of hepatic fibrosis represent a challenge in modern Hepatology. Although traditional histological staging systems remain the “best standard”, they are not able to quantify liver fibrosis as a dynamic process and may not accurately substage cirrhosis. This review aims to compare the currently used non-invasive methods of measuring liver fibrosis and provide an update in current tissue-based digital techniques developed for this purpose, that may prove of value in daily clinical practice. PMID:27708509

  9. Development of a new extracorporeal whole-liver perfusion system.

    PubMed

    Naruse, Katsutoshi; Sakai, Yasuyuki; Guo, Lei; Natori, Takeshi; Shindoh, Junichi; Karasawa, Yasuaki; Iida, Yuhki; Kojima, Kentaro; Michishita, Kazuya; Makuuchi, Masatoshi

    2003-01-01

    We have developed a new extracorporeal whole-liver accommodation device in which a whole swine liver is placed in a physiological state by modeling the intraabdominal arrangement in the pig body, with the liver supported by a special inferior vena cava tube. Furthermore, we employed a diaphragm-type artificial heart in our system to produce pulsatile blood flow through the hepatic artery, which is considered to be indispensable to dilate peripheral vessels and supply oxygenated whole blood to the peripheral liver tissue. Beneficial effects were demonstrated in visual findings and bile juice secretion. The color of the liver surface in our system remained bright red, indicating that the liver vessels were well drained and free from congestion, and bile juice secretion was maintained at more than 10 ml/h throughout the perfusion period. Our system exhibited excellent ammonia removal and urea nitrogen synthesis, and serum aspartate aminotransferase levels showed no increase, indicating the absence of hepatocyte destruction. Histological findings showed that the liver could expand appropriately and was free from compression caused by its own weight. In conclusion, our original liver accommodation device enabled appropriate expansion of the whole liver and supplied adequate oxygenated blood to peripheral areas by means of a pulsatile pump.

  10. Xenotransplantation of neonatal porcine liver cells.

    PubMed

    Garkavenko, O; Emerich, D F; Muzina, M; Muzina, Z; Vasconcellos, A V; Ferguson, A B; Cooper, I J; Elliott, R B

    2005-01-01

    Xenotransplantation of porcine liver cell types may provide a means of overcoming the shortage of suitable donor tissues to treat hepatic diseases characterized by inherited inborn errors of metabolism or protein production. Here we report the successful isolation, culture, and xenotransplantation of liver cells harvested from 7- to 10-day-old piglets. Liver cells were isolated and cultured immediately after harvesting. Cell viability was excellent (>90%) over the duration of the in vitro studies (3 weeks) and the cultured cells continued to significantly proliferate. These cells also retained their normal secretory and metabolic capabilities as determined by continued release of albumin, factor 8, and indocyanin green (ICG) uptake. After 3 weeks in culture, porcine liver cells were loaded into immunoisolatory macro devices (Theracyte devices) and placed into the intraperitoneal cavity of immunocompetant CD1 mice. Eight weeks later, the devices were retrieved and the cells analyzed for posttransplant determinations of survival and function. Post mortem analysis confirmed that the cell-loaded devices were biocompatible, and were well-tolerated without inducing any notable inflammatory reaction in the tissues immediately surrounding the encapsulated cells. Finally, the encapsulated liver cells remained viable and functional as determined by histologic analyses and ICG uptake/release. The successful harvesting, culturing, and xenotransplantation of functional neonatal pig liver cells support the continued development of this approach for treating a range of currently undertreated or intractable hepatic diseases.

  11. Anti-fatty liver effects of oils from Zingiber officinale and Curcuma longa on ethanol-induced fatty liver in rats.

    PubMed

    Nwozo, Sarah Onyenibe; Osunmadewa, Damilola Adeola; Oyinloye, Babatunji Emmanuel

    2014-01-01

    The present study is aimed at evaluating the protective effects of oils from Zingiber officinale (ginger) and Curcuma longa (turmeric) on acute ethanol-induced fatty liver in male Wistar rats. Ferric reducing antioxidant power activity and oxygen radical absorbance capacity of the oils were evaluated ex vivo. Rats were pretreated for 28 d with standard drug (Livolin Forte) and oils from Z. officinale and C. longa before they were exposed to 45% ethanol (4.8 g/kg) to induce acute fatty liver. Histological changes were observed and the degree of protection was measured by using biochemical parameters such as alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities. Serum triglyceride (TG) level, total cholesterol (TC) level and the effects of both oils on reduced gluthatione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and hepatic malondialdehyde (MDA) levels were estimated. Oils from Z. officinale and C. longa at a dose of 200 mg/kg showed hepatoprotection by decreasing the activities of serum enzymes, serum TG, serum TC and hepatic MDA, while they significantly restored the level of GSH as well as GST and SOD activities. Histological examination of rats tissues was related to the obtained results. From the results it may be concluded that oils from Z. officinale and C. longa (200 mg/kg) exhibited hepatoprotective activity in acute ethanol-induced fatty liver and Z. officinale oil was identified to have better effects than C. longa oil.

  12. Quantification of Liver Iron with MRI: State of the Art and Remaining Challenges

    PubMed Central

    Hernando, Diego; Levin, Yakir S; Sirlin, Claude B; Reeder, Scott B

    2015-01-01

    Liver iron overload is the histological hallmark of hereditary hemochromatosis and transfusional hemosiderosis, and can also occur in chronic hepatopathies. Iron overload can result in liver damage, with the eventual development of cirrhosis, liver failure and hepatocellular carcinoma. Assessment of liver iron levels is necessary for detection and quantitative staging of iron overload, and monitoring of iron-reducing treatments. This article discusses the need for non-invasive assessment of liver iron, and reviews qualitative and quantitative methods with a particular emphasis on MRI. Specific MRI methods for liver iron quantification include signal intensity ratio as well as R2 and R2* relaxometry techniques. Methods that are in clinical use, as well as their limitations, are described. Remaining challenges, unsolved problems, and emerging techniques to provide improved characterization of liver iron deposition are discussed. PMID:24585403

  13. Steatorrhea in patients with liver disease

    PubMed Central

    Williams, C. N.; Sidorov, J. J.

    1971-01-01

    Intestinal function was studied in 26 patients with seven types of acute and chronic liver disease, documented by liver biopsy. Steatorrhea, defined by a stool fat higher than 6 g. per day, was present in 18 of 23 consecutive patients studied, an incidence of 78.3%. Two patients with infectious hepatitis associated with steatorrhea studied previously were added and the 20 cases were analyzed. The malabsorption found was confined to fat and fat-soluble vitamins; stool excretion varied from 6.1 to 22 g. per day in the seven groups studied. No histological abnormality was seen on jejunal biopsy, serum vitamin B12, D-xylose and Schilling tests were normal, and no radiological findings associated with malabsorption were detected in the small bowel. It is concluded that steatorrhea is a common finding in a wide variety of acute and chronic liver diseases and cannot be attributed to a primary defect of the small bowel. PMID:5150072

  14. Fibrosis assessment in chronic hepatitis C--is the liver biopsy still necessary? The pathologist point of view.

    PubMed

    Moroşan, Eugenia; Mihailovici, Maria-Sultana

    2014-01-01

    The aim of this study was to compare the histological stage of fibrosis determined by liver biopsy with the stage of fibrosis assessed by Fibroscan, to analyze the correspondences and inconsistencies between obtained values and to discuss the role of the microscopic exam, from the pathologist point of view. The study group consisted of 185 patients diagnosed with chronic hepatitis. Serological tests diagnosed chronic hepatitis C in 183 patients, and chronic hepatitis B and C for 2 patients. The patients were evaluated to determine the stage of fibrosis using two methods: liver biopsy and elastography (Fibroscan). Based on the pathologic evaluation, 124 cases were diagnosed as moderate chronic hepatitis (score 6-8), and the remaining 60 cases as severe hepatitis (score 9-12). Comparison of data from examination of liver biopsy with that obtained by Fibroscan examination revealed overlapping and divergent aspects. The fibrosis stage established through liver biopsy did not always coincide with the one assigned by liver stiffness measurement, particularly for intermediate stages F2 and F3. The best overlap was noted for F0-F1 and F4 stages, which indicates the evident ability of transient elastography to separate patients with minimal or no fibrosis from patients with extensive fibrosis. Our data concurs with the literature, which confirms presence of differences between Fibroscan and biopsy. From the point of view of the pathologist, liver biopsy still remains a valuable instrument, offering a relevant image of liver changes--as it is regarded more rather a selective than routine technique.

  15. Angiosarcoma of the liver in Great Britain in proximity to vinyl chloride sites.

    PubMed

    Elliott, P; Kleinschmidt, I

    1997-01-01

    To study the incidence of angiosarcoma of the liver in England and Wales 1979-86 and Scotland 1975-87. To investigate whether any non-occupational neighbourhood cases occurred near a vinyl chloride site. This is a geographical study of incident cases among the general population of Great Britain. Diagnosis of angiosarcoma of the liver was based mainly on the national cancer registry, the world register of cases among vinyl chloride workers, and the register of cases (including histological review) maintained by the Health and Safety Executive. Proximity (< 10 km) of residence to a vinyl chloride site was based on postcode of address at the time of diagnosis. 55 cases were ascribed to angiosarcoma of the liver in England and Wales with a further six cases in Scotland (annual incidence in Great Britain from all sources of around 1.4 cases per 10 million population). There were two cases with documented exposure to Thorotrast, and 10 cases among vinyl chloride workers. There were no vinyl chloride sites in Scotland. Among the 25 cases in England and Wales with histological diagnosis after review by a panel of pathologists, only 15 were confirmed as angiosarcoma, and one of the two Scottish cases after histological review was also confirmed. Overall, 11 cases ascribed to angiosarcoma were resident within 10 km of a vinyl chloride site; nine were vinyl chloride workers, one further case on histological review was not considered to have been correctly diagnosed as angiosarcoma, and the remaining case, confirmed as angiosarcoma, was employed at a vinyl chloride factory during the late 1950s, although not as a vinyl chloride worker. The incidence of angiosarcoma of the liver in Great Britain remains extremely rare. The one confirmed case in a non-vinyl chloride worker within 10 km of a site must nevertheless be presumed to have been exposed to vinyl chloride in the workplace. In the period of study, there were no confirmed non-occupationally exposed cases of angiosarcoma

  16. Angiosarcoma of the liver in Great Britain in proximity to vinyl chloride sites.

    PubMed Central

    Elliott, P; Kleinschmidt, I

    1997-01-01

    OBJECTIVES: To study the incidence of angiosarcoma of the liver in England and Wales 1979-86 and Scotland 1975-87. To investigate whether any non-occupational neighbourhood cases occurred near a vinyl chloride site. METHODS: This is a geographical study of incident cases among the general population of Great Britain. Diagnosis of angiosarcoma of the liver was based mainly on the national cancer registry, the world register of cases among vinyl chloride workers, and the register of cases (including histological review) maintained by the Health and Safety Executive. Proximity (< 10 km) of residence to a vinyl chloride site was based on postcode of address at the time of diagnosis. RESULTS: 55 cases were ascribed to angiosarcoma of the liver in England and Wales with a further six cases in Scotland (annual incidence in Great Britain from all sources of around 1.4 cases per 10 million population). There were two cases with documented exposure to Thorotrast, and 10 cases among vinyl chloride workers. There were no vinyl chloride sites in Scotland. Among the 25 cases in England and Wales with histological diagnosis after review by a panel of pathologists, only 15 were confirmed as angiosarcoma, and one of the two Scottish cases after histological review was also confirmed. Overall, 11 cases ascribed to angiosarcoma were resident within 10 km of a vinyl chloride site; nine were vinyl chloride workers, one further case on histological review was not considered to have been correctly diagnosed as angiosarcoma, and the remaining case, confirmed as angiosarcoma, was employed at a vinyl chloride factory during the late 1950s, although not as a vinyl chloride worker. CONCLUSION: The incidence of angiosarcoma of the liver in Great Britain remains extremely rare. The one confirmed case in a non-vinyl chloride worker within 10 km of a site must nevertheless be presumed to have been exposed to vinyl chloride in the workplace. In the period of study, there were no confirmed non

  17. Hepatoprotective Effect of Citral on Acetaminophen-Induced Liver Toxicity in Mice.

    PubMed

    Uchida, Nancy Sayuri; Silva-Filho, Saulo Euclides; Cardia, Gabriel Fernando Esteves; Cremer, Edivaldo; Silva-Comar, Francielli Maria de Souza; Silva, Expedito Leite; Bersani-Amado, Ciomar Aparecida; Cuman, Roberto Kenji Nakamura

    2017-01-01

    High doses of acetaminophen (APAP) lead to acute liver damage. In this study, we evaluated the effects of citral in a murine model of hepatotoxicity induced by APAP. The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase ( γ GT) were determined to evaluate the hepatoprotective effects of citral. The livers were used to determine myeloperoxidase (MPO) activity and nitric oxide (NO) production and in histological analysis. The effect of citral on leukocyte migration and antioxidant activity was evaluated in vitro. Citral pretreatment decreased significantly the levels of ALT, AST, ALP, and γ GT, MPO activity, and NO production. The histopathological analysis showed an improvement of hepatic lesions in mice after citral pretreatment. Citral inhibited neutrophil migration and exhibited antioxidant activity. Our results suggest that citral protects the liver against liver toxicity induced by APAP.

  18. Potential mechanisms of hepatitis B virus induced liver injury

    PubMed Central

    Suhail, Mohd; Abdel-Hafiz, Hany; Ali, Ashraf; Fatima, Kaneez; Damanhouri, Ghazi A; Azhar, Esam; Chaudhary, Adeel GA; Qadri, Ishtiaq

    2014-01-01

    Chronic active hepatitis (CAH) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma. The histological end points of CAH are chronic inflammation, fibrosis and cirrhosis which are coupled with increased DNA synthesis in cirrhotic vs healthy normal livers. The potential mechanism involved in CAH includes a combination of processes leading to liver cell necrosis, inflammation and cytokine production and liver scaring (fibrosis). The severity of liver damage is regulated by Hepatitis B virus genotypes and viral components. The viral and cellular factors that contribute to liver injury are discussed in this article. Liver injury caused by the viral infection affects many cellular processes such as cell signaling, apoptosis, transcription, DNA repair which in turn induce radical effects on cell survival, growth, transformation and maintenance. The consequence of such perturbations is resulted in the alteration of bile secretion, gluconeogenesis, glycolysis, detoxification and metabolism of carbohydrates, proteins, fat and balance of nutrients. The identification and elucidation of the molecular pathways perturbed by the viral proteins are important in order to design effective strategy to minimize and/or restore the hepatocytes injury. PMID:25253946

  19. The spinoglenoid ligament. Anatomy, morphology, and histological findings.

    PubMed

    Plancher, Kevin D; Peterson, Robert K; Johnston, Jack C; Luke, Timothy A

    2005-02-01

    Dysfunction of the distal branch of the suprascapular nerve has been reported in athletes involved in throwing or overhead sports. The consistent presence of a dynamic anatomic structure, the spinoglenoid ligament, overlying the nerve in the spinoglenoid notch may be a contributing factor to the dysfunction of this nerve. The purpose of this study was to report the anatomy, morphology, and histological characteristics of the spinoglenoid ligament. The spinoglenoid ligaments of fifty-eight fresh-frozen cadaver shoulders were dissected to evaluate their anatomic dimensions, histological characteristics, and relationship to the suprascapular nerve, the posterior part of the capsule, and the glenoid rim. The spinoglenoid ligament was harvested, with its insertions on the scapular spine and on the capsule and glenoid left intact, for the histological analysis. Dissection revealed that a spinoglenoid ligament was present in all specimens. The ligament was found to form an irregular quadrangular shape. On gross examination, the deep fibers of the ligament extended from the lateral aspect of the scapular spine to the posterior part of the glenoid and the superficial fibers blended with the posterior aspect of the shoulder capsule. Histological sections demonstrated Sharpey fibers inserting into bone at the scapular spine and blending with the posterior aspect of the shoulder capsule to insert into the posterior surface of the glenoid, findings that confirmed the ligamentous nature of this structure. This study revealed the presence of the spinoglenoid ligament in all of the shoulders that were examined, with some variation in the size of the ligament.

  20. Hepatic cholesterol ester hydrolase in human liver disease.

    PubMed

    Simon, J B; Poon, R W

    1978-09-01

    Human liver contains an acid cholesterol ester hydrolase (CEH) of presumed lysosomal origin, but its significance is unknown. We developed a modified CEH radioassay suitable for needle biopsy specimens and measured hepatic activity of this enzyme in 69 patients undergoing percutaneous liver biopsy. Histologically normal livers hydrolyzed 5.80 +/- 0.78 SEM mumoles of cholesterol ester per hr per g of liver protein (n, 10). Values were similar in alcoholic liver disease (n, 17), obstructive jaundice (n, 9), and miscellaneous hepatic disorders (n, 21). In contrast, mean hepatic CEH activity was more than 3-fold elevated in 12 patients with acute hepatitis, 21.05 +/- 2.45 SEM mumoles per hr per g of protein (P less than 0.01). In 2 patients studied serially, CEH returned to normal as hepatitis resolved. CEH activity in all patients paralleled SGOT levels (r, 0.84; P less than 0.01). There was no correlation with serum levels of free or esterified cholesterol nor with serum activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. These studies confirm the presence of CEH activity in human liver and show markedly increased activity in acute hepatitis. The pathogenesis and clinical significance of altered hepatic CEH activity in liver disease require further study.

  1. Ex vivo adenoviral gene transfer of constitutively activated STAT3 reduces post-transplant liver injury and promotes regeneration in a 20% rat partial liver transplant model.

    PubMed

    Huda, Kamrul A S M; Guo, Lei; Haga, Sanae; Murata, Hiroshi; Ogino, Tetsuya; Fukai, Moto; Yagi, Takahito; Iwagaki, Hiromi; Tanaka, Noriaki; Ozaki, Michitaka

    2006-05-01

    Signal transducer and activator of transcription-3 (STAT3) is one of the most important transcription factors for liver regeneration. This study was designed to examine the effects of constitutively activated STAT3 (STAT3-C) on post-transplant liver injury and regeneration in a rat 20% partial liver transplant (PLTx) model by ex vivo adenoviral gene transfer. Adenovirus encoding the STAT3-C gene was introduced intraportally into liver grafts and clamped for 30 min during cold preservation. After orthotopic PLTx, liver graft/body weights and serum biochemistry were monitored, and both a histological study and DNA binding assay were performed. STAT3-C protein expression and its binding to DNA in the liver graft were confirmed by Western blotting and electrophoretic mobility shift assay (EMSA), respectively. This treatment modality promoted post-Tx liver regeneration effectively and rapidly. The serum levels of alanine aminotransferase/aspartate aminotransferase (AST/ALT) and bilirubin decreased in rats with STAT3-C. However, albumin (a marker of liver function) did not. Ex vivo gene transfer of STAT3-C to liver grafts reduced post-Tx injury and promoted liver regeneration. Thus, the activation of STAT3 in the liver graft may be a potentially effective clinical strategy for improving the outcome of small-for-size liver transplantation.

  2. Seasonal variations in PM composition from Beijing, China drive liver oxidative stress

    NASA Astrophysics Data System (ADS)

    Pardo, M.; Rudich, Y.

    2017-12-01

    Air pollution can cause oxidative stress, inflammation and adverse health effects, but the underlying biological mechanisms are not completely understood. In order to understand how seasonal and chemical variations drive health impacts, we investigated the oxidative stress and inflammation in mice exposed to extracts (water and DCM) from urban PM collected in Beijing (China). Higher levels of pollution components were detected in the heating season (HS, winter) than in the non-heating season (NHS, summer). Higher concentrations of PM were measured in the heating season, mostly from coal and wood burning used for domestic heating. This was accompanied by increased levels of polyaromatic hydrocarbons (PAHs) in the DCM extracts. An increased inflammatory response was detected in the lung and liver with DCM extracts compared to the water extracts, and mostly in the winter aerosol. Reduced antioxidant response was observed in the lung, whereas it was activated in the liver. Gene expression of the Nrf2 transcription factor (A master regulator of stress response that controls the basal oxidative capacity and induces the expression of antioxidant response) and its related genes were induced. In the liver, higher levels of lipid peroxidation adducts were measured, correlated with histologic analysis that revealed morphologic features of damage/proliferation in the liver, indicating oxidative and toxic damage. Altogether, our study suggests that the acute effects of PM can vary by the season with the largest effect observed in winter than summer in Beijing, and that some secondary organs may be susceptible for exposure damage. This suggests that the liver is a potential organ to be influenced from PM especially by PAHs

  3. Diagnostic Value of Anti-Hepatitis C Virus (HCV) Core Immunoglobulin M in Recurrence of HCV Infection after Orthotopic Liver Transplantation†

    PubMed Central

    Casino, Carmela; Lilli, Daniela; Rivanera, Daniela; Comanducci, Antonella; Rossi, Massimo; Casciaro, Giovanni; Pecorella, Irene; Alfani, Dario; Mancini, Carlo

    1999-01-01

    The significance of anti-hepatitis C virus (HCV) core immunoglobulin M (IgM) and its relationship with genotypes, alanine aminotransferase abnormality, and histological data were studied for 18 patients who had undergone orthotopic liver transplantation due to HCV-related end-stage disease. During follow-up, IgM response seemed to be associated with the recurrence of HCV infection but did not correlate with abnormal alanine aminotransferase levels and histological data. In addition, the results of this study indicated that the detection of HCV RNA is critical for diagnosis of reinfection in liver transplantation. PMID:10405433

  4. The role of serum hyaluronic acid determination in the diagnosis of liver fibrosis.

    PubMed

    Gudowska, Monika; Cylwik, Bogdan; Chrostek, Lech

    2017-01-01

    The common pathway leading to liver fibrosis and cirrhosis is growing deposition of extracellular matrix (ECM). It results from molecular and histological rearrangement of collagens, glycoproteins and hyaluronans. Hyaluronic acid is a chief component of the extracellular matrix of connective tissues and plays the main structural role in the formation of ECM. The most important organ involved in the synthesis of hyaluronic acid is the liver. In this paper the meaning of hyaluronic acid in the diagnostics of liver diseases is discussed. Here, we focus on the described changes of hyaluronic acid concentration in the pathological processes of the liver, including alcoholic and non-alcoholic liver diseases. The results of published clinical studies have shown its high diagnostic sensitivity, which probably enables its application in laboratory diagnosis.

  5. How to interpret liver function tests in heart failure patients?

    PubMed

    Çağlı, Kumral; Başar, Fatma Nurcan; Tok, Derya; Turak, Osman; Başar, Ömer

    2015-05-01

    Cardiac hepatopathy has generally been used to describe any liver damage caused by cardiac disorders in the absence of other possible causes of liver damage. Although there is no consensus on the terminology used, cardiac hepatopathy can be examined as congestive hepatopathy (CH) and acute cardiogenic liver injury (ACLI). CH is caused by passive venous congestion of the liver that generally occurs in the setting of chronic cardiac conditions such as chronic HF, constrictive pericarditis, tricuspid regurgitation, or right-sided heart failure (HF) of any cause, and ACLI is most commonly associated with acute cardiocirculatory failure resulting from acute myocardial infarction, acute decompensated HF, or myocarditis. Histologically, CH is characterized by sinusoidal dilation, replacement of hepatocytes with red blood cells extravasating from the sinusoids, and necrosis/apoptosis of zone 3 of the Rappaport acinus, and it could progress to cirrhosis in advanced cases. In ACLI, however, massive necrosis of zone 3 is the main histological finding. Primary laboratory findings of CH are elevated serum cholestasis markers including bilirubin, alkaline phosphatase, and γ-glutamyl-transpeptidase levels, whereas those of ACLI are a striking elevation in transaminase and lactate dehydrogenase levels. Both CH and ACLI have a prognostic value for identifying cardiovascular events and mortality and have some special implications in the management of patients undergoing ventricular assist device implantation or cardiac transplantation. There is no specific treatment for CH or ACLI other than treatment of the underlying cardiac disorder.

  6. Nucleus segmentation in histology images with hierarchical multilevel thresholding

    NASA Astrophysics Data System (ADS)

    Ahmady Phoulady, Hady; Goldgof, Dmitry B.; Hall, Lawrence O.; Mouton, Peter R.

    2016-03-01

    Automatic segmentation of histological images is an important step for increasing throughput while maintaining high accuracy, avoiding variation from subjective bias, and reducing the costs for diagnosing human illnesses such as cancer and Alzheimer's disease. In this paper, we present a novel method for unsupervised segmentation of cell nuclei in stained histology tissue. Following an initial preprocessing step involving color deconvolution and image reconstruction, the segmentation step consists of multilevel thresholding and a series of morphological operations. The only parameter required for the method is the minimum region size, which is set according to the resolution of the image. Hence, the proposed method requires no training sets or parameter learning. Because the algorithm requires no assumptions or a priori information with regard to cell morphology, the automatic approach is generalizable across a wide range of tissues. Evaluation across a dataset consisting of diverse tissues, including breast, liver, gastric mucosa and bone marrow, shows superior performance over four other recent methods on the same dataset in terms of F-measure with precision and recall of 0.929 and 0.886, respectively.

  7. Multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease severity.

    PubMed

    Pavlides, Michael; Banerjee, Rajarshi; Tunnicliffe, Elizabeth M; Kelly, Catherine; Collier, Jane; Wang, Lai Mun; Fleming, Kenneth A; Cobbold, Jeremy F; Robson, Matthew D; Neubauer, Stefan; Barnes, Eleanor

    2017-07-01

    The diagnosis of non-alcoholic steatohepatitis and fibrosis staging are central to non-alcoholic fatty liver disease assessment. We evaluated multiparametric magnetic resonance in the assessment of non-alcoholic steatohepatitis and fibrosis using histology as standard in non-alcoholic fatty liver disease. Seventy-one patients with suspected non-alcoholic fatty liver disease were recruited within 1 month of liver biopsy. Magnetic resonance data were used to define the liver inflammation and fibrosis score (LIF 0-4). Biopsies were assessed for steatosis, lobular inflammation, ballooning and fibrosis and classified as non-alcoholic steatohepatitis or simple steatosis, and mild or significant (Activity ≥2 and/or Fibrosis ≥2 as defined by the Fatty Liver Inhibition of Progression consortium) non-alcoholic fatty liver disease. Transient elastography was also performed. Magnetic resonance success rate was 95% vs 59% for transient elastography (P<.0001). Fibrosis stage on biopsy correlated with liver inflammation and fibrosis (r s =.51, P<.0001). The area under the receiver operating curve using liver inflammation and fibrosis for the diagnosis of cirrhosis was 0.85. Liver inflammation and fibrosis score for ballooning grades 0, 1 and 2 was 1.2, 2.7 and 3.5 respectively (P<.05) with an area under the receiver operating characteristic curve of 0.83 for the diagnosis of ballooning. Patients with steatosis had lower liver inflammation and fibrosis (1.3) compared to patients with non-alcoholic steatohepatitis (3.0) (P<.0001); area under the receiver operating characteristic curve for the diagnosis of non-alcoholic steatohepatitis was 0.80. Liver inflammation and fibrosis scores for patients with mild and significant non-alcoholic fatty liver disease were 1.2 and 2.9 respectively (P<.0001). The area under the receiver operating characteristic curve of liver inflammation and fibrosis for the diagnosis of significant non-alcoholic fatty liver disease was 0

  8. Examination of the liver in personnel working with liquid rocket propellant

    PubMed Central

    Petersen, Palle; Bredahl, Erik; Lauritsen, Ove; Laursen, Thomas

    1970-01-01

    Petersen, P., Bredahl, E., Lauritsen, O., and Laursen, T. (1970).Brit. J. industr. Med.,27, 141-146. Examination of the liver in personnel working with liquid rocket propellants. Personnel working with liquid rocket propellants were subjected to routine health examinations, including liver function tests, as the propellant, unsymmetrical dimethylhydrazine (UDMH) is potentially toxic to the liver. In 46 persons the concentrations of serum alanine aminotransferase (SGPT) were raised. Liver biopsy was performed in 26 of these men; 6 specimens were pathological (fatty degeneration), 5 were uncertain, and 15 were normal. All 6 pathological biopsies were from patients with a raised SGPT at the time of biopsy. Of the 15 persons with a normal liver biopsy, 14 had a normal SGPT, while one (who was an alcoholic) had a raised SGPT. The connection between SGPT and histology of the liver, as well as the possible causal relation between the pathological findings and exposure to UDMH, is discussed. Images PMID:5428632

  9. Technetium-99m galactosyl-neoglycoalbumin (Tc-NGA) liver imaging: Application in liver transplantation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Woodle, E.S.; Ward, R.E.; Vera, D.R.

    1985-05-01

    Tc-NGA is a new liver imaging agent which binds to hepatic binding protein (HBP), a hepatocyte-specific membrane receptor. The purpose of the present study was to evaluate the potential role of Tc-NGA imaging in liver transplantation. The molar Tc-NGA dose was standardized according to patient weight (0.7 nmole/kg). After a 30 minute dynamic imaging study (5 mCi, IV), kinetic analysis of time activity data (heart, liver), provided values for receptor concentration, (HBP), and hepatic blood flow, Q. Eleven Tc-NGA imaging studies were performed in transplant candidates and 22 studies were performed in seven transplant recipients. Preservation damage was manifested bymore » diffuse patchiness in tracer distribution which resolved during the following two weeks. Histologically proven, localized hepatic infarcts were demonstrated in three recipients. Lobar infarction was demonstrated in one recipient. Hepatic regeneration was later demonstrated in this patient after hepatic lobectomy. Hepatic blood flow was markedly decreased in the early postoperative period, but improved with time. Increased (HBP) was demonstrated with regeneration. Markedly decreased (HBP) and Q were obtained in several candidates who died awaiting transplantation. These studies indicate that TC-NGA liver imaging provides a valuable new means for: (1) evaluation of preservation damage, (2) early demonstration of hepatic infarction, (3) evaluation of hepatic rejection, and (4) selection of patients for hepatic transplantation.« less

  10. Extended normothermic extracorporeal perfusion of isolated human liver after warm ischaemia: a preliminary report.

    PubMed

    Bellomo, Rinaldo; Marino, Bruno; Starkey, Graeme; Fink, Michael; Wang, Bao Zhong; Eastwood, Glenn M; Peck, Leah; Young, Helen; Houston, Shane; Skene, Alison; Opdam, Helen; Jones, Robert

    2014-09-01

    Donation after circulatory death (DCD) livers are at markedly increased risk of primary graft dysfunction and biliary tract ischaemia. Normothermic extracorporeal liver perfusion (NELP) may increase the ability to transplant DCD livers and may allow their use for artificial extracorporeal liver support of patients with fulminant liver failure. We conducted two proof-of-concept experiments using human livers after DCD to assess the feasibility and functional efficacy of NELP over an extended period. We applied extracorporeal membrane oxygenation, parenteral nutrition, separate hepatic artery and portal vein perfusion and physiological perfusion pressures to two livers obtained after DCD. We achieved NELP and evidence of liver function (bile production, paracetamol removal and maintenance of normal lactate levels) in both livers; one for 24 hours and the other for 43 hours. Histological examination showed areas of patchy ischaemia but preserved biliary ducts and canaliculi. Our experiments justify further investigations of the feasibility and efficacy of extended DCD liver preservation by ex-vivo perfusion.

  11. A role for transforming growth factor-{beta} apoptotic signaling pathway in liver injury induced by ingestion of water contaminated with high levels of Cr(VI)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rafael, A.I.; Almeida, A.; Santos, P.

    2007-10-15

    Hexavalent chromium [Cr(VI)] exposure is commonly associated with lung cancer. Although other adverse health effects have been reported, some authors, on assuming that orally ingested Cr(VI) is efficiently detoxified upon reduction by body fluids, believe that Cr(VI) do not target cells other than respiratory tract cells. In rodents, ingested Cr(VI)-contaminated water was reported to induce, in the liver, increases in TGF-{beta} transcripts. As TGF-{beta} dependent signaling pathways are closely associated with hepatic injury, the present study was undertaken addressing two specific issues: the effects of ingestion of water contaminated with high levels of Cr(VI) in rat liver structure and function;more » and the role of the TGF-{beta} pathway in Cr(VI)-induced liver injury. Examination of Wistar rats exposed to 20 ppm Cr(VI)-contaminated water for 10 weeks showed increased serum glucose and alanine aminotransferase (ALT) levels. Liver histological examination revealed hepatocellular apoptosis, further confirmed by immunohystochemical study of Caspase 3 expression. Liver gene expression analysis revealed increased expression of Smad2/Smad4 and Dapk, suggesting the involvement of the TGF-{beta} pathway in the apoptotic process. Since no changes in Smad3 expression were observed it appears apoptosis is using a Smad3-independent pathway. Increased expression of both Caspase 8 and Daxx genes suggests also the involvement of the Fas pathway. Gene expression analysis also revealed that a p160{sup ROCK}-Rho-independent pathway operates, leading to cell contraction and membrane blebbing, characteristic apoptotic features. These findings suggest that either the amount of Cr(VI) ingested overwhelmed the body fluids reductive capacity or some Cr(VI) escapes the reductive protection barrier, thus targeting the liver and inducing apoptosis.« less

  12. Molecular, histologic, and trace mineral characterization of metacarpophalangeal and metatarsophalangeal joint hyperextension in juvenile llamas.

    PubMed

    Semevolos, Stacy A; Reed, Shannon K

    2011-04-01

    To evaluate molecular and histologic characteristics of the superficial digital flexor tendon (SDFT), deep digital flexor tendon (DDFT), and suspensory ligament (SL) and assess trace-mineral concentrations in serum, liver, and hair of juvenile llamas with metacarpophalangeal and metatarsophalangeal joint hyperextension. 12 juvenile llamas (6 with bilateral hyperextension of metacarpophalangeal joints, metatarsophalangeal joints, or both and 6 clinically normal control llamas). Radiography and ultrasonography of metacarpophalangeal and metatarsophalangeal regions were performed. Llamas were euthanized, and SDFT, DDFT, and SL samples were collected for histologic evaluation of collagen and elastin content and orientation, proteoglycan content, and collagen type III immunohistochemistry. Total RNA was isolated from SL tissue, and gene expression of collagen types I and III, lysyl oxidase, and matrix metalloproteinase-13 was evaluated via real-time quantitative reverse transcriptase PCR assay. Liver, serum, and hair samples were evaluated for trace mineral content. Collagen type III gene expression and proteoglycan content were significantly increased in SL samples of affected juvenile llamas, compared with those of control llamas. No difference was detected in collagen and elastin content and orientation or in gene expression of collagen type I, lysyl oxidase, or matrix metalloproteinase-13 between groups. Affected llamas had significantly increased serum molybdenum and decreased liver cobalt concentrations, compared with values for control llamas. Increased collagen type III gene expression and proteoglycan content in SL samples of affected juvenile llamas provided evidence of ongoing SL matrix repair. Trace mineral differences may have been attributable to dietary imbalances in affected llamas.

  13. RNA-seq analysis of broiler liver transcriptome reveals novel responses to high ambient temperature.

    PubMed

    Coble, Derrick J; Fleming, Damarius; Persia, Michael E; Ashwell, Chris M; Rothschild, Max F; Schmidt, Carl J; Lamont, Susan J

    2014-12-10

    In broilers, high ambient temperature can result in reduced feed consumption, digestive inefficiency, impaired metabolism, and even death. The broiler sector of the U.S. poultry industry incurs approximately $52 million in heat-related losses annually. The objective of this study is to characterize the effects of cyclic high ambient temperature on the transcriptome of a metabolically active organ, the liver. This study provides novel insight into the effects of high ambient temperature on metabolism in broilers, because it is the first reported RNA-seq study to characterize the effect of heat on the transcriptome of a metabolic-related tissue. This information provides a platform for future investigations to further elucidate physiologic responses to high ambient temperature and seek methods to ameliorate the negative impacts of heat. Transcriptome sequencing of the livers of 8 broiler males using Illumina HiSeq 2000 technology resulted in 138 million, 100-base pair single end reads, yielding a total of 13.8 gigabases of sequence. Forty genes were differentially expressed at a significance level of P-value < 0.05 and a fold-change ≥ 2 in response to a week of cyclic high ambient temperature with 27 down-regulated and 13 up-regulated genes. Two gene networks were created from the function-based Ingenuity Pathway Analysis (IPA) of the differentially expressed genes: "Cell Signaling" and "Endocrine System Development and Function". The gene expression differences in the liver transcriptome of the heat-exposed broilers reflected physiological responses to decrease internal temperature, reduce hyperthermia-induced apoptosis, and promote tissue repair. Additionally, the differential gene expression revealed a physiological response to regulate the perturbed cellular calcium levels that can result from high ambient temperature exposure. Exposure to cyclic high ambient temperature results in changes at the metabolic, physiologic, and cellular level that can be

  14. Protective effects of melatonin against thioacetamide-induced liver fibrosis in rats.

    PubMed

    Czechowska, G; Celinski, K; Korolczuk, A; Wojcicka, G; Dudka, J; Bojarska, A; Reiter, R J

    2015-08-01

    The aim of this study was to determine the effect of melatonin on thioacetamide (TAA) induced liver fibrosis in rats. The antifibrotic effects of melatonin were assessed by determining activity indirect markers of fibrosis: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), and proinflammatory cytokines: interleukin 6 (IL-6), interleukin-1beta (IL-1β), tumour necrosis factor alpha (TNF-α), transforming growth factor-beta (TGF-β) and platelet-derived growth factor (PDGF). Parameters of oxidative stress: oxidised glutathione (GSSG), reduced glutathione (GSH) and presaged activity of paraoxonase 1 (PON-1), an antioxidative enzyme were determined. Inflammatory changes and fibrosis extent were evaluated histologically. Experiments were carried out in Wistar rats. Animals were divided into 4 groups: I - controls, water ad libitum for 12 weeks, group II - TAA, 300 mg/L ad libitum for 12 weeks, III - melatonin, 10 mg/kg b.w. intraperitoneally (i.p.) daily for 4 weeks, IV - TAA, 300 mg/L ad libitum for 12 weeks followed by melatonin, 10 mg/kg/b.w. i.p. daily for 4 weeks. Results of serum determinations demonstrated significantly lower activity of AST, ALT and AP in the group receiving TAA followed by melatonin compared to the group receiving only TAA. Immunoenzymatic findings on effect of melatonin on concentration of proinflammatory cytokines confirmed these data. Biochemical examinations in liver homogenates revealed statistically significant improvement (concentration of GSH increases and concentration of GSSG decreases) in animals with TAA-induced liver damage receiving melatonin. Moreover, the activity of PON-1 toward phenyl acetate and paraoxon was increased in liver homogenates and serum in the group receiving TAA followed by melatonin compared to the TAA group without melatonin treatment. Microscopic evaluation disclosed inhibitory effects of melatonin on inflammatory changes and extent of liver fibrosis.

  15. The utility of Xenon-133 liver scan in the diagnosis and management of nonalcoholic fatty liver disease.

    PubMed

    Al-Busafi, Said A; Ghali, Peter; Wong, Philip; Novales-Diaz, Javier A; Deschênes, Marc

    2012-03-01

    Nonalcoholic fatty liver disease (NAFLD) is an important and common condition affecting approximately 20% of the general population. Given the limitation of radiological investigations, diagnosis often requires a liver biopsy. To compare Xenon-133 (Xe-133) liver scanning with ultrasonography in the diagnosis of NAFLD. From January 2003 to February 2007, 258 consecutive patients with suspected NAFLD underwent Xe-133 liver scanning at Royal Victoria Hospital (Montreal, Quebec). Of these, 43 patients underwent ultrasonography and liver biopsy for the evaluation of NAFLD. Patients with other liver diseases and significant alcohol consumption were excluded. Two nuclear medicine physicians assessed liver Xe-133 uptake and measured the grade of steatosis using a standardized protocol. The degree of steatosis was determined from biopsy specimens assessed by two hepatopathologists. NAFLD was identified by liver biopsy in 35 of 43 patients (81.4%). Xe-133 scan demonstrated 94.3% sensitivity (95% CI 81.4% to 98.4%) and 87.5% specificity (95% CI 52.9% to 99.4%) for the presence of NAFLD. The positive and negative predictive values for detection of steatosis by Xe-133 scan were 97.1% (95% CI 85.1% to 99.8%) and 77.8% (95% CI 45.3% to 93.7%), respectively. The positive and negative likelihood ratios were 7.54 (95% CI 1.20 to 47.26) and 0.07 (95% CI 0.02 to 0.26), respectively. Two patients with NAFLD (5.7%) who had a negative Xe-133 scan result had histologically mild steatosis (<10%). The grade of steatosis on liver biopsy was highly correlated with the results of the Xe-133 scan (r=0.87; P<0.001). The sensitivity and specificity of ultrasound in diagnosing steatosis were 62.9% and 75%, respectively. Xe-133 liver scan proved to be a safe, reliable, noninvasive method for diagnosing and quantifying hepatic steatosis, and was superior to ultrasound.

  16. Interleukin-10 to tumor necrosis factor-alpha ratio is a predictive biomarker in nonalcoholic fatty liver disease: interleukin-10 to tumor necrosis factor-alpha ratio in steatohepatitis.

    PubMed

    Hashem, Reem M; Mahmoud, Mona F; El-Moselhy, Mohamed A; Soliman, Hala M

    2008-10-01

    Fatty liver disease is commonly associated with diabetes mellitus (DM). Insulin resistance (IR) as an investigative biomarker is only concerned with fatty liver that results from DM type 2 associated with metabolic syndrome. Irrespective of IR, DM is generally characterized by overproduction of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), whereas action of the latter is modulated by the anti-inflammatory cytokine interleukin-10 (IL-10). The aim of this study was to investigate the efficacy of using TNF-alpha alone or IL-10/TNF-alpha ratio compared to IR, as a promising biomarker for fatty liver assessment in DM. Furthermore, we hypothesized that using garlic as an immunomodulator may decrease TNF-alpha and increase IL-10 production to improve steatohepatitis. DM was induced metabolically by a high-fat diet to bring about IR, or chemically by alloxan, producing insulin deficiency, in male albino rats. Garlic powder was supplemented (15 mg/kg per day) for 3 weeks. Fatty liver was depicted histologically and biochemically (aspartic aminotransferase, alanine aminotransferase, HOMA-IR, TNF-alpha, IL-10, IL-10/TNF-alpha ratio). We found that, in contrast to obese rats, garlic decreased IL-10/TNF-alpha ratio, despite decreasing TNF-alpha in alloxan diabetic rats in agreement with the histology, which revealed more prominent improvement in the obese group. Moreover, the effect of garlic was not linked to improvement of IR in obese rats. We conclude that IL-10/TNF-alpha ratio may be considered as a convenient biomarker for investigation of fatty liver of different grades, apart from being associated with IR, and immunomodulation of this ratio in favor of increasing it may exert significant improvement.

  17. Second Harmonic Generation Reveals Subtle Fibrosis Differences in Adult and Pediatric Nonalcoholic Fatty Liver Disease.

    PubMed

    Liu, Feng; Zhao, Jing-Min; Rao, Hui-Ying; Yu, Wei-Miao; Zhang, Wei; Theise, Neil D; Wee, Aileen; Wei, Lai

    2017-11-20

    Investigate subtle fibrosis similarities and differences in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using second harmonic generation (SHG). SHG/two-photon excitation fluorescence imaging quantified 100 collagen parameters and determined qFibrosis values by using the nonalcoholic steatohepatitis (NASH) Clinical Research Network (CRN) scoring system in 62 adult and 36 pediatric NAFLD liver specimens. Six distinct parameters identified differences among the NASH CRN stages with high accuracy (area under the curve, 0835-0.982 vs 0.885-0.981, adult and pediatric). All portal region parameters showed similar changes across early stages 0, 1C, and 2, in both groups. Parameter values decreased in adults with progression from stage 1A/B to 2 in the central vein region. In children, aggregated collagen parameters decreased, but nearly all distributed collagen parameters increased from stage 1A/B to 2. SHG analysis accurately reproduces NASH CRN staging in NAFLD, as well as reveals differences and similarities between adult and pediatric collagen deposition not captured by currently available quantitative methods. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  18. Effects of glyphosate and its commercial formulation, Roundup® Ultramax, on liver histology of tadpoles of the neotropical frog, Leptodactylus latrans (amphibia: Anura).

    PubMed

    Bach, Nadia C; Marino, Damián J G; Natale, Guillermo S; Somoza, Gustavo M

    2018-07-01

    In the last years, the agricultural expansion has led to an increased use of pesticides, with glyphosate as the most widely used worldwide. This is also the situation in Argentina, where glyphosate formulations are the most commercialized herbicides. It is known that glyphosate formulations are much more toxic than the active ingredient, and this difference in toxicity can be attributed to the adjuvants present in the formula. In this context, the aim of the present study was to evaluate and compare sub-lethal histological effects of the glyphosate formulation Roundup Ultramax and glyphosate active ingredient on Leptodactylus latrans tadpoles at Gosner-stage 36. Semi-static bioassays were performed using 96 h of exposure with Roundup Ultramax formulation (RU; 0.37-5.25 mg a.e./L), glyphosate (GLY; 3-300 mg/L), and a control group. RU exposure showed an increment in the melanomacrophagic cells (MMc) and melanomacrophagic centers (MMCs) from 0.37 mg a.e./L. GLY exposure showed a significant increment in the number of MMc from 15 mg/L, and of MMCs from 3 mg/L. Also, histopathological lesions were observed in the liver of tadpoles exposed to both, GLY and RU. These lesions included: lipidosis and hepatic congestion, but only RU showed significant differences respect to control, with a LOEC value of 2.22 mg a.e./L for both effects. In sum, this study represents the first evidence of adverse effects of glyphosate and RU formulation on the liver of anuran larvae at concentrations frequently found in the environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Antioxidant properties of proanthocyanidins attenuate carbon tetrachloride (CCl4)-induced steatosis and liver injury in rats via CYP2E1 regulation.

    PubMed

    Dai, Ning; Zou, Yuan; Zhu, Lei; Wang, Hui-Fang; Dai, Mu-Gen

    2014-06-01

    Liver steatosis is characterized by lipid dysregulation and fat accumulation in the liver and can lead to oxidative stress in liver. Since proanthocyanidins are present in plant-based foods and have powerful antioxidant properties, we investigated whether proanthocyanidins can prevent oxidative stress and subsequent liver injury. Carbon tetrachloride (CCl4) treatment can cause steatosis in rats that models both alcoholic and non-alcoholic fatty liver disease in humans. We pre-treated rats by oral administration of proanthocyanidins extracted from grape seeds 7 days prior to intragastrically administering CCl4. Proanthocyanidin treatment continued for an additional 2 weeks, after which time liver and serum were harvested, and mediators of liver injury, oxidative stress, and histological features were evaluated. CCl4-treated rats exhibited significant increases in the following parameters as compared to non-treated rats: fat droplets in the liver, liver injury (ALT, AST), and DNA damage (8-OHdG). Additionally, CCl4 treatment decreased antioxidant enzymes SOD, GSH, GPX, and CAT in the liver due to their rapid depletion after battling against oxidative stress. Compared to CCl4-treated rats, treatment with proanthocyanidins effectively suppressed lipid accumulation, liver injury, DNA damage, as well as restored antioxidant enzyme levels. Further investigation revealed that proanthocyanidins treatment also inhibited expression of CYP2E1 in liver, which prevented the initial step of generating free radicals from CCl4. The data presented here show that treatment with orally administered proanthocyanidins prevented liver injury in the CCl4-induced steatosis model, likely through exerting antioxidant actions to suppress oxidative stress and inhibiting the free radical-generating CYP2E1 enzyme.

  20. Validation of goose liver fat measurement by QCT and CSE-MRI with biochemical extraction and pathology as reference.

    PubMed

    Xu, Li; Duanmu, Yangyang; Blake, Glen M; Zhang, Chenxin; Zhang, Yong; Brown, Keenan; Wang, Xiaoqi; Wang, Peng; Zhou, Xingang; Zhang, Manling; Wang, Chao; Guo, Zhe; Guglielmi, Giuseppe; Cheng, Xiaoguang

    2018-05-01

    This study aimed to validate the accuracy and reliability of quantitative computed tomography (QCT) and chemical shift encoded magnetic resonance imaging (CSE-MRI) to assess hepatic steatosis. Twenty-two geese with a wide range of hepatic steatosis were collected. After QCT and CSE-MRI examinations, the liver of each goose was removed and samples were taken from the left lobe, upper and lower half of the right lobe for biochemical measurement and histology. Fat percentages by QCT and proton density fat fraction by MRI (MRI-PDFF) were measured within the sample regions of biochemical measurement and histology. The accuracy of QCT and MR measurements were assessed through Spearman correlation coefficients (r) and Passing and Bablok regression equations using biochemical measurement as the "gold standard". Both QCT and MRI correlated highly with chemical extraction [r = 0.922 (p < 0.001) and r = 0.949 (p < 0.001) respectively]. Chemically extracted triglyceride was accurately predicted by both QCT liver fat percentages (Y = 0.6 + 0.866 × X) and by MRI-PDFF (Y = -1.8 + 0.773 × X). QCT and CSE-MRI measurements of goose liver fat were accurate and reliable compared with biochemical measurement. • QCT and CSE-MRI can measure liver fat content accurately and reliably • Histological grading of hepatic steatosis has larger sampling variability • QCT and CSE-MRI have potential in the clinical setting.

  1. An immunohistochemical study of retinol-binding protein (RBP) in livers of free-living polar bears (Ursus maritimus) from east Greenland.

    PubMed

    Heier, Annabelle; Sonne, Christian; Gröne, Andrea; Leifsson, Pall S; Dietz, Rune; Born, Erik W; Bacciarini, Luca N

    2005-09-01

    From 1999 to 2002 samples from 114 free-ranging polar bears (Ursus maritimus) were collected in the municipality of Scoresby Sound, East Greenland, to detect levels of organochlorines and potential histopathologic changes. Livers of 16 female polar bears from this group were evaluated histologically and analyzed for hepatic retinol-binding protein by immunohistochemistry. Retinol-binding protein is the main transport protein for retinol, an important vitamin A metabolite in the polar bear. Only mild pathologic changes were noted on histologic evaluation of the livers. Small lymphocytic or lymphohistiocytic infiltrates were present in all the livers. Small lipid granulomas, mild periportal fibrosis, and bile duct proliferation were found in several cases. Immunohistochemistry for retinol-binding protein of hepatic tissue from free-ranging polar bears showed no distinct difference in staining intensity by a number of criteria: age, season (fasting and nonfasting), or lactation status. The staining was diffuse to finely stippled in the cytoplasm and showed very little variation among the animals. Because of the lack of macroscopic changes and the absence of severe histologic liver lesions, these polar bears were assumed to be healthy. The diffuse cytoplasmic retinol-binding protein staining in hepatocytes of free-ranging polar bears varies markedly from the prominent granular, less intense staining of captive polar bears investigated previously.

  2. Pneumatic Distension of Ventricular Mural Architecture Validated Histologically.

    PubMed

    Burg, M C; Lunkenheimer, P; Niederer, P; Brune, C; Redmann, K; Smerup, M; Spiegel, U; Becker, F; Maintz, D; Heindel, W; Anderson, R H

    2016-11-01

    Purpose: There are ongoing arguments as to how cardiomyocytes are aggregated together within the ventricular walls. We used pneumatic distension through the coronary arteries to exaggerate the gaps between the aggregated cardiomyocytes, analyzing the pattern revealed using computed tomography, and validating our findings by histology. Methods: We distended 10 porcine hearts, arresting 4 in diastole by infusion of cardioplegic solutions, and 4 in systole by injection of barium chloride. Mural architecture was revealed by computed tomography, measuring also the angulations of the long chains of cardiomyocytes. We prepared the remaining 2 hearts for histology by perfusion with formaldehyde. Results: Increasing pressures of pneumatic distension elongated the ventricular walls, but produced insignificant changes in mural thickness. The distension exaggerated the spaces between the aggregated cardiomyocytes, compartmenting the walls into epicardial, central, and endocardial regions, with a feathered arrangement of transitions between them. Marked variation was noted in the thicknesses of the parts in the different ventricular segments, with no visible anatomical boundaries between them. Measurements of angulations revealed intruding and extruding populations of cardiomyocytes that deviated from a surface-parallel alignment. Scrolling through the stacks of tomographic images revealed marked spiraling of the aggregated cardiomyocytes when traced from base to apex. Conclusion: Our findings call into question the current assumption that cardiomyocytes are uniformly aggregated together in a tangential fashion. There is marked heterogeneity in the architecture of the different ventricular segments, with the aggregated units never extending in a fully transmural fashion. Key Points: • Pneumographic computed tomography reveals an organized structure of the ventricular walls.• Aggregated cardiomyocytes form a structured continuum, with marked regional heterogeneity

  3. Protection effect of piper betel leaf extract against carbon tetrachloride-induced liver fibrosis in rats.

    PubMed

    Young, Shun-Chieh; Wang, Chau-Jong; Lin, Jing-Jing; Peng, Pei-Ling; Hsu, Jui-Ling; Chou, Fen-Pi

    2007-01-01

    Piper betel leaves (PBL) are used in Chinese folk medicine for the treatment of various disorders. PBL has the biological capabilities of detoxication, antioxidation, and antimutation. In this study, we evaluated the antihepatotoxic effect of PBL extract on the carbon tetrachloride (CCl(4))-induced liver injury in a rat model. Fibrosis and hepatic damage, as reveled by histology and the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were induced in rats by an administration of CCl(4) (8%, 1 ml/kg body weight) thrice a week for 4 weeks. PBL extract significantly inhibited the elevated AST and ALT activities caused by CCl(4) intoxication. It also attenuated total glutathione S-transferase (GST) activity and GST alpha isoform activity, and on the other hand, enhanced superoxide dismutase (SOD) and catalase (CAT) activities. The histological examination showed the PBL extract protected liver from the damage induced by CCl(4) by decreasing alpha-smooth muscle actin (alpha-sma) expression, inducing active matrix metalloproteinase-2 (MMP2) expression though Ras/Erk pathway, and inhibiting TIMP2 level that consequently attenuated the fibrosis of liver. The data of this study support a chemopreventive potential of PBL against liver fibrosis.

  4. Hepatoprotective Effect of Citral on Acetaminophen-Induced Liver Toxicity in Mice

    PubMed Central

    Silva-Filho, Saulo Euclides; Cardia, Gabriel Fernando Esteves; Cremer, Edivaldo; Bersani-Amado, Ciomar Aparecida

    2017-01-01

    High doses of acetaminophen (APAP) lead to acute liver damage. In this study, we evaluated the effects of citral in a murine model of hepatotoxicity induced by APAP. The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) were determined to evaluate the hepatoprotective effects of citral. The livers were used to determine myeloperoxidase (MPO) activity and nitric oxide (NO) production and in histological analysis. The effect of citral on leukocyte migration and antioxidant activity was evaluated in vitro. Citral pretreatment decreased significantly the levels of ALT, AST, ALP, and γGT, MPO activity, and NO production. The histopathological analysis showed an improvement of hepatic lesions in mice after citral pretreatment. Citral inhibited neutrophil migration and exhibited antioxidant activity. Our results suggest that citral protects the liver against liver toxicity induced by APAP. PMID:28717379

  5. Comparative Proteomic Analysis of Liver Steatosis and Fibrosis after Oral Hepatotoxicant Administration in Sprague-Dawley Rats.

    PubMed

    McDyre, B Claire; AbdulHameed, Mohamed Diwan M; Permenter, Matthew G; Dennis, William E; Baer, Christine E; Koontz, Jason M; Boyle, Molly H; Wallqvist, Anders; Lewis, John A; Ippolito, Danielle L

    2018-02-01

    The past decade has seen an increase in the development and clinical use of biomarkers associated with histological features of liver disease. Here, we conduct a comparative histological and global proteomics analysis to identify coregulated modules of proteins in the progression of hepatic steatosis or fibrosis. We orally administered the reference chemicals bromobenzene (BB) or 4,4'-methylenedianiline (4,4'-MDA) to male Sprague-Dawley rats for either 1 single administration or 5 consecutive daily doses. Livers were preserved for histopathology and global proteomics assessment. Analysis of liver sections confirmed a dose- and time-dependent increase in frequency and severity of histopathological features indicative of lipid accumulation after BB or fibrosis after 4,4'-MDA. BB administration resulted in a dose-dependent increase in the frequency and severity of inflammation and vacuolation. 4,4'-MDA administration resulted in a dose-dependent increase in the frequency and severity of periportal collagen accumulation and inflammation. Pathway analysis identified a time-dependent enrichment of biological processes associated with steatogenic or fibrogenic initiating events, cellular functions, and toxicological states. Differentially expressed protein modules were consistent with the observed histology, placing physiologically linked protein networks into context of the disease process. This study demonstrates the potential for protein modules to provide mechanistic links between initiating events and histopathological outcomes.

  6. Systematic review of bariatric surgery liver biopsies clarifies the natural history of liver disease in patients with severe obesity.

    PubMed

    Bedossa, Pierre; Tordjman, Joan; Aron-Wisnewsky, Judith; Poitou, Christine; Oppert, Jean-Michel; Torcivia, Adriana; Bouillot, Jean-Luc; Paradis, Valerie; Ratziu, Vlad; Clément, Karine

    2017-09-01

    Non-alcoholic fatty liver disease (NAFLD) is a frequent complication of morbid obesity, but its severity varies greatly and thus there is a strong need to better define its natural history in these patients. Liver biopsies were systematically performed in 798 consecutive patients with severe obesity undergoing bariatric surgery. Histology was compared with clinical, biological, anthropometrical and body composition characteristics. Patients with presumably normal liver (n=179, 22%) were significantly younger at bariatric surgery than patients with NAFLD (37.0 vs 44.4 years, p<0.0001). However, both groups showed quite similar obesity duration, since patients with presumably normal liver reported the onset of obesity at a significantly younger age than those with NAFLD (14.8 vs 20.0 year, p<0.0001). The trunk/limb fat mass ratio increased according to liver disease severity (presumably normal liver: 1.00, steatosis: 1.21, non-alcoholic steatohepatitis (NASH): 1.34, p<0.0001), although the total body fat mass decreased (presumably normal liver: 50%, steatosis: 49.1%, NASH: 47.4%, p<0.0001). The volume of subcutaneous adipocytes increased according to severity of liver disease but only in female patients (presumably normal liver: 8543 picolitres, steatosis: 9156 picolitres, NASH: 9996 picolitres). These results suggest that young adults are more prone to store fat in subcutaneous tissue and reach the threshold of bariatric surgery indication before their liver is damaged. A shift of fat storage from subcutaneous to visceral adipose tissue compartment is associated with liver damages. Liver might also be targeted by subcutaneous hypertrophic adipocytes in females since hypertrophic adipocytes are more exposed to lipolysis and to the production of inflammatory mediators. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. Phylogenetic characterization of a novel herpesvirus found in the liver and lungs of a Chilean flamingo (Phoenicopterus chilensis).

    PubMed

    Coverdill, Christopher C; Barnes, Julie A; Garner, Michael M; Hinton, Kevin L; Childress, April L; Wellehan, James F X

    2016-05-01

    A novel herpesvirus was detected in a 17-day-old Chilean flamingo (Phoenicopterus chilensis) with pneumonia, hepatopathy, and severe anemia that was housed in California. Postmortem examination identified a pale, enlarged liver, mildly increased fluid in the lungs, and red foci in the spleen. Histologic examination revealed marked hepatic necrosis with syncytia, splenic necrosis, and interstitial pneumonia with eosinophilic intranuclear inclusions within hepatocytes and in unidentified cells of the lung. Transmission electron microscopy identified virions consistent with a herpesvirus in the nucleus and cytoplasm of degenerative hepatocytes. Nested consensus PCR, sequencing, and phylogenetic analysis identified a novel herpesvirus within the genus Iltovirus in the subfamily Alphaherpesvirinae. © 2016 The Author(s).

  8. Influence of diabetes on liver injury induced by antitubercular drugs and on silymarin hepatoprotection in rats.

    PubMed

    Srivastava, R K; Sharma, S; Verma, S; Arora, B; Lal, H

    2008-12-01

    Isoniazid, rifampicin and pyrazinamide during short-course chemotherapy for tuberculosis can result in liver injury. The coexistence of tuberculosis and diabetes is common in patients who receive inadequate treatment. The risk of hepatotoxicity from many toxicants is increased in diabetic rats. Silymarin provides protection against liver injury caused by many hepatotoxicants, including antitubercular drugs (ATDs). In the wake of increased severity of ATD-induced hepatotoxicity in diabetes we report here the results of a study on the influence of diabetes on silymarin hepatoprotection in rats. Rats with diabetes induced via intraperitoneally injected streptozotocin (50 mg/kg), nondiabetic rats and insulin-treated diabetic rats received isoniazid (7.5 mg/kg/day), rifampicin (10 mg/kg/day) and pyrazinamide (35 mg/kg/day) orally (p.o.) with or without silymarin (100 mg/kg/day p.o.) treatment for 45 days. Compared to nondiabetic rats, liver function tests and histological changes of liver revealed exaggerated liver injury in diabetic rats caused by ATDs which was evident by 5- to 8-fold increases in serum levels of marker enzymes (aspartate and alanine aminotransferase, alkaline phosphatase and gamma-glutamyltranspeptidase) and 1- to 2-fold increases in bilirubin accompanied by a 2-fold decrease in total serum proteins, intense fatty and inflammatory infiltrations, necrosis and fibrosis. Coadministration of silymarin provided protection against ATD hepatotoxicity in all animals. However, insulin-treated diabetic animals showed greater silymarin-induced hepatoprotection against ATD-induced liver injury, which was characterized by near normal levels of marker enzymes, an increase in total proteins and normal hepatic structure. These results thus indicate that diabetes exaggerates ATD-induced liver injury and attenuates silymarin-induced hepatoprotection. However, insulin treatment for diabetes offers greater silymarin-induced hepatoprotection against ATD-induced liver

  9. GDF‑15 prevents LPS and D‑galactosamine‑induced inflammation and acute liver injury in mice.

    PubMed

    Li, Min; Song, Kui; Huang, Xiaowen; Fu, Simao; Zeng, Qiyi

    2018-06-27

    Growth differentiation factor‑15 (GDF‑15) is a transforming growth factor (TGF)‑β superfamily member with a poorly characterized biological activity, speculated to be implicated in several diseases. The present study aimed to determine whether GDF‑15 participates in sepsis‑induced acute liver injury in mice. Lipopolysaccharide (LPS) and D‑galactosamine (D‑GalN) were administered to mice to induce acute liver injury. Survival of mice, histological changes in liver tissue, and levels of inflammatory biomarkers in serum and liver tissue were evaluated following treatment with GDF‑15. The underlying mechanism was investigated by western blotting, ELISA, flow cytometry, and reverse transcription‑quantitative polymerase chain reaction using Kupffer cells. The results demonstrated that GDF‑15 prevented LPS/D‑GalN‑induced death, increase in inflammatory cell infiltration and serum alanine aminotransferase and aspartate aminotransferase activities. In addition, GDF‑15 treatment reduced the production of hepatic malondialdehyde and myeloperoxidase, and attenuated the increase of interleukin (IL)‑6, tumor necrosis factor (TNF)‑α, and IL‑1β expression in serum and liver tissue, accompanied by inducible nitric oxide synthase (iNOS) inactivation in the liver. Similar changes in the expression of inflammatory cytokines, IL‑6, TNF‑α and IL‑1β, and iNOS activation were observed in the Kupffer cells. Further mechanistic experiments revealed that GDF‑15 effectively protected against LPS‑induced nuclear factor (NF)‑κB pathway activation by regulating TGFβ‑activated kinase 1 (TAK1) phosphorylation in Kupffer cells. In conclusion, GDF‑15 reduced the activation of pro‑inflammatory factors, and prevented LPS‑induced liver injury, most likely by disrupting TAK1 phosphorylation, and consequently inhibiting the activation of the NF‑κB pathway in the liver.

  10. Large hepatocellular carcinoma in a non-cirrhotic liver with peritoneal and omental metastasis in a healthy man: a case report.

    PubMed

    Herath, H M M T B; Kulatunga, Aruna

    2017-02-08

    Liver cancer is the second leading cause of cancer death in men worldwide. Hepatocellular carcinoma usually develops in the setting of cirrhosis or chronic inflammation. Major risk factors for developing hepatocellular carcinoma are chronic hepatitis B or C virus infection, alcoholic cirrhosis, and nonalcoholic fatty liver disease. The most frequent locations for hepatocellular carcinoma to metastasize are the lungs, portal vein, bones, and regional lymph nodes. A 41-year-old Sri Lankan man presented with progressive abdominal distension and on examination was found to have a palpable irregular mass in the left lobe of his liver with moderate ascites. His ascitic fluid was an exudate without malignant cells. An ultrasound scan and contrast-enhanced computed tomography of his abdomen showed a large contrast-enhancing lesion in the left lobe of his liver without features of cirrhosis. Laparoscopic assessment revealed peritoneal and omental deposits. Histology of the biopsies taken from the liver lesion, omental deposits, and peritoneal deposits supported a diagnosis of hepatocellular carcinoma. His liver biochemistry was normal and hepatitis serology was negative. He is abstinent from alcohol and did not have metabolic syndrome. It is rare for a young patient to develop hepatocellular carcinoma with a normal liver without chronic hepatitis B or C infection, or any other risk factors. Intraperitoneal metastasis of non-ruptured hepatocellular carcinoma is also very rare. Here we report a rare case of a 41-year-old man with a large hepatocellular carcinoma in a non-cirrhotic liver without chronic hepatitis who presented with peritoneal and omental metastasis.

  11. Dual-echo, chemical shift gradient-echo magnetic resonance imaging to quantify hepatic steatosis: Implications for living liver donation.

    PubMed

    Rinella, Mary E; McCarthy, Richard; Thakrar, Kiran; Finn, John Paul; Rao, Sambasiva M; Koffron, Alan J; Abecassis, Michael; Blei, Andres T

    2003-08-01

    In living liver donation, a fatty liver poses risks for both recipient and donor. Currently, liver biopsy is the standard for assessing the presence and extent of steatosis. The goals of this study were to correlate a steatosis index derived from magnetic resonance imaging (MRI) to the histologic grade on biopsy as well as to determine the topographic distribution of steatosis within the liver. We examined the ability of dual-echo, chemical shift gradient-echo MRI to predict the degree of steatosis on liver biopsy. A total of 22 subjects received both a liver biopsy and detailed MRI evaluation. These individuals included 15 potential living donors and 7 patients with nonalcoholic fatty liver disease. MRI steatosis index was then compared with histologic grade on liver biopsy. The topographic distribution of hepatic steatosis was determined from those subjects in whom MRI detected hepatic steatosis. The steatosis index had a positive correlation with grade of steatosis on liver biopsy (correlation coefficient, 0.84). There was no significant variation in the degree of steatosis among segments. A steatosis index of >0.2 had good positive and negative predictive value for the presence of significant steatosis (>15%) on biopsy. Our quantitative MRI protocol can predict the degree of hepatic steatosis when it is minimal to moderate, and may obviate the need for liver biopsy for the purpose of quantification of steatosis in living donors. Fat saturation added to the MRI protocol may further improve diagnostic accuracy. This technique may be applicable to the larger population with hepatic steatosis.

  12. Gut microbiota and liver diseases

    PubMed Central

    Minemura, Masami; Shimizu, Yukihiro

    2015-01-01

    Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases. PMID:25684933

  13. The value of different insulin resistance indices in assessment of non-alcoholic fatty liver disease in overweight/obese children.

    PubMed

    El-Karaksy, Hanaa M; El-Raziky, Mona S; Fouad, Hanan M; Anwar, Ghada M; El-Mougy, Fatma M; El-Koofy, Nehal M; El-Hennawy, Ahmad M

    2015-01-01

    The aim of the present study was to determine the association between insulin resistance (IR) and both non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) in a group of Egyptian overweight/obese children and adolescents and to evaluate different IR indices in detection of NAFLD. The study included 76 overweight/obese children aged 2-15 years; 52.6% were males. Laboratory analysis included fasting blood glucose, serum insulin, lipid profile, liver biochemical profile, and liver ultrasound. IR was calculated using the following indices; the homeostasis model assessment method (HOMA-IR), the quantitative insulin-sensitivity check index (QUICKI) and hepatic insulin sensitivity. The National Cholesterol Education Program Adult Treatment Panel III criteria were used to estimate prevalence of MetS. Liver biopsy was done when medically indicated and accepted by parents. IR was detected in 43.4% and 34.2% by using QUICKI and HOMA, respectively. MetS was detected in 36.8% and NAFLD was detected in 45.5% among those performing liver biopsy. Cases with NAFLD had more frequent IR than children with normal histology. QUICKI showed significant difference between normal subjects and both steatosis and non-alcoholic steatohepatitis; while HOMA-IR was sensitive in cases with NASH only. MetS was present in 100% of patients with NASH and in 75% of those with steatosis and they were all obese. Patients with NASH had significantly higher ALT than those with normal histology. IR was significantly associated with NAFLD. QUICKI is considered more sensitive than HOMA-IR in differentiating simple steatosis from normal liver histology. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  14. Serological markers of hepatitis B in patients with alcoholic liver disease: a multi-centre survey

    PubMed Central

    Hislop, WS; Follett, EAC; Bouchier, IAD; MacSween, RNM

    1981-01-01

    In a study of 195 patients derived from five centres in northern Britain and with histologically confirmed alcoholic liver disease we have found an increased prevalence of serological markers of hepatitis B. This increased prevalence was found in each of the five centres; the overall frequency ranged from 11% sero-positivity in fatty liver, 12% in alcoholic hepatitis and 27% in cirrhosis. PMID:7276216

  15. Involvement of catalase in the protective benefits of metformin in mice with oxidative liver injury.

    PubMed

    Dai, Jie; Liu, Mingwei; Ai, Qing; Lin, Ling; Wu, Kunwei; Deng, Xinyu; Jing, Yuping; Jia, Mengying; Wan, Jingyuan; Zhang, Li

    2014-06-05

    Metformin is a commonly used anti-diabetic drug with AMP-activated protein kinase (AMPK)-dependent hypoglycemic activities. Recent studies have revealed its anti-inflammatory and anti-oxidative properties. In the present study, the anti-oxidative potential of metformin and its potential mechanisms were investigated in a mouse model with carbon tetrachloride (CCl₂)-induced severe oxidative liver injury. Our results showed that treatment with metformin significantly attenuated CCl₂-induced elevation of serum aminotransferases and hepatic histological abnormalities. The alleviated liver injury was associated with decreased hepatic contents of oxidized glutathione (GSSG) and malondialdehyde (MDA). In addition, metformin treatment dose-dependently enhanced the activities of catalase (CAT) and decreased CCl₄-induced elevation of hepatic H₂O₂ levels, but it had no obvious effects on the protein level of CAT. We also found that metformin increased the level of phosphorylated AMP-activated protein kinase (AMPK), but treatment with AMPK activator AICAR had no obvious effects on CAT activity. A molecular docking analysis indicated that metformin might interact with CAT via hydrogen bonds. These data suggested that metformin effectively alleviated CCl₄-induced oxidative liver injury in mice and these hepatoprotective effects might be associated with CAT. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Dietary exposure of mink to carp from Saginaw Bay, Michigan: 2. Hematology and liver pathology

    USGS Publications Warehouse

    Heaton, S. N.; Bursian, S.J.; Giesy, J.P.; Tillitt, D. E.; Render, J. A.; Jones, P.D.; Verbrugge, D.A.; Kubiak, T.J.; Aulerich, R.J.

    1995-01-01

    The effects of consumption of environmental contaminants contained in carp (Cyprinus carpio)from Saginaw Bay, Michigan on various hematological parameters and liver integrity of adult female mink (Mustela vison) were determined. Mink were fed diets that contained 0 (control), 10, 20, or 40% carp prior to and throughout the reproductive period (182 days). The diets contained 0.015, 0.72, 1.53, and 2.56 mg polychlorinated biphenyls (PCBs)/kg diet and 1.0, 19, 40, and 81 pg 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs)/g diet, respectively. Mink fed the diets containing carp showed a general dose-dependent occurrence of clinical signs commonly associated with chlorinated hydrocarbon toxicity, including listlessness, nervousness when approached, anorexia, and melena. Erythrocyte counts were less in mink exposed to Saginaw Bay carp than in controls, while the number of white blood cells was greater than in controls. Significant differences (p<0.05) in the concentrations of neutrophils, lymphocytes, monocytes, and eosinophils were also found between the control and carp-fed groups, but are considered to be of limited clinical or biological importance. Hematocrit values for the mink fed the 20 and 40% carp diets were significantly less than those of mink in the control and 10% carp groups. There were no significant differences in hemoglobin concentrations among the groups. Necropsies revealed enlarged yellowish livers in many of the carp-fed mink, especially those fed the 40% carp diet. Liver, spleen, and lung weights of carp-fed mink were significantly greater than those of control mink. Histopathologic examination of the livers revealed various degrees of congestion, hepatocellular fatty changes, and scattered portal lymphocytic infiltration which were most prevalent in mink fed the carp diets. These clinical signs, hematological effects, and histologic alterations are similar to those previously described for chlorinated hydrocarbon toxicoses in mink.

  17. Dai-kenchu-to attenuates rat sinusoidal obstruction syndrome by inhibiting the accumulation of neutrophils in the liver.

    PubMed

    Narita, Masato; Hatano, Etsuro; Tamaki, Nobuyuki; Yamanaka, Kenya; Yanagida, Atsuko; Nagata, Hiromitsu; Asechi, Hiroyuki; Takada, Yasutsugu; Ikai, Iwao; Uemoto, Shinji

    2009-06-01

    Sinusoidal obstruction syndrome (SOS) is drug-induced liver injury that occurs in patients who receive hematopoietic cell transplantation and oxaliplatin-contained chemotherapy. The aim of study was to investigate the pharmacological treatment of SOS using a traditional Japanese medicine, Dai-kenchu-to (DKT). Male Sprague-Dawley rats were treated with monocrotaline (MCT) to induce SOS. The rats were divided into three groups: control, MCT and MCT+DKT groups. In the MCT+DKT group, DKT was gavaged at 12 h after MCT treatment and given every 12 h until the end of the protocol. The rats of MCT group were treated with water instead of DKT. At 48 h after MCT treatment, blood and liver samples were collected. In the MCT+DKT group, the macroscopic and histological findings revealed liver congestion, sinusoidal alteration and the destruction of sinusoidal lining, which were comparable with those of the MCT group. However, the area of hepatic necrosis and serum AST levels significantly decreased in the MCT+DKT group compared with those of the MCT group. Treatment with DKT resulted in the reduction of neutrophil accumulation, myeloperoxidase activity and the expression of cytokine-induced neutrophil chemoattractant (CINC) and intracellular adhesion molecule-1 (ICAM-1) mRNA in the liver compared with those of the MCT group. Treatment with processed ginger, one of the ingredients in DKT, resulted in similar effects to those shown by DKT. Dai-kenchu-to attenuates MCT-induced liver injury by preventing neutrophil-induced liver injury through blockage of upregulation of CINC and ICAM-1 mRNA level.

  18. Antioxidant Properties of Proanthocyanidins Attenuate Carbon Tetrachloride (CCl4)–Induced Steatosis and Liver Injury in Rats via CYP2E1 Regulation

    PubMed Central

    Zou, Yuan; Zhu, Lei; Wang, Hui-Fang; Dai, Mu-Gen

    2014-01-01

    Abstract Liver steatosis is characterized by lipid dysregulation and fat accumulation in the liver and can lead to oxidative stress in liver. Since proanthocyanidins are present in plant-based foods and have powerful antioxidant properties, we investigated whether proanthocyanidins can prevent oxidative stress and subsequent liver injury. Carbon tetrachloride (CCl4) treatment can cause steatosis in rats that models both alcoholic and non-alcoholic fatty liver disease in humans. We pre-treated rats by oral administration of proanthocyanidins extracted from grape seeds 7 days prior to intragastrically administering CCl4. Proanthocyanidin treatment continued for an additional 2 weeks, after which time liver and serum were harvested, and mediators of liver injury, oxidative stress, and histological features were evaluated. CCl4-treated rats exhibited significant increases in the following parameters as compared to non-treated rats: fat droplets in the liver, liver injury (ALT, AST), and DNA damage (8-OHdG). Additionally, CCl4 treatment decreased antioxidant enzymes SOD, GSH, GPX, and CAT in the liver due to their rapid depletion after battling against oxidative stress. Compared to CCl4-treated rats, treatment with proanthocyanidins effectively suppressed lipid accumulation, liver injury, DNA damage, as well as restored antioxidant enzyme levels. Further investigation revealed that proanthocyanidins treatment also inhibited expression of CYP2E1 in liver, which prevented the initial step of generating free radicals from CCl4. The data presented here show that treatment with orally administered proanthocyanidins prevented liver injury in the CCl4-induced steatosis model, likely through exerting antioxidant actions to suppress oxidative stress and inhibiting the free radical–generating CYP2E1 enzyme. PMID:24712752

  19. Effects of curcumin on antioxidative activities and cytokine production in Jian carp (Cyprinus carpio var. Jian) with CCl4-induced liver damage.

    PubMed

    Cao, Liping; Ding, Weidong; Du, Jingliang; Jia, Rui; Liu, Yingjuan; Zhao, Caiyuan; Shen, Yujin; Yin, Guojun

    2015-03-01

    We investigated the protective effects of curcumin on liver-damaged Cyprinus carpio var. Jian (Jian carp). The carp were fed 0.1%, 0.5%, or 1.0% curcumin for 60 days, then injected intraperitoneally with 30% carbon tetrachloride solution. Liver and blood samples were collected to measure the liver index, serum- and liver-associated enzymes, liver histology, nuclear factor-κB (NF-κB)/c-Rel, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-12 mRNA expression, and the level of NF-κB/c-Rel protein in the liver, and for a comet assay. We found that 0.5% and 1.0% curcumin significantly reduced the CCl(4)-induced increase in the liver index. The comet assay showed that the tail moment, olive tail moment, tail length, and tail DNA% improved in fish pretreated with 0.5 or 1.0% curcumin. CCl(4)-induced histological changes, including extensive hepatocyte degeneration, indistinct cell borders, nuclear condensation, and karyolysis were clearly reduced after treatment with 0.5% and 1.0% curcumin. Moreover, 0.5% and 1.0% curcumin significantly inhibited the CCl(4)-induced increase in serum glutamic oxaloacetic transaminase and promoted the restoration of superoxide dismutase in the liver; 1.0% curcumin significantly reduced serum glutamic pyruvic transaminase and lactate dehydrogenase and hepatic malondialdehyde, but significantly increased the total antioxidant capacity and glutathione levels in the liver. The CCl(4)-induced upregulation of NF-κB/c-Rel, IL-1β, and TNF-α mRNAs and NF-κB/c-Rel protein levels was inhibited by 0.5% and 1.0% curcumin, and IL-12 mRNA was reduced by all three doses of curcumin. The effects of curcumin on the liver index, enzymes, histological changes, and cytokines were dose-dependent. Our results indicate that curcumin reduces CCl(4)-induced liver damage in Jian carp by upregulating antioxidative activities and inhibiting NF-κB, IL-1β, TNF-α, and IL-12 expression. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Toxicogenomic analysis of N-nitrosomorpholine induced changes in rat liver: Comparison of genomic and proteomic responses and anchoring to histopathological parameters

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Oberemm, A., E-mail: axel.oberemm@bfr.bund.d; Ahr, H.-J.; Bannasch, P.

    2009-12-01

    A common animal model of chemical hepatocarcinogenesis was used to examine the utility of transcriptomic and proteomic data to identify early biomarkers related to chemically induced carcinogenesis. N-nitrosomorpholine, a frequently used genotoxic model carcinogen, was applied via drinking water at 120 mg/L to male Wistar rats for 7 weeks followed by an exposure-free period of 43 weeks. Seven specimens of each treatment group (untreated control and 120 mg/L N-nitrosomorpholine in drinking water) were sacrificed at nine time points during and after N-nitrosomorpholine treatment. Individual samples from the liver were prepared for histological and toxicogenomic analyses. For histological detection of preneoplasticmore » and neoplastic tissue areas, sections were stained using antibodies against the placental form of glutathione-S-transferase (GST-P). Gene and protein expression profiles of liver tissue homogenates were analyzed using RG-U34A Affymetrix rat gene chips and two-dimensional gel electrophoresis-based proteomics, respectively. In order to compare results obtained by histopathology, transcriptomics and proteomics, GST-P-stained liver sections were evaluated morphometrically, which revealed a parallel time course of the area fraction of preneoplastic lesions and gene plus protein expression patterns. On the transcriptional level, an increase of hepatic GST-P expression was detectable as early as 3 weeks after study onset. Comparing deregulated genes and proteins, eight species were identified which showed a corresponding expression profile on both expression levels. Functional analysis suggests that these genes and corresponding proteins may be useful as biomarkers of early hepatocarcinogenesis.« less

  1. Histological spectrum of angiofibroma of soft tissue: histological and genetic analysis of 13 cases.

    PubMed

    Yamada, Yuichi; Yamamoto, Hidetaka; Kohashi, Kenichi; Ishii, Takeaki; Iura, Kunio; Maekawa, Akira; Bekki, Hirofumi; Otsuka, Hiroshi; Yamashita, Kyoko; Tanaka, Hiroyuki; Hiraki, Tsubasa; Mukai, Munenori; Shirakawa, Atsuko; Shinnou, Yoko; Jinno, Mari; Yanai, Hiroyuki; Taguchi, Kenichi; Maehara, Yoshihiko; Iwamoto, Yukihide; Oda, Yosinao

    2016-09-01

    Angiofibroma of soft tissue (AFST) is a rare soft tissue neoplasm characterized by a fibroblastic cytomorphology and a prominent vascular structure. AFSTs possess a novel fusion gene, i.e. NCOA2-AHRR/AHRR-NCOA2 or GTF2I-NCOA2, providing a useful approach to diagnosing AFST. Morphologically, AFSTs span a wide spectrum, making diagnosis a challenge. The aim of this study was to review AFST cases and to report previously unknown histological features, which we confirmed by genetic analysis. We reviewed 276 cases diagnosed as solitary fibrous tumours/haemangiopericytomas (232 cases), unclassified tumours of fibroblastic differentiation (36 cases), and recently diagnosed AFSTs (eight cases), and retrieved 13 cases compatible with AFST. Immunohistochemical staining was performed for these cases, all 13 of which were analysed by reverse transcription polymerase chain reaction and fluorescence in-situ hybridization. The histological findings were as follows: amianthoid fibres, extravasation of red blood cells, haemosiderin deposition, aggregates of foamy histiocytes, cystic change, necrosis, and haemorrhage. Immunohistochemically, the tumour cells were positive for epithelial membrane antigen (four of 13 cases), desmin (six of 13 cases), CD163 (13 of 13 cases), CD68 (seven of 13 cases), oestrogen receptor (13 of 13 cases), progesterone receptor (three of 13 cases), and STAT6 (one of 13 cases, weak nuclear staining), but they were negative for CD34, α-smooth muscle actin, muscle-specific actin, S100, pan-cytokeratin, MDM2, and CDK4. The AHRR-NCOA2 fusion gene was detected in eight cases, and NCOA2 gene rearrangement in nine cases. We revealed the previously unreported histological variation and immunohistochemical findings of AFST, and confirmed them by using genetic methods. The results suggested that AFST should be considered in the diagnosis of fibrous or fibrohistiocytic tumours with the above histological features. © 2016 John Wiley & Sons Ltd.

  2. [Interferon-alpha and liver fibrosis in patients with chronic damage due to hepatitis C virus].

    PubMed

    Gonzalez-Huezo, María Sarai; Gallegos-Orozco, Juan Fernando

    2003-01-01

    The present review focuses on the published information published regarding the effects of interferon alpha therapy on liver fibrosis in patients with chronic liver damage secondary to hepatitis C infection. Data reviewed included results of the in vitro effects of interferon on hepatic cell line cultures with regards to indirect markers of fibrosis, activation of hepatic stellate cells and oxidative stress response. In the clinical arena, there is current clear evidence of a favorable histological outcome in patients with sustained viral response to interferon therapy. For this reason, the current review focuses more on the histological outcomes regarding liver fibrosis in patients who have not attained viral response to therapy (non-responders) or who already have biopsy defined cirrhosis. Data in these patients were analyzed according to the results of objective testing of fibrosis through the assessment of liver biopsy and its change during time, specially because the morbidity and mortality of this disease is directly related to the complications of liver cirrhosis and not necessarily to the persistence of the hepatitis C virus. Lastly, it is concluded that the process of liver fibrosis/cirrhosis is a dynamic one and that there is some evidence to support the usefulness of interferon alpha therapy as a means to halt or retard the progression of hepatic fibrosis. The result of current clinical trials in which interferon therapy is being used to modify the progression of fibrosis in non-responders or cirrhotic patients is eagerly awaited.

  3. Histological findings in protocol biopsies following pediatric liver transplant: Low incidence of abnormalities at 5 years.

    PubMed

    Sheikh, Amin; Chau, Kai Y; Evans, Helen M

    2018-05-11

    Histological abnormalities, including chronic hepatitis, fibrosis, and steatosis, are increasingly reported in liver biopsies of children after LT. These changes may be progressive and represent a form of rejection. Liver biochemistry is often initially normal. Our LT program began in 2002, utilizing tacrolimus and low-dose steroids for the first year post-LT. Patients undergo a protocol biopsy at 1 year post-LT prior to stopping steroids, then at 5 years and every 5 years thereafter. Target tacrolimus levels are 5-8 μg/L and 3-5 μg/L after 3 and 12 months, respectively. Between 2002 and 2009, 51 LT were performed; 50 (98%) and 49 (96%) patients survived for 1 and 5 years, respectively. A total of 43 patients (median age at LT 2.3 years) underwent a protocol biopsy at 1 year (16 male; median time post-LT 12.5 months), and 44 (20 male; median time post-LT 5.1 years) at 5 years. By 5 years, 3 had transferred to adult services; 1 was re-transplanted for graft failure and 1 moved overseas. Biopsies were reviewed by 2 pathologists. Most patients (31/44) were on tacrolimus monotherapy at 5 years. At 1 and 5 years, 29 of 43 (67.5%) and 31 of 44 (71%) biopsies were normal, respectively. Two of 44 had chronic allograft hepatitis at 5 years. Two of 43 and 1 of 44 had isolated fibrosis, 3 of 43 and 3 of 44 steatosis, and 3 of 43 and 4 of 44 acute rejection at 1 and 5 years, respectively. Other findings included predominantly biliary changes (6/43 & 3/44 at 1 and 5 years, respectively). Tacrolimus levels at 5 years were slightly higher than anticipated (median trough level 5.8 μg/L). With an immunosuppressive regimen of tacrolimus and low-dose steroids for 1 year followed by tacrolimus monotherapy thereafter, the majority of PLB were normal and no progressive changes were observed at 5 years. Compared to other LT programs, we have lower rates of chronic allograft hepatitis, steatosis, and fibrosis at 5 years. However, the tacrolimus levels at 5

  4. Diclofenac affects kidney histology in the three-spined stickleback (Gasterosteus aculeatus) at low μg/L concentrations.

    PubMed

    Näslund, Johanna; Fick, Jerker; Asker, Noomi; Ekman, Elisabet; Larsson, D G Joakim; Norrgren, Leif

    2017-08-01

    Diclofenac, a commonly used non-steroidal anti-inflammatory drug, is considered for regulation under the European water framework directive. This is because effects on fish have been reported at concentrations around those regularly found in treated sewage effluents (∼1μg/L). However, a recent publication reports no effects on fish at 320μg/L. In this study, three-spined sticklebacks (Gasterosteus aculeatus) were exposed to 0, 4.6, 22, 82 and 271μg/L diclofenac in flow-through systems for 28days using triplicate aquaria per concentration. At the highest concentration, significant mortalities were observed already after 21days (no mortalities found up to 22μg/L). Histological analysis revealed a significant increase in the proportion of renal hematopoietic tissue (renal hematopoietic hyperplasia) after 28days at the lowest concentration and at all higher concentrations, following a clear dose-response pattern. Skin ulcerations of the jaw were noted by macroscopic observations, primarily at the two highest concentrations. No histological changes were observed in the liver. There was an increase in the relative hepatic mRNA levels of c7 (complement component 7), a gene involved in the innate immune system, at 22μg/L and at all higher concentrations, again following a clear dose-response. The bioconcentration factor was stable across concentrations, but lower than reported for rainbow trout, suggesting lower internal exposure to the drug in the stickleback. In conclusion, this study demonstrates that diclofenac causes histological changes in the three-spined stickleback at low μg/L concentrations, which cause concern for fish populations exposed to treated sewage effluents. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Performance and limitations of steatosis biomarkers in patients with nonalcoholic fatty liver disease.

    PubMed

    Fedchuk, L; Nascimbeni, F; Pais, R; Charlotte, F; Housset, C; Ratziu, V

    2014-11-01

    Several steatosis biomarkers are available with limited independent validation. To determine diagnostic value and limitations of several steatosis biomarkers using liver biopsy as reference standard in a large cohort of patients with suspected NAFLD. Three hundred and twenty-four consecutive liver biopsies were included. Histological steatosis was categorised as none (<5%), mild (5-33%), moderate (33-66%) and severe (>66%). Five steatosis biomarkers were measured: fatty liver index (FLI), NAFLD liver fat score (NAFLD-LFS), hepatic steatosis index (HSI), visceral adiposity index (VAI) and triglyceride × glucose (TyG) index. Steatosis grades prevalence was: none 5%, mild 39%, moderate 30% and severe 27%. Except for VAI, the steatosis biomarkers showed a linear trend across the steatosis grades. However, their correlation with the histological amount of steatosis was only weak-moderate. All steatosis biomarkers had an adequate diagnostic accuracy for the presence of steatosis: AUROCs for FLI, LFS, HSI, VAI and TyG were 0.83, 0.80, 0.81, 0.92 and 0.90. However, their ability to quantify steatosis was poor: none of them distinguished between moderate and severe steatosis and the AUROCs for predicting steatosis >33% were 0.65, 0.72, 0.65, 0.59 and 0.59 for FLI, LFS, HSI, VAI and TyG. Both fibrosis and inflammation significantly confounded the association between steatosis biomarkers and steatosis. The steatosis biomarkers were all correlated with HOMA-IR, independent from histological steatosis. All five steatosis biomarkers can diagnose steatosis and are correlated with insulin resistance. They are confounded by fibrosis and inflammation, and do not accurately quantify steatosis; this may limit their clinical utility. More research is needed to identify truly independent and quantitative markers of steatosis. © 2014 John Wiley & Sons Ltd.

  6. CXC chemokine ligand 4 (Cxcl4) is a platelet-derived mediator of experimental liver fibrosis.

    PubMed

    Zaldivar, Mirko Moreno; Pauels, Katrin; von Hundelshausen, Philipp; Berres, Marie-Luise; Schmitz, Petra; Bornemann, Jörg; Kowalska, M Anna; Gassler, Nikolaus; Streetz, Konrad L; Weiskirchen, Ralf; Trautwein, Christian; Weber, Christian; Wasmuth, Hermann E

    2010-04-01

    Liver fibrosis is a major cause of morbidity and mortality worldwide. Platelets are involved in liver damage, but the underlying molecular mechanisms remain elusive. Here, we investigate the platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) as a molecular mediator of fibrotic liver damage. Serum concentrations and intrahepatic messenger RNA of CXCL4 were measured in patients with chronic liver diseases and mice after toxic liver injury. Platelet aggregation in early fibrosis was determined by electron microscopy in patients and by immunohistochemistry in mice. Cxcl4(-/-) and wild-type mice were subjected to two models of chronic liver injury (CCl(4) and thioacetamide). The fibrotic phenotype was analyzed by histological, biochemical, and molecular analyses. Intrahepatic infiltration of immune cells was investigated by fluorescence-activated cell sorting, and stellate cells were stimulated with recombinant Cxcl4 in vitro. The results showed that patients with advanced hepatitis C virus-induced fibrosis or nonalcoholic steatohepatitis had increased serum levels and intrahepatic CXCL4 messenger RNA concentrations. Platelets were found directly adjacent to collagen fibrils. The CCl(4) and thioacetamide treatment led to an increase of hepatic Cxcl4 levels, platelet activation, and aggregation in early fibrosis in mice. Accordingly, genetic deletion of Cxcl4 in mice significantly reduced histological and biochemical liver damage in vivo, which was accompanied by changes in the expression of fibrosis-related genes (Timp-1 [tissue inhibitor of matrix metalloproteinase 1], Mmp9 [matrix metalloproteinase 9], Tgf-beta [transforming growth factor beta], IL10 [interleukin 10]). Functionally, Cxcl4(-/-) mice showed a strongly decreased infiltration of neutrophils (Ly6G) and CD8(+) T cells into the liver. In vitro, recombinant murine Cxcl4 stimulated the proliferation, chemotaxis, and chemokine expression of hepatic stellate cells. The results underscore an important role

  7. Nonalcoholic Fatty Liver Disease: MR Imaging of Liver Proton Density Fat Fraction to Assess Hepatic Steatosis

    PubMed Central

    Tang, An; Tan, Justin; Sun, Mark; Hamilton, Gavin; Bydder, Mark; Wolfson, Tanya; Gamst, Anthony C.; Middleton, Michael; Brunt, Elizabeth M.; Loomba, Rohit; Lavine, Joel E.; Schwimmer, Jeffrey B.

    2013-01-01

    Purpose: To evaluate the diagnostic performance of magnetic resonance (MR) imaging–estimated proton density fat fraction (PDFF) for assessing hepatic steatosis in nonalcoholic fatty liver disease (NAFLD) by using centrally scored histopathologic validation as the reference standard. Materials and Methods: This prospectively designed, cross-sectional, internal review board–approved, HIPAA-compliant study was conducted in 77 patients who had NAFLD and liver biopsy. MR imaging–PDFF was estimated from magnitude-based low flip angle multiecho gradient-recalled echo images after T2* correction and multifrequency fat modeling. Histopathologic scoring was obtained by consensus of the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network Pathology Committee. Spearman correlation, additivity and variance stabilization for regression for exploring the effect of a number of potential confounders, and receiver operating characteristic analyses were performed. Results: Liver MR imaging–PDFF was systematically higher, with higher histologic steatosis grade (P < .001), and was significantly correlated with histologic steatosis grade (ρ = 0.69, P < .001). The correlation was not confounded by age, sex, lobular inflammation, hepatocellular ballooning, NASH diagnosis, fibrosis, or magnetic field strength (P = .65). Area under the receiver operating characteristic curves was 0.989 (95% confidence interval: 0.968, 1.000) for distinguishing patients with steatosis grade 0 (n = 5) from those with grade 1 or higher (n = 72), 0.825 (95% confidence interval: 0.734, 0.915) to distinguish those with grade 1 or lower (n = 31) from those with grade 2 or higher (n = 46), and 0.893 (95% confidence interval: 0.809, 0.977) to distinguish those with grade 2 or lower (n = 58) from those with grade 3 (n = 19). Conclusion: MR imaging–PDFF showed promise for assessment of hepatic steatosis grade in patients with NAFLD. For validation, further studies with larger sample sizes are

  8. Nonalcoholic fatty liver disease: MR imaging of liver proton density fat fraction to assess hepatic steatosis.

    PubMed

    Tang, An; Tan, Justin; Sun, Mark; Hamilton, Gavin; Bydder, Mark; Wolfson, Tanya; Gamst, Anthony C; Middleton, Michael; Brunt, Elizabeth M; Loomba, Rohit; Lavine, Joel E; Schwimmer, Jeffrey B; Sirlin, Claude B

    2013-05-01

    To evaluate the diagnostic performance of magnetic resonance (MR) imaging-estimated proton density fat fraction (PDFF) for assessing hepatic steatosis in nonalcoholic fatty liver disease (NAFLD) by using centrally scored histopathologic validation as the reference standard. This prospectively designed, cross-sectional, internal review board-approved, HIPAA-compliant study was conducted in 77 patients who had NAFLD and liver biopsy. MR imaging-PDFF was estimated from magnitude-based low flip angle multiecho gradient-recalled echo images after T2* correction and multifrequency fat modeling. Histopathologic scoring was obtained by consensus of the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network Pathology Committee. Spearman correlation, additivity and variance stabilization for regression for exploring the effect of a number of potential confounders, and receiver operating characteristic analyses were performed. Liver MR imaging-PDFF was systematically higher, with higher histologic steatosis grade (P < .001), and was significantly correlated with histologic steatosis grade (ρ = 0.69, P < .001). The correlation was not confounded by age, sex, lobular inflammation, hepatocellular ballooning, NASH diagnosis, fibrosis, or magnetic field strength (P = .65). Area under the receiver operating characteristic curves was 0.989 (95% confidence interval: 0.968, 1.000) for distinguishing patients with steatosis grade 0 (n = 5) from those with grade 1 or higher (n = 72), 0.825 (95% confidence interval: 0.734, 0.915) to distinguish those with grade 1 or lower (n = 31) from those with grade 2 or higher (n = 46), and 0.893 (95% confidence interval: 0.809, 0.977) to distinguish those with grade 2 or lower (n = 58) from those with grade 3 (n = 19). MR imaging-PDFF showed promise for assessment of hepatic steatosis grade in patients with NAFLD. For validation, further studies with larger sample sizes are needed. © RSNA, 2013.

  9. Shared liver-like transcriptional characteristics in liver metastases and corresponding primary colorectal tumors.

    PubMed

    Cheng, Jun; Song, Xuekun; Ao, Lu; Chen, Rou; Chi, Meirong; Guo, You; Zhang, Jiahui; Li, Hongdong; Zhao, Wenyuan; Guo, Zheng; Wang, Xianlong

    2018-01-01

    Background & Aims : Primary tumors of colorectal carcinoma (CRC) with liver metastasis might gain some liver-specific characteristics to adapt the liver micro-environment. This study aims to reveal potential liver-like transcriptional characteristics associated with the liver metastasis in primary colorectal carcinoma. Methods: Among the genes up-regulated in normal liver tissues versus normal colorectal tissues, we identified "liver-specific" genes whose expression levels ranked among the bottom 10% ("unexpressed") of all measured genes in both normal colorectal tissues and primary colorectal tumors without metastasis. These liver-specific genes were investigated for their expressions in both the primary tumors and the corresponding liver metastases of seven primary CRC patients with liver metastasis using microdissected samples. Results: Among the 3958 genes detected to be up-regulated in normal liver tissues versus normal colorectal tissues, we identified 12 liver-specific genes and found two of them, ANGPTL3 and CFHR5 , were unexpressed in microdissected primary colorectal tumors without metastasis but expressed in both microdissected liver metastases and corresponding primary colorectal tumors (Fisher's exact test, P < 0.05). Genes co-expressed with ANGPTL3 and CFHR5 were significantly enriched in metabolism pathways characterizing liver tissues, including "starch and sucrose metabolism" and "drug metabolism-cytochrome P450". Conclusions: For primary CRC with liver metastasis, both the liver metastases and corresponding primary colorectal tumors may express some liver-specific genes which may help the tumor cells adapt the liver micro-environment.

  10. Thermodiffusion for continuous quantification of hepatic microcirculation--validation and potential in liver transplantation.

    PubMed

    Klar, E; Kraus, T; Bleyl, J; Newman, W H; Bowman, H F; Hofmann, W J; Kummer, R; Bredt, M; Herfarth, C

    1999-09-01

    Hepatic microcirculation is a main determinant of reperfusion injury and graft quality in liver transplantation. Methods available for the quantification of hepatic microcirculation are indirect, are invasive, or preclude postoperative application. The aim of this study was the validation of thermodiffusion in a new modification allowing long-term use in the clinical setting. In six pigs Doppler flowmeters were positioned around the hepatic artery and portal vein for the measurement of total liver blood flow. Liver perfusion was quantified by thermodiffusion and compared to H(2) clearance as an established technique under baseline conditions, during different degrees of portal venous obstruction and during occlusion of the hepatic artery. Thermodiffusion measurements were recorded for five days postoperatively followed by histological evaluation of the hepatic puncture site. Perfusion data obtained by thermodiffusion were significantly correlated to H(2) clearance (r = 0.94, P < 0. 001) and to liver blood flow (r = 0.9, P < 0.05). The agreement between thermodiffusion and H(2) clearance was excellent (mean difference -2.1 ml/100 g/min; limits of agreement -12.5 and 8.3 ml/100 g/min). Occlusion of the portal vein or hepatic artery was immediately detected by thermodiffusion, indicating a decrease of perfusion by 64 +/- 7% or 27 +/- 5% of baseline, respectively. Perfusion values at baseline and during vascular occlusion were reproducible during the entire observation period. Histological changes of the liver tissue adjacent to the thermodiffusion probes were minute and did not influence long-term measurements. In vivo validation proved that enhanced thermodiffusion is a minimally invasive technique for the continuous, real-time quantification of hepatic microcirculation. Changes in liver perfusion can be safely detected over several days postoperatively. The implication for liver transplantation has led to the clinical application of thermodiffusion. Copyright 1999

  11. Impact of donor histology on survival following liver transplantation for chronic hepatitis C virus infection: a Scandinavian single-center experience.

    PubMed

    Ydreborg, Magdalena; Westin, Johan; Lagging, Martin; Castedal, Maria; Friman, Styrbjörn

    2012-06-01

    Survival following liver transplantation for hepatitis C virus (HCV) infection is affected by several factors. The aims of this single-center study were to evaluate survival from 1992 to 2006 in HCV-infected liver transplant recipients and to identify factors influencing patient and graft survival, with particular focus on donor liver histopathology. Survival among 84 patients transplanted for HCV-related liver disease at the Sahlgrenska University Hospital during the above period was evaluated. Median follow-up time was 57 months (range 28-87). A perioperative liver biopsy from the donor liver graft was available in 68 cases. Biopsies were assessed for fibrosis, necroinflammatory activity, and degree of steatosis. Patient and graft survival according to relevant factors including donor histopathology were analyzed by Kaplan-Meier analysis. We found an association between donor liver fibrosis and patient survival (p = 0.016) as well as between graft survival and portal inflammation in the donor liver (p = 0.026). Both these associations remained significant in multivariate analysis (p = 0.007 and 0.017 respectively). Moreover, recipient age over 60 was found predictive of patient survival and repeated steroid boluses or steroid-resistant rejection of graft survival. Donor age was high throughout the study period. Histopathological features, especially portal inflammation and stage of fibrosis, in the donor liver may deleteriously affect graft and patient survival following HCV-related liver transplantation. Thus, pretransplant evaluation of donor histopathology may be of value in the selection of donors for transplantation of HCV-positive individuals, especially among donors older than 60 years.

  12. Hepatic fat quantification using the two-point Dixon method and fat color maps based on non-alcoholic fatty liver disease activity score.

    PubMed

    Hayashi, Tatsuya; Saitoh, Satoshi; Takahashi, Junji; Tsuji, Yoshinori; Ikeda, Kenji; Kobayashi, Masahiro; Kawamura, Yusuke; Fujii, Takeshi; Inoue, Masafumi; Miyati, Tosiaki; Kumada, Hiromitsu

    2017-04-01

    The two-point Dixon method for magnetic resonance imaging (MRI) is commonly used to non-invasively measure fat deposition in the liver. The aim of the present study was to assess the usefulness of MRI-fat fraction (MRI-FF) using the two-point Dixon method based on the non-alcoholic fatty liver disease activity score. This retrospective study included 106 patients who underwent liver MRI and MR spectroscopy, and 201 patients who underwent liver MRI and histological assessment. The relationship between MRI-FF and MR spectroscopy-fat fraction was used to estimate the corrected MRI-FF for hepatic multi-peaks of fat. Then, a color FF map was generated with the corrected MRI-FF based on the non-alcoholic fatty liver disease activity score. We defined FF variability as the standard deviation of FF in regions of interest. Uniformity of hepatic fat was visually graded on a three-point scale using both gray-scale and color FF maps. Confounding effects of histology (iron, inflammation and fibrosis) on corrected MRI-FF were assessed by multiple linear regression. The linear correlations between MRI-FF and MR spectroscopy-fat fraction, and between corrected MRI-FF and histological steatosis were strong (R 2  = 0.90 and R 2  = 0.88, respectively). Liver fat variability significantly increased with visual fat uniformity grade using both of the maps (ρ = 0.67-0.69, both P < 0.001). Hepatic iron, inflammation and fibrosis had no significant confounding effects on the corrected MRI-FF (all P > 0.05). The two-point Dixon method and the gray-scale or color FF maps based on the non-alcoholic fatty liver disease activity score were useful for fat quantification in the liver of patients without severe iron deposition. © 2016 The Japan Society of Hepatology.

  13. Effect of Tridax procumbens (Linn.) on bile duct ligation-induced liver fibrosis in rats.

    PubMed

    Joshi, P P; Patil, S D; Silawat, N; Deshmukh, P T

    2011-12-01

    The present study was undertaken to clarify whether methanolic extract of Tridax procumbens prevents liver fibrosis in rat. The hepatic fibrosis was induced by 28 days of bile duct ligation in rats. The 4-week treatment with Tridex procumbens reduced the serum aspartate aminotransferase (U L⁻¹), glutamate pyruvate transaminase (U L⁻¹), alkaline phosphatase (IU L⁻¹), lactate dehydrogenase (IU L⁻¹), total bilirubin (mg dL⁻¹), direct bilirubin (mg dL⁻¹) and hydroxyproline (mg gm⁻¹) content in liver and improved the histological appearance of liver section. The results of this study led us to conclude that T. procumbens can reduce the degree of hepatocellular damage and may become antifibrotic agent for liver fibrosis.

  14. Histological heterogeneity in primary and metastatic classic combined hepatocellular-cholangiocarcinoma: a case series.

    PubMed

    De Vito, Claudio; Sarker, Debashis; Ross, Paul; Heaton, Nigel; Quaglia, Alberto

    2017-11-01

    Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare and aggressive primary liver cancer with both hepatocellular and cholangiocellular differentiation. Due to its bi-phenotypic component, cHCC-CC is a heterogeneous tumour and histopathological analysis of metastatic deposits is poorly characterized. In this retrospective study, we describe four patients in whom the histology from resected specimens of both primary and recurrent and/or metastatic tumour was available for comparison and immunohistochemical characterization. Our study shows that recurrent or metastatic deposits replicate the heterogeneity of the primary cHCC-CC, that even originally small foci of divergent differentiation can become predominant later on and that hepatocellular and cholangiocellular components can show different tropism in distant organs. In our experience, the behaviour of recurrent/metastatic cHCC-CC is unpredictable and histological examination is necessary to guide treatment options at present.

  15. Effect of Colesevelam on Liver Fat Quantified by Magnetic Resonance in Nonalcoholic Steatohepatitis: A Randomized Controlled Trial

    PubMed Central

    Le, Thuy-Anh; Chen, Joshua; Changchien, Christopher; Peterson, Michael R; Kono, Yuko; Patton, Heather; Cohen, Benjamin L; Brenner, David; Sirlin, Claude; Loomba, Rohit

    2012-01-01

    Bile acid sequestrants (BAS) lower plasma low density lipoprotein levels and improve glycemic control. Colestimide, a BAS, has been claimed by computed tomography to reduce liver fat. Therefore, we examined the efficacy of colesevelam, a potent BAS, to decrease liver fat in patients with biopsy-proven nonalcoholic steatohepatitis (NASH). Liver fat was measured by a novel magnetic resonance imaging (MRI) technique, the proton-density-fat-fraction (PDFF), as well as by conventional MR spectroscopy (MRS). Fifty patients with biopsy-proven NASH were randomly assigned to either colesevelam 3.75 g/day orally or placebo for 24 weeks. The primary outcome was change in liver fat as measured by MRI-PDFF in colocalized regions of interest within each of the nine liver segments. Compared with placebo, colesevelam increased liver fat by MRI-PDFF in all nine segments of the liver with a mean difference of 5.6% (P = 0.002). We cross-validated the MRI-PDFF-determined fat content with that assessed by colocalized MRS; the latter showed a mean difference of 4.9% (P = 0.014) in liver fat between the colesevelam and the placebo arms. MRI-PDFF correlated strongly with MRS-determined hepatic fat content (r2 = 0.96, P < 0.0001). Liver biopsy assessment of steatosis, cellular injury, and lobular inflammation did not detect any effect of treatment. Conclusion: Colesevelam increases liver fat in patients with NASH as assessed by MRI as well as MRS without significant changes seen on histology. Thus, MRI and MRS may be better than histology to detect longitudinal changes in hepatic fat in NASH. Underlying mechanisms and whether the small MR-detected increase in liver fat has clinical consequences is not known. (Hepatology 2012;56:922–932) PMID:22431131

  16. A history of obesity leaves an inflammatory fingerprint in liver and adipose tissue

    PubMed Central

    Fischer, I P; Irmler, M; Meyer, C W; Sachs, S J; Neff, F; Hrabě de Angelis, M; Beckers, J; Tschöp, M H; Hofmann, S M; Ussar, S

    2018-01-01

    Background/Objectives: Dieting is a popular yet often ineffective way to lower body weight, as the majority of people regain most of their pre-dieting weights in a relatively short time. The underlying molecular mechanisms driving weight regain and the increased risk for metabolic disease are still incompletely understood. Here we investigate the molecular alterations inherited from a history of obesity. Methods: In our model, male high-fat diet (HFD)-fed obese C57BL/6J mice were switched to a low caloric chow diet, resulting in a decline of body weight to that of lean mice. We measured body composition, as well as metrics of glucose, insulin and lipid homeostasis. This was accompanied by histological and gene expression analysis of adipose tissue and liver to assess adipose tissue inflammation and hepatosteatosis. Moreover, acute hypothalamic response to (re-) exposure to HFD was assessed by qPCR. Results & Conclusions: Within 7 weeks after diet switch, most obesity-associated phenotypes, such as body mass, glucose intolerance and blood metabolite levels were reversed. However, hepatic inflammation, hepatic steatosis as well as hypertrophy and inflammation of perigonadal, but not subcutaneous, adipocytes persisted in formerly obese mice. Transcriptional profiling of liver and perigonadal fat revealed an upregulation of pathways associated with immune function and cellularity. Thus, we show that weight reduction leaves signs of inflammation in liver and perigonadal fat, indicating that persisting proinflammatory signals in liver and adipose tissue could contribute to an increased risk of formerly obese subjects to develop the metabolic syndrome upon recurring weight gain. PMID:28901330

  17. Apnoeic-hypopnoeic episodes during obstructive sleep apnoea are associated with histological nonalcoholic steatohepatitis.

    PubMed

    Mishra, Poonam; Nugent, Clarke; Afendy, Arian; Bai, Chunhong; Bhatia, Priya; Afendy, Mariam; Fang, Yun; Elariny, Hazem; Goodman, Zachary; Younossi, Zobair M

    2008-09-01

    Nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnoea are associated with metabolic syndrome and atherosclerotic heart disease. This study evaluates the potential association between the NAFLD subtypes and a number of polysomnographical (PSG) parameters. This study included patients undergoing bariatric surgery with extensive clinical and histological data for whom complete PSG data before surgery were also available. Excess alcohol intake and other causes of liver disease were excluded. Apnoea, hypopnoea and apnoea-hypopnoea index (AHI) were calculated as described previously. In this study, a total of 101 patients [77 nonalcoholic steatohepatitis (NASH) and 22 non-NASH controls] with PSG data were included (age 42.9 +/- 11.4 years, body mass index 51.6 +/- 9.5 kg/m(2), fasting serum glucose 117.4 +/- 53.4 mg/dl, fasting serum triglycerides 171.3 +/- 82.9 mg/dl, 58% hypertension and 33% diabetes mellitus). Subjects with histological NASH had significantly lower lowest desaturation (77 vs. 85%, P=0.006), lower mean nocturnal oxygen saturation (91 vs. 93%, P=0.05), higher AHI (35 vs. 22, P=0.03), higher respiratory disturbance index (46 vs. 21, P=0.02) and higher alanine aminotransferase/aspartate aminotransferase ratio (1.4 vs. 1.3, P=0.05) compared with non-NASH controls. In multivariate analysis, the lowest desaturation (P=0.04) was independently associated with histological NASH. Lowest desaturation and mean nocturnal oxygen saturation were significantly lower in subjects with fibrosis (76 vs. 85%, P=0.004 and 90.4 vs. 93.0%, P=0.02). Our results suggest that the frequent nocturnal hypoxic episodes in NAFLD patients may be a risk factor for developing NASH. Additional studies are needed to study the effect of optimizing sleep apnoea management on the outcomes of patients with NAFLD.

  18. Hepatoprotective Effect of Cuscuta campestris Yunck. Whole Plant on Carbon Tetrachloride Induced Chronic Liver Injury in Mice.

    PubMed

    Peng, Wen-Huang; Chen, Yi-Wen; Lee, Meng-Shiou; Chang, Wen-Te; Tsai, Jen-Chieh; Lin, Ying-Chih; Lin, Ming-Kuem

    2016-12-07

    Cuscuta seeds and whole plant have been used to nourish the liver and kidney. This study was aimed to investigate the hepatoprotective activity of the ethanol extract of Cuscuta campestris Yunck. whole plant (CC EtOH ). The hepatoprotective effect of CC EtOH (20, 100 and 500 mg/kg) was evaluated on carbon tetrachloride (CCl₄)-induced chronic liver injury. Serum alanine aminotransferase, aspartate aminotransferase, triglyceride and cholesterol were measured and the fibrosis was histologically examined. CC EtOH exhibited a significant inhibition of the increase of serum alanine aminotransferase, aspartate aminotransferase, triglyceride and cholesterol. Histological analyses showed that fibrosis of liver induced by CCl₄ were significantly reduced by CC EtOH . In addition, 20, 100 and 500 mg/kg of the extract decreased the level of malondialdehyde (MDA) and enhanced the activities of anti-oxidative enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver. We demonstrate that the hepatoprotective mechanisms of CC EtOH were likely to be associated to the decrease in MDA level by increasing the activities of antioxidant enzymes such as SOD, GPx and GRd. In addition, our findings provide evidence that C. campestris Yunck. whole plant possesses a hepatoprotective activity to ameliorate chronic liver injury.

  19. Hepatoprotective Effect of Cuscuta campestris Yunck. Whole Plant on Carbon Tetrachloride Induced Chronic Liver Injury in Mice

    PubMed Central

    Peng, Wen-Huang; Chen, Yi-Wen; Lee, Meng-Shiou; Chang, Wen-Te; Tsai, Jen-Chieh; Lin, Ying-Chih; Lin, Ming-Kuem

    2016-01-01

    Cuscuta seeds and whole plant have been used to nourish the liver and kidney. This study was aimed to investigate the hepatoprotective activity of the ethanol extract of Cuscuta campestris Yunck. whole plant (CCEtOH). The hepatoprotective effect of CCEtOH (20, 100 and 500 mg/kg) was evaluated on carbon tetrachloride (CCl4)-induced chronic liver injury. Serum alanine aminotransferase, aspartate aminotransferase, triglyceride and cholesterol were measured and the fibrosis was histologically examined. CCEtOH exhibited a significant inhibition of the increase of serum alanine aminotransferase, aspartate aminotransferase, triglyceride and cholesterol. Histological analyses showed that fibrosis of liver induced by CCl4 were significantly reduced by CCEtOH. In addition, 20, 100 and 500 mg/kg of the extract decreased the level of malondialdehyde (MDA) and enhanced the activities of anti-oxidative enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver. We demonstrate that the hepatoprotective mechanisms of CCEtOH were likely to be associated to the decrease in MDA level by increasing the activities of antioxidant enzymes such as SOD, GPx and GRd. In addition, our findings provide evidence that C. campestris Yunck. whole plant possesses a hepatoprotective activity to ameliorate chronic liver injury. PMID:27941627

  20. Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver.

    PubMed

    Chukijrungroat, Natsasi; Khamphaya, Tanaporn; Weerachayaphorn, Jittima; Songserm, Thaweesak; Saengsirisuwan, Vitoon

    2017-08-01

    The role of gender in the progression of fatty liver due to chronic high-fat high-fructose diet (HFFD) has not been studied. The present investigation assessed whether HFFD induced hepatic perturbations differently between the sexes and examined the potential mechanisms. Male, female, and ovariectomized (OVX) Sprague-Dawley rats were fed either a control diet or HFFD for 12 wk. Indexes of liver damage and hepatic steatosis were analyzed biochemically and histologically together with monitoring changes in hepatic gene and protein expression. HFFD induced a higher degree of hepatic steatosis in females, with significant increases in proteins involved in hepatic lipogenesis, whereas HFFD significantly induced liver injury, inflammation, and oxidative stress only in males. Interestingly, a significant increase in hepatic fibroblast growth factor 21 (FGF21) protein expression was observed in HFFD-fed males but not in HFFD-fed females. Ovarian hormone deprivation by itself led to a significant reduction in FGF21 with hepatic steatosis, and HFFD further aggravated hepatic fat accumulation in OVX rats. Importantly, estrogen replacement restored hepatic FGF21 levels and reduced hepatic steatosis in HFFD-fed OVX rats. Collectively, our results indicate that male rats are more susceptible to HFFD-induced hepatic inflammation and that the mechanism underlying this sex dimorphism is mediated through hepatic FGF21 expression. Our findings reveal sex differences in the development of HFFD-induced fatty liver and indicate the protective role of estrogen against HFFD-induced hepatic steatosis. Copyright © 2017 the American Physiological Society.

  1. Computed tomography findings in liver fibrosis and cirrhosis.

    PubMed

    Huber, A; Ebner, L; Montani, M; Semmo, N; Roy Choudhury, K; Heverhagen, J; Christe, A

    2014-02-19

    Computed tomography (CT) is inferior to the fibroscan and laboratory testing in the noninvasive diagnosis of liver fibrosis. On the other hand, CT is a frequently used diagnostic tool in modern medicine. The auxiliary finding of clinically occult liver fibrosis in CT scans could result in an earlier diagnosis. The aim of this study was to analyse quantifiable direct signs of liver remodelling in CT scans to depict liver fibrosis in a precirrhotic stage. Retrospective review of 148 abdominal CT scans (80 liver cirrhosis, 35 precirrhotic fibrosis and 33 control patients). Fibrosis and cirrhosis were histologically proven. The diameters of the three main hepatic veins were measured 1-2 cm before their aperture into the inferior caval vein. The width of the caudate and the right hepatic lobe were divided, and measured horizontally at the level of the first bifurcation of the right portal vein in axial planes (caudate-right-lobe ratio). A combination of both (sum of liver vein diameters divided by the caudate-right lobe ratio) was defined as the ld/crl ratio. These metrics were analysed for the detection of liver fibrosis and cirrhosis. An ld/crl-r <24 showed a sensitivity of 83% and a specificity of 76% for precirrhotic liver fibrosis. Liver cirrhosis could be detected with a sensitivity of 88% and a specificity of 82% if ld/crl-r <20. An ld/crl-r <24 justifies laboratory testing and a fibroscan. This could bring forward the diagnosis and patients would profit from early treatment in a potentially reversible stage of disease.

  2. Liver regeneration after different degrees of portal vein ligation.

    PubMed

    Lauber, David Tibor; Tihanyi, Dóra Krisztina; Czigány, Zoltán; Kovács, Tibor; Budai, András; Drozgyik, Dóra; Fülöp, András; Szijártó, Attila

    2016-06-15

    Selective portal vein ligation (PVL) is followed by ipsilateral atrophy and contralateral hypertrophy of the liver lobes. Although the atrophy-hypertrophy complex induced by PVL is a well-documented phenomenon, the effect of different degrees of extended portal vein occlusion on liver regeneration is not known. The aim of this study was to assess the effects of different degrees of portal occlusion on portal pressure and liver regeneration. Male Wistar rats (n = 96; 220-250 g) were randomized into three groups and underwent 70%, 80%, or 90% portal vein ligation, respectively. The portal pressure was measured immediately and 24, 48, 72, 120, and 168 h after PVL (n = 6/group/time point). The hepatic lobes and the spleen were weighed, and liver regeneration ratio was calculated. Changes in liver histology and the mitotic activity were assessed on hematoxylin-eosin stained slides. Higher degree of portal occlusion triggered a stronger regenerative response (regeneration ratio of PVL 70%168h = 2.23 ± 0.13, PVL 80%168h = 3.11 ± 0.37, PVL 90%168h = 4.68 ± 0.48) PVL led to an immediate increase in portal pressure, the value of which changed proportionally to the mass of liver tissue deprived of portal perfusion (PVL 70%acute = 17 ± 2 mm Hg, PVL 80%acute = 19 ± 1 mm Hg, PVL 90%acute = 26 ± 4 mm Hg). Findings in histology showed necro-apoptotic lesions in the atrophic liver lobes and increased mitotic cell count in the hypertrophic lobes. The mitotic cell count of PVL 90% peaked earlier and at a significantly higher value than of PVL 70% and PVL 80% (PVL 9024h%: 96.0 ± 3.5 PVL 70%48h: 64.0 ± 2.1, PVL 80%48h: 56.3 ± 4.0). The mitotic index after 24 h showed a strong correlation with the acute portal hypertension. A higher degree of portal vein occlusion leads to a greater regenerative response, presumably triggered by the proportional increase in portal pressure, which supports the role of the so-called "blood-flow" theory of PVL-triggered liver

  3. Metabolic Syndrome: Nonalcoholic Fatty Liver Disease.

    PubMed

    Williams, Tracy

    2015-08-01

    Although nonalcoholic fatty liver disease (NAFLD) is not one of the defining criteria for metabolic syndrome, it is a common hepatic manifestation. NAFLD includes a spectrum of histologic findings ranging from simple steatosis, known as nonalcoholic fatty liver, to nonalcoholic steatohepatitis (NASH). To make the diagnosis of NAFLD, other etiologies of steatosis or hepatitis, such as hepatotoxic drugs, excessive alcohol intake, congenital errors of metabolism, or viral hepatitis, must be ruled out. After ruling out other conditions, the diagnosis of NAFLD often is made clinically, but a definitive diagnosis of NASH requires liver biopsy. As with other complications of metabolic syndrome, insulin resistance is thought to be an underlying etiology of NAFLD. Management strategies attempt to reverse or improve insulin resistance while minimizing liver damage. The strongest evidence supports lifestyle modifications with weight loss, but there is some evidence to support bariatric surgery, medical therapy with insulin-sensitizing agents, and/or pharmacotherapy to promote weight loss. Cardiovascular disease is the major cause of mortality in patients with NAFLD, so management must include modification of cardiovascular risk factors. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  4. Improved noninvasive prediction of liver fibrosis by liver stiffness measurement in patients with nonalcoholic fatty liver disease accounting for controlled attenuation parameter values.

    PubMed

    Petta, Salvatore; Wong, Vincent Wai-Sun; Cammà, Calogero; Hiriart, Jean-Baptiste; Wong, Grace Lai-Hung; Marra, Fabio; Vergniol, Julien; Chan, Anthony Wing-Hung; Di Marco, Vito; Merrouche, Wassil; Chan, Henry Lik-Yuen; Barbara, Marco; Le-Bail, Brigitte; Arena, Umberto; Craxì, Antonio; de Ledinghen, Victor

    2017-04-01

    Liver stiffness measurement (LSM) frequently overestimates the severity of liver fibrosis in nonalcoholic fatty liver disease (NAFLD). Controlled attenuation parameter (CAP) is a new parameter provided by the same machine used for LSM and associated with both steatosis and body mass index, the two factors mostly affecting LSM performance in NAFLD. We aimed to determine whether prediction of liver fibrosis by LSM in NAFLD patients is affected by CAP values. Patients (n = 324) were assessed by clinical and histological (Kleiner score) features. LSM and CAP were performed using the M probe. CAP values were grouped by tertiles (lower 132-298, middle 299-338, higher 339-400 dB/m). Among patients with F0-F2 fibrosis, mean LSM values, expressed in kilopascals, increased according to CAP tertiles (6.8 versus 8.6 versus 9.4, P = 0.001), and along this line the area under the curve of LSM for the diagnosis of F3-F4 fibrosis was progressively reduced from lower to middle and further to higher CAP tertiles (0.915, 0.848-0.982; 0.830, 0.753-0.908; 0.806, 0.723-0.890). As a consequence, in subjects with F0-F2 fibrosis, the rates of false-positive LSM results for F3-F4 fibrosis increased according to CAP tertiles (7.2% in lower versus 16.6% in middle versus 18.1% in higher). Consistent with this, a decisional flowchart for predicting fibrosis was suggested by combining both LSM and CAP values. In patients with NAFLD, CAP values should always be taken into account in order to avoid overestimations of liver fibrosis assessed by transient elastography. (Hepatology 2017;65:1145-1155). © 2016 by the American Association for the Study of Liver Diseases.

  5. [Protective effect of garlic oil given at different time against acute liver injury induced by CCl4].

    PubMed

    Zhang, Gui-li; Zeng, Tao; Wang, Qing-shan; Zhao, Xiu-lan; Song, Fu-yong; Xie, Ke-qin

    2010-03-01

    To observe and compare the protective effect of garlic oil against carbon tetrachloride (CCL)-induced acute liver injury. The experiments include 4 preventive groups and 2 therapeutic groups. In every preventive and therapeutic group, the mice were randomized into 6 groups with 15 each, including one negative control group, one solvent control group, one CCl4 model group and 3 garlic oil groups (25, 50, and 100 mg/kg body weight). Before given a single gavage of CCl4 (80 mg/kg), the mice were pretreated with garlic oil by gavage in preventive group 1 (30 days, once daily), preventive group 2 (5 days, once daily), preventive group 3 (ahead of 2 h, once), preventive group 4 (immediately, once) or the vehicle (corn oil, 10 ml/kg) in solvent control group. In therapeutic groups, the mice were gavaged garlic oil 2 h (once, in therapeutic 1) or for 5 days (once daily, in therapeutic 2) after administration CCl. After 24 h of the last administration, blood was collected and centrifuged at 2500 r/min at 4 degrees C for 10 min, and serum was removed to measure ALT and AST activities. The liver was dissected, weighed to calculate the liver coefficient (relative liver weight). At the same time, the liver samples were studied by histological examinations. Compared with negative group, the liver coefficient and the activities of ALT and AST in serum of model group were increased remarkably (P < 0.01). Compared with CCl model group, the liver coefficient and the activities of ALT and AST in serum were decreased significantly (P < 0.01) by garlic oil dose-dependently in each preventive group. Simultaneously, histological assessment showed that garlic oil effectively alleviated hepatocyte injuries induced by CCl4. Comparing the preventive effects of garlic oil in every group, it was better in preventive group 3 than others. However, all indexes and histological examinations in therapeutic group 1 did not show the difference with those of CCl4 model group. In therapeutic group 2

  6. Mapping of the circulating metabolome reveals α-ketoglutarate as a predictor of morbid obesity-associated non-alcoholic fatty liver disease.

    PubMed

    Rodríguez-Gallego, E; Guirro, M; Riera-Borrull, M; Hernández-Aguilera, A; Mariné-Casadó, R; Fernández-Arroyo, S; Beltrán-Debón, R; Sabench, F; Hernández, M; del Castillo, D; Menendez, J A; Camps, J; Ras, R; Arola, L; Joven, J

    2015-02-01

    Obesity severely affects human health, and the accompanying non-alcoholic fatty liver disease (NAFLD) is associated with high morbidity and mortality. Rapid and non-invasive methods to detect this condition may substantially improve clinical care. We used liquid and gas chromatography-quadruple time-of-flight-mass spectrometry (LC/GC-QTOF-MS) analysis in a non-targeted metabolomics approach on the plasma from morbidly obese patients undergoing bariatric surgery to gain a comprehensive measure of metabolite levels. On the basis of these findings, we developed a method (GC-QTOF-MS) for the accurate quantification of plasma α-ketoglutarate to explore its potential as a novel biomarker for the detection of NAFLD. Plasma biochemical differences were observed between patients with and without NAFLD indicating that the accumulation of lipids in hepatocytes decreased β-oxidation energy production, reduced liver function and altered glucose metabolism. The results obtained from the plasma analysis suggest pathophysiological insights that link lipid and glucose disturbances with α-ketoglutarate. Plasma α-ketoglutarate levels are significantly increased in obese patients compared with lean controls. Among obese patients, the measurement of this metabolite differentiates between those with or without NAFLD. Data from the liver were consistent with data from plasma. Clinical utility was assessed, and the results revealed that plasma α-ketoglutarate is a fair-to-good biomarker in patients (n=230). Other common laboratory liver tests used in routine application did not favourably compare. Plasma α-ketoglutarate is superior to common liver function tests in obese patients as a surrogate biomarker of NAFLD. The measurement of this biomarker may potentiate the search for a therapeutic approach, may decrease the need for liver biopsy and may be useful in the assessment of disease progression.

  7. Free phenolic acids from the seaweed Halimeda monile with antioxidant effect protecting against liver injury.

    PubMed

    Mancini-Filho, Jorge; Novoa, Alexis Vidal; González, Ana Elsa Batista; de Andrade-Wartha, Elma Regina S; de O e Silva, Ana Mara; Pinto, José Ricardo; Mancini, Dalva Assunção Portari

    2009-01-01

    Phenolic compounds are found in seaweed species together with other substances presenting antioxidant activity. The objective of this work was to evaluate the antioxidant activity of the free phenolic acids (FPA) fraction from the seaweed Halimeda monile, and its activity to protect the expression of hepatic enzymes in rats, under experimental CCl4 injury. The antioxidant activity was measured by the DPPH method. The FPA fraction (80 mg/kg, p.o.) was administered during 20 consecutive days to rats. The peroxidation was performed by thiobarbituric acid reactive substances (TBARS). The SOD and CAT enzymatic expressions were measured by RT/PCR. The histology technique was used to evaluate liver injuries. The expression of both, CAT and SOD genes, was more preserved by FPA. Only partial injury could be observed by histology in the liver of rats receiving FPA as compared with the control group; and CCl4 administration induced 60% more peroxidation as compared with the rats receiving FPA. These data suggest that FPA could modulate the antioxidant enzymes and oxidative status in the liver through protection against adverse effects induced by chemical agents.

  8. CHEMICAL CHARACTERIZATION OF A HYPOGLYCEMIC EXTRACT FROM CUCURBITA FICIFOLIA BOUCHE THAT INDUCES LIVER GLYCOGEN ACCUMULATION IN DIABETIC MICE

    PubMed Central

    Jessica, Garcia Gonzalez; Mario, Garcia Lorenzana; Alejandro, Zamilpa; Cesar, Almanza Perez Julio; Ivan, Jasso Villagomez E; Ruben, Roman Ramos; Javier, Alarcon-Aguilar Francisco

    2017-01-01

    Background: The aqueous extract of Cucurbita ficifolia (C. ficifolia) fruit has demonstrated hypoglycemic effect, which may be attributed to some components in the extract. However, the major secondary metabolites in this fruit have not yet been identified and little is known about its extra-pancreatic action, in particular, on liver carbohydrate metabolism. Therefore, in addition to the isolation and structural elucidation of the principal components in the aqueous extract of C. ficifolia, the aim of this study was to determine whether or not the hypoglycemic effect of the aqueous extract of Cucurbita ficifolia (C. ficifolia) fruit is due to accumulation of liver glycogen in diabetic mice. Materials and Methods: The aqueous extract from fruit of C. ficifolia was fractionated and its main secondary metabolites were purified and chemically characterized (NMR and GC-MS). Alloxan-induced diabetic mice received daily by gavage the aqueous extract (30 days). The liver glycogen content was quantified by spectroscopic method and by PAS stain; ALT and AST by spectrometric method; glycogen synthase, glycogen phosphorylase and GLUT2 by Western blot; the mRNA expression of GLUT2 and glucagon-receptor by RT-PCR; while serum insulin was quantified by ELISA method. A liver histological analysis was also performed by H&E stain. Results: Chemical fingerprint showed five majoritarian compounds in the aqueous extract of C. ficifolia: p-coumaric acid, p-hydroxybenzoic acid, salicin, stigmast-7,2,2-dien-3-ol and stigmast-7-en-3-ol. The histological analysis showed accumulation of liver glycogen. Also, increased glycogen synthase and decreased glycogen phosphorylase were observed. Interestingly, the histological architecture evidenced a liver-protective effect due the extract. Conclusion: Five compounds were identified in C. ficifolia aqueous extract. The hypoglycemic effect of this extract may be partially explained by liver glycogen accumulation. The bioactive compound responsible

  9. Familial association of specific histologic types of ovarian malignancy with other malignancies.

    PubMed

    Lorenzo Bermejo, Justo; Rawal, Rajesh; Hemminki, Kari

    2004-04-01

    Population-based data on the familial association of specific histologic types of ovarian malignancy with other malignancies are limited. Such data may help to elucidate etiologic differences among histologic types of ovarian malignancy. The nationwide Swedish Family-Cancer Database, which includes 10.3 million individuals and 20,974 ovarian carcinomas, was used to calculate standardized incidence ratios and 95% confidence intervals for age- and histology-specific ovarian malignancies in women whose parents or siblings were affected with malignancies at the most common disease sites. Ovarian malignancy was found to be associated with ovarian, laryngeal, breast, endometrial, liver, and colon carcinoma, as well as myeloma; epithelial ovarian malignancy was found to be associated with ovarian, endometrial, and skin malignancies and with melanoma and myeloma; papillary serous cystadenocarcinoma was found to be associated with ovarian and skin malignancies and with myeloma; and endometrioid carcinoma was found to be associated with endometrial, ovarian, and prostate malignancies and with melanoma. For younger women (ages 40-45 years) whose mothers were affected with endometrial malignancies, the risk of developing endometrioid carcinoma was slightly greater than the risk of developing papillary serous cystadenocarcinoma. Specific types of ovarian malignancy may be associated with specific familial disease sites, with such associations depending on age at diagnosis; the strength of the observed associations varied according to histology. Associations were found between endometrioid carcinoma and endometrial malignancy and between serous carcinoma and Hodgkin disease. Copyright 2004 American Cancer Society.

  10. Correlation between liver cell necrosis and circulating alanine aminotransferase after ischaemia/reperfusion injuries in the rat liver.

    PubMed

    Knudsen, Anders R; Andersen, Kasper J; Hamilton-Dutoit, Stephen; Nyengaard, Jens R; Mortensen, Frank V

    2016-04-01

    Circulating liver enzymes such as alanine transaminase are often used as markers of hepatocellular damage. Ischaemia/reperfusion (I/R) injury is an inevitable consequence of prolonged liver ischaemia. The aim of this study was to examine the correlation between liver enzymes and volume of liver cell necrosis after ischaemia/reperfusion injuries, using design-unbiased stereological methods. Forty-seven male Wistar rats were subjected to 1 h of partial liver ischaemia, followed by either 4 or 24 h of reperfusion. Within each group, one-third of animals were subjected to ischaemic preconditioning and one-third to ischaemic postconditioning. At the end of reperfusion, blood and liver samples were collected for analysis. The volume of necrotic liver tissue was subsequently correlated to circulating markers of I/R injury. Correlation between histological findings and circulating markers was performed using Pearson's correlation coefficient. Alanine transferase peaked after 4 h of reperfusion; however, at this time-point, only mild necrosis was observed, with a Pearson's correlation coefficient of 0.663 (P = 0.001). After 24 h of reperfusion, alanine aminotransferase was found to be highly correlated to the degree of hepatocellular necrosis R = 0.836 (P = 0.000). Furthermore, alkaline phosphatase (R = 0.806) and α-2-macroglobulin (R = 0.655) levels were also correlated with the degree of necrosis. We show for the first time that there is a close correlation between the volume of hepatocellular necrosis and alanine aminotransferase levels in a model of I/R injury. This is especially apparent after 24 h of reperfusion. Similarly, increased levels of alkaline phosphatase and α-2-macroglobulin are correlated to the volume of liver necrosis. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  11. Fibrinogen Gamma Chain Mutations Provoke Fibrinogen and Apolipoprotein B Plasma Deficiency and Liver Storage

    PubMed Central

    Callea, Francesco; Giovannoni, Isabella; Sari, Sinan; Guldal, Esendagli; Dalgic, Buket; Akyol, Gulen; Sogo, Tsuyoshi; Al-Hussaini, Abdulrahman; Maggiore, Giuseppe; Bartuli, Andrea; Boldrini, Renata; Francalanci, Paola; Bellacchio, Emanuele

    2017-01-01

    p.R375W (Fibrinogen Aguadilla) is one out of seven identified mutations (Brescia, Aguadilla, Angers, Al du Pont, Pisa, Beograd, and Ankara) causing hepatic storage of the mutant fibrinogen γ. The Aguadilla mutation has been reported in children from the Caribbean, Europe, Japan, Saudi Arabia, Turkey, and China. All reported children presented with a variable degree of histologically proven chronic liver disease and low plasma fibrinogen levels. In addition, one Japanese and one Turkish child had concomitant hypo-APOB-lipoproteinemia of unknown origin. We report here on an additional child from Turkey with hypofibrinogenemia due to the Aguadilla mutation, massive hepatic storage of the mutant protein, and severe hypo-APOB-lipoproteinemia. The liver biopsy of the patient was studied by light microscopy, electron microscopy (EM), and immunohistochemistry. The investigation included the DNA sequencing of the three fibrinogen and APOB–lipoprotein regulatory genes and the analysis of the encoded protein structures. Six additional Fibrinogen Storage Disease (FSD) patients with either the Aguadilla, Ankara, or Brescia mutations were investigated with the same methodology. A molecular analysis revealed the fibrinogen gamma p.R375W mutation (Aguadilla) but no changes in the APOB and MTTP genes. APOB and MTTP genes showed no abnormalities in the other study cases. Light microscopy and EM studies of liver tissue samples from the child led to the demonstration of the simultaneous accumulation of both fibrinogen and APOB in the same inclusions. Interestingly enough, APOB-containing lipid droplets were entrapped within the fibrinogen inclusions in the hepatocytic Endoplasmic Reticulum (ER). Similar histological, immunohistochemical, EM, and molecular genetics findings were found in the other six FSD cases associated with the Aguadilla, as well as with the Ankara and Brescia mutations. The simultaneous retention of fibrinogen and APOB-lipoproteins in FSD can be detected in

  12. Hepatitis C as a cause of chronic liver disease in northern Pakistan.

    PubMed

    Malik, I A; Ahmad, N; Luqman, M; Legters, L J; Khalil-Ullah; Zaheeruddin; Ahmed, A; Bukhtiari, N; Nabi, S; Mubarik, A

    1992-03-01

    The antibodies to hepatitis C virus (HCV) were tested in 45 histologically confirmed cases of chronic liver disease. Twelve cases had chronic hepatitis, 24 cirrhosis and 9 hepatocellular carcinoma. Anti-HCV was detected in 6 patients. Two (16.67%) were suffering from chronic hepatitis, 3 (12.5%) had cirrhosis and one (11.11%) hepatocellular carcinoma. None of the anti-HCV positive cases had past history of blood transfusion. The patients of chronic liver disease in this study had a much higher prevalence of HBV infection which indicates that in northern Pakistan hepatitis C virus infection is not a common cause of chronic liver disease whereas HBV infection plays an aetiological role in a much larger number of these cases.

  13. Proteomic analysis of liver in rats chronically exposed to fluoride.

    PubMed

    Pereira, Heloísa Aparecida Barbosa da Silva; Leite, Aline de Lima; Charone, Senda; Lobo, Janete Gualiume Vaz Madureira; Cestari, Tania Mary; Peres-Buzalaf, Camila; Buzalaf, Marília Afonso Rabelo

    2013-01-01

    Fluoride (F) is a potent anti-cariogenic element, but when ingestion is excessive, systemic toxicity may be observed. This can occur as acute or chronic responses, depending on both the amount of F and the time of exposure. The present study identified the profile of protein expression possibly associated with F-induced chronic hepatotoxicity. Weanling male Wistar rats (three-weeks old) were divided into three groups and treated with drinking water containing 0, 5 or 50 mg/L F for 60 days (n=6/group). At this time point, serum and livers were collected for F analysis, which was done using the ion-sensitive electrode, after hexamethyldisiloxane-facilitated diffusion. Livers were also submitted to histological and proteomic analyses (2D-PAGE followed by LC-MS/MS). Western blotting was done for confirmation of the proteomic data A dose-response was observed in serum F levels. In the livers, F levels were significantly increased in the 50 mg/L F group compared to groups treated with 0 and 5 mg/L F. Liver morphometric analysis did not reveal alterations in the cellular structures and lipid droplets were present in all groups. Proteomic quantitative intensity analysis detected 33, 44, and 29 spots differentially expressed in the comparisons between control vs. 5 mg/L F, control vs. 50 mg/L F, and 5 mg/L vs. 50 mg/L F, respectively. From these, 92 proteins were successfully identified. In addition, 18, 1, and 5 protein spots were shown to be exclusive in control, 5, and 50 mg/L F, respectively. Most of proteins were related to metabolic process and pronounced alterations were seen for the high-F level group. In F-treated rats, changes in the apolipoprotein E (ApoE) and GRP-78 expression may account for the F-induced toxicity in the liver. This can contribute to understanding the molecular mechanisms underlying hepatoxicity induced by F, by indicating key-proteins that should be better addressed in future studies.

  14. Remote ischemic preconditioning protects liver ischemia-reperfusion injury by regulating eNOS-NO pathway and liver microRNA expressions in fatty liver rats.

    PubMed

    Duan, Yun-Fei; An, Yong; Zhu, Feng; Jiang, Yong

    2017-08-15

    Ischemic preconditioning (IPC) is a strategy to reduce ischemia-reperfusion (I/R) injury. The protective effect of remote ischemic preconditioning (RIPC) on liver I/R injury is not clear. This study aimed to investigate the roles of RIPC in liver I/R in fatty liver rats and the involvement of endothelial nitric oxide synthase-nitric oxide (eNOS-NO) pathway and microRNA expressions in this process. A total of 32 fatty rats were randomly divided into the sham group, I/R group, RIPC group and RIPC+I/R group. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and nitric oxide (NO) were measured. Hematoxylin-eosin staining was used to observe histological changes of liver tissues, TUNEL to detect hepatocyte apoptosis, and immunohistochemistry assay to detect heat shock protein 70 (HSP70) expression. Western blotting was used to detect liver inducible NOS (iNOS) and eNOS protein levels and real-time quantitative polymerase chain reaction to detect miR-34a, miR-122 and miR-27b expressions. Compared with the sham and RIPC groups, serum ALT, AST and iNOS in liver tissue were significantly higher in other two groups, while serum NO and eNOS in liver tissue were lower, and varying degrees of edema, degeneration and inflammatory cell infiltration were found. Cell apoptosis number was slightly lower in the RIPC+I/R group than that in I/R group. Compared with the sham group, HSP70 expressions were significantly increased in other three groups (all P<0.05). Compared with the sham and RIPC groups, elevated miR-34a expressions were found in I/R and RIPC+I/R groups (P<0.05). MiR-122 and miR-27b were found significantly decreased in I/R and RIPC+I/R groups compared with the sham and RIPC groups (all P<0.05). RIPC can reduce fatty liver I/R injury by affecting the eNOS-NO pathway and liver microRNA expressions. Copyright © 2017 The Editorial Board of Hepatobiliary & Pancreatic Diseases International. Published by Elsevier B.V. All rights reserved.

  15. Dihydroartemisinin alleviates bile duct ligation-induced liver fibrosis and hepatic stellate cell activation by interfering with the PDGF-βR/ERK signaling pathway.

    PubMed

    Chen, Qin; Chen, Lianyun; Kong, Desong; Shao, Jiangjuan; Wu, Li; Zheng, Shizhong

    2016-05-01

    Liver fibrosis represents a frequent event following chronic insult to trigger wound healing responses in the liver. Activation of hepatic stellate cells (HSCs), which is a pivotal event during liver fibrogenesis, is accompanied by enhanced expressions of a series of marker proteins and pro-fibrogenic signaling molecules. Artemisinin, a powerful antimalarial medicine, is extracted from the Chinese herb Artemisia annua L., and can inhibit the proliferation of cancer cells. Dihydroartemisinin (DHA), the major active metabolite of artemisinin, is able to attenuate lung injury and fibrosis. However, the effect of DHA on liver fibrosis remains unclear. The aim of this study was to investigate the effect of DHA on bile duct ligation-induced injury and fibrosis in rats. DHA improved the liver histological architecture and attenuated collagen deposition in the fibrotic rat liver. Experiments in vitro showed that DHA inhibited the proliferation of HSCs and arrested the cell cycle at the S checkpoint by altering several cell-cycle regulatory proteins. Moreover, DHA reduced the protein expressions of a-SMA, α1 (I) collagen and fibronectin, being associated with interference of the platelet-derived growth factor β receptor (PDGF-βR)-mediated ERK pathway. These data collectively revealed that DHA relieved liver fibrosis possibly by targeting HSCs via the PDGF-βR/ERK pathway. DHA may be a therapeutic antifibrotic agent for the treatment of hepatic fibrosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. The Comparison between Circadian Oscillators in Mouse Liver and Pituitary Gland Reveals Different Integration of Feeding and Light Schedules

    PubMed Central

    Bur, Isabelle M.; Zouaoui, Sonia; Fontanaud, Pierre; Coutry, Nathalie; Molino, François; Martin, Agnès O.; Mollard, Patrice; Bonnefont, Xavier

    2010-01-01

    The mammalian circadian system is composed of multiple peripheral clocks that are synchronized by a central pacemaker in the suprachiasmatic nuclei of the hypothalamus. This system keeps track of the external world rhythms through entrainment by various time cues, such as the light-dark cycle and the feeding schedule. Alterations of photoperiod and meal time modulate the phase coupling between central and peripheral oscillators. In this study, we used real-time quantitative PCR to assess circadian clock gene expression in the liver and pituitary gland from mice raised under various photoperiods, or under a temporal restricted feeding protocol. Our results revealed unexpected differences between both organs. Whereas the liver oscillator always tracked meal time, the pituitary circadian clockwork showed an intermediate response, in between entrainment by the light regimen and the feeding-fasting rhythm. The same composite response was also observed in the pituitary gland from adrenalectomized mice under daytime restricted feeding, suggesting that circulating glucocorticoids do not inhibit full entrainment of the pituitary clockwork by meal time. Altogether our results reveal further aspects in the complexity of phase entrainment in the circadian system, and suggest that the pituitary may host oscillators able to integrate multiple time cues. PMID:21179516

  17. Liver Injury from Herbal and Dietary Supplements

    PubMed Central

    Navarro, Victor; Khan, Ikhlas; Björnsson, Einar; Seeff, Leonard B.; Serrano, Jose; Hoofnagle, Jay H.

    2017-01-01

    Herbal and dietary supplements (HDS) are used increasingly both in the United States and worldwide and HDS induced liver injury in the U.S. has increased proportionally. Current challenges in the diagnosis and management of HDS-induced liver injury were the focus of a 2-day research symposium sponsored by the American Association for the Study of Liver Disease and the National Institutes of Health. HDS-induced liver injury now accounts for 20% of cases of hepatotoxicity in the United States based on research data. The major implicated agents include anabolic steroids, green tea extract, and multi-ingredient nutritional supplements (MINS). Anabolic steroids marketed as bodybuilding supplements typically induce a prolonged cholestatic, but ultimately self-limiting liver injury that has a distinctive serum biochemical as well as histological phenotype. Green tea extract and many other products, in contrast, tend to cause an acute-hepatitis like injury. Currently, however, the majority of cases of HDS-associated liver injury are due to MINS, and the component responsible for the toxicity is usually unknown or can only be suspected. HDS-induced liver injury presents many clinical and research challenges, in diagnosis, identification of the responsible constituents, treatment and prevention. Also important are improvements in regulatory oversight of non-prescription products to guarantee their constituents and insure purity and safety. The confident identification of injurious ingredients within HDS will require strategic alignments among clinicians, chemists, and toxicologists. The ultimate goal should be to prohibit or more closely regulate potentially injurious ingredients and thus promote public safety. PMID:27677775

  18. LIVER DAMAGE IN MICE TREATED WITH 4-(p-DIMETHYLAMINOSTYRYL) QUINOLINE, A RADIOMIMETIC AGENT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Davis, M.L.; Gude, W.D.; Asano, M.

    1963-10-01

    The effects of intravenous injections of the radiomimetic agent 4-(p- dimethylaminostyryl)quinoline on the liver were studied in mice of the RF/Up and (101 x C3H) F/sub 1/ strains. The effects were assessed by use of the Bromsulphalcin (BSP) liver function test and histologic examimation of liver sections. Liver cell lipoid vacuolation was noted within 1 hour after injection of 4 mg of the drug and was very severe before 24 hours had elapsed. BSP testing on succeeding days indicated progressive liver damage that reached a peak on the sixth day in the RF/Up mice and on the third day inmore » the (101 x C3H) F/sub 1/ mice. This was accompanied by extensive liver cell necrosis, especially in the central part of the lobule. Resolution of the lesions occurred gradually over the 17-day observation period, but residual cytologic changes were still present at the end of this time. (P.C.H.)« less

  19. Liver failure with coagulopathy, hyperammonemia and cyclic vomiting in a toddler revealed to have combined heterozygosity for genes involved with ornithine transcarbamylase deficiency and Wilson disease.

    PubMed

    Mira, Valerie; Boles, Richard G

    2012-01-01

    A girl with a 2 month history of cyclic episodes of vomiting, diarrhea, and lethargy lasting 2-3 days each presented with acute hepatopathy (ALT 3,500 IU/L) with coagulopathy (PT 55 s) and hyperammonemia (207 μmol/L) at age 1½ years. Biochemical and molecular analyzes revealed ornithine transcarbamylase (OTC) deficiency. While laboratory signs of mild hepatocellular dysfunction are common in OTC deficiency, substantial liver failure with coagulopathy is generally not seen, although four others cases have been reported, three of which presented with cyclic vomiting. Further evaluation in our case revealed elevated urine (198.8 μg/g creatinine) and liver (103 μg/g dry weight) copper content, and a heterozygous mutation in the Wilson disease gene, ATP7B. Our patient, now aged 5 years, has remained in excellent health with normal growth and development on fasting avoidance, a modified vegan diet, and sodium phenylbutyrate.These five cases demonstrate that generalized liver dysfunction/failure is a potential serious complication of OTC deficiency, although not a common one, and suggests that an ALT and PT should be obtained in OTC patients during episodes of hyperammonemia. Cyclic vomiting is a known presentation of OTC deficiency; it is not known if comorbid liver failure predisposes toward this phenotype. We propose that the heterozygote state in ATP7B increases the liver copper content, thus predisposing our patient with OTC deficiency to develop liver failure during a hyperammonemic episode. Our present case is an example of the opportunity of molecular diagnostics to identify putative modifier genes in patients with atypical presentations of genetic disorders.

  20. Chronic intermittent hypoxia predisposes to liver injury.

    PubMed

    Savransky, Vladimir; Nanayakkara, Ashika; Vivero, Angelica; Li, Jianguo; Bevans, Shannon; Smith, Philip L; Torbenson, Michael S; Polotsky, Vsevolod Y

    2007-04-01

    Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH). OSA is associated with nonalcoholic steatohepatitis (NASH) in obese subjects. The aim of this study was to investigate the effects of CIH on the liver in the absence of obesity. Lean C57BL/6J mice (n = 15) on a regular chow diet were exposed to CIH for 12 weeks and compared with pair-fed mice exposed to intermittent air (IA, n = 15). CIH caused liver injury with an increase in serum ALT (224 +/- 39 U/l versus 118 +/- 22 U/l in the IA group, P < 0.05), whereas AST and alkaline phosphatase were unchanged. CIH also induced hyperglycemia, a decrease in fasting serum insulin levels, and mild elevation of fasting serum total cholesterol and triglycerides (TG). Liver TG content was unchanged, whereas cholesterol content was decreased. Histology showed swelling of hepatocytes, no evidence of hepatic steatosis, and marked accumulation of glycogen in hepatocytes. CIH led to lipid peroxidation of liver tissue with a malondialdehyde (MDA)/free fatty acids (FFA) ratio of 0.54 +/- 0.07 mmol/mol versus 0.30 +/- 0.01 mmol/mol in control animals (P < 0.01), and increased levels of active nuclear factor kappaB (NF-kappaB) in the nuclear fraction of hepatocytes, suggesting that CIH induced oxidative stress in the liver. Finally, CIH greatly exacerbated acetaminophen-induced liver toxicity, causing fulminant hepatocellular injury. In the absence of obesity, CIH leads to mild liver injury via oxidative stress and excessive glycogen accumulation in hepatocytes and sensitizes the liver to a second insult, whereas NASH does not develop.

  1. Liver injury from herbal and dietary supplements.

    PubMed

    Navarro, Victor J; Khan, Ikhlas; Björnsson, Einar; Seeff, Leonard B; Serrano, Jose; Hoofnagle, Jay H

    2017-01-01

    Herbal and dietary supplements (HDS) are used increasingly both in the United States and worldwide, and HDS-induced liver injury in the United States has increased proportionally. Current challenges in the diagnosis and management of HDS-induced liver injury were the focus of a 2-day research symposium sponsored by the American Association for the Study of Liver Disease and the National Institutes of Health. HDS-induced liver injury now accounts for 20% of cases of hepatotoxicity in the United States based on research data. The major implicated agents include anabolic steroids, green tea extract, and multi-ingredient nutritional supplements. Anabolic steroids marketed as bodybuilding supplements typically induce a prolonged cholestatic but ultimately self-limiting liver injury that has a distinctive serum biochemical as well as histological phenotype. Green tea extract and many other products, in contrast, tend to cause an acute hepatitis-like injury. Currently, however, the majority of cases of HDS-associated liver injury are due to multi-ingredient nutritional supplements, and the component responsible for the toxicity is usually unknown or can only be suspected. HDS-induced liver injury presents many clinical and research challenges in diagnosis, identification of the responsible constituents, treatment, and prevention. Also important are improvements in regulatory oversight of nonprescription products to guarantee their constituents and ensure purity and safety. The confident identification of injurious ingredients within HDS will require strategic alignments among clinicians, chemists, and toxicologists. The ultimate goal should be to prohibit or more closely regulate potentially injurious ingredients and thus promote public safety. (Hepatology 2017;65:363-373). © 2016 by the American Association for the Study of Liver Diseases.

  2. Epidermal growth factor receptor restoration rescues the fatty liver regeneration in mice.

    PubMed

    Zimmers, Teresa A; Jin, Xiaoling; Zhang, Zongxiu; Jiang, Yanlin; Koniaris, Leonidas G

    2017-10-01

    Hepatic steatosis is a common histological finding in obese patients. Even mild steatosis is associated with delayed hepatic regeneration and poor outcomes following liver resection or transplantation. We sought to identify and target molecular pathways that mediate this dysfunction. Lean mice and mice made obese through feeding of a high-fat, hypercaloric diet underwent 70 or 80% hepatectomy. After 70% resection, obese mice demonstrated 100% survival but experienced increased liver injury, reduced energy stores, reduced mitoses, increased necroapoptosis, and delayed recovery of liver mass. Increasing liver resection to 80% was associated with mortality of 40% in lean and 80% in obese mice ( P < 0.05). Gene expression profiling showed decreased epidermal growth factor receptor (EGFR) in fatty liver. Meta-analysis of expression studies in mice, rats, and patients also demonstrated reduction of EGFR in fatty liver. In mice, both EGFR and phosphorylated EGFR decreased with increasing percent body fat. Hydrodynamic transfection of EGFR plasmids in mice corrected fatty liver regeneration, reducing liver injury, increasing proliferation, and improving survival after 80% resection. Loss of EGFR expression is rate limiting for liver regeneration in obesity. Therapies directed at increasing EGFR in steatosis might promote liver regeneration and survival following hepatic resection or transplantation. Copyright © 2017 the American Physiological Society.

  3. Early and Long-Term Outcomes of Patients Undergoing Liver Resection and Diaphragm Excision for Advanced Colorectal Liver Metastases

    PubMed Central

    Lordan, Jeffrey T; Riga, Angela; Worthington, Tim R; Karanjia, Nariman D

    2009-01-01

    INTRODUCTION At present, liver resection offers the best long-term outcome and only chance for cure in patients with colorectal liver metastases. However, there are no large series that report the early and long-term outcomes of patients who require simultaneous diaphragm excision. This study was designed to investigate these patients. PATIENTS AND METHODS A total of 285 consecutive liver resections were performed over a 10-year period. Of these, 258 had liver resections alone and 27 underwent liver resection and simultaneous diaphragm excision. Data were collected prospectively and analysed retrospectively. Pre-operative assessment was standardised. The outcomes between the two groups were compared. RESULT There was no difference in age, hospital stay or intra-operative blood loss. The diaphragm was histologically involved in four out of 27 resections. As a result, the cancer involved resection margin incidence was greater in the liver resection and diaphragm excision group (14.8% versus 3.9%; P = 0.12). The median tumour size was also different between the two groups (60 mm versus 30 mm; P = 0.001). The liver and diaphragm resection group had a greater peri-operative complication rate (44.4% versus 21.3%; P = 0.02) and mortality (7.4% versus 1.6%; P = 0.25). Overall and disease-free survival was significantly worse in the group who underwent simultaneous diaphragm excision and liver resection (P = 0.04 and P = 0.005, respectively). Diaphragm invasion was found to be an independent predictor of poor overall outcome (P = 0.02). CONCLUSION Liver resection and simultaneous diaphragm excision have a greater incidence of peri-operative morbidity and mortality and a significantly worse long-term outcome compared with liver resection alone. However, these data suggest that liver resection in the presence of diaphragm invasion may still offer a favourable outcome compared with chemotherapy treatment alone. Therefore, we believe that diaphragm involvement by tumour should

  4. Fatty liver promotes fibrosis in monkeys consuming high fructose.

    PubMed

    Cydylo, Michael A; Davis, Ashley T; Kavanagh, Kylie

    2017-02-01

    Nonalcoholic fatty liver diseases (NAFLD) are related to development of liver fibrosis which currently has few therapeutic options. Rodent models of NAFLD inadequately model the fibrotic aspects of the disease and fail to demonstrate the spectrum of cardiometabolic diseases without genetic manipulation. This study aimed to document a monkey model of fatty liver and fibrosis, which naturally develop cardiometabolic disease pathophysiologies. Twenty-seven cynomolgus monkeys (Macaca fascicularis) fed diets either low or high in simple carbohydrates, supplied as fructose [control and high-fructose diet (HRr)], on low-fat, cholesterol-free background were studied. The HFr was consumed for up to 7 years, and liver tissue was histologically evaluated for fat and fibrosis extent. The HFr diet increased steatosis, and its extent was related to duration of fructose exposure. Lipid droplet size also increased with HFr duration; however, compared with control, the lipid droplets were smaller on average. Fibrosis extent was significantly greater with fructose feeding and was predicted by fructose exposure, extent of fatty liver, and age. These data are the first to demonstrate that high-carbohydrate diets alone can generate both liver fat and fibrosis and thus allow further study of mechanisms and therapeutic options in the translational animal model. © 2017 The Obesity Society.

  5. Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of Mouse Revealed by a High-throughput Targeted Metabolomics Approach

    NASA Astrophysics Data System (ADS)

    Yu, Nanyang; Wei, Si; Li, Meiying; Yang, Jingping; Li, Kan; Jin, Ling; Xie, Yuwei; Giesy, John P.; Zhang, Xiaowei; Yu, Hongxia

    2016-04-01

    Perfluorooctanoic acid (PFOA), a perfluoroalkyl acid, can result in hepatotoxicity and neurobehavioral effects in animals. The metabolome, which serves as a connection among transcriptome, proteome and toxic effects, provides pathway-based insights into effects of PFOA. Since understanding of changes in the metabolic profile during hepatotoxicity and neurotoxicity were still incomplete, a high-throughput targeted metabolomics approach (278 metabolites) was used to investigate effects of exposure to PFOA for 28 d on brain and liver of male Balb/c mice. Results of multivariate statistical analysis indicated that PFOA caused alterations in metabolic pathways in exposed individuals. Pathway analysis suggested that PFOA affected metabolism of amino acids, lipids, carbohydrates and energetics. Ten and 18 metabolites were identified as potential unique biomarkers of exposure to PFOA in brain and liver, respectively. In brain, PFOA affected concentrations of neurotransmitters, including serotonin, dopamine, norepinephrine, and glutamate in brain, which provides novel insights into mechanisms of PFOA-induced neurobehavioral effects. In liver, profiles of lipids revealed involvement of β-oxidation and biosynthesis of saturated and unsaturated fatty acids in PFOA-induced hepatotoxicity, while alterations in metabolism of arachidonic acid suggesting potential of PFOA to cause inflammation response in liver. These results provide insight into the mechanism and biomarkers for PFOA-induced effects.

  6. Metabolic syndrome after pediatric liver transplantation.

    PubMed

    Kosola, Silja; Lampela, Hanna; Makisalo, Heikki; Lohi, Jouko; Arola, Johanna; Jalanko, Hannu; Pakarinen, Mikko

    2014-10-01

    Half of adult liver transplantation (LT) recipients develop metabolic syndrome, but the prevalence after childhood LT remains unknown. We conducted a national cross-sectional study of all living patients who had undergone LT between 1987 and 2007 at an age less than 18 years. We gathered information on blood pressure, body composition, serum lipids, glucose metabolism, and histological liver fat content. The diagnostic criteria for metabolic syndrome of the American Heart Association and the International Diabetes Federation were used. After a median post-LT follow-up time of 12 years, half of all patients had no components of metabolic syndrome. The prevalence of overweight/obesity was 20%, and the prevalence of hypertension was 24%. Serum triglycerides were high in 9%, and high-density lipoprotein levels were low in 23%. Fasting glucose levels were impaired in 14%, but none had diabetes. Altogether, 9 patients (14%) had metabolic syndrome. Moderate liver steatosis found in protocol liver biopsy samples was associated with the accumulation of metabolic syndrome features (P = 0.01). No significant associations were found between immunosuppressive medications and metabolic syndrome. In conclusion, the prevalence of metabolic syndrome after childhood LT is similar to the prevalence in the general population of the same age. Guidelines for the general population, therefore, seem valid for the prevention and treatment of metabolic syndrome after pediatric LT as well. © 2014 American Association for the Study of Liver Diseases.

  7. Quantitative Assessment of Liver Fat with Magnetic Resonance Imaging and Spectroscopy

    PubMed Central

    Reeder, Scott B.; Cruite, Irene; Hamilton, Gavin; Sirlin, Claude B.

    2011-01-01

    Hepatic steatosis is characterized by abnormal and excessive accumulation of lipids within hepatocytes. It is an important feature of diffuse liver disease, and the histological hallmark of non-alcoholic fatty liver disease (NAFLD). Other conditions associated with steatosis include alcoholic liver disease, viral hepatitis, HIV and genetic lipodystrophies, cystic fibrosis liver disease, and hepatotoxicity from various therapeutic agents. Liver biopsy, the current clinical gold standard for assessment of liver fat, is invasive and has sampling errors, and is not optimal for screening, monitoring, clinical decision making, or well-suited for many types of research studies. Non-invasive methods that accurately and objectively quantify liver fat are needed. Ultrasound (US) and computed tomography (CT) can be used to assess liver fat but have limited accuracy as well as other limitations. Magnetic resonance (MR) techniques can decompose the liver signal into its fat and water signal components and therefore assess liver fat more directly than CT or US. Most magnetic resonance (MR) techniques measure the signal fat-fraction (the fraction of the liver MR signal attributable to liver fat), which may be confounded by numerous technical and biological factors and may not reliably reflect fat content. By addressing the factors that confound the signal fat-fraction, advanced MR techniques measure the proton density fat-fraction (the fraction of the liver proton density attributable to liver fat), which is a fundamental tissue property and a direct measure of liver fat content. These advanced techniques show promise for accurate fat quantification and are likely to be commercially available soon. PMID:22025886

  8. Seventh-day syndrome: a catastrophic event after liver transplantation: case report.

    PubMed

    Pereira, M; Ferreira, I; Gandara, J; Ferreira, S; Lopes, V; Coelho, A; Vizcaino, R; Marinho, A; Daniel, J; Miranda, H P

    2015-05-01

    Seventh-day syndrome (7DS) is an early serious complication of liver transplantation, characterized by sudden failure of a previously normally functioning liver graft ∼1 week after the surgery. Although it is an uncommon event, it has major associated mortality. As its etiology is yet to be recognized, the only currently available treatment is retransplantation. We present 3 cases of orthotopic liver transplantation recipients who had an initial uneventful recovery after surgery followed by a dramatic rise of serum liver enzyme levels ∼7 days later and hepatic failure with subsequent graft loss and death despite high-dose immunosuppressive therapy. Histologic findings showed massive centrolobular hemorrhage and hepatocellular necrosis with reduced inflammation. It is essential to review and accumulate more clinical and laboratory information to better understand this syndrome and to better prevent and treat it. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Geraniol attenuates 2-acetylaminofluorene induced oxidative stress, inflammation and apoptosis in the liver of wistar rats.

    PubMed

    Hasan, Syed Kazim; Sultana, Sarwat

    2015-01-01

    2-Acetylaminofluorene (2-AAF), is a well-known liver toxicant, generally used to induce tumors in laboratory animals. Geraniol (GE), a monoterpene found in essential oils of herbs and fruits, has been known to possess preventive efficacy against chemically induced toxicities. The present study was designed to analyze the protective effect of GE against 2-AAF induced oxidative stress, inflammation, hyperproliferation and apoptotic tissue damage in the liver of female Wistar rats. 2-AAF (0.02% w/w in diet) was administered and subjected to partial hepatectomy, as a mitogenic stimulus for the induction of hyperproliferation of liver tissue. GE was pre-treated orally at two different doses (100 and 200 mg/kg b.wt.) dissolved in corn oil. GE pre-treatment significantly ameliorated 2-AAF induced oxidative damage by diminishing tissue lipid peroxidation accompanied by the increase in enzymatic activities of catalase, glutathione peroxidase, glutathione reductase, superoxide dismutase and reduced glutathione content. The level of serum toxicity markers (AST, ALT, LDH) was found to be decreased. Pre-treatment with GE downregulated the expression of caspase-3,9, COX-2, NFkB, PCNA, iNOS, VEGF and significantly decreased disintegration of DNA. Histological findings further revealed that GE significantly restores the architecture of liver tissue. In the light of the above observations it may be concluded that GE may be used as preventive agent against 2-AAF induced oxidative stress, inflammation, hyperproliferation and apoptotic damage.

  10. Lymph node toxoplasmosis. Follow-up of 237 histologically diagnosed and serologically verified cases.

    PubMed

    Miettinen, M; Saxén, L; Saxén, E

    1980-01-01

    The clinical features, histology and follow-up of lymph node toxoplasmosis are presented in the light of 237 histologically and serologically verified cases. Lymph node toxoplasmosis is a disease with mild symptoms, and in most patients the enlarged lymph nodes were the only sign. Three fourths of the patients were women and the majority were under 40 years of age. The clinical picture was not specific, but suggestive features included a relatively short history, presence of the nodes in the neck and relative lymphocytosis in peripheral blood. Histological changes in the lymph nodes were characteristic. The most important features were strong hyperplasia but preserved general structure with small groups of epithelioid cells both in the paracortical area and in the germinal centers. Strands of monocytoid cells were usually found. 80% of the cases with typical histology also had high antibody titers, and in more than 85% of the cases with high antibodies, the lymph nodes presented a typical picture of toxoplasmosis. The follow-up revealed that lymph node toxoplasmosis. The follow-up revealed that lymph node toxoplasmosis is a disease without complications, nor is there any connection with malignant lymphomas.

  11. Molecular pathogenesis and clinical consequences of iron overload in liver cirrhosis.

    PubMed

    Sikorska, Katarzyna; Bernat, Agnieszka; Wroblewska, Anna

    2016-10-01

    The liver, as the main iron storage compartment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Excessive accumulation of iron is an important risk factor in liver disease progression to cirrhosis and hepatocellular carcinoma. Here, we review the literature on the molecular pathogenesis of iron overload and its clinical consequences in chronic liver diseases. PubMed was searched for English-language articles on molecular genesis of primary and secondary iron overload, as well as on their association with liver disease progression. We have also included literature on adjuvant therapeutic interventions aiming to alleviate detrimental effects of excessive body iron load in liver cirrhosis. Excess of free, unbound iron induces oxidative stress, increases cell sensitivity to other detrimental factors, and can directly affect cellular signaling pathways, resulting in accelerated liver disease progression. Diagnosis of liver cirrhosis is, in turn, often associated with the identification of a pathological accumulation of iron, even in the absence of genetic background of hereditary hemochromatosis. Iron depletion and adjuvant therapy with antioxidants are shown to cause significant improvement of liver functions in patients with iron overload. Phlebotomy can have beneficial effects on liver histology in patients with excessive iron accumulation combined with compensated liver cirrhosis of different etiology. Excessive accumulation of body iron in liver cirrhosis is an important predictor of liver failure and available data suggest that it can be considered as target for adjuvant therapy in this condition.

  12. Liver histological changes and lipid peroxidation in the amphibian Ambystoma mexicanum induced by sediment elutriates from the Lake Xochimilco.

    PubMed

    Ortiz-Ordoñez, Esperanza; López-López, Eugenia; Sedeño-Díaz, Jacinto Elías; Uría, Esther; Morales, Ignacio Andrés; Pérez, María Estela; Shibayama, Mineko

    2016-08-01

    Lacustrine sediments accumulate pollutants that input from the lake watershed and can be released to the water column by sediment resuspension; thus, pollutants can change their bioavailability and exert adverse effects to aquatic biota. Shallow-urban lakes are particularly susceptible to receive pollutants from urban discharges and sediment resuspension. Lake Xochimilco, in Mexico City, an urban-shallow lake, faces multiple problems: urban sprawl, overexploitation of aquifers, drying of springs, discharge of wastewater from treatment plants, and sediment resuspension. The aquatic biota living in this ecosystem is continuously exposed to the release of pollutants from the sediments. We assessed the risk that pollutants released from sediments from Lake Xochimilco, Touristic (TZ) and Agriculture zone (AZ), can exert on a native amphibian species of the lake (Ambystoma mexicanum) through exposure bioassays to sediment elutriates. We evaluate alterations in the amphibian by three approaches: biochemical (level of lipid peroxidation, LPO), cellular (ultrastructure) and the liver histology of A. mexicanum and we compare them with a batch control. Additionally, we assessed heavy metals (Pb, Cd and Hg) in elutriates. Elutriates from TZ showed the highest concentrations of the metals assessed. Organisms exposed to sediment elutriates from either study sites showed higher LPO values than control organisms (p<0.05). Organisms exposed to elutriates from the TZ showed the most conspicuous damages: hepatic vasodilation of sinusoids, capillaries with erythrocytes, leukocyte infiltration and cytoplasmic vacuolation in hepatocytes. The biological responses assessed reflected the risk that faces A. mexicanum when is exposed for prolonged periods to sediment resuspension in Lake Xochimilco. Copyright © 2016. Published by Elsevier B.V.

  13. Inclusion bodies of aggregated hemosiderins in liver macrophages.

    PubMed

    Hayashi, Hisao; Tatsumi, Yasuaki; Wakusawa, Shinya; Shigemasa, Ryota; Koide, Ryoji; Tsuchida, Ken-Ichi; Morotomi, Natsuko; Yamashita, Tetsuji; Kumagai, Kotaro; Ono, Yukiya; Hayashi, Kazuhiko; Ishigami, Masatoshi; Goto, Hidemi; Kato, Ayako; Kato, Koichi

    2017-12-01

    Hemosiderin formation is a structural indication of iron overload. We investigated further adaptations of the liver to excess iron. Five patients with livers showing iron-rich inclusions larger than 2 µm were selected from our database. The clinical features of patients and structures of the inclusions were compared with those of 2 controls with mild iron overload. All patients had severe iron overload with more than 5000 ng/mL of serum ferritin. Etiologies were variable, from hemochromatosis to iatrogenic iron overload. Their histological stages were either portal fibrosis or cirrhosis. Inclusion bodies were ultra-structurally visualized as aggregated hemosiderins in the periportal macrophages. X-ray analysis always identified, in addition to a large amount of iron complexes including oxygen and phosphorus, a small amount of copper and sulfur in the mosaic matrixes of inclusions. There were no inclusions in the control livers. Inclusion bodies, when the liver is loaded with excess iron, may appear in the macrophages as isolated organella of aggregated hemosiderins. Trace amounts of copper-sulfur complexes were always identified in the mosaic matrices of the inclusions, suggesting cuproprotein induction against excess iron. In conclusion, inclusion formation in macrophages may be an adaptation of the liver loaded with excess iron.

  14. Non-invasive fibrosis tests are correlated with necroinflammatory actvity of liver in patients with chronic hepatitis B.

    PubMed

    Ozyalvacli, G; Kucukbayrak, A; Kurt, M; Gurel, K; Gunes, O; Ustun, C; Akdeniz, H

    2014-01-01

    The gold standarda method used for assessing necroinflammatory activity and fibrosis in the liver is a liver biopsy which has many disadvantages. Therefore, many investigators have been trying to develop non-invasive tests for predicting liver fibrosis score (LFS) of these patients. The aim of this study is to describe the relationship between certain non-invasive fibrosis markers with LFS and histological activity index (HAI) detected histopathologically by liver biopsy in chronic hepatitis B patients. A total of 54 patients who had undergone a liver biopsy with the diagnosis of chronic HBV infection were included in the study. Ishak scoring was used for the evaluation of liver fibrosis, and a modified Knodell HAI was used for demonstration of necroinflammation. In this study, non-invasive fibrosis tests were calculated as described in previous studies. Histological acitivity index was positively correlated with age, age/platelet index, cirrhosis discriminant score (CDS), AST/platelet ratio index (APRI), AST/platelet/GGT/AFP index (APGA), fibro-quotient (Fibro-Q), Goteburg University Cirrhosis Index (Guci), and Platelet/Age/Phosphatase/AFP/AST index (PAPAS). When divided into two groups according to HAI, Guci and APGA were found significantly different both in >4 and >4 HAI groups than the other group. In ROC analysis performed for LFS; PAPAS, APGA, FFI and APRI were the markers having the highest AUC levels, and in ROC analysis performed for HAI; Guci, APRI and APGA were the markers with the highest AUC levels. APRI, APGA and GUCI tests may be helpful in prediction of necroinflammatory scores in the liver.

  15. Histopathological and histochemical changes in the liver of Bagrus bayad caused by environmental pollution.

    PubMed

    Gaber, Hanan S; Ibrahim, Seham A; El-Kasheif, Midhat A

    2015-09-01

    This study focused on two areas (Abu-Zaabal and El-Tal El-Kabir) of the Ismailia canal. The samples represented the effect of the factories' effluent discharge onto the canal. Physical characteristics (water temperature and pH) and chemical characteristics (total hardness, dissolved oxygen, biological oxygen demand and chemical oxygen demand) were measured to identify the water quality in the two areas of the Ismailia canal. These measurements showed slight variations between the two stations. Additionally, the histological and histochemical analyses in the liver of Bagrus bayad fish samples were done. Histological studies of liver showed more severe degeneration in the fish samples of El-Tal El-Kabir station. Histochemical studies on protein and glycogen contents in the liver of B. bayad showed a progressive decrease in their staining intensity to bromophenol blue and periodic acid Schiff at two stations. This study, therefore, concludes that Ismailia canal water (Abu-Zaabal and El-Tall El-Kabir) stations create metabolic crisis and impairment in fish liver. The depletion in the levels of protein and glycogen points leads to the exhaustion of cell energy that is of high demand for fish during stressful conditions. Therefore, it is imperative for the authorities concerned to ensure that treated effluent discharge comply with acceptable standards to save our environment from destruction. © The Author(s) 2013.

  16. A multi-mineral natural product inhibits liver tumor formation in C57BL/6 mice

    PubMed Central

    Aslam, Muhammad N.; Bergin, Ingrid; Naik, Madhav; Hampton, Anna; Allen, Ron; Kunkel, Steven L.; Rush, Howard; Varani, James

    2012-01-01

    C57BL/6 mice were maintained for up to 18-months on high-fat and low-fat diets with or without a multi-mineral-supplement derived from the skeletal remains of the red marine algae Lithothamnion calcareum. Numerous grossly observable liver masses were visible in animals on the “western-style” high-fat diet sacrificed at 12 and 18 months. The majority of the masses were in male mice (20 out of 100 males versus 3 out of 100 females; p=0.0002). There were more liver masses in animals on the high-fat diet than on the low-fat diet (15 out of 50 on high-fat versus 5 out of 50 on low-fat; p=0.0254). The multi-mineral supplement reduced the number of liver masses in mice on both diets (3 out of 25 male mice in the low-fat diet group without the supplement versus 1 out of 25 mice with supplement; 12 of 25 male mice in the high-fat diet group without the supplement versus 3 of 25 mice with supplement [p=0.0129]). Histological evaluation revealed a total of 17 neoplastic lesions (9 adenomas and 8 hepatocellular carcinomas), and 18 pre-neoplastic lesions. Out of 8 hepatocellular carcinomas, 7 were found in unsupplemented diet groups. Steatosis was widely observed in livers with and without grossly observable masses, but the multi-mineral supplement had no effect on the incidence of steatosis or its severity. Taken together, these findings suggest that a multi-mineral-rich natural product can protect mice against neoplastic and pre-neoplastic proliferative liver lesions that may develop in the face of steatosis. PMID:22222483

  17. Bone morphogenetic protein 9 as a key regulator of liver progenitor cells in DDC-induced cholestatic liver injury.

    PubMed

    Addante, Annalisa; Roncero, Cesáreo; Almalé, Laura; Lazcanoiturburu, Nerea; García-Álvaro, María; Fernández, Margarita; Sanz, Julián; Hammad, Seddik; Nwosu, Zeribe C; Lee, Se-Jin; Fabregat, Isabel; Dooley, Steven; Ten Dijke, Peter; Herrera, Blanca; Sánchez, Aránzazu

    2018-05-11

    Bone morphogenetic protein 9 (BMP9) interferes with liver regeneration upon acute injury, while promoting fibrosis upon carbon tetrachloride-induced chronic injury. We have now addressed the role of BMP9 in 3,5 diethoxicarbonyl-1,4 dihydrocollidine (DDC)-induced cholestatic liver injury, a model of liver regeneration mediated by hepatic progenitor cell (known as oval cell), exemplified as ductular reaction and oval cell expansion. WT and BMP9KO mice were submitted to DDC diet. Livers were examined for liver injury, fibrosis, inflammation and oval cell expansion by serum biochemistry, histology, RT-qPCR and western blot. BMP9 signalling and effects in oval cells were studied in vitro using western blot and transcriptional assays, plus functional assays of DNA synthesis, cell viability and apoptosis. Crosslinking assays and short hairpin RNA approaches were used to identify the receptors mediating BMP9 effects. Deletion of BMP9 reduces liver damage and fibrosis, but enhances inflammation upon DDC feeding. Molecularly, absence of BMP9 results in overactivation of PI3K/AKT, ERK-MAPKs and c-Met signalling pathways, which together with an enhanced ductular reaction and oval cell expansion evidence an improved regenerative response and decreased damage in response to DDC feeding. Importantly, BMP9 directly targets oval cells, it activates SMAD1,5,8, decreases cell growth and promotes apoptosis, effects that are mediated by Activin Receptor-Like Kinase 2 (ALK2) type I receptor. We identify BMP9 as a negative regulator of oval cell expansion in cholestatic injury, its deletion enhancing liver regeneration. Likewise, our work further supports BMP9 as an attractive therapeutic target for chronic liver diseases. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Hepatoprotective effects of lycopene on liver enzymes involved in methionine and xenobiotic metabolism in hyperhomocysteinemic rats.

    PubMed

    Yefsah-Idres, Aicha; Benazzoug, Yasmina; Otman, Amel; Latour, Alizée; Middendorp, Sandrine; Janel, Nathalie

    2016-06-15

    Hyperhomocysteinemia, defined by an increased plasma homocysteine level, is commonly associated with chronic liver diseases. A link between the elevated homocysteine level and oxidative stress has been demonstrated. Indeed the pathogenesis of liver diseases in the case of hyperhomocysteinemia could be due to this production of oxidative stress. Many studies have demonstrated the antioxidative properties of lycopene, a carotenoid. Therefore, the present study was designed to induce hyperhomocysteinemia in male Wistar rats in order to analyze the effect of lycopene supplementation on homocysteine metabolism, on phase I and phase II xenobiotic-metabolizing enzyme activities, and on liver injury by histological examination and analysis of biochemical markers. We found that rats with a high methionine diet showed abnormal histological features, with an increase of serum homocysteine, alanine aminotransferase and aspartate aminotransferase levels, decreased hepatic cystathionine beta synthase and S-adenosyl-homocysteine hydrolase activities and an increased hepatic malondialdehyde level. We demonstrated the reversal effect of lycopene supplementation on hyperhomocysteinemia. Taken together, these findings provide additional clues on the hepatoprotective effects of lycopene.

  19. [Studying the hepatoprotector effect of bemithyl on a model of chronic toxic liver damage].

    PubMed

    Oskovityĭ, S V; Bezborodkina, N N; Zarubina, I V; Mironova, O P; Kudrivtsev, B N; Shulenin, S N

    2006-01-01

    A prophylactic and therapeutic introduction of the synthetic adaptogen bemithyl (2-ethylthiobensimidasole hydrobromide) produces a hepatoprotector effect in rats with experimental cirrhosis. The drug exhibits an anticytolytic activity, restores liver participation in the pigment exchange, and normalizes the function of the microsomal oxidation system responsible for the metabolism of xenobiotics. The treatment with bemithyl also leads to a certain improvement of a histologic picture of the damaged liver and to a decrease in the degree of fibrosis. The drug is also capable of increasing the activity of the antioxidant system and inhibiting the process of lipid peroxidation of proteins and lipids in the liver.

  20. Gene Therapy for Liver Transplantation Using Adenoviral Vectors: CD40–CD154 Blockade by Gene Transfer of CD40Ig Protects Rat Livers from Cold Ischemia and Reperfusion Injury

    PubMed Central

    Ke, Bibo; Shen, Xiu-Da; Gao, Feng; Busuttil, Ronald W.; Löwenstein, Pedro R.; Castro, Maria G.; Kupiec-Weglinski, Jerzy W.

    2010-01-01

    Liver injury induced by ischemia/reperfusion (I/R) is the prime factor in delayed or loss graft function following transplantation. CD4+ T lymphocytes are key cellular mediators of antigen-independent inflammatory response triggered by I/R. We attempted to modulate rat liver I/R injury by targeted gene therapy with CD40Ig, which blocks the CD40–CD154 costimulation pathway. One hundred percent of Ad-CD40Ig-pretreated orthotopic liver transplants (OLTs) subjected to 24 h of cold (4°C) ischemia survived >14 days (vs 50% in untreated/Ad-β-gal groups). Ad-CD40Ig treatment decreased sGOT levels and depressed neutrophil infiltration, compared with controls. These functional data correlated with histological Suzuki’s grading of hepatic injury, which in untreated/Ad-β-gal groups showed severe necrosis (>60%) and moderate to severe sinusoidal congestion; the Ad-CD40Ig-pretreated group revealed minimal sinusoidal congestion/necrosis. Unlike in controls, OLT expression of mRNA coding for IL-2/IFN-γ remained depressed, whereas that of IL-4/IL-13 reciprocally increased in the Ad-CD40Ig group. Ad-CD40Ig reduced frequency of TUNEL+ cells and proapoptotic Caspase-3, but enhanced antioxidant HO-1 and antiapoptotic Bcl-2/Bcl-xl expression. Thus, prolonged blockade of CD40–CD154 by CD40Ig exerts potent cytoprotection against hepatic I/R injury. These results provide the rationale for a novel gene therapy approach to maximize the organ donor pool through the safer use of liver transplants exposed to prolonged cold ischemia. PMID:14741776

  1. Early detection of liver steatosis by magnetic resonance imaging in rats infused with glucose and intralipid solutions and correlation to insulin levels.

    PubMed

    d'Assignies, Gaspard; Fontés, Ghislaine; Kauffmann, Claude; Latour, Martin; Gaboury, Louis; Boulanger, Yvan; Van Beers, Bernard E; Soulez, Gilles; Poitout, Vincent; Tang, An

    2013-12-01

    Magnetic resonance (MR) techniques allow noninvasive fat quantification. We aimed to investigate the accuracy of MR imaging (MRI), MR spectroscopy (MRS) and histological techniques to detect early-onset liver steatosis in three rat phenotypes assigned to an experimental glucolipotoxic model or a control group. This study was approved by the institutional committee for the protection of animals. Thirty-two rats (13 young Wistar, 6 old Wistar and 13 diabetic Goto-Kakizaki rats) fed a standard diet were assigned to a 72h intravenous infusion of glucose and Intralipid fat emulsion or a saline infusion. Plasma insulin levels were measured. Steatosis was quantified in ex vivo livers with gradient-recalled multi-echo MRI, MRS and histology as fat fractions (FF). A significant correlation was found between multi-echo MRI-FF and MRS-FF (r=0.81, p<0.01) and a weaker correlation was found between histology and MRS-FF (r=0.60, p<0.01). MRS and MRI accurately distinguished young Wistar and Goto-Kakizaki rats receiving the glucose+Intralipid infusion from those receiving the saline control whereas histology did not. Significant correlations were found between MRI or MRS and insulin plasma level (r=0.63, p<0.01; r=0.57, p<0.01), and between MRI or MRS and C-peptide concentration (r=0.54, p<0.01; r=0.44, p<0.02). Multi-echo MRI and MRS may be more sensitive to measure early-onset liver steatosis than histology in an experimental glucolipotoxic rat model. © 2013.

  2. Experimental study of osthole on treatment of hyperlipidemic and alcoholic fatty liver in animals

    PubMed Central

    Song, Fang; Xie, Mei-Lin; Zhu, Lu-Jia; Zhang, Ke-Ping; Xue, Jie; Gu, Zhen-Lun

    2006-01-01

    AIM: To evaluate the effects of osthole on fatty liver, and investigate the possible mechanism. METHODS: A quail model with hyperlipidemic fatty liver and rat model with alcoholic fatty liver were set up by feeding high fat diet and alcohol, respectively. These experimental animals were then treated with osthole 5-20 mg/kg for 6 wk, respectively. Whereafter, the lipid in serum and hepatic tissue, and coefficient of hepatic weight were measured. RESULTS: After treatment with osthole the levels of serum total cholesterol (TC), triglyceride (TG), lower density lipoprotein-cholesterol (LDL-C), coefficient of hepatic weight, and the hepatic tissue contents of TC and TG were significantly decreased. The activity of superoxide dismutase (SOD) in liver was improved. In alcohol-induced fatty liver rats, the level of malondialdehyde (MDA) in liver was decreased. In high fat-induced fatty liver quails, glutathione peroxidase (GSH-PX) in liver was significantly improved. The histological evaluation of liver specimens demonstrated that the osthole dramatically decreased lipid accumulation. CONCLUSION: These results suggested that osthole had therapeutic effects on both alcohol and high fat-induced fatty liver. The mechanism might be associated with its antioxidation. PMID:16865778

  3. The effect of the angiotensin II receptor, type 1 receptor antagonists, losartan and telmisartan, on thioacetamide-induced liver fibrosis in rats.

    PubMed

    Czechowska, G; Celinski, K; Korolczuk, A; Wojcicka, G; Dudka, J; Bojarska, A; Madro, A; Brzozowski, T

    2016-08-01

    It has been reported previously that the density of angiotensin II receptors is increased in the rat liver in experimentally-induced fibrosis. We hypothesized that pharmacological blockade of angiotensin receptors may produce beneficial effects in models of liver fibrosis. In this study, we used the widely used thioacetamide (TAA)-induced model of liver fibrosis (300 mg/L TAA ad libitum for 12 weeks). Rats received daily injections (i.p), lasting 4 weeks of the angiotensin II type 1 receptor antagonists, losartan 30 mg/kg (TAA + L) or telmisartan 10 mg/kg (TAA + T) and were compared to rat that received TAA alone. Chronic treatment with losartan and telmisartan was associated with a significant reduction in the activity of alkaline phosphatase, and decreased concentrations of tumor necrosis factor-alpha and transforming growth factor beta-1 compared to controls. We also found a significant reduction interleukin-6 in rats receiving telmisartan (P < 0.05) but not losartan. Both treatments increased the concentration of liver glutathione along with a concomitant decrease of GSSG compared to controls. In addition, increased paraoxonase 1 activity was observed in the serum of rats receiving telmisartan group compared to the TAA alone controls. Finally, histological evaluation of liver sections revealed losartan and telmisartan treatment was associated with reduced inflammation and liver fibrosis. Taken together, these results indicate that both telmisartan and losartan have anti-inflammatory and anti-oxidative properties in the TAA model of liver fibrosis. These finding add support to a growing body of literature indicating a potentially important role for the angiotensin system in liver fibrosis and indicate angiotensin antagonists may be useful agents for fibrosis treatment.

  4. The inhibitor of differentiation-1 (Id1) enables lung cancer liver colonization through activation of an EMT program in tumor cells and establishment of the pre-metastatic niche.

    PubMed

    Castañón, Eduardo; Soltermann, Alex; López, Inés; Román, Marta; Ecay, Margarita; Collantes, María; Redrado, Miriam; Baraibar, Iosune; López-Picazo, José María; Rolfo, Christian; Vidal-Vanaclocha, Fernando; Raez, Luis; Weder, Walter; Calvo, Alfonso; Gil-Bazo, Ignacio

    2017-08-28

    Id1 promotes carcinogenesis and metastasis, and predicts prognosis of non-small cell lung cancer (NSCLC)-adenocarcionoma patients. We hypothesized that Id1 may play a critical role in lung cancer colonization of the liver by affecting both tumor cells and the microenvironment. Depleted levels of Id1 in LLC (Lewis lung carcinoma cells, LLC shId1) significantly reduced cell proliferation and migration in vitro. Genetic loss of Id1 in the host tissue (Id1 -/- mice) impaired liver colonization and increased survival of Id1 -/- animals. Histologically, the presence of Id1 in tumor cells of liver metastasis was responsible for liver colonization. Microarray analysis comparing liver tumor nodules from Id1 +/+ mice and Id1 -/- mice injected with LLC control cells revealed that Id1 loss reduces the levels of EMT-related proteins, such as vimentin. In tissue microarrays containing 532 NSCLC patients' samples, we found that Id1 significantly correlated with vimentin and other EMT-related proteins. Id1 loss decreased the levels of vimentin, integrinβ1, TGFβ1 and snail, both in vitro and in vivo. Therefore, Id1 enables both LLC and the host microenvironment for an effective liver colonization, and may represent a novel therapeutic target to avoid NSCLC liver metastasis. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Evaluation of liver regeneration diet supplemented with omega-3 fatty acids: experimental study in rats.

    PubMed

    Silva, Rosilda Mendes da; Malafaia, Osvaldo; Torres, Orlando Jorge Martins; Czeczko, Nicolau Gregori; Marinho Junior, Carlos Hespanha; Kozlowski, Ronaldo Kiviatcoski

    2015-01-01

    to evaluate liver regeneration in rats after partial hepatectomy of 60% with and without action diet supplemented with fatty acids through the study of the regenerated liver weight, laboratory parameters of liver function and histological study. thirty-six Wistar rats, males, adults were used, weighing between 195 and 330 g assigned to control and groups. The supplementation group received the diet by gavage and were killed after 24h, 72h and seven days. Evaluation of regeneration occurred through analysis of weight gain liver, serum aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidase, and mitosis of the liver stained with H&E. the diet supplemented group showed no statistical difference (p>0.05) on the evolution of weights. Administration of fatty acids post-hepatectomy had significant reduction in gamma glutamyltransferase levels and may reflect liver regeneration. Referring to mitotic index, it did not differ between period of times among the groups. supplementation with fatty acids in rats undergoing 60% hepatic resection showed no significant interference related to liver regeneration.

  6. A Chemoenzymatic Histology Method for O-GlcNAc Detection.

    PubMed

    Aguilar, Aime Lopez; Hou, Xiaomeng; Wen, Liuqing; Wang, Peng G; Wu, Peng

    2017-12-14

    Modification of nuclear and cytoplasmic proteins by the addition or removal of O-GlcNAc dynamically impacts multiple biological processes. Here, we present the development of a chemoenzymatic histology method for the detection of O-GlcNAc in tissue specimens. We applied this method to screen murine organs, uncovering specific O-GlcNAc distribution patterns in different tissue structures. We then utilized our histology method for O-GlcNAc detection in human brain specimens from healthy donors and donors with Alzheimer's disease and found higher levels of O-GlcNAc in specimens from healthy donors. We also performed an analysis using a multiple cancer tissue array, uncovering different O-GlcNAc levels between healthy and cancerous tissues, as well as different O-GlcNAc cellular distributions within certain tissue specimens. This chemoenzymatic histology method therefore holds great potential for revealing the biology of O-GlcNAc in physiopathological processes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Non-invasive assessment of liver fibrosis by transient elastography in post transfusional iron overload.

    PubMed

    Mirault, Tristan; Lucidarme, Damien; Turlin, Bruno; Vandevenne, Philippe; Gosset, Pierre; Ernst, Olivier; Rose, Christian

    2008-04-01

    Liver fibrosis, assessed by biopsy, is the main complication of post transfusional liver iron overload. Transient elastography (TE) is a new, non invasive method able to measure liver stiffness (LS) caused by fibrosis. We prospectively evaluated the predictive value of LS measurement for liver fibrosis evaluation in 15 chronically transfused patients and compared these results with the METAVIR histological fibrosis stage from liver biopsies. Mean TE values significantly differed in patients with severe fibrosis (METAVIR F3, F4): 9.1 (+/-3.7 SD) kPa from those with mild or no fibrosis (METAVIR F0, F1, F2): 5.9 (+/-1.8 SD) kPa (P = 0.046). TE value above 6.25 kPa (Se = 80%; Sp = 70%; AUROC = 0.820) identified patients at risk for severe fibrosis (Negative Predictive Value 88%; Positive Predictive Value 57%). Transient elastography appears to be a reliable tool to evaluate liver fibrosis in post-transfusional iron overload.

  8. Ability of natural astaxanthin from shrimp by-products to attenuate liver oxidative stress in diabetic rats.

    PubMed

    Sila, Assaâd; Kamoun, Zeineb; Ghlissi, Zohra; Makni, Mohamed; Nasri, Moncef; Sahnoun, Zouhaier; Nedjar-Arroume, Naima; Bougatef, Ali

    2015-04-01

    Reactive oxygen species play a crucial role in the pathogenesis of diabetes and its complications. The present study was undertaken, in vivo, to examine the protective effect of astaxanthin extracted from the shell waste of deep-water pink shrimp (Parapenaeus longirostris) against oxidative stress of alloxanic adult male rats. Alloxan treatment revealed a significant elevation in plasma glycemia and lipid parameters such as total lipid, total cholesterol and triglycerides compared to the control group (C). In addition, liver malonaldialdehyde levels (MDA), an index of lipid peroxidation, significantly increased compared to control group. The activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) and reduced glutathione (GSH) levels decreased significantly compared to control group. Moreover, diabetic rats presented a significant increase in the activities of aspartate transaminase (AST) alanine transaminase (ALT) and alkaline phosphatase (ALP) in plasma, indicating considerable hepatocellular injury. Astaxanthin treatment restores these parameters near to control values. Histological studies on the liver tissue of alloxan and astaxanthin treated rats confirmed the protective effects of astaxanthin. The results revealed that astaxanthin may be helpful in preventing diabetic complications in adult rats by reversing hepatotoxicity. It can be one of the ingredients in a number of healthy products. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  9. Impact factors and the optimal parameter of acoustic structure quantification in the assessment of liver fibrosis.

    PubMed

    Huang, Yang; Liu, Guang-Jian; Liao, Bing; Huang, Guang-Liang; Liang, Jin-Yu; Zhou, Lu-Yao; Wang, Fen; Li, Wei; Xie, Xiao-Yan; Wang, Wei; Lu, Ming-De

    2015-09-01

    The aims of the present study are to assess the impact factors on acoustic structure quantification (ASQ) ultrasound and find the optimal parameter for the assessment of liver fibrosis. Twenty healthy volunteers underwent ASQ examinations to evaluate impact factors in ASQ image acquisition and analysis. An additional 113 patients with liver diseases underwent standardized ASQ examinations, and the results were compared with histologic staging of liver fibrosis. We found that the right liver displayed lower values of ASQ parameters than the left (p = 0.000-0.021). Receive gain experienced no significant impact except gain 70 (p = 0.193-1.000). With regard to different diameter of involved vessels in regions of interest, the group ≤2.0 mm differed significantly with the group 2.1-5.0 mm (p = 0.000-0.033) and the group >5.0 mm (p = 0.000-0.062). However, the region of interest size (p = 0.438-1.000) and depth (p = 0.072-0.764) had no statistical impact. Good intra- and inter-operator reproducibilities were found in both image acquisitions and offline image analyses. In the liver fibrosis study, the focal disturbance ratio had the highest correlation with histologic fibrosis stage (r = 0.67, p < 0.001). In conclusion, the testing position, receive gain and involved vessels were the main factors in ASQ examinations and focal disturbance ratio was the optimal parameter in the assessment of liver fibrosis. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  10. [Clinical and biochemical characteristics in patients with histology compatible with steatothepatitis in National Hospital Arzobispo Loayza, Lima, Peru, from 2010 to 2012].

    PubMed

    Alegría Matos, Paola Hilda; Tafur Cabello, Kelly Stephanie; Lozano Miranda, Adelina; Loza Munarriz, Cesar; Lozano Miranda, Zenaida

    2015-01-01

    Describe the clinical and biochemical characteristics of patients with histopathological findings compatible with steatohepatitis of HNAL patients between 2010-2012. Determine the frequency of alcoholic and non-alcoholic steatohepatitis, presence of metabolic syndrome and other factors associated to non-alcoholic steatohepatitis, its main indications for liver biopsy and biochemical characteristics according to the severity of the histological findings. We evaluated all histological slides of liver biopsies of the period between 2010-2012, of which, those with the diagnosis of steatohepatitis were selected. Their medical records were then reviewed. 32 patients met inclusion criteria. 28 were female and 4 male, the average age was 49±12 years. Two patients had a history of chronic alcohol consumption, representing the group of alcoholic steatohepatitis. The more frequent clinical finding in patients with NASH (non-alcoholic steatohepatitis), was obesity (37%). 50% of patients had AST/ALT ratio <1. Among population studied, non-alcoholic steatohepatitis was more common than alcoholic steatohepatitis, being obesity the most associated factor.

  11. Persistent organic pollutants and histological lesions in Mayan catfish Ariopsis assimilis from the Bay of Chetumal, Mexico.

    PubMed

    Noreña-Barroso, E; Simá-Alvarez, R; Gold-Bouchot, G; Zapata-Pérez, O

    2004-02-01

    Livers of catfish (Ariopsis assimilis) from the Bay of Chetumal were analyzed for organochlorine compounds and hydrocarbons as part of a study to diagnose the environmental health of the Bay after a catfish mass mortality that occurred in 1996. The presence of histological lesions in several organs of the fish as result of chemical exposure was also evaluated. The concentrations of organic pollutants found in the Bay may be considered high if compared to the levels reported for sites affected by chemical pollution. High prevalences of cellular alteration histopathologies were found in liver, including hepatic tumors. The presence of some lesions may be related statistically to environmental pollution in the Bay, specially with chlorinated compounds.

  12. Relationship between in vivo chlorzoxazone hydroxylation, hepatic cytochrome P450 2E1 content and liver injury in obese non-alcoholic fatty liver disease patients.

    PubMed

    Orellana, Myriam; Rodrigo, Ramón; Varela, Nelson; Araya, Julia; Poniachik, Jaime; Csendes, Attila; Smok, Gladys; Videla, Luis A

    2006-01-01

    The aim of the present study was to test the hypothesis that induction of cytochrome P450 2E1 (CYP2E1) in the liver of patients with non-alcoholic fatty liver disease (NAFLD) is correlated both with the in vivo activity of the cytochrome and with the development of liver injury. For this purpose, the liver content of CYP2E1 was determined by Western blot and the CYP2E1 activity by the in vivo hydroxylation of chlorzoxazone (CLZ). The study groups were obese women with an average body mass index (BMI) of 40.3kg/m(2), who underwent therapeutic gastroplasty or gastrectomy with a gastro-jejunal anastomosis. Further, the hepatic histology was determined to establish the pathological score grouping the subjects into three categories: control, steatosis and steatohepatitis. The liver CYP2E1 content and the CLZ hydroxylation of obese patients with steatosis and, particularly, with steatohepatitis were significantly higher than controls and correlated positively with both the severity of the liver damage. These data provide evidence that CYP2E1 would be involved in the mechanism of liver injury found in obese NAFLD patients. Also, the correlation between liver CYP2E1 content and in vivo CLZ hydroxylation would validate the latter as a reliable indicator of liver injury in NAFLD, thus providing a simple and not invasive method to study these patients.

  13. Protection of the liver against CCl4-induced injury by intramuscular electrotransfer of a kallistatin-encoding plasmid.

    PubMed

    Diao, Yong; Zhao, Xiao-Feng; Lin, Jun-Sheng; Wang, Qi-Zhao; Xu, Rui-An

    2011-01-07

    To investigate the effect of transgenic expression of kallistatin (Kal) on carbon tetrachloride (CCl(4))-induced liver injury by intramuscular (im) electrotransfer of a Kal-encoding plasmid formulated with poly-L-glutamate (PLG). The pKal plasmid encoding Kal gene was formulated with PLG and electrotransferred into mice skeletal muscle before the administration of CCl4. The expression level of Kal was measured. The serum biomarker levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malonyldialdehyde (MDA), and tumor necrosis factor (TNF)-α were monitored. The extent of CCl4-induced liver injury was analyzed histopathologically. The transgene of Kal was sufficiently expressed after an im injection of plasmid formulated with PLG followed by electroporation. In the Kal gene-transferred mice, protection against CCl4-induced liver injury was reflected by significantly decreased serum ALT, AST, MDA and TNF-α levels compared to those in control mice (P<0.01 to 0.05 in a dose-dependent manner). Histological observations also revealed that hepatocyte necrosis, hemorrhage, vacuolar change and hydropic degeneration were apparent in mice after CCl4 administration. In contrast, the damage was markedly attenuated in the Kal gene-transferred mice. The expression of hepatic fibrogenesis marker transforming growth factor-β1 was also reduced in the pKal transferred mice. Intramuscular electrotransfer of plasmid pKal which was formulated with PLG significantly alleviated the CCl4-induced oxidative stress and inflammatory response, and reduced the liver damage in a mouse model.

  14. Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function

    PubMed Central

    Watson, Christa Y; Molina, Ramon M; Louzada, Andressa; Murdaugh, Kimberly M; Donaghey, Thomas C; Brain, Joseph D

    2015-01-01

    Background Zinc oxide engineered nanoparticles (ZnO ENPs) have potential as nanomedicines due to their inherent properties. Studies have described their pulmonary impact, but less is known about the consequences of ZnO ENP interactions with the liver. This study was designed to describe the effects of ZnO ENPs on the liver and Kupffer cells after intravenous (IV) administration. Materials and methods First, pharmacokinetic studies were conducted to determine the tissue distribution of neutron-activated 65ZnO ENPs post-IV injection in Wistar Han rats. Then, a noninvasive in vivo method to assess Kupffer cell phagosomal motility was employed using ferromagnetic iron particles and magnetometry. We also examined whether prior IV injection of ZnO ENPs altered Kupffer cell bactericidal activity on circulating Pseudomonas aeruginosa. Serum and liver tissues were collected to assess liver-injury biomarkers and histological changes, respectively. Results We found that the liver was the major site of initial uptake of 65ZnO ENPs. There was a time-dependent decrease in tissue levels of 65Zn in all organs examined, refecting particle dissolution. In vivo magnetometry showed a time-dependent and transient reduction in Kupffer cell phagosomal motility. Animals challenged with P. aeruginosa 24 hours post-ZnO ENP injection showed an initial (30 minutes) delay in vascular bacterial clearance. However, by 4 hours, IV-injected bacteria were cleared from the blood, liver, spleen, lungs, and kidneys. Seven days post-ZnO ENP injection, creatine phosphokinase and aspartate aminotransferase levels in serum were significantly increased. Histological evidence of hepatocyte damage and marginated neutrophils were observed in the liver. Conclusion Administration of ZnO ENPs transiently inhibited Kupffer cell phagosomal motility and later induced hepatocyte injury, but did not alter bacterial clearance from the blood or killing in the liver, spleen, lungs, or kidneys. Our data show that

  15. Osteolipomatous metaplasia in the liver of cameloids

    USGS Publications Warehouse

    Stroud, R.K.; Griner, L.A.; Higgins, W.Y.

    1982-01-01

    An aged male Bactrian camel (Camelus ferus f. bactriana), originally from the San Diego Zoo, died suddenly. Necropsy showed acute bloat and chronic liver disease. In samples of liver tissue fixed in 10% neutral buffered formalin, approximately 25% of the total volume of tissue was comprised of multiple white to cream-colored circumscribed nodules up to 1 cm in diameter, which were gritty when cut (fig. 1).Samples of liver were cut at 6 μm for histologic examination. Microscopically, the nodules consisted of aggregations of large, vacuolated cells resembling fat cells with spicules of mature bone scattered throughout many nodules (fig. 2). Most nodules were circumscribed but not encapsulated. Single or small clusters of vacuolated cells, however, were scattered diffusely in the hepatic parenchyma surrounding the nodules. We found cholangitis and peribiliary fibrosis in some areas, but no generalized cirrhosis. Degeneration of hepatocytes was seen in some areas peripheral to the nodules. Compression of the hepatic architecture was evident in the liver parenchyma surrounding some nodules, but the primary change was infiltrative rather than expansive. Foci of lymphocytes and a few neutrophils were present in some nodules. Hematopoietic cells, described as a characteristic of myelolipomas, were not found in any of the nodules examined [2, 4].

  16. Effects of oral administration of energy drinks on blood chemistry, tissue histology and brain acetylcholine in rabbits.

    PubMed

    Ebuehi, O A T; Ajayl, O E; Onyeulor, A L; Awelimobor, D

    2011-01-01

    Energy drinks are canned or bottled carbonated beverages that contain large amounts of caffeine and sugar with additional ingredients, such as B-Vitamins, amino acids and herbal stimulants. Previous reports have shown that consumption of large amounts of these energy drinks may result in adverse health consequences. The present study is to ascertain if oral administration of energy drinks, such as "power horse" and "red bull", may affect blood chemistry, tissue histology and acetyl choline levels in rabbits. Five ml of power horse and red bull energy drinks, caffeine and saline (control) were orally administered daily for 36 days to rabbits. Body weight, feed and water intake were measured every other day. The blood samples were taken by cardiac puncture for blood chemistry measurement and their liver, heart and brain tissues were used for histological assay. The plasma, liver, brain and heart acetylcholine levels were also determined. There were no significant differences in the body weight, feed intake and organ weights of rabbits administered energy drinks or caffeine as compared to the control. The blood chemistry results showed that the activities of the aspartate and alanine amino transferase, concentrations of plasma creatinine, uric acid and albumin were increased in the control as compared to the red bull and caffeine administered rabbits. The concentrations of total protein, total cholesterol, triglyceride, high density lipoprotein (HDL) and low density lipoprotein (LDL) and glucose concentrations were increased in power horse and red bull administered rabbits as compared to caffeine administered rabbits and control rabbits. The concentrations of plasma and brain acetylcholine of rabbits administered power horse and red bull were significantly higher than in the control, while it was lower in liver and heart acetyl choline levels. The histopathological findings of the brain and liver show that there were no obvious histopathological abnormalities in the

  17. Correlation between acoustic radiation force impulse (ARFI)-based tissue elasticity measurements and perfusion parameters acquired by perfusion CT in cirrhotic livers: a proof of principle.

    PubMed

    Esser, Michael; Bitzer, Michael; Kolb, Manuel; Fritz, Jan; Kurucay, Mustafa; Ruff, Christer; Horger, Marius

    2018-06-13

    To investigate whether liver stiffness measured by acoustic radiation force impulse (ARFI) sonoelastography always correlates with the liver perfusion parameters quantified by perfusion CT in patients with known liver cirrhosis. Sonoelastography and perfusion CT were performed in 50 patients (mean age 65.5; range 45-87 years) with liver cirrhosis, who were classified according to Child-Pugh into class A (30/50, 60%), B (17/50, 34%), and C (3/50, 6%). For standardized ARFI measurements in the left liver lobe at a depth of 4 cm, a convex 6-MHz probe was used. CT examinations were performed using 80 kV, 100 mAs, and 50 ml of iodinated contrast agent injected at 5 ml/s. Using standardized region-of-interest measurements, we quantified arterial, portal venous, and total liver perfusion. There was a significant linear correlation between tissue stiffness and arterial liver perfusion (p = 0.015), and also when limiting the analysis to patients with histology (p = 0.019). In addition, there was a positive correlation between the total blood supply (arterial + portal-venous liver perfusion) to the liver and tissue stiffness (p = 0.001; with histology, p = 0.027). Shear wave velocity increased with higher Child-Pugh stages (p = 0.013). The degree of tissue stiffness in cirrhotic livers correlates expectedly-even if only moderately-with the magnitude of arterial liver perfusion and total liver perfusion. As such, liver elastography remains the leading imaging tool in assessing liver fibrosis.

  18. Liver Ischemic Preconditioning (IPC) Improves Intestinal Microbiota Following Liver Transplantation in Rats through 16s rDNA-Based Analysis of Microbial Structure Shift

    PubMed Central

    Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen

    2013-01-01

    Background Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The “gut-liver axis” closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). Methods The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Principal Findings Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Conclusion Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of

  19. Liver ischemic preconditioning (IPC) improves intestinal microbiota following liver transplantation in rats through 16s rDNA-based analysis of microbial structure shift.

    PubMed

    Ren, Zhigang; Cui, Guangying; Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen

    2013-01-01

    Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The "gut-liver axis" closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further

  20. The Impact of Liver Cell Injury on Health-Related Quality of Life in Patients with Chronic Liver Disease

    PubMed Central

    Alt, Yvonne; Grimm, Anna; Schlegel, Liesa; Grambihler, Annette; Kittner, Jens M.; Wiltink, Jörg; Galle, Peter R.; Wörns, Marcus A.; Schattenberg, Jörn M.

    2016-01-01

    Background Patients with chronic liver disease often suffer from unspecific symptoms and report severe impairment in the quality of life. The underlying mechanisms are multifactorial and include disease-specific but also liver related causes. The current analysis evaluated the association of hepatocellular apoptosis in non-viral chronic liver disease and health-related quality of life (HRQL). Furthermore we examined factors, which influence patient's physical and mental well-being. Methods A total of 150 patients with non-infectious chronic liver disease were included between January 2014 and June 2015. The German version of the Chronic Liver Disease Questionnaire (CLDQ-D), a liver disease specific instrument to assess HRQL, was employed. Hepatocellular apoptosis was determined by measuring Cytokeratin 18 (CK18, M30 Apoptosense ELISA). Results Female gender (5.24 vs. 5.54, p = 0.04), diabetes mellitus type II (4.75 vs. 5.46, p<0.001) and daily drug intake (5.24 vs. 6.01, p = 0.003) were associated with a significant impairment in HRQL. HRQL was not significantly different between the examined liver diseases. Levels of CK18 were the highest in patients with NASH compared to all other disease entities (p<0.001). Interestingly, CK18 exhibited significant correlations with obesity (p<0.001) and hyperlipidemia (p<0.001). In patients with cirrhosis levels of CK18 correlated with the MELD score (r = 0.18, p = 0.03) and were significantly higher compared to patients without existing cirrhosis (265.5 U/l vs. 186.9U/l, p = 0.047). Additionally, CK18 showed a significant correlation with the presence and the degree of hepatic fibrosis (p = 0.003) and inflammation (p<0.001) in liver histology. Finally, there was a small negative association between CLDQ and CK18 (r = -0.16, p = 0.048). Conclusion Different parameters are influencing HRQL and CK18 levels in chronic non-viral liver disease and the amount of hepatocellular apoptosis correlates with the impairment in HRQL in