[Antioxidant activity of hepatotropic preparations in the treatment of chronic diseases of the liver].

PubMed

Loginov, A S; Matiushin, B N; Sukhareva, G V; Tkachev, V D

1988-01-01

Hepatotropic drugs were shown to decrease blood lipid peroxidation activity (LPO) in patients with chronic diffuse liver diseases. A positive time course of LPO indices was noted in the treatment of chronic active hepatitis and liver cirrhosis of moderate activity. Comparison of antioxidant features of the drugs were suggestive of a noticeable effect of trophopar and essential in patients with chronic active hepatitis, trophopar in patients with liver lipodystrophy, and drugs of a silimarina series in patients with liver cirrhosis. Under clinical conditions the effect of the drugs on LPO processes was less noticeable than in experiments in vitro. It is assumed that the pharmacological effect of the hepatotropic drugs is associated with their antioxidant activity.

Spatially constrained incoherent motion method improves diffusion-weighted MRI signal decay analysis in the liver and spleen

PubMed Central

Taimouri, Vahid; Afacan, Onur; Perez-Rossello, Jeannette M.; Callahan, Michael J.; Mulkern, Robert V.; Warfield, Simon K.; Freiman, Moti

2015-01-01

Purpose: To evaluate the effect of the spatially constrained incoherent motion (SCIM) method on improving the precision and robustness of fast and slow diffusion parameter estimates from diffusion-weighted MRI in liver and spleen in comparison to the independent voxel-wise intravoxel incoherent motion (IVIM) model. Methods: We collected diffusion-weighted MRI (DW-MRI) data of 29 subjects (5 healthy subjects and 24 patients with Crohn’s disease in the ileum). We evaluated parameters estimates’ robustness against different combinations of b-values (i.e., 4 b-values and 7 b-values) by comparing the variance of the estimates obtained with the SCIM and the independent voxel-wise IVIM model. We also evaluated the improvement in the precision of parameter estimates by comparing the coefficient of variation (CV) of the SCIM parameter estimates to that of the IVIM. Results: The SCIM method was more robust compared to IVIM (up to 70% in liver and spleen) for different combinations of b-values. Also, the CV values of the parameter estimations using the SCIM method were significantly lower compared to repeated acquisition and signal averaging estimated using IVIM, especially for the fast diffusion parameter in liver (CVIV IM = 46.61 ± 11.22, CVSCIM = 16.85 ± 2.160, p < 0.001) and spleen (CVIV IM = 95.15 ± 19.82, CVSCIM = 52.55 ± 1.91, p < 0.001). Conclusions: The SCIM method characterizes fast and slow diffusion more precisely compared to the independent voxel-wise IVIM model fitting in the liver and spleen. PMID:25832079

Automated two-point dixon screening for the evaluation of hepatic steatosis and siderosis: comparison with R2-relaxometry and chemical shift-based sequences.

PubMed

Henninger, B; Zoller, H; Rauch, S; Schocke, M; Kannengiesser, S; Zhong, X; Reiter, G; Jaschke, W; Kremser, C

2015-05-01

To evaluate the automated two-point Dixon screening sequence for the detection and estimated quantification of hepatic iron and fat compared with standard sequences as a reference. One hundred and two patients with suspected diffuse liver disease were included in this prospective study. The following MRI protocol was used: 3D-T1-weighted opposed- and in-phase gradient echo with two-point Dixon reconstruction and dual-ratio signal discrimination algorithm ("screening" sequence); fat-saturated, multi-gradient-echo sequence with 12 echoes; gradient-echo T1 FLASH opposed- and in-phase. Bland-Altman plots were generated and correlation coefficients were calculated to compare the sequences. The screening sequence diagnosed fat in 33, iron in 35 and a combination of both in 4 patients. Correlation between R2* values of the screening sequence and the standard relaxometry was excellent (r = 0.988). A slightly lower correlation (r = 0.978) was found between the fat fraction of the screening sequence and the standard sequence. Bland-Altman revealed systematically lower R2* values obtained from the screening sequence and higher fat fraction values obtained with the standard sequence with a rather high variability in agreement. The screening sequence is a promising method with fast diagnosis of the predominant liver disease. It is capable of estimating the amount of hepatic fat and iron comparable to standard methods. • MRI plays a major role in the clarification of diffuse liver disease. • The screening sequence was introduced for the assessment of diffuse liver disease. • It is a fast and automated algorithm for the evaluation of hepatic iron and fat. • It is capable of estimating the amount of hepatic fat and iron.

Factors predicting non-alcoholic steatohepatitis (NASH) and advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD).

PubMed

Tasneem, Abbas Ali; Luck, Nasir Hassan; Majid, Zain

2018-04-01

Introduction To determine the factors predicting non-alcoholic steatohepatitis (NASH) and advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Methodology All patients aged >18 years and having a fatty liver on abdominal ultrasound (US), presenting from January 2011 to January 2017, were included. A liver biopsy was performed on all the patients. Results Of 96 patients undergoing liver biopsy for non-alcoholic fatty liver disease (NAFLD), 76 (79.2%) were men. On liver US, diffuse fatty liver (DFL) was noted in 68 (70.8%) patients. Liver biopsy showed non-alcoholic steatohepatitis (NASH) in 78 (81.3%) patients. Factors associated with NASH were male gender, body mass index (BMI) > 27 kg/m 2 , DFL and raised alanine aminotransferase (ALT). A GULAB score (based on gender, US liver findings, lipid (fasting) levels, ALT level and BMI) of ≥5 predicted NASH with 82.05% sensitivity. Factors associated with advanced fibrosis in NAFLD were age >40 years, diabetes mellitus, AST/ALT ratio > 1 and raised GGT. Conclusion NASH is common in patients with male gender, high BMI, DFL on liver US, raised ALT and GULAB score ≥5.

Hypervitaminosis A-induced hepatic fibrosis in a cat.

PubMed

Guerra, Juliana M; Daniel, Alexandre G T; Aloia, Thiago P A; de Siqueira, Adriana; Fukushima, André R; Simões, Denise M N; Reche-Júior, Archivaldo; Cogliati, Bruno

2014-03-01

The excessive intake of vitamin A in the form of vitamin concentrate, supplement or vitamin-rich liver can result in hypervitaminosis A in man and animals. Although osteopathologies resulting from chronic vitamin A intoxication in cats are well characterized, no information is available concerning feline hypervitaminosis A-induced liver disease. We report the first case of hepatic stellate cell lipidosis and hepatic fibrosis in a domestic cat that had been fed a diet based on raw beef liver. Radiographic examination revealed exostoses and ankylosis between vertebrae C1 and T7, compatible with deforming cervical spondylosis. Necropsy showed a slightly enlarged and light yellow to bronze liver. Microscopic and ultrastructural analyses of liver tissues revealed diffuse and severe liver fibrosis associated with hepatic stellate cell hyperplasia and hypertrophy. These cells showed immunopositive staining for α-smooth muscle actin and desmin markers. The necropsy findings of chronic liver disease coupled with osteopathology supported the diagnosis of hypervitaminosis A. As in human hepatology, if there is dietary evidence to support increased intake of vitamin A, then hypervitaminosis A should be considered in the differential diagnosis of chronic liver disease in cats.

Cross-sectional investigation of correlation between hepatic steatosis and IVIM perfusion on MR imaging.

PubMed

Lee, James T; Liau, Joy; Murphy, Paul; Schroeder, Michael E; Sirlin, Claude B; Bydder, Mark

2012-05-01

The purpose of this study was to investigate the relationship between liver fat fraction (FF) and diffusion parameters derived from the intravoxel incoherent motion (IVIM) model. Thirty-six subjects with suspected nonalcoholic fatty liver disease underwent diffusion-weighted magnetic resonance imaging with 10 b-values and spoiled gradient recalled echo imaging with six echoes for fat quantification. Correlations were measured between FF, transverse relaxivity (R2), diffusivity (D) and perfusion fraction (f). The primary finding was that no significant correlation was obtained for D vs. FF or f vs. FF. Significant correlations were obtained for D vs. R2 (r=-0.490, P=.002) and f vs. D (r=-0.458, P=.005). The conclusion is that hepatic steatosis does not affect measurement of perfusion or diffusion and therefore is unlikely to confound the use of apparent diffusivity to evaluate hepatic fibrosis. Copyright © 2012 Elsevier Inc. All rights reserved.

Primary sclerosing cholangitis

PubMed Central

Silveira, Marina G; Lindor, Keith D

2008-01-01

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts, resulting in end-stage liver disease and reduced life expectancy. PSC primarily affects young and middle-aged men, often in association with underlying inflammatory bowel disease. The etiology of PSC includes immune-mediated components and elements of undefined nature. A cholestatic picture of liver biochemistries with elevations in serum alkaline phosphatase, nonspecific autoantibodies such as perinuclear antineutrophilic antibody, antinuclear antibodies and smooth muscle antibodies, and diffuse multifocal biliary strictures, resulting in a ‘beaded’ appearance on radiographic studies, are the hallmarks of the disease. No effective medical therapy is currently available, although clinical studies are in progress. Ursodeoxycholic acid at high doses (28 mg/kg/day to 30 mg/kg/day) is the most promising agent but is unproven so far. Liver transplantation is currently the only life-extending therapy for patients with end-stage disease, although recurrent disease can be observed in the transplanted liver. The multiple complications of PSC include pruritus, fatigue, vitamin deficiencies, metabolic bone disease, peristomal varices, bacterial cholangitis, dominant biliary strictures, gallbladder stones and polyps, and malignancy, particularly cholangiocarcinoma, which is the most lethal complication of PSC. PMID:18701947

Pulmonary changes in liver transplant candidates with hepatitis C cirrhosis.

PubMed

Al-Moamary, M S; Gorka, T; Al-Traif, I H; Al-Jahdali, H H; Al-Shimemeri, A A; Al-Kanway, B; Abdulkareeem, A A; Abdulkareeem, A A

2001-12-01

Several studies have shown that pulmonary abnormalities are common in patients with end-stage liver disease. However, most of these studies were conducted on patients with heterogeneous etiologies. Therefore, we studied these changes in a homogenous group of hepatitis C cirrhotic patients who were potential candidates for liver transplantation. The charts of 81 patients from King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia with hepatitis C cirrhosis who were evaluated for liver transplantation were reviewed. The following data was retrieved: echocardiography with micro-bubble study, arterial blood gases, and pulmonary function tests of 81 candidates and reviewed over 3 years from 1994 to 1997. The mean age was 53 (+/-9) years with male to female ratio of 1.4:1. Echocardiographic micro-bubble study, revealed 4 of 62 (7%) had an intrapulmonary shunt. Arterial blood gases results were pH of 7.44 (+/-0.4), partial arterial tension of carbon dioxide of 33 mm Hg (+/-4), partial arterial tension of oxygen of 84 mm Hg (+/-12), and alveolar-arterial gradient of 30 mm Hg (+/-10). Eleven percent had obstructive airway disease, 17% had restrictive lung impairment, and 43% had reduced diffusion capacity. Seventy five percent of patients with reduced diffusion capacity had normal lung volumes. Various pulmonary function test abnormalities did not lead to significant differences in arterial blood gases. Pulmonary changes were frequent in liver transplant candidates with hepatitis C virus cirrhosis with reduced diffusion capacity being the most. Apart from the effect of hepatopulmonary syndrome on arterial oxygenation, other pulmonary abnormalities were not significantly different.

Comparison of T2, T1rho, and diffusion metrics in assessment of liver fibrosis in rats.

PubMed

Zhang, Hui; Yang, Qihua; Yu, Taihui; Chen, Xiaodong; Huang, Jingwen; Tan, Cui; Liang, Biling; Guo, Hua

2017-03-01

To evaluate the value of T 2 , T 1 rho, and diffusion metrics in assessment of liver fibrosis in rats. Liver fibrosis in a rat model (n = 72) was induced by injection of carbon tetrachloride (CCl 4 ) at 3T. T 2 , T 1 rho, and diffusion parameters (apparent diffusion coefficient (ADC), D true ) via spin echo (SE) diffusion-weighted imaging (DWI) and stimulated echo acquisition mode (STEAM) DWI with three diffusion times (DT: 80, 106, 186 msec) were obtained in surviving rats with hepatic fibrosis (n = 52) and controls (n = 8). Liver fibrosis stage (F0-F6) was identified based on pathological results using the traditional liver fibrosis staging method for rodents. Nonparametric statistical methods and receiver operating characteristic (ROC) curve analysis were employed to determine the diagnostic accuracy. Mean T 2 , T 1 rho, ADC, and D true with DT = 186 msec correlated with the severity of fibrosis with r = 0.73, 0.83, -0.83, and -0.85 (all P < 0.001), respectively. The average areas under the ROC curve at different stages for T 1 rho and diffusion parameters (DT = 186 msec) were larger than those of T 2 and SE DWI (0.92, 0.92, and 0.92 vs. 0.86, 0.82, and 0.83). The corresponding average sensitivity and specificity for T 1 rho and diffusion parameters with a long DT were larger (89.35 and 88.90, 88.36 and 89.97, 90.16 and 87.13) than T 2 and SE DWI (90.28 and 79.93, 85.30 and 77.64, 78.21 and 82.41). The performances of T 1 rho and D true (DT = 186 msec) were comparable (average AUC: 0.92 and 0.92). Among the evaluated sequences, T 1 rho and STEAM DWI with a long DT may serve as superior imaging biomarkers for assessing liver fibrosis and monitoring disease severity. 1 J. Magn. Reson. Imaging 2017;45:741-750. © 2016 International Society for Magnetic Resonance in Medicine.

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

High-resolution diffusion and relaxation-edited magic angle spinning 1H NMR spectroscopy of intact liver tissue.

PubMed

Rooney, O M; Troke, J; Nicholson, J K; Griffin, J L

2003-11-01

High-resolution magic angle spinning (HRMAS) (1)H NMR spectroscopy is ideal for monitoring the metabolic environment within tissues, particularly when spectra are weighted by physical properties such as T(1) and T(2) relaxation times and apparent diffusion coefficients (ADCs). In this study, spectral-editing using T(1) and T(2) relaxation times and ADCs at variable diffusion times was used in conjunction with HRMAS (1)H NMR spectroscopy at 14.1 T in liver tissue. To enhance the sensitivity of ADC measurements to low molecular weight metabolites a T(2) spin echo was included in a standard stimulated gradient spin-echo sequence. Fatty liver induced in rats by chronic orotic acid feeding was investigated using this modified sequence. An increase in the combined ADC for the co-resonant peaks glucose, betaine, and TMAO during fatty liver disease was detected (ADCs = 0.60 +/- 0.11 and 0.35 +/- 0.1 * 10(-9) m(2)s(-1) (n = 3) for rats fed with and without orotic acid), indicative of a reduction in glucose and betaine and an increase in TMAO. Copyright 2003 Wiley-Liss, Inc.

Liver diffusivity in healthy volunteers and patients with chronic liver disease: Comparison of breath-hold and free-breathing techniques

PubMed Central

Eatesam, Mamak; Noworolski, Susan M; Tien, Phyllis C; Nystrom, Michelle; Dodge, Jennifer L.; Merriman, Raphael B.; Qayyum, Aliya

2011-01-01

Purpose To compare liver ADC obtained with breath-hold and free-breathing diffusion weighted imaging (DWI) in healthy volunteers and patients with liver disease. Materials and Methods Twenty-eight subjects, 12 healthy volunteers and 16 patients (9 NAFLD, 7 chronic active HCV), underwent breath-hold (BH) and free-breathing (FB) DWI MRI at 1.5T. Pearson’s correlation coefficient was used to determine correlation while paired t-tests assessed differences between BH and FB ADC. Estimated bias was calculated using the Bland-Altman method. Results Liver ADC (×10−3 mm2/sec) was lower on BH for all groups (mean difference 0.36±0.20; p<0.01). ADC was higher in healthy volunteers (BH 1.80±0.18; FB 2.24±0.20) compared to NAFLD patients (BH 1.43±0.27; FB 1.78±0.28) (p<0.001) and HCV patients (BH 1.63±0.191; FB 1.88±0.12). Overall correlation between BH and FB ADC was (r =0.75), greatest in NAFLD (r =0.90) compared to the correlation in HCV (r =0.24) and healthy subjects (r =0.34). Bland-Altman plots did not show agreement in mean absolute difference and estimated bias between subjects. Conclusion Correlation between BH and FB liver ADC is moderate indicating that BH and FB should not be used interchangeably. Additionally, the lower ADC values in BH versus FB should be accounted for when comparing different liver DWI studies. PMID:22034200

Liver diffusivity in healthy volunteers and patients with chronic liver disease: comparison of breathhold and free-breathing techniques.

PubMed

Eatesam, Mamak; Noworolski, Susan M; Tien, Phyllis C; Nystrom, Michelle; Dodge, Jennifer L; Merriman, Raphael B; Qayyum, Aliya

2012-01-01

To compare liver ADC obtained with breathhold and free-breathing diffusion weighted imaging (DWI) in healthy volunteers and patients with liver disease. Twenty-eight subjects, 12 healthy volunteers and 16 patients (9 NAFLD, 7 chronic active HCV), underwent breathhold (BH) and free-breathing (FB) DWI MRI at 1.5 Tesla. Pearson's correlation coefficient was used to determine correlation while paired t-tests assessed differences between BH and FB ADC. Estimated bias was calculated using the Bland-Altman method. Liver ADC (×10(-3) mm(2) /s) was lower on BH for all groups (mean difference 0.36 ± 0.20; P < 0.01). ADC was higher in healthy volunteers (BH 1.80 ± 0.18; FB 2.24 ± 0.20) compared with NAFLD patients (BH 1.43 ± 0.27; FB 1.78 ± 0.28) (P < 0.001) and HCV patients (BH 1.63 ± 0.191; FB 1.88 ± 0.12). Overall correlation between BH and FB ADC was (r = 0.75), greatest in NAFLD (r = 0.90) compared with the correlation in HCV (r = 0.24) and healthy subjects (r = 0.34). Bland-Altman plots did not show agreement in mean absolute difference and estimated bias between subjects. Correlation between BH and FB liver ADC is moderate indicating that BH and FB should not be used interchangeably. Additionally, the lower ADC values in BH versus FB should be accounted for when comparing different liver DWI studies. Copyright © 2011 Wiley-Liss, Inc.

Review of MR Elastography Applications and Recent Developments

PubMed Central

Glaser, Kevin J.; Manduca, Armando; Ehman, Richard L.

2012-01-01

The technique of MR elastography (MRE) has emerged as a useful modality for quantitatively imaging the mechanical properties of soft tissues in vivo. Recently, MRE has been introduced as a clinical tool for evaluating chronic liver disease, but many other potential applications are being explored. These applications include measuring tissue changes associated with diseases of the liver, breast, brain, heart, and skeletal muscle including both focal lesions (e.g., hepatic, breast, and brain tumors) and diffuse diseases (e.g., fibrosis and multiple sclerosis). The purpose of this review article is to summarize some of the recent developments of MRE and to highlight some emerging applications. PMID:22987755

[Current practice in MR imaging of the liver].

PubMed

Kanematsu, M; Kondo, H; Matsuo, M; Hoshi, H

2001-12-01

MR imaging, which is able to evaluate T1- and T2-relaxation time, fat, hemorrhage, metal deposition, blood flow, perfusion, diffusion, and so on, has offered more information for the diagnosis of diffuse and focal hepatic diseases than CT. The spoiled-GRE sequence with high contrast resolution and ease of the aimed contrast capture derived from the k-space property, with the use of a phased-array multicoil, have remarkably increased the value of gadolinium-enhanced dynamic MR diagnosis of the liver. In recent years, the clinical use of ferumoxide has begun, and issues concerning the superiority or inferiority and combination of contrast media are being debated. This paper describes the value, role, and clinical practice of unenhanced, gadolinium-enhanced, and ferumoxide-enhanced MR imaging of the liver based on knowledge obtained in our institution, with some reference to the literature.

Hepatic lipidosis associated with cobalt deficiency in Omani goats.

PubMed

Johnson, E H; Muirhead, D E; Annamalai, K; King, G J; Al-Busaidy, R; Hameed, M S

1999-06-01

Livers from 36 of 684 (5.3%) apparently healthy goats examined at an abattoir in the greater Muscat area of Oman exhibited gross pathological findings characterized by extremely pale, friable, fatty livers encompassing the entire organ. Histopathologically, diffuse hepatic lipidosis and occasional bile duct proliferation were observed. Periodic acid Schiff-positive, diastase-resistant pigment was observed in the macrophages lining the sinusoids. These histopathological lesions were consistent with those characteristic of ovine white liver disease. Cobalt analysis revealed that normal livers had six times more cobalt and a 3-fold less fat content than those measured in the fatty livers. This is the first report of an association between cobalt deficiency and hepatic lipidosis in Omani goats.

Imaging patterns and focal lesions in fatty liver: a pictorial review.

PubMed

Venkatesh, Sudhakar K; Hennedige, Tiffany; Johnson, Geoffrey B; Hough, David M; Fletcher, Joel G

2017-05-01

Non-alcoholic fatty liver disease is the most common cause of chronic liver disease and affects nearly one-third of US population. With the increasing trend of obesity in the population, associated fatty change in the liver will be a common feature observed in imaging studies. Fatty liver causes changes in liver parenchyma appearance on imaging modalities including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) and may affect the imaging characteristics of focal liver lesions (FLLs). The imaging characteristics of FLLs were classically described in a non-fatty liver. In addition, focal fatty change and focal fat sparing may also simulate FLLs. Knowledge of characteristic patterns of fatty change in the liver (diffuse, geographical, focal, subcapsular, and perivascular) and their impact on the detection and characterization of FLL is therefore important. In general, fatty change may improve detection of FLLs on MRI using fat suppression sequences, but may reduce sensitivity on a single-phase (portal venous) CT and conventional ultrasound. In patients with fatty liver, MRI is generally superior to ultrasound and CT for detection and characterization of FLL. In this pictorial essay, we describe the imaging patterns of fatty change in the liver and its effect on detection and characterization of FLLs on ultrasound, CT, MRI, and PET.

Guided percutaneous fine-needle aspiration biopsy of the liver

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

Ho, C.S.; McLoughlin, M.J.; Tao, L.C.

1981-04-01

Forty patients with suspected malignant disease of the liver underwent percutaneous fine-needle aspiration biopsy with radioisotope scintigraphic and fluoroscopic guidance. The needle was aimed at focal defects identified on the liver scan and several passes were made. When the scan was diffusely abnormal, the liver was widely sampled with multiple passes. Thirty patients were eventually considered to have malignant disease and aspiration biopsy was positive in 28 (93%) of these patients, including 25 of 26 with liver metastases (96%). There were two false-positive results and one minor complication. In 24 patients, conventional wide-bore needle biopsy was also performed. In thismore » group, 16 patients had a final diagnosis of hepatic malignancy. Aspiration biopsies were positive in 14 of these (87%) and conventional needle biopsies were positive in four (25%). Guided percutaneous fine-needle aspiration biopsy is recommended for pathologic diagnosis of hepatic malignancy because of its simplicity, high yield, and reasonable safety.« less

Value of 3 Tesla diffusion-weighted magnetic resonance imaging for assessing liver fibrosis

PubMed Central

Papalavrentios, Lavrentios; Sinakos, Emmanouil; Chourmouzi, Danai; Hytiroglou, Prodromos; Drevelegas, Konstantinos; Constantinides, Manos; Drevelegas, Antonios; Talwalkar, Jayant; Akriviadis, Evangelos

2015-01-01

Background Limited data are available regarding the role of magnetic resonance imaging (MRI), particularly the new generation 3 Tesla technology, and especially diffusion-weighted imaging (DWI) in predicting liver fibrosis. The aim of our pilot study was to assess the clinical performance of the apparent diffusion coefficient (ADC) of liver parenchyma for the assessment of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Methods 18 patients with biopsy-proven NAFLD underwent DWI with 3 Tesla MRI. DWI was performed with single-shot echo-planar technique at b values of 0-500 and 0-1000 s/mm2. ADC was measured in four locations in the liver and the mean ADC value was used for analysis. Staging of fibrosis was performed according to the METAVIR system. Results The median age of patients was 52 years (range 23-73). The distribution of patients in different fibrosis stages was: 0 (n=1), 1 (n=7), 2 (n=1), 3 (n=5), 4 (n=4). Fibrosis stage was poorly associated with ADC at b value of 0-500 s/mm2 (r= -0.30, P=0.27). However it was significantly associated with ADC at b value of 0-1000 s/mm2 (r= -0.57, P=0.01). For this b value (0-1000 s/mm2) the area under receiver-operating characteristic curve was 0.93 for fibrosis stage ≥3 and the optimal ADC cut-off value was 1.16 ×10-3 mm2/s. Conclusion 3 Tesla DWI can possibly predict the presence of advanced fibrosis in patients with NAFLD. PMID:25608776

Value of 3 Tesla diffusion-weighted magnetic resonance imaging for assessing liver fibrosis.

PubMed

Papalavrentios, Lavrentios; Sinakos, Emmanouil; Chourmouzi, Danai; Hytiroglou, Prodromos; Drevelegas, Konstantinos; Constantinides, Manos; Drevelegas, Antonios; Talwalkar, Jayant; Akriviadis, Evangelos

2015-01-01

Limited data are available regarding the role of magnetic resonance imaging (MRI), particularly the new generation 3 Tesla technology, and especially diffusion-weighted imaging (DWI) in predicting liver fibrosis. The aim of our pilot study was to assess the clinical performance of the apparent diffusion coefficient (ADC) of liver parenchyma for the assessment of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). 18 patients with biopsy-proven NAFLD underwent DWI with 3 Tesla MRI. DWI was performed with single-shot echo-planar technique at b values of 0-500 and 0-1000 s/mm 2 . ADC was measured in four locations in the liver and the mean ADC value was used for analysis. Staging of fibrosis was performed according to the METAVIR system. The median age of patients was 52 years (range 23-73). The distribution of patients in different fibrosis stages was: 0 (n=1), 1 (n=7), 2 (n=1), 3 (n=5), 4 (n=4). Fibrosis stage was poorly associated with ADC at b value of 0-500 s/mm 2 (r= -0.30, P=0.27). However it was significantly associated with ADC at b value of 0-1000 s/mm 2 (r= -0.57, P=0.01). For this b value (0-1000 s/mm 2 ) the area under receiver-operating characteristic curve was 0.93 for fibrosis stage ≥3 and the optimal ADC cut-off value was 1.16 ×10 -3 mm 2 /s. 3 Tesla DWI can possibly predict the presence of advanced fibrosis in patients with NAFLD.

3.0 Tesla magnetic resonance imaging: A new standard in liver imaging?

PubMed Central

Girometti, Rossano

2015-01-01

An ever-increasing number of 3.0 Tesla (T) magnets are installed worldwide. Moving from the standard of 1.5 T to higher field strength implies a number of potential advantage and drawbacks, requiring careful optimization of imaging protocols or implementation of novel hardware components. Clinical practice and literature review suggest that state-of-the-art 3.0 T is equivalent to 1.5 T in the assessment of focal liver lesions and diffuse liver disease. Therefore, further technical improvements are needed in order to fully exploit the potential of higher field strength. PMID:26244063

3.0 Tesla magnetic resonance imaging: A new standard in liver imaging?

PubMed

Girometti, Rossano

2015-07-28

An ever-increasing number of 3.0 Tesla (T) magnets are installed worldwide. Moving from the standard of 1.5 T to higher field strength implies a number of potential advantage and drawbacks, requiring careful optimization of imaging protocols or implementation of novel hardware components. Clinical practice and literature review suggest that state-of-the-art 3.0 T is equivalent to 1.5 T in the assessment of focal liver lesions and diffuse liver disease. Therefore, further technical improvements are needed in order to fully exploit the potential of higher field strength.

Fuzzy similarity measures for ultrasound tissue characterization

NASA Astrophysics Data System (ADS)

Emara, Salem M.; Badawi, Ahmed M.; Youssef, Abou-Bakr M.

1995-03-01

Computerized ultrasound tissue characterization has become an objective means for diagnosis of diseases. It is difficult to differentiate diffuse liver diseases, namely cirrhotic and fatty liver from a normal one, by visual inspection from the ultrasound images. The visual criteria for differentiating diffused diseases is rather confusing and highly dependent upon the sonographer's experience. The need for computerized tissue characterization is thus justified to quantitatively assist the sonographer for accurate differentiation and to minimize the degree of risk from erroneous interpretation. In this paper we used the fuzzy similarity measure as an approximate reasoning technique to find the maximum degree of matching between an unknown case defined by a feature vector and a family of prototypes (knowledge base). The feature vector used for the matching process contains 8 quantitative parameters (textural, acoustical, and speckle parameters) extracted from the ultrasound image. The steps done to match an unknown case with the family of prototypes (cirr, fatty, normal) are: Choosing the membership functions for each parameter, then obtaining the fuzzification matrix for the unknown case and the family of prototypes, then by the linguistic evaluation of two fuzzy quantities we obtain the similarity matrix, then by a simple aggregation method and the fuzzy integrals we obtain the degree of similarity. Finally, we find that the similarity measure results are comparable to the neural network classification techniques and it can be used in medical diagnosis to determine the pathology of the liver and to monitor the extent of the disease.

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.

Use of transfer learning to detect diffuse degenerative hepatic diseases from ultrasound images in dogs: A methodological study.

PubMed

Banzato, T; Bonsembiante, F; Aresu, L; Gelain, M E; Burti, S; Zotti, A

2018-03-01

The aim of this methodological study was to develop a deep convolutional neural network (DNN) to detect degenerative hepatic disease from ultrasound images of the liver in dogs and to compare the diagnostic accuracy of the newly developed DNN with that of serum biochemistry and cytology on the same samples, using histopathology as a standard. Dogs with suspected hepatic disease that had no prior history of neoplastic disease, no hepatic nodular pathology, no ascites and ultrasonography performed 24h prior to death were included in the study (n=52). Ultrasonography and serum biochemistry were performed as part of the routine clinical evaluation. On the basis of histopathology, dogs were categorised as 'normal' (n=8), or having 'vascular abnormalities'(n=8), or 'inflammatory'(n=0), 'neoplastic' (n=4) or 'degenerative'(n=32) disease; dogs with 'neoplastic' disease were excluded from further analysis. On cytological evaluation, dogs were categorised as 'normal' (n=11), or having 'inflammatory' (n=0), 'neoplastic' (n=4) or 'degenerative' (n=37) disease. Dogs were categorised as having 'degenerative' (n=32) or 'non-degenerative' (n=16) liver disease for analysis due to the limited sample size. The DNN was developed using a transfer learning methodology on a pre-trained neural network that was retrained and fine-tuned to our data set. The resultant DNN had a high diagnostic accuracy for degenerative liver disease (area under the curve 0.91; sensitivity 100%; specificity 82.8%). Cytology and serum biochemical markers (alanine transaminase and aspartate transaminase) had poor diagnostic accuracy in the detection of degenerative liver disease. The DNN outperformed all the other non-invasive diagnostic tests in the detection of degenerative liver disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

Assessing liver fibrosis: comparison of arterial enhancement fraction and diffusion-weighted imaging.

PubMed

Bonekamp, David; Bonekamp, Susanne; Ou, Hsin-You; Torbenson, Michael S; Corona-Villalobos, Celia Pamela; Mezey, Esteban; Kamel, Ihab R

2014-11-01

Noninvasive markers have been developed to reduce the need for liver biopsy. The aim of this study was to compare the strength of association of the arterial enhancement fraction (AEF), apparent diffusion coefficient (ADC), and serum biomarkers for staging hepatic fibrosis. Eighty-five patients with chronic liver disease underwent triple-phase contrast-enhanced MRI, used to calculate AEF, and diffusion-weighted MRI (b = 0,750 s/mm(2) ), used to calculate ADC. Hepatic fibrosis was staged according METAVIR criteria. The overall association of the four biomarkers (AEF, ADC, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, and aspartate aminotransferase to platelet ratio index [APRI]) was compared using nonparametric tests and receiver operating characteristic (ROC) curve, using histopathologic analysis as the reference standard. AEF and ADC values differed significantly between histopathologic fibrosis stages. AEF values correlated with fibrosis stage, ADC values correlated negatively with fibrosis stage. Compared with ADC, AEF showed a trend toward an improved capability of discriminating fibrosis stages. A weighted composite score of AEF and ADC had significantly better diagnostic accuracy than ADC alone (P ≤ 0.023). Imaging parameters had a significantly better diagnostic accuracy than AST/ALT ratio or APRI. AEF may be able to detect the presence of mild, moderate, and advanced liver fibrosis, and its value is increased with concomitant use of ADC. © 2013 Wiley Periodicals, Inc.

Hepatitis, gallbladder hydrops, splenomegaly, and ascites in a child with scarlet fever.

PubMed

Wang, Li Yueh; Young, Ton-Ho

2012-11-01

We report a case of scarlet fever associated with hepatitis, gallbladder hydrops, splenomegaly, and ascites in a 15-year-old girl. The girl presented with fever and skin rash. Leukocyte, liver enzyme, and serum C-reactive protein concentrations were elevated. Ultrasonography revealed marked gallbladder wall thickening, diffuse liver parenchymal disease with moderate splenomegaly, and moderate ascites throughout the abdominal and pelvic cavities. Blood cultures for group A β-hemolytic streptococci were negative. Complete recovery was facilitated with antibiotic treatment.

Alpha-mannosidosis in goats caused by the swainsonine-containing plant Ipomoea verbascoidea

USDA-ARS?s Scientific Manuscript database

A disease of the nervous system is reported in goats in the semiarid region of northeastern Brazil. Histological examination showed diffuse vacuolation of neurons and epithelial cells of the pancreas, thyroid, renal tubules, and liver. The swainsonine-containing plant Ipomoea verbascoidea was found ...

Primary hyperoxaluria in an adult presenting with end-stage renal failure together with hypercalcemia and hypothyroidism.

PubMed

Karadag, Serhat; Gursu, Meltem; Aydin, Zeki; Uzun, Sami; Dogan, Oner; Ozturk, Savas; Kazancioglu, Rumeyza

2011-10-01

Primary hyperoxaluria (PH) is a rare genetic disorder characterized by overproduction of oxalate due to specific enzyme deficiencies in glyoxylate metabolism. The primary clinical presentation is in the form of recurrent urolithiasis, progressive nephrocalcinosis, end-stage renal disease, and systemic oxalosis. Herein, we present a case of PH who was diagnosed at 47 years of age after 6 years on hemodialysis. He presented with fatigue, anorexia, weight loss, and was found to have cachexia, diffuse edema, hepatomegaly, ascites, hypercalcemia, hyperphosphatemia, hypoalbuminemia, low parathyroid hormone levels, lytic and resorptive areas in the vertebrae, diffusely increased echogenity of the liver, multiple renal stones, and bilateral nephrocalcinosis. Bone marrow biopsy showed calcium oxalate crystals and crystal granulomas. The liver biopsy could not be performed. The absence of an identifiable reason for secondary forms, the severity of the clinical presentation, and pathological findings led to the diagnosis of PH2. He died while waiting for a potential liver and kidney donor. The presented case is consistent with the literature as he had renal stone disease in the third decade and end-stage renal disease in the fifth decade. Hypercalcemia was thought to be due to osteoclast-stimulating activity of macrophages constituting the granuloma. Erythropoietin-resistant anemia and hypothyroidism were thought to be due to accumulation of oxalate in the bone marrow and thyroid gland, respectively. It is very important to keep in mind the possibility of PH when faced with a patient with nephrocalcinosis and oxalate stone disease. © 2011 The Authors; Hemodialysis International © 2011 International Society for Hemodialysis.

A rare case of isolated macronodular hepatic tuberculosis (Tuberculous) in an immunocompetent patient.

PubMed

Kayar, Yusuf; Ekinci, Iskender; Turkdogan, Figen Tunali; Atay, Musa; Soytas, Rabia Bag; Kayar, Nuket Bayram

2015-11-01

Tuberculosis is one of the most common and well described infectious diseases, with a world wide distribution and a vast spectrum of clinical manifestations. There are three forms of hepatic tuberculosis. Diffuse hepatic involvement with pulmonary or miliary tuberculosis, diffuse hepatic infiltration without recognizable pulmonary involvement is the second form and the third very rare form presents as a focal/local tuberculoma or abscess. In this case report we describe an unusual appearance of macronodular tuberculomas of the liver.

A successful case of deceased donor liver transplantation for a patient with intrahepatic arterioportal fistula.

PubMed

Takagi, Kosei; Yagi, Takahito; Yoshida, Ryuichi; Shinoura, Susumu; Umeda, Yuzo; Nobuoka, Daisuke; Watanabe, Nobuyuki; Kuise, Takashi; Sui, Kenta; Hirose, Akira; Tsuboi, Makiko; Ogasawara, Mitsunari; Iwasaki, Shinji; Saibara, Toshiji; Fujiwara, Toshiyoshi

2016-12-01

Intrahepatic arterioportal fistula (IAPF) is a rare cause of portal hypertension that is often difficult to treat with interventional radiology or surgery. Liver transplantation for IAPF is extremely rare. We report a case of bilateral diffuse IAPF with severe portal hypertension requiring deceased donor liver transplantation (DDLT). A 51-year-old woman with no past medical history was admitted to another hospital complaining of abdominal distension and marasmus. A computed tomography scan and digital subtraction angiography indicated a massive pleural effusion, ascites, and a very large IAPF. Several attempts of interventional embolization of the feeding artery failed to ameliorate arterioportal shunt flow. As ruptures of the esophageal varices became more frequent, hepatic encephalopathy worsened. After repeated, uncontrollable attacks of hepatic coma, the patient was referred to our facility for further treatment. Surgical approaches to IAPF other than liver transplantation were challenging because of diffuse collateralization; therefore, we placed the patient on the national waiting list for DDLT. Although her Model for End-Stage Liver Disease score was relatively low, she received a DDLT 2 months after the waiting period. The postoperative course was uneventful, and the patient was discharged 44 days after her transplant. Liver transplantation may be a valid treatment option for uncontrollable IAPF with severe portal hypertension. © 2016 The Authors Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.

Novel Application of Extracorporeal Photopheresis as Treatment of Graft-versus-Host Disease Following Liver Transplantation.

PubMed

Brown, Timothy J; Gentry, Cathy; Hammer, Suntrea T G; Hwang, Christine S; Vusirikala, Madhuri; Patel, Prapti A; Matevosyan, Karén; Tujios, Shannan R; Mufti, Arjmand R; Collins, Robert H

2017-01-01

A 48-year-old man with hepatitis C virus (HCV) cirrhosis complicated by hepatocellular carcinoma underwent liver transplantation. His course was complicated by fever, diarrhea, abdominal pain, and pancytopenia. He developed a diffuse erythematous rash, which progressed to erythroderma. Biopsies of the colon and skin were consistent with acute graft-versus-host disease. Donor-derived lymphocytes were present in the peripheral blood. The patient was treated with corticosteroids and cyclosporine; however, he had minimal response to intensive immunosuppressive therapy. Extracorporeal photopheresis was initiated as a salvage therapy. He had a dramatic response, and his rash, diarrhea, and pancytopenia resolved. He is maintained on minimal immunosuppression 24 months later.

Fumarylacetoacetate hydrolase deficient pigs are a novel large animal model of metabolic liver disease

PubMed Central

Hickey, Raymond D.; Mao, Shennen A.; Glorioso, Jaime; Lillegard, Joseph B.; Fisher, James E.; Amiot, Bruce; Rinaldo, Piero; Harding, Cary O.; Marler, Ronald; Finegold, Milton J.; Grompe, Markus; Nyberg, Scott L.

2014-01-01

Hereditary tyrosinemia type I (HT1) is caused by deficiency in fumarylacetoacetate hydrolase (FAH), an enzyme that catalyzes the last step of tyrosine metabolism. The most severe form of the disease presents acutely during infancy, and is characterized by severe liver involvement, most commonly resulting in death if untreated. Generation of FAH+/− pigs was previously accomplished by adeno-associated virus-mediated gene knockout in fibroblasts and somatic cell nuclear transfer. Subsequently, these animals were outbred and crossed to produce the first FAH−/− pigs. FAH-deficiency produced a lethal defect in utero that was corrected by administration of 2-(2-nitro-4-trifluoromethylbenzyol)-1,3 cyclohexanedione (NTBC) throughout pregnancy. Animals on NTBC were phenotypically normal at birth; however, animals were euthanized approximately four weeks after withdrawal of NTBC due to clinical decline and physical examination findings of severe liver injury and encephalopthy consistent with acute liver failure. Biochemical and histological analyses, characterized by diffuse and severe hepatocellular damage, confirmed the diagnosis of severe liver injury. FAH−/− pigs provide the first genetically engineered large animal model of a metabolic liver disorder. Future applications of FAH−/− pigs include discovery research as a large animal model of HT1 and spontaneous acute liver failure, and preclinical testing of efficacy of liver cell therapies, including transplantation of hepatocytes, liver stem cells, and pluripotent stem cell-derived hepatocytes. PMID:24879068

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

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.

Detection of Hepatic Fibrosis in Ex Vivo Liver Samples Using an Open-Photoacoustic-Cell Method: Feasibility Study

NASA Astrophysics Data System (ADS)

Stolik, S.; Fabila, D. A.; de la Rosa, J. M.; Escobedo, G.; Suárez-Álvarez, K.; Tomás, S. A.

2015-09-01

Design of non-invasive and accurate novel methods for liver fibrosis diagnosis has gained growing interest. Different stages of liver fibrosis were induced in Wistar rats by intraperitoneally administering different doses of carbon tetrachloride. The liver fibrosis degree was conventionally determined by means of histological examination. An open-photoacoustic-cell (OPC) technique for the assessment of liver fibrosis was developed and is reported here. The OPC technique is based on the fact that the thermal diffusivity can be accurately measured by photoacoustics taking into consideration the photoacoustic signal amplitude versus the modulation frequency. This technique measures directly the heat generated in a sample, due to non-radiative de-excitation processes, following the absorption of light. The thermal diffusivity was measured with a home-made open-photoacoustic-cell system that was specially designed to perform the measurement from ex vivo liver samples. The human liver tissue showed a significant increase in the thermal diffusivity depending on the fibrosis stage. Specifically, liver samples from rats exhibiting hepatic fibrosis showed a significantly higher value of the thermal diffusivity than for control animals.

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.

Gastroesphageal Variceal Hemorrhage Induced by Metastatic Liver Tumor of Lung Cancer

PubMed Central

Honda, Takayuki; Kobayashi, Hiroaki; Saiki, Masafumi; Sogami, Yusuke; Miyashita, Yoshihiro; Inase, Naohiko

2012-01-01

Gastroesophageal variceal hemorrhage is a lethal complication of portal hypertension. Liver cirrhosis is often the principal cause of the portal hypertensive state. Malignant tumors coexist with portal hypertension in some cases. Non-small-cell lung cancer (NSCLC) is likely to become metastatic. Liver is a frequent site of cancer metastasis, but diffuse hepatic sinusoidal metastasis is uncommon as a metastatic form of NSCLC. This report describes a patient with gastroesophageal variceal hemorrhage owing to a metastatic liver tumor of NSCLC. The patient, a male smoker with stage IV NSCLC, was free of any hepatitis viral infection and had no alcohol addiction. Liver dysfunction and liver disease had never been pointed out in his medical history. His tumor harbored an L858R epidermal growth factor receptor mutation. Gefitinib was initiated but had to be ceased because of interstitial lung disease. Sequential steroid therapy was effective and bevacizumab-containing chemotherapy was commenced. Both chemotherapy regimens produced favorable effects against the metastatic liver tumor, eliciting atrophic change regardless of the chemotherapy-free interval. One day the patient was admitted to our hospital because of black stool and hypotension. Upper gastrointestinal endoscopy revealed a beaded appearance of the gastroesophageal varix with bloody gastric contents. The portal hypertension might have been caused by changes in portal vein hemodynamics induced by the conformational changes underlying the favorable response of the liver tumor to molecular targeted chemotherapy and notable regression. PMID:23275780

Basic investigation on acoustic velocity change imaging method for quantitative assessment of fat content in human liver

NASA Astrophysics Data System (ADS)

Mano, Kazune; Tanigawa, Shohei; Hori, Makoto; Yokota, Daiki; Wada, Kenji; Matsunaka, Toshiyuki; Morikawa, Hiroyasu; Horinaka, Hiromichi

2016-07-01

Fatty liver is a disease caused by the excess accumulation of fat in the human liver. The early diagnosis of fatty liver is very important, because fatty liver is the major marker linked to metabolic syndrome. We already proposed the ultrasonic velocity change imaging method to diagnose fatty liver by using the fact that the temperature dependence of ultrasonic velocity is different in water and in fat. For the diagonosis of a fatty liver stage, we attempted a feasibility study of the quantitative assessment of the fat content in the human liver using our ultrasonic velocity change imaging method. Experimental results showed that the fat content in the tissue mimic phantom containing lard was determined by its ultrasonic velocity change in the flat temperature region formed by a circular warming ultrasonic transducer with an acoustic lens having an appropriate focal length. By considering the results of our simulation using a thermal diffusion equation, we determined whether this method could be applied to fatty liver assessment under the condition that the tissue had the thermal relaxation effect caused by blood flow.

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

Swaminath, Anand; Knox, Jennifer J.; Brierley, James D.

Purpose: The purpose of this study was to quantify unexpected liver volume reductions in patients treated with sorafenib prior to and during liver radiation therapy (RT). Methods and Materials: Fifteen patients were treated in a phase 1 study of sorafenib for 1 week, followed by concurrent sorafenib-RT (in 6 fractions). Patients had either focal cancer (treated with stereotactic body RT [SBRT]) or diffuse disease (treated with whole-liver RT). Liver volumes were contoured and recorded at planning (day 0) from the exhale CT. After 1 week of sorafenib (day 8), RT image guidance at each fraction was performed using cone beam CT (CBCT).more » Planning liver contours were propagated and modified on the reconstructed exhale CBCT. This was repeated in 12 patients treated with SBRT alone without sorafenib. Three subsequent patients (2 sorafenib-RT and 1 non-sorafenib) were also assessed with multiphasic helical breath-hold CTs. Results: Liver volume reductions on CBCT were observed in the 15 sorafenib-RT patients (median decrease of 68 cc, P=.02) between day 0 and 8; greater in the focal (P=.025) versus diffuse (P=.52) cancer stratum. Seven patients (47%) had reductions larger than the 95% intraobserver contouring error. Liver reductions were also observed from multiphasic CTs in the 2 additional sorafenib-RT patients between days 0 and 8 (decreases of 232.5 cc and 331.7 cc, respectively) and not in the non-sorafenib patient (increase of 92 cc). There were no significant changes in liver volume between planning and first RT in 12 patients with focal cancer treated with SBRT alone (median increase, 4.8 cc, P=.86). Conclusions: Liver volume reductions were observed after 7 days of sorafenib, prior to RT, most marked in patients with focal liver tumors, suggesting an effect of sorafenib on normal liver. Careful assessment of potential liver volume changes immediately prior to SBRT may be necessary in patients in sorafenib or other targeted therapies.« less

The value of liver magnetic resonance imaging in patients with findings of resectable pancreatic cancer on computed tomography.

PubMed

Chew, Cindy; O'Dwyer, Patrick J

2016-06-01

Accurate staging of patients with pancreatic cancer is important to avoid unnecessary operations. The aim of this study was to prospectively assess the impact of magnetic resonance (MR) imaging on preoperative staging of liver in patients with findings of resectable pancreatic cancer on computed tomography (CT). All patients who presented to a tertiary referral centre with pancreatic cancer between April 2012 and December 2013 were included in the study. Patients with findings of resectable disease on CT underwent further liver diffusion-weighted MR imaging, using a hepatocyte-specific contrast agent. A total of 583 patients with pancreatic cancer were referred. 69 (11.8%) had resectable disease on CT. Of these 69 patients, 16 (23.2%) had liver metastases on MR imaging, while 6 (8.7%) had indeterminate lesions. Of the 16 patients with positive MR imaging findings of liver metastases, 11 died of pancreatic cancer, with a mean survival time of nine months (95% confidence interval [CI] 5.22-14.05). The mean survival time of the 47 patients with negative MR imaging findings was 16 months (95% CI 14.33-18.10; p = 0.001). Subsequently, 22 of these patients underwent surgery, and only 1 (4.5%) patient was found to have liver metastasis at surgery. The results of the present study indicate that MR imaging improves the staging of disease in patients with resectable pancreatic cancer. Copyright: © Singapore Medical Association.

Magnetic Resonance Spectroscopy for Evaluating Portal-Systemic Encephalopathy in Patients with Chronic Hepatic Schistosomiasis Japonicum.

PubMed

Li, Ying; Mei, Lihong; Qiang, Jinwei; Ju, Shuai; Zhao, Shuhui

2016-12-01

Portal-systemic encephalopathy (PSE) is classified as type B hepatic encephalopathy. Portal-systemic shunting rather than liver dysfunction is the main cause of PSE in chronic hepatic schistosomiasis japonicum (HSJ) patients. Owing to lack of detectable evidence of intrinsic liver disease, chronic HSJ patients with PSE are frequently clinically undetected or misdiagnosed, especially chronic HSJ patients with covert PSE (subclinical encephalopathy). In this study, we investigated whether magnetic resonance spectroscopy (MRS) could be a useful tool for diagnosing PSE in chronic HSJ patients. Magnetic resonance (MR) T1-weighted imaging, diffusion-weighted imaging, and MRS were performed in 41 chronic HSJ patients with suspected PSE and in 21 age-matched controls. The T1 signal intensity index (T1SI) and apparent diffusion coefficient (ADC) value were obtained in the Globus pallidus. Liver function was also investigated via serum ammonia and liver function tests. Higher T1SI and ADC values, increased lactate and glutamine levels, and decreased myo-inositol were found in the bilateral Globus pallidus in chronic HSJ patients with PSE. No significantly abnormal serum ammonia or liver function tests were observed in chronic HSJ patients with PSE. On the basis of these findings, we propose a diagnostic procedure for PSE in chronic HSJ patients. This study reveals that MRS can be useful for diagnosing PSE in chronic HSJ patients.

Comparison of low and high frequency transducers in the detection of liver metastases.

PubMed

Schacherer, D; Wrede, C; Obermeier, F; Schölmerich, J; Schlottmann, K; Klebl, F

2006-09-01

To evaluate the benefit of the additional use of a high frequency ultrasound probe (7.5 MHz) in finding suspicious liver lesions compared to the examination using a 3.5-MHz transducer only. One hundred and fifty-seven patients with underlying malignant disease were examined with both transducers using one of three ultrasound machines (Siemens Sonoline Elegra, GE Healthcare Logic 9, or Hitachi EUB-8500). Findings on hepatic lesions were collected on a standardised documentation sheet and evaluated by descriptive statistics. Ninety-three patients (59.2% of all patients) showed no evident liver lesion on conventional ultrasound with the 3.5 MHz probe. In 29 patients (18.5%) new suspicious liver lesions were found by using the high frequency transducer. Thirteen of these 29 patients (44.8%) were suspected to suffer from diffuse infiltration of the liver with malignant lesions or at least 10 additional visible lesions. In 14 patients, no liver lesion had been known before high frequency ultrasound examination. The size of newly described liver lesions ranged from 2 mm to 1.5 cm. Time needed for the additional examination with the high frequency transducer ranged between 1 and 15 min with an average of 4.0 min. The additional use of a high frequency transducer in patients with underlying malignant disease slightly extends the examination time, but reveals new, potentially malignant hepatic lesions in almost every fifth patient.

Hepatosplenic Gamma Delta T-Cell Lymphoma (HSGDTCL): Two Rare Case Reports from Western India.

PubMed

Madabhavi, Irappa; Modi, Gaurang; Panchal, Harsha; Patel, Apurva; Revannasiddaiah, Swaroop; Anand, Asha; Parikh, Sonia; Joshi, Kshitij; Sarkar, Malay

2017-10-01

Peripheral T cell lymphomas are a heterogeneous group of post-thymic, mature lymphoid malignancies, accounting for approximately 10-15% of all non-Hodgkin's lymphomas. Hepatosplenic T-cell lymphoma (HSGDTCL) is a rare entity, which is characterized by primary extra nodal disease with typical sinusoidal or sinusal infiltration of the liver and the spleen, respectively by expression of the T-cell receptor γδ chain, and by a number of other frequent clinicopathologic features, including aggressive course of disease. Secondary involvement of liver by hematopoietic malignancies is much more common as compared to primary liver involvement. Primary involvement of liver by non- Hodgkin's lymphoma (NHL) is documented and mostly DLBCL (diffuse large B cell lymphoma) type. But, T cell lymphoma primarily arising from liver is very rare. It occurred commonly in immunocompromised patients and prognosis is very poor. Here, we present two case reports of Hepatosplenic gamma-delta T-cell lymphoma (HSGDTCL) and both are immunocompetent patients. Liver biopsy from the mass and subsequent IHC (immunohistochemistry) were performed for the purpose of diagnosis, which were positive for LCA (leukocyte common antigen), CD2 and negative for CD5, CD20 and CD79a. First patient was a 63-year-old female with hepatitis C virus seropositivity presented with liver mass simulating hepatocellular carcinoma. Second patient was a 60-year- old male, chronic alcoholic patient, presented with liver mass and lytic bony lesion in pelvis. Both patients were managed with conventional CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone) and showed complete response after 4 cycles of chemotherapy. After completion of 6 cycles of chemotherapy, both patients remained under 6-month surveillance period for any recurrence of the disease.

Utility of Diffusion-Weighted MRI to Detect Changes in Liver Diffusion in Benign and Malignant Distal Bile Duct Obstruction: The Influence of Choice of b-Values.

PubMed

Karan, Belgin; Erbay, Gurcan; Koc, Zafer; Pourbagher, Aysin; Yildirim, Sedat; Agildere, Ahmet Muhtesem

2016-11-01

The study sought to evaluate the potential of diffusion-weighted magnetic resonance imaging to detect changes in liver diffusion in benign and malignant distal bile duct obstruction and to investigate the effect of the choice of b-values on apparent diffusion coefficient (ADC). Diffusion-weighted imaging was acquired with b-values of 200, 600, 800, and 1000 s/mm 2 . ADC values were obtained in 4 segments of the liver. The mean ADC values of 16 patients with malignant distal bile duct obstruction, 14 patients with benign distal bile duct obstruction, and a control group of 16 healthy patients were compared. Mean ADC values for 4 liver segments were lower in the malignant obstruction group than in the benign obstruction and control groups using b = 200 s/mm 2 (P < .05). Mean ADC values of the left lobe medial and lateral segments were lower in the malignant obstruction group than in the benign obstructive and control groups using b = 600 s/mm 2 (P < .05). Mean ADC values of the right lobe posterior segment were lower in the malignant and benign obstruction groups than in the control group using b = 1000 s/mm 2 (P < .05). Using b = 800 s/mm 2 , ADC values of all 4 liver segments in each group were not significantly different (P > .05). There were no correlations between the ADC values of liver segments and liver function tests. Measurement of ADC shows good potential for detecting changes in liver diffusion in patients with distal bile duct obstruction. Calculated ADC values were affected by the choice of b-values. Copyright © 2016 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Shear-Wave Elastography for the Estimation of Liver Fibrosis in Chronic Liver Disease: Determining Accuracy and Ideal Site for Measurement

PubMed Central

Dhyani, Manish; Vij, Abhinav; Bhan, Atul K.; Halpern, Elkan F.; Méndez-Navarro, Jorge; Corey, Kathleen E.; Chung, Raymond T.

2015-01-01

Purpose To evaluate the accuracy of shear-wave elastography (SWE) for staging liver fibrosis in patients with diffuse liver disease (including patients with hepatitis C virus [HCV]) and to determine the relative accuracy of SWE measurements obtained from different hepatic acquisition sites for staging liver fibrosis. Materials and Methods The institutional review board approved this single-institution prospective study, which was performed between January 2010 and March 2013 in 136 consecutive patients who underwent SWE before their scheduled liver biopsy (age range, 18–76 years; mean age, 49 years; 70 men, 66 women). Informed consent was obtained from all patients. SWE measurements were obtained at four sites in the liver. Biopsy specimens were reviewed in a blinded manner by a pathologist using METAVIR criteria. SWE measurements and biopsy results were compared by using the Spearman correlation and receiver operating characteristic (ROC) curve analysis. Results SWE values obtained at the upper right lobe showed the highest correlation with estimation of fibrosis (r = 0.41, P < .001). Inflammation and steatosis did not show any correlation with SWE values except for values from the left lobe, which showed correlation with steatosis (r = 0.24, P = .004). The area under the ROC curve (AUC) in the differentiation of stage F2 fibrosis or greater, stage F3 fibrosis or greater, and stage F4 fibrosis was 0.77 (95% confidence interval [CI]: 0.68, 0.86), 0.82 (95% CI: 0.75, 0.91), and 0.82 (95% CI: 0.70, 0.95), respectively, for all subjects who underwent liver biopsy. The corresponding AUCs for the subset of patients with HCV were 0.80 (95% CI: 0.67, 0.92), 0.82 (95% CI: 0.70, 0.95), and 0.89 (95% CI: 0.73, 1.00). The adjusted AUCs for differentiating stage F2 or greater fibrosis in patients with chronic liver disease and those with HCV were 0.84 and 0.87, respectively. Conclusion SWE estimates of liver stiffness obtained from the right upper lobe showed the best correlation with liver fibrosis severity and can potentially be used as a noninvasive test to differentiate intermediate degrees of liver fibrosis in patients with liver disease. © RSNA, 2014 Online supplemental material is available for this article. PMID:25393946

IVIM diffusion-weighted imaging of the liver at 3.0 T: Comparison with 1.5 T

PubMed Central

Cui, Yong; Dyvorne, Hadrien; Besa, Cecilia; Cooper, Nancy; Taouli, Bachir

2015-01-01

Purpose To compare intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) of the liver between 1.5 T and 3.0 T in terms of parameter quantification and inter-platform reproducibility. Materials and methods In this IRB approved prospective study, 19 subjects (17 patients with chronic liver disease and 2 healthy volunteers) underwent two repeat scans at 1.5 T and 3.0 T. Each scan included IVIM DWI using 16 b values from 0 to 800 s/mm2. A single observer measured IVIM parameters for each platform and estimated signal to noise ratio (eSNR) at b0, 200, 400 and 800 s/mm2. Wilcoxon paired tests were used to compare liver eSNR and IVIM parameters. Inter-platform reproducibility was assessed by calculating within-subject coefficient of variation (CV) and Bland–Altman limits of agreement. An ice water phantom was used to test ADC variability between the two MRI systems. Results The mean invitro difference in ADC between the two platforms was 6.8%. eSNR was significantly higher at 3.0T for all selected b values (p = 0.006–0.020), except for b0 (p = 0.239). Liver IVIM parameters were significantly different between 1.5 T and 3.0 T (p = 0.005–0.044), except for ADC (p = 0.748). The inter-platform reproducibility of true diffusion coefficient (D) and ADC were good, with mean CV of 10.9% and 11.1%, respectively. Perfusion fraction (PF) and pseudodiffusion coefficient (D*) showed more limited inter-platform reproducibility (mean CV of 22.6% for PF and 46.9% for D*). Conclusion Liver D and ADC values showed good reproducibility between 1.5 T and 3.0 T platforms; while there was more variability in PF, and large variability in D* parameters between the two platforms. These findings may have implications for drug trials assessing the role of IVIM DWI in tumor response and liver fibrosis. PMID:26393236

Minimal hepatic encephalopathy in children with chronic liver disease: Prevalence, pathogenesis and magnetic resonance-based diagnosis.

PubMed

Srivastava, Anshu; Chaturvedi, Saurabh; Gupta, Rakesh Kumar; Malik, Rohan; Mathias, Amrita; Jagannathan, Naranamangalam R; Jain, Sunil; Pandey, Chandra Mani; Yachha, Surender Kumar; Rathore, Ram Kishor Singh

2017-03-01

Data on minimal hepatic encephalopathy (MHE) in children is scarce. We aimed to study MHE in children with chronic liver disease (CLD) and to validate non-invasive objective tests which can assist in its diagnosis. We evaluated 67 children with CLD (38 boys; age 13 [7-18] years) and 37 healthy children to determine the prevalence of MHE. We also assessed the correlation of MHE with changes in brain metabolites by magnetic resonance spectroscopy ( 1 HMRS), diffusion tensor imaging (DTI) derived metrics, blood ammonia and inflammatory cytokines (interleukin-6 [IL6], tumor necrosis factor alpha [TNF-α]). In addition, the accuracy of MR-based investigations for diagnosis of MHE in comparison to neuropsychological tests was analysed. Thirty-four (50.7%) children with CLD had MHE on neuropsychological tests. MHE patients had higher BA (30.5 [6-74] vs. 14 [6-66]μmol/L; p=0.02), IL-6 (8.3 [4.7-28.7] vs. 7.6 [4.7-20.7]pg/ml; p=0.4) and TNF-α (17.8 [7.8-65.5] vs. 12.8 [7.5-35]pg/ml; p=0.06) than No-MHE. 1 HMRS showed higher glutamine (2.6 [2.1-3.3] vs. 2.4 [2.0-3.1]; p=0.02), and lower choline (0.20 [0.14-0.25] vs. 0.22 [0.17-0.28]; p=0.1) and myo-inositol (0.25 [0.14-0.41] vs. 0.29 [0.21-0.66]; p=0.2) in MHE patients than those without MHE. Mean diffusivity (MD) on DTI was significantly higher in 6/11 brain areas in patients with MHE vs. no MHE. Brain glutamine had a significant positive correlation with blood ammonia, IL-6, TNF-α and MD of various brain regions. Neuropsychological tests showed a negative correlation with blood ammonia, IL6, TNF-α, glutamine and MD. Frontal white matter MD had a sensitivity and specificity of 73.5% and 100% for diagnosing MHE. In children with CLD, 50% have MHE. There is a significant positive correlation between markers of hyperammonemia, inflammation and brain edema and these correlate negatively with neuropsychological tests. MD on DTI is a reliable tool for diagnosing MHE. Fifty percent of children with chronic liver disease develop minimal hepatic encephalopathy (MHE) and perform poorly on neuropsychological testing. These children have raised blood ammonia, inflammatory cytokines and mild cerebral edema on diffusion tensor imaging as compared to children without MHE. The higher the ammonia, inflammatory cytokines and cerebral edema levels the poorer the performance on neuropsychological assessment. The estimation of mean diffusivity on diffusion tensor imaging is an objective and reliable method for diagnosing MHE. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Quality Improvement of Liver Ultrasound Images Using Fuzzy Techniques.

PubMed

Bayani, Azadeh; Langarizadeh, Mostafa; Radmard, Amir Reza; Nejad, Ahmadreza Farzaneh

2016-12-01

Liver ultrasound images are so common and are applied so often to diagnose diffuse liver diseases like fatty liver. However, the low quality of such images makes it difficult to analyze them and diagnose diseases. The purpose of this study, therefore, is to improve the contrast and quality of liver ultrasound images. In this study, a number of image contrast enhancement algorithms which are based on fuzzy logic were applied to liver ultrasound images - in which the view of kidney is observable - using Matlab2013b to improve the image contrast and quality which has a fuzzy definition; just like image contrast improvement algorithms using a fuzzy intensification operator, contrast improvement algorithms applying fuzzy image histogram hyperbolization, and contrast improvement algorithms by fuzzy IF-THEN rules. With the measurement of Mean Squared Error and Peak Signal to Noise Ratio obtained from different images, fuzzy methods provided better results, and their implementation - compared with histogram equalization method - led both to the improvement of contrast and visual quality of images and to the improvement of liver segmentation algorithms results in images. Comparison of the four algorithms revealed the power of fuzzy logic in improving image contrast compared with traditional image processing algorithms. Moreover, contrast improvement algorithm based on a fuzzy intensification operator was selected as the strongest algorithm considering the measured indicators. This method can also be used in future studies on other ultrasound images for quality improvement and other image processing and analysis applications.

Quality Improvement of Liver Ultrasound Images Using Fuzzy Techniques

PubMed Central

Bayani, Azadeh; Langarizadeh, Mostafa; Radmard, Amir Reza; Nejad, Ahmadreza Farzaneh

2016-01-01

Background: Liver ultrasound images are so common and are applied so often to diagnose diffuse liver diseases like fatty liver. However, the low quality of such images makes it difficult to analyze them and diagnose diseases. The purpose of this study, therefore, is to improve the contrast and quality of liver ultrasound images. Methods: In this study, a number of image contrast enhancement algorithms which are based on fuzzy logic were applied to liver ultrasound images - in which the view of kidney is observable - using Matlab2013b to improve the image contrast and quality which has a fuzzy definition; just like image contrast improvement algorithms using a fuzzy intensification operator, contrast improvement algorithms applying fuzzy image histogram hyperbolization, and contrast improvement algorithms by fuzzy IF-THEN rules. Results: With the measurement of Mean Squared Error and Peak Signal to Noise Ratio obtained from different images, fuzzy methods provided better results, and their implementation - compared with histogram equalization method - led both to the improvement of contrast and visual quality of images and to the improvement of liver segmentation algorithms results in images. Conclusion: Comparison of the four algorithms revealed the power of fuzzy logic in improving image contrast compared with traditional image processing algorithms. Moreover, contrast improvement algorithm based on a fuzzy intensification operator was selected as the strongest algorithm considering the measured indicators. This method can also be used in future studies on other ultrasound images for quality improvement and other image processing and analysis applications. PMID:28077898

Assessment of functional liver reserve: old and new in 99mTc-sulfur colloid scintigraphy.

PubMed

Matesan, Manuela M; Bowen, Stephen R; Chapman, Tobias R; Miyaoka, Robert S; Velez, James W; Wanner, Michele F; Nyflot, Matthew J; Apisarnthanarax, Smith; Vesselle, Hubert J

2017-07-01

A semiquantitative assessment of hepatic reticuloendothelial system function using colloidal particles scintigraphy has been proposed previously as a surrogate for liver function evaluation. In this article, we present an updated method for the overall assessment of technetium-99m (Tc)-sulfur colloid (SC) biodistribution that combines information from planar and attenuation-corrected Tc-SC single-photon emission computed tomography (SPECT) images. The imaging protocol described here was developed as an easy-to-implement method to assess overall and regional liver function changes associated with chronic liver disease. Thirty patients with chronic liver disease and primary liver cancers underwent Tc-SC whole-body planar imaging and upper-abdomen SPECT/computed tomography (CT) imaging before external beam radiation therapy. Liver plus spleen and bone marrow counts as a fraction of whole-body total counts were calculated from SC planar imaging. Attenuation correction Tc-SC images were rigidly coregistered with treatment planning CT images that contained liver and spleen regions-of-interest. Ratios of total liver counts to total spleen counts were obtained from the aligned Tc-SC SPECT and CT images, and were subsequently used to separate liver plus spleen counts obtained on the planar images. This hybrid SPECT/CT and planar scintigraphy approach yielded an updated estimation of whole-body SC distribution. These biodistribution estimates were compared with historical data for reference. Statistical associations of Tc-SC biodistribution to liver function parameters and liver disease scoring systems (Child-Pugh) were evaluated by Spearman rank correlation. Percentages of Tc-SC uptake ranged from 19.3 to 77.3% for the liver; 3.4 to 40.7% for the spleen; and 19.0 to 56.7% for the bone marrow. Spearman's correlation coefficient showed a significant statistical association between Child-Pugh score and bone marrow uptake at 0.55 (P≤0.05), liver uptake at 0.71 (P≤0.001), spleen uptake at 0.56 (P≤0.05), and spleen plus bone marrow uptake at 0.71 (P≤0.001). There was also a good correlation of SC uptake percentages with individual quantitative liver function components such as albumin and total bilirubin, and qualitative liver function components (varices, portal hypertension, ascites). For albumin: r=0.64 (P<0.001) compared with liver uptake percentage from the whole-body counts, r=0.49 (P<0.001) compared with splenic uptake percentage, and r=0.45 (P≤0.05) compared with bone marrow uptake percentage. We describe a novel liver function quantitative assessment method that combines whole-body planar images and SPECT/CT attenuation-corrected images of Tc-SC distribution. Attenuation-corrected SC images provide valuable regional liver function information, which is a unique feature compared with other imaging methods available. The results of our study indicate that the Tc-SC uptake by the liver, spleen, and bone marrow correlates with liver function parameters in patients with diffuse liver disease and the correlation with liver disease severity is slightly better for liver uptake percentages than for individual values of bone marrow and spleen uptake percentages.

Detecting jaundice by using digital image processing

NASA Astrophysics Data System (ADS)

Castro-Ramos, J.; Toxqui-Quitl, C.; Villa Manriquez, F.; Orozco-Guillen, E.; Padilla-Vivanco, A.; Sánchez-Escobar, JJ.

2014-03-01

When strong Jaundice is presented, babies or adults should be subject to clinical exam like "serum bilirubin" which can cause traumas in patients. Often jaundice is presented in liver disease such as hepatitis or liver cancer. In order to avoid additional traumas we propose to detect jaundice (icterus) in newborns or adults by using a not pain method. By acquiring digital images in color, in palm, soles and forehead, we analyze RGB attributes and diffuse reflectance spectra as the parameter to characterize patients with either jaundice or not, and we correlate that parameters with the level of bilirubin. By applying support vector machine we distinguish between healthy and sick patients.

Diffusion MRI with Semi-Automated Segmentation Can Serve as a Restricted Predictive Biomarker of the Therapeutic Response of Liver Metastasis

PubMed Central

Stephen, Renu M.; Jha, Abhinav K.; Roe, Denise J.; Trouard, Theodore P.; Galons, Jean-Philippe; Kupinski, Matthew A.; Frey, Georgette; Cui, Haiyan; Squire, Scott; Pagel, Mark D.; Rodriguez, Jeffrey J.; Gillies, Robert J.; Stopeck, Alison T.

2015-01-01

Purpose To assess the value of semi-automated segmentation applied to diffusion MRI for predicting the therapeutic response of liver metastasis. Methods Conventional diffusion weighted magnetic resonance imaging (MRI) was performed using b-values of 0, 150, 300 and 450 s/mm2 at baseline and days 4, 11 and 39 following initiation of a new chemotherapy regimen in a pilot study with 18 women with 37 liver metastases from primary breast cancer. A semi-automated segmentation approach was used to identify liver metastases. Linear regression analysis was used to assess the relationship between baseline values of the apparent diffusion coefficient (ADC) and change in tumor size by day 39. Results A semi-automated segmentation scheme was critical for obtaining the most reliable ADC measurements. A statistically significant relationship between baseline ADC values and change in tumor size at day 39 was observed for minimally treated patients with metastatic liver lesions measuring 2–5 cm in size (p = 0.002), but not for heavily treated patients with the same tumor size range (p = 0.29), or for tumors of smaller or larger sizes. ROC analysis identified a baseline threshold ADC value of 1.33 μm2/ms as 75% sensitive and 83% specific for identifying non-responding metastases in minimally treated patients with 2–5 cm liver lesions. Conclusion Quantitative imaging can substantially benefit from a semi-automated segmentation scheme. Quantitative diffusion MRI results can be predictive of therapeutic outcome in selected patients with liver metastases, but not for all liver metastases, and therefore should be considered to be a restricted biomarker. PMID:26284600

Diffusion MRI with Semi-Automated Segmentation Can Serve as a Restricted Predictive Biomarker of the Therapeutic Response of Liver Metastasis.

PubMed

Stephen, Renu M; Jha, Abhinav K; Roe, Denise J; Trouard, Theodore P; Galons, Jean-Philippe; Kupinski, Matthew A; Frey, Georgette; Cui, Haiyan; Squire, Scott; Pagel, Mark D; Rodriguez, Jeffrey J; Gillies, Robert J; Stopeck, Alison T

2015-12-01

To assess the value of semi-automated segmentation applied to diffusion MRI for predicting the therapeutic response of liver metastasis. Conventional diffusion weighted magnetic resonance imaging (MRI) was performed using b-values of 0, 150, 300 and 450s/mm(2) at baseline and days 4, 11 and 39 following initiation of a new chemotherapy regimen in a pilot study with 18 women with 37 liver metastases from primary breast cancer. A semi-automated segmentation approach was used to identify liver metastases. Linear regression analysis was used to assess the relationship between baseline values of the apparent diffusion coefficient (ADC) and change in tumor size by day 39. A semi-automated segmentation scheme was critical for obtaining the most reliable ADC measurements. A statistically significant relationship between baseline ADC values and change in tumor size at day 39 was observed for minimally treated patients with metastatic liver lesions measuring 2-5cm in size (p=0.002), but not for heavily treated patients with the same tumor size range (p=0.29), or for tumors of smaller or larger sizes. ROC analysis identified a baseline threshold ADC value of 1.33μm(2)/ms as 75% sensitive and 83% specific for identifying non-responding metastases in minimally treated patients with 2-5cm liver lesions. Quantitative imaging can substantially benefit from a semi-automated segmentation scheme. Quantitative diffusion MRI results can be predictive of therapeutic outcome in selected patients with liver metastases, but not for all liver metastases, and therefore should be considered to be a restricted biomarker. Copyright © 2015 Elsevier Inc. All rights reserved.

I Vivo Quantitative Ultrasound Imaging and Scatter Assessments.

NASA Astrophysics Data System (ADS)

Lu, Zheng Feng

There is evidence that "instrument independent" measurements of ultrasonic scattering properties would provide useful diagnostic information that is not available with conventional ultrasound imaging. This dissertation is a continuing effort to test the above hypothesis and to incorporate quantitative ultrasound methods into clinical examinations for early detection of diffuse liver disease. A well-established reference phantom method was employed to construct quantitative ultrasound images of tissue in vivo. The method was verified by extensive phantom tests. A new method was developed to measure the effective attenuation coefficient of the body wall. The method relates the slope of the difference between the echo signal power spectrum from a uniform region distal to the body wall and the echo signal power spectrum from a reference phantom to the body wall attenuation. The accuracy obtained from phantom tests suggests further studies with animal experiments. Clinically, thirty-five healthy subjects and sixteen patients with diffuse liver disease were studied by these quantitative ultrasound methods. The average attenuation coefficient in normals agreed with previous investigators' results; in vivo backscatter coefficients agreed with the results from normals measured by O'Donnell. Strong discriminating power (p < 0.001) was found for both attenuation and backscatter coefficients between fatty livers and normals; a significant difference (p < 0.01) was observed in the backscatter coefficient but not in the attenuation coefficient between cirrhotic livers and normals. An in vivo animal model of steroid hepatopathy was used to investigate the system sensitivity in detecting early changes in canine liver resulting from corticosteroid administration. The average attenuation coefficient slope increased from 0.7 dB/cm/MHz in controls to 0.82 dB/cm/MHz (at 6 MHz) in treated animals on day 14 into the treatment, and the backscatter coefficient was 26times 10^{ -4}cm^{-1}sr^{-1} in controls compared with 74times 10^{-4}cm^{-1}sr^ {-1} (at 6 MHz) in treated animals. A simplified quantitative approach using video image signals was developed. Results derived both from the r.f. signal analysis and from the video signal analysis are sensitive to the changes in the liver in this animal model.

First molecular detection and characterization of Marek's disease virus in red-crowned cranes (Grus japonensis): a case report.

PubMed

Lian, Xue; Ming, Xin; Xu, Jiarong; Cheng, Wangkun; Zhang, Xunhai; Chen, Hongjun; Ding, Chan; Jung, Yong-Sam; Qian, Yingjuan

2018-04-03

Marek's disease virus (MDV) resides in the genus Mardivirus in the family Herpesviridae. MDV is a highly contagious virus that can cause neurological lesions, lymphocytic proliferation, immune suppression, and death in avian species, including Galliformes (chickens, quails, partridges, and pheasants), Strigiformes (owls), Anseriformes (ducks, geese, and swans), and Falconiformes (kestrels). In 2015, two red-crowned cranes died in Nanjing (Jiangsu, China). It was determined that the birds were infected with Marek's disease virus by histopathological examination, polymerase chain reaction (PCR), gene sequencing and sequence analysis of tissue samples from two cranes. Gross lesions included diffuse nodules in the skin, muscle, liver, spleen, kidney, gizzard and heart, along with liver enlargement and gizzard mucosa hemorrhage. Histopathological assay showed that infiltrative lymphocytes and mitotic figures existed in liver and heart. The presence of MDV was confirmed by PCR. The sequence analysis of the Meq gene showed 100% identity with Md5, while the VP22 gene showed the highest homology with CVI988. Furthermore, the phylogenetic analysis of the VP22 and Meq genes suggested that the MDV (from cranes) belongs to MDV serotype 1. We describe the first molecular detection of Marek's disease in red-crowned cranes based on the findings previously described. To our knowledge, this is also the first molecular identification of Marek's disease virus in the order Gruiformes and represents detection of a novel MDV strain.

Liver Function Assessment by Magnetic Resonance Imaging.

PubMed

Ünal, Emre; Akata, Deniz; Karcaaltincaba, Musturay

2016-12-01

Liver function assessment by hepatocyte-specific contrast-enhanced magnetic resonance imaging is becoming a new biomarker. Liver function can be assessed by T1 mapping (reduction rate) and signal intensity measurement (relative enhancement ratio) before and after GD-EOB-DTPA (gadoxetic acid) administration, as alternative to Tc-99m galactosyl serum albumin scintigraphy, 99m Tc-labeled mebrofenin scintigraphy, and indocyanine green clearance test. Magnetic resonance imaging assessment of liver function can enable diagnosis of cirrhosis, nonalcoholic fatty liver disease associated fibrosis and steatohepatitis, primary sclerosing cholangitis, toxic hepatitis, and chemotherapy and radiotherapy-related changes, which may be only visible on hepatobiliary phase images. Simple visual assessment of signal intensity at hepatobiliary phase images is important for the diagnosis of different patterns of liver dysfunction including diffuse, lobar, segmental, and subsegmental forms. Furthermore, preoperative assessment of liver function is feasible before oncologic hepatic surgery, which may be important to prevent posthepatectomy liver failure and to estimate future remnant volume. Functional magnetic resonance cholangiography obtained by T1-weighted images at hepatobiliary phase can allow diagnosis of acalculous cholecystitis, biliary leakage, bile reflux to the stomach, sphincter of oddi dysfunction, and lesions with communication to biliary tree. Functional information can be easily obtained when Gd-EOB-DTPA is used for liver magnetic resonance imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

Diffuse reflectance spectroscopy of liver tissue

NASA Astrophysics Data System (ADS)

Reistad, Nina; Nilsson, Jan; Vilhelmsson Timmermand, Oskar; Sturesson, Christian; Andersson-Engels, Stefan

2015-06-01

Diffuse reflectance spectroscopy (DRS) with a fiber-optic contact probe is a cost-effective, rapid, and non-invasive optical method used to extract diagnosis information of tissue. By combining commercially available VIS- and NIR-spectrometers with various fiber-optic contact-probes, we have access to the full wavelength range from around 400 to 1600 nm. Using this flexible and portable spectroscopy system, we have acquired ex-vivo DRS-spectra from murine, porcine, and human liver tissue. For extracting the tissue optical properties from the measured spectra, we have employed and compared predictions from two models for light propagation in tissue, diffusion theory model (DT) and Monte Carlo simulations (MC). The focus in this work is on the capacity of this DRS-technique in discriminating metastatic tumor tissue from normal liver tissue as well as in assessing and characterizing damage to non-malignant liver tissue induced by preoperative chemotherapy for colorectal liver metastases.

[Alcohol intake--a two-edged sword. Part 1: metabolism and pathogenic effects of alcohol].

PubMed

Ströhle, Alexander; Wolters, Maike; Hahn, Andreas

2012-08-01

From the biomedical point of view alcohol is a Janus-faced dietary component with a dose-dependent effect varying from cardiovascular protection to cytotoxicity. Alcohol is absorbed in the upper gastrointestinal tract by passive diffusion, is quickly distributed throughout body water and is mostly eliminated through oxidation. The enzymatically-catalyzed oxidative degradation to acetaldehyde and further to acetate is primarily localized in the liver. In case of a low blood alcohol concentration (<0.5 per thousand) alcohol is predominantely metabolized by the enzyme aldehyde dehydrogenase; higher blood concentrations (>0.5 per thousand) are increasingly oxidized by the microsomal ethanoloxidizing system (MEOS). Alcohol consumption induces several metabolic reactions as well as acute effects on the central nervous system. Chronic alcohol consumption to some extent irreparably damages nearly every organ with the liver being particularly concerned. There are three stages of alcohol-induced liver disease (fatty liver, alcohol hepatitis, liver cirrhosis) and the liver damages mainly result from reaction products of alcohol degradation (acetaldehyde, NADH and reactive oxygen species). An especially dreaded clinical complication of the alcohol-induced liver disease is the hepatic encephalopathy. Its pathogenesis is a multifactorial and self-perpetuating process with the swelling of astrocytes being a crucial point. Swollen astrocytes induce several reactions such as oxidative/nitrosative stress, impaired signal transduction, protein modifications and a modified gene expression profile. The swelling of astrocytes and the change in neuronal activity are attributed to several neurotoxins, especially ammonia and aromatic amino acids. In alcohol addicted subjects multiple micronutrient deficiencies are common. The status of folic acid, thiamine, pyridoxine and zinc is especially critical.

Imaging mechanical properties of hepatic tissue by magnetic resonance elastography

NASA Astrophysics Data System (ADS)

Yin, Meng; Rouviere, Olivier; Burgart, Lawrence J.; Fidler, Jeff L.; Manduca, Armando; Ehman, Richard L.

2006-03-01

PURPOSE: To assess the feasibility of a modified phase-contrast MRI technique (MR Elastography) for quantitatively assessing the mechanical properties of hepatic tissues by imaging propagating acoustic shear waves. MATERIALS AND METHODS: Both phantom and human studies were performed to develop and optimize a practical imaging protocol by visualizing and investigating the diffraction field of shear waves generated from pneumatic longitudinal drivers. The effects of interposed ribs in a transcostal approach were also investigated. A gradient echo MRE pulse sequence was adapted for shear wave imaging in the liver during suspended respiration, and then tested to measure hepatic shear stiffness in 13 healthy volunteers and 1 patient with chronic liver disease to determine the potential of non-invasively detecting liver fibrosis. RESULTS: Phantom studies demonstrate that longitudinal waves generated by the driver are mode-converted to shear waves in a distribution governed by diffraction principles. The transcostal approach was determined to be the most effective method for generating shear waves in human studies. Hepatic stiffness measurements in the 13 normal volunteers demonstrated a mean value of 2.0+/-0.2kPa. The shear stiffness measurement in the patient was much higher at 8.5kPa. CONCLUSION: MR Elastography of the liver shows promise as a method to non-invasively detect and characterize diffuse liver disease, potentially reducing the need for biopsy to diagnose hepatic fibrosis.

Inflammatory cells in minor salivary glands of patients with chronic hepatitis C: immunophenotype, pattern of distribution, and comparison with liver samples.

PubMed

Caldeira, Patrícia Carlos; Oliveira e Silva, Karla Rachel; Vidigal, Paula Vieira Teixeira; Grossmann, Soraya de Mattos Camargo; do Carmo, Maria Auxiliadora Vieira

2014-05-01

To characterize the immunophenotype and the distribution of the inflammatory infiltrate (INF) in salivary glands (SG) of patients with chronic hepatitis C, comparing with laboratorial data (genotype, viral load, METAVIR, and HCV RNA in SG), and liver. INF was classified as diffuse or focal. Immunohistochemistry for CD3, CD20, CD8, CD4, CD57, CD68, and S100 was performed in 61 SG and 59 livers. Diffuse INF was more common in SG than in liver. CD3(+), CD20(+), and CD8(+) were the most frequent cells in both tissues, with few CD57(+), CD68(+), and S100(+) cells. CD4(+) cells were common in liver, but rare in SG. Liver presented higher indexes for all markers, except S100(+) (p<0.05). Higher CD3(+), CD20(+), and CD8(+) (p<0.05) were observed in SG with focal infiltrate than with diffuse infiltrate. In liver, CD20(+) and CD3(+) were higher in focal infiltrate, and CD68(+) in diffuse infiltrate (p<0.05). Comparisons with laboratorial data did not show statistical significance. The INF in SG was mainly composed by T and B lymphocytes, mostly cytotoxic T cells. The glandular INF can present differences in composition according to its distribution. A more intense inflammation was observed in liver, but similar cell types were identified in SG, except for CD4(+). Copyright © 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Persistence of chicken anemia virus antigen and inclusions in spontaneous cases of Marek's disease visceral lymphomas in broiler chickens at slaughterhouses.

PubMed

Ahmed, Mohamed Sabry; Ono, Hiroki; Sasaki, Jun; Ochiai, Kenji; Goryo, Masanobu

2016-06-01

The chicken anemia virus (CAV) and Marek's disease virus (MDV) infect chickens worldwide; a single or dual infection by these viruses has a great impact on poultry production. In the present study, we examined the existence of CAV antigen and its inclusions in Marek's disease (MD) lymphomas in chickens in the slaughterhouses of Iwate prefecture, Japan. Forty-nine spleens and 13 livers with different degrees of nodular lesions were histopathologically examined at our laboratory. Grossly, the tested organs showed various sizes and anatomical architectures. Based on the cellular morphology and the infiltrative nature of the neoplastic lymphocytes, MD was confirmed in 76% (37/49) of the spleens and 92% (12/13) of the livers. The lesions of MD, according to the pattern of lymphocytic accumulation in the affected organs, were divided into multifocal, coalesced and diffuse. CAV intranuclear inclusion bodies were detected within the small and the large bizarre lymphocytes of the MD lymphomas in 2 livers and 9 spleens, and the immunostaining test for CAV confirmed the persistence of CAV antigens and inclusions in the neoplastic cells. This study demonstrated the persistence of CAV infection within the neoplastic cells of naturally occurring MD lymphomas in chickens.

Relationship between Non-Alcoholic Fatty Liver Disease and Breast Cancer.

PubMed

Nseir, William; Abu-Rahmeh, Zuhair; Tsipis, Alex; Mograbi, Julnar; Mahamid, Mahmud

2017-04-01

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease which refers to the presence of hepatic steatosis. Breast cancer is now the most common cancer in women and is the leading cause of death from cancer among women. To assess the relationship between NAFLD and newly diagnosed cases of breast cancer. The results of mammography screening examinations in women referred to the Breast Center, Holy Family Hospital, Nazareth during a 4 year period were collected. We identified cases of women who were newly diagnosed with breast cancer and who underwent abdominal computed tomography (CT) within 1 month of the diagnosis. The control group comprised 73 women with normal mammography and breast ultrasonography who underwent abdominal CT within 3 months from the date of the breast cancer screening during the same study period. The control cases were matched by age and body mass index (BMI). We compared the cases with the controls in terms of the presence of diffuse hepatic fatty liver and other known risk factors for breast cancer. Of the 133 women who were screened, 73 with new diagnosis of breast cancer were eligible for the study. NAFLD was found in 33 of the women with breast cancer and in 12 in the control group (45.2% vs.16.4%, respectively, P = 0.002). Multivariate analysis showed NAFLD (odds ratio 2.82, 95% confidence interval 1.2-5.5, P = 0.016) to be associated with breast cancer. NAFLD is associated with breast cancer.

Ultrasound image texture processing for evaluating fatty liver in peripartal dairy cows

NASA Astrophysics Data System (ADS)

Amin, Viren R.; Bobe, Gerd; Young, Jerry; Ametaj, Burim; Beitz, Donald

2001-07-01

The objective of this work is to characterize the liver ultrasound texture as it changes in diffuse disease of fatty liver. This technology could allow non-invasive diagnosis of fatty liver, a major metabolic disorder in early lactation dairy cows. More than 100 liver biopsies were taken from fourteen dairy cows, as a part of the USDA-funded study for effects of glucagon on prevention and treatment of fatty liver. Up to nine liver biopsies were taken from each cow during peripartal period of seven weeks and total lipid content was determined chemically. Just before each liver biopsy was taken, ultrasonic B-mode images were digitally captured using a 3.5 or 5 MHz transducer. Effort was made to capture images that were non-blurred, void of large blood vessels and multiple echoes, and of consistent texture. From each image, a region-of-interest of size 100-by-100 pixels was processed. Texture parameters were calculated using algorithms such as first and second order statistics, 2D Fourier transformation, co-occurrence matrix, and gradient analysis. Many cows had normal liver (3% to 6% total lipid) and a few had developed fatty liver with total lipid up to 15%. The selected texture parameters showed consistent change with changing lipid content and could potentially be used to diagnose early fatty liver non-invasively. The approach of texture analysis algorithms and initial results on their potential in evaluating total lipid percentage is presented here.

The Role of Diffusion-Weighted Magnetic Resonance Imaging in the Differential Diagnosis of Simple and Hydatid Cysts of the Liver.

PubMed

Aksoy, S; Erdil, I; Hocaoglu, E; Inci, E; Adas, G T; Kemik, O; Turkay, R

2018-02-01

The present study indicates that simple and hydatid cysts in liver are a common health problem in Turkey. The aim of the study is to differentiate different types of hydatid cysts from simple cysts by using diffusion-weighted images. In total, 37 hydatid cysts and 36 simple cysts in the liver were diagnosed. We retrospectively reviewed the medical records of the patients who had both ultrasonography and magnetic resonance imaging. We measured apparent diffusion coefficient (ADC) values of all the cysts and then compared the findings. There was no statistically meaningful difference between the ADC values of simple cysts and type 1 hydatid cysts. However, for the other types of hydatid cysts, it is possible to differentiate hydatid cysts from simple cysts using the ADC values. Although in our study we cannot differentiate between type I hydatid cysts and simple cysts in the liver, diffusion-weighted images are very useful to differentiate different types of hydatid cysts from simple cysts using the ADC values.

Improved differentiation between hepatic hemangioma and metastases on diffusion-weighted MRI by measurement of standard deviation of apparent diffusion coefficient.

PubMed

Hardie, Andrew D; Egbert, Robert E; Rissing, Michael S

2015-01-01

Diffusion-weighted magnetic resonance imaging (DW-MR) can be useful in the differentiation of hemangiomata from liver metastasis, but improved methods other than by mean apparent diffusion coefficient (mADC) are needed. A retrospective review identified 109 metastatic liver lesions and 86 hemangiomata in 128 patients who had undergone DW-MR. For each lesion, mADC and the standard deviation of the mean ADC (sdADC) were recorded and compared by receiver operating characteristic analysis. Mean mADC was higher in benign hemangiomata (1.52±0.12 mm(2)/s) than in liver metastases (1.33±0.18 mm(2)/s), but there was significant overlap in values. The mean sdADC was lower in hemangiomata (101±17 mm(2)/s) than metastases (245±25 mm(2)/s) and demonstrated no overlap in values, which was significantly different (P<.0001). Hemangiomata may be better able to be differentiated from liver metastases on the basis of sdADC than by mADC, although further studies are needed. Copyright © 2015 Elsevier Inc. All rights reserved.

Development of Hepatocellular Carcinoma in a Murine Model of Nonalcoholic Steatohepatitis Induced by Use of a High-Fat/Fructose Diet and Sedentary Lifestyle

PubMed Central

Dowman, Joanna K.; Hopkins, Laurence J.; Reynolds, Gary M.; Nikolaou, Nikolaos; Armstrong, Matthew J.; Shaw, Jean C.; Houlihan, Diarmaid D.; Lalor, Patricia F.; Tomlinson, Jeremy W.; Hübscher, Stefan G.; Newsome, Philip N.

2014-01-01

Obesity is increasingly prevalent, strongly associated with nonalcoholic liver disease, and a risk factor for numerous cancers. Here, we describe the liver-related consequences of long-term diet-induced obesity. Mice were exposed to an extended obesity model comprising a diet high in trans-fats and fructose corn syrup concurrent with a sedentary lifestyle. Livers were assessed histologically using the nonalcoholic fatty liver disease (NAFLD) activity score (Kleiner system). Mice in the American Lifestyle-Induced Obesity Syndrome (ALIOS) model developed features of early nonalcoholic steatohepatitis at 6 months (mean NAFLD activity score = 2.4) and features of more advanced nonalcoholic steatohepatitis at 12 months, including liver inflammation and bridging fibrosis (mean NAFLD activity score = 5.0). Hepatic expression of lipid metabolism and insulin signaling genes were increased in ALIOS mice compared with normal chow-fed mice. Progressive activation of the mouse hepatic stem cell niche in response to ALIOS correlated with steatosis, fibrosis, and inflammation. Hepatocellular neoplasms were observed in 6 of 10 ALIOS mice after 12 months. Tumors displayed cytological atypia, absence of biliary epithelia, loss of reticulin, alteration of normal perivenular glutamine synthetase staining (absent or diffuse), and variable α-fetoprotein expression. Notably, perivascular tumor cells expressed hepatic stem cell markers. These studies indicate an adipogenic lifestyle alone is sufficient for the development of nonalcoholic steatohepatitis, hepatic stem cell activation, and hepatocarcinogenesis in wild-type mice. PMID:24650559

Is there evidence for more than two diffusion components in abdominal organs? - A magnetic resonance imaging study in healthy volunteers.

PubMed

Wurnig, Moritz C; Germann, Manon; Boss, Andreas

2018-01-01

The most commonly applied model for the description of diffusion-weighted imaging (DWI) data in perfused organs is bicompartmental intravoxel incoherent motion (IVIM) analysis. In this study, we assessed the ground truth of underlying diffusion components in healthy abdominal organs using an extensive DWI protocol and subsequent computation of apparent diffusion coefficient 'spectra', similar to the computation of previously described T 2 relaxation spectra. Diffusion datasets of eight healthy subjects were acquired in a 3-T magnetic resonance scanner using 68 different b values during free breathing (equidistantly placed in the range 0-1005 s/mm 2 ). Signal intensity curves as a function of the b value were analyzed in liver, spleen and kidneys using non-negative least-squares fitting to a distribution of decaying exponential functions with minimum amplitude energy regularization. In all assessed organs, the typical slow- and fast-diffusing components of the IVIM model were detected [liver: true diffusion D = (1.26 ± 0.01) × 10 -3 mm 2 /s, pseudodiffusion D* = (270 ± 44) × 10 -3 mm 2 /s; kidney cortex: D = (2.26 ± 0.07) × 10 -3 mm 2 /s, D* = (264 ± 78) × 10 -3 mm 2 /s; kidney medulla: D = (1.57 ± 0.28) × 10 -3 mm 2 /s, D* = (168 ± 18) × 10 -3 mm 2 /s; spleen: D = (0.91 ± 0.01) × 10 -3 mm 2 /s, D* = (69.8 ± 0.50) × 10 -3 mm 2 /s]. However, in the liver and kidney, a third component between D and D* was found [liver: D' = (43.8 ± 5.9) × 10 -3 mm 2 /s; kidney cortex: D' = (23.8 ± 11.5) × 10 -3 mm 2 /s; kidney medulla: D' = (5.23 ± 0.93) × 10 -3 mm 2 /s], whereas no third component was detected in the spleen. Fitting with a diffusion kurtosis model did not lead to a better fit of the resulting curves to the acquired data compared with apparent diffusion coefficient spectrum analysis. For a most accurate description of diffusion properties in the liver and the kidneys, a more sophisticated model seems to be required including three diffusion components. Copyright © 2017 John Wiley & Sons, Ltd.

How Effective Are Percutaneous Liver-Directed Therapies in Patients with Non-Colorectal Liver Metastases?

PubMed Central

Vogl, Thomas J.; Emam, Ahmed; Naguib, Nagy N.; Eichler, Katrin; Zangos, Stefan

2015-01-01

Summary Background The purpose of this review is to demonstrate the clinical indications, technical developments, and outcome of liver-directed therapies in interventional oncology of non-colorectal liver metastases. Methods Liver-directed therapies are classified into vascular transarterial techniques such as chemoperfusion (TACP), chemoembolization (TACE), radioembolization (selective internal radiation therapy (SIRT)), and chemosaturation, as well as thermal ablation techniques like microwave ablation (MWA), radiofrequency ablation (RFA), laser-induced thermotherapy (LITT), cryotherapy, and irreversible electroporation (IRE). The authors searched the database PubMed using the following terms: ‘image-guided tumor ablation’, ‘thermal ablation therapies’, ‘liver metastases of uveal melanoma’, ‘neuroendocrine carcinoma’, ‘breast cancer’, and ‘non-colorectal liver metastases’. Results Various combinations of the above-mentioned therapy protocols are possible. In neuroendocrine carcinomas, oligonodular liver metastases are treated successfully via thermal ablation like RFA, LITT, or MWA, and diffuse involvement via TACE or SIRT. Although liver involvement in breast cancer is a systemic disease, non-responding nodular metastases can be controlled via RFA or LITT. In ocular or cutaneous melanoma, thermal ablation is rarely considered as an interventional treatment option, as opposed to TACE, SIRT, or chemosaturation. Rarely liver-directed therapies are used in pancreatic cancer, most likely due to problems such as biliary digestive communications after surgery and the risk of infections. Rare indications for thermal ablation are liver metastases of other primary cancers like non-small cell lung, gastric, and ovarian cancer. Conclusion Interventional oncological techniques play a role in patients with liver-dominant metastases. PMID:26889144

Can diffusion-weighted imaging distinguish between benign and malignant pediatric liver tumors?

PubMed

Caro-Domínguez, Pablo; Gupta, Abha A; Chavhan, Govind B

2018-01-01

There are limited data on utility of diffusion-weighted imaging (DWI) in the evaluation of pediatric liver lesions. To determine whether qualitative and quantitative DWI can be used to differentiate benign and malignant pediatric liver lesions. We retrospectively reviewed MRIs in children with focal liver lesions to qualitatively evaluate lesions noting diffusion restriction, T2 shine-through, increased diffusion, hypointensity on DWI and apparent diffusion coefficient (ADC) maps, and intermediate signal on both, and to measure ADC values. Pathology confirmation or a combination of clinical, laboratory and imaging features, and follow-up was used to determine final diagnosis. We included 112 focal hepatic lesions in 89 children (median age 11.5 years, 51 female), of which 92 lesions were benign and 20 malignant. Interobserver agreement was almost perfect for both qualitative (kappa 0.8735) and quantitative (intraclass correlation coefficient [ICC] 0.96) diffusion assessment. All malignant lesions showed diffusion restriction. Most benign lesions other than abscesses were not restricted. There was significant association of qualitative restriction with malignancy and non-restriction with benignancy (Fisher exact test P<0.0001). Mean normalized ADC values of malignant lesions (1.23x10 -3  mm 2 /s) were lower than benign lesions (1.62x10 -3  mm 2 /s; Student's t-test, P<0.015). However, there was significant overlap of ADC between benign and malignant lesions, with wide range for each diagnosis. Receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.63 for predicting malignancy using an ADC cut-off value of ≤1.20x10 -3  mm 2 /s, yielding a sensitivity of 78% and a specificity of 54% for differentiating malignant from benign lesions. Qualitative diffusion restriction in pediatric liver lesions is a good predictor of malignancy and can help to differentiate between benign and malignant lesions, in conjunction with conventional MR sequences. Even though malignant lesions demonstrated significantly lower ADC values than benign lesions, the use of quantitative diffusion remains limited in its utility for distinguishing them because of the significant overlap and wide ranges of ADC values.

Simultaneous Multislice Accelerated Free-Breathing Diffusion-Weighted Imaging of the Liver at 3T.

PubMed

Obele, Chika C; Glielmi, Christopher; Ream, Justin; Doshi, Ankur; Campbell, Naomi; Zhang, Hoi Cheung; Babb, James; Bhat, Himanshu; Chandarana, Hersh

2015-10-01

To perform image quality comparison between accelerated multiband diffusion acquisition (mb2-DWI) and conventional diffusion acquisition (c-DWI) in patients undergoing clinically indicated liver MRI. In this prospective study 22 consecutive patients undergoing clinically indicated liver MRI on a 3-T scanner equipped to perform multiband diffusion-weighed imaging (mb-DWI) were included. DWI was performed with single-shot spin-echo echo-planar technique with fat-suppression in free breathing with matching parameters when possible using c-DWI, mb-DWI, and multiband DWI with a twofold acceleration (mb2-DWI). These diffusion sequences were compared with respect to various parameters of image quality, lesion detectability, and liver ADC measurements. Accelerated mb2-DWI was 40.9% faster than c-DWI (88 vs. 149 s). Various image quality parameter scores were similar or higher on mb2-DWI when compared to c-DWI. The overall image quality score (averaged over the three readers) was significantly higher for mb-2 compared to c-DWI for b = 0 s/mm(2) (3.48 ± 0.52 vs. 3.21 ± 0.54; p = 0.001) and for b = 800 s/mm(2) (3.24 ± 0.76 vs. 3.06 ± 0.86; p = 0.010). Total of 25 hepatic lesions were visible on mb2-DWI and c-DWI, with identical lesion detectability. There was no significant difference in liver ADC between mb2-DWI and c-DWI (p = 0.12). Bland-Altman plot demonstrates lower mean liver ADC with mb2-DWI compared to c-DWI (by 0.043 × 10(-3) mm(2)/s or 3.7% of the average ADC). Multiband technique can be used to increase acquisition speed nearly twofold for free-breathing DWI of the liver with similar or improved overall image quality and similar lesion detectability compared to conventional DWI.

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].

Effect of disease progression on liver apparent diffusion coefficient values in a murine model of NASH at 11.7 Tesla MRI.

PubMed

Anderson, Stephan W; Soto, Jorge A; Milch, Holly N; Ozonoff, Al; O'Brien, Michael; Hamilton, James A; Jara, Hernan J

2011-04-01

To evaluate the apparent diffusion coefficient (ADC) values of liver in a murine model of non-alcoholic steatohepatitis using 11.7 Tesla (T) MRI. This animal study was IACUC approved. Seventeen male C57BL/6 mice were divided into control (n = 3) and experimental groups (n = 14) fed a methionine-deficient choline-deficient (MCD) diet to induce steatohepatitis. Livers underwent ex vivo diffusion-weighted MR imaging and ADC maps were calculated. A pathologist determined subjective scores of steatosis, classified from 0 to 3. Digital image analysis was used to determine percentage areas of steatosis. Graphs comparing ADC to subjective and digital image analysis (DIA) determinations of steatosis were plotted. Subjective assessments of steatosis ranged up to values of 3 and DIA determined areas of steatosis to range up to approximately 16%. ADC values approximated 800 × 10(-6) mm(2) /s (range, 749-811 × 10(-6) mm(2) /s, mean 786 × 10(-6) mm(2) /s) in controls and 500 × 10(-6) mm(2) /s (range, 478-733 × 10(-6) mm(2) /s, mean 625 × 10(-6) mm(2) /s) in experimental mice. Moderate correlation between ADC and subjective scores of steatosis (R = -0.56) was observed. Strong correlation between ADC values and percentage areas of steatosis was between ADC values and percentage areas of steatosis was observed greater (R = -0.81) and very strong correlation was observed with the exclusion of a single outlying data point (R = -0.91). Based on the comparison of ADC values and steatosis determinations by DIA, increasing degrees of steatosis are seen to result in decreased hepatic ADC values. Copyright © 2011 Wiley-Liss, Inc.

Longitudinal brain white matter alterations in minimal hepatic encephalopathy before and after liver transplantation.

PubMed

Lin, Wei-Che; Chou, Kun-Hsien; Chen, Chao-Long; Chen, Hsiu-Ling; Lu, Cheng-Hsien; Li, Shau-Hsuan; Huang, Chu-Chung; Lin, Ching-Po; Cheng, Yu-Fan

2014-01-01

Cerebral edema is the common pathogenic mechanism for cognitive impairment in minimal hepatic encephalopathy. Whether complete reversibility of brain edema, cognitive deficits, and their associated imaging can be achieved after liver transplantation remains an open question. To characterize white matter integrity before and after liver transplantation in patients with minimal hepatic encephalopathy, multiple diffusivity indices acquired via diffusion tensor imaging was applied. Twenty-eight patients and thirty age- and sex-matched healthy volunteers were included. Multiple diffusivity indices were obtained from diffusion tensor images, including mean diffusivity, fractional anisotropy, axial diffusivity and radial diffusivity. The assessment was repeated 6-12 month after transplantation. Differences in white matter integrity between groups, as well as longitudinal changes, were evaluated using tract-based spatial statistical analysis. Correlation analyses were performed to identify first scan before transplantation and interval changes among the neuropsychiatric tests, clinical laboratory tests, and diffusion tensor imaging indices. After transplantation, decreased water diffusivity without fractional anisotropy change indicating reversible cerebral edema was found in the left anterior cingulate, claustrum, postcentral gyrus, and right corpus callosum. However, a progressive decrease in fractional anisotropy and an increase in radial diffusivity suggesting demyelination were noted in temporal lobe. Improved pre-transplantation albumin levels and interval changes were associated with better recoveries of diffusion tensor imaging indices. Improvements in interval diffusion tensor imaging indices in the right postcentral gyrus were correlated with visuospatial function score correction. In conclusion, longitudinal voxel-wise analysis of multiple diffusion tensor imaging indices demonstrated different white matter changes in minimal hepatic encephalopathy patients. Transplantation improved extracellular cerebral edema and the results of associated cognition tests. However, white matter demyelination may advance in temporal lobe.

Nodular regenerative hyperplasia: Evolving concepts on underdiagnosed cause of portal hypertension

PubMed Central

Hartleb, Marek; Gutkowski, Krzysztof; Milkiewicz, Piotr

2011-01-01

Nodular regenerative hyperplasia (NRH) is a rare liver condition characterized by a widespread benign transformation of the hepatic parenchyma into small regenerative nodules. NRH may lead to the development of non-cirrhotic portal hypertension. There are no published systematic population studies on NRH and our current knowledge is limited to case reports and case series. NRH may develop via autoimmune, hematological, infectious, neoplastic, or drug-related causes. The disease is usually asymptomatic, slowly or non-progressive unless complications of portal hypertension develop. Accurate diagnosis is made by histopathology, which demonstrates diffuse micronodular transformation without fibrous septa. Lack of perinuclear collagen tissue distinguishes NRH from typical regenerative nodules in the cirrhotic liver. While the initial treatment is to address the underlying disease, ultimately the therapy is directed to the management of portal hypertension. The prognosis of NRH depends on both the severity of the underlying illness and the prevention of secondary complications of portal hypertension. In this review we detail the epidemiology, pathogenesis, diagnosis, management, and prognosis of NRH. PMID:21472097

Adverse effects of chronic exposure to nonylphenol on non-alcoholic fatty liver disease in male rats

PubMed Central

Yu, Jie; Yang, Xuesong; Luo, Ya; Yang, Xuefeng; Yang, Mengxue; Yang, Jin; Zhou, Jie; Gao, Feng; He, Liting; Xu, Jie

2017-01-01

Endocrine-disrupting chemical (EDC) has been thought to play a role in non-alcoholic fatty liver disease (NAFLD). However, the toxic effects of Nonylphenol (NP), an EDC, on non-alcoholic fatty liver disease have never been elaborated. This study aimed to investigate whether exposure to NP could induce NAFDL, a promoting effect of high-sucrose-high-fat diet (HSHFD) on the adverse effects caused by NP was evaluated. Fourth eight male rats were assigned to four groups and each group was treated with a specific testing sample: normal-diet (ND) control group (C-ND); normal diet plus NP (180mg/kg/day) group (NP-ND); high-sucrose-high-fat-diet control group (C-HSHFD); HSHFD plus NP (180mg/kg/day) group (NP-HSHFD). At the age of 80 day, sonogram presents diffusely increased hepatic echogenicity in the NP-HSHFD group. The oblique diameter of liver in the NP-HSHFD group was significantly bigger than that in both the C-ND and NP-ND groups. At the age of 90 day, exposure to NP-HSHFD and NP-ND caused a significant increase in NP concentration in liver as compared to the C-ND group. The rats in the groups treated with NP+ND, HSHFD and NP+HSHFD produced significant increases in the body weight, fat weight and FMI, respectively, when compared to the C-ND group. The liver weight and hepatosomatic indexes (HIS) of rats in the NP-HSHFD group are higher than those in the C-HSHFD group. Exposure to NP-HSHFD induced the increases in plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) as compared to the C-ND group. Morphological examination of liver tissue from rats exposed to NP+HSHFD shown steatosis with marked accumulation of lipid droplets, hepatocellular ballooning degeneration and inflammatory cell infiltration. Chronic exposure to NP might induce NAFLD in male rats. The high-sucrose-high-fat diet accelerates and exacerbates the development of NAFLD caused by NP exposure. PMID:28686624

Development of hepatocellular carcinoma in a murine model of nonalcoholic steatohepatitis induced by use of a high-fat/fructose diet and sedentary lifestyle.

PubMed

Dowman, Joanna K; Hopkins, Laurence J; Reynolds, Gary M; Nikolaou, Nikolaos; Armstrong, Matthew J; Shaw, Jean C; Houlihan, Diarmaid D; Lalor, Patricia F; Tomlinson, Jeremy W; Hübscher, Stefan G; Newsome, Philip N

2014-05-01

Obesity is increasingly prevalent, strongly associated with nonalcoholic liver disease, and a risk factor for numerous cancers. Here, we describe the liver-related consequences of long-term diet-induced obesity. Mice were exposed to an extended obesity model comprising a diet high in trans-fats and fructose corn syrup concurrent with a sedentary lifestyle. Livers were assessed histologically using the nonalcoholic fatty liver disease (NAFLD) activity score (Kleiner system). Mice in the American Lifestyle-Induced Obesity Syndrome (ALIOS) model developed features of early nonalcoholic steatohepatitis at 6 months (mean NAFLD activity score = 2.4) and features of more advanced nonalcoholic steatohepatitis at 12 months, including liver inflammation and bridging fibrosis (mean NAFLD activity score = 5.0). Hepatic expression of lipid metabolism and insulin signaling genes were increased in ALIOS mice compared with normal chow-fed mice. Progressive activation of the mouse hepatic stem cell niche in response to ALIOS correlated with steatosis, fibrosis, and inflammation. Hepatocellular neoplasms were observed in 6 of 10 ALIOS mice after 12 months. Tumors displayed cytological atypia, absence of biliary epithelia, loss of reticulin, alteration of normal perivenular glutamine synthetase staining (absent or diffuse), and variable α-fetoprotein expression. Notably, perivascular tumor cells expressed hepatic stem cell markers. These studies indicate an adipogenic lifestyle alone is sufficient for the development of nonalcoholic steatohepatitis, hepatic stem cell activation, and hepatocarcinogenesis in wild-type mice. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

[Liver Atrophy and Failure Associated with Paclitaxel and Bevacizumab Combination Therapy for Metastatic Breast Cancer].

PubMed

Yamamoto, Mari; Ikeda, Masahiko; Kubo, Shinichiro; Tsukioki, Takahiro; Nakamoto, Shougo

2016-07-01

We managed 6 cases of severe liver atrophy and failure associated with paclitaxel and bevacizumab combination therapy (PB therapy)for HER2-negative metastatic breast cancer. In this case-controlstudy, we examined the records of these 6 patients to investigate past treatment, medication history, and degree of atrophy, and compared their data with that of 67 patients without liver atrophy. The degree of the liver atrophy used SYNAPSE VINCENT®of the image analysis software. The results showed that patients with liver atrophy had a longer pretreatment period than those without liver atrophy(33.5 months vs 15.5 months), and they also experienced a longer median time to treatment failure with PB therapy than other patients(11 months vs 6 months). The ratio of individuals presenting with diffuse liver metastasis among patients with liver metastasis was 80% with liver atrophy, compared to 8% without liver atrophy. The degree of liver atrophy was an average of 67%in terms of volume ratio before/after PB therapy(57-82%). The individualwith the greatest extent of liver atrophy died of liver failure, not as a result of breast cancer progression. The direct causal link between bevacizumab and liver atrophy and failure is unclear, but the individuals in this study had a long previous history of treatment, and diffuse liver metastases may develop in patients undergoing long periods of PB therapy, which may also cause liver atrophy; therefore, the possibility of liver failure should be considered in such cases.

Acute on chronic liver failure in a patient with sickle cell anaemia (HbSS)

PubMed Central

Im, Dana DaEun; Essien, Utibe; DePasse, Jacqueline W; Chiappa, Victor

2015-01-01

A man in his late 40s with sickle cell anaemia (HbSS) presented to the emergency department with 2 weeks of diffuse oedema, increased abdominal girth and dyspnoea. His anasarca was thought to be indicative of an acute decompensation of his known liver cirrhosis with transfusion-induced haemosiderosis. While his anasarca improved with diuresis, his direct hyperbilirubinaemia suddenly worsened without any signs of haemolysis, biliary disease or obstruction. He also developed an acute worsening in serum creatinine (1.17–7.0 mg/dL in 7 days) despite subsequent treatment for presumed hepatorenal syndrome (HRS). Given his clinical decline, the patient's goals of care were transitioned to comfort measures only. His clinical presentation and rapid liver and renal deterioration were most typical of sickle cell intrahepatic cholestasis (SCIC). SCIC can lead to rapid deterioration in renal function and can be mistaken for HRS. When SCIC is suspected, consideration of exchange transfusions should be made early. PMID:26135492

Diffuse Reflectance Spectroscopy for Surface Measurement of Liver Pathology.

PubMed

Nilsson, Jan H; Reistad, Nina; Brange, Hannes; Öberg, Carl-Fredrik; Sturesson, Christian

2017-01-01

Liver parenchymal injuries such as steatosis, steatohepatitis, fibrosis, and sinusoidal obstruction syndrome can lead to increased morbidity and liver failure after liver resection. Diffuse reflectance spectroscopy (DRS) is an optical measuring method that is fast, convenient, and established. DRS has previously been used on the liver with an invasive technique consisting of a needle that is inserted into the parenchyma. We developed a DRS system with a hand-held probe that is applied to the liver surface. In this study, we investigated the impact of the liver capsule on DRS measurements and whether liver surface measurements are representative of the whole liver. We also wanted to confirm that we could discriminate between tumor and liver parenchyma by DRS. The instrumentation setup consisted of a light source, a fiber-optic contact probe, and two spectrometers connected to a computer. Patients scheduled for liver resection due to hepatic malignancy were included, and DRS measurements were performed on the excised liver part with and without the liver capsule and alongside a newly cut surface. To estimate the scattering parameters and tissue chromophore volume fractions, including blood, bile, and fat, the measured diffuse reflectance spectra were applied to an analytical model. In total, 960 DRS spectra from the excised liver tissue of 18 patients were analyzed. All factors analyzed regarding tumor versus liver tissue were significantly different. When measuring through the capsule, the blood volume fraction was found to be 8.4 ± 3.5%, the lipid volume fraction was 9.9 ± 4.7%, and the bile volume fraction was 8.2 ± 4.6%. No differences could be found between surface measurements and cross-sectional measurements. In measurements with/without the liver capsule, the differences in volume fraction were 1.63% (0.75-2.77), -0.54% (-2.97 to 0.32), and -0.15% (-1.06 to 1.24) for blood, lipid, and bile, respectively. This study shows that it is possible to manage DRS measurements through the liver capsule and that surface DRS measurements are representative of the whole liver. The results are consistent with data published earlier on the combination of liver chromophores. The results encourage us to proceed with in vivo measurements for further quantification of the liver's composition and assessment of parenchymal damage such as steatosis and fibrosis grade. © 2016 S. Karger AG, Basel.

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

MRI-based staging of hepatic fibrosis: Comparison of intravoxel incoherent motion diffusion-weighted imaging with magnetic resonance elastography.

PubMed

Ichikawa, Shintaro; Motosugi, Utaroh; Morisaka, Hiroyuki; Sano, Katsuhiro; Ichikawa, Tomoaki; Enomoto, Nobuyuki; Matsuda, Masanori; Fujii, Hideki; Onishi, Hiroshi

2015-07-01

To evaluate the use of intravoxel incoherent motion (IVIM) imaging for staging hepatic fibrosis, and compare its staging ability with that of magnetic resonance elastography (MRE). This study included 129 patients with pathologically staged liver fibrosis, and 53 patients with healthy livers. All patients underwent both MRE and IVIM imaging. Four diffusivity indices were calculated with 11 b-values; slow diffusion coefficient related to molecular diffusion (D), fast diffusion coefficient related to perfusion in micro-vessels (D*), perfusion-related diffusion fraction (f), and apparent diffusion coefficient (ADC). Receiver operating characteristic curve analysis was performed to determine the accuracy of IVIM imaging and MRE for staging hepatic fibrosis. D*, f, and ADC values decreased significantly with fibrosis stage (P < 0.0124), and liver stiffness increased (P < 0.0001). The Az value of MRE was significantly higher than that of D* for all fibrosis stages (D* vs. MRE for ≥ F1, 0.851 vs. 0.992 [P < 0.0001]; ≥ F2, 0.898 vs. 0.998 [P = 0.0003]; ≥ F3, 0.904 vs. 0.995 [P = 0.0004]; F4, 0.885 vs. 0.996 [P < 0.0001]). IVIM imaging is a useful technique for evaluating hepatic fibrosis, but MRE is better able to discriminate fibrosis stages than IVIM imaging. © 2014 Wiley Periodicals, Inc.

Metabonomics Research Progress on Liver Diseases.

PubMed

Yu, Mengqian; Zhu, Ying; Cong, Qingwei; Wu, Chunyan

2017-01-01

Metabolomics as the new omics technique develops after genomics, transcriptomics, and proteomics and has rapid development at present. Liver diseases are worldwide public health problems. In China, chronic hepatitis B and its secondary diseases are the common liver diseases. They can be diagnosed by the combination of history, virology, liver function, and medical imaging. However, some patients seldom have relevant physical examination, so the diagnosis may be delayed. Many other liver diseases, such as drug-induced liver injury (DILI), alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), and autoimmune liver diseases, still do not have definite diagnostic markers; the diagnosis consists of history, medical imaging, and the relevant score. As a result, the clinical work becomes very complex. So it has broad prospects to explore the specific and sensitive biomarkers of liver diseases with metabolomics. In this paper, there are several summaries which are related to the current research progress and application of metabolomics on biomarkers of liver diseases.

Hepatocellular Carcinoma in the Cirrhotic Liver: Evaluation Using Computed Tomography and Magnetic Resonance Imaging.

PubMed

Coskun, Mehmet

2017-03-01

Hepatocellular carcinoma is the fifth most common tumor in patients worldwide and the third most common cause of cancer-related death, after lung and stomach cancer. Cirrhosis of the liver is the strongest predisposing factor for hepatocellular carcinoma, with approximately 80% of cases of hepatocellular carcinoma developing in a cirrhotic liver. The annual incidence of hepatocellular carcinoma is 2.0% to 6.6% in patients with cirrhosis compared with 0.4% in patients without cirrhosis. The 5-year survival rates of patients undergoing curative therapies for hepatocellular carcinoma, including liver transplant, hepatic resection, and percutaneous ablative techniques, range between 40% and 75%. Orthotropic liver transplant offers the prima facie cure for both hepatocellular carcinoma and liver cirrhosis. In hepatocellular carcinoma confined to the liver without macrovascular invasion, patients with a single tumor ≤ 5 cm or up to 3 tumors ≤ 3 cm each had a 5-year survival rate of 75% and a disease-free survival rate of 83%. In the adult population, liver transplant for hepatocellular carcinoma yields good results for patients whose tumor masses do not exceed the Milan criteria. The diagnosis of hepatocellular carcinoma using imaging tests has had a substantial impact on transplant decisions. Radiologists should be aware of this responsibility and exercise the utmost scrutiny before making a diagnosis of hepatocellular carcinoma. Erroneous diagnosis of hepatocellular carcinoma based on imaging tests could deny deserving patients the opportunity of a life-saving liver transplant and result in unnecessary liver transplants for others. Contrast-enhanced magnetic resonance imaging and helical computed tomography are the best imaging techniques currently available for the noninvasive diagnosis of hepatocellular carcinoma. With technological advances in hardware and software, diffusion-weighted imaging can be readily applied to the liver with resulting improved image quality.

Radiologic-Pathologic Analysis of Contrast-enhanced and Diffusion-weighted MR Imaging in Patients with HCC after TACE: Diagnostic Accuracy of 3D Quantitative Image Analysis

PubMed Central

Chapiro, Julius; Wood, Laura D.; Lin, MingDe; Duran, Rafael; Cornish, Toby; Lesage, David; Charu, Vivek; Schernthaner, Rüdiger; Wang, Zhijun; Tacher, Vania; Savic, Lynn Jeanette; Kamel, Ihab R.

2014-01-01

Purpose To evaluate the diagnostic performance of three-dimensional (3Dthree-dimensional) quantitative enhancement-based and diffusion-weighted volumetric magnetic resonance (MR) imaging assessment of hepatocellular carcinoma (HCChepatocellular carcinoma) lesions in determining the extent of pathologic tumor necrosis after transarterial chemoembolization (TACEtransarterial chemoembolization). Materials and Methods This institutional review board–approved retrospective study included 17 patients with HCChepatocellular carcinoma who underwent TACEtransarterial chemoembolization before surgery. Semiautomatic 3Dthree-dimensional volumetric segmentation of target lesions was performed at the last MR examination before orthotopic liver transplantation or surgical resection. The amount of necrotic tumor tissue on contrast material–enhanced arterial phase MR images and the amount of diffusion-restricted tumor tissue on apparent diffusion coefficient (ADCapparent diffusion coefficient) maps were expressed as a percentage of the total tumor volume. Visual assessment of the extent of tumor necrosis and tumor response according to European Association for the Study of the Liver (EASLEuropean Association for the Study of the Liver) criteria was performed. Pathologic tumor necrosis was quantified by using slide-by-slide segmentation. Correlation analysis was performed to evaluate the predictive values of the radiologic techniques. Results At histopathologic examination, the mean percentage of tumor necrosis was 70% (range, 10%–100%). Both 3Dthree-dimensional quantitative techniques demonstrated a strong correlation with tumor necrosis at pathologic examination (R2 = 0.9657 and R2 = 0.9662 for quantitative EASLEuropean Association for the Study of the Liver and quantitative ADCapparent diffusion coefficient, respectively) and a strong intermethod agreement (R2 = 0.9585). Both methods showed a significantly lower discrepancy with pathologically measured necrosis (residual standard error [RSEresidual standard error] = 6.38 and 6.33 for quantitative EASLEuropean Association for the Study of the Liver and quantitative ADCapparent diffusion coefficient, respectively), when compared with non-3Dthree-dimensional techniques (RSEresidual standard error = 12.18 for visual assessment). Conclusion This radiologic-pathologic correlation study demonstrates the diagnostic accuracy of 3Dthree-dimensional quantitative MR imaging techniques in identifying pathologically measured tumor necrosis in HCChepatocellular carcinoma lesions treated with TACEtransarterial chemoembolization. © RSNA, 2014 Online supplemental material is available for this article. PMID:25028783

Does apparent diffusion coefficient predict the degree of liver regeneration of donor and recipient after living donor liver transplantation?

PubMed

Morita, Koichiro; Nishie, Akihiro; Asayama, Yoshiki; Ishigami, Kousei; Ushijima, Yasuhiro; Takayama, Yukihisa; Okamoto, Daisuke; Fujita, Nobuhiro; Ikegami, Toru; Yoshizumi, Tomoharu; Shirabe, Ken; Honda, Hiroshi

2017-05-01

To elucidate the relationship between the ADCs of the liver graft and the remnant liver and the degree of liver regeneration in LDLT. 15 recipients and 15 corresponding donors underwent magnetic resonance imaging and computed tomography 1-2 weeks after living donor liver transplantation (LDLT). For diffusion-weighted imaging (DWI), a single-shot echo-planar sequence with b-factors of 0, 500, and 1000s/mm 2 was scanned. ADCs of the liver parenchyma were calculated at b factors of 0 and 500 and 1000 (ADC 0-500-1000) or 0 and 500 (ADC 0-500) or 500 and 1000 (ADC 500-1000). The liver volume ratio at LDLT, the mean ADCs and the regeneration rate were compared between the graft and the remnant liver using paired-t tests. The mean liver volume ratio of the recipients (41.3±9.8%) tended to be smaller than that of the donors (51.8±13.8%). The mean ADC 0-500 of the remnant liver (1.72±0.33) was significantly higher than that of the graft (1.43±0.32). The regeneration rate of the graft (2.07±0.41) was significantly higher than that of the remnant liver (1.53±0.49). ADC 0-500 can describe differences in blood perfusion between liver grafts and the remnant liver according to the degree of liver regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

Test-retest reliability of diffusion tensor imaging of the liver at 3.0 T.

PubMed

Girometti, Rossano; Maieron, Marta; Lissandrello, Giovanni; Bazzocchi, Massimo; Zuiani, Chiara

2015-06-01

This study was done to evaluate test-retest reliability of liver diffusion tensor imaging (LDTI). Ten healthy volunteers (median age 23 years) underwent two LDTI scans on a 3.0 T magnet during two imaging sessions separated by 2 weeks (session-1/-2, respectively). Fifteen gradient directions and b values of 0-1,000 s/mm(2) were used. Two radiologists in consensus assessed liver apparent diffusion coefficient (ADC) and fraction of anisotropy (FA) values on ADC and FA maps at four reference levels, namely: right upper level (RUL), right lower level (RLL), left upper level (LUL) and left lower level (LLL). We then assessed (a) whether ADC and FA values overlapped when measured on different levels within the same imaging session or between different imaging sessions; (b) the degree of variability on an intra-session and inter-session basis, respectively, using the coefficient of variation (CV). In sessions 1 and 2, the ADC/FA values were significantly larger in the left liver lobe (LUL/LLL) compared to right liver lobe (RUL/RLL) (p < 0.05/6). Intra-session CVs were 9.51 % (session 1) and 9.73 % (session 2) for ADC, and 12.93 % (session 1) and 11.82 % (session 2) for FA, respectively. When comparing RUL, RLL, LUL and LLL on an inter-session basis, CVs were 6.52, 8.20, 6.52 and 11.06 % for ADC, and 15.42, 15.80, 15.42 and 6.80 % for FA, respectively. LDTI provides consistent and repeatable measurements. However, since larger left lobe ADC/FA values can be attributed to artefacts, right lobe values should be considered the most reliable measurements of water diffusivity within the liver.

An autologous in situ tumor vaccination approach for hepatocellular carcinoma. 2. Tumor-specific immunity and cure after radio-inducible suicide gene therapy and systemic CD40-ligand and Flt3-ligand gene therapy in an orthotopic tumor model.

PubMed

Kawashita, Yujo; Deb, Niloy J; Garg, Madhur K; Kabarriti, Rafi; Fan, Zuoheng; Alfieri, Alan A; Roy-Chowdhury, Jayanta; Guha, Chandan

2014-08-01

Diffuse hepatocellular carcinoma (HCC) is a lethal disease that radiation therapy (RT) currently has a limited role in treating because of the potential for developing fatal radiation-induced liver disease. However, recently diffuse HCC, "radio-inducible suicide gene therapy" has been shown to enhance local tumor control and residual microscopic disease within the liver for diffuse HCC, by using a combination of chemoactivation and molecular radiosensitization. We have demonstrated that the addition of recombinant adenovirus-expressing human Flt3 ligand (Adeno-Flt3L) after radio-inducible suicide gene therapy induced a Th1-biased, immune response and enhanced tumor control in an ectopic model of HCC. We hypothesized that sequential administration of recombinant adenovirus-expressing CD40L (Adeno-CD40L) could further potentiate the efficacy of our trimodal therapy with RT + HSV-TK + Adeno-Flt3L. We examined our hypothesis in an orthotopic model of diffuse HCC using BNL1ME A.7R.1 (BNL) cells in Balb/c mice. BNL murine hepatoma cells (5 × 10(4)) transfected with an expression vector of HSV-TK under the control of a radiation-inducible promoter were injected intraportally into BALB/cJ mice. Fourteen days after the HCC injection, mice were treated with a 25 Gy dose of radiation to the whole liver, followed by ganciclovir (GCV) treatment and systemic adenoviral cytokine gene therapy (Flt3L or CD40L or both). Untreated mice died in 27 ± 4 days. Radiation therapy alone had a marginal effect on survival (median = 35 ± 7 days) and the addition of HSV-TK/GCV gene therapy improved the median survival to 47 ± 6 days. However, the addition of Adeno-Flt3L to radiation therapy and HSV-TK/GCV therapy significantly (P = 0.0005) increased survival to a median of 63 ± 20 days with 44% (7/16) of the animals still alive 116 days after tumor implantation. The curative effect of Flt3L was completely abolished when using immunodeficient nude mice or mice depleted for CD4, CD8 and natural killer cells. The addition of Adeno-CD40L further improved the median survival of animals to 80 ± 15 days and this effect was abolished only when using anti-CD8 antibodies. Chromium-51 (51Cr) release assay showed cytotoxic T lymphocyte (CTL) activation, suggesting efficient dendritic cell (DC) activation with CTL activation after the treatment. Furthermore, when surviving mice were rechallenged with BNL-ETK cells on the foot pad, RT + HSV-TK/GCV + Flt3L + CD40L-treated mice developed a small tumor on day 56 but the tumor eventually disappeared after 105 days. Mice treated with RT + HSV-TK/GCV + Flt3L showed a slowed tumor growth curve compared with untreated mice. Therefore, combination therapy using Flt3L to induce DC proliferation and CD40L to enhance DC maturation holds great promise for immunomodulation of radiation therapy to enhance HCC tumor control and prevent progression of disease in patients with diffuse HCC.

[Extracorporeal reconstruction of arteries of a transplant of the liver for its subsequent implantation and surgical aspects of arterial anatomy the hepatoduodenal area].

PubMed

Khubutiia, M Sh; Guliaev, V A; Novruzbekov, M S; Lemenev, V L; Driaev, V T

2014-01-01

Orthotopic liver transplantation (OLT) remains the only and radical method of treating patients with terminal stages of chronic diffuse hepatic diseases (cirrhoses), of patients with various congenital metabolic lesions of the liver, autoimmune diseases characterized by lesions of bile ducts, as well as series of both primary and secondary tumorous hepatic lesions. Liver transplantation is one of the most complicated operative interventions. Difficulty of OLT is determined by multifactorial and well-coordinated work of various medical services at the pre-, intra- and postoperative stage of management. One of the important components of success in transplantation consists in providing adequate arterial blood flow of the transplanted organ, which is achieved by extracorporeal reconstruction of the transplant. Variants of arterial blood supply of the liver are observed in each third donor. These anatomical peculiarities increase probability of a surgical error, which is considerably higher if not taking into consideration the complicated anatomy of the donor organ and its misalignment with the anatomical peculiarities of the recipient. Surgeon's responsibility is especially great during taking out the liver from the donor, as well as during its preparation for implantation. Procurement of the liver and pancreas from the same donor for transplantation to two different recipients may be accompanied and followed by the so-called conflict of interests which the surgeon has to decide in favour of the both during procurement of the organ for its extracorporeal processing. The sequence of the presented surgical manipulations on hepatic and pancreatic vessels, as well as anatomical reference points make it possible to preserve the vessels of the maximum length for the both organs. A wide variety of the structure of hepatic vessels may be divided into three types, depending upon the number of the sources of arterial blood supply.

Hepatocellular carcinoma with both fibrolamellar and classical components: an unusual morphological pattern.

PubMed

Castro-Villabón, Diana; Barrera-Herrera, Luis E; Rodríguez-Urrego, Paula A; Hudacko, Rachel; Vera, Alonso; Álvarez, Johanna; Andrade, Rafael; López, Rocío

2015-01-01

Fibrolamellar carcinoma (FLC) is an uncommon form of primary liver malignancy with unique clinical, histological, and biological characteristics. It is usually seen in young adults without underlying liver disease. Histologically, it shows large cells with abundant eosinophilic cytoplasm, large vesicular nuclei, prominent nucleoli, and lamellar type fibrosis. In contrast, classical hepatocellular carcinoma (HCC) is typically present in elderly male patients with cirrhosis. It is the most common histological subtype, and it is characterized by its resemblance to the normal liver, both in its growth pattern and its cytology. The unusual case of a liver carcinoma that presented with histological features of both FLC and classical HCC is herein reported. This was the case of a 37-year-old female complaining of diffuse abdominal discomfort and epigastric pain for two months. She was referred to us for further management after she was diagnosed with HCC in a noncirrhotic liver. She underwent a left-sided hepatectomy. A yellow nodular mass with well-defined borders and a necrotic center was present in the resection specimen. The morphological features and immunohistochemical studies were consistent with a diagnosis of FLC mixed with classical HCC. The patient was followed up for five months, and no signs of recurrence were evident.

[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.

The global burden of liver disease: the major impact of China.

PubMed

Wang, Fu-Sheng; Fan, Jian-Gao; Zhang, Zheng; Gao, Bin; Wang, Hong-Yang

2014-12-01

Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus [HBV]), nonalcoholic fatty liver disease, and alcoholic liver disease, affect approximately 300 million people. The establishment of the Expanded Program on Immunization in 1992 has resulted in a substantial decline in the number of newly HBV-infected patients; however, the number of patients with alcoholic and nonalcoholic fatty liver diseases is rising at an alarming rate. Liver cancer, one of the most deadly cancers, is the second-most common cancer in China. Approximately 383,000 people die from liver cancer every year in China, which accounts for 51% of the deaths from liver cancer worldwide. Over the past 10 years, China has made some significant efforts to shed its "leader in liver diseases" title by investing large amounts of money in funding research, vaccines, and drug development for liver diseases and by recruiting many Western-trained hepatologists and scientists. Over the last two decades, hepatologists and scientists in China have made significant improvements in liver disease prevention, diagnosis, management, and therapy. They have been very active in liver disease research, as shown by the dramatic increase in the number of publications in Hepatology. Nevertheless, many challenges remain that must be tackled collaboratively. In this review, we discuss the epidemiology and characteristics of liver diseases and liver-related research in China. © 2014 by the American Association for the Study of Liver Diseases.

THE RESPONSE OF DISSEMINATED RETICULUM CELL SARCOMA TO THE INTRAVENOUS INJECTION OF COLLOIDAL RADIOACTIVE GOLD

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

Rubin, Philip; Levitt, Seymour H.

1963-06-15

Case histories of two patients treated with colloidal radiogold for diffuse reticulum cell sarcoma are presented. Further analysis of the method is suggested by the unusually long survival time of one of the patients. It was concluded that, although external radiotherapy remains the treatment of choice in localized reticulum cell sarcoma, intravenous colloidal radiogold may be a useful agent in lymphosarcomas with diffuse minute neoplastic liver and spleen involvements. Intravenous colloidal radiogold can produce bone marrow depression and thrombocytopenia which can lead to death. This factor tends to argue against therapeutic use of the agent. It is suggested that nomore » more than 50 mC Au/sup 198/ intravenously should be used for treatment of this disease. (R.M.G.)« less

Liver fibrosis: in vivo evaluation using intravoxel incoherent motion-derived histogram metrics with histopathologic findings at 3.0 T.

PubMed

Hu, Fubi; Yang, Ru; Huang, Zixing; Wang, Min; Zhang, Hanmei; Yan, Xu; Song, Bin

2017-12-01

To retrospectively determine the feasibility of intravoxel incoherent motion (IVIM) imaging based on histogram analysis for the staging of liver fibrosis (LF) using histopathologic findings as the reference standard. 56 consecutive patients (14 men, 42 women; age range, 15-76, years) with chronic liver diseases (CLDs) were studied using IVIM-DWI with 9 b-values (0, 25, 50, 75, 100, 150, 200, 500, 800 s/mm 2 ) at 3.0 T. Fibrosis stage was evaluated using the METAVIR scoring system. Histogram metrics including mean, standard deviation (Std), skewness, kurtosis, minimum (Min), maximum (Max), range, interquartile (Iq) range, and percentiles (10, 25, 50, 75, 90th) were extracted from apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) maps. All histogram metrics among different fibrosis groups were compared using one-way analysis of variance or nonparametric Kruskal-Wallis test. For significant parameters, receivers operating characteristic curve (ROC) analyses were further performed for the staging of LF. Based on their METAVIR stage, the 56 patients were reclassified into three groups as follows: F0-1 group (n = 25), F2-3 group (n = 21), and F4 group (n = 10). The mean, Iq range, percentiles (50, 75, and 90th) of D* maps between the groups were significant differences (all P < 0.05). Area under the ROC curve (AUC) of the mean, Iq range, 50, 75, and 90th percentile of D* maps for identifying significant LF (≥F2 stage) was 0.901, 0.859, 0.876, 0.943, and 0.886 (all P < 0.0001), respectively; for diagnosing severe fibrosis or cirrhosis (F4), AUC was 0.917, 0.922, 0.943, 0.985, and 0.939 (all P < 0.0001), respectively. The histogram metrics of ADC, D, and f maps demonstrated no significant difference among the groups (all P > 0.05). Histogram analysis of D* map derived from IVIM can be used to stage liver fibrosis in patients with CLDs and provide more quantitative information beyond the mean value.

Diffusion, outcomes and implementation of minimally invasive liver surgery: a snapshot from the I Go MILS (Italian Group of Minimally Invasive Liver Surgery) Registry.

PubMed

Aldrighetti, Luca; Ratti, Francesca; Cillo, Umberto; Ferrero, Alessandro; Ettorre, Giuseppe Maria; Guglielmi, Alfredo; Giuliante, Felice; Calise, Fulvio

2017-09-01

The Italian Group of MILS (I Go MILS) prospective registry was established in 2014 with the goals to create a hub for data and projects on a national basis and to promote the diffusion and implementation of MILS programs on a national scale. The primary endpoint of the present study is to give a snapshot of the real diffusion and outcomes of MILS in Italy, while analyzing the role of the registry in the implementation of MILS programs nationwide. The I Go MILS Registry is a prospective and intention-to-treat registry opened to any Italian center performing MILS, without restriction criteria based on number of procedures. The Registry is developed through the eClinical, an electronic platform for the management of clinical trials and is based on 34 clinical variables, regarding indication, intra- and postoperative course. Clinical outcomes and data regarding implementation of MILS activity have been analyzed for the aim of the study. Between November 2014 and June 2017, data from 1678 MILS performed in 48 centers have been collected (mean number of procedures per center 35, range 1-302). 22% of procedures were performed for benign and 78% for malignant disease (HCC constituted the 49.1% and CRLM the 31.2% of malignant tumors). Major liver resections (>3 liver segments), including right and left hepatectomies, trisectionectomies and ALPPS procedures were 10% of the series. Mean blood loss was 200 ± 230 mL Morbidity rate was 20.5% and mortality was 0.3%. 10.4% of cases were converted to open approach. Median length of stay was 5 days. MILS/total resections ratio in 13 experienced centers increased from 14 to 30% after Registry establishment. MILS programs are well established in Italy, with progressive increase both in the number of cases and in the numerosity of centers. The I Go MILS Registry is playing a crucial role in monitoring the development of MILS in the real world on a national basis while giving a significant contribution to the implementation of MILS programs.

Mast cell sarcoma of the larynx.

PubMed Central

Horny, H P; Parwaresch, M R; Kaiserling, E; Müller, K; Olbermann, M; Mainzer, K; Lennert, K

1986-01-01

A 74 year old woman presented with a primary subglottic tumour. Neither cutaneous mastocytosis (urticaria pigmentosa) nor spread to the bone marrow, liver, or spleen were detected. About two years after initial manifestation of the tumour nodular skin metastases appeared, as well as local recurrence in the larynx. Despite chemotherapy and radiation the disease progressed and was fatal. The terminal phase was characterised by generalisation of the mast cell tumour with diffuse infiltration of bone marrow and, shortly before death, leukaemic transformation. The patient died four years after onset of disease with symptoms of a hemorrhagic diathesis. As far as we know this is the first case of mast cell sarcoma to be reported in man. Images PMID:3088063

A disease-specific quality of life instrument for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: CLDQ-NAFLD.

PubMed

Younossi, Zobair M; Stepanova, Maria; Henry, Linda; Racila, Andrei; Lam, Brian; Pham, Huong T; Hunt, Sharon

2017-08-01

Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are the most common causes of chronic liver disease with known negative impact on patients' health-related quality of life. Our aim was to validate a disease-specific health-related quality of life instrument useful for efficacy trials involving patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. From a long item selection questionnaire, we selected relevant items which, by factor analysis, were grouped into domains constituting Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version. The developed instrument was subjected to internal validity, test-retest reliability and construct validity assessment using standard methods. For development of the Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version instrument, a 75-item-long item selection questionnaire was administered to 25 patients with non-alcoholic fatty liver disease. After item reduction, factor analysis found that 98.7% of variance in the remaining items would be explained by six factors. Thus, the resulting Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version instrument had 36 items grouped into six domains: Abdominal Symptoms, Activity, Emotional, Fatigue, Systemic Symptoms, and Worry. The independent validation group included another 104 patients with non-alcoholic fatty liver disease. The Cronbach's alphas of 0.74-0.90 suggested good to excellent internal consistency of the domains. Furthermore, the presence of obesity and history of depression were discriminated best by Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version scores (P<.05). The domains' correlations with the most relevant domains of Short Form-36 exceeded 0.70. Test-retest reliability in a subgroup of patients (N=27) demonstrated no significant within-patient variability with multiple administrations (all median differences were zero, all P>.15, intraclass correlations .76-.88). The Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version is a disease-specific health-related quality of life instrument developed and validated using an established methodology and useful for clinical trials of non-alcoholic fatty liver disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Diagnosis of focal liver lesions suspected of metastases by diffusion-weighted imaging (DWI): systematic comparison favors free-breathing technique.

PubMed

Baltzer, Pascal A T; Schelhorn, Juliane; Benndorf, Matthias; Dietzel, Matthias; Kaiser, Werner A

2013-01-01

Two echo planar imaging diffusion-weighted imaging (DWI) techniques [one breath hold (DWI(bh)), repetition time/echo time (TR/TE) 2100/62 ms; one at free breathing (DWI(fb)), TR/TE 2000/65 ms] were compared regarding diagnosis of focal liver lesions (FLLs) in 45 patients with suspected liver metastasis without prior treatment. Apparent diffusion coefficient values of 46 benign and 67 malignant FLLs were analyzed by receiver operating characteristics (ROC) analysis. DWI(fb) detected more malignant lesions than DWI(bh) (P=.002). Lesion size ≤10 mm was associated with FLLs missed by DWI(bh) (P=.018). Area under the ROC curve of DWI(fb) (0.801) was higher compared to that of DWI(bh) (0.669, P<.0113), demonstrating the diagnostic superiority of DWI(fb). Copyright © 2013 Elsevier Inc. All rights reserved.

The increasing burden of potentially preventable liver disease among adult liver transplant recipients: A comparative analysis of liver transplant indication by era in Australia and New Zealand.

PubMed

Howell, Jessica; Balderson, Glenda; Hellard, Margaret; Gow, Paul; Strasser, Simone; Stuart, Katherine; Wigg, Alan; Jeffrey, Gary; Gane, Ed; Angus, Peter W

2016-02-01

Hepatitis C (HCV), hepatitis B (HBV), alcohol-related liver disease (ALD), and non-alcohol-related fatty liver disease (NAFLD) are leading indications for adult liver transplantation in Australia and New Zealand. However, these diseases are potentially preventable through effective primary and/or secondary prevention strategies. This study evaluates the relative contribution of potentially preventable liver diseases to liver transplant numbers in Australia and New Zealand over time. Prospectively recorded clinical, demographic, and outcome data were collected from the Australian and New Zealand Liver Transplant Registry for all primary adult liver transplants performed in Australia and New Zealand from 1 January 1985 until 31 December 2012. Potentially preventable liver disease was defined as HBV, HCV, NAFLD, ALD, and HCC. The etiology of liver disease leading to liver transplantation and the proportion of preventable liver disease-related liver transplantation was compared between Era 1 (1985-1993), Era 2 (1994-2003), and Era 3 (2004-2012). Overall, 1252 of 3266 adult primary liver transplants (38.3%) were performed for potentially preventable liver disease. There was a significant increase in the proportion of liver transplants because of preventable liver disease from 21.2% (93 of 439) in Era 1, to 49.8% (623 of 1252) in Era 2 and 63.5% (1000 of 1575) in Era 3 (P < 0.0001). Over time, there was a significant increase in HCV (P < 0.0001), ALD (P = 0.002), and NAFLD (P < 0.0001) as a primary indication for adult liver transplant, whereas HBV has significantly decreased from Era 1 to Era 3 as an indication for transplant (P < 0.0001). The number of transplants performed for HCC also increased across Eras (P < 0.0001), with 84% due to underlying potentially preventable liver disease. Since 2004, the majority of primary adult liver transplants within Australia and New Zealand have been because of potentially preventable liver diseases and the prevalence of these diseases has increased over time. This finding represents an opportunity for clinicians to make a significant impact on the overall burden of advanced liver disease in Australia and New Zealand by improving primary and secondary prevention measures. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Liver transplant for cholestatic liver diseases.

PubMed

Carrion, Andres F; Bhamidimarri, Kalyan Ram

2013-05-01

Cholestatic liver diseases include a group of diverse disorders with different epidemiology, pathophysiology, clinical course, and prognosis. Despite significant advances in the clinical care of patients with cholestatic liver diseases, liver transplant (LT) remains the only definitive therapy for end-stage liver disease, regardless of the underlying cause. As per the United Network for Organ Sharing database, the rate of cadaveric LT for cholestatic liver disease was 18% in 1991, 10% in 2000, and 7.8% in 2008. This review summarizes the available evidence on various common and rare cholestatic liver diseases, disease-specific issues, and pertinent aspects of LT. Copyright © 2013 Elsevier Inc. All rights reserved.

Tyzzer's disease in a red panda (Ailurus fulgens fulgens).

PubMed

Langan, J; Bemis, D; Harbo, S; Pollock, C; Schumacher, J

2000-12-01

A debilitated 9-yr-old female red panda (Ailurus fulgens fulgens) with a recent history of corticosteroid administration displayed anorexia, depression, and diarrhea for 2 days. Blood work revealed a moderate nonregenerative anemia, leukocytosis, hypokalemia, hyperbilirubinemia, and mildly elevated alanine aminotransferase and aspartate aminotransferase. Serology was negative for occult heartworm, Toxoplasma gondii, feline leukemia virus, feline infectious peritonitis, feline immunodeficiency virus, and canine distemper virus. Electron microscopy of the feces demonstrated corona-like virus particles. The panda died 3 days after initial presentation. Histologic findings included multifocal, acute, hepatic necrosis and diffuse, necrotizing colitis. Liver and colon lesions contained intracellular, curved, spore-forming, gram-negative, silver-positive rods morphologically consistent with Clostridium piliforme. This panda most likely contracted Tyzzer's disease subsequent to having a compromised immune system after corticosteroid administration and concurrent disease.

The Global Burden of Liver Disease: The Major Impact of China

PubMed Central

Wang, Fu-Sheng; Fan, Jian-Gao; Zhang, Zheng; Gao, Bin; Wang, Hong-Yang

2016-01-01

Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus, HBV), nonalcoholic fatty liver disease and alcoholic liver disease affect approximately 300 million people. The establishment of the Expanded Program on Immunization in 1992 has resulted in a substantial decline in the number of newly HBV-infected patients; however, the number of patients with alcoholic and nonalcoholic fatty liver diseases is rising at an alarming rate. Liver cancer, one of the most deadly cancers, is the second most common cancer in China. Approximately 383,000 people die from liver cancer every year in China, which accounts for 51% of the deaths from liver cancer worldwide. Over the past 10 years, China has made some significant efforts to shed its “leader in liver diseases” title by investing large amounts of money in funding research, vaccines and drug development for liver diseases, and by recruiting many Western-trained hepatologists and scientists. Over the last two decades, hepatologists and scientists in China have made significant improvements in liver disease prevention, diagnosis, management and therapy. They have been very active in liver disease research, as shown by the dramatic increase in the number of publications in Hepatology. Nevertheless, many challenges remain that must be tackled collaboratively. In this review, we discuss the epidemiology and characteristics of liver diseases and liver-related research in China. PMID:25164003

PNPLA3 I148M polymorphism, clinical presentation, and survival in patients with hepatocellular carcinoma.

PubMed

Valenti, Luca; Motta, Benedetta Maria; Soardo, Giorgio; Iavarone, Massimo; Donati, Benedetta; Sangiovanni, Angelo; Carnelutti, Alessia; Dongiovanni, Paola; Rametta, Raffaela; Bertelli, Cristina; Facchetti, Floriana; Colombo, Massimo; Fargion, Silvia; Fracanzani, Anna Ludovica

2013-01-01

Aim of this study was to evaluate whether the PNPLA3 I148M polymorphism, previously associated with hepatocellular carcinoma (HCC) risk, influences the clinical presentation of HCC and survival. we considered 460 consecutive HCC patients referred to tertiary care centers in Northern Italy, 353 with follow-up data. Homozygosity for PNPLA3 148M at risk allele was enriched in HCC patients with alcoholic liver disease or nonalcoholic fatty liver disease (ALD&NAFLD: relative risk 5.9, 95% c.i. 3.5-9.9; other liver diseases: relative risk 1.9, 95% c.i. 1.1-3.4). In ALD&NAFLD patients, the PNPLA3 148M allele was associated with younger age, shorter history of cirrhosis, less advanced (Child A) cirrhosis at HCC diagnosis, and lower HCC differentiation grade (p<0.05). Homozygosity for PNPLA3 148M was associated with reduced survival in the overall series (p = 0.009), and with a higher number of HCC lesions at presentation (p = 0.007) and reduced survival in ALD&NAFLD patients (p = 0.003; median survival 30, 95% c.i. 20-39 vs. 45, 95% c.i. 38-52 months), but not in those with HCC related to other etiologies (p = 0.86; 48, 95% c.i. 32-64 vs. 55, 95% c.i. 43-67 months). At multivariate Cox regression analysis, homozygosity for PNPLA3 148M was the only negative predictor of survival in ALD&NAFLD patients (HR of death 1.57, 95% c.i. 1.12-2.78). PNPLA3 148M is over-represented in ALD&NAFLD HCC patients, and is associated with occurrence at a less advanced stage of liver disease in ALD&NAFLD. In ALD&NAFLD, PNPLA3 148M is associated with more diffuse HCC at presentation, and with reduced survival.

Liver Disease in Sri Lanka.

PubMed

Wijewantha, Hasitha S

2017-01-01

Liver disease in Sri Lanka is mainly due to alcoholic liver disease and nonalcoholic fatty liver disease. In contrast to other South Asian countries, the prevalence of hepatitis B and C is low in Sri Lanka and prevalence of hepatitis A is intermediate. The few reported cases of hepatitis E in Sri Lanka are mainly in people who have traveled to neighboring South Asian countries. Wilson's disease, autoimmune hepatitis, hemochromatosis, drug-induced liver disease, and primary biliary cirrhosis are recognized causes of liver disease in Sri Lanka. Pyogenic and amebic liver abscesses and dengue infection are the other causes of liver disease. Some of the commonly used plants as traditional herbal medicine in Sri Lanka have been shown to have deleterious effects on the liver in animal studies. Considering the high popularity of traditional herbal medicine in the country, it is likely that herbal medicine is an etiological factor for liver disease in Sri Lanka, but no published data are available. Address reprint requests to: Wijewantha HS. Liver Disease in Sri Lanka. Euroasian J Hepato-Gastroenterol 2017;7(1):78-81.

Progression of Liver Disease

MedlinePlus

... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

Quantitative liver ADC measurements using diffusion-weighted MRI at 3 Tesla: evaluation of reproducibility and perfusion dependence using different techniques for respiratory compensation.

PubMed

Larsen, Nis Elbrønd; Haack, Søren; Larsen, Lars Peter Skovgaard; Pedersen, Erik Morre

2013-10-01

Diffusion weighted imaging (DWI) of the liver suffers from low signal to noise making 3 Tesla (3 T) an attractive option, but 3 T data is scarce. It was the aim to study the influence of different b values and respiratory compensation methods (RCM) on the apparent diffusion coefficient (ADC) level and on ADC reproducibility at 3 T. Ten healthy volunteers and 12 patients with malignant liver lesions underwent repeated (2-22 days) breathhold, free-breathing and respiratory triggered DWI at 3 T using b values between 0 and 1,000 s/mm(2). The ADCs changed up to 150% in healthy livers and up to 48% in malignant lesions depending on b value combinations. Best ADC reproducibility in healthy livers were obtained with respiratory triggering (95% limits of agreement: ±0.12) and free-breathing (±0.14). In malignant lesions equivalent reproducibility was obtained with less RCM dependence. The use of a lower maximum b value (b = 500) decreased reproducibility (±0.14 to ±0.32) in both normal liver and malignant lesions. Large differences in absolute ADC values and reproducibility caused by varying combinations of clinically realistic b values were demonstrated. Different RCMs caused smaller differences. Lowering maximum b value to 500 increased limits of agreement up to a factor of two. Serial ADC changes larger than approximately 15% can be detected confidently on an individual basis in both malignant lesions and normal liver parenchyma at 3 T using appropriate b values and respiratory compensation.

Microencapsulation of Hepatocytes and Mesenchymal Stem Cells for Therapeutic Applications.

PubMed

Meier, Raphael P H; Montanari, Elisa; Morel, Philippe; Pimenta, Joël; Schuurman, Henk-Jan; Wandrey, Christine; Gerber-Lemaire, Sandrine; Mahou, Redouan; Bühler, Leo H

2017-01-01

Encapsulated hepatocyte transplantation and encapsulated mesenchymal stem cell transplantation are newly developed potential treatments for acute and chronic liver diseases, respectively. Cells are microencapsulated in biocompatible semipermeable alginate-based hydrogels. Microspheres protect cells against antibodies and immune cells, while allowing nutrients, small/medium size proteins and drugs to diffuse inside and outside the polymer matrix. Microencapsulated cells are assessed in vitro and designed for experimental transplantation and for future clinical applications.Here, we describe the protocol for microencapsulation of hepatocytes and mesenchymal stem cells within hybrid poly(ethylene glycol)-alginate hydrogels.

Effects of Melatonin on Liver Injuries and Diseases

PubMed Central

Zhang, Jiao-Jiao; Meng, Xiao; Li, Ya; Zhou, Yue; Xu, Dong-Ping; Li, Sha; Li, Hua-Bin

2017-01-01

Liver injuries and diseases are serious health problems worldwide. Various factors, such as chemical pollutants, drugs, and alcohol, could induce liver injuries. Liver diseases involve a wide range of liver pathologies, including hepatic steatosis, fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocarcinoma. Despite all the studies performed up to now, therapy choices for liver injuries and diseases are very few. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries and diseases remains a priority. Melatonin is a well-known natural antioxidant, and has many bioactivities. There are numerous studies investigating the effects of melatonin on liver injuries and diseases, and melatonin could regulate various molecular pathways, such as inflammation, proliferation, apoptosis, metastasis, and autophagy in different pathophysiological situations. Melatonin could be used for preventing and treating liver injuries and diseases. Herein, we conduct a review summarizing the potential roles of melatonin in liver injuries and diseases, paying special attention to the mechanisms of action. PMID:28333073

Acute-on-chronic and Decompensated Chronic Liver Failure: Definitions, Epidemiology, and Prognostication.

PubMed

Olson, Jody C

2016-07-01

Chronic liver disease is the fifth leading cause of death worldwide and represents a major burden for the health care community. Cirrhosis is a progressive disease resulting in end-stage liver failure, which in the absence of liver transplantation is fatal. Acute-on-chronic liver failure carries high short-term mortality but is potentially reversible. Viral hepatitis, alcohol, and nonalcoholic fatty liver disease remain the principal causes of liver disease. Though treatments exist for hepatitis B and C, they remain unavailable to many with these diseases. This article reviews the epidemiology of advanced liver disease and the concept of acute-on-chronic liver failure. Copyright © 2016 Elsevier Inc. All rights reserved.

Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

ClinicalTrials.gov

2013-01-24

Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

Liver disease - resources

MedlinePlus

Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation -- www.liverfoundation.org Children's Liver Association for Support Services (C.L.A.S.S.) -- www. ...

Endoscopic management of biliary complications following liver transplantation after donation from cardiac death donors.

PubMed

Croome, Kris P; McAlister, Vivian; Adams, Paul; Marotta, Paul; Wall, William; Hernandez-Alejandro, Roberto

2012-09-01

Previous studies have shown a higher incidence of biliary complications following donation after cardiac death (DCD) liver transplantation compared with donation after brain death (DBD) liver transplantation. The endoscopic management of ischemic type biliary strictures in patients who have undergone DCD liver transplants needs to be characterized further. A retrospective institutional review of all patients who underwent DCD liver transplant from January 2006 to September 2011 was performed. These patients were compared with all patients who underwent DBD liver transplantation in the same time period. A descriptive analysis of all DCD patients who developed biliary complications and their subsequent endoscopic management was also performed. Of the 36 patients who received DCD liver transplants, 25% developed biliary complications compared with 13% of patients who received DBD liver transplants (P=0.062). All DCD allograft recipients who developed biliary complications became symptomatic within three months of transplantation. Ischemic type biliary strictures in DCD allograft recipients included disseminated biliary strictures in two patients, biliary strictures of the hepatic duct bifurcation in three patients and biliary strictures of the donor common hepatic duct in three patients. There was a trend toward increasing incidence of total biliary complications in recipients of DCD liver allografts compared with those receiving DBD livers, and the rate of diffuse ischemic cholangiopathy was significantly higher. Focal ischemic type biliary strictures can be treated effectively in DCD liver transplant recipients with favourable results. Diffuse ischemic type biliary strictures in DCD liver transplant recipients ultimately requires retransplantation.

Alcoholic liver disease: The gut microbiome and liver crosstalk

PubMed Central

Hartmann, Phillipp; Seebauer, Caroline T.; Schnabl, Bernd

2015-01-01

Alcoholic liver disease is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with alcoholic liver disease have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing the mucosal gut barrier or preventing cellular responses to microbial products protect from experimental alcoholic liver disease. Therefore, intestinal dysbiosis and pathological bacterial translocation appear fundamental for the pathogenesis of alcoholic liver disease. This review highlights causes for intestinal dysbiosis and pathological bacterial translocation, their relationship and consequences for alcoholic liver disease. We also discuss how the liver affects the intestinal microbiota. PMID:25872593

MRI to assess renal structure and function.

PubMed

Artunc, Ferruh; Rossi, Cristina; Boss, Andreas

2011-11-01

In addition to excellent anatomical depiction, MRI techniques have expanded to study functional aspects of renal physiology, such as renal perfusion, glomerular filtration rate (GFR) or tissue oxygenation. This review will focus on current developments with an emphasis on clinical applicability. The method of GFR determination is largely heterogeneous and still has weaknesses. However, the technique of employing liver disappearance curves has been shown to be accurate in healthy persons and patients with chronic kidney disease. In potential kidney donors, complete evaluation of kidney anatomy and function can be accomplished in a single-stop investigation. Techniques without contrast media can be utilized to measure renal tissue oxygenation (blood oxygen level-dependent MRI) or perfusion (arterial spin labeling) and could aid in the diagnosis and treatment of ischemic renal diseases, such as renal artery stenosis. Diffusion imaging techniques may provide information on spatially restricted water diffusion and tumor cellularity. Functional MRI opens new horizons in studying renal physiology and pathophysiology in vivo. Although extensively utilized in research, labor-intensive postprocessing and lack of standardization currently limit the clinical applicability of functional MRI. Further studies are necessary to evaluate the clinical value of functional magnetic resonance techniques for early discovery and characterization of kidney disease.

Changes in Water Mobility Measured by Diffusion MRI Predict Response of Metastatic Breast Cancer to Chemotherapy

PubMed Central

Theilmann, Rebecca J; Borders, Rebecca; Trouard, Theodore P; Xia, Guowei; Outwater, Eric; Ranger-Moore, James; Gillies, Robert J; Stopeck, Alison

2004-01-01

Abstract A goal of oncology is the individualization of patient care to optimize therapeutic responses and minimize toxicities. Achieving this will require noninvasive, quantifiable, and early markers of tumor response. Preclinical data from xenografted tumors using a variety of antitumor therapies have shown that magnetic resonance imaging (MRI)-measured mobility of tissue water (apparent diffusion coefficient of water, or ADCw) is a biomarker presaging cell death in the tumor. This communication tests the hypothesis that changes in water mobility will quantitatively presage tumor responses in patients with metastatic liver lesions from breast cancer. A total of 13 patients with metastatic breast cancer and 60measurable liver lesionsweremonitored by diffusion MRI after initiation of new courses of chemotherapy. MR images were obtained prior to, and at 4, 11, and 39 days following the initiation of therapy for determination of volumes and ADCw values. The data indicate that diffusion MRI can predict response by 4 or 11 days after commencement of therapy, depending on the analytic method. The highest concordance was observed in tumor lesions that were less than 8 cm3 in volume at presentation. These results suggest that diffusion MRI can be useful to predict the response of liver metastases to effective chemotherapy. PMID:15720810

Pulmonary and hepatic lesions caused by the dehydropyrrolizidine alkaloid-producing plants Crotalaria juncea and Crotalaria retusa in donkeys.

PubMed

Pessoa, C R M; Pessoa, A F A; Maia, L A; Medeiros, R M T; Colegate, S M; Barros, S S; Soares, M P; Borges, A S; Riet-Correa, F

2013-09-01

The effects and susceptibility of donkeys to Crotalaria juncea and Crotalaria retusa poisoning were determined at high and low doses. Seeds of C. juncea containing 0.074% of dehydropyrrolizidine alkaloids (DHPAs) (isohemijunceines 0.05%, trichodesmine 0.016%, and junceine 0.008%) were administered to three donkeys at 0.3, 0.6 and 1 g/kg body weight (g/kg) daily for 365 days. No clinical signs were observed and, on liver and lung biopsies, the only lesion was a mild liver megalocytosis in the donkeys ingesting 0.6 and 1 g/kg/day. Two other donkeys that received daily doses of 3 and 5 g seed/kg showed initial respiratory signs 70 and 40 days after the start of the administration, respectively. The donkeys were euthanized following severe respiratory signs and the main lung lesions were proliferation of Clara cells and interstitial fibrosis. Three donkeys ingested seeds of C. retusa containing 5.99% of monocrotaline at daily doses of 0.025, 0.05 and 0.1 g/kg for 365 days. No clinical signs were observed and, on liver and lung biopsies, the only lesion was moderate liver megalocytosis in each of the three donkeys. One donkey that received a single dose of 5 g/kg of C. retusa seeds and another that received 1 g/kg daily for 7 days both showed severe clinical signs and died with diffuse centrilobular liver necrosis. No lung lesions were observed. Another donkey that received a single dose of 2.5 g/kg of C. retusa seeds showed no clinical signs. The hepatic and pneumotoxic effects observed are consistent with an etiology involving DHPAs. Furthermore, the occurrence of lung or liver lesions correlates with the type of DHPAs contained in the seeds. Similarly as has been reported for horses, the data herein suggest that in donkeys some DHPAs are metabolized in the liver causing liver disease, whereas others are metabolized in the lung by Clara cells causing lung disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Targeting Dysbiosis for the Treatment of Liver Disease.

PubMed

Anand, Gobind; Zarrinpar, Amir; Loomba, Rohit

2016-02-01

The gut microbiome is composed of a vast number of microbes in the gastrointestinal tract, which benefit host metabolism, aid in digestion, and contribute to normal immune function. Alterations in microbial composition can result in intestinal dysbiosis, which has been implicated in several diseases including obesity, inflammatory bowel disease, and liver diseases. Over the past several years, significant interactions between the intestinal microbiota and liver have been discovered, with possible mechanisms for the development as well as progression of liver disease and promising therapeutic targets to either prevent or halt the progression of liver disease. In this review the authors examine mechanisms of dysbiosis-induced liver disease; highlight current knowledge regarding the role of dysbiosis in nonalcoholic liver disease, alcoholic liver disease, and cirrhosis; and discuss potential therapeutic targets. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Liver diseases in the elderly].

PubMed

Bruguera, Miguel

2014-11-01

Liver diseases in the elderly have aroused less interest than diseases of other organs, since the liver plays a limited role in aging. There are no specific liver diseases of old age, but age-related anatomical and functional modifications of the liver cause changes in the frequency and clinical behavior of some liver diseases compared with those in younger patients. This review discusses the most important features of liver function in the healthy elderly population, as well as the features of the most prevalent liver diseases in this age group, especially the diagnostic approach to the most common liver problems in the elderly: asymptomatic elevation of serum transaminases and jaundice. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Fatty Liver Disease

MedlinePlus

... fatty liver disease that is not related to heavy alcohol use. There are two kinds: Simple fatty ... disease? Alcoholic fatty liver disease is due to heavy alcohol use. Your liver breaks down most of ...

Near-infrared fluorescence cholangiography with indocyanine green for biliary atresia. Real-time imaging during the Kasai procedure: a pilot study.

PubMed

Hirayama, Yutaka; Iinuma, Yasushi; Yokoyama, Naoyuki; Otani, Tetsuya; Masui, Daisuke; Komatsuzaki, Naoko; Higashidate, Naruki; Tsuruhisa, Shiori; Iida, Hisataka; Nakaya, Kengo; Naito, Shinichi; Nitta, Koju; Yagi, Minoru

2015-12-01

Hepatoportoenterostomy (HPE) with the Kasai procedure is the treatment of choice for biliary atresia (BA) as the initial surgery. However, the appropriate level of dissection level of the fibrous cone (FC) of the porta hepatis (PH) is frequently unclear, and the procedure sometimes results in unsuccessful outcomes. Recently, indocyanine green near-infrared fluorescence imaging (ICG-FCG) has been developed as a form of real-time cholangiography. We applied this technique in five patients with BA to visualize the biliary flow at the PH intraoperatively. ICG was injected intravenously the day before surgery as the liver function test, and the liver was observed with a near-infrared camera system during the operation while the patient's feces was also observed. In all patients, the whole liver fluoresced diffusely with ICG-containing stagnant bile, whereas no extrahepatic structures fluoresced. The findings of the ICG fluorescence pattern of the PH after dissection of the FC were classified into three types: spotty fluorescence, one patient; diffuse weak fluorescence, three patients; and diffuse strong fluorescence, one patient. In all five patients, the feces evacuated after HPE showed distinct fluorescent spots, although that obtained before surgery showed no fluorescence. One patient with diffuse strong fluorescence who did not achieve JF underwent living related liver transplantation six months after the initial HPE procedure. Four patients, including three cases involving diffuse weak fluorescence and one case involving spotty fluorescence showed weak fluorescence compared to that of the surrounding liver surface. We were able to detect the presence of bile excretion at the time of HPE intraoperatively and successfully evaluated the extent of bile excretion using this new technique. Furthermore, the ICG-FCG findings may provide information leading to a new classification and potentially function as an indicator predicting the clinical outcomes after HPE.

Diffusion-weighted imaging of the liver with multiple b values: effect of diffusion gradient polarity and breathing acquisition on image quality and intravoxel incoherent motion parameters--a pilot study.

PubMed

Dyvorne, Hadrien A; Galea, Nicola; Nevers, Thomas; Fiel, M Isabel; Carpenter, David; Wong, Edmund; Orton, Matthew; de Oliveira, Andre; Feiweier, Thorsten; Vachon, Marie-Louise; Babb, James S; Taouli, Bachir

2013-03-01

To optimize intravoxel incoherent motion (IVIM) diffusion-weighted (DW) imaging by estimating the effects of diffusion gradient polarity and breathing acquisition scheme on image quality, signal-to-noise ratio (SNR), IVIM parameters, and parameter reproducibility, as well as to investigate the potential of IVIM in the detection of hepatic fibrosis. In this institutional review board-approved prospective study, 20 subjects (seven healthy volunteers, 13 patients with hepatitis C virus infection; 14 men, six women; mean age, 46 years) underwent IVIM DW imaging with four sequences: (a) respiratory-triggered (RT) bipolar (BP) sequence, (b) RT monopolar (MP) sequence, (c) free-breathing (FB) BP sequence, and (d) FB MP sequence. Image quality scores were assessed for all sequences. A biexponential analysis with the Bayesian method yielded true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (PF) in liver parenchyma. Mixed-model analysis of variance was used to compare image quality, SNR, IVIM parameters, and interexamination variability between the four sequences, as well as the ability to differentiate areas of liver fibrosis from normal liver tissue. Image quality with RT sequences was superior to that with FB acquisitions (P = .02) and was not affected by gradient polarity. SNR did not vary significantly between sequences. IVIM parameter reproducibility was moderate to excellent for PF and D, while it was less reproducible for D*. PF and D were both significantly lower in patients with hepatitis C virus than in healthy volunteers with the RT BP sequence (PF = 13.5% ± 5.3 [standard deviation] vs 9.2% ± 2.5, P = .038; D = [1.16 ± 0.07] × 10(-3) mm(2)/sec vs [1.03 ± 0.1] × 10(-3) mm(2)/sec, P = .006). The RT BP DW imaging sequence had the best results in terms of image quality, reproducibility, and ability to discriminate between healthy and fibrotic liver with biexponential fitting.

Type I Glycogen Storage Disease

MedlinePlus

... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

Comparison of breathhold, navigator-triggered, and free-breathing diffusion-weighted MRI for focal hepatic lesions.

PubMed

Choi, Ji Soo; Kim, Myeong-Jin; Chung, Yong Eun; Kim, Kyung Ah; Choi, Jin-Young; Lim, Joon Seok; Park, Mi-Suk; Kim, Ki Whang

2013-07-01

To compare the breathhold, navigator-triggered, and free-breathing techniques in diffusion-weighted magnetic resonance imaging (MRI) for the evaluation of focal liver lesions on a 3.0T system. Fifty-two patients (36 men, 16 women; mean age, 56.4 years) with focal liver lesions underwent breathhold, navigator-triggered, and free-breathing diffusion-weighted imaging (DWI) of the liver on a 3.0 Tesla (T) system. All sequences were performed with b values of 50 and 800 s/mm(2) and identical parameters except for signal averages (two for navigator-triggered, one for breathhold, and four for free-breathing) and repetition time (3389 ms for navigator-triggered, 1500 ms for breathhold, and 4400 ms for free-breathing). A total of 74 lesions (50 malignant, 24 benign) were evaluated. The signal-to-noise ratios (SNR) of the liver and lesions, contrast-to-noise ratios (CNR) of each lesion, and ADC values of the liver and lesions were compared for each DWI sequence. The detection sensitivity and characterization accuracy were also compared. The SNRs of the liver and lesions were significantly lower for breathhold DWI than for non-breathhold DWI (navigator-triggered and free-breathing DWI) for all b values. The CNRs of the lesions were also significantly lower for breathhold DWI than for non-breathhold DWI. The ADC values of the liver and focal lesions measured using the three DWI techniques were not significantly different and showed good correlation. For lesion detection and characterization, there were no significant differences between breathhold and non-breathhold DWI. Both breathhold and non-breathhold DWI are comparable for the detection or characterization of focal liver lesions at 3.0T; however, non-breathhold DWI provides higher SNR and CNR than breathhold DWI. In addition, although free-breathing and navigator-triggered DWI sequences show similar performance for 3.0T liver imaging, free-breathing DWI is more time efficient than navigator-triggered DWI. Copyright © 2013 Wiley Periodicals, Inc.

A 33-year-old white female with abdominal pain, nausea, vomiting and hypotension.

PubMed

Westfall, M D; Lumpkin, J

1993-01-01

A thirty-three year old female presented to our emergency department complaining of severe abdominal pain, nausea, and vomiting. On physical examination she was hypotensive with a firm, tender abdomen, cervical motion tenderness and a diffuse erythematous rash. A surgical diagnosis of Acute Pelvic Inflammatory Disease was made during laparoscopy. Coagulant studies, liver function tests, culture results, and the desquamation of the patient's palms led to the additional diagnosis of Toxic Shock Syndrome. A literature search failed to reveal any similar cases of Pelvic Inflammatory Disease (PID) and Toxic Shock Syndrome (TSS) occurring concomitantly. Patients may present severely ill with either of these disease entities but potential for serious illness is greater when both of these syndromes occur in the same patient. We conclude that in patients with a similar presentation, the symptoms should not be attributed completely to PID without further investigation and consideration of a concomitant disease process including TSS.

Magnetic Resonance Imaging of Liver Metastasis.

PubMed

Karaosmanoglu, Ali Devrim; Onur, Mehmet Ruhi; Ozmen, Mustafa Nasuh; Akata, Deniz; Karcaaltincaba, Musturay

2016-12-01

Liver magnetic resonance imaging (MRI) is becoming the gold standard in liver metastasis detection and treatment response assessment. The most sensitive magnetic resonance sequences are diffusion-weighted images and hepatobiliary phase images after Gd-EOB-DTPA. Peripheral ring enhancement, diffusion restriction, and hypointensity on hepatobiliary phase images are hallmarks of liver metastases. In patients with normal ultrasonography, computed tomography (CT), and positron emission tomography (PET)-CT findings and high clinical suspicion of metastasis, MRI should be performed for diagnosis of unseen metastasis. In melanoma, colon cancer, and neuroendocrine tumor metastases, MRI allows confident diagnosis of treatment-related changes in liver and enables differential diagnosis from primary liver tumors. Focal nodular hyperplasia-like nodules in patients who received platinum-based chemotherapy, hypersteatosis, and focal fat can mimic metastasis. In cancer patients with fatty liver, MRI should be preferred to CT. Although the first-line imaging for metastases is CT, MRI can be used as a problem-solving method. MRI may be used as the first-line method in patients who would undergo curative surgery or metastatectomy. Current limitation of MRI is low sensitivity for metastasis smaller than 3mm. MRI fingerprinting, glucoCEST MRI, and PET-MRI may allow simpler and more sensitive diagnosis of liver metastasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Chronic liver disease and 90-day mortality in 21,359 patients following peptic ulcer bleeding--a Nationwide Cohort Study.

PubMed

Holland-Bill, L; Christiansen, C F; Gammelager, H; Mortensen, R N; Pedersen, L; Sørensen, H T

2015-03-01

Bleeding is a serious and frequent complication of peptic ulcer disease. Hepatic dysfunction can cause coagulopathy and increases the risk of peptic ulcer bleeding. However, whether chronic liver disease increases mortality after peptic ulcer bleeding remains unclear. To examine the prognostic impact of chronic liver disease on mortality after peptic ulcer bleeding. We used population-based medical registries to conduct a cohort study of all Danish residents hospitalised with incident peptic ulcer bleeding from 2004 through 2011. We identified patients diagnosed with liver cirrhosis or non-cirrhotic chronic liver disease before their admission for peptic ulcer bleeding. We then computed 90-day mortality after peptic ulcer bleeding based on the Kaplan-Meier method (1 - survival function) and used a Cox regression model to estimate mortality rate ratios (MRRs), controlling for potential confounders. We identified 21,359 patients hospitalised with peptic ulcer bleeding. Among these, 653 (3.1%) had a previous diagnosis of liver cirrhosis and 474 (2.2%) had a history of non-cirrhotic chronic liver disease. Patients with liver cirrhosis and non-cirrhotic chronic liver disease had a cumulative 90-day mortality of 25.3% and 20.7%, respectively, compared to 18.3% among patients without chronic liver disease. Liver cirrhosis was associated with an adjusted 90-day MRR of 2.38 (95% CI: 2.02-2.80), compared to 1.49 (95% CI: 1.22-1.83) among patients with non-cirrhotic chronic liver disease. Patients with chronic liver disease, particularly liver cirrhosis, are at increased risk of death within 90 days after hospitalisation for peptic ulcer bleeding compared to patients without chronic liver disease. © 2015 John Wiley & Sons Ltd.

Leptospira Exposure and Patients with Liver Diseases: A Case-Control Seroprevalence Study

PubMed Central

Alvarado-Esquivel, Cosme; Sánchez-Anguiano, Luis Francisco; Hernández-Tinoco, Jesús; Ramos-Nevárez, Agar; Margarita Cerrillo-Soto, Sandra; Alberto Guido-Arreola, Carlos

2016-01-01

The seroepidemiology of Leptospira infection in patients suffering from liver disease has been poorly studied. Information about risk factors associated with infection in liver disease patients may help in the optimal planning of preventive measures. We sought to determine the association of Leptospira IgG seroprevalence and patients with liver diseases, and to determine the characteristics of the patients with Leptospira exposure. We performed a case-control study of 75 patients suffering from liver diseases and 150 age- and gender-matched control subjects. Diagnoses of liver disease included liver cirrhosis, steatosis, chronic hepatitis, acute hepatitis, and amoebic liver abscess. Sera of participants were analyzed for the presence of anti- Leptospira IgG antibodies using a commercially available enzyme immunoassay. Anti-Leptospira IgG antibodies were found in 17 (22.7%) of 75 patients and in 15 (10.0%) of 150 control subjects (OR = 2.32; 95% CI: 1.09-4.94; P=0.03). This is the first age- and gender-matched case control study about Leptospira seroprevalence in patients with liver diseases. Results indicate that Leptospira infection is associated with chronic and acute liver diseases. Results warrants for additional studies on the role of Leptospira exposure in chronic liver disease. PMID:27493589

Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease.

PubMed

Reilly, Norelle R; Lebwohl, Benjamin; Hultcrantz, Rolf; Green, Peter H R; Ludvigsson, Jonas F

2015-06-01

Non-alcoholic fatty liver disease is a common cause of chronic liver disease. Celiac disease alters intestinal permeability and treatment with a gluten-free diet often causes weight gain, but so far there are few reports of non-alcoholic fatty liver disease in patients with celiac disease. Population-based cohort study. We compared the risk of non-alcoholic fatty liver disease diagnosed from 1997 to 2009 in individuals with celiac disease (n = 26,816) to matched reference individuals (n = 130,051). Patients with any liver disease prior to celiac disease were excluded, as were individuals with a lifetime diagnosis of alcohol-related disorder to minimize misclassification of non-alcoholic fatty liver disease. Cox regression estimated hazard ratios for non-alcoholic fatty liver disease were determined. During 246,559 person-years of follow-up, 53 individuals with celiac disease had a diagnosis of non-alcoholic fatty liver disease (21/100,000 person-years). In comparison, we identified 85 reference individuals diagnosed with non-alcoholic fatty liver disease during 1,488,413 person-years (6/100,000 person-years). This corresponded to a hazard ratio of 2.8 (95% CI 2.0-3.8), with the highest risk estimates seen in children (HR = 4.6; 95% CI 2.3-9.1). The risk increase in the first year after celiac disease diagnosis was 13.3 (95% CI 3.5-50.3) but remained significantly elevated even beyond 15 years after the diagnosis of celiac disease (HR = 2.5; 95% CI 1.0-5.9). Individuals with celiac disease are at increased risk of non-alcoholic fatty liver disease compared to the general population. Excess risks were highest in the first year after celiac disease diagnosis, but persisted through 15 years after diagnosis with celiac disease. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

[Intestinal lymphangiectasis secondary to cicatricial fibrosis of mesenteric nodes: a nosologic entity?].

PubMed

Molas, G; Ponsot, P; Amouyal, P; Vallin, J; Vitaux, J; Paolaggi, J A; Potet, F

1990-01-01

Exsudative enteropathy was suspected in a 27-year-old man with lower limb edema, hypoprotidemia and hypoalbuminemia. Gastrointestinal mucosa, kidney, liver, and heart were normal. Laparoscopy showed diffuse small intestine lymphangiectasia. This diagnosis was confirmed by the microscopic examination of several biopsies obtained at laparotomy. Pathological examination of peritoneal, lymph nodes, and liver biopsies showed fibrous thickening of the peritoneum and fibrosis of the lymph nodes. Our patient has been followed for 16 years. Substantial improvement of clinical symptoms was obtained by following a special salt-free diet containing short-chain triglycerides. However biochemical abnormalities have persisted. Exsudative enteropathy due to intestinal lymphangiectasia may be observed in heart and liver diseases as well as in malignant affections of mesenteric lymph nodes. If these conditions are excluded, intestinal lymphangiectasia may be considered as a primitive lymph vessel malformation. The discovery of primitive intestinal lymphangiectasia in an adult cannot be attributed to congenital abnormalities alone. Fibrosis encountered in some cases suggests that an inflammatory process of unknown origin may trigger the onset of intestinal lymphangiectasia.

Nutritional support for treatment of hepatic lipidosis in a llama.

PubMed

Van Saun, R J; Callihan, B R; Tornquist, S J

2000-11-15

A 3-year-old female llama that was 3 months into her first lactation and 10 weeks pregnant was evaluated for anorexia of 24 hours' duration. On physical examination, the llama was in lateral recumbency, bradycardic, tachypneic, and hyperthermic. Palpation per rectum confirmed the presence of a possible dry fecal mass in the spiral colon. A tissue biopsy specimen of the liver was obtained, and histologic examination revealed moderate diffuse lipid accumulation within the hepatocytes. Lactated Ringer's solution was administered for rehydration, and partial parenteral nutrition was then initiated. Hepatic lipidosis is a disease characterized by abnormal accumulation of lipid in the liver and is associated with high mortality in camelids. Anorexia associated with hepatic lipidosis promotes further lipid mobilization and fatty infiltration of the liver. Partial parenteral nutrition with enteral supplementation may be used to maintain adequate energy intake and minimize further lipid mobilization. The distinctive metabolism of camelids may require higher amino acid supplementation relative to nonprotein calories in parenteral solutions than those traditionally provided to other species. Treatment with insulin may be effective

Current Status of Herbal Medicines in Chronic Liver Disease Therapy: The Biological Effects, Molecular Targets and Future Prospects

PubMed Central

Hong, Ming; Li, Sha; Tan, Hor Yue; Wang, Ning; Tsao, Sai-Wah; Feng, Yibin

2015-01-01

Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study. PMID:26633388

Current Status of Herbal Medicines in Chronic Liver Disease Therapy: The Biological Effects, Molecular Targets and Future Prospects.

PubMed

Hong, Ming; Li, Sha; Tan, Hor Yue; Wang, Ning; Tsao, Sai-Wah; Feng, Yibin

2015-12-02

Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study.

Bilateral native nephrectomy to reduce oxalate stores in children at the time of combined liver-kidney transplantation for primary hyperoxaluria type 1.

PubMed

Lee, Eliza; Ramos-Gonzalez, Gabriel; Rodig, Nancy; Elisofon, Scott; Vakili, Khashayar; Kim, Heung Bae

2018-05-01

Primary hyperoxaluria type-1 (PH-1) is a rare genetic disorder in which normal hepatic metabolism of glyoxylate is disrupted resulting in diffuse oxalate deposition and end-stage renal disease (ESRD). While most centers agree that combined liver-kidney transplant (CLKT) is the appropriate treatment for PH-1, perioperative strategies for minimizing recurrent oxalate-related injury to the transplanted kidney remain unclear. We present our management of children with PH-1 and ESRD on hemodialysis (HD) who underwent CLKT at our institution from 2005 to 2015. On chart review, three patients (2 girls, 1 boy) met study criteria. Two patients received deceased-donor split-liver grafts, while one patient received a whole liver graft. All patients underwent bilateral native nephrectomy at transplant to minimize the total body oxalate load. Median preoperative serum oxalate was 72 μmol/L (range 17.8-100). All patients received HD postoperatively until predialysis serum oxalate levels fell <20 μmol/L. All patients, at a median of 7.5 years of follow-up (range 6.5-8.9), demonstrated stable liver and kidney function. While CLKT remains the definitive treatment for PH-1, bilateral native nephrectomy at the time of transplant reduces postoperative oxalate stores and may mitigate damage to the renal allograft.

Diffusion kurtosis imaging of the liver at 3 Tesla: in vivo comparison to standard diffusion-weighted imaging.

PubMed

Budjan, Johannes; Sauter, Elke A; Zoellner, Frank G; Lemke, Andreas; Wambsganss, Jens; Schoenberg, Stefan O; Attenberger, Ulrike I

2018-01-01

Background Functional techniques like diffusion-weighted imaging (DWI) are gaining more and more importance in liver magnetic resonance imaging (MRI). Diffusion kurtosis imaging (DKI) is an advanced technique that might help to overcome current limitations of DWI. Purpose To evaluate DKI for the differentiation of hepatic lesions in comparison to conventional DWI at 3 Tesla. Material and Methods Fifty-six consecutive patients were examined using a routine abdominal MR protocol at 3 Tesla which included DWI with b-values of 50, 400, 800, and 1000 s/mm 2 . Apparent diffusion coefficient maps were calculated applying a standard mono-exponential fit, while a non-Gaussian kurtosis fit was used to obtain DKI maps. ADC as well as Kurtosis-corrected diffusion ( D) values were quantified by region of interest analysis and compared between lesions. Results Sixty-eight hepatic lesions (hepatocellular carcinoma [HCC] [n = 25]; hepatic adenoma [n = 4], cysts [n = 18]; hepatic hemangioma [HH] [n = 18]; and focal nodular hyperplasia [n = 3]) were identified. Differentiation of malignant and benign lesions was possible based on both DWI ADC as well as DKI D-values ( P values were in the range of 0.04 to < 0.0001). Conclusion In vivo abdominal DKI calculated using standard b-values is feasible and enables quantitative differentiation between malignant and benign liver lesions. Assessment of conventional ADC values leads to similar results when using b-values below 1000 s/mm 2 for DKI calculation.

Primary hepatic neuroendocrine tumor after 4 years tumor-free follow-up.

PubMed

Lambrescu, Ioana Maria; Martin, Sorina; Cima, Luminita; Herlea, Vlad; Badiu, Corin; Fica, Simona

2015-06-01

A primary hepatic neuroendocrine tumour (PHNET) is a very rare disease. The liver represents the preferential site for neuroendocrine tumors' metastases. A 45-year old Caucasian female who presented with nausea, vomiting, diarrhea, accompanied by diffuse abdominal pain was found to have on contrast-enhanced computer tomography an encapsulated, partially cystic liver mass. The patient underwent an uneventful left atypical hepatic resection. Histopatological and immunohistochemical examination revealed a slowly growing (G1) hepatic neuroendocrine tumour. Post surgery, the specific neuroendocrine markers (serum Chromogranin A and 24h urinary 5 hydroxy-indolacetic acid) were within normal range. Further functional imaging investigations were performed. No other lesions were found making probable the diagnosis of PHNET. The patient is presently after 4 years of follow-up with no local recurrence or distant metastases. The diagnosis of PHNET is a medical challenge that requires a thorough long term follow-up in order to exclude an occult primary neuroendocrine tumour.

Tissue Distribution of Enrofloxacin in African Clawed Frogs (Xenopus laevis) after Intramuscular and Subcutaneous Administration

PubMed Central

Felt, Stephen; Papich, Mark G; Howard, Antwain; Long, Tyler; McKeon, Gabriel; Torreilles, Stéphanie; Green, Sherril

2013-01-01

As part of an enrofloxacin pharmacokinetic study, concentrations of enrofloxacin and ciprofloxacin (metabolite) were measured in various tissues (brain, heart, kidney, liver, lung, and spleen) collected from treated (subcutaneous delivery, n = 3; intramuscular delivery, n = 3; untreated controls, n = 2) adult female Xenopus laevis by using HPLC. Enrofloxacin was rapidly absorbed after administration by either route and readily diffused into all sampled tissues. Enrofloxacin and ciprofloxacin were present in the tissue samples collected at 8 h. The highest average tissue concentrations for enrofloxacin were found in kidney, with the lowest concentrations in liver. Ciprofloxacin tissue concentrations paralleled but were always lower than those of enrofloxacin for all time points and tissues except brain and kidney. These results, together with previously published pharmacokinetic data and known minimal inhibitory concentrations of common pathogenic bacteria, provide a strong evidence-based rationale for choosing enrofloxacin to treat infectious diseases in X. laevis. PMID:23562103

Tissue distribution of enrofloxacin in African clawed frogs (Xenopus laevis) after intramuscular and subcutaneous administration.

PubMed

Felt, Stephen; Papich, Mark G; Howard, Antwain; Long, Tyler; McKeon, Gabriel; Torreilles, Stéphanie; Green, Sherril

2013-03-01

As part of an enrofloxacin pharmacokinetic study, concentrations of enrofloxacin and ciprofloxacin (metabolite) were measured in various tissues (brain, heart, kidney, liver, lung, and spleen) collected from treated (subcutaneous delivery, n = 3; intramuscular delivery, n = 3; untreated controls, n = 2) adult female Xenopus laevis by using HPLC. Enrofloxacin was rapidly absorbed after administration by either route and readily diffused into all sampled tissues. Enrofloxacin and ciprofloxacin were present in the tissue samples collected at 8 h. The highest average tissue concentrations for enrofloxacin were found in kidney, with the lowest concentrations in liver. Ciprofloxacin tissue concentrations paralleled but were always lower than those of enrofloxacin for all time points and tissues except brain and kidney. These results, together with previously published pharmacokinetic data and known minimal inhibitory concentrations of common pathogenic bacteria, provide a strong evidence-based rationale for choosing enrofloxacin to treat infectious diseases in X. laevis.

Optimization of intra-voxel incoherent motion imaging at 3.0 Tesla for fast liver examination.

PubMed

Leporq, Benjamin; Saint-Jalmes, Hervé; Rabrait, Cecile; Pilleul, Frank; Guillaud, Olivier; Dumortier, Jérôme; Scoazec, Jean-Yves; Beuf, Olivier

2015-05-01

Optimization of multi b-values MR protocol for fast intra-voxel incoherent motion imaging of the liver at 3.0 Tesla. A comparison of four different acquisition protocols were carried out based on estimated IVIM (DSlow , DFast , and f) and ADC-parameters in 25 healthy volunteers. The effects of respiratory gating compared with free breathing acquisition then diffusion gradient scheme (simultaneous or sequential) and finally use of weighted averaging for different b-values were assessed. An optimization study based on Cramer-Rao lower bound theory was then performed to minimize the number of b-values required for a suitable quantification. The duration-optimized protocol was evaluated on 12 patients with chronic liver diseases No significant differences of IVIM parameters were observed between the assessed protocols. Only four b-values (0, 12, 82, and 1310 s.mm(-2) ) were found mandatory to perform a suitable quantification of IVIM parameters. DSlow and DFast significantly decreased between nonadvanced and advanced fibrosis (P < 0.05 and P < 0.01) whereas perfusion fraction and ADC variations were not found to be significant. Results showed that IVIM could be performed in free breathing, with a weighted-averaging procedure, a simultaneous diffusion gradient scheme and only four optimized b-values (0, 10, 80, and 800) reducing scan duration by a factor of nine compared with a nonoptimized protocol. Preliminary results have shown that parameters such as DSlow and DFast based on optimized IVIM protocol can be relevant biomarkers to distinguish between nonadvanced and advanced fibrosis. © 2014 Wiley Periodicals, Inc.

Accuracy of apparent diffusion coefficient value measurement on PACS workstation: A comparative analysis.

PubMed

El Kady, Reem M; Choudhary, Arabinda Kumar; Tappouni, Rafel

2011-03-01

The purpose of this article is to evaluate the accuracy of apparent diffusion coefficient (ADC) measurements made with a PACS workstation compared with measurements made with a dedicated workstation, which is currently considered the reference standard. A retrospective review was performed in liver lesions from 79 patients using three MRI platforms. The final diagnosis was established by liver biopsy in 31 patients and by dynamic MRI and follow-up, both clinical and radiologic as indicated, in 48 patients. Each lesion that was clearly demonstrable on the ADC map was measured with a commercial dedicated postprocessing workstation and again with a PACS system. A two-sample t test was used to determine the statistically significant differences between the two ADC measurements. A total of 79 patients with 120 liver lesions were included. ADC values measured on the workstation were 0.4-4.38 × 10(-3) mm(2)/s. The ADC values measured on the PACS were 0.42-4.35 × 10(-3) mm(2)/s. The T value was -1.113, with 119 degrees of freedom, and the significance level was 0.268, which implies no significant difference between the two different measuring systems for all pathologic abnormalities and MRI scanners used. ADC values measured on a routine PACS workstation are as accurate as the values obtained on a dedicated specialized workstation. ADC value measurement on the routine PACS will save time and lead to increased utilization, which, in turn, will lead to an improved understanding of the different disease processes and their clinical management.

Cell Death and Cell Death Responses in Liver Disease: Mechanisms and Clinical Relevance

PubMed Central

Luedde, Tom; Kaplowitz, Neil; Schwabe, Robert F.

2015-01-01

Summary Hepatocellular death is present in almost all types of human liver disease and is used as a sensitive parameter for the detection of acute and chronic liver disease of viral, toxic, metabolic, or autoimmune origin. Clinical data and animal models suggest that hepatocyte death is the key trigger of liver disease progression, manifested by the subsequent development of inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Modes of hepatocellular death differ substantially between liver diseases. Different modes of cell death such as apoptosis, necrosis, and necroptosis trigger specific cell death responses and promote progression of liver disease through distinct mechanisms. In this review, we first discuss molecular mechanisms by which different modes of cell death, damage-associated molecular patterns, and specific cell death responses contribute to the development of liver disease. We then review the clinical relevance of cell death, focusing on biomarkers; the contribution of cell death to drug-induced, viral, and fatty liver disease and liver cancer; and evidence for cell death pathways as therapeutic targets. PMID:25046161

Control of oxygen tension recapitulates zone-specific functions in human liver microphysiology systems.

PubMed

Lee-Montiel, Felipe T; George, Subin M; Gough, Albert H; Sharma, Anup D; Wu, Juanfang; DeBiasio, Richard; Vernetti, Lawrence A; Taylor, D Lansing

2017-10-01

This article describes our next generation human Liver Acinus MicroPhysiology System (LAMPS). The key demonstration of this study was that Zone 1 and Zone 3 microenvironments can be established by controlling the oxygen tension in individual devices over the range of ca. 3 to 13%. The oxygen tension was computationally modeled using input on the microfluidic device dimensions, numbers of cells, oxygen consumption rates of hepatocytes, the diffusion coefficients of oxygen in different materials and the flow rate of media in the MicroPhysiology System (MPS). In addition, the oxygen tension was measured using a ratiometric imaging method with the oxygen sensitive dye, Tris(2,2'-bipyridyl) dichlororuthenium(II) hexahydrate (RTDP) and the oxygen insensitive dye, Alexa 488. The Zone 1 biased functions of oxidative phosphorylation, albumin and urea secretion and Zone 3 biased functions of glycolysis, α1AT secretion, Cyp2E1 expression and acetaminophen toxicity were demonstrated in the respective Zone 1 and Zone 3 MicroPhysiology System. Further improvements in the Liver Acinus MicroPhysiology System included improved performance of selected nonparenchymal cells, the inclusion of a porcine liver extracellular matrix to model the Space of Disse, as well as an improved media to support both hepatocytes and non-parenchymal cells. In its current form, the Liver Acinus MicroPhysiology System is most amenable to low to medium throughput, acute through chronic studies, including liver disease models, prioritizing compounds for preclinical studies, optimizing chemistry in structure activity relationship (SAR) projects, as well as in rising dose studies for initial dose ranging. Impact statement Oxygen zonation is a critical aspect of liver functions. A human microphysiology system is needed to investigate the impact of zonation on a wide range of liver functions that can be experimentally manipulated. Because oxygen zonation has such diverse physiological effects in the liver, we developed and present a method for computationally modeling and measuring oxygen that can easily be implemented in all MPS models. We have applied this method in a liver MPS in which we are then able to control oxygenation in separate devices and demonstrate that zonation-dependent hepatocyte functions in the MPS recapitulate what is known about in vivo liver physiology. We believe that this advance allows a deep experimental investigation on the role of zonation in liver metabolism and disease. In addition, modeling and measuring oxygen tension will be required as investigators migrate from PDMS to plastic and glass devices.

Control of oxygen tension recapitulates zone-specific functions in human liver microphysiology systems

PubMed Central

Lee-Montiel, Felipe T; George, Subin M; Sharma, Anup D; Wu, Juanfang; DeBiasio, Richard; Vernetti, Lawrence A; Taylor, D Lansing

2017-01-01

This article describes our next generation human Liver Acinus MicroPhysiology System (LAMPS). The key demonstration of this study was that Zone 1 and Zone 3 microenvironments can be established by controlling the oxygen tension in individual devices over the range of ca. 3 to 13%. The oxygen tension was computationally modeled using input on the microfluidic device dimensions, numbers of cells, oxygen consumption rates of hepatocytes, the diffusion coefficients of oxygen in different materials and the flow rate of media in the MicroPhysiology System (MPS). In addition, the oxygen tension was measured using a ratiometric imaging method with the oxygen sensitive dye, Tris(2,2′-bipyridyl) dichlororuthenium(II) hexahydrate (RTDP) and the oxygen insensitive dye, Alexa 488. The Zone 1 biased functions of oxidative phosphorylation, albumin and urea secretion and Zone 3 biased functions of glycolysis, α1AT secretion, Cyp2E1 expression and acetaminophen toxicity were demonstrated in the respective Zone 1 and Zone 3 MicroPhysiology System. Further improvements in the Liver Acinus MicroPhysiology System included improved performance of selected nonparenchymal cells, the inclusion of a porcine liver extracellular matrix to model the Space of Disse, as well as an improved media to support both hepatocytes and non-parenchymal cells. In its current form, the Liver Acinus MicroPhysiology System is most amenable to low to medium throughput, acute through chronic studies, including liver disease models, prioritizing compounds for preclinical studies, optimizing chemistry in structure activity relationship (SAR) projects, as well as in rising dose studies for initial dose ranging. Impact statement Oxygen zonation is a critical aspect of liver functions. A human microphysiology system is needed to investigate the impact of zonation on a wide range of liver functions that can be experimentally manipulated. Because oxygen zonation has such diverse physiological effects in the liver, we developed and present a method for computationally modeling and measuring oxygen that can easily be implemented in all MPS models. We have applied this method in a liver MPS in which we are then able to control oxygenation in separate devices and demonstrate that zonation-dependent hepatocyte functions in the MPS recapitulate what is known about in vivo liver physiology. We believe that this advance allows a deep experimental investigation on the role of zonation in liver metabolism and disease. In addition, modeling and measuring oxygen tension will be required as investigators migrate from PDMS to plastic and glass devices. PMID:28409533

The Effects of Physical Exercise on Fatty Liver Disease

PubMed Central

van der Windt, Dirk J.; Sud, Vikas; Zhang, Hongji; Tsung, Allan; Huang, Hai

2018-01-01

The increasing prevalence of obesity has made nonalcoholic fatty liver disease (NAFLD) the most common chronic liver disease. As a consequence, NAFLD and especially its inflammatory form nonalcoholic steatohepatitis (NASH) are the fastest increasing etiology of end-stage liver disease and hepatocellular carcinoma. Physical inactivity is related to the severity of fatty liver disease irrespective of body weight, supporting the hypothesis that increasing physical activity through exercise can improve fatty liver disease. This review summarizes the evidence for the effects of physical exercise on NAFLD and NASH. Several clinical trials have shown that both aerobic and resistance exercise reduce the hepatic fat content. From clinical and basic scientific studies, it is evident that exercise affects fatty liver disease through various pathways. Improved peripheral insulin resistance reduces the excess delivery of free fatty acids and glucose for free fatty acid synthesis to the liver. In the liver, exercise increases fatty acid oxidation, decreases fatty acid synthesis, and prevents mitochondrial and hepatocellular damage through a reduction of the release of damage-associated molecular patterns. In conclusion, physical exercise is a proven therapeutic strategy to improve fatty liver disease. PMID:29212576

Parenchymal signal intensity in 3-T body MRI of dogs with hematopoietic neoplasia.

PubMed

Feeney, Daniel A; Sharkey, Leslie C; Steward, Susan M; Bahr, Katherine L; Henson, Michael S; Ito, Daisuke; O'Brien, Timothy D; Jessen, Carl R; Husbands, Brian D; Borgatti, Antonella; Modiano, Jaime F

2013-04-01

We performed a preliminary study involving 10 dogs to assess the applicability of body MRI for staging of canine diffuse hematopoietic neoplasia. T1-weighted (before and after intravenous gadolinium), T2-weighted, in-phase, out-of-phase, and short tau inversion recovery pulse sequences were used. By using digital region of interest (ROI) and visual comparison techniques, relative parenchymal organ (medial iliac lymph nodes, liver, spleen, kidney cortex, and kidney medulla) signal intensity was quantified as less than, equal to, or greater than that of skeletal muscle in 2 clinically normal young adult dogs and 10 dogs affected with either B-cell lymphoma (n = 7) or myelodysplastic syndrome (n = 3). Falciform fat and urinary bladder were evaluated to provide additional perspective regarding signal intensity from the pulse sequences. Dogs with nonfocal disease could be distinguished from normal dogs according to both the visual and ROI signal-intensity relationships. In normal dogs, liver signal intensity on the T2-weighted sequence was greater than that of skeletal muscle by using either the visual or ROI approach. However in affected dogs, T2-weighted liver signal intensity was less than that of skeletal muscle by using either the ROI approach (10 of 10 dogs) or the visual approach (9 of 10 dogs). These findings suggest that the comparison of relative signal intensity among organs may have merit as a research model for infiltrative parenchymal disease (ROI approach) or metabolic effects of disease; this comparison may have practical clinical applicability (visual comparison approach) as well.

Parenchymal Signal Intensity in 3-T Body MRI of Dogs with Hematopoietic Neoplasia

PubMed Central

Feeney, Daniel A; Sharkey, Leslie C; Steward, Susan M; Bahr, Katherine L; Henson, Michael S; Ito, Daisuke; O'Brien, Timothy D; Jessen, Carl R; Husbands, Brian D; Borgatti, Antonella; Modiano, Jaime F

2013-01-01

We performed a preliminary study involving 10 dogs to assess the applicability of body MRI for staging of canine diffuse hematopoietic neoplasia. T1-weighted (before and after intravenous gadolinium), T2-weighted, in-phase, out-of-phase, and short tau inversion recovery pulse sequences were used. By using digital region of interest (ROI) and visual comparison techniques, relative parenchymal organ (medial iliac lymph nodes, liver, spleen, kidney cortex, and kidney medulla) signal intensity was quantified as less than, equal to, or greater than that of skeletal muscle in 2 clinically normal young adult dogs and 10 dogs affected with either B-cell lymphoma (n = 7) or myelodysplastic syndrome (n = 3). Falciform fat and urinary bladder were evaluated to provide additional perspective regarding signal intensity from the pulse sequences. Dogs with nonfocal disease could be distinguished from normal dogs according to both the visual and ROI signal-intensity relationships. In normal dogs, liver signal intensity on the T2-weighted sequence was greater than that of skeletal muscle by using either the visual or ROI approach. However in affected dogs, T2-weighted liver signal intensity was less than that of skeletal muscle by using either the ROI approach (10 of 10 dogs) or the visual approach (9 of 10 dogs). These findings suggest that the comparison of relative signal intensity among organs may have merit as a research model for infiltrative parenchymal disease (ROI approach) or metabolic effects of disease; this comparison may have practical clinical applicability (visual comparison approach) as well. PMID:23582424

A Different Perspective for Management of Diabetes Mellitus: Controlling Viral Liver Diseases.

PubMed

Zhao, Yingying; Xing, Huichun

2017-01-01

Knowing how to prevent and treat diabetes mellitus (DM) earlier is essential to improving outcomes. Through participating in synthesis and catabolism of glycogen, the liver helps to regulate glucose homeostasis. Viral related liver diseases are associated with glycometabolism disorders, which means effective management of viral liver diseases may be a therapeutic strategy for DM. The present article reviews the correlation between DM and liver diseases to give an update of the management of DM rooted by viral liver diseases.

Impact of Liver Indicators on Clinical Outcome in Patients Undergoing Transcatheter Aortic Valve Implantation.

PubMed

Wendt, Daniel; Kahlert, Philipp; Canbay, Ali; Knipp, Stephan; Thoenes, Martin; Cremer, Gordina; Al-Rashid, Fadi; Jánosi, Rolf-Alexander; El-Chilali, Karim; Kamler, Markus; El Gabry, Mohamed; Marx, Philipp; Dohle, Daniel Sebastian; Tsagakis, Konstantinos; Benedik, Jaroslav; Gerken, Guido; Rassaf, Tienush; Jakob, Heinz; Thielmann, Matthias

2017-10-01

Liver dysfunction increases death and morbidity after cardiac operations. There are currently no data evaluating liver function in patients undergoing transcatheter aortic valve replacement (TAVR). We aimed therefore to evaluate our TAVR results in regard to liver function. A total of 640 consecutive TAVR patients were evaluated. Of those, 11 patients presented with chronic liver disease before TAVR. The Model for End-Stage Liver Disease score was used to measure liver function in these patients. The primary study end point was 30-day mortality in patients presenting with liver dysfunction. Secondary study end point was liver enzymes after TAVR. The mean Model for End-Stage Liver Disease score in patients with chronic liver disease was 16.8 ± 6.2 (median, 18; range, 7 to 26). The 30-day mortality was 9.1% (57 of 629) in patients presenting without liver disease and 9.1% (1 of 11) in patients with liver disease (p = 1.00). Patients with chronic liver disease showed significantly higher preoperative levels of γ-glutamyl transpeptidase (p < 0.001). After TAVR, we observed a significant increase in alanine aminotransferase on postoperative day 3 compared with preoperative values (p < 0.001), accompanied by a decrease in albumin (p < 0.001). Liver cirrhosis per se is not considered as a contraindication for cardiac operations. In the present study, we did not observe a higher 30-day mortality rate in liver cirrhotic patients undergoing TAVR, suggesting TAVR as a feasible alternative with acceptable outcomes in patients with chronic liver disease. Moreover, the present study is the first to evaluate liver variables in patients undergoing TAVR. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Preclinical Models for Investigation of Herbal Medicines in Liver Diseases: Update and Perspective

PubMed Central

Tan, Hor-Yue; San-Marina, Serban; Wang, Ning; Hong, Ming; Li, Sha; Li, Lei; Cheung, Fan; Wen, Xiao-Yan; Feng, Yibin

2016-01-01

Liver disease results from a dynamic pathological process associated with cellular and genetic alterations, which may progress stepwise to liver dysfunction. Commonly, liver disease begins with hepatocyte injury, followed by persistent episodes of cellular regeneration, inflammation, and hepatocyte death that may ultimately lead to nonreversible liver failure. For centuries, herbal remedies have been used for a variety of liver diseases and recent studies have identified the active compounds that may interact with liver disease-associated targets. Further study on the herbal remedies may lead to the formulation of next generation medicines with hepatoprotective, antifibrotic, and anticancer properties. Still, the pharmacological actions of vast majority of herbal remedies remain unknown; thus, extensive preclinical studies are important. In this review, we summarize progress made over the last five years of the most commonly used preclinical models of liver diseases that are used to screen for curative herbal medicines for nonalcoholic fatty liver disease, liver fibrosis/cirrhosis, and liver. We also summarize the proposed mechanisms associated with the observed liver-protective, antifibrotic, and anticancer actions of several promising herbal medicines and discuss the challenges faced in this research field. PMID:26941826

Neutrophil gelatinase‐associated lipocalin level is a prognostic factor for survival in rat and human chronic liver diseases

PubMed Central

Yoshikawa, Kyoko; Iwasa, Motoh; Kojima, Shinichi; Yoshizawa, Naohiko; Tempaku, Mina; Sugimoto, Ryosuke; Yamamoto, Norihiko; Sugimoto, Kazushi; Kobayashi, Yoshinao; Hasegawa, Hiroshi; Takei, Yoshiyuki

2017-01-01

Chronic liver disease patients often have complications, such as hepatocellular carcinoma (HCC) and acute bacterial infection. Model for end‐stage liver disease and Child‐Pugh scores are useful prognostic factors for chronic liver diseases but not for all chronic conditions, such as HCC. Our investigative aim targeted the prognostic abilities of neutrophil gelatinase‐associated lipocalin (NGAL) in rat and human chronic liver diseases. Blood NGAL levels were measured by enzyme‐linked immunosorbent assay in rats with cirrhosis and 96 patients with chronic liver disease and HCC. We examined the correlation between blood NGAL levels and liver functions as well as survival. In our rat model, liver NGAL expression was assessed by immunostaining, real‐time quantitative polymerase chain reaction, and immunoblot. In rats with cirrhosis, blood NGAL levels were continuously and significantly elevated in the deceased group and were significantly correlated with liver functions. Liver NGAL, toll‐like receptor 4, and interleukin‐6 levels were increased in the deceased group compared to the survival group. Blood NGAL levels were significantly correlated with liver NGAL levels, indicating blood NGAL was derived from the liver. In patients with chronic liver disease, blood NGAL levels were associated with liver function and renal function. Blood NGAL levels were significantly increased in patients with chronic liver disease with HCC compared to without HCC. For the survival group, 38 out of 96 patients were dead in the average follow‐up period of 9.9 months. The patients with blood NGAL ≤119 ng/mL had significantly longer rates of survival compared to patients with blood NGAL >119 ng/mL. Conclusion: Blood NGAL predicts the survival rate in rat and human chronic liver diseases. Our findings suggest blood NGAL may be prognostic of survival in chronic liver diseases complicated by HCC. (Hepatology Communications 2017;1:946–956) PMID:29404502

The utility of uric acid assay in dogs as an indicator of functional hepatic mass.

PubMed

Hill, J M; Leisewitz, A L; Goddard, A

2011-06-01

Uric acid was used as a test for liver disease before the advent of enzymology. Three old studies criticised uric acid as a test of liver function. Uric acid, as an end-product of purine metabolism in the liver, deserved re-evaluation as a liver function test. Serum totalbile acids are widely accepted as the most reliable liver function test. This study compared the ability of serum uric acid concentration to assess liver function with that of serum pre-prandial bile acids in dogs. In addition, due to the renal excretion of uric acid the 2 assays were also compared in a renal disease group. Using a control group of healthy dogs, a group of dogs with congenital vascular liver disease, a group of dogs with non-vascular parenchymal liver diseases and a renal disease group, the ability of uric acid and pre-prandial bile acids was compared to detect reduced functional hepatic mass overall and in the vascular or parenchymal liver disease groups separately. Sensitivities, specificities and predictive value parameters were calculated for each test. The medians of uric acid concentration did not differ significantly between any of the groups, whereas pre-prandial bile acids medians were significantly higher in the liver disease groups compared with the normal and renal disease group of dogs. The sensitivity of uric acid in detecting liver disease overall was 65% while the specificity of uric acid in detecting liver disease overall was 59%. The sensitivity and specificity of uric acid in detecting congenital vascular liver disease was 68% and 59%, respectively. The sensitivity and specificity of uric acid in detecting parenchymal liver disease was 63% and 60%, respectively. The overall positive and negative predictive values for uric acid in detecting liver disease were poor and the data in this study indicated uric acid to be an unreliable test of liver function. In dogs suffering from renal compromise serum uric acid concentrations may increase into the abnormal range due to its renal route of excretion.

Management of alcohol misuse in patients with liver diseases

PubMed Central

Peng, Jennifer L; Patel, Milan Prakash; McGee, Breann; Liang, Tiebing; Chandler, Kristina; Tayarachakul, Sucharat; O’Connor, Sean; Liangpunsakul, Suthat

2017-01-01

Excessive alcohol use not only causes alcoholic liver disease (ALD) but also increases the risk of liver-related mortality in patients who already have other chronic liver diseases. Screening for alcohol misuse or alcohol use disorder (AUD) among patients with underlying liver disease is essential. This clinical review covers what is known about ALD, the impact of alcohol in patients with underlying liver diseases, current management of alcohol misuse and AUD, and the management of alcohol misuse and AUD specifically in patients with liver diseases. Several treatment options for alcohol misuse and AUD exist such as psychosocial intervention and behavioral and pharmacological therapies. The strategies used in the treatment of alcohol misuse and AUD are still applicable in those who consume alcohol and have underlying liver disease. However, certain medications still need to be carefully used due to potentially worsening already compromised liver function. Screening of ongoing alcohol use in subjects with liver disease is important, and prompt intervention is needed to prevent the associated morbidity and mortality from the detrimental effects of continued alcohol use on underlying liver disease. Considering alcoholism is a complex disease, probably a multidisciplinary approach combining psychotherapy and comprehensive medical care will be the most effective. Future research could focus on identifying additional treatment options for addressing the psychotherapy component since the self-determination and will to quit drinking alcohol can play such a crucial role in promoting abstinence. PMID:27940551

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.

Causes of altered liver function tests - the role of alpha-1 antitrypsin.

PubMed

Stollenwerk, J; Schepke, M; Biecker, E

2016-09-01

Altered liver function tests are a common finding in clinical practice. Our retrospective study aimed to identify the diagnoses in a non-selected cohort of patients with altered liver tests and to investigate whether alpha-1 antitrypsin genotyping should be part of the diagnostic workup. 501 patients who were admitted to our outpatient clinic for further evaluation of altered liver function tests were included in the study. The patients underwent a standardized diagnostic program with history taking, physical examination, laboratory tests and ultrasonography. Liver biopsy was performed if appropriate. More than 50 % of the patients had nonalcoholic fatty liver disease. Alcoholic and drug-induced liver injury were found in 8.6 % and 7 % of patients, respectively. Chronic hepatitis B and C, autoimmune liver disease and inherited causes of liver disease made up for approximately 16 % of the diagnoses. The remaining patients were diagnosed with kryptogenic liver disease or had miscellaneous diagnoses. In 3.7 % of the genotyped patients, the alpha-1 antitrypsin genotype PiMZ was found. Nonalcoholic fatty liver disease is nowadays the most frequent cause of altered liver tests. Alcoholic liver disease might be underrepresented in our study since these patients less often seek medical attention or the diagnosis is already made by the primary care physician. Drug-induced liver injury was found in more patients than expected and might therefore be underdiagnosed in practice. The alpha-1 antitrypsin genotype PiMZ was found in absence of other possible causes of liver disease, indicating that the PiMZ genotype is itself a risk factor for liver disease. Genotyping for alpha-1 antitrypsin should therefore be done when other causes for altered liver function tests have been ruled out. © Georg Thieme Verlag KG Stuttgart · New York.

Nutritional Needs and Support for Children with Chronic Liver Disease

PubMed Central

Yang, Christine H.; Yoo, Eric R.; Kerner, John A.

2017-01-01

Malnutrition has become a dangerously common problem in children with chronic liver disease, negatively impacting neurocognitive development and growth. Furthermore, many children with chronic liver disease will eventually require liver transplantation. Thus, this association between malnourishment and chronic liver disease in children becomes increasingly alarming as malnutrition is a predictor of poorer outcomes in liver transplantation and is often associated with increased morbidity and mortality. Malnutrition requires aggressive and appropriate management to correct nutritional deficiencies. A comprehensive review of the literature has found that infants with chronic liver disease (CLD) are particularly susceptible to malnutrition given their low reserves. Children with CLD would benefit from early intervention by a multi-disciplinary team, to try to achieve nutritional rehabilitation as well as to optimize outcomes for liver transplant. This review explains the multifactorial nature of malnutrition in children with chronic liver disease, defines the nutritional needs of these children, and discusses ways to optimize their nutritional. PMID:29035331

Liver Transplant

MedlinePlus

... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

Role of innate immunity and the microbiota in liver fibrosis: crosstalk between the liver and gut

PubMed Central

Seki, Ekihiro; Schnabl, Bernd

2012-01-01

Liver fibrosis occurs as a wound-healing scar response following chronic liver inflammation including alcoholic liver disease, non-alcoholic steatohepatitis, viral hepatitis, cholestatic liver disease and autoimmune liver diseases. The liver has a unique vascular system within the gastrointestinal tract, as the majority of the liver's blood supply comes from the intestine through the portal vein. When the intestinal barrier function is disrupted, an increase in intestinal permeability leads to the translocation of intestine-derived bacterial products such as lipopolysaccharide (LPS) and unmethylated CpG containing DNA to the liver via the portal vein. These gut-derived bacterial products stimulate innate immune receptors, namely Toll-like receptors (TLRs), in the liver. TLRs are expressed on Kupffer cells, endothelial cells, dendritic cells, biliary epithelial cells, hepatic stellate cells, and hepatocytes. TLRs activate these cells to contribute to acute and chronic liver diseases. This review summarizes recent studies investigating the role of TLRs, intestinal microbiota and bacterial translocation in liver fibrosis, alcoholic liver disease and non-alcoholic steatohepatitis. PMID:22124143

Application of Induced Pluripotent Stem Cells in Liver Diseases

PubMed Central

Yu, Yue; Wang, Xuehao; Nyberg, Scott L.

2014-01-01

Tens of millions of patients are affected by liver disease worldwide. Many of these patients can benefit from therapy involving hepatocyte transplantation. Liver transplantation is presently the only proven treatment for many medically refractory liver diseases including end-stage liver failure and inherited metabolic liver disease. However, the shortage in transplantable livers prevents over 40% of listed patients per year from receiving a liver transplant; many of these patients die before receiving an organ offer or become too sick to transplant. Therefore, new therapies are needed to supplement whole-organ liver transplantation and reduce mortality on waiting lists worldwide. Furthermore, the remarkable regenerative capacity of hepatocytes in vivo is exemplified by the increasing number of innovative cell-based therapies and animal models of human liver disorders. Induced pluripotent stem cells (iPSCs) have similar properties to those of embryonic stem cells (ESCs) but bypass the ethical concerns of embryo destruction. Therefore, generation of hepatocyte-like cells (HLCs) using iPSC technology may be beneficial for the treatment of severe liver diseases, screening of drug toxicities, basic research of several hepatocytic disorders, and liver transplantation. Here we briefly summarize the growing number of potential applications of iPSCs for treatment of liver disease. PMID:26858888

Liver disease

MedlinePlus

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Benign Liver Tumors

MedlinePlus

... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

Liver Function Tests

MedlinePlus

... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

Diagnostic value of diffusion weighted MRI and ADC in differential diagnosis of cavernous hemangioma of the liver.

PubMed

Tokgoz, Ozlem; Unlu, Ebru; Unal, Ilker; Serifoglu, Ismail; Oz, Ilker; Aktas, Elif; Caglar, Emrah

2016-03-01

To investigate the use of diffusion weighted magnetic resonance imaging (DWI) and the apparent diffusion coefficient (ADC) values in the diagnosis of hemangioma. The study population consisted of 72 patients with liver masses larger than 1 cm (72 focal lesions). DWI examination with a b value of 600 s/mm2 was carried out for all patients. After DWI examination, an ADC map was created and ADC values were measured for 72 liver masses and normal liver tissue (control group). The average ADC values of normal liver tissue and focal liver lesions, the "cut-off" ADC values, and the diagnostic sensitivity and specificity of the ADC map in diagnosing hemangioma, benign and malignant lesions were researched. Of the 72 liver masses, 51 were benign and 21 were malignant. Benign lesions comprised 38 hemangiomas and 13 simple cysts. Malignant lesions comprised 9 hepatocellular carcinomas, and 12 metastases. The highest ADC values were measured for cysts (3.782±0.53×10(-3) mm(2)/s) and hemangiomas (2.705±0.63×10(-3) mm(2)/s). The average ADC value of hemangiomas was significantly higher than malignant lesions and the normal control group (p<0.001). The average ADC value of cysts were significantly higher when compared to hemangiomas and normal control group (p<0.001). To distinguish hemangiomas from malignant liver lesions, the "cut-off" ADC value of 1.800×10(-3) mm(2)/s had a sensitivity of 97.4% and a specificity of 90.9%. To distinguish hemangioma from normal liver parenchyma the "cut-off" value of 1.858×10(-3) mm(2)/s had a sensitivity of 97.4% and a specificity of 95.7%. To distinguish benign liver lesions from malignant liver lesions the "cut-off" value of 1.800×10(-3) mm(2)/s had a sensitivity of 96.1% and a specificity of 90.0%. DWI and quantitative measurement of ADC values can be used in differential diagnosis of benign and malignant liver lesions and also in the diagnosis and differentiation of hemangiomas. When dynamic examination cannot distinguish cases with vascular metastasis and lesions from hemangioma, DWI and ADC values can be useful in the primary diagnosis and differential diagnosis. The technique does not require contrast material, so it can safely be used in patients with renal failure.

Coeliac disease in autoimmune liver disease: a cross-sectional study and a systematic review.

PubMed

Mirzaagha, Foroozandeh; Azali, Sepideh Hagh; Islami, Farhad; Zamani, Farhad; Khalilipour, Elias; Khatibian, Morteza; Malekzadeh, Reza

2010-09-01

Several studies have reported an association between coeliac disease and autoimmune liver disease, but there is little information on the prevalence of coeliac disease in certain autoimmune liver diseases, particularly from non-European, non-American countries. To investigate prevalence of coeliac disease in autoimmune liver disease in Iran and to summarize previous literature. We investigated prevalence of coeliac disease among 100 autoimmune liver disease patients and compared it with the prevalence in healthy individuals. We also performed an extensive search of the English literature in PubMed Database. We found substantially elevated prevalence of coeliac disease in patients with overlap syndrome (10-15%) compared to the general population (0.1-1%). To a lesser extent, the prevalence was high in patients with autoimmune hepatitis (2-4%). In our systematic review, prevalence of coeliac disease in autoimmune hepatitis in the majority of studies was 4% or more; several studies also reported such prevalence in primary biliary cirrhosis. Since coeliac disease is common among patients with autoimmune liver disease, screening autoimmune liver disease patients for coeliac disease is indicated. Although the magnitude of benefit from a gluten-free diet in reversing autoimmune liver disease in patients with coeliac disease is controversial, it may reduce the risk of further complications of coeliac disease. Copyright (c) 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Alcoholic Liver Disease: Pathogenesis and Current Management

PubMed Central

Osna, Natalia A.; Donohue, Terrence M.; Kharbanda, Kusum K.

2017-01-01

Excessive alcohol consumption is a global healthcare problem. The liver sustains the greatest degree of tissue injury by heavy drinking because it is the primary site of ethanol metabolism. Chronic and excessive alcohol consumption produces a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, and fibrosis/cirrhosis. Steatosis is the earliest response to heavy drinking and is characterized by the deposition of fat in hepatocytes. Steatosis can progress to steatohepatitis, which is a more severe, inflammatory type of liver injury. This stage of liver disease can lead to the development of fibrosis, during which there is excessive deposition of extracellular matrix proteins. The fibrotic response begins with active pericellular fibrosis, which may progress to cirrhosis, characterized by excessive liver scarring, vascular alterations, and eventual liver failure. Among problem drinkers, about 35 percent develop advanced liver disease because a number of disease modifiers exacerbate, slow, or prevent alcoholic liver disease progression. There are still no FDA-approved pharmacological or nutritional therapies for treating patients with alcoholic liver disease. Cessation of drinking (i.e., abstinence) is an integral part of therapy. Liver transplantation remains the life-saving strategy for patients with end-stage alcoholic liver disease. PMID:28988570

LiverAtlas: a unique integrated knowledge database for systems-level research of liver and hepatic disease.

PubMed

Zhang, Yanqiong; Yang, Chunyuan; Wang, Shaochuang; Chen, Tao; Li, Mansheng; Wang, Xue; Li, Dongsheng; Wang, Kang; Ma, Jie; Wu, Songfeng; Zhang, Xueli; Zhu, Yunping; Wu, Jinsheng; He, Fuchu

2013-09-01

A large amount of liver-related physiological and pathological data exist in publicly available biological and bibliographic databases, which are usually far from comprehensive or integrated. Data collection, integration and mining processes pose a great challenge to scientific researchers and clinicians interested in the liver. To address these problems, we constructed LiverAtlas (http://liveratlas.hupo.org.cn), a comprehensive resource of biomedical knowledge related to the liver and various hepatic diseases by incorporating 53 databases. In the present version, LiverAtlas covers data on liver-related genomics, transcriptomics, proteomics, metabolomics and hepatic diseases. Additionally, LiverAtlas provides a wealth of manually curated information, relevant literature citations and cross-references to other databases. Importantly, an expert-confirmed Human Liver Disease Ontology, including relevant information for 227 types of hepatic disease, has been constructed and is used to annotate LiverAtlas data. Furthermore, we have demonstrated two examples of applying LiverAtlas data to identify candidate markers for hepatocellular carcinoma (HCC) at the systems level and to develop a systems biology-based classifier by combining the differential gene expression with topological features of human protein interaction networks to enhance the ability of HCC differential diagnosis. LiverAtlas is the most comprehensive liver and hepatic disease resource, which helps biologists and clinicians to analyse their data at the systems level and will contribute much to the biomarker discovery and diagnostic performance enhancement for liver diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Interactions Between the Intestinal Microbiome and Liver Diseases

PubMed Central

Schnabl, Bernd; Brenner, David A.

2014-01-01

The human intestine harbors a diverse community of microbes that promote metabolism and digestion in their symbiotic relationship with the host. Disturbance of its homeostasis can result in disease. We review factors that disrupt intestinal homeostasis and contribute to non-alcoholic fatty liver disease (NAFLD), steatohepatitis (NASH), alcoholic liver disease, and cirrhosis. Liver disease has long been associated with qualitative and quantitative (overgrowth) dysbiotic changes in the intestinal microbiota. Extrinsic factors, such as the Western diet and alcohol, contribute to these changes. Dysbiosis results in intestinal inflammation, a breakdown of the intestinal barrier, and translocation of microbial products in animal models. However, the contribution of the intestinal microbiome to liver disease goes beyond simple translocation of bacterial products that promote hepatic injury and inflammation. Microbial metabolites produced in a dysbiotic intestinal environment and host factors are equally important in the pathogenesis of liver disease. We review how the combination of liver insult and disruptions in intestinal homeostasis contribute to liver disease. PMID:24440671

Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research

PubMed Central

Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu

2015-01-01

Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and ‘-omics’-based read-outs are still in their infancy, but show great promise. . In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. PMID:26073454

Acute hepatitis A and B in patients with chronic liver disease: prevention through vaccination.

PubMed

Keeffe, Emmet B

2005-10-01

Retrospective and prospective studies have demonstrated that the occurrence of acute hepatitis A in patients with chronic liver disease is associated with higher rates of morbidity and mortality than in previously healthy individuals with acute hepatitis A. The mortality associated with acute hepatitis A may be particularly high in patients with preexisting chronic hepatitis C. Although acute hepatitis B in patients with preexisting chronic liver disease is less well studied, worse outcomes than in previously healthy individuals are apparent. However, numerous studies convincingly demonstrate that chronic hepatitis B virus coinfection with hepatitis C virus (or hepatitis D virus) is associated with an accelerated natural history of liver disease and worse outcomes. These observations led to studies that demonstrated the safety and efficacy of hepatitis A and hepatitis B vaccination in patients with mild-to-moderate chronic liver disease. Hepatitis A and B vaccination is less effective in patients with advanced liver disease, especially after decompensation, such as in patients awaiting liver transplantation, and in liver transplant recipients. The emerging lower rates of inherent immunity in younger individuals, higher morbidity and mortality of acute hepatitis A or B superimposed on chronic liver disease, and greater vaccine efficacy in milder forms of chronic liver disease suggest that it is a reasonable policy to recommend hepatitis A and B vaccination in patients early in the natural history of chronic liver disease.

Coffee and Liver Disease.

PubMed

Wadhawan, Manav; Anand, Anil C

2016-03-01

Coffee is the most popular beverage in the world. Consumption of coffee has been shown to benefit health in general, and liver health in particular. This article reviews the effects of coffee intake on development and progression of liver disease due to various causes. We also describe the putative mechanisms by which coffee exerts the protective effect. The clinical evidence of benefit of coffee consumption in Hepatitis B and C, as well as nonalcoholic fatty liver disease and alcoholic liver disease, has also been presented. Coffee consumption is associated with improvement in liver enzymes (ALT, AST, and GGTP), especially in individuals with risk for liver disease. Coffee intake more than 2 cups per day in patients with preexisting liver disease has been shown to be associated with lower incidence of fibrosis and cirrhosis, lower hepatocellular carcinoma rates, as well as decreased mortality.

Abnormal hepatic biochemistries and clinical liver disease in patients with primary Sjögren's syndrome.

PubMed

Montaño-Loza, Aldo J; Crispín-Acuña, José Carlos; Remes-Troche, José María; Uribe, Misael

2007-01-01

Patients with primary Sjögren's syndrome may present liver involvement. Our goals were to establish the prevalence of abnormal hepatic biochemistries and clinical liver disease in patients with primary Sjögren's syndrome and correlate their presence with other clinical and laboratory features. Ninety-five patients with diagnosis of primary Sjögren's syndrome were studied. Data on gender, age, clinical features, liver biochemistries, tests of inflammation and autoimmunity, and concomitant diseases were collected. Forty-two patients (44%) had abnormal hepatic biochemistries, and of these 19 patients (20%) had clinical liver disease. Patients with abnormal hepatic biochemistries had higher frequency of autoimmune hypotiroidism, arthritis, vasculitis, Raynaud's phenomenon, higher sedimentation rate,and higher frequency of antinuclear and antimitochondrial antibodies than patients with normal liver biochemistries (P < 0.05 for each). Patients with clinical liver disease had higher frequency of arthritis, vasculitis, and higher frequency of antimitochondrial antibodies than patients without clinical liver disease (P < 0.05 for each). Twenty-one patients had diagnosis of a specific liver disease, such as hepatitis C virus infection (n = 11), autoimmune hepatitis (n = 2), primary biliary cirrhosis (n =5),nonalcoholic fatty liver disease (n = 2), and hepatitis B virus infection (n = 1). In half of patients with liver involvement a definitive cause could not be identified. Liver involvement is frequently found in patients with primary Sjögren's syndrome, and its presence is associated with clinical features of systemic disease, and markers of autoimmunity and inflammation. There may be a subgroup of patients with liver involvement secondary to primary Sjögren's syndrome.

The Role of Akt in Chronic Liver Disease and Liver Regeneration.

PubMed

Morales-Ruiz, Manuel; Santel, Ansgar; Ribera, Jordi; Jiménez, Wladimiro

2017-02-01

The liver is continuously exposed to diverse insults, which may culminate in pathological processes causing liver disease. An effective therapeutic strategy for chronic liver disease should control the causal factors of the disease and stimulate functional liver regeneration. Preclinical studies have shown that interventions aimed at maintaining Akt activity in a dysfunctional liver meet most of the criteria. Although the central function of Akt is cell survival, other cellular aspects such as glucose uptake, glycogen synthesis, cell-cycle progression, and lipid metabolism have been shown to be prominent functions of Akt in the context of hepatic physiology. In this review, the authors describe the benefits of the Akt signaling pathway, emphasizing its importance in coordinating proper cellular growth and differentiation during liver regeneration, hepatic function, and liver disease. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Systemic Venous Inflow to the Liver Allograft to Overcome Diffuse Splanchnic Venous Thrombosis

PubMed Central

Darius, Tom; Goffette, Pierre; Lerut, Jan

2015-01-01

Diffuse splanchnic venous thrombosis (DSVT), formerly defined as contraindication for liver transplantation (LT), is a serious challenge to the liver transplant surgeon. Portal vein arterialisation, cavoportal hemitransposition and renoportal anastomosis, and finally combined liver and small bowel transplantation are all possible alternatives to deal with this condition. Five patients with preoperatively confirmed extensive splanchnic venous thrombosis were transplanted using cavoportal hemitransposition (4x) and renoportal anastomosis (1x). Median follow-up was 58 months (range: 0,5 to 130 months). Two patients with previous radiation-induced peritoneal injury died, respectively, 18 days and 2 months after transplantation. The three other patients had excellent long-term survival, despite the fact that two of them needed a surgical reintervention for severe gastrointestinal bleeding. Extensive splanchnic venous thrombosis is no longer an absolute contraindication to liver transplantation. Although cavoportal hemitransposition and renoportal anastomosis undoubtedly are life-saving procedures allowing for ensuring adequate allograft portal flow, careful follow-up of these patients remains necessary as both methods are unable to completely eliminate the complications of (segmental) portal hypertension. PMID:26539214

Identification of Plants That Inhibit Lipid Droplet Formation in Liver Cells: Rubus suavissimus Leaf Extract Protects Mice from High-Fat Diet-Induced Fatty Liver by Directly Affecting Liver Cells

PubMed Central

Takahashi, Tomohiro; Sugawara, Wataru; Takiguchi, Yuya; Takizawa, Kento; Nakabayashi, Ami; Nakamura, Mitsuo; Nagano-Ito, Michiyo; Ichikawa, Shinichi

2016-01-01

Fatty liver disease is a condition in which abnormally large numbers of lipid droplets accumulate in liver cells. Fatty liver disease induces inflammation under conditions of oxidative stress and may result in cancer. To identify plants that protect against fatty liver disease, we examined the inhibitory effects of plant extracts on lipid droplet formation in mouse hepatoma cells. A screen of 98 water extracts of plants revealed 4 extracts with inhibitory effects. One of these extracts, Rubus suavissimus S. Lee (Tien-cha or Chinese sweet tea) leaf extract, which showed strong inhibitory effects, was tested in a mouse fatty liver model. In these mouse experiments, intake of the plant extract significantly protected mice against fatty liver disease without affecting body weight gain. Our results suggest that RSE directly affects liver cells and protects them from fatty liver disease. PMID:27429636

Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review.

PubMed

Reardon, Jillian; Hussaini, Trana; Alsahafi, Majid; Azalgara, Vladimir Marquez; Erb, Siegfried R; Partovi, Nilufar; Yoshida, Eric M

2016-09-28

Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions. Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase. No search limits were applied. Additionally, references of the included studies were reviewed to identify additional articles. Results: The literature search yielded articles meeting inclusion criteria for the following indications: non-alcoholic fatty liver disease (n = 5); alcoholic liver disease (n = 2); autoimmune hepatitis (n = 6), liver transplant (n = 2) and viral hepatitis (n = 9). Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease, autoimmune hepatitis and hepatitis B and C infections. In contrast, liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation. The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease. In the prospective trials reviewed, adverse effects associated with the bile acids were limited to minor gastrointestinal complaints (most often, diarrhea) and did not occur at increased frequency as compared to controls. As administration of bile acids was often limited to durations of 12 months or less, long-term side effects for non-cholestatic indications cannot be excluded. Conclusions: Based on the available literature, bile acids cannot be widely recommended for non-cholestatic liver diseases at present.

Diabetes, plasma glucose and incidence of fatty liver, cirrhosis and liver cancer: A prospective study of 0.5 million people.

PubMed

Pang, Yuanjie; Kartsonaki, Christiana; Turnbull, Iain; Guo, Yu; Clarke, Robert; Chen, Yiping; Bragg, Fiona; Yang, Ling; Bian, Zheng; Millwood, Iona Y; Hao, Juanzhi; Han, Xianyong; Zang, Yajing; Chen, Junshi; Li, Liming; Holmes, Michael V; Chen, Zhengming

2018-05-07

The prevalence of diabetes is increasing rapidly in China. However, evidence is limited about its effects on chronic liver diseases and liver cancer. We aimed to examine the associations of diabetes with chronic liver diseases and liver cancer and of random plasma glucose (RPG) with these liver diseases among participants without diabetes in Chinese adults, and to assess the possible interaction by hepatitis B virus (HBV) infection. The prospective China Kadoorie Biobank recruited 512,891 adults. During 10 years of follow-up, 2,568 liver cancer, 2,082 cirrhosis, 1,298 hospitalised non-alcoholic fatty liver disease (NAFLD), and 244 hospitalised alcoholic liver disease (ALD) were recorded among 503,993 participants without prior history of cancer or chronic liver diseases at baseline. Cox regression was used to estimate hazard ratios (HRs) for each disease by diabetes status (previously diagnosed or screen-detected) and, among those without previously diagnosed diabetes, by levels of RPG. Overall 5.8% of participants had diabetes at baseline. Compared with those without diabetes, individuals with diabetes had adjusted HRs of 1.49 (95% CI 1.30-1.70) for liver cancer, 1.81 (1.57-2.09) for cirrhosis, 1.76 (1.47-2.16) for NAFLD, and 2.24 (1.42-3.54) for ALD. The excess risks decreased but remained elevated in those with longer duration. Among those without previously diagnosed diabetes, RPG was positively associated with liver diseases, with adjusted HRs per 1 mmol/L higher RPG of 1.04 (1.03-1.06) for liver cancer, 1.07 (1.05-1.09) for cirrhosis, 1.07 (1.05-1.10) for NAFLD, and 1.10 (1.05-1.15) for ALD. These associations did not differ by HBV infection. In Chinese adults, diabetes and higher blood glucose levels among those without known diabetes are associated with increased risks of liver cancer and major chronic liver diseases. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Hepatic parenchymal preserving technique in the management of diffuse bilateral neuroendocrine tumour liver metastases: a feasible approach

PubMed Central

Nadler, Ashlie; Cukier, Moises; Milot, Laurent; Singh, Simron; Law, Calvin H.

2014-01-01

Background Aggressive surgical resection of neuroendocrine tumour liver metastases (NET-LM) is associated with symptomatic relief. Debulking up to 90% of tumour burden, even with positive margins, may be beneficial. However, patients with diffuse hepatic metastases may not qualify for resection owing to associated insufficient remnant liver parenchyma. The purpose of this study is to describe an early experience with a hepatic parenchymal preserving (HPP) approach. Methods We retrospectively reviewed our institutional neuroendocrine tumours database to identify patients with NET-LM, including symptomatic patients with extensive bilobar involvement, who underwent virtual volumetric assessment (VVA) combined with HPP resection between October 2008 and July 2011. Results Our study involved 9 patients. The median number of liver metastases resected was 10 (range 4–50). Symptomatic improvement was observed in all patients. Immediate postoperative normalization of 5-HIAA 24-hour urine levels occurred in 89% of patients. Symptomatic and biochemical response remained stable or improved in 75% of patients at 12 months of follow-up. Four patients had postoperative complications. There was no 90-day mortality. Conclusion The described HPP approach is feasible and safe. Most patients experienced symptomatic and biochemical improvement. This reproducible approach could expand surgical resection options for patients with NET-LM and diffuse bilobar involvement. PMID:24666455

Enzymatic liver function capacity correlates with disease severity of patients with liver cirrhosis: a study with the LiMAx test.

PubMed

Malinowski, Maciej; Jara, Maximilian; Lüttgert, Katja; Orr, James; Lock, Johan Friso; Schott, Eckart; Stockmann, Martin

2014-12-01

Assessment and quantification of actual liver function is crucial in patients with chronic liver disease to monitor disease progression and predict individual prognosis. Mathematical models, such as model for end-stage liver disease, are used for risk stratification of patients with chronic liver disease but do not include parameters that reflect the actual functional state of the liver. We aimed to evaluate the potential of a (13)C-based liver function test as a stratification tool by comparison with other liver function tests and clinical parameters in a large sample of healthy controls and cirrhotic patients. We applied maximum liver function capacity (LiMAx) to evaluate actual liver function in 347 patients with cirrhosis and in 86 controls. LiMAx showed strong negative correlation with Child-Pugh Score (r = -0.707; p < 0.001), MELD (r = -0.686; p < 0.001) and liver function tests. LiMAx was lower in patients with liver cirrhosis compared to healthy controls [99 (57-160) µg/kg/h vs. 412 (365-479) µg/kg/h, p < 0.001] and differed among Child-Pugh classes [a: 181 (144-227) µg/kg/h, b: 96 (62-132) µg/kg/h and c: 52 (37-81) µg/kg/h; p < 0.001]. When stratified patients according to disease severity, LiMAx results were not different between cirrhotic patients and cirrhotic patients with transjugular intrahepatic portosystemic shunt. LiMAx appears to provide reliable information on remnant enzymatic liver function in chronic liver disease and allows graduation of disease severity.

Comparison and reproducibility of ADC measurements in breathhold, respiratory triggered, and free-breathing diffusion-weighted MR imaging of the liver.

PubMed

Kwee, Thomas C; Takahara, Taro; Koh, Dow-Mu; Nievelstein, Rutger A J; Luijten, Peter R

2008-11-01

To compare and determine the reproducibility of apparent diffusion coefficient (ADC) measurements of the normal liver parenchyma in breathhold, respiratory triggered, and free-breathing diffusion-weighted magnetic resonance imaging (DWI). Eleven healthy volunteers underwent three series of DWI. Each DWI series consisted of one breathhold, one respiratory triggered, and two free-breathing (thick and thin slice acquisition) scans of the liver, at b-values of 0 and 500 s/mm2. ADCs of the liver parenchyma were compared by using nonparametric tests. Reproducibility was assessed by the Bland-Altman method. Mean ADCs (in 10(-3) mm2/sec) in respiratory triggered DWI (2.07-2.27) were significantly higher than mean ADCs in breathhold DWI (1.57-1.62), thick slice free-breathing DWI (1.62-1.65), and thin slice free-breathing DWI (1.57-1.66) (P<0.005). Ranges of mean difference in ADC measurement+/-limits of agreement between two scans were -0.02-0.05+/-0.16-0.24 in breathhold DWI, -0.14-0.20+/-0.59-0.60 in respiratory triggered DWI, -0.03-0.03+/-0.20-0.29 in thick slice free-breathing DWI, and -0.01-0.09+/-0.21-0.29 in thin slice free-breathing DWI. ADC measurements of the normal liver parenchyma in respiratory triggered DWI are significantly higher and less reproducible than in breathhold and free-breathing DWI. Copyright (c) 2008 Wiley-Liss, Inc.

[Disease burden of liver cancer in the Chinese population, in 1990 and 2013].

PubMed

Wang, L J; Yin, P; Liu, Y N; Liu, J M; Qi, J L; Zhou, M G

2016-06-01

To analyze the disease burden of liver cancer in the Chinese population in 1990 and 2013. Data from Global Burden of Diseases 2013 (GBD2013) was used to analyze the disease burden of liver cancer in China. The main outcome measurements would include mortality and disability-adjusted life years (DALY). Again, GBD global standard population in 2013 was used as the reference population to calculate the age-standardized rate. Related changes on percentage from 1990 to 2013 were calculated to analyze the changing patterns of disease burden for liver cancer in China. In 2013, a total of 358 100 people died of liver cancer, with the crude death rate as 25.85/100 000, in China. Number of deaths due to liver cancer secondary to hepatitis B was 163 600 (accounting for 45.69%). Number of deaths due to liver cancer secondary to hepatitis C was 134 200 (accounting for 37.48%) with DALY due to liver cancer appeared as 40.80 million person years. In 2013, the leading causes of DALY related to liver cancer was liver cancer secondary to hepatitis B, followed by liver cancer secondary to hepatitis C, liver cancer secondary to alcohol use, other liver cancers, with related DALYs as 4 652.0, 3 394.3, 964.3 and 592.1 thousands person years, respectively. The disease burdens of liver cancer secondary to various kinds of liver cancer were significantly higher in males than in females. Compared with 1990, the standardized mortality of liver cancer reduced by 25.00%, the DALY attributable to liver cancer increased by 16.95% and the standardized DALY rate attributable to liver cancer reduced by 33.47%. The burden of liver cancer secondary to hepatitis C became more serious and the standardized death rate increased by 106.18%, together with the standardized DALY rate increased by 91.68% in the past 23 years. Disease burden of liver cancer among young adults and the elderly were most serious. When comparing with the data in 1990, the standardized DALY rate showed declining trend in all the age groups, with the most seen in the 5-14 year group. The standardized DALY rate, secondary to hepatitis B had a 46.37% decrease in the 5-14 year olds. The standardized DALY rate secondary to hepatitis C showed an increasing trend in all the age groups. Liver cancer had been one of the serious diseases that causing heavy disease burden in China. In recent years, the disease burden of liver cancer secondary to hepatitis B decreased but the disease burden of liver cancer secondary to hepatitis C significantly increased. Disease burden on liver cancer in male population was significantly higher than that in females, showing that related targeted prevention and control measures should be imminently carried out.

Magnetic Resonance Elastography and Other Magnetic Resonance Imaging Techniques in Chronic Liver Disease: Current Status and Future Directions.

PubMed

Tan, Cher Heng; Venkatesh, Sudhakar Kundapur

2016-09-15

Recent advances in the noninvasive imaging of chronic liver disease have led to improvements in diagnosis, particularly with magnetic resonance imaging (MRI). A comprehensive evaluation of the liver may be performed with the quantification of the degree of hepatic steatosis, liver iron concentration, and liver fibrosis. In addition, MRI of the liver may be used to identify complications of cirrhosis, including portal hypertension, ascites, and the development of hepatocellular carcinoma. In this review article, we discuss the state of the art techniques in liver MRI, namely, magnetic resonance elastography, hepatobiliary phase MRI, and liver fat and iron quantification MRI. The use of these advanced techniques in the management of chronic liver diseases, including nonalcoholic fatty liver disease, will be elaborated.

Magnetic Resonance Elastography and Other Magnetic Resonance Imaging Techniques in Chronic Liver Disease: Current Status and Future Directions

PubMed Central

Tan, Cher Heng; Venkatesh, Sudhakar Kundapur

2016-01-01

Recent advances in the noninvasive imaging of chronic liver disease have led to improvements in diagnosis, particularly with magnetic resonance imaging (MRI). A comprehensive evaluation of the liver may be performed with the quantification of the degree of hepatic steatosis, liver iron concentration, and liver fibrosis. In addition, MRI of the liver may be used to identify complications of cirrhosis, including portal hypertension, ascites, and the development of hepatocellular carcinoma. In this review article, we discuss the state of the art techniques in liver MRI, namely, magnetic resonance elastography, hepatobiliary phase MRI, and liver fat and iron quantification MRI. The use of these advanced techniques in the management of chronic liver diseases, including non-alcoholic fatty liver disease, will be elaborated. PMID:27563019

New advances in molecular mechanisms and emerging therapeutic targets in alcoholic liver diseases

PubMed Central

Williams, Jessica A; Manley, Sharon; Ding, Wen-Xing

2014-01-01

Alcoholic liver disease is a major health problem in the United States and worldwide. Chronic alcohol consumption can cause steatosis, inflammation, fibrosis, cirrhosis and even liver cancer. Significant progress has been made to understand key events and molecular players for the onset and progression of alcoholic liver disease from both experimental and clinical alcohol studies. No successful treatments are currently available for treating alcoholic liver disease; therefore, development of novel pathophysiological-targeted therapies is urgently needed. This review summarizes the recent progress on animal models used to study alcoholic liver disease and the detrimental factors that contribute to alcoholic liver disease pathogenesis including miRNAs, S-adenosylmethionine, Zinc deficiency, cytosolic lipin-1β, IRF3-mediated apoptosis, RIP3-mediated necrosis and hepcidin. In addition, we summarize emerging adaptive protective effects induced by alcohol to attenuate alcohol-induced liver pathogenesis including FoxO3, IL-22, autophagy and nuclear lipin-1α. PMID:25278688

Hemochromatosis

MedlinePlus

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Galactosemia

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Temporal trends in population-based death rates associated with chronic liver disease and liver cancer in the United States over the last 30 years.

PubMed

Kim, Yuhree; Ejaz, Aslam; Tayal, Amit; Spolverato, Gaya; Bridges, John F P; Anders, Robert A; Pawlik, Timothy M

2014-10-01

The health and economic burden from liver disease in the United States is substantial and rising. The objective of this study was to characterize temporal trends in mortality from chronic liver disease and liver cancer and the incidence of associated risk factors using population-based data over the past 30 years. Population-based mortality data were obtained from the National Vital Statistics System, and population estimates were derived from the national census for US adults (aged >45 years). Crude death rates (CDRs), age-adjusted death rates (ADRs), and average annual percentage change (AAPC) statistics were calculated. In total, 690,414 deaths (1.1%) were attributable to chronic liver disease, whereas 331,393 deaths (0.5%) were attributable to liver cancer between 1981 and 2010. The incidence of liver cancer was estimated at 7.1 cases per 100,000 population. Mortality rates from chronic liver disease and liver cancer increased substantially over the past 3 decades, with ADRs of 23.7 and 16.6 per 100,000 population in 2010, respectively. The AAPC from 2006 to 2010 demonstrated an increased ADR for chronic liver disease (AAPC, 1.5%; 95% confidence interval, 0.3%-2.8%) and liver cancer (AAPC, 2.6%; 95% confidence interval, 2.4%-2.7%). A comprehensive approach that involves primary and secondary prevention, increased access to treatment, and more funding for liver-related research is needed to address the high death rates associated with chronic liver disease and liver cancer in the United States. © 2014 American Cancer Society.

Texture analysis of B-mode ultrasound images to stage hepatic lipidosis in the dairy cow: A methodological study.

PubMed

Banzato, Tommaso; Fiore, Enrico; Morgante, Massimo; Manuali, Elisabetta; Zotti, Alessandro

2016-10-01

Hepatic lipidosis is the most diffused hepatic disease in the lactating cow. A new methodology to estimate the degree of fatty infiltration of the liver in lactating cows by means of texture analysis of B-mode ultrasound images is proposed. B-mode ultrasonography of the liver was performed in 48 Holstein Friesian cows using standardized ultrasound parameters. Liver biopsies to determine the triacylglycerol content of the liver (TAGqa) were obtained from each animal. A large number of texture parameters were calculated on the ultrasound images by means of a free software. Based on the TAGqa content of the liver, 29 samples were classified as mild (TAGqa<50mg/g), 6 as moderate (50mg/g100mg/g) and 13 as severe (TAG>100mg/g) in steatosis. Stepwise linear regression analysis was performed to predict the TAGqa content of the liver (TAGpred) from the texture parameters calculated on the ultrasound images. A five-variable model was used to predict the TAG content from the ultrasound images. The regression model explained 83.4% of the variance. An area under the curve (AUC) of 0.949 was calculated for <50mg/g vs >50mg/g of TAGqa; using an optimal cut-off value of 72mg/g TAGpred had a sensitivity of 86.2% and a specificity of 84.2%. An AUC of 0.978 for <100mg/g vs >100mg/g of TAGqa was calculated; using an optimal cut-off value of 89mg/g, TAGpred sensitivity was 92.3% and specificity was 88.6%. Texture analysis of B-mode ultrasound images may therefore be used to accurately predict the TAG content of the liver in lactating cows. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prospective comparison of magnetic resonance imaging to transient elastography and serum markers for liver fibrosis detection.

PubMed

Dyvorne, Hadrien A; Jajamovich, Guido H; Bane, Octavia; Fiel, M Isabel; Chou, Hsin; Schiano, Thomas D; Dieterich, Douglas; Babb, James S; Friedman, Scott L; Taouli, Bachir

2016-05-01

Establishing accurate non-invasive methods of liver fibrosis quantification remains a major unmet need. Here, we assessed the diagnostic value of a multiparametric magnetic resonance imaging (MRI) protocol including diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE)-MRI and magnetic resonance elastography (MRE) in comparison with transient elastography (TE) and blood tests [including ELF (Enhanced Liver Fibrosis) and APRI] for liver fibrosis detection. In this single centre cross-sectional study, we prospectively enrolled 60 subjects with liver disease who underwent multiparametric MRI (DWI, DCE-MRI and MRE), TE and blood tests. Correlation was assessed between non-invasive modalities and histopathologic findings including stage, grade and collagen content, while accounting for covariates such as age, sex, BMI, HCV status and MRI-derived fat and iron content. ROC curve analysis evaluated the performance of each technique for detection of moderate-to-advanced liver fibrosis (F2-F4) and advanced fibrosis (F3-F4). Magnetic resonance elastography provided the strongest correlation with fibrosis stage (r = 0.66, P < 0.001), inflammation grade (r = 0.52, P < 0.001) and collagen content (r = 0.53, P = 0.036). For detection of moderate-to-advanced fibrosis (F2-F4), AUCs were 0.78, 0.82, 0.72, 0.79, 0.71 for MRE, TE, DCE-MRI, DWI and APRI, respectively. For detection of advanced fibrosis (F3-F4), AUCs were 0.94, 0.77, 0.79, 0.79 and 0.70, respectively. Magnetic resonance elastography provides the highest correlation with histopathologic markers and yields high diagnostic performance for detection of advanced liver fibrosis and cirrhosis, compared to DWI, DCE-MRI, TE and serum markers. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Gd-EOB-DTPA-enhanced T1ρ imaging vs diffusion metrics for assessment liver inflammation and early stage fibrosis of nonalcoholic steatohepatitis in rabbits.

PubMed

Xie, Yuanliang; Zhang, Hongfeng; Jin, Chaoling; Wang, Xiang; Wang, Xiaoqi; Chen, Jingting; Xu, Yikai

2018-05-01

To assess the value of T1ρ,T1ρ on hepatobiliary phase (HBP) and diffusion metrics in staging of Non-alcoholic fatty liver disease (NAFLD) activity scores, inflammation, fibrosis in NASH rabbits model. Non-alcoholic steatohepatitis (NASH) rabbits model was induced by feeding a varied duration of high-fat, high-cholesterol diet. T1ρ,T1ρ (HBP) 20min after administration of Gd-EOB-DTPA, and Intravoxel incoherent motion imaging (IVIM) diffusion-weighted imaging were performed on a 3.0T magnetic resonance (MR) imaging unit. The diagnostic value of each parameter for NAS, inflammation and fibrosis severity were determined. T1ρ (r=0.658) and T1ρ (HBP) (r=0.750) have strong association with NASH overall activity, T1ρ (HBP) is strongly relevant to inflammation stage (r=0.812). There was negative association between f and inflammation (r=-0.480), whilst no significant relation between other three parameters (apparent diffusion coefficient (ADC), pseudo-diffusion coefficient (D*) and true diffusion coefficient (D)) and inflammation or overall activity. The areas under the receiver operating characteristic curves (AUCs) of f, ADC, T1ρ and T1ρ-HBP were 0.871, 0.728, 0.849 and 0.949 for differentiating NASH; 0.731, 0.552, 0.925 and 0.922 for G2-3 inflammation; and 0.767, 0.625, 0.816, and 0.882 for S1-2 fibrosis. Comparison of ROC curve showed T1ρ (HBP) had an optimal diagnostic performance for NASH [T1ρ (HBP) vs ADC, AUC:0.949 vs 0.728, P=0.043], inflammation [T1ρ (HBP) vs ADC, AUC:0.922 vs 0.552, P=0.003], fibrosis [T1ρ (HBP) vs ADC, AUC:0.882 vs 0.625, P=0.046]. The combination of T1ρ (HBP)+perfusion fraction (f) showed highest diagnostic value for NASH (AUC:0.971), inflammation (AUC:0.935). Among T1ρ imaging and IVIM diffusion metrics, combination of T1rho (HBP)+f was found to be superior noninvasive imaging biomarker for NASH activity assessment. Copyright © 2017 Elsevier Inc. All rights reserved.

Survival Outcomes After Intracranial Hemorrhage in Liver Disease.

PubMed

Lagman, Carlito; Nagasawa, Daniel T; Azzam, Daniel; Sheppard, John P; Chen, Cheng Hao Jacky; Ong, Vera; Nguyen, Thien; Prashant, Giyarpuram N; Niu, Tianyi; Tucker, Alexander M; Kim, Won; Kaldas, Fady M; Pouratian, Nader; Busuttil, Ronald W; Yang, Isaac

2018-05-15

Survival outcomes for patients with liver disease who suffer an intracranial hemorrhage (ICH) have not been thoroughly investigated. To understand survival outcomes for 3 groups: (1) patients with an admission diagnosis of liver disease (end-stage liver disease [ESLD] or non-ESLD) who developed an ICH in the hospital, (2) patients with ESLD who undergo either operative vs nonoperative management, and (3) patients with ESLD on the liver transplant waitlist who developed an ICH in the hospital. We retrospectively reviewed hospital charts from March 2006 through February 2017 of patients with liver disease and an ICH evaluated by the neurosurgery service at a single academic medical center. The primary outcome was survival. We included a total of 53 patients in this study. The overall survival for patients with an admission diagnosis of liver disease who developed an ICH (n = 29, 55%) in the hospital was 22%. Of those patients with an admission diagnosis of liver disease, 27 patients also had ESLD. Kaplan-Meier analysis found no significant difference in survival for ESLD patients (n = 33, 62%) according to operative status. There were 11 ESLD patients on the liver transplant waitlist. The overall survival for patients with ESLD on the liver transplant waitlist who suffered an in-hospital ICH (n = 7, 13%) was 14%. ICH in the setting of liver disease carries a grave prognosis. Also, a survival advantage for surgical hematoma evacuation in ESLD patients is not clear.

Liver Biopsy in Chronic Liver Diseases: Is There a Favorable Benefit: Risk Balance?

PubMed

Larrey, Dominique; Meunier, Lucy; Ursic-Bedoya, José

2017-01-01

Liver biopsy is still useful in selected clinical situations in which it is the only tool to obtain information necessary for the diagnosis, the prognosis, and the decision for treatment. Main examples are viral hepatitis with confounding co-morbidities, non alcoholic fatty liver disease, and autoimmune liver diseases.

Increasing burden of liver cancer despite extensive use of antiviral agents in a hepatitis B virus-endemic population.

PubMed

Choi, Jonggi; Han, Seungbong; Kim, Namkug; Lim, Young-Suk

2017-11-01

Most mortalities from liver disease and liver cancer worldwide are attributable to hepatitis B virus (HBV) and hepatitis C virus. Despite remarkable advances in the treatment of HBV over past decades, limited population-level data are available regarding its impact on burden of liver disease and liver cancer. Mortality data from liver disease and liver cancer were obtained from the national death certificate database of Korea, an HBV-endemic country, between 1999 and 2013, and were analyzed by Joinpoint analysis. For liver disease, number of annual deaths decreased by 62.3% (95% confidence interval [CI], 62.0-62.6), crude death rate (CDR) decreased by 64.6% (95% CI, 64.3-64.9) from 21.2 to 7.5 per 100,000 population, and age-standardized death rate (ADR) declined by 75.0% (95% CI, 74.7-75.3), between 1999 and 2013. In contrast, for liver cancer, number of annual deaths increased by 17.8% (95% CI, 17.6-18.0) and CDR increased by 10.2% (95% CI, 10.0-10.4) from 20.5 to 22.6, although ADR decreased by 26.9% (95% CI, 26.6-27.2). The annual number of patients receiving oral antiviral agents against HBV increased from 1,716 to 187,226 during the study period. The increase in mean age at death from liver disease was significantly greater than that from liver cancer (8.8 vs. 6.1 years: P = 0.02). Marked reduction in liver disease mortality by widespread use of antiviral treatments against HBV may increase the life expectancy and number of patients at risk of developing liver cancer, inadvertently leading to increased burden of liver cancer in an HBV-endemic population. The competing nature between death from liver disease and that from liver cancer should be carefully considered in establishing a health care policy. (Hepatology 2017;66:1454-1463). © 2017 by the American Association for the Study of Liver Diseases.

Genetics of liver disease: From pathophysiology to clinical practice.

PubMed

Karlsen, Tom H; Lammert, Frank; Thompson, Richard J

2015-04-01

Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990 s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Diffusion-weighted Imaging of the Liver with Multiple b Values: Effect of Diffusion Gradient Polarity and Breathing Acquisition on Image Quality and Intravoxel Incoherent Motion Parameters—A Pilot Study

PubMed Central

Dyvorne, Hadrien A.; Galea, Nicola; Nevers, Thomas; Fiel, M. Isabel; Carpenter, David; Wong, Edmund; Orton, Matthew; de Oliveira, Andre; Feiweier, Thorsten; Vachon, Marie-Louise; Babb, James S.

2013-01-01

Purpose: To optimize intravoxel incoherent motion (IVIM) diffusion-weighted (DW) imaging by estimating the effects of diffusion gradient polarity and breathing acquisition scheme on image quality, signal-to-noise ratio (SNR), IVIM parameters, and parameter reproducibility, as well as to investigate the potential of IVIM in the detection of hepatic fibrosis. Materials and Methods: In this institutional review board–approved prospective study, 20 subjects (seven healthy volunteers, 13 patients with hepatitis C virus infection; 14 men, six women; mean age, 46 years) underwent IVIM DW imaging with four sequences: (a) respiratory-triggered (RT) bipolar (BP) sequence, (b) RT monopolar (MP) sequence, (c) free-breathing (FB) BP sequence, and (d) FB MP sequence. Image quality scores were assessed for all sequences. A biexponential analysis with the Bayesian method yielded true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (PF) in liver parenchyma. Mixed-model analysis of variance was used to compare image quality, SNR, IVIM parameters, and interexamination variability between the four sequences, as well as the ability to differentiate areas of liver fibrosis from normal liver tissue. Results: Image quality with RT sequences was superior to that with FB acquisitions (P = .02) and was not affected by gradient polarity. SNR did not vary significantly between sequences. IVIM parameter reproducibility was moderate to excellent for PF and D, while it was less reproducible for D*. PF and D were both significantly lower in patients with hepatitis C virus than in healthy volunteers with the RT BP sequence (PF = 13.5% ± 5.3 [standard deviation] vs 9.2% ± 2.5, P = .038; D = [1.16 ± 0.07] × 10−3 mm2/sec vs [1.03 ± 0.1] × 10−3 mm2/sec, P = .006). Conclusion: The RT BP DW imaging sequence had the best results in terms of image quality, reproducibility, and ability to discriminate between healthy and fibrotic liver with biexponential fitting. © RSNA, 2012 PMID:23220895

Alagille Syndrome

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Newborn Jaundice

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Reye Syndrome

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In vivo quantitative visualization of hypochlorous acid in the liver using a novel selective two-photon fluorescent probe

NASA Astrophysics Data System (ADS)

Wang, Haolu; Jayachandran, Aparna; Gravot, Germain; Liang, Xiaowen; Thorling, Camilla A.; Zhang, Run; Liu, Xin; Roberts, Michael S.

2016-11-01

Hypochlorous acid (HOCl) plays a vital role in physiological events and diseases. During hepatic ischemia-reperfusion (I/R) injury, HOCl is generated by neutrophils and diffuses into hepatocytes, causing oxidant stress-mediated injury. Although many probes have been developed to detect HOCl, most were difficult to be distinguished from endogenous fluorophores in intravital imaging and only can be employed under one-photon microscopy. A novel iridium(III) complex-based ferrocene dual-signaling chemosensor (Ir-Fc) was designed and synthesized. Ir-Fc exhibited a strong positive fluorescent response only in the presence of HOCl, whereas negligible fluorescent signals were observed upon the additions of other reactive oxygen/nitrogen species and metal ions. There was a good linear relationship between probe responsive fluorescent intensity and HOCl concentration. Ir-Fc was then intravenously injected into BALB/c mice at the final concentration of 50 μM and the mouse livers were imaged using multiphoton microscopy (MPM). In the I/R liver, reduced autofluorescence was detected by MPM, indicating the hepatocyte necrosis. Remarkable enhancement of red fluorescence was observed in hepatocytes with decreased autofluorescence, indicating the reaction of Ir-Fc with endogenous HOCl molecules. The cellular concentration of HOCl was first calculated based on the intensity of MPM images. No obvious toxic effects were observed in histological examination of major organs after Ir-Fc injection. In summary, Ir-Fc has low cytotoxicity, high specificity to HOCl, and rapid "off-on" fluorescence. It is suitable for dynamic quantitatively monitoring HOCl generation using MPM at the cellular level. This technique can be readily extended to examination of liver diseases and injury.

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.

IL-17A, MCP-1, CCR-2, and ABCA1 polymorphisms in children with non-alcoholic fatty liver disease.

PubMed

Akbulut, Ulas Emre; Emeksiz, Hamdi Cihan; Citli, Senol; Cebi, Alper Han; Korkmaz, Hatice Ayca Ata; Baki, Gaye

2018-05-05

The prevalence of non-alcoholic fatty liver disease in children has risen significantly, owing to the worldwide childhood obesity epidemic in the last two decades. Non-alcoholic fatty liver disease is closely linked to sedentary lifestyle, increased body mass index, and visceral adiposity. In addition, individual genetic variations also have a role in the development and progression of non-alcoholic fatty liver disease. The aim of this study was to investigate the gene polymorphisms of MCP-1 (-2518 A/G) (rs1024611), CCR-2 (190 G/A) (rs1799864), ABCA1 (883 G/A) (rs4149313), and IL-17A (-197 G/A) (rs2275913) in obese Turkish children with non-alcoholic fatty liver disease. The study recruited 186 obese children aged 10-17 years, including 101 children with non-alcoholic fatty liver disease and 85 children without non-alcoholic fatty liver disease. Anthropometric measurements, insulin resistance, a liver panel, a lipid profile, liver ultrasound examination, and genotyping of the four variants were performed. No difference was found between the groups in respect to age and gender, body mass index, waist/hip ratio, or body fat ratio. In addition to the elevated ALT levels, AST and GGT levels were found significantly higher in the non-alcoholic fatty liver disease group compared to the non non-alcoholic fatty liver disease group (p<0.05). The A-allele of IL-17A (-197 G/A) (rs2275913) was associated with non-alcoholic fatty liver disease (odds ratio 2.05, 95% confidence interval: 1.12-3.77, p=0.02). The findings of this study suggest that there may be an association between IL-17A (-197 G/A) (rs2275913) polymorphism and non-alcoholic fatty liver disease development in obese Turkish children. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Columbid herpesvirus-1 in two Cooper's hawks (Accipiter cooperii) with fatal inclusion body disease.

PubMed

Pinkerton, Marie E; Wellehan, James F X; Johnson, April J; Childress, April L; Fitzgerald, Scott D; Kinsel, Michael J

2008-07-01

We report two separate naturally occurring cases of fatal herpesviral disease in Cooper's Hawks (Accipiter cooperii). Gross lesions included splenomegaly and hepatomegaly, with diffuse pale mottling or scattered small white foci. Histologic lesions included splenic and hepatic necrosis associated with eosinophilic intranuclear inclusion bodies characteristic of herpesvirus. In one case, necrosis and inclusions were also noted in bone marrow, thymus, bursa of Fabricius, thyroid gland, parathyroid gland, ceca, and the enteric system. Transmission electron microscopy demonstrated viral particles typical of herpesvirus within hepatocyte nuclei and budding from the nuclear membrane. Herpesviral DNA was amplified via polymerase chain reaction (PCR) of paraffin-embedded liver and spleen, and sequence data were consistent with columbid herpesvirus-1, an alphaherpesvirus of Rock Pigeons (Columba livia). PCR results provide evidence that this disease is transmitted to raptors via Rock Pigeons, most likely through ingestion of Rock Pigeons as prey.

Non-Alcoholic Fatty Liver Disease in HIV Infection.

PubMed

Macías, Juan; Pineda, Juan A; Real, Luis M

2017-01-01

Non-alcoholic fatty liver disease is one of the most frequent chronic hepatic conditions worldwide. The spectrum of non-alcoholic fatty liver disease goes from hepatic steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Risk factors for non-alcoholic fatty liver disease are metabolic, mainly obesity and the accompanying consequences. Treatment and prevention of non-alcoholic fatty liver disease should target those metabolic abnormalities. The frequency of and the factors associated with hepatic steatosis in HIV infection seem to be similar to those reported in the general population, though direct comparisons are lacking. Hepatic steatosis in HIV infection may also be secondary to antiretroviral drugs or HCV-related factors in HCV-coinfected subjects. However, more recent data suggest that hepatic steatosis in HIV infection represents true non-alcoholic fatty liver disease. As such, management of non-alcoholic fatty liver disease in HIV infection should follow the same principles as in the general population.

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 chronic non-viral liver diseases. These findings support the role of liver-protective therapies for the improvement of the quality of life in chronic liver disease. PMID:26990427

Drug-induced Liver Injury

PubMed Central

David, Stefan; Hamilton, James P

2011-01-01

Drug-induced liver injury (DILI) is common and nearly all classes of medications can cause liver disease. Most cases of DILI are benign, and improve after drug withdrawal. It is important to recognize and remove the offending agent as quickly as possible to prevent the progression to chronic liver disease and/or acute liver failure. There are no definite risk factors for DILI, but pre-existing liver disease and genetic susceptibility may predispose certain individuals. Although most patients have clinical symptoms that are identical to other liver diseases, some patients may present with symptoms of systemic hypersensitivity. Treatment of drug and herbal-induced liver injury consists of rapid drug discontinuation and supportive care targeted to alleviate unwanted symptoms. PMID:21874146

Hepatic artery resistive index (HARI) and non-alcoholic fatty liver disease (NAFLD) fibrosis score in NAFLD patients: cut-off suggestive of non-alcoholic steatohepatitis (NASH) evolution.

PubMed

Tana, Claudio; Tana, Marco; Rossi, Stefano; Silingardi, Mauro; Schiavone, Cosima

2016-09-01

Conventional ultrasound (US) is reliable to reveal the presence of non-alcoholic fatty liver disease (NAFLD), but it is neither sensitive nor specific to reveal fibrosis clues, except in advanced stages where signs of cirrhosis are evident. NALFD fibrosis score is a non-invasive parameter that predicts well the presence of significant fibrosis, but correlations with US parameters are lacking. The aim of this study was, therefore, to compare resistive index of hepatic artery (HARI) of NAFLD patients with different severity degrees of diffuse fatty liver disease vs HARI of controls, and to compare HARI of NAFLD patients with different NAFLD fibrosis scores vs HARI of controls. This was a spontaneous, no-profit observational study conducted in our US department between December 2013 and July 2014. Patients with NAFLD with different severity of disease and healthy controls were included. Echogenicity and size of liver and spleen, maximum portal vein velocity, RI, peak systolic velocity (PSV), and end diastolic velocity (EDV) of splenic artery, PSV, EDV, and RI of hepatic artery, and NAFLD fibrosis score were acquired and compared between groups. HARI was significantly lower in NAFLD patients than controls (p < 0.0001). A significant difference was also found between the groups of NAFLD severity (p < 0.0001). There was also a difference between HARI of NAFLD patients with different NAFLD fibrosis scores vs HARI of controls (p < 0.0001) with a positive correlation between HARI and NAFLD fibrosis score. Conventional Doppler US can be helpful to detect NAFLD patients with the risk of fibrous tissue accumulation. HARI tends to exceed the range of controls for patients with NAFLD fibrosis score greater than 0.675. The detection of HARI greater than 0.9 in NAFLD patients, regardless of the US degree of severity of steatosis, might suggest the execution of biopsy to predict the risk of progression to steatohepatitis and fibrous tissue accumulation. Low values of HARI may be expression of lower risk, which does not necessitate any biopsy.

Performance of non-invasive models of fibrosis in predicting mild to moderate fibrosis in patients with non-alcoholic fatty liver disease.

PubMed

Siddiqui, Mohammad S; Patidar, Kavish R; Boyett, Sherry; Luketic, Velimir A; Puri, Puneet; Sanyal, Arun J

2016-04-01

In non-alcoholic fatty liver disease, presence of fibrosis is predictive of long-term liver-related complications. Currently, there are no reliable and non-invasive means of quantifying fibrosis in those with non-alcoholic fatty liver disease. Therefore, we aimed to evaluate the performance of a panel of non-invasive models in predicting fibrosis in non-alcoholic fatty liver disease. The accuracy of FibroMeter non-alcoholic fatty liver disease, fibrosis 4 and four other non-invasive models in predicting fibrosis in those with biopsy proven non-alcoholic fatty liver disease was compared. These models were constructed post hoc in patients who had necessary clinical information collected within 2 months of a liver biopsy. The areas under receiver operating characteristics curves were compared for each model using Delong analysis. Optimum cut-off for each model and fibrosis stage were calculated using the Youden index. The area under receiver operating characteristics curves for F ≥ 1 fibrosis for fibrosis 4 and FibroMeter non-alcoholic fatty liver disease was 0.821 and 0.801 respectively. For F ≥ 3, the area under receiver operating characteristics curves was 0.866 for fibrosis 4 and 0.862 for FibroMeter non-alcoholic fatty liver disease. Delong analysis showed the area under receiver operating characteristics curves was statistically different for fibrosis 4 and FibroMeter non-alcoholic fatty liver disease compared with BARD, BAAT and aspartate aminotransferase:alanine aminotransferase ratio for F ≥ 1 and F ≥ 3. Area under receiver operating characteristics curves were significantly different for fibrosis 4 and FibroMeter non-alcoholic fatty liver disease for F ≥ 3 compared with non-alcoholic fatty liver disease fibrosis score. At a fixed sensitivity of 90%, FibroMeter non-alcoholic fatty liver disease had the highest specificity for F ≥ 1 (52.4%) and F ≥ 3 (63.8%). In contrast, at a fixed specificity of 90%, fibrosis 4 outperformed other models with a sensitivity of 60.2% for F ≥ 1 and 70.6% for F ≥ 3 fibrosis. These non-invasive models of fibrosis can predict varying degrees of fibrosis from routinely collected clinical information in non-alcoholic fatty liver disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Lower Muscle Endurance in Patients with Alcoholic Liver Disease

ERIC Educational Resources Information Center

Andersen, Henning; Aagaard, Niels K.; Jakobsen, Johannes; Dorup, Inge; Vilstrup, Hendrik

2012-01-01

Patients with alcoholic liver disease often complain of restricted physical capacity, which could be due to decreased muscle endurance. The aim of this study was to assess the muscular endurance in patients with alcoholic liver disease. In a cross sectional study, 24 patients with alcoholic liver disease and 22 controls were evaluated using…

Correlation Of Deviance In Arterial Oxygenation With Severity Of Chronic Liver Disease.

PubMed

Shaukat, Al-Aman; Zar, Adnan; Zuhaid, Muhammad; Afridi, Safa Saadat

2016-01-01

Hepatitis B and C related chronic liver diseases have led to development of a serious threat to the people of South Asia. The main aim of this study was to evaluate the correlation of magnitude of arterial deoxygention to the severity of liver disease. It was a hospital based cross-sectional descriptive study, carried out in the Medical Department of Khyber Teaching Hospital Peshawar. All in all 115 patients were assessed for the severity of the liver diseases and were correlated with arterial deoxygenation using linear regression models. Male to female ratio was 1.5:1. Males infected with hepatitis B, hepatitis C and both were 9, 60 and 1, while females suffered from hepatitis B, Hepatitis C and both were 2, 42 and 1 respectively. The linear relationship between A-a DO2 with severity of liver disease showed positive correlation while PO2 showed negative correlation with severity of liver disease. There was a positive correlation between A-a DO2 and severity of liver diseases while PO2 and severity of liver diseases showed negative correlation.

Discharge Disposition After Stroke in Patients With Liver Disease.

PubMed

Parikh, Neal S; Merkler, Alexander E; Schneider, Yecheskel; Navi, Babak B; Kamel, Hooman

2017-02-01

Liver disease is associated with both hemorrhagic and thrombotic processes, including an elevated risk of intracranial hemorrhage. We sought to assess the relationship between liver disease and outcomes after stroke, as measured by discharge disposition. Using administrative claims data, we identified a cohort of patients hospitalized with stroke in California, Florida, and New York from 2005 to 2013. The predictor variable was liver disease. All diagnoses were defined using validated diagnosis codes. Ordinal logistic regression was used to analyze the association between liver disease and worsening discharge disposition: home, nursing/rehabilitation facility, or death. Secondarily, multiple logistic regression was used to analyze the association between liver disease and in-hospital mortality. Models were adjusted for demographics, vascular risk factors, and comorbidities. We identified 121 428 patients with intracerebral hemorrhage and 703 918 with ischemic stroke. Liver disease was documented in 13 584 patients (1.7%). Liver disease was associated with worse discharge disposition after both intracerebral hemorrhage (global odds ratio, 1.28; 95% confidence interval, 1.19-1.38) and ischemic stroke (odds ratio, 1.23; 95% confidence interval, 1.17-1.29). Similarly, liver disease was associated with in-hospital death after both intracerebral hemorrhage (odds ratio, 1.33; 95% confidence interval, 1.23-1.44) and ischemic stroke (odds ratio, 1.60; 95% confidence interval, 1.51-1.71). Liver disease was associated with worse hospital discharge disposition and in-hospital mortality after stroke, suggesting worse functional outcomes. © 2016 American Heart Association, Inc.

Primary Sclerosing Cholangitis (PSC)

MedlinePlus

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Probiotics in Pediatric Liver Disease.

PubMed

Miloh, Tamir

2015-01-01

The gut-liver axis involves complex interaction between the intestinal microbiome and the liver parenchyma. Probiotics are live microorganisms that are used in a variety of diseases. With currently only 2 randomized-controlled studies (one with Lactobacillus GG and the other with VSL #3), data are scarce to support the clinical effect of probiotic use in children with nonalcoholic fatty liver disease. There is evidence that probiotics decrease the risk of necrotizing enterocolitis and thereby reduce the prevalence of total parenteral nutrition-induced chronic liver disease. Probiotics are used with a few reported positive outcomes in patients with cystic fibrosis and familial hypercholesterolemia and may be promising in other liver conditions. Probiotics are generally safe and well tolerated in children, premature infants, and in patients after liver transplantation. Large, prospective, randomized clinical trials are needed to evaluate the benefit of probiotics in children with liver diseases.

Hepatitis A and B superimposed on chronic liver disease: vaccine-preventable diseases.

PubMed

Keeffe, Emmet B

2006-01-01

A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations.

Hepatitis A and B Superimposed on Chronic Liver Disease: Vaccine-Preventable Diseases

PubMed Central

Keeffe, Emmet B

2006-01-01

A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations. PMID:18528476

Alcoholic Liver Disease and Liver Transplantation.

PubMed

Gallegos-Orozco, Juan F; Charlton, Michael R

2016-08-01

Excessive alcohol use is a common health care problem worldwide and is associated with significant morbidity and mortality. Alcoholic liver disease represents the second most frequent indication for liver transplantation in North America and Europe. The pretransplant evaluation of patients with alcoholic liver disease should aim at identifying those at high risk for posttransplant relapse of alcohol use disorder, as return to excessive drinking can be deleterious to graft and patient survival. Carefully selected patients with alcoholic liver disease, including those with severe alcoholic hepatitis, will have similar short-term and long-term outcomes when compared with other indications for liver transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

The Effects of Betaine on the Nuclear Fractal Dimension, Chromatin Texture, and Proliferative Activity in Hepatocytes in Mouse Model of Nonalcoholic Fatty Liver Disease.

PubMed

Vesković, Milena; Labudović-Borović, Milica; Zaletel, Ivan; Rakočević, Jelena; Mladenović, Dušan; Jorgačević, Bojan; Vučević, Danijela; Radosavljević, Tatjana

2018-04-01

The effects of betaine on hepatocytes chromatin architecture changes were examined by using fractal and gray-level co-occurrence matrix (GLCM) analysis in methionine/choline-deficient (MCD) diet-induced, nonalcoholic fatty liver disease (NAFLD). Male C57BL/6 mice were divided into groups: (1) Control: standard diet; (2) BET: standard diet and betaine supplementation through drinking water (solution 1.5%); (3) MCD group: MCD diet for 6 weeks; (4) MCD+BET: fed with MCD diet + betaine for 6 weeks. Liver tissue was collected for histopathology, immunohistochemistry, and determination of fractal dimension and GLCM parameters. MCD diet induced diffuse micro- and macrovesicular steatosis accompanied with increased Ki67-positive hepatocyte nuclei. Steatosis and Ki67 immunopositivity were less prominent in the MCD+BET group compared with the MCD group. Angular second moment (ASM) and inverse difference moment (IDM) (textural homogeneity markers) were significantly increased in the MCD+BET group versus the MCD group (p<0.001), even though no difference between the MCD and the control group was evident. Heterogeneity parameters, contrast, and correlation were significantly increased in the MCD group versus the control (p<0.001). On the other hand, betaine treatment significantly reduced correlation, contrast, and entropy compared with the MCD group (p<0.001). Betaine attenuated MCD diet-induced NAFLD by reducing fat accumulation and inhibiting hepatocyte proliferation. Betaine supplementation increased nuclear homogeneity and chromatin complexity with reduction of entropy, contrast, and correlation.

Characterization and differentiation of autoimmune versus viral liver involvement in patients with Sjögren's syndrome.

PubMed

Ramos-Casals, Manuel; Sánchez-Tapias, Jose-María; Parés, Albert; Forns, Xavier; Brito-Zerón, Pilar; Nardi, Norma; Vazquez, Pilar; Vélez, Desirée; Arias, Isabel; Bové, Albert; Plaza, Joan; Rodés, Juan; Font, Josep

2006-08-01

To analyze the prevalence and clinical significance of liver involvement in patients with Sjögren's syndrome (SS), focusing on the characterization and differentiation of autoimmune versus chronic viral liver disease. We investigated liver involvement (clinical signs, analytical data, chronic viral infections, and autoantibodies) in 475 consecutive patients with SS. All patients fulfilled 4 or more of the 1993 European Community Study Group criteria for SS. Liver involvement was detected in 129 (27%) patients. After ruling out chronic illnesses or use of hepatotoxic drugs, the main etiologies were chronic viral liver disease in 64 (13%) cases [chronic hepatitis C virus (HCV) infection in 63 and HBV infection in one] and autoimmune liver diseases in 24 (5%; primary biliary cirrhosis in 16 patients and type-1 autoimmune hepatitis in 8). The analytical liver profile was not useful in differentiating between viral and autoimmune liver disease. In contrast, patients with SS and autoimmune liver disease presented higher mean values of erythrocyte sedimentation rate (p = 0.044), circulating gammaglobulins (p = 0.007), and a higher prevalence of antinuclear antibodies (p < 0.001), antimitochondrial antibodies (p < 0.001), anti-smooth muscle antibodies (p = 0.026), anti-Ro/SSA (p < 0.001), and anti-La/SSB (p = 0.01), while patients with chronic viral liver disease had a higher frequency of cryoglobulinemia (p < 0.001) and hypocomplementemia (p < 0.001). Chronic viral liver disease (associated overwhelmingly with HCV) was the main cause of liver involvement in our patients with SS, with a prevalence of 13%, nearly 3-fold greater than that observed for autoimmune liver involvement. The immunological pattern played a key role in the differentiation of viral (predominance of cryoglobulins and low complement levels) and autoimmune (higher frequency of autoantibodies) liver involvement.

The Role of Oxidative Stress and Antioxidants in Liver Diseases

PubMed Central

Li, Sha; Tan, Hor-Yue; Wang, Ning; Zhang, Zhang-Jin; Lao, Lixing; Wong, Chi-Woon; Feng, Yibin

2015-01-01

A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed. PMID:26540040

Review article: the gut microbiome as a therapeutic target in the pathogenesis and treatment of chronic liver disease.

PubMed

Woodhouse, C A; Patel, V C; Singanayagam, A; Shawcross, D L

2018-01-01

Mortality from chronic liver disease is rising exponentially. The liver is intimately linked to the gut via the portal vein, and exposure to gut microbiota and their metabolites translocating across the gut lumen may impact upon both the healthy and diseased liver. Modulation of gut microbiota could prove to be a potential therapeutic target. To characterise the changes in the gut microbiome that occur in chronic liver disease and to assess the impact of manipulation of the microbiome on the liver. We conducted a PubMed search using search terms including 'microbiome', 'liver' and 'cirrhosis' as well as 'non-alcoholic fatty liver disease', 'steatohepatitis', 'alcohol' and 'primary sclerosing cholangitis'. Relevant articles were also selected from references of articles and review of the ClinicalTrials.gov website. Reduced bacterial diversity, alcohol sensitivity and the development of gut dysbiosis are seen in several chronic liver diseases, including non-alcoholic fatty liver disease, alcohol-related liver disease and primary sclerosing cholangitis. Perturbations in gut commensals could lead to deficient priming of the immune system predisposing the development of immune-mediated diseases. Furthermore, transfer of stool from an animal with the metabolic syndrome may induce steatosis in a healthy counterpart. Patients with cirrhosis develop dysbiosis, small bowel bacterial overgrowth and increased gut wall permeability, allowing bacterial translocation and uptake of endotoxin inducing hepatic and systemic inflammation. Manipulation of the gut microbiota with diet, probiotics or faecal microbiota transplantation to promote the growth of "healthy" bacteria may ameliorate the dysbiosis and alter prognosis. © 2017 John Wiley & Sons Ltd.

An epidemiological study of the association of coffee with chronic liver disease.

PubMed

Walton, H B; Masterton, G S; Hayes, P C

2013-11-01

Chronic liver disease affects 855 people per million in the UK. Previous studies have reported that coffee appears protective against the development of abnormal liver enzymes, hepatic fibrosis and cirrhosis. The aim of this study, the first in a Scottish population, was to compare coffee consumption in patients with liver disease and that of control populations to determine correlations between coffee intake and the incidence of non-cancerous liver disease and with Child's-Pugh and model for end-stage liver disease (MELD) scores. Two hundred and eighty-six patients attending the liver outpatient department at the Royal Infirmary of Edinburgh completed a questionnaire regarding coffee consumption and lifestyle factors. Control questionnaires were also completed by 100 orthopaedic outpatients and 120 medical students. Patients with cirrhosis (n = 95) drank significantly less coffee than those without cirrhosis (p = <0.001). There was no correlation between Child's-Pugh (-0.018) and MELD scores (-0.132) with coffee consumption. Coffee drinking is associated with a reduced prevalence of cirrhosis in patients with chronic liver disease. However, there was no significant difference in the amount of coffee drunk by liver patients and the control groups. It is possible that by changing the amount of coffee drunk, the development of cirrhosis in liver disease could be postponed.

Gut microbiome and liver diseases.

PubMed

Tilg, Herbert; Cani, Patrice D; Mayer, Emeran A

2016-12-01

The gut microbiota has recently evolved as a new important player in the pathophysiology of many intestinal and extraintestinal diseases. The liver is the organ which is in closest contact with the intestinal tract, and is exposed to a substantial amount of bacterial components and metabolites. Various liver disorders such as alcoholic liver disease, non-alcoholic liver disease and primary sclerosing cholangitis have been associated with an altered microbiome. This dysbiosis may influence the degree of hepatic steatosis, inflammation and fibrosis through multiple interactions with the host's immune system and other cell types. Whereas few results from clinical metagenomic studies in liver disease are available, evidence is accumulating that in liver cirrhosis an oral microbiome is overrepresented in the lower intestinal tract, potentially contributing to disease process and severity. A major role for the gut microbiota in liver disorders is also supported by the accumulating evidence that several complications of severe liver disease such as hepatic encephalopathy are efficiently treated by various prebiotics, probiotics and antibiotics. A better understanding of the gut microbiota and its components in liver diseases might provide a more complete picture of these complex disorders and also form the basis for novel therapies. 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/.

Burden of liver disease in Europe: epidemiology and analysis of risk factors to identify prevention policies.

PubMed

Pimpin, Laura; Cortez-Pinto, Helena; Negro, Francesco; Corbould, Emily; Lazarus, Jeffrey V; Webber, Laura; Sheron, Nick

2018-05-16

The burden of liver disease in Europe continues to grow. We aimed to describe the epidemiology of liver diseases and their risk factors in European countries, and identify public health interventions that could impact on these risk factors to reduce the burden of liver disease. As part of the HEPAHEALTH project, commissioned by EASL, we extracted information on historical and current prevalence and mortality from national and international literature and databases on liver disease in 35 countries in the WHO European region, as well as historical and recent prevalence data on their main determinants; alcohol consumption, obesity and hepatitis B and C virus infections. We extracted information from peer-reviewed and grey literature to identify public health interventions targeting these risk factors. The epidemiology of liver disease is diverse and countries cluster with similar pictures, although the exact composition of diseases and the trends in risk factors which drive them is varied. Prevalence and mortality data indicate that increasing cirrhosis and liver cancer may be linked to dramatic increases in harmful alcohol consumption in Northern European countries, and viral hepatitis epidemics in Eastern and Southern European countries. Countries with historically low levels of liver disease may experience an increase in non-alcoholic fatty liver disease in the future, given the rise of obesity across the majority of European countries. Interventions exist for curbing harmful alcohol use, reducing obesity, preventing or treating viral hepatitis, and screening for liver disease at an early stage. Liver disease in Europe is a serious issue, with increasing cirrhosis and liver cancer. The public health and hepatology communities are uniquely placed to implement measures aimed at reducing their causes: harmful alcohol consumption, child and adult obesity prevalence and chronic infection with hepatitis viruses, which will in turn reduce the burden of liver disease. The European region has seen dramatic increases in liver disease mortality and morbidity in recent decades as a result of changes in the underlying risk factors: excessive alcohol consumption, obesity and viral hepatitis. However, there are highly effective ways to combat these, for example increasing the price of alcohol, making it less readily available, reducing the number of calories, sugar and fat in foods we consume, or screening people earlier to treat them more effectively. The time is now for governments, the health system and individuals to implement the changes required to substantially reduce the burden of liver disease. Copyright © 2018. Published by Elsevier B.V.

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 0.89. Multiparametric magnetic resonance is a promising technique with good diagnostic accuracy for non-alcoholic fatty liver disease histological parameters, and can potentially identify patients with non-alcoholic steatohepatitis and cirrhosis. © 2017 The Authors Liver International Published by John Wiley & Sons Ltd.

Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review

PubMed Central

Reardon, Jillian; Hussaini, Trana; Alsahafi, Majid; Azalgara, Vladimir Marquez; Erb, Siegfried R.; Partovi, Nilufar; Yoshida, Eric M.

2016-01-01

Abstract Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions. Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase. No search limits were applied. Additionally, references of the included studies were reviewed to identify additional articles. Results: The literature search yielded articles meeting inclusion criteria for the following indications: non-alcoholic fatty liver disease (n = 5); alcoholic liver disease (n = 2); autoimmune hepatitis (n = 6), liver transplant (n = 2) and viral hepatitis (n = 9). Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease, autoimmune hepatitis and hepatitis B and C infections. In contrast, liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation. The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease. In the prospective trials reviewed, adverse effects associated with the bile acids were limited to minor gastrointestinal complaints (most often, diarrhea) and did not occur at increased frequency as compared to controls. As administration of bile acids was often limited to durations of 12 months or less, long-term side effects for non-cholestatic indications cannot be excluded. Conclusions: Based on the available literature, bile acids cannot be widely recommended for non-cholestatic liver diseases at present. PMID:27777888

The nutritional geometry of liver disease including non-alcoholic fatty liver disease.

PubMed

Simpson, Stephen J; Raubenheimer, David; Cogger, Victoria C; Macia, Laurence; Solon-Biet, Samantha M; Le Couteur, David G; George, Jacob

2018-02-01

Nutrition has a profound effect on chronic liver disease, especially non-alcoholic fatty liver disease (NAFLD). Most observational studies and clinical trials have focussed on the effects of total energy intake, or the intake of individual macronutrients and certain micronutrients, such as vitamin D, on liver disease. Although these studies have shown the importance of nutrition on hepatic outcomes, there is not yet any unifying framework for understanding the relationship between diet and liver disease. The Geometric Framework for Nutrition (GFN) is an innovative model for designing nutritional experiments or interpreting nutritional data that can determine the effects of nutrients and their interactions on animal behaviour and phenotypes. Recently the GFN has provided insights into the relationship between dietary energy and macronutrients on obesity and ageing in mammals including humans. Mouse studies using the GFN have disentangled the effects of macronutrients on fatty liver and the gut microbiome. The GFN is likely to play a significant role in disentangling the effects of nutrients on liver disease, especially NAFLD, in humans. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Interaction between periodontitis and liver diseases

PubMed Central

Han, Pengyu; Sun, Dianxing; Yang, Jie

2016-01-01

Periodontitis is an oral disease that is highly prevalent worldwide, with a prevalence of 30–50% of the population in developed countries, but only ~10% present with severe forms. It is also estimated that periodontitis results in worldwide productivity losses amounting to ~54 billion USD yearly. In addition to the damage it causes to oral health, periodontitis also affects other types of disease. Numerous studies have confirmed the association between periodontitis and systemic diseases, such as diabetes, respiratory disease, osteoporosis and cardiovascular disease. Increasing evidence also indicated that periodontitis may participate in the progression of liver diseases, such as non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma, as well as affecting liver transplantation. However, to the best of our knowledge, there are currently no reviews elaborating upon the possible links between periodontitis and liver diseases. Therefore, the current review summarizes the human trials and animal experiments that have been conducted to investigate the correlation between periodontitis and liver diseases. Furthermore, in the present review, certain mechanisms that have been postulated to be responsible for the role of periodontitis in liver diseases (such as bacteria, pro-inflammatory mediators and oxidative stress) are considered. The aim of the review is to introduce the hypothesis that periodontitis may be important in the progression of liver disease, thus providing dentists and physicians with an improved understanding of this issue. PMID:27588170

Sugar-sweetened beverage, diet soda, and fatty liver disease in the Framingham Heart Study cohorts.

PubMed

Ma, Jiantao; Fox, Caroline S; Jacques, Paul F; Speliotes, Elizabeth K; Hoffmann, Udo; Smith, Caren E; Saltzman, Edward; McKeown, Nicola M

2015-08-01

Non-alcoholic fatty liver disease affects ∼30% of US adults, yet the role of sugar-sweetened beverages and diet soda on these diseases remains unknown. We examined the cross-sectional association between intake of sugar-sweetened beverages or diet soda and fatty liver disease in participants of the Framingham Offspring and Third Generation cohorts. Fatty liver disease was defined using liver attenuation measurements generated from computed tomography in 2634 participants. Alanine transaminase concentration, a crude marker of fatty liver disease, was measured in 5908 participants. Sugar-sweetened beverage and diet soda intake were estimated using a food frequency questionnaire. Participants were categorized as either non-consumers or consumers (3 categories: 1 serving/month to <1 serving/week, 1 serving/week to <1 serving/day, and ⩾1 serving/day) of sugar-sweetened beverages or diet soda. After adjustment for age, sex, smoking status, Framingham cohort, energy intake, alcohol, dietary fiber, fat (% energy), protein (% energy), diet soda intake, and body mass index, the odds ratios of fatty liver disease were 1, 1.16 (0.88, 1.54), 1.32 (0.93, 1.86), and 1.61 (1.04, 2.49) across sugar-sweetened beverage consumption categories (p trend=0.04). Sugar-sweetened beverage consumption was also positively associated with alanine transaminase levels (p trend=0.007). We observed no significant association between diet soda intake and measures of fatty liver disease. In conclusion, we observed that regular sugar-sweetened beverage consumption was associated with greater risk of fatty liver disease, particularly in overweight and obese individuals, whereas diet soda intake was not associated with measures of fatty liver disease. Copyright © 2015 European Association for the Study of the Liver. All rights reserved.

The Potential and Action Mechanism of Polyphenols in the Treatment of Liver Diseases

PubMed Central

Li, Sha; Cheung, Fan

2018-01-01

Liver disease, involving a wide range of liver pathologies from fatty liver, hepatitis, and fibrosis to cirrhosis and hepatocellular carcinoma, is a serious health problem worldwide. In recent years, many natural foods and herbs with abundant phytochemicals have been proposed as health supplementation for patients with hepatic disorders. As an important category of phytochemicals, natural polyphenols have attracted increasing attention as potential agents for the prevention and treatment of liver diseases. The striking capacities in remitting oxidative stress, lipid metabolism, insulin resistance, and inflammation put polyphenols in the spotlight for the therapies of liver diseases. It has been reported that many polyphenols from a wide range of foods and herbs exert therapeutic effects on liver injuries via complicated mechanisms. Therefore, it is necessary to have a systematical review to sort out current researches to help better understand the potentials of polyphenols in liver diseases. In this review, we aim to summarize and update the existing evidence of natural polyphenols in the treatment of various liver diseases by in vitro, in vivo, and clinical studies, while special attention is paid to the action mechanisms. PMID:29507653

The Relationship Between Fatty Liver Disease and Periodontal Disease

DTIC Science & Technology

2017-03-22

Periodontitis is a highly prevalent and destructive chronic disease. Numerous studies support an association between periodontal disease and other...systemic diseases (diabetes, cardiovascular disease, chronic kidney disease, adverse pregnancy outcome, etc.). Non-alcoholic fatty liver disease is a... chronic inflammatory disease that is characterized by accumulation of triglycerides and fat in the liver which may lead to fibrosis and even cirrhosis

Diffusion-weighted imaging of the liver at 3 T using section-selection gradient reversal: emphasis on chemical shift artefacts and lesion conspicuity.

PubMed

Lee, J S; Kim, Y K; Jeong, W K; Choi, D; Lee, W J

2015-04-01

To assess the value of section-selection gradient reversal (SSGR) in liver diffusion-weighted imaging (DWI) by comparing it to conventional DWI with an emphasis on chemical shift artefacts and lesion conspicuity. Forty-eight patients (29 men and 19 women; age range 33-80 years) with 48 liver lesions underwent two DWI examinations using spectral presaturation with inversion recovery fat suppression with and without SSGR at 3 T. Two reviewers evaluated each DWI (b = 100 and b = 800 image) with respect to chemical shift artefacts and liver lesion conspicuity using five-point scales and performed pairwise comparisons between the two DWIs. The signal-to-noise ratio (SNR) of the liver and the lesion and the lesion-liver contrast-to-noise ratio (CNR) were also calculated. SSGR-DWI was significantly better than conventional DWI with respect to chemical shift artefacts and lesion conspicuity in both separate reviews and pairwise comparisons (p < 0.05). There were significant differences in the SNR of the liver (b = 100 and b = 800 images) and lesion (b = 800) between SSGR-DWI and conventional DWI (p < 0.05). Applying the SSGR method to DWI using SPIR fat suppression at 3 T could significantly reduce chemical shift artefacts without incurring additional acquisition time or SNR penalties, which leads to increased conspicuity of focal liver lesions. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Quantification of liver fat: A comprehensive review.

PubMed

Goceri, Evgin; Shah, Zarine K; Layman, Rick; Jiang, Xia; Gurcan, Metin N

2016-04-01

Fat accumulation in the liver causes metabolic diseases such as obesity, hypertension, diabetes or dyslipidemia by affecting insulin resistance, and increasing the risk of cardiac complications and cardiovascular disease mortality. Fatty liver diseases are often reversible in their early stage; therefore, there is a recognized need to detect their presence and to assess its severity to recognize fat-related functional abnormalities in the liver. This is crucial in evaluating living liver donors prior to transplantation because fat content in the liver can change liver regeneration in the recipient and donor. There are several methods to diagnose fatty liver, measure the amount of fat, and to classify and stage liver diseases (e.g. hepatic steatosis, steatohepatitis, fibrosis and cirrhosis): biopsy (the gold-standard procedure), clinical (medical physics based) and image analysis (semi or fully automated approaches). Liver biopsy has many drawbacks: it is invasive, inappropriate for monitoring (i.e., repeated evaluation), and assessment of steatosis is somewhat subjective. Qualitative biomarkers are mostly insufficient for accurate detection since fat has to be quantified by a varying threshold to measure disease severity. Therefore, a quantitative biomarker is required for detection of steatosis, accurate measurement of severity of diseases, clinical decision-making, prognosis and longitudinal monitoring of therapy. This study presents a comprehensive review of both clinical and automated image analysis based approaches to quantify liver fat and evaluate fatty liver diseases from different medical imaging modalities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Distribution of liver disease in a cohort of immigrants in Sicily: analysis of day-hospital admissions in a migration medicine unit.

PubMed

Affronti, Marco; Affronti, Andrea; Soresi, Maurizio; Giannitrapani, Lydia; Campagna, Elisa; Tramuto, Fabio; Brunori, Giuseppe; Montalto, Giuseppe

2014-09-01

The objective of this study was to evaluate the frequency of liver disease and its aetiology in a cohort of immigrants. We retrospectively examined the hospital discharge charts of all the immigrant patients presenting at our day hospital from July 2009 to June 2013, and after evaluating the anamnestic, clinical and laboratory data on these charts we identified subjects with liver disease and its various aetiologies. The total sample population consisted of 1218 patients, of whom 112 (9.2%) had a diagnosis of liver disease. More than two-thirds of the latter (67.8%) came from Africa, while 15.2% were from Asia and 17.0% from Eastern Europe. In most patients the disease was related to HBV (44.6%), followed by alcohol (25%) and then HCV or cryptogenic disease (both 15.2%). Forty-six patients had undergone liver biopsy, which showed eight cases of varying degrees of liver steatosis, 29 cases with a variable severity of chronic liver disease, eight cases with a definite picture of liver cirrhosis and one case of alcoholic hepatitis. These data show that a significant proportion of our immigrant population has liver disease and that the most frequent cause is hepatitis B infection.

Quality of life following liver transplantation: a comparative study between Familial Amyloid Neuropathy and liver disease patients

PubMed Central

2009-01-01

Background It has been demonstrated in many studies that quality of life can be improved after liver transplantation in patients with liver disease. Nevertherless quality of life improvement in specific groups of transplantated patients such as those with Familial Amyloid Polineuropathy hasn't yet been explored. The present study aimed to compare the change in quality of life following liver transplantation between patients with Familial Amyloid Polineuropathy (FAP) and patients with liver disease. Results Patient's mental quality of life showed an improvement in all liver disease patients, and a worsening in FAP patients, resulting in a significant difference between the two groups. Regarding physical quality of life, although a similar improvement was seen in both groups, FAP patients had significantly less improvement than the sub-group of decompensated liver disease (Child-Pugh B and C). Conclusion It is concluded that liver transplantation has a less beneficial impact in FAP patient's physical quality of life, probably because they are not so much disabled by their disease at the moment of liver transplantation. The lesser improvement in mental quality of life of FAP patients may be due to their particular psychological profile and greater expectations towards transplantation. PMID:19604387

Whole-body MRI including diffusion-weighted MRI compared with 5-HTP PET/CT in the detection of neuroendocrine tumors

PubMed Central

Carlbom, Lina; Caballero-Corbalán, José; Granberg, Dan; Sörensen, Jens; Eriksson, Barbro; Ahlström, Håkan

2017-01-01

Aim We wanted to explore if whole-body magnetic resonance imaging (MRI) including diffusion-weighted (DW) and liver-specific contrast agent-enhanced imaging could be valuable in lesion detection of neuroendocrine tumors (NET). [11C]-5-Hydroxytryptophan positron emission tomography/computed tomography (5-HTP PET/CT) was used for comparison. Materials and methods Twenty-one patients with NET were investigated with whole-body MRI, including DW imaging (DWI) and contrast-enhanced imaging of the liver, and whole-body 5-HTP PET/CT. Seven additional patients underwent upper abdomen MRI including DWI, liver-specific contrast agent-enhanced imaging, and 5-HTP PET/CT. Results There was a patient-based concordance of 61% and a lesion-based concordance of 53% between the modalities. MRI showed good concordance with PET in detecting bone metastases but was less sensitive in detecting metastases in mediastinal lymph nodes. MRI detected more liver metastases than 5-HTP PET/CT. Conclusion Whole-body MRI with DWI did not detect all NET lesions found with whole-body 5-HTP PET/CT. Our findings indicate that MRI of the liver including liver-specific contrast agent-enhanced imaging and DWI could be a useful complement to whole-body 5-HTP PET/CT. PMID:27894208

Association of PNPLA3 I148M Variant With Chronic Viral Hepatitis, Autoimmune Liver Diseases and Outcomes of Liver Transplantation

PubMed Central

Geng, Ning; Xin, Yong-Ning; Xia, Harry Hua-Xiang; Jiang, Man; Wang, Jian; Liu, Yang; Chen, Li-Zhen; Xuan, Shi-Ying

2015-01-01

Context: The PNPLA3 I148M variant has been recognized as a genetic determinant of liver fat content and a genetic risk factor of liver damage progression associated with steatohepatitis. The I148M variant is associated with many chronic liver diseases. However, its potential association with inflammatory and autoimmune liver diseases has not been established. Evidence Acquisition: We systemically reviewed the potential associations of I148M variant with chronic viral hepatitis, autoimmune liver diseases and the outcome of liver transplantation, explored the underlying molecular mechanisms and tried to translate them into more individualized decision-making and personalized medicine. Results: There were associations between I148M variant and chronic viral hepatitis and autoimmune liver diseases and differential associations of I148M variant in donors and recipients with post-liver transplant outcomes. I148M variant may activate the development of steatosis caused by host metabolic disorders in chronic viral hepatitis, but few researches were found to illustrate the mechanisms in autoimmune liver diseases. The peripherally mediated mechanism (via extrahepatic adipose tissue) may play a principal role in triglyceride accumulation regardless of adiponutrin activity in the graft liver. Conclusions: Evidences have shown the associations between I148M variant and mentioned diseases. I148M variant induced steatosis may be involved in the mechanism of chronic viral hepatitis and genetic considered personalized therapies, especially for PSC male patients. It is also crucial to pay attention to this parameter in donor selection and prognosis estimation in liver transplantation. PMID:26034504

A case of rectal carcinoma with skin and bone marrow metastasis with concurrent extensive visceral involvement; unusual and dismal co-incidence.

PubMed

Arslan, Cagatay; Sen, Cenk Ahmet; Ortac, Ragip

2015-06-01

Novel systemic therapies and modern surgical and ablative approaches have improved the survival rates for the patients with metastatic colorectal cancer. However, there are still patients with poor prognosis and underlying mechanisms that could not be defined clearly. Metastatic colorectal cancer patients with skin metastasis have a poor prognosis. A 45-year-old man, who presented with large bowel obstruction, was diagnosed with metastatic rectal adenocarcinoma. Unresectable liver metastases were found at diagnosis. FOLFOX plus bevacizumab treatment was started, but the patient developed bowel obstruction after the third cycle. Therefore, ileostomy was performed. Multiple skin, lung, liver and bone metastases appeared during that time. Bone marrow biopsy demonstrated diffuse infiltration by adenocarcinoma cells. Even though partial remission was achieved after 4 cycles of FOLFIRI-cetuximab, the disease progressed after the 8th cycle. The patient lost his life due to disease progression 8 months after the diagnosis. Bone marrow and skin are unusual sites of metastasis for colorectal carcinoma. Metastases in bone marrow and skin develop at later stages of metastatic disease. This patient lived only 4 months after the development of skin and bone marrow metastases. Skin and bone marrow metastases may be the harbingers of short survival. Biopsy of metastatic sites is crucial for diagnosis and detailed molecular analysis. Molecular pathway alterations underlying worse disease course may be found, and hence probable targets for drug improvement may be indicated.

Betaine chemistry, roles, and potential use in liver disease.

PubMed

Day, Christopher R; Kempson, Stephen A

2016-06-01

Betaine is the trimethyl derivative of glycine and is normally present in human plasma due to dietary intake and endogenous synthesis in liver and kidney. Betaine is utilized in the kidney primarily as an osmoprotectant, whereas in the liver its primary role is in metabolism as a methyl group donor. In both organs, a specific betaine transporter mediates cellular uptake of betaine from plasma. The abundance of both betaine and the betaine transporter in liver greatly exceeds that of other organs. The remarkable contributions of betaine to normal human and animal health are summarized together with a discussion of the mechanisms and potential beneficial effects of dietary betaine supplements on liver disease. A significant amount of data from animal models of liver disease indicates that administration of betaine can halt and even reverse progression of the disruption of liver function. Betaine is well-tolerated, inexpensive, effective over a wide range of doses, and is already used in livestock feeding practices. The accumulated data indicate that carefully controlled additional investigations in humans are merited. The focus should be on the long-term use of betaine in large patient populations with liver diseases characterized by development of fatty liver, especially non-alcoholic fatty liver disease and alcoholic liver disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Coffee Intake Is Associated with a Lower Liver Stiffness in Patients with Non-Alcoholic Fatty Liver Disease, Hepatitis C, and Hepatitis B.

PubMed

Hodge, Alexander; Lim, Sarah; Goh, Evan; Wong, Ophelia; Marsh, Philip; Knight, Virginia; Sievert, William; de Courten, Barbora

2017-01-10

There is emerging evidence for the positive effects or benefits of coffee in patients with liver disease. We conducted a retrospective cross-sectional study on patients with non-alcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV), and hepatitis B virus (HBV) infection to determine the effects of coffee intake on a non-invasive marker of liver fibrosis: liver stiffness assessed by transient elastography (TE). We assessed coffee and tea intake and measured TE in 1018 patients with NAFLD, HCV, and HBV (155 with NAFLD, 378 with HCV and 485 with HBV). Univariate and multivariate regression models were performed taking into account potential confounders. Liver stiffness was higher in males compared to females ( p < 0.05). Patients with HBV had lower liver stiffness than those with HCV and NAFLD. After adjustment for age, gender, smoking, alcohol consumption, M or XL probe, and disease state (NAFLD, HCV, and HBV status), those who drank 2 or more cups of coffee per day had a lower liver stiffness ( p = 0.044). Tea consumption had no effect ( p = 0.9). Coffee consumption decreases liver stiffness, which may indicate less fibrosis and inflammation, independent of disease state. This study adds further evidence to the notion of coffee maybe beneficial in patients with liver disease.

Significance of increased expression of decoy receptor 3 in chronic liver disease.

PubMed

Kim, S; Kotoula, V; Hytiroglou, P; Zardavas, D; Zhang, L

2009-08-01

Considerable evidence has indicated that apoptosis plays an important role in hepatocyte death in chronic liver disease. However, the cellular and molecular mechanisms underlying liver regeneration in these diseases are largely unknown. Plausibly, certain molecules expressed to counteract apoptosis might provide survival advantage of certain liver cells. Therefore, we investigated a possible expression of decoy receptor 3 of the tumour necrosis factor receptor family in chronic liver diseases since decoy receptor 3 is known to inhibit apoptosis mediated by pro-apoptotic tumour necrosis factor family ligands including Fas ligand. A series of liver biopsies from patients with different stages of fibrosis were subjected to immunohistochemistry and in situ hybridization. Both decoy receptor 3 protein and mRNA were mainly expressed in biliary epithelial cells and infiltrating lymphocytes in the diseased livers. Most noticeably, intense decoy receptor 3 expression was observed in newly developing biliary ductules in regenerative nodules as well as dysplastic nodules of cirrhotic livers. In addition, decoy receptor 3 secretion in hepatocellular carcinoma cells in culture was via the activation of mitogen-activated protein kinases. Decoy receptor 3 was specifically expressed in chronic liver diseases and hepatocellular carcinoma cells, and decoy receptor 3 might facilitate the survival of liver cells by exerting its anti-apoptotic activity during the progression of liver cirrhosis and hepatocarcinogenesis.

Periodontal disease and liver cirrhosis: A systematic review

PubMed Central

2015-01-01

Objectives: Studies suggest that periodontal disease, a source of subclinical and persistent infection, may be associated with various systemic conditions, including liver cirrhosis. The aim of this study was to examine the literature and determine the relationship between periodontal disease and liver cirrhosis and to identify opportunities and directions for future research in this area. Methods: A systematic review of English articles in the PubMed, EMBASE, and Scopus databases was conducted using search terms including ‘liver cirrhosis’, ‘end-stage liver disease’, ‘liver diseases’, ‘oral health’, ‘periodontal disease’, ‘mouth disease’, ‘gingivitis’, and ‘periodontitis’. Results: Thirteen studies published between 1981 and 2014 were found to include data on oral health and periodontal disease in cirrhotic patients. Studies indicated an increased incidence of periodontal disease in patients with liver cirrhosis, measured with several different periodontal indices. The reported prevalence of periodontal disease in cirrhosis patients ranged from 25.0% to 68.75% in four studies and apical periodontitis was found in 49%–79% of the patients. One study found that mortality was lower among patients who underwent dental treatment versus non-treated patients. Another study suggested an association between periodontal disease and the progression of liver cirrhosis, but data are sparse and conflicting as to whether periodontal disease is correlated to cirrhosis aetiology and severity. Conclusion: Despite the clinical reality of periodontal disease in liver cirrhosis patients, there are few published studies. Before clinical implications can be addressed, more data on the prevalence of and correlation between periodontal disease and liver cirrhosis aetiology, duration, and progression are needed. PMID:26770799

The emerging role of mast cells in liver disease.

PubMed

Jarido, Veronica; Kennedy, Lindsey; Hargrove, Laura; Demieville, Jennifer; Thomson, Joanne; Stephenson, Kristen; Francis, Heather

2017-08-01

The depth of our knowledge regarding mast cells has widened exponentially in the last 20 years. Once thought to be only important for allergy-mediated events, mast cells are now recognized to be important regulators of a number of pathological processes. The revelation that mast cells can influence organs, tissues, and cells has increased interest in mast cell research during liver disease. The purpose of this review is to refresh the reader's knowledge of the development, type, and location of mast cells and to review recent work that demonstrates the role of hepatic mast cells during diseased states. This review focuses primarily on liver diseases and mast cells during autoimmune disease, hepatitis, fatty liver disease, liver cancer, and aging in the liver. Overall, these studies demonstrate the potential role of mast cells in disease progression.

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.

Evaluation of a low-carbohydrate diet-based preparation protocol without fasting for cardiac PET/MR imaging.

PubMed

Nensa, Felix; Tezgah, E; Schweins, K; Goebel, J; Heusch, P; Nassenstein, K; Schlosser, T; Poeppel, T D

2017-06-01

Assessment of increased glucose uptake in inflammatory or malignant myocardial disease using PET/MRI relies on uptake suppression in normal myocardium. We evaluated the efficacy of a ≥24 hours high-fat, low-carbohydrate, and protein-permitted diet (HFLCPP) in combination with unfractionated heparin for suppression of "physiologic" myocardial glucose uptake. PET/MRI was successfully performed in 89 patients. HFLCPP was started ≥24 hours prior to PET/MRI. All patients received i.v. injection of unfractionated heparin (50 IU·kg -1 ) 15 minutes prior to FDG administration. Left ventricular FDG uptake was visually evaluated by two readers. Diffuse myocardial uptake exceeding liver uptake, isolated uptake in the lateral wall, or diffuse uptake in the entire circumference of the heart base were defined as failed suppression. Homogeneous myocardial uptake below liver uptake with/without focal uptake was defined as successful suppression. Success rate was 84%. Suppression was unsuccessful in 14 patients. No significant influence of gender (P = .40) or age (P = .21) was found. However, insufficient suppression was more common in patients younger than 45 years (20% vs 7%). PET/MR imaging completion rate was >97%. A HFLCPP diet in combination with unfractionated heparin was successfully implemented for cardiac PET/MRI and resulted in a sufficient suppression of myocardial FDG uptake in 84% of patients.

Review article: the endocannabinoid system in liver disease, a potential therapeutic target.

PubMed

Basu, P P; Aloysius, M M; Shah, N J; Brown, R S

2014-04-01

Endocannabinoids are a family of potent lipid-soluble molecules, acting on the cannabinoid (CB) receptors that mediate the effects of marijuana. The CB receptors, endocannabinoids and the enzymes involved in their synthesis and degradation are located in the brain and peripheral tissues, including the liver. To review the current understanding of the role of the endocannabinoid system in liver disease-associated pathophysiological conditions, and drugs targeting the endocannabinoid system as therapy for liver disease. Original articles and reviews were used to summarise the relevant pre-clinical and clinical research findings relating to this topic. The endocannabinoid system as a whole plays an important role in liver diseases (i.e. non-alcoholic liver disease, alcoholic liver disease, hepatic encephalopathy and autoimmune hepatitis) and related pathophysiological conditions (i.e. altered hepatic haemodynamics, cirrhotic cardiomyopathy, metabolic syndrome and ischaemia/reperfusion disease). Pharmacological targeting of the endocannabinoid system has had success as treatment for patients with liver disease, but adverse events led to withdrawal of marketing approval. However, there is optimism over novel therapeutics targeting the endocannabinoid system currently in the pre-clinical stage of development. The endocannabinoid system plays an important role in the pathophysiology of liver disease and its associated conditions. While some drugs targeting the endocannabinoid system have deleterious neurological adverse events, there is promise for a newer generation of therapies that do not cross the blood-brain barrier. © 2014 John Wiley & Sons Ltd.

[Current epidemiological status of causes of disease among patients with liver disease hospitalized in Department of Infectious Diseases in a large general hospital within the past 20 years].

PubMed

Zhao, R H; Ma, K; Hu, J; Chen, C X; Qi, J Y

2018-02-20

Objective: To investigate the causes of disease among patients with liver disease hospitalized in Department of Infectious Diseases in our hospital and the changes in such causes within the past 20 years. Methods: A retrospective analysis was performed for the clinical data of 7570 patients who were admitted to our hospital from January 1995 to December 2015. The chi-square test was used for the statistical analysis of constituent ratio. Results: Of all 7570 patients with liver disease, 4930 (65.13%) had viral hepatitis, 332 (4.39%) had immune disease, 215 (2.84%) had drug-induced liver injury, 192 (2.54%) had fatty liver disease, 88 (1.16%) had schistosome-induced liver disease, 160 (2.11%) had inherited metabolic diseases, and 20 (0.13%) had vascular disease; 689 (9.1%) still had no clear cause of disease at discharge. The proportion of patients with viral hepatitis was 77.61% in the first 10 years and 59.19% in the last 10 years ( P < 0.01). As for liver disease caused by hepatotropic virus, there were significant increases in the proportion of patients with hepatitis C or hepatitis E from the first to the last 10 years (hepatitis C: 2.24% vs 15.56%, P < 0.01; hepatitis E: 18.61% vs 23.07%, P < 0.05), while there were significant reductions in the proportion of patients with hepatitis B (68.14% vs 60.01%, P < 0.05) or hepatitis A (10.7% vs 1.36%, P < 0.05). The proportion of patients with immune diseases was 0.82% in the first 10 years and 6.08% in the last 10 years ( P < 0.01). There were also certain changes in the proportion of patients with liver disease caused by other reasons. Conclusion: There is a large proportion of patients with viral hepatitis among patients with liver disease hospitalized in Department of Infectious Diseases in a large general hospital, especially hepatitis B and E caused by hepatotropic virus. There is a certain change in the epidemiology of liver disease within the past 20 years, with a reduction in the proportion of patients with viral hepatitis and an increase in the proportion of patients with non-infectious liver diseases. There is a large proportion of patients with unknown causes of liver disease.

Evaluation of abnormal liver function tests.

PubMed

Agrawal, Swastik; Dhiman, Radha K; Limdi, Jimmy K

2016-04-01

Incidentally detected abnormality in liver function tests is a common situation encountered by physicians across all disciplines. Many of these patients do not have primary liver disease as most of the commonly performed markers are not specific for the liver and are affected by myriad factors unrelated to liver disease. Also, many of these tests like liver enzyme levels do not measure the function of the liver, but are markers of liver injury, which is broadly of two types: hepatocellular and cholestatic. A combination of a careful history and clinical examination along with interpretation of pattern of liver test abnormalities can often identify type and aetiology of liver disease, allowing for a targeted investigation approach. Severity of liver injury is best assessed by composite scores like the Model for End Stage Liver Disease rather than any single parameter. In this review, we discuss the interpretation of the routinely performed liver tests along with the indications and utility of quantitative tests. 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/

Psychiatric morbidity in patients with alcoholic liver disease.

PubMed

Ewusi-Mensah, I; Saunders, J B; Wodak, A D; Murray, R M; Williams, R

1983-11-12

Seventy one patients with alcoholic liver disease and an equal number with non-alcoholic liver disease were interviewed using the schedule for affective disorders and schizophrenia. Forty seven (66%) of the group with alcoholic liver disease had or had had psychiatric illnesses compared with 23 (32%) of the control group (p less than 0.001). Affective disorder, particularly major depression, neurotic disorders, and antisocial personality, were all more common among the patients with alcoholic liver disease than the controls. No patient had schizophrenia or other forms of psychosis. Among the patients with alcoholic liver disease 11 men (24%) and 14 women (54%) had an affective or a neurotic disorder that had antedated their heavy drinking, and 30 (77%) of those who had had such a problem at any time had symptoms at the time of interview. Abstinence from alcohol is essential for patients with severe alcoholic liver disease. In view of the high prevalence of psychiatric disorders in these patients psychiatric assessment is important to increase the patients' likelihood of complying with such advice.

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.

Hepatocellular carcinoma: short-term reproducibility of apparent diffusion coefficient and intravoxel incoherent motion parameters at 3.0T.

PubMed

Kakite, Suguru; Dyvorne, Hadrien; Besa, Cecilia; Cooper, Nancy; Facciuto, Marcelo; Donnerhack, Claudia; Taouli, Bachir

2015-01-01

To evaluate short-term test-retest and interobserver reproducibility of IVIM (intravoxel incoherent motion) diffusion parameters and ADC (apparent diffusion coefficient) of hepatocellular carcinoma (HCC) and liver parenchyma at 3.0T. In this prospective Institutional Review Board (IRB)-approved study, 11 patients were scanned twice using a free-breathing single-shot echo-planar-imaging, diffusion-weighted imaging (DWI) sequence using 4 b values (b = 0, 50, 500, 1000 s/mm(2)) and IVIM DWI using 16 b values (0-800 s/mm(2)) at 3.0T. IVIM parameters (D: true diffusion coefficient, D*: pseudodiffusion coefficient, PF: perfusion fraction) and ADC (using 4 b and 16 b) were calculated. Short-term test-retest and interobserver reproducibility of IVIM parameters and ADC were assessed by measuring correlation coefficient, coefficient of variation (CV), and Bland-Altman limits of agreements (BA-LA). Fifteen HCCs were assessed in 10 patients. Reproducibility of IVIM metrics in HCC was poor for D* and PF (mean CV 60.6% and 37.3%, BA-LA: -161.6% to 135.3% and -66.2% to 101.0%, for D* and PF, respectively), good for D and ADC (CV 19.7% and <16%, BA-LA -57.4% to 36.3% and -38.2 to 34.1%, for D and ADC, respectively). Interobserver reproducibility was on the same order of test-retest reproducibility except for PF in HCC. Reproducibility of diffusion parameters was better in liver parenchyma compared to HCC. Poor reproducibility of D*/PF and good reproducibility for D/ADC were observed in HCC and liver parenchyma. These findings may have implications for trials using DWI in HCC. © 2014 Wiley Periodicals, Inc.

Liver Diseases

MedlinePlus

Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases: Diseases caused by viruses, such as hepatitis ...

[Non-invasive assessment of fatty liver].

PubMed

Egresi, Anna; Lengyel, Gabriella; Hagymási, Krisztina

2015-04-05

As the result of various harmful effects (infectious agents, metabolic diseases, unhealthy diet, obesity, toxic agents, autoimmune processes) hepatic damage may develop, which can progress towards liver steatosis, and fibrosis as well. The most common etiological factors of liver damages are hepatitis B and C infection, alcohol consumption and non-alcoholic fatty liver disease. Liver biopsy is considered as the gold standard for the diagnosis of chronic liver diseases. Due to the dangers and complications of liver biopsy, studies are focused on non-invasive markers and radiological imaging for liver steatosis, progression of fatty liver, activity of the necroinflammation and the severity of the fibrosis. Authors review the possibilities of non-invasive assessment of liver steatosis. The statistical features of the probes (positive, negative predictive values, sensitivity, specificity) are reviewed. The role of radiological imaging is also discussed. Although the non-invasive methods discussed in this article are useful to assess liver steatosis, further studies are needed to validate to follow progression of the diseases and to control therapeutic response.

Quantitative in vivo optical tomography of cancer progression & vasculature development in adult zebrafish

PubMed Central

Kumar, Sunil; Lockwood, Nicola; Ramel, Marie-Christine; Correia, Teresa; Ellis, Matthew; Alexandrov, Yuriy; Andrews, Natalie; Patel, Rachel; Bugeon, Laurence; Dallman, Margaret J.; Brandner, Sebastian; Arridge, Simon; Katan, Matilda; McGinty, James; Frankel, Paul; French, Paul M.W.

2016-01-01

We describe a novel approach to study tumour progression and vasculature development in vivo via global 3-D fluorescence imaging of live non-pigmented adult zebrafish utilising angularly multiplexed optical projection tomography with compressive sensing (CS-OPT). This “mesoscopic” imaging method bridges a gap between established ~μm resolution 3-D fluorescence microscopy techniques and ~mm-resolved whole body planar imaging and diffuse tomography. Implementing angular multiplexing with CS-OPT, we demonstrate the in vivo global imaging of an inducible fluorescently labelled genetic model of liver cancer in adult non-pigmented zebrafish that also present fluorescently labelled vasculature. In this disease model, addition of a chemical inducer (doxycycline) drives expression of eGFP tagged oncogenic K-RASV12 in the liver of immune competent animals. We show that our novel in vivo global imaging methodology enables non-invasive quantitative imaging of the development of tumour and vasculature throughout the progression of the disease, which we have validated against established methods of pathology including immunohistochemistry. We have also demonstrated its potential for longitudinal imaging through a study of vascular development in the same zebrafish from early embryo to adulthood. We believe that this instrument, together with its associated analysis and data management tools, constitute a new platform for in vivo cancer studies and drug discovery in zebrafish disease models. PMID:27259259

Zebrafish: An Important Tool for Liver Disease Research

PubMed Central

Goessling, Wolfram; Sadler, Kirsten C.

2016-01-01

As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration. PMID:26319012

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.

Endocannabinoids in liver disease and hepatic encephalopathy.

PubMed

Magen, Iddo; Avraham, Yosefa; Berry, Elliot; Mechoulam, Raphael

2008-01-01

Chronic liver disease results from a variety of causes such as hepatitis virus infections, autoimmune processes and alcohol consumption. Its complications include fat deposition, hemodynamic changes and fibrosis. Clinically there may be progression to portal-hypertension and porto-systemic encephalopathy. Pioneering research from the laboratory of Kunos at NIH has stressed the importance of endocannabinoids (ECs) as mediators of some of the pathological processes in chronic liver disease. The present review summarizes the literature on the association between ECs and liver disease, as well as the therapeutic potential of ECs and exogenous cannabinoids in liver disease with emphasis on hepatic encephalopathy.

Microbiota-Liver Axis in Hepatic Disease

PubMed Central

Chassaing, Benoit; Etienne-Mesmin, Lucie; Gewirtz, Andrew T.

2014-01-01

Accumulating evidence indicates that the gut microbiota, long appreciated to be a key determinant of intestinal inflammation, is also playing a key role in chronic inflammatory disease of the liver. Such studies have yielded a general central hypothesis whereby microbiota products activate the innate immune system to drive pro-inflammatory gene expression thus promoting chronic inflammatory disease of the liver. This article reviews the background supporting this hypothesis, outlines how it can potentially explain classic and newly emerging epidemiological chronic inflammatory liver disease, and discusses potential therapeutic means to manipulate the microbiota so as to prevent and/or treat liver disease. PMID:23703735

Eliminating the blood-flow confounding effect in intravoxel incoherent motion (IVIM) using the non-negative least square analysis in liver.

PubMed

Gambarota, Giulio; Hitti, Eric; Leporq, Benjamin; Saint-Jalmes, Hervé; Beuf, Olivier

2017-01-01

Tissue perfusion measurements using intravoxel incoherent motion (IVIM) diffusion-MRI are of interest for investigations of liver pathologies. A confounding factor in the perfusion quantification is the partial volume between liver tissue and large blood vessels. The aim of this study was to assess and correct for this partial volume effect in the estimation of the perfusion fraction. MRI experiments were performed at 3 Tesla with a diffusion-MRI sequence at 12 b-values. Diffusion signal decays in liver were analyzed using the non-negative least square (NNLS) method and the biexponential fitting approach. In some voxels, the NNLS analysis yielded a very fast-decaying component that was assigned to partial volume with the blood flowing in large vessels. Partial volume correction was performed by biexponential curve fitting, where the first data point (b = 0 s/mm 2 ) was eliminated in voxels with a very fast-decaying component. Biexponential fitting with partial volume correction yielded parametric maps with perfusion fraction values smaller than biexponential fitting without partial volume correction. The results of the current study indicate that the NNLS analysis in combination with biexponential curve fitting allows to correct for partial volume effects originating from blood flow in IVIM perfusion fraction measurements. Magn Reson Med 77:310-317, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Localization of ABCG5 and ABCG8 proteins in human liver, gall bladder and intestine

PubMed Central

Klett, Eric L; Lee, Mi-Hye; Adams, David B; Chavin, Kenneth D; Patel, Shailendra B

2004-01-01

Background The molecular mechanisms that regulate the entry of dietary sterols into the body and their removal via hepatobiliary secretion are now beginning to be defined. These processes are specifically disrupted in the rare autosomal recessive disease, Sitosterolemia (MIM 210250). Mutations in either, but not both, of two genes ABCG5 or ABCG8, comprising the STSL locus, are now known to cause this disease and their protein products are proposed to function as heterodimers. Under normal circumstances cholesterol, but not non-cholesterol sterols, is preferentially absorbed from the diet. Additionally, any small amounts of non-cholesterol sterols that are absorbed are rapidly taken up by the liver and preferentially excreted into bile. Based upon the defects in sitosterolemia, ABCG5 and ABCG8 serve specifically to exclude non-cholesterol sterol entry at the intestinal level and are involved in sterol excretion at the hepatobiliary level. Methods Here we report the biochemical and immuno-localization of ABCG5 and ABCG8 in human liver, gallbladder and intestine using cell fractionation and immunohistochemical analyses. Results We raised peptide antibodies against ABCG5 and ABCG8 proteins. Using human liver samples, cell fractionation studies showed both proteins are found in membrane fractions, but they did not co-localize with caveolin-rafts, ER, Golgi or mitochondrial markers. Although their distribution in the sub-fractions was similar, they were not completely contiguous. Immunohistochemical analyses showed that while both proteins were readily detectable in the liver, ABCG5 was found predominately lining canalicular membranes, whereas ABCG8 was found in association with bile duct epithelia. At the cellular level, ABCG5 appeared to be apically expressed, whereas ABCG8 had a more diffuse expression pattern. Both ABCG5 and ABCG8 appeared to localize apically as shown by co-localization with MRP2. The distribution patterns of ABCG5 and ABCG8 in the gallbladder were very similar to each other. In the small intestine both ABCG5 and ABCG8 appear to line the brush border. However, at the level of the enterocyte, the cellular distribution patterns of ABCG5 and ABCG8 differed, such that ABCG5 was more diffuse, but ABCG8 was principally apical. Using standard deglycosylation methods, ABCG5 and ABCG8 do not appear to be glycosylated, suggesting a difference between human and mouse proteins. Conclusion We report the distribution patterns of ABCG5 and ABCG8 in human tissues. Cell fractionation studies showed that both proteins co-fractionated in general, but could also be found independent of each other. As predicted, they are expressed apically in both intestine and liver, although their intracellular expression patterns are not completely congruent. These studies support the concept of heterodimerization of ABCG5 and ABCG8, but also support the notion that these proteins may have an independent function. PMID:15383151

Anesthesia for Patients With Liver Disease

PubMed Central

Rahimzadeh, Poupak; Safari, Saeid; Faiz, Seyed Hamid Reza; Alavian, Seyed Moayed

2014-01-01

Context: Liver plays an important role in metabolism and physiological homeostasis in the body. This organ is unique in its structure and physiology. So it is necessary for an anesthesiologist to be familiar with various hepatic pathophysiologic conditions and consequences of liver dysfunction. Evidence Acquisition: We searched MEDLINE (Pub Med, OVID, MD Consult), SCOPUS and the Cochrane database for the following keywords: liver disease, anesthesia and liver disease, regional anesthesia in liver disease, epidural anesthesia in liver disease and spinal anesthesia in liver disease, for the period of 1966 to 2013. Results: Although different anesthetic regimens are available in modern anesthesia world, but anesthetizing the patients with liver disease is still really tough. Spinal or epidural anesthetic effects on hepatic blood flow and function is not clearly investigated, considering both the anesthetic drug-induced changes and outcomes. Regional anesthesia might be used in patients with advanced liver disease. In these cases lower drug dosages are used, considering the fact that locally administered drugs have less systemic effects. In case of general anesthesia it seems that using inhalation agents (Isoflurane, Desflurane or Sevoflurane), alone or in combination with small doses of fentanyl can be considered as a reasonable regimen. When administering drugs, anesthetist must realize and consider the substantially changed pharmacokinetics of some other anesthetic drugs. Conclusions: Despite the fact that anesthesia in chronic liver disease is a scary and pretty challenging condition for every anesthesiologist, this hazard could be diminished by meticulous attention on optimizing the patient’s condition preoperatively and choosing appropriate anesthetic regimen and drugs in this setting. Although there are paucity of statistics and investigations in this specific group of patients but these little data show that with careful monitoring and considering the above mentioned rules a safe anesthesia could be achievable in these patients. PMID:25031586

Cirrhosis and autoimmune liver disease: Current understanding

PubMed Central

Liberal, Rodrigo; Grant, Charlotte R

2016-01-01

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids. PMID:27729952

Limited Knowledge of Acetaminophen in Patients with Liver Disease.

PubMed

Saab, Sammy; Konyn, Peter G; Viramontes, Matthew R; Jimenez, Melissa A; Grotts, Jonathan F; Hamidzadah, Wally; Dang, Veronica P; Esmailzadeh, Negin L; Choi, Gina; Durazo, Francisco A; El-Kabany, Mohamed M; Han, Steven-Huy B; Tong, Myron J

2016-12-28

Background and Aims: Unintentional acetaminophen overdose remains the leading cause of acute liver failure in the United States. Patients with underlying liver disease are at higher risk of poor outcomes from acetaminophen overdose. Limited knowledge of acetaminophen may be a preventable contributor to elevated rates of overdose and thus acute liver failure. The purpose of this study is to assess knowledge of acetaminophen dosing and presence of acetaminophen in common combination products in patients with liver disease. Methods: We performed a cross-sectional study of patients with liver disease at the Pfleger Liver Institute at the University of California, Los Angeles between June 2015 and August 2016. Patients completed a demographic questionnaire and an acetaminophen knowledge survey. Additional information was obtained from the medical record. Results: Of 401 patients with liver disease, 30 (15.7%) were able to correctly identify that people without liver disease can safely take up to 4 g/day of acetaminophen. The majority of patients (79.9%-86.8%) did not know that Norco® (hydrocone/acetaminophen), Vicodin® (hydrocone/acetaminophen) and Percocet® (oxycodone/acetaminophen) contained acetaminophen. Only 45.3% of the patients knew that Tylenol® #3 contained acetaminophen. Conclusions: We conclude that patients with liver disease have critically low levels of knowledge of acetaminophen, putting them at risk both of acetaminophen overdose, as well as undermedication, and inadequate management of chronic pain. We recommend an increase in education efforts regarding acetaminophen dosage and its safety in the setting of liver disease. Increasing education for those at risk of low acetaminophen knowledge is essential to minimizing acetaminophen overdose rates and optimizing pain management.

[Are non-invasive tests going to replace liver biopsy for diagnosis of liver fibrosis?].

PubMed

Restellini, Sophie; Spahr, Laurent

2012-06-27

Liver fibrosis is associated with chronic liver diseases, and may evolve into cirrhosis that may be complicated by liver failure and portal hypertension. Detection and quantification of liver fibrosis is a key point in the follow-up of patients with chronic liver diseases. Liver biopsy is the gold standard method to assess and quantify fibrosis, but its invasiveness is a limiting factor in everyday clinical practice. Non invasive markers using either biological or radiological parameters have been developed and may decrease the need for liver biopsy in some cases. However, information is limited to fibrosis, and cut-offs values and diagnostic accuracies for significant fibrosis may vary according to the etiology of liver disease. Liver biopsy allows the assessment of intermediate stages of fibrosis and describes accompanying lesions.

Is the iron regulatory hormone hepcidin a risk factor for alcoholic liver disease?

PubMed Central

Harrison-Findik, Duygu Dee

2009-01-01

Despite heavy consumption over a long period of time, only a small number of alcoholics develop alcoholic liver disease. This alludes to the possibility that other factors, besides alcohol, may be involved in the progression of the disease. Over the years, many such factors have indeed been identified, including iron. Despite being crucial for various important biological processes, iron can also be harmful due to its ability to catalyze Fenton chemistry. Alcohol and iron have been shown to interact synergistically to cause liver injury. Iron-mediated cell signaling has been reported to be involved in the pathogenesis of experimental alcoholic liver disease. Hepcidin is an iron-regulatory hormone synthesized by the liver, which plays a pivotal role in iron homeostasis. Both acute and chronic alcohol exposure suppress hepcidin expression in the liver. The sera of patients with alcoholic liver disease, particularly those exhibiting higher serum iron indices, have also been reported to display reduced prohepcidin levels. Alcohol-mediated oxidative stress is involved in the inhibition of hepcidin promoter activity and transcription in the liver. This in turn leads to an increase in intestinal iron transport and liver iron storage. Hepcidin is expressed primarily in hepatocytes. It is noteworthy that both hepatocytes and Kupffer cells are involved in the progression of alcoholic liver disease. However, the activation of Kupffer cells and TNF-α signaling has been reported not to be involved in the down-regulation of hepcidin expression by alcohol in the liver. Alcohol acts within the parenchymal cells of the liver to suppress the synthesis of hepcidin. Due to its crucial role in the regulation of body iron stores, hepcidin may act as a secondary risk factor in the progression of alcoholic liver disease. The clarification of the mechanisms by which alcohol disrupts iron homeostasis will allow for further understanding of the pathogenesis of alcoholic liver disease. PMID:19291818

Antioxidants in liver health

PubMed Central

Casas-Grajales, Sael; Muriel, Pablo

2015-01-01

Liver diseases are a worldwide medical problem because the liver is the principal detoxifying organ and maintains metabolic homeostasis. The liver metabolizes various compounds that produce free radicals (FR). However, antioxidants scavenge FR and maintain the oxidative/antioxidative balance in the liver. When the liver oxidative/antioxidative balance is disrupted, the state is termed oxidative stress. Oxidative stress leads to deleterious processes in the liver and produces liver diseases. Therefore, restoring antioxidants is essential to maintain homeostasis. One method of restoring antioxidants is to consume natural compounds with antioxidant capacity. The objective of this review is to provide information pertaining to various antioxidants found in food that have demonstrated utility in improving liver diseases. PMID:26261734

Folate, Alcohol, and Liver Disease

PubMed Central

Medici, Valentina; Halsted, Charles H.

2013-01-01

Alcoholic liver disease (ALD) is typically associated with folate deficiency, which is the result of reduced dietary folate intake, intestinal malabsorption, reduced liver uptake and storage, and increased urinary folate excretion. Folate deficiency favors the progression of liver disease through mechanisms that include its effects on methionine metabolism with consequences for DNA synthesis and stability and the epigenetic regulation of gene expression involved in pathways of liver injury. This paper reviews the pathogenesis of alcoholic liver disease with particular focus on ethanol-induced alterations in methionine metabolism which may act in synergy with folate deficiency to decrease antioxidant defense as well as DNA stability while regulating epigenetic mechanisms of relevant gene expressions. We also review the current evidence available on potential treatments of alcoholic liver disease based on correcting abnormalities in methionine metabolism and the methylation regulation of relevant gene expressions. PMID:23136133

Intrahepatic portal hypertension secondary to metastatic carcinoma of the prostate.

PubMed

Attila, Tan; Datta, Milton W; Sudakoff, Gary; Abu-Hajir, Majed; Massey, Benson T

2007-02-01

While the liver is a common site of metastasis, tumor metastases are not a common cause of portal hypertension. We report a case of a patient with symptomatic portal hypertension due to diffuse metastatic prostate carcinoma infiltration of liver parenchyma that was not appreciated with routine imaging.

Systematic review: The model for end-stage liver disease--should it replace Child-Pugh's classification for assessing prognosis in cirrhosis?

PubMed

Cholongitas, E; Papatheodoridis, G V; Vangeli, M; Terreni, N; Patch, D; Burroughs, A K

2005-12-01

Prognosis in cirrhotic patients has had a resurgence of interest because of liver transplantation and new therapies for complications of end-stage cirrhosis. The model for end-stage liver disease score is now used for allocation in liver transplantation waiting lists, replacing Child-Turcotte-Pugh score. However, there is debate as whether it is better in other settings of cirrhosis. To review studies comparing the accuracy of model for end-stage liver disease score vs. Child-Turcotte-Pugh score in non-transplant settings. Transjugular intrahepatic portosystemic shunt studies (with 1360 cirrhotics) only one of five, showed model for end-stage liver disease to be superior to Child-Turcotte-Pugh to predict 3-month mortality, but not for 12-month mortality. Prognosis of cirrhosis studies (with 2569 patients) none of four showed significant differences between the two scores for either short- or long-term prognosis whereas no differences for variceal bleeding studies (with 411 cirrhotics). Modified Child-Turcotte-Pugh score, by adding creatinine, performed similarly to model for end-stage liver disease score. Hepatic encephalopathy and hyponatraemia (as an index of ascites), both components of Child-Turcotte-Pugh score, add to the prognostic performance of model for end-stage liver disease score. Based on current literature, model for end-stage liver disease score does not perform better than Child-Turcotte-Pugh score in non-transplant settings. Modified Child-Turcotte-Pugh and model for end-stage liver disease scores need further evaluation.

Is the skin a sanctuary for breast cancer cells during treatment with anti-HER2 antibodies?

PubMed

Graziano, Vincenzo; Scognamiglio, Maria Teresa; Zilli, Marinella; Giampietro, Jamara; Vici, Patrizia; Natoli, Clara; Grassadonia, Antonino

2015-01-01

The occurrence of skin metastases is a common event in patients affected by advanced breast cancer, usually associated with systemic disease progression. Here we describe 2 cases of diffuse cutaneous metastases from HER2-overexpressing breast cancer occurring despite a dramatic response in liver and bone, respectively, during treatment with anti-HER2 antibodies Trastuzumab and Pertuzumab. We discuss the reasons for this discrepancy and suggest a possible implication of impaired immune response in the skin. Future research should provide strategies to overcome the induction of immune privilege in the skin in order to avoid discontinuation of effective treatments.

Model for End-Stage Liver Disease, Model for Liver Transplantation Survival and Donor Risk Index as predictive models of survival after liver transplantation in 1,006 patients.

PubMed

Aranzana, Elisa Maria de Camargo; Coppini, Adriana Zuolo; Ribeiro, Maurício Alves; Massarollo, Paulo Celso Bosco; Szutan, Luiz Arnaldo; Ferreira, Fabio Gonçalves

2015-06-01

Liver transplantation has not increased with the number of patients requiring this treatment, increasing deaths among those on the waiting list. Models predicting post-transplantation survival, including the Model for Liver Transplantation Survival and the Donor Risk Index, have been created. Our aim was to compare the performance of the Model for End-Stage Liver Disease, the Model for Liver Transplantation Survival and the Donor Risk Index as prognostic models for survival after liver transplantation. We retrospectively analyzed the data from 1,270 patients who received a liver transplant from a deceased donor in the state of São Paulo, Brazil, between July 2006 and July 2009. All data obtained from the Health Department of the State of São Paulo at the 15 registered transplant centers were analyzed. Patients younger than 13 years of age or with acute liver failure were excluded. The majority of the recipients had Child-Pugh class B or C cirrhosis (63.5%). Among the 1,006 patients included, 274 (27%) died. Univariate survival analysis using a Cox proportional hazards model showed hazard ratios of 1.02 and 1.43 for the Model for End-Stage Liver Disease and the Model for Liver Transplantation Survival, respectively (p<0.001). The areas under the ROC curve for the Donor Risk Index were always less than 0.5, whereas those for the Model for End-Stage Liver Disease and the Model for Liver Transplantation Survival were significantly greater than 0.5 (p<0.001). The cutoff values for the Model for End-Stage Liver Disease (≥29.5; sensitivity: 39.1%; specificity: 75.4%) and the Model for Liver Transplantation Survival (≥1.9; sensitivity 63.9%, specificity 54.5%), which were calculated using data available before liver transplantation, were good predictors of survival after liver transplantation (p<0.001). The Model for Liver Transplantation Survival displayed similar death prediction performance to that of the Model for End-Stage Liver Disease. A simpler model involving fewer variables, such as the Model for End-Stage Liver Disease, is preferred over a complex model involving more variables, such as the Model for Liver Transplantation Survival. The Donor Risk Index had no significance in post-transplantation survival in our patients.

Thromboelastometry

PubMed Central

Dumitrescu, Gabriel; Januszkiewicz, Anna; Ågren, Anna; Magnusson, Maria; Wahlin, Staffan; Wernerman, Jan

2017-01-01

Abstract The severity of liver disease is assessed by scoring systems, which include the conventional coagulation test prothrombin time-the international normalized ratio (PT-INR). However, PT-INR is not predictive of bleeding in liver disease and thromboelastometry (ROTEM) has been suggested to give a better overview of the coagulation system in these patients. It has now been suggested that coagulation as reflected by tromboelastomety may also be used for prognostic purposes. The objective of our study was to investigate whether thrombelastometry may discriminate the degree of liver insufficiency according to the scoring systems Child Pugh and Model for End-stage Liver Disease (MELD). Forty patients with chronic liver disease of different etiologies and stages were included in this observational cross-sectional study. The severity of liver disease was evaluated using the Child-Pugh score and the MELD score, and blood samples for biochemistry, conventional coagulation tests, and ROTEM were collected at the time of the final assessment for liver transplantation. Statistical comparisons for the studied parameters with scores of severity were made using Spearman correlation test and receiver-operating characteristic (ROC) curves. Spearman correlation coefficients indicated that the thromboelastometric parameters did not correlate with Child-Pugh or MELD scores. The ROC curves of the thromboelastometric parameters could not differentiate advanced stages from early stages of liver cirrhosis. Standard ROTEM cannot discriminate the stage of chronic liver disease in patients with severe chronic liver disease. PMID:28591054

Functional characterization of liver-associated lymphocytes in patients with liver metastasis.

PubMed

Winnock, M; Garcia-Barcina, M; Huet, S; Bernard, P; Saric, J; Bioulac-Sage, P; Gualde, N; Balabaud, C

1993-10-01

The liver-associated lymphocytes (LAL) population is mainly composed of cells with natural killer (NK) activity expressing the CD3+/-CD56+ phenotype. No evident difference has been found in the phenotypic data between patients with benign or malignant liver disease. In this study, the cytotoxic pattern of this population has been characterized from patients who underwent an operation for benign or metastatic liver disease. LAL were isolated by sinusoidal high-pressure lavage from partial hepatectomies. Phenotype was characterized by flow cytometry, and cytotoxicity was evaluated by standard 4-hour 51Cr release assays against NK and lymphokine-activated killer (LAK)-sensitive targets. In patients with benign liver disease, LAL showed spontaneous high levels of NK activity and LAK activity compared with peripheral blood lymphocytes. In patients with metastatic liver disease, no difference was observed in the levels of NK activity between LAL and peripheral blood, and the level of LAK activity was far lower than that expressed in patients with benign liver disease. These results show that the cytotoxic pattern of peripheral blood lymphocytes does not mirror that of LAL. In patients with benign liver disease, LAL are in a state of activation, whereas the decreased level of LAL cytotoxicity in patients with metastatic liver disease suggests that the cytotoxic activity of these cells could be inhibited by the presence of suppressive factors.

[Various pathways leading to the progression of chronic liver diseases].

PubMed

Egresi, Anna; Lengyel, Gabriella; Somogyi, Anikó; Blázovics, Anna; Hagymási, Krisztina

2016-02-21

As the result of various effects (viruses, metabolic diseases, nutritional factors, toxic agents, autoimmune processes) abnormal liver function, liver steatosis and connective tissue remodeling may develop. Progression of this process is complex including various pathways and a number of factors. The authors summarize the factors involved in the progression of chronic liver disease. They describe the role of cells and the produced inflammatory mediators and cytokines, as well as the relationship between the disease and the intestinal flora. They emphasize the role of oxidative stress, mitochondrial dysfunction and cell death in disease progression. Insulin resistance and micro-elements (iron, copper) in relation to liver damage are also discussed, and genetic and epigenetic aspects underlying disease progression are summarized. Discovery of novel treatment options, assessment of the effectiveness of treatment, as well as the success and proper timing of liver transplantation may depend on a better understanding of the process of disease progression.

Perioperative management of liver surgery-review on pathophysiology of liver disease and liver failure.

PubMed

Gasteiger, Lukas; Eschertzhuber, Stephan; Tiefenthaler, Werner

2018-01-01

An increasing number of patients present for liver surgery. Given the complex pathophysiological changes in chronic liver disease (CLD), it is pivotal to understand the fundamentals of chronic and acute liver failure. This review will give an overview on related organ dysfunction as well as recommendations for perioperative management and treatment of liver failure-related symptoms.

Evaluation of fatty liver fibrosis in rabbits using real-time shear wave elastography

PubMed Central

LU, YONGPING; WEI, JIA; TANG, YUEYUE; YUAN, YUAN; HUANG, YANLING; ZHANG, YONG; LI, YUNYAN

2014-01-01

The aim of the present study was to detect the elastic modulus (stiffness) of the livers of rabbits with non-alcoholic and alcoholic fatty liver disease using real-time shear wave elastography (SWE), and to investigate the fibrosis development process in the formation of fatty liver. The stiffness of the fatty livers in rabbit models prepared via feeding with alcohol or a high-fat diet were measured using a real-time SWE ultrasound system and a 4–15-MHz linear array probe, and the liver stiffness was compared with the pathological staging of the disease. The stiffness of the liver was positively correlated with the degree of pathological change in fatty liver disease (P<0.01). The stiffness of the liver in the alcoholic fatty liver group was higher compared with that in the non-alcoholic fatty liver and control groups, and the stiffness in the non-alcoholic fatty liver group was higher than that in the control group (P<0.01). Real-time SWE objectively identified the trend in the changing stiffness of the liver and noninvasively detected the development of fibrosis in the progression of non-alcoholic and alcoholic fatty liver disease. PMID:25009583

Natural Medicines Used in the Traditional Tibetan Medical System for the Treatment of Liver Diseases

PubMed Central

Li, Qi; Li, Hai-Jiao; Xu, Tong; Du, Huan; Huan Gang, Chen-Lei; Fan, Gang; Zhang, Yi

2018-01-01

Liver disease is one of the most risk factors threatening human health. It is of great significance to find drugs that can treat liver diseases, especially for acute and chronic hepatitis, non-alcoholic fatty liver disease, and liver cancer. The search for drugs with good efficacy from traditional natural medicines has attracted more and more attention. Tibetan medicine, one of the China's traditional medical systems, has been widely used by the Tibetan people for the prevention and treatment of liver diseases for hundreds of years. The present paper summarized the natural Tibetan medicines that have been used in Tibetan traditional system of medicine to treat liver diseases by bibliographic investigation of 22 Tibetan medicine monographs and drug standards. One hundred and ninety three species including 181 plants, 7 animals, and 5 minerals were found to treat liver diseases in traditional Tibetan medicine system. The most frequently used species are Carthamus tinctorius, Brag-zhun, Swertia chirayita, Swertia mussotii, Halenia elliptica, Herpetospermum pedunculosum, and Phyllanthus emblica. Their names, families, medicinal parts, traditional uses, phytochemicals information, and pharmacological activities were described in detail. These natural medicines might be a valuable gift from the old Tibetan medicine to the world, and would be potential drug candidates for the treatment of liver diseases. Further studies are needed to prove their medicinal values in liver diseases treatment, identify bioactive compounds, elucidate the underlying mechanism of action, and clarify their side effects or toxicity with the help of modern phytochemical, pharmacological, metabonomics, and/or clinical trial methods. PMID:29441019

Challenge of liver disease in systemic lupus erythematosus: Clues for diagnosis and hints for pathogenesis

PubMed Central

Bessone, Fernando; Poles, Natalia; Roma, Marcelo G

2014-01-01

Systemic lupus erythematosus (SLE) encompass a broad spectrum of liver diseases. We propose here to classify them as follows: (1) immunological comorbilities (overlap syndromes); (2) non-immunological comorbilities associated to SLE; and (3) a putative liver damage induced by SLE itself, referred to as “lupus hepatitis”. In the first group, liver injury can be ascribed to overlapping hepatopathies triggered by autoimmune mechanisms other than SLE occurring with higher incidence in the context of lupus (e.g., autoimmune hepatitis, primary biliary cirrhosis). The second group includes non-autoimmune liver diseases, such as esteatosis, hepatitis C, hypercoagulation state-related liver lesions, hyperplasic parenchymal and vascular lesions, porphyria cutanea tarda, and drug-induced hepatotoxicity. Finally, the data in the literature to support the existence of a hepatic disease produced by SLE itself, or the occurrence of a SLE-associated prone condition that increases susceptibility to acquire other liver diseases, is critically discussed. The pathological mechanisms underlying each of these liver disorders are also reviewed. Despite the high heterogeneity in the literature regarding the prevalence of SLE-associated liver diseases and, in most cases, lack of histopathological evidence or clinical studies large enough to support their existence, it is becoming increasingly apparent that liver is an important target of SLE. Consequently, biochemical liver tests should be routinely carried out in SLE patients to discard liver disorders, particularly in those patients chronically exposed to potentially hepatotoxic drugs. Diagnosing liver disease in SLE patients is always challenging, and the systematization of the current information carried out in this review is expected to be of help both to attain a better understanding of pathogenesis and to build an appropriate work-up for diagnosis. PMID:25018850

Extracorporeal Bioartificial Liver for Treating Acute Liver Diseases

PubMed Central

Kumar, Ashok; Tripathi, Anuj; Jain, Shivali

2011-01-01

Abstract: Liver is a vital organ of the human body performing myriad of essential functions. Liver-related ailments are often life-threatening and dramatically deteriorate the quality of life of patients. Management of acute liver diseases requires adequate support of various hepatic functions. Thus far, liver transplantation has been proven as the only effective solution for acute liver diseases. However, broader application of liver transplantation is limited by demand for lifelong immunosuppression, shortage of organ donors, relative high morbidity, and high cost. Therefore, research has been focused on attempting to develop alternative support systems to treat liver diseases. Earlier attempts have been made to use nonbiological therapies based on the use of conventional detoxification procedures such as filtration and dialysis. However, the absence of liver cells in such techniques reduced the overall survival rate of the patients and led to inadequate essential liver-specific functions. As a result, there has been growing interest in the development of biological therapy-based extracorporeal liver support systems as a bridge to liver transplantation or to support the ailing liver. A bioartificial liver support is an extracorporeal device through which plasma is circulated over living and functionally active hepatocytes packed in a bioreactor with the aim to aid the diseased liver until it regenerates or until a suitable graft for transplantation is available. This review article gives a brief overview of efficacy of various liver support systems that are currently available. Also, the development of advanced liver support systems, which has been analyzed for improving the important system component such as cell source and other culture and circulation conditions for the maintenance of the liver-specific functions, have been described. PMID:22416599

Sugar-sweetened beverage, diet soda, and fatty liver disease in the Framingham Heart Study cohorts

PubMed Central

Ma, Jiantao; Fox, Caroline S.; Jacques, Paul F.; Speliotes, Elizabeth K.; Hoffmann, Udo; Smith, Caren E.; Saltzman, Edward; McKeown, Nicola M.

2016-01-01

Background & Aims Non-alcoholic fatty liver disease affects ~30% of US adults, yet the role of sugar-sweetened beverages and diet soda on these diseases remains unknown. We examined the cross-sectional association between intake of sugar-sweetened beverages or diet soda and fatty liver disease in participants of the Framingham Offspring and Third Generation cohorts. Methods Fatty liver disease was defined using liver attenuation measurements generated from computed tomography in 2634 participants. Alanine transaminase concentration, a crude marker of fatty liver disease, was measured in 5908 participants. Sugar-sweetened beverage and diet soda intake were estimated using a food frequency questionnaire. Participants were categorized as either non-consumers or consumers (3 categories: 1 serving/month to <1 serving/week, 1 serving/week to <1 serving/-day, and ⩾1 serving/day) of sugar-sweetened beverages or diet soda. Results After adjustment for age, sex, smoking status, Framingham cohort, energy intake, alcohol, dietary fiber, fat (% energy), protein (% energy), diet soda intake, and body mass index, the odds ratios of fatty liver disease were 1, 1.16 (0.88, 1.54), 1.32 (0.93, 1.86), and 1.61 (1.04, 2.49) across sugar-sweetened beverage consumption categories (p trend = 0.04). Sugar-sweetened beverage consumption was also positively associated with alanine transaminase levels (p trend = 0.007). We observed no significant association between diet soda intake and measures of fatty liver disease. Conclusion In conclusion, we observed that regular sugar-sweetened beverage consumption was associated with greater risk of fatty liver disease, particularly in overweight and obese individuals, whereas diet soda intake was not associated with measures of fatty liver disease. PMID:26055949

Serum gastrin concentrations in dogs with liver disorders.

PubMed

Mazaki-Tovi, M; Segev, G; Yas-Natan, E; Lavy, E

2012-07-07

Dogs with liver disorders often display gastrointestinal signs that may be triggered by ulceration. The liver is important for inactivation of some forms of gastrin. Therefore, hypergastrinaemia has been implicated in the pathogenesis of gastrointestinal ulcerations related to liver dysfunction. The aim of this study was to determine serum gastrin concentrations in dogs with liver disease. Fasted blood samples were collected from 15 dogs with newly diagnosed liver disease and 18 healthy dogs. Gastrin concentrations were significantly lower in dogs with congenital portosystemic shunt compared with healthy dogs (P=0.003). No significant difference (P=0.6) in gastrin concentration was revealed between dogs with hepatocellular disease and healthy dogs. Serum gastrin concentrations were not significantly associated with the occurrence of vomiting, anorexia, diarrhoea, or melaena in dogs with liver disorders. These findings did not provide support for the role of hypergastrinaemia in the development of gastrointestinal signs associated with liver disease in dogs. Decreased serum concentrations of gastrin in a dog with liver disease may suggest the presence of portosystemic shunt. Further investigation is warranted to determine the importance of hyopogastrinaemia in congenital postosystemic shunts in dogs and to evaluate potential alterations in serum gastrin concentrations in specific hepatocellular diseases.

Prevalence and causes of abnormal liver function in patients with coeliac disease.

PubMed

Casella, Giovanni; Antonelli, Elisabetta; Di Bella, Camillo; Villanacci, Vincenzo; Fanini, Lucia; Baldini, Vittorio; Bassotti, Gabrio

2013-08-01

Coeliac disease patients frequently display mild elevation of liver enzymes and this abnormality usually normalizes after gluten-free diet. To investigate the cause and prevalence of altered liver function tests in coeliac patients, basally and after 1 year of gluten-free diet. Data from 245 untreated CD patients (196 women and 49 men, age range 15-80 years) were retrospectively analysed and the liver function tests before and after diet, as well as associated liver pathologies, were assessed. Overall, 43/245 (17.5%) patients had elevated values of one or both aminotransferases; the elevation was mild (<5 times the upper reference limit) in 41 (95%) and marked (>10 times the upper reference limit) in the remaining 2 (5%) patients. After 1 year of gluten-free diet, aminotransferase levels normalized in all but four patients with HCV infection or primary biliary cirrhosis. In coeliac patients, hypertransaminaseaemia at diagnosis and the lack of normalization of liver enzymes after 12 months of diet suggest coexisting liver disease. In such instance, further evaluation is recommended to exclude the liver disease. Early recognition and treatment of coeliac disease in patients affected by liver disease are important to improve the liver function and prevent complications. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Liver diseases: The pathogenetic role of the gut microbiome and the potential of treatment for its modulation].

PubMed

Aitbaev, K A; Murkamilov, I T; Fomin, V V

The paper gives an update on the role of the gut microbiome (GM) in the development of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, alcoholic liver disease, liver cirrhosis (LC), and its complications, such as hepatic encephalopathy (HE) and hepatocellular carcinoma (HCC), and discusses the possibilities of its correction with prebiotics, probiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). The pathophysiology of the liver diseases in question demonstrates some common features that are characterized by pathogenic changes in the composition of the gastrointestinal tract microflora, by intestinal barrier impairments, by development of endotoxemia, by increased liver expression of proinflammatory factors, and by development of liver inflammation. In progressive liver disease, the above changes are more pronounced, which contributes to the development of LC, HE, and HCC. GM modulation using prebiotics, probiotics, synbiotics, antibiotics, and FMT diminishes dysbacteriosis, strengthens the intestinal mucosal barrier, reduces endotoxemia and liver damage, and positively affects the clinical manifestations of HE. Further investigations are needed, especially in humans, firstly, to assess a relationship of GM to the development of liver diseases in more detail and, secondly, to obtain evidence indicating the therapeutic efficacy of GM-modulating agents in large-scale, well-designed, randomized, controlled, multicenter studies.

Reprint of: Nutrition in the Management of Cirrhosis and its Neurological Complications☆

PubMed Central

Bémeur, Chantal; Butterworth, Roger F.

2015-01-01

Malnutrition is a common feature of chronic liver diseases that is often associated with a poor prognosis including worsening of clinical outcome, neuropsychiatric complications as well as outcome following liver transplantation. Nutritional assessment in patients with cirrhosis is challenging owing to confounding factors related to liver failure. The objectives of nutritional intervention in cirrhotic patients are the support of liver regeneration, the prevention or correction of specific nutritional deficiencies and the prevention and/or treatment of the complications of liver disease per se and of liver transplantation. Nutritional recommendations target the optimal supply of adequate substrates related to requirements linked to energy, protein, carbohydrates, lipids, vitamins and minerals. Some issues relating to malnutrition in chronic liver disease remain to be addressed including the development of an appropriate well-validated nutritional assessment tool, the identification of mechanistic targets or therapy for sarcopenia, the development of nutritional recommendations for obese cirrhotic patients and liver-transplant recipients and the elucidation of the roles of vitamin A hepatotoxicity, as well as the impact of deficiencies in riboflavin and zinc on clinical outcomes. Early identification and treatment of malnutrition in chronic liver disease has the potential to lead to better disease outcome as well as prevention of the complications of chronic liver disease and improved transplant outcomes. PMID:26041952

Nuclear Receptor Variants in Liver Disease

PubMed Central

Müllenbach, Roman; Weber, Susanne N.; Lammert, Frank

2012-01-01

This review aims to provide a snapshot of the actual state of knowledge on genetic variants of nuclear receptors (NR) involved in regulating important aspects of liver metabolism. It recapitulates recent evidence for the application of NR in genetic diagnosis of monogenic (“Mendelian”) liver disease and their use in clinical diagnosis. Genetic analysis of multifactorial liver diseases such as viral hepatitis or fatty liver disease identifies key players in disease predisposition and progression. Evidence from these analyses points towards a role of NR polymorphisms in common diseases, linking regulatory networks to complex and variable phenotypes. The new insights into NR variants also offer perspectives and cautionary advice for their use as handles towards diagnosis and treatment. PMID:22523693

Development of a decision support tool for primary care management of patients with abnormal liver function tests without clinically apparent liver disease: a record-linkage population cohort study and decision analysis (ALFIE).

PubMed

Donnan, P T; McLernon, D; Dillon, J F; Ryder, S; Roderick, P; Sullivan, F; Rosenberg, W

2009-04-01

To determine the natural history of abnormalities in liver function tests (LFTs), derive predictive algorithms for liver disease and identify the most cost-effective strategies for further investigation. MEDLINE database from 1966 to September 2006, EMBASE, CINAHL and the Cochrane Library. Population-based retrospective cohort study set in primary care in Tayside, Scotland, between 1989 and 2003. Participants were patients with no obvious signs of liver disease and registered with a general practitioner (GP). The study followed up those with an incident batch of LFTs in primary care to subsequent liver disease or mortality over a maximum of 15 years. The health technologies being assessed were primary care LFTs, viral and autoantibody tests, ultrasound and liver biopsy. Measures used were the epidemiology of liver disease in Tayside (ELDIT) database, time-to-event modelling, predictive algorithms derived using the Weibull survival model, decision analyses from an NHS perspective, cost-utility analyses, and one-way and two-way sensitivity analyses. A total of 95,977 patients had 364,194 initial LFTs, with a median follow-up of 3.7 years. Of these, 21.7% had at least one abnormal liver function test (ALFT) and 1090 (1.14%) developed liver disease. Elevated transaminases were strongly associated with diagnosed liver disease, with hazard ratios (HRs) of 4.23 [95% CI (confidence interval) 3.55-5.04] for mild levels and 12.67 (95% CI 9.74-16.47) for severe levels versus normal. For gamma-glutamyltransferase (GGT), these HRs were 2.54 (95% CI 2.17-2.96) and 13.44 (10.71-16.87) respectively. Low albumin was strongly associated with all cause mortality, with ratios of 2.65 (95% CI 2.47-2.85) for mild levels and 4.99 (95% CI 4.26-5.84) for severe levels. Sensitivity for predicting events over 5 years was low and specificity was high. Follow-up time was split into baseline to 3 months, 3 months to 1 year and over 1 year. All LFTs were predictive of liver disease, and high probability of liver disease was associated with being female, methadone use, alcohol dependency and deprivation. The shorter-term models had overall c-statistics of 0.85 and 0.72 for outcome of liver disease at 3 months and 1 year respectively, and 0.88 and 0.82 for all cause mortality at 3 months and 1 year respectively. Calibration was good for models predicting liver disease. Discrimination was low for models predicting events at over 1 year. In cost-utility analyses, retesting dominated referral as an option. However, using the predictive algorithms to identify the top percentile at high risk of liver disease, retesting had an incremental cost-utility ratio of 7588 pounds relative to referral. GGT should be included in the batch of LFTs in primary care. If the patient in primary care has no obvious liver disease and a low or moderate risk of liver disease, retesting in primary care is the most cost-effective option. If the patient with ALFTs in primary care has a high risk of liver disease, retesting depends on the willingness to pay of the NHS. Cut-offs are arbitrary and in developing decision aids it is important to treat the LFT results as continuous variables.

Chronically Inflamed Livers Up-regulate Expression of Inhibitory B7 Family Members

PubMed Central

Kassel, Rachel; Cruise, Michael W.; Iezzoni, Julia C.; Taylor, Nicholas A.; Pruett, Timothy L.; Hahn, Young S.

2010-01-01

Hepatitis B virus (HBV), hepatitis C virus (HCV), autoimmune hepatitis (AIH), and non-alcoholic fatty liver disease (NAFLD) can induce chronic liver disease. The PD-1 inhibitory pathway assists in T cell response regulation during acute and chronic inflammation and participates in the progression of inflammatory liver disease. To examine whether PD-1 and its ligands, B7-H1 and B7-DC, are modulated during chronic necroinflammatory liver disease, we investigated expression profiles in normal patients and patients with the aforementioned conditions. Relative to liver biopsies from normal individuals, those from patients with chronic necroinflammatory liver diseases (HBV, HCV, and AIH) contain increased numbers of PD-1 expressing lymphocytes. Kupffer cells, liver sinusoidal endothelial cells (LSECs), and leukocytes express PD-1 ligands. We also detect PD-1 ligands on hepatocytes within biopsies and on isolated cells. All forms of chronic necroinflammatory liver disease examined correlate with increased B7-H1 and B7-DC expression on Kupffer cells, LSECs, and leukocytes. The degree of necroinflammation correlates with expression levels of PD-1 family members. These results demonstrate that expression of PD-1/PD-1 ligands links more directly with the degree of inflammation than with the underlying etiology of liver damage. The PD-1 pathway may assist the liver in protecting itself from immune-mediated destruction. PMID:19739236

Coffee Intake Is Associated with a Lower Liver Stiffness in Patients with Non-Alcoholic Fatty Liver Disease, Hepatitis C, and Hepatitis B

PubMed Central

Hodge, Alexander; Lim, Sarah; Goh, Evan; Wong, Ophelia; Marsh, Philip; Knight, Virginia; Sievert, William; de Courten, Barbora

2017-01-01

There is emerging evidence for the positive effects or benefits of coffee in patients with liver disease. We conducted a retrospective cross-sectional study on patients with non-alcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV), and hepatitis B virus (HBV) infection to determine the effects of coffee intake on a non-invasive marker of liver fibrosis: liver stiffness assessed by transient elastography (TE). We assessed coffee and tea intake and measured TE in 1018 patients with NAFLD, HCV, and HBV (155 with NAFLD, 378 with HCV and 485 with HBV). Univariate and multivariate regression models were performed taking into account potential confounders. Liver stiffness was higher in males compared to females (p < 0.05). Patients with HBV had lower liver stiffness than those with HCV and NAFLD. After adjustment for age, gender, smoking, alcohol consumption, M or XL probe, and disease state (NAFLD, HCV, and HBV status), those who drank 2 or more cups of coffee per day had a lower liver stiffness (p = 0.044). Tea consumption had no effect (p = 0.9). Coffee consumption decreases liver stiffness, which may indicate less fibrosis and inflammation, independent of disease state. This study adds further evidence to the notion of coffee maybe beneficial in patients with liver disease. PMID:28075394

The Epidemiology of Liver Diseases Unique to Pregnancy in a US Community: A Population-Based Study.

PubMed

Allen, Alina M; Kim, W Ray; Larson, Joseph J; Rosedahl, Jordan K; Yawn, Barbara P; McKeon, Kimberly; Hay, J Eileen

2016-02-01

Little is known in the United States about the epidemiology of liver diseases that develop only during (are unique to) pregnancy. We investigated the incidence of liver diseases unique to pregnancy in Olmsted County, Minnesota, and long-term maternal and fetal outcomes. We identified 247 women with liver diseases unique to pregnancy from 1996 through 2010 using the Rochester Epidemiology Project database. The crude incidence rate was calculated by the number of liver disease cases divided by 35,101 pregnancies. Of pregnant women with liver diseases, 134 had preeclampsia with liver dysfunction, 72 had hemolysis-associated increased levels of liver enzymes and low-platelet (HELLP) syndrome, 26 had intrahepatic cholestasis of pregnancy, 14 had hyperemesis gravidarum with abnormal liver enzymes, and 1 had acute fatty liver of pregnancy. The crude incidence of liver diseases unique to pregnancy was 0.77%. Outcomes were worse among women with HELLP or preeclampsia than the other disorders--of women with HELLP, 70% had a premature delivery, 4% had abruptio placentae, 3% had acute kidney injury, and 3% had infant death. Of women with preeclampsia, 56.0% had a premature delivery, 4% had abruptio placentae, 3% had acute kidney injury, and 0.7% had infant death. After 7 median years of follow-up (range, 0-18 years), 14% of the women developed recurrent liver disease unique to pregnancy; the proportions were highest in women with initial hyperemesis gravidarum (36%) or intrahepatic cholestasis of pregnancy (35%). Women with preeclampsia were more likely to develop subsequent hepatobiliary diseases. We found the incidence of liver disease unique to pregnancy in Olmsted County, Minnesota, to be lower than that reported from Europe or US tertiary referral centers. Maternal and fetal outcomes in Olmsted County were better than those reported from other studies, but fetal mortality was still high (0.7%-3.0%). Women with preeclampsia or HELLP are at higher risk for peripartum complications and subsequent development of comorbidities. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Nutritional Considerations for Dogs and Cats with Liver Disease.

PubMed

Norton, Rebecca D; Lenox, Catherine E; Manino, Paul; Vulgamott, James C

2016-01-01

The goals of nutritional management of liver disease in the dog and cat are directed at treating the clinical manifestations as opposed to treating the underlying cause. Specifically, the clinician strives to avoid overwhelming the remaining metabolic capacities of the damaged liver while providing sufficient nutrients for regeneration. A brief overview of liver diseases and associated clinical signs encountered in the dog and cat and a review of specific nutrients are discussed as well as amounts and sources of nutrients recommended to meet nutritional goals in the diseased liver.

Liver transplant using donors after cardiac death: a single-center approach providing outcomes comparable to donation after brain death.

PubMed

Vanatta, Jason M; Dean, Amanda G; Hathaway, Donna K; Nair, Satheesh; Modanlou, Kian A; Campos, Luis; Nezakatgoo, Nosratollah; Satapathy, Sanjaya K; Eason, James D

2013-04-01

Organ donation after cardiac death remains an available resource to meet the demand for transplant. However, concern persists that outcomes associated with donation after cardiac death liver allografts are not equivalent to those obtained with organ donation after brain death. The aim of this matched case control study was to determine if outcomes of liver transplants with donation after cardiac death donors is equivalent to outcomes with donation after brain death donors by controlling for careful donor and recipient selection, surgical technique, and preservation solution. A retrospective, matched case control study of adult liver transplant recipients at the University of Tennessee/Methodist University Hospital Transplant Institute, Memphis, Tennessee was performed. Thirty-eight donation after cardiac death recipients were matched 1:2, with 76 donation after brain death recipients by recipient age, recipient laboratory Model for End Stage Liver Disease score, and donor age to form the 2 groups. A comprehensive approach that controlled for careful donor and recipient matching, surgical technique, and preservation solution was used to minimize warm ischemia time, cold ischemia time, and ischemia-reperfusion injury. Patient and graft survival rates were similar in both groups at 1 and 3 years (P = .444 and P = .295). There was no statistically significant difference in primary nonfunction, vascular complications, or biliary complications. In particular, there was no statistically significant difference in ischemic-type diffuse intrahepatic strictures (P = .107). These findings provide further evidence that excellent patient and graft survival rates expected with liver transplants using organ donation after brain death donors can be achieved with organ donation after cardiac death donors without statistically higher rates of morbidity or mortality when a comprehensive approach that controls for careful donor and recipient matching, surgical technique, and preservation solution is used.

Hepatitis C: What Happens in End-Stage Liver Disease?

MedlinePlus

... diseases or liver diseases (hepatologist). Newer, more-effective hepatitis C treatments can eliminate the virus in many people, reducing the risk of end-stage liver disease. With Michael F. Picco, ... and natural history of hepatitis C virus infection. http://www.uptodate.com/home. Accessed ...

Oral Anticoagulation in Patients With Liver Disease.

PubMed

Qamar, Arman; Vaduganathan, Muthiah; Greenberger, Norton J; Giugliano, Robert P

2018-05-15

Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are "auto-anticoagulated" and thus protected from thrombotic events. Warfarin and non-vitamin K-antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

To screen or not to screen? Celiac antibodies in liver diseases

PubMed Central

Narciso-Schiavon, Janaína Luz; Schiavon, Leonardo Lucca

2017-01-01

Celiac disease (CD) is a systemic immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals. The typical symptoms are anemia, diarrhea, fatigue, weight loss, and abdominal pain. CD has been reported in patients with primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis, aminotransferase elevations, nonalcoholic fatty liver disease, hepatitis B, hepatitis C, portal hypertension and liver cirrhosis. We evaluate recommendations for active screening for CD in patients with liver diseases, and the effect of a gluten-free diet in these different settings. Active screening for CD is recommended in patients with liver diseases, particularly in those with autoimmune disorders, steatosis in the absence of metabolic syndrome, noncirrhotic intrahepatic portal hypertension, cryptogenic cirrhosis, and in the context of liver transplantation. In hepatitis C, diagnosis of CD can be important as a relative contraindication to interferon use. Gluten-free diet ameliorates the symptoms associated with CD; however, the associated liver disease may improve, remain the same, or progress. PMID:28223722

Management of adults with paediatric-onset chronic liver disease: strategic issues for transition care.

PubMed

Vajro, Pietro; Ferrante, Lorenza; Lenta, Selvaggia; Mandato, Claudia; Persico, Marcello

2014-04-01

Advances in the management of children with chronic liver disease have enabled many to survive into adulthood with or without their native livers, so that the most common of these conditions are becoming increasingly common in adult hepatology practice. Because the aetiologies of chronic liver disease in children may vary significantly from those in adulthood, adults with paediatric-onset chronic liver disease may often present with clinical manifestations unfamiliar to their adulthood physician. Transition of medical care to adult practice requires that the adulthood medical staff (primary physicians and subspecialists) have a comprehensive knowledge of childhood liver disease and their implications, and of the differences in caring for these patients. Pending still unavailable Scientific Society guidelines, this article examines causes, presentation modes, evaluation, management, and complications of the main paediatric-onset chronic liver diseases, and discusses key issues to aid in planning a program of transition from paediatric to adult patients. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Insights from Genome-Wide Association Analyses of Nonalcoholic Fatty Liver Disease

PubMed Central

Kahali, Bratati; Halligan, Brian; Speliotes, Elizabeth K.

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) is caused by hepatic steatosis, which can progress to nonalcoholic steatohepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma in the absence of excessive alcohol consumption. Nonalcoholic fatty liver disease will become the number one cause of liver disease worldwide by 2020. Nonalcoholic fatty liver disease is correlated albeit imperfectly with obesity and other metabolic diseases such as diabetes, hyperlipidemia, and cardiovascular disease, but exactly how having one of these diseases contributes to the development of other metabolic diseases is only now being elucidated. Development of NAFLD and related metabolic diseases is genetically influenced in the population, and recent genome-wide association studies (GWASs) have discovered genetic variants that associate with these diseases. These GWAS-associated variants cannot only help us to identify individuals at high risk of developing NAFLD, but also to better understand its pathophysiology so that we can develop more effective treatments for this disease and related metabolic diseases in the future. PMID:26676813

Diffusion weighted magnetic resonance imaging and its recent trend—a survey

PubMed Central

Chilla, Geetha Soujanya; Tan, Cher Heng

2015-01-01

Since its inception in 1985, diffusion weighted magnetic resonance imaging has been evolving and is becoming instrumental in diagnosis and investigation of tissue functions in various organs including brain, cartilage, and liver. Even though brain related pathology and/or investigation remains as the main application, diffusion weighted magnetic resonance imaging (DWI) is becoming a standard in oncology and in several other applications. This review article provides a brief introduction of diffusion weighted magnetic resonance imaging, challenges involved and recent advancements. PMID:26029644

Epidemiology and mortality of liver abscess in end-stage renal disease dialysis patients: Taiwan national cohort study.

PubMed

Hong, Chon-Seng; Chung, Kun-Ming; Huang, Po-Chang; Wang, Jhi-Joung; Yang, Chun-Ming; Chu, Chin-Chen; Chio, Chung-Ching; Chang, Fu-Lin; Chien, Chih-Chiang

2014-01-01

To determine the incidence rates and mortality of liver abscess in ESRD patients on dialysis. Using Taiwan's National Health Insurance Research Database, we collected data from all ESRD patients who initiated dialysis between 2000 and 2006. Patients were followed until death, end of dialysis, or December 31, 2008. Predictors of liver abscess and mortality were identified using Cox models. Of the 53,249 incident dialysis patients identified, 447 were diagnosed as having liver abscesses during the follow-up period (224/100,000 person-years). The cumulative incidence rate of liver abscess was 0.3%, 1.1%, and 1.5% at 1 year, 5 years, and 7 years, respectively. Elderly patients and patients on peritoneal dialysis had higher incidence rates. The baseline comorbidities of diabetes mellitus, polycystic kidney disease, malignancy, chronic liver disease, biliary tract disease, or alcoholism predicted development of liver abscess. Overall in-hospital mortality was 10.1%. The incidence of liver abscess is high among ESRD dialysis patients. In addition to the well known risk factors of liver abscess, two other important risk factors, peritoneal dialysis and polycystic kidney disease, were found to predict liver abscess in ESRD dialysis patients.

Psychiatric morbidity in patients with alcoholic liver disease.

PubMed Central

Ewusi-Mensah, I; Saunders, J B; Wodak, A D; Murray, R M; Williams, R

1983-01-01

Seventy one patients with alcoholic liver disease and an equal number with non-alcoholic liver disease were interviewed using the schedule for affective disorders and schizophrenia. Forty seven (66%) of the group with alcoholic liver disease had or had had psychiatric illnesses compared with 23 (32%) of the control group (p less than 0.001). Affective disorder, particularly major depression, neurotic disorders, and antisocial personality, were all more common among the patients with alcoholic liver disease than the controls. No patient had schizophrenia or other forms of psychosis. Among the patients with alcoholic liver disease 11 men (24%) and 14 women (54%) had an affective or a neurotic disorder that had antedated their heavy drinking, and 30 (77%) of those who had had such a problem at any time had symptoms at the time of interview. Abstinence from alcohol is essential for patients with severe alcoholic liver disease. In view of the high prevalence of psychiatric disorders in these patients psychiatric assessment is important to increase the patients' likelihood of complying with such advice. PMID:6416437

Liver cirrhosis in selected autoimmune diseases: a nationwide cohort study in Taiwan.

PubMed

Tung, Chien-Hsueh; Lai, Ning-Seng; Lu, Ming-Chi; Lee, Ching-Chih

2016-02-01

The association between autoimmune diseases and liver cirrhosis has rarely been explored in Asian populations, an endemic area of viral hepatitis. The aim of this study was to investigate the comparative risk of liver cirrhosis among a group of selective autoimmune diseases in Taiwanese patients and to identify groups of high risk. This retrospective study was a nationwide, population-based study and used Taiwan's National Health Insurance Research Database. A total of 29,856 patients with definite diagnosis of selected autoimmune diseases (Registry of Taiwan Catastrophic Illness Database, ACR classification) at the starting time point of January 1, 2005, were enrolled in this study. After tracked for a 5-year period, the endpoints were diagnosis of liver cirrhosis (in accordance with International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM codes 571). The control group was composed of other patients in the same database and consisted of randomly selected 753,495 sex- and age-matched non-autoimmune disease patients. The Cox proportional hazard regression model was used to calculate the risk of liver cirrhosis after adjusting for certain variables such as comorbidity, living area, and socioeconomic status. Among the patients with selected autoimmune diseases, 1987 liver cirrhosis were observed. Patients with psoriasis had a significantly increased risk of liver cirrhosis (HR 1.87, 95 % CI 1.25-2.81) than control group without psoriasis. The risk of liver cirrhosis was significantly lower in patients with rheumatoid arthritis (HR 0.29, 95 % CI 0.19-0.44). There is a gradient of risk of liver cirrhosis among the autoimmune diseases; the specific risks need to be investigated on the basis of hypotheses. Conventional immunosuppressive drug administration should be carefully implemented by regular monitoring of liver condition in order to avoid causing an adverse effect of chronic liver fibrosis.

Limited Knowledge of Acetaminophen in Patients with Liver Disease

PubMed Central

Saab, Sammy; Konyn, Peter G.; Viramontes, Matthew R.; Jimenez, Melissa A.; Grotts, Jonathan F.; Hamidzadah, Wally; Dang, Veronica P.; Esmailzadeh, Negin L.; Choi, Gina; Durazo, Francisco A.; El-Kabany, Mohamed M.; Han, Steven-Huy B.; Tong, Myron J.

2016-01-01

Abstract Background and Aims: Unintentional acetaminophen overdose remains the leading cause of acute liver failure in the United States. Patients with underlying liver disease are at higher risk of poor outcomes from acetaminophen overdose. Limited knowledge of acetaminophen may be a preventable contributor to elevated rates of overdose and thus acute liver failure. The purpose of this study is to assess knowledge of acetaminophen dosing and presence of acetaminophen in common combination products in patients with liver disease. Methods: We performed a cross-sectional study of patients with liver disease at the Pfleger Liver Institute at the University of California, Los Angeles between June 2015 and August 2016. Patients completed a demographic questionnaire and an acetaminophen knowledge survey. Additional information was obtained from the medical record. Results: Of 401 patients with liver disease, 30 (15.7%) were able to correctly identify that people without liver disease can safely take up to 4 g/day of acetaminophen. The majority of patients (79.9%–86.8%) did not know that Norco® (hydrocone/acetaminophen), Vicodin® (hydrocone/acetaminophen) and Percocet® (oxycodone/acetaminophen) contained acetaminophen. Only 45.3% of the patients knew that Tylenol® #3 contained acetaminophen. Conclusions: We conclude that patients with liver disease have critically low levels of knowledge of acetaminophen, putting them at risk both of acetaminophen overdose, as well as undermedication, and inadequate management of chronic pain. We recommend an increase in education efforts regarding acetaminophen dosage and its safety in the setting of liver disease. Increasing education for those at risk of low acetaminophen knowledge is essential to minimizing acetaminophen overdose rates and optimizing pain management. PMID:28097095

Microbiota and the liver.

PubMed

Shen, Ting-Chin David; Pyrsopoulos, Nikolaos; Rustgi, Vinod K

2018-04-01

The gut microbiome outnumbers the human genome by 150-fold and plays important roles in metabolism, immune system education, tolerance development, and prevention of pathogen colonization. Dysbiosis has been associated with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and alcoholic liver disease (ALD) as well as cirrhosis and complications. This article provides an overview of this relationship. Liver Transplantation 24 539-550 2018 AASLD. © 2018 by the American Association for the Study of Liver Diseases.

Zebrafish: an important tool for liver disease research.

PubMed

Goessling, Wolfram; Sadler, Kirsten C

2015-11-01

As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Assessment of the fatty liver index as an indicator of hepatic steatosis for predicting incident diabetes independently of insulin resistance in a Korean population.

PubMed

Jung, C H; Lee, W J; Hwang, J Y; Yu, J H; Shin, M S; Lee, M J; Jang, J E; Leem, J; Park, J-Y; Kim, H-K

2013-04-01

Fatty liver disease, especially non-alcoholic fatty liver disease, is considered to be the hepatic manifestation of the metabolic syndrome, both closely associated with insulin resistance. Furthermore, fatty liver disease assessed by ultrasonography is known to be a predictor of the development of Type 2 diabetes mellitus. However, it remains unclear whether fatty liver disease plays a role in the pathogenesis of Type 2 diabetes independently of insulin resistance. In this study, we investigated whether fatty liver disease assessed by the fatty liver index can predict the development of Type 2 diabetes independently of systemic insulin resistance. We examined the clinical and laboratory data of 7860 subjects without diabetes who underwent general routine health evaluations at the Asan Medical Center in 2007 and had returned for follow-up examinations in 2011. Fatty liver index was calculated using an equation that considers serum triglyceride levels, γ-glutamyltransferase, waist circumference and BMI. During a 4-year period, 457 incident diabetes cases (5.8%) were identified. The odds ratios for the development of Type 2 diabetes were significantly higher in the group with a fatty liver index ≥ 60 (fatty liver index-positive) than in the group with a fatty liver index < 20 (fatty liver index-negative) after adjusting for various confounding variables including homeostasis model assessment of insulin resistance. Odds ratios were significant regardless of the insulin resistance status at baseline. Our results suggest that fatty liver index as a simple surrogate indicator of hepatic steatosis is valuable in identifying subjects at high risk for Type 2 diabetes. In addition, fatty liver disease itself contributes to the development of Type 2 diabetes independently of systemic insulin resistance. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

High coffee intake is associated with lower grade nonalcoholic fatty liver disease: the role of peripheral antioxidant activity.

PubMed

Gutiérrez-Grobe, Ylse; Chávez-Tapia, Norberto; Sánchez-Valle, Vicente; Gavilanes-Espinar, Juan Gabriel; Ponciano-Rodríguez, Guadalupe; Uribe, Misael; Méndez-Sánchez, Nahum

2012-01-01

Some phytochemicals present in coffee have a potential antioxidant role which seems to protect the human body against cardiovascular diseases, liver disease and malignancies. Nonalcoholic fatty liver disease is a common disease with limited therapeutic options. This study investigated the antioxidant effect of coffee by measuring antioxidant enzymes and lipid peroxidation markers in patients with nonalcoholic fatty liver disease. We performed a case-control study at the University Hospital, Mexico City. Anthropometric, metabolic, dietary and biochemical variables of all patients were determined and compared. The presence of nonalcoholic fatty liver disease was established by ultrasonography. All patients completed a dietary questionnaire in order to determine their of coffee consumption. Catalase, superoxide dismutase and thiobarbituric acid reactive substances were measured in all of the patients. Seventy-three subjects with and 57 without nonalcoholic fatty liver disease were included. Patients with nonalcoholic fatty liver disease had significantly higher body mass index, blood glucose, homeostasis model of assessment-insulin resistance and insulin values in comparison to patients without nonalcoholic fatty liver disease. On the one hand, there was a significant difference in coffee intake between the groups (p < 0.05, for all comparisons). There was no significant difference between groups in catalase (0.39 ± 0.74 vs. 0.28 ± 0.69 nM/min/mL), superoxide dismutase (5.4 ± 3.45 vs. 4.7 ± 2.1 U/mL) or thiobarbituric acid-reactive substances (4.05 ± 1.87 vs. 3.94 ± 1.59 µM/mL). A high intake of coffee has a protective effect against nonalcoholic fatty liver disease however there was no significant difference in the antioxidant variables analyzed.

Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) in HIV.

PubMed

Rockstroh, Jürgen Kurt

2017-04-01

Abnormal liver enzymes (LE) are common in patients infected with the human immunodeficiency virus (HIV) even in the absence of viral hepatitis or alcohol abuse. With availability of antiretroviral combination therapy, life expectancy has improved dramatically and as a consequence the spectrum of liver disease is changing. Increased reports on the development of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) in HIV coinfected patients raise questions around prevalence, clinical manifestations, and clinical outcome of these liver diseases in HIV coinfection. Moreover, the potential impact of combination antiretroviral therapy as well as direct HIV effects on the emergence of non-alcoholic fatty liver disease needs to be explored. This review summarizes the recent literature on NAFLD and NASH in HIV.

Clinical epidemiology and disease burden of nonalcoholic fatty liver disease

PubMed Central

Perumpail, Brandon J; Khan, Muhammad Ali; Yoo, Eric R; Cholankeril, George; Kim, Donghee; Ahmed, Aijaz

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis. PMID:29307986

Etiology and mode of presentation of chronic liver diseases in India: A multi centric study.

PubMed

Mukherjee, Partha S; Vishnubhatla, Sreenivas; Amarapurkar, Deepak N; Das, Kausik; Sood, Ajit; Chawla, Yogesh K; Eapen, Chundamannil E; Boddu, Prabhakar; Thomas, Varghese; Varshney, Subodh; Hidangmayum, Diamond Sharma; Bhaumik, Pradip; Thakur, Bhaskar; Acharya, Subrat K; Chowdhury, Abhijit

2017-01-01

There is a paucity of health policy relevant data for chronic liver disease from India, impeding formulation of an interventional strategy to address the issue. A prospective, multicentric study to delineate the etiology and clinical profile of chronic liver disease in India is reported here. A centrally coordinated and monitored web-based data repository was developed (Feb, 2010 to Jan, 2013) and analyzed. Eleven hospitals from different parts of India participated. Data were uploaded into a web based proforma and monitored by a single centre according to a standardized protocol. 1.28% (n = 266621) of all patients (n = 20701383) attending the eleven participating hospitals of India had liver disease. 65807 (24·68%) were diagnosed for the first time (new cases). Of these, 13014 (19·77%, median age 43 years, 73% males) cases of chronic liver disease were finally analyzed. 33.9% presented with decompensated cirrhosis. Alcoholism (34·3% of 4413) was the commonest cause of cirrhosis while Hepatitis B (33·3%) was predominant cause of chronic liver disease in general and non-cirrhotic chronic liver disease (40·8% out of 8163). There was significant interregional differences (hepatitis C in North, hepatitis B in East and South, alcohol in North-east, Non-alcoholic Fatty Liver Disease in West) in the predominant cause of chronic liver disease. Hepatitis B (46·8% of 438 cases) was the commonest cause of hepatocellular Cancer.11·7% had diabetes. Observations of our study will help guide a contextually relevant liver care policy for India and could serve as a framework for similar endeavor in other developing countries as well.

A Comparative Study of Liver Disease Care in the USA and Urban and Rural China.

PubMed

Yang, Ming; Wu, Elizabeth; Rao, Huiying; Du, Fanny H; Xie, Angela; Cheng, Shanna; Rodd, Cassandra; Lin, Andy; Wei, Lai; Lok, Anna S

2016-10-01

Chronic liver disease is a major cause of morbidity and mortality in the USA and China, but the etiology of liver disease, medical practice, and patient expectations in these two countries are different. To compare patient knowledge about their liver disease, patient satisfaction with liver disease care, and patient medical decision-making preference in the USA and China. Three cohorts of established adult patients with liver disease seen in liver clinics in Ann Arbor, USA, and Beijing (urban) and Hebei (rural), China, completed a survey between May and September 2014. A total of 990 patients (395 USA, 398 Beijing, and 197 Hebei) were analyzed. Mean liver disease knowledge score (maximum 5) in the USA, Beijing, and Hebei patients was 4.1, 3.6, and 3.0, respectively (p < 0.001). US patients had a greater preference for collaborative decision-making: 71.8 % preferred to make treatment decisions together with the doctor, while most Chinese patients (74.6 % Beijing and 84.8 % Hebei) preferred passive decision-making. Mean satisfaction score (maximum 85) in the USA was higher than in Beijing, which in turn was higher than in Hebei (78.2 vs. 66.5 vs. 60.3, p < 0.001). There was a positive correlation between liver disease knowledge score and satisfaction score (r = 0.27, p < 0.001) and with collaborative medical decision-making (r = 0.22, p < 0.001) when responses from all sites were combined. Liver disease knowledge and patient satisfaction were greatest in the USA, followed by Beijing and then Hebei patients. Understanding these differences and associated factors may help to improve patient outcomes.

CD4+ Foxp3+ T cells promote aberrant immunoglobulin G production and maintain CD8+ T-cell suppression during chronic liver disease.

PubMed

Tedesco, Dana; Thapa, Manoj; Gumber, Sanjeev; Elrod, Elizabeth J; Rahman, Khalidur; Ibegbu, Chris C; Magliocca, Joseph F; Adams, Andrew B; Anania, Frank; Grakoui, Arash

2017-02-01

Persistent hepatotropic viral infections are a common etiologic agent of chronic liver disease. Unresolved infection can be attributed to nonfunctional intrahepatic CD8+ T-cell responses. In light of dampened CD8 + T-cell responses, liver disease often manifests systemically as immunoglobulin (Ig)-related syndromes due to aberrant B-cell functions. These two opposing yet coexisting phenomena implicate the potential of altered CD4 + T-cell help. Elevated CD4 + forkhead box P3-positive (Foxp3+) T cells were evident in both human liver disease and a mouse model of chemically induced liver injury despite marked activation and spontaneous IgG production by intrahepatic B cells. While this population suppressed CD8 + T-cell responses, aberrant B-cell activities were maintained due to expression of CD40 ligand on a subset of CD4 + Foxp3+ T cells. In vivo blockade of CD40 ligand attenuated B-cell abnormalities in a mouse model of liver injury. A phenotypically similar population of CD4 + Foxp3+, CD40 ligand-positive T cells was found in diseased livers explanted from patients with chronic hepatitis C infection. This population was absent in nondiseased liver tissues and peripheral blood. Liver disease elicits alterations in the intrahepatic CD4 + T-cell compartment that suppress T-cell immunity while concomitantly promoting aberrant IgG mediated manifestations. (Hepatology 2017;65:661-677). © 2016 by the American Association for the Study of Liver Diseases.

Resected Hepatocellular Carcinoma in a Patient with Crohn's Disease on Azathioprine

PubMed Central

Heron, Valérie; Fortinsky, Kyle Joshua; Spiegle, Gillian; Hilzenrat, Nir; Szilagyi, Andrew

2016-01-01

Hepatocellular carcinoma rarely occurs in patients without underlying cirrhosis or liver disease. While inflammatory bowel disease has been linked to certain forms of liver disease, hepatocellular carcinoma is exceedingly rare in these patients. We report the twelfth case of hepatocellular carcinoma in a patient with Crohn's disease. The patient is a 61-year-old with longstanding Crohn's disease who was treated with azathioprine and was found to have elevated liver enzymes and a new 3-cm liver mass on ultrasound. A complete workup for underlying liver disease was unremarkable and liver biopsy revealed hepatocellular carcinoma. The patient underwent a hepatic resection, and there is no evidence of recurrence at the 11-month follow-up. The resection specimen showed no evidence of cancer despite the initial biopsy revealing hepatocellular carcinoma. This case represents the third biopsy-proven complete spontaneous regression of hepatocellular carcinoma. Although large studies have failed to show a definite link between azathioprine and hepatocellular carcinoma, the relationship remains concerning given the multiple case reports suggesting a possible association. Clinicians should exercise a high degree of suspicion in patients with Crohn's disease who present with elevated liver enzymes, especially those on azathioprine therapy. PMID:27403102

Intestinal microbiota in liver disease.

PubMed

Haque, Tanvir R; Barritt, A Sidney

2016-02-01

The intestinal microbiota have emerged as a topic of intense interest in gastroenterology and hepatology. The liver is on the front line as the first filter of nutrients, toxins and bacterial metabolites from the intestines and we are becoming increasingly aware of interactions among the gut, liver and immune system as important mediators of liver health and disease. Manipulating the microbiota with therapeutic intent is a rapidly expanding field. In this review, we will describe what is known about the contribution of intestinal microbiota to liver homeostasis; the role of dysbiosis in the pathogenesis of liver disease including alcoholic and non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma; and the therapeutic manifestations of altering intestinal microbiota via antibiotics, prebiotics, probiotics and fecal microbiota transplantation. Copyright © 2016. Published by Elsevier Ltd.

Hepatic steatosis and fibrosis: Non-invasive assessment

PubMed Central

Karanjia, Rustam N; Crossey, Mary M E; Cox, I Jane; Fye, Haddy K S; Njie, Ramou; Goldin, Robert D; Taylor-Robinson, Simon D

2016-01-01

Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and non-invasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy. PMID:28018096

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.

Liver Disease in the HIV-Infected Individual

PubMed Central

Price, Jennifer C.; Thio, Chloe L.

2010-01-01

Since the advent of effective antiretroviral therapy (ART) for human immunodeficiency virus-1 (HIV), there has been a substantial decrease in deaths related to acquired immunodeficiency syndrome (AIDS). However, in the ART-era liver disease is now the most common non-AIDS related cause of death among HIV-infected patients, accounting for 14-18% of all deaths in this population and almost half of deaths among hospitalized HIV-infected patients. Just as the burden of non-AIDS morbidity and mortality has changed in the ART-era, the types of liver disease the clinician is likely to encounter among these patients have changed as well. This review will discuss the causes of liver disease in the HIV-infected population in the ART-era, including chronic hepatitis C virus, chronic hepatitis B virus, medication-related hepatotoxicity, alcohol abuse, nonalcoholic fatty liver disease, and AIDS-related liver diseases. PMID:20851211

Usefulness of chemical-shift MRI in discriminating increased liver echogenicity in glycogenosis.

PubMed

Pozzato, C; Dall'asta, C; Radaelli, G; Torcoletti, M; Formenti, A; Riva, E; Cornalba, G; Pontiroli, A E

2007-11-01

Glycogen storage diseases are inherited defects which cause accumulation of glycogen in the tissues. Hepatic steatosis is defined as accumulation of fat within hepatocytes. On sonography, liver shows increased echogenicity both in glycogen storage diseases and steatosis. Liver hyperechogenicity in glycogen storage diseases may depend on accumulation of glycogen and/or fat. Chemical-shift magnetic resonance imaging can discriminate tissues only containing water from those containing both fat and water. The primary aim of the present study was to evaluate the usefulness of liver chemical-shift magnetic resonance imaging for detecting liver steatosis in patients with metabolic impairment due to glycogen storage diseases. Twelve patients with type I (n=8) or type III (n=4) glycogen storage diseases were studied and compared to 12 obese-overweight subjects with known liver steatosis. As control group 12 lean normal voluntary subjects were recruited. Liver was evaluated by sonography and chemical-shift magnetic resonance imaging to calculate hepatic fat fraction. A significant difference in echogenicity between patients with glycogen storage diseases and normal subjects was observed (p<0.05), while this difference was not present between overweight-obese and glycogen storage diseases patients. On the contrary, fat fraction was similar between glycogen storage diseases patients and normal subjects and different between glycogen storage diseases patients and overweight-obese (p<0.05). The present data suggest that chemical-shift magnetic resonance imaging may exclude fat deposition as a cause of liver hyperechogenicity in subjects with glycogen storage diseases.

Hepatic protoporphyrin metabolism in patients with advanced protoporphyric liver disease.

PubMed Central

Bloomer, J. R.

1997-01-01

Protoporphyria is a genetic disorder in which liver damage is caused by the toxic effect of protoporphyrin accumulation in the liver. In this study protoporphyrin was measured in the resected livers of 7 patients who had liver transplantation and an additional patient from whom liver tissue was obtained post mortem. Comparison of liver, erythrocyte and serum protoporphyrin levels demonstrated a marked gradient between these compartments: erythrocyte, 5781 +/- 655 micrograms/dl; serum, 384 +/- 102 micrograms/dl; liver 377,238 +/- 55,568 micrograms/100 gm wet weight, (mean +/- SE). Protoporphyrin levels in bile of 3 patients were 55,559, and 1,153 micrograms/dl, indicating a gradient between liver and bile as well. Examination of the livers by polarization microscopy and electron microscopy demonstrated protoporphyrin pigment crystals. In one patient who had recurrent liver disease after transplantation, the protoporphyrin concentration in the graft at the time of death was similar to that in the resected liver. These data indicate that liver protoporphyrin levels in patients with advanced protoporphyric liver disease are much higher than levels in blood and bile, in part because protoporphyrin forms crystalline deposits in liver tissue. Thus, progressive hepatic accumulation of protoporphyrin occurs in the face of impaired biliary excretion. An intrinsic defect in hepatic excretion of protoporphyrin is probably not necessary for this condition to develop because liver disease can occur in the graft following transplantation. PMID:9626752

Liver Disease in Mitochondrial Disorders

PubMed Central

Lee, Way S.; Sokol, Ronald J.

2013-01-01

Liver involvement, a common feature in childhood mitochondrial hepatopathies, particularly in the neonatal period, may manifest as neonatal acute liver failure, hepatic steatohepatitis, cholestasis, or cirrhosis with chronic liver failure of insidious onset. There are usually significant neuromuscular symptoms, multisystem involvement, and lactic acidemia. The liver disease is usually progressive and eventually fatal. Current medical therapy of mitochondrial hepatopathies is largely ineffective, and the prognosis is usually poor. The role of liver transplantation in patients with liver failure remains poorly defined because of the systemic nature of the disease that does not respond to transplantation. Several specific molecular defects (mutations in nuclear genes such as SCO1, BCS1L, POLG, DGUOK, and MPV17 and deletion or rearrangement of mitochondrial DNA) have been identified in recent years. Prospective, longitudinal multicenter studies will be needed to address the gaps in our knowledge in these rare liver diseases. PMID:17682973

[Utility of Fibroscan in the evaluation of liver fibrosis].

PubMed

Carrión, José A

2009-01-01

Chronic liver diseases produce a progressive accumulation of collagenous fiber in the liver parenchyma. For years, liver biopsy has been the gold standard to quantify liver fibrosis. Currently, non-invasive alternatives are available to quantify fibrosis. Transient elastography (TE) or Fibroscan quantifies liver rigidity, which is proportional to the grade of liver fibrosis. Studies are available that have evaluated the reliability and limitations of TE in healthy individuals, in patients with acute hepatitis, in distinct chronic liver diseases and in liver transplant recipients. TE is reliable for the diagnosis of liver cirrhosis (F4) and significant fibrosis (F2) but its values may vary according to the patient's characteristics and the etiology of the disease. TE can avoid liver biopsy in 90% of patients with cirrhosis and in up to 70% of those with significant fibrosis when combined with other non-invasive methods.

Liver and lung transplantation in cystic fibrosis: an adult cystic fibrosis centre's experience.

PubMed

Sivam, S; Al-Hindawi, Y; Di Michiel, J; Moriarty, C; Spratt, P; Jansz, P; Malouf, M; Plit, M; Pleass, H; Havryk, A; Bowen, D; Haber, P; Glanville, A R; Bye, P T P

2016-07-01

Liver disease develops in one-third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation. © 2016 Royal Australasian College of Physicians.

The impact of human immune deficiency virus and hepatitis C coinfection on white matter microstructural integrity.

PubMed

Heaps-Woodruff, J M; Wright, P W; Ances, B M; Clifford, D; Paul, R H

2016-06-01

The purpose of the present study is to examine the integrity of white matter microstructure among individuals coinfected with HIV and HCV using diffusion tensor imaging (DTI). Twenty-five HIV+ patients, 21 HIV+/HCV+ patients, and 25 HIV- controls were included in this study. All HIV+ individuals were stable on combination antiretroviral therapy (cART; ≥3 months). All participants completed MRI and neuropsychological measures. Clinical variables including liver function, HIV-viral load, and CD4 count were collected from the patient groups. DTI metrics including mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) from five subregions of the corpus callosum were compared across groups. The HIV+/HCV+ group and HIV+ group were similar in terms of HIV clinical variables. None of the participants met criteria for cirrhosis or fibrosis. Within the anterior corpus callosum, significant differences were observed between both HIV+ groups compared to HIV- controls on DTI measures. HIV+ and HIV+/HCV+ groups had significantly lower FA values and higher MD and RD values compared to HIV- controls; however, no differences were present between the HIV+ and HIV+/HCV+ groups. Duration of HIV infection was significantly related to DTI metrics in total corpus callosum FA only, but not other markers of HIV disease burden or neurocognitive function. Both HIV+ and HIV+/HCV+ individuals had significant alterations in white matter integrity within the corpus callosum; however, there was no evidence for an additive effect of HCV coinfection. The association between DTI metrics and duration of HIV infection suggests that HIV may continue to negatively impact white matter integrity even in well-controlled disease.

Burden of Gastrointestinal and Liver Diseases in Iran: Estimates Based on the Global Burden of Disease, Injuries, and Risk Factors Study, 2010.

PubMed

Malekzadeh, Fatemeh; Sepanlou, Sadaf Ghajarieh; Poustchi, Hossein; Naghavi, Mohsen; Forouzanfar, Mohammad Hossein; Shahraz, Saeid; Moradi-Lakeh, Maziar; Malekzadeh, Reza

2015-07-01

BACKGROUND Gastrointestinal and liver diseases (GILD) constitute a noteworthy portion of causes of death and disability in Iran. However, data on their prevalence and burden is sparse in Iran. The Global Burden of Disease (GBD) study in 2010 has provided invaluable comprehensive data on the burden of GILD in Iran. METHODS Estimations of death, years of life lost due to premature death (YLL), years of life lost due to disability (YLD), disability-adjusted life years (DALY), life expectancy, and healthy life expectancy have been reported for 291 diseases, 67 risk factors, 1160 sequelae, for both sexes and 19 age groups, form 1990 to 2010 for 187 countries. In the current paper, 5 major categories of gastrointestinal (GI) and liver diseases have been investigated as follows: GI infectious diseases, GI and liver cancers, liver infections, chronic end stage liver disease, and other digestive diseases. RESULTS Among women, 7.6% of all deaths and 3.9% of all DALYs were due to digestive and liver diseases in 2010. The respective figures in men were 7.8% of deaths and 4.6% of DALYs. The most important cause of death among children under 5 is diarrhea. Among adults between 15 to 49 years old, the main causes of death are GI and liver cancers and cirrhosis, while diarrhea still remains a major cause of DALY. Among adults 50 years and above, GI and liver cancers and cirrhosis are the main causes of both deaths and DALYs. Gastritis and duodenitis, diarrheal diseases, gall bladder and bile duct diseases, acute hepatitis A, peptic ulcer disease, appendicitis, and acute hepatitis A mainly cause disability rather than death. CONCLUSION GBD study provides invaluable source of data on burden of GILD in Iran. However, there exist limitations, namely overestimation of burden of liver cancer and underestimation of the burden of GI diseases that are usually diagnosed in outpatient settings. The collaboration of scientists across the world and specifically those from developing countries is necessary for improving the accuracy of future updates of GBD in these countries.

How can primary care enhance end-of-life care for liver disease? Qualitative study of general practitioners’ perceptions and experiences

PubMed Central

Standing, Holly; Jarvis, Helen; Orr, James; Exley, Catherine; Hudson, Mark; Kaner, Eileen; Hanratty, Barbara

2017-01-01

Background Liver disease is the third most common cause of premature death in the UK. The symptoms of terminal liver disease are often difficult to treat, but very few patients see a palliative care specialist and a high proportion die in hospital. Primary care has been identified as a setting where knowledge and awareness of liver disease is poor. Little is known about general practitioners’ (GPs) perceptions of their role in managing end-stage liver disease. Objective To explore GPs’ experiences and perceptions of how primary care can enhance end-of-life care for patients with liver disease. Design Qualitative interview study, thematic analysis. Participants Purposive sample of 25 GPs from five regions of England. Results GPs expressed a desire to be more closely involved in end-of-life care for patients with liver disease but identified a number of factors that constrained their ability to contribute. These fell into three main areas; those relating directly to the condition, (symptom management and the need to combine a palliative care approach with ongoing medical interventions); issues arising from patients’ social circumstances (stigma, social isolation and the social consequences of liver disease) and deficiencies in the organisation and delivery of services. Collaborative working with support from specialist hospital clinicians was regarded as essential, with GPs acknowledging their lack of experience and expertise in this area. Conclusions End-of-life care for patients with liver disease merits attention from both primary and secondary care services. Development of care pathways and equitable access to symptom relief should be a priority. PMID:28864486

Increased risk of chronic liver disease in patients with bipolar disorder: A population-based study.

PubMed

Hsu, Jer-Hwa; Chien, I-Chia; Lin, Ching-Heng

2016-01-01

This study aimed to investigate the prevalence and incidence of chronic liver disease in patients with bipolar disorder. We used a random sample of 766,427 subjects aged ≥18 years from the National Health Research Institute database in the year 2005. Subjects with at least one primary diagnosis of bipolar disorder in 2005 were identified. Patients with a primary or secondary diagnosis of chronic liver disease were also defined. We compared the prevalence and associated factors of chronic liver disease between patients with bipolar disorder and the general population in 2005. We also compared the incidence of chronic liver disease in patients with bipolar disorder and the general population from 2006 to 2010. The prevalence of chronic liver disease in patients with bipolar disorder (13.9%) was 2.68 times higher than that of the general population (5.8%) in 2005. The average annual incidence of chronic liver disease in patients with bipolar disorder from 2006 to 2010 was also higher than that of the general population (2.95% vs. 1.73%; risk ratio: 1.71; 95% confidence interval: 1.46-2.01). Patients with bipolar disorder had a significantly higher prevalence and incidence of chronic liver disease than those in the general population, and younger patients with bipolar disorder have a much higher prevalence and incidence than those in the general population. Male sex, second-generation antipsychotic or antidepressant use, and hyperlipidemia were associated factors for chronic liver disease in patients with bipolar disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

The association between continuous positive airway pressure therapy and liver disease development in obstructive sleep apnea/hypopnea syndrome patients: a nationwide population-based cohort study in Taiwan.

PubMed

Hang, Liang-Wen; Chen, Chi-Fung; Wang, Chang-Bi; Wu, Trong-Neng; Liang, Wen-Miin; Chou, Tzu-Chieh

2017-05-01

Studies on the association between continuous positive airway pressure (CPAP) treatment and liver diseases such as non-alcoholic fatty liver disease (NAFLD) and cirrhosis in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) are limited. To the best of our knowledge, none exists that makes use of a national database in an Asian population. This study aims to evaluate the effects of CPAP treatment on patients with these two disorders in a retrospective, population-based study in Taiwan. Using the Taiwan National Health Insurance claims database, this study collected the data of OSAHS patients diagnosed between 2000 and 2008 and divided them into CPAP treatment and non-CPAP treatment groups. All subjects were followed up until 2010. Liver disease incidence and risk were calculated. The CPAP group had a lower cumulative incidence rate of developing liver disease than the non-CPAP group within the observation periods (p < 0.001). After adjusting for age, gender, urbanization level, and comorbidities, the CPAP treatment group showed a lower risk of developing liver disease compared with the non-CPAP treatment group (sub-aHR of 0.66 (95% CI 0.55-0.80), p < 0.001). Our observations suggest that CPAP treatment may play an important role to delay the progression of liver disease in OSAHS patients and decreases the incidence of liver disease among OSAHS patients. Thus, CPAP therapy may be a feasible way to decrease the risk of liver disease among patients with OSAHS.

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 liver disease and fulminant hepatic failure and the only way to prevent and treat these patients is by liver transplantation.

Clinical characteristics, healthcare costs, and resource utilization in hepatitis C vary by genotype.

PubMed

Goolsby Hunter, Alyssa; Rosenblatt, Lisa; Patel, Chad; Blauer-Peterson, Cori; Anduze-Faris, Beatrice

2017-05-01

In the United States, approximately 3 million people are infected with hepatitis C virus (HCV). Genotypes of HCV variably affect disease progression and treatment response. However, the relationships between HCV genotypes and liver disease progression, healthcare resource utilization, and healthcare costs have not been fully explored. In this retrospective study of patients with chronic hepatitis C (CHC), healthcare claims from a large US health plan were used to collect data on patient demographic and clinical characteristics. Main outcome measures include healthcare resource utilization (HCRU) and healthcare costs. Linked laboratory data provided genotype and select measures to determine liver disease severity. The sample (mean age 50.6 years, 63.5% male) included 10,331 patients, of whom 79.1% had genotype (GT)1, 12.8% had GT2, and 8.1% had GT3. Descriptive analyses demonstrated variation by HCV genotype in liver and non-liver related comorbidities, liver disease severity, and healthcare costs. The highest percentage of patients with liver-related comorbidities and advanced liver disease was found among those with GT3. Meanwhile, patients with GT2 had lower HCRU and the lowest costs, and patients with GT1 had the highest total all-cause costs. These differences may reflect differing rates of non-liver-related comorbidities and all-cause care. Multivariable analyses showed that genotype was a significant predictor of costs and liver disease severity: compared with patients having GT1, those with GT3 were significantly more likely to have advanced liver disease. Patients with GT2 were significantly less likely to have advanced disease and more likely to have lower all-cause costs. Results may not be generalizable to patients outside the represented commercial insurance plans, and analysis of a prevalent population may underestimate HCRU and costs relative to a sample of treated patients. These results suggest that liver disease progression varies by genotype and that CHC patients with GT3 appear to have more severe liver disease. These findings highlight the importance of effective HCV treatment for all patients and support guidelines for treatment of high-risk patients, including those with GT3.

Consensus Statement on Dose Modifications of Antidiabetic Agents in Patients with Hepatic Impairment

PubMed Central

Gangopadhyay, Kalyan Kumar; Singh, Parminder

2017-01-01

Liver disease is an important cause of mortality in type 2 diabetes mellitus (T2DM). It is estimated that diabetes is the most common cause of liver disease in the United States. Virtually, entire spectrum of liver disease is seen in T2DM including abnormal liver enzymes, nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, and acute liver failure. The treatment of diabetes mellitus (DM) in cirrhotic patients has particular challenges as follows: (1) about half the patients have malnutrition; (2) patients already have advanced liver disease when clinical DM is diagnosed; (3) most of the oral antidiabetic agents (ADAs) are metabolized in the liver; (4) patients often have episodes of hypoglycemia. The aim of this consensus group convened during the National Insulin Summit 2015, Puducherry, was to focus on the challenges with glycemic management, with particular emphasis to safety of ADAs across stages of liver dysfunction. Published literature, product labels, and major clinical guidelines were reviewed and summarized. The drug classes included are biguanides (metformin), the second- or third-generation sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and currently available insulins. Consensus recommendations have been drafted for glycemic targets and dose modifications of all ADAs. These can aid clinicians in managing patients with diabetes and liver disease. PMID:28459036

The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers.

PubMed

Lai, G Y; Weinstein, S J; Albanes, D; Taylor, P R; McGlynn, K A; Virtamo, J; Sinha, R; Freedman, N D

2013-09-03

Coffee intake is associated with reduced risk of liver cancer and chronic liver disease as reported in previous studies, including prospective ones conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, although preparation methods affect coffee constituents, it is unknown whether different methods affect disease associations. We evaluated the association of coffee intake with incident liver cancer and chronic liver disease mortality in 27,037 Finnish male smokers, aged 50-69, in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who recorded their coffee consumption and were followed up to 24 years for incident liver cancer or chronic liver disease mortality. Multivariate relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models. Coffee intake was inversely associated with incident liver cancer (RR per cup per day=0.82, 95% CI: 0.73-0.93; P-trend across categories=0.0007) and mortality from chronic liver disease (RR=0.55, 95% CI: 0.48-0.63; P-trend<0.0001). Inverse associations persisted in those without diabetes, HBV- and HCV-negative cases, and in analyses stratified by age, body mass index, alcohol and smoking dose. We observed similar associations for those drinking boiled or filtered coffee. These findings suggest that drinking coffee may have benefits for the liver, irrespective of whether coffee was boiled or filtered.

Grave's Disease and Primary Biliary Cirrhosis-An Unusual and Challenging Association.

PubMed

Shetty, Shiran; Rajasekaran, Senthilkumar; Venkatakrishnan, Leela

2014-03-01

Jaundice in Grave's diseases is uncommon, but when it does occur, complication of thyrotoxicosis (heart failure/infection) or intrinsic liver disease should be considered. Grave's disease can cause asymptomatic elevation of liver enzymes, jaundice and rarely acute liver failure. It is associated with other autoimmune diseases like autoimmune hepatitis, or primary biliary cirrhosis. The cause of jaundice in Grave's disease is multifactorial.

Grave's Disease and Primary Biliary Cirrhosis—An Unusual and Challenging Association

PubMed Central

Shetty, Shiran; Rajasekaran, Senthilkumar; Venkatakrishnan, Leela

2013-01-01

Jaundice in Grave's diseases is uncommon, but when it does occur, complication of thyrotoxicosis (heart failure/infection) or intrinsic liver disease should be considered. Grave's disease can cause asymptomatic elevation of liver enzymes, jaundice and rarely acute liver failure. It is associated with other autoimmune diseases like autoimmune hepatitis, or primary biliary cirrhosis. The cause of jaundice in Grave's disease is multifactorial. PMID:25755537

Alpha-1-antitrypsin phenotypes in adult liver disease patients

PubMed Central

Alempijevic, Tamara; Milutinovic, Aleksandra Sokic; Kovacevic, Nada

2009-01-01

Alpha-1-antitrypsin (AAT) is an important serine protease inhibitor in humans. Hereditary alpha-1-antitrypsin deficiency (AATD) affects lungs and liver. Liver disease caused by AATD in paediatric patients has been previously well documented. However, the association of liver disease with alpha-1-antitrypsin gene polymorphisms in adults is less clear. Therefore, we aimed to study AAT polymorphisms in adults with liver disease. We performed a case-control study. AAT polymorphisms were investigated by isoelectric focusing in 61 patients with liver cirrhosis and 9 patients with hepatocellular carcinoma. The control group consisted of 218 healthy blood donors. A significant deviation of observed and expected frequency of AAT phenotypes from Hardy-Weinberg equilibrium (chi-square = 34.77, df 11, P = 0.000) in the patient group was caused by a higher than expected frequency of Pi ZZ homozygotes (f = 0.0143 and f = 0.0005, respectively, P = 0.000). In addition, Pi M homozygotes were more frequent in patients than in controls (63% and 46%, respectively, P = 0.025). Our study results show that Pi ZZ homozygosity in adults could be associated with severe liver disease. Presence of Pi M homozygosity could be associated with liver disease via some mechanism different from Z allele-induced liver damage through accumulation of AAT polymers. PMID:19961268

Changes in plasma chemistry after drug-induced liver disease or muscle necrosis in racing pigeons (Columba livia domestica).

PubMed

Lumeij, J T; Meidam, M; Wolfswinkel, J; Van der Hage, M H; Dorrestein, G M

1988-01-01

Changes in plasma variables as a result of liver damage induced by ethylene glycol (group A) or D-galactosamine (group B) and of muscle damage induced by doxycycline were compared. Plasma bile acid concentration was both a specific and a sensitive indicator of liver disease. Another specific, but less sensitive indicator of liver disease was 7-GT. Plasma AS AT activity was the most sensitive indicator of disease of the liver, but was not specific, since increased ASAT activities were also seen during muscle disease. ALAT activity was slightly more sensitive to liver damage than 7-GT, but was also not specific, being increased also after muscle damage. Plasma GLDH activity was increased only as a result of extensive liver necrosis. AP activity was of no value for detecting liver disease in the pigeon. CK activity was specific for muscle injury, though the activities of ALAT, ASAT and LD were also increased. Because of its long elimination half-life, increased ALAT activity persisted for 9 days after muscle damage, whereas CK activity returned to reference values within 3 days. LDH was a poor indicator of damage to liver and muscle, despite its relatively high tissue concentrations in both tissues. The rapid disappearance rate of LDH from plasma probably explains this observation.

Fatty acid composition in serum correlates with that in the liver and non-alcoholic fatty liver disease activity scores in mice fed a high-fat diet.

PubMed

Wang, Xing-He; Li, Chun-Yan; Muhammad, Ishfaq; Zhang, Xiu-Ying

2016-06-01

In this study, we investigated the correlation between the serum fatty acid composition and hepatic steatosis, inflammation, hepatocellular ballooning scores, and liver fatty acids composition in mice fed a high-fat diet. Livers were collected for non-alcoholic fatty liver disease score analysis. Fatty acid compositions were analysed by gas chromatography. Correlations were determined by Pearson correlation coefficient. Exposed to a high-fat diet, mice developed fatty liver disease with varying severity without fibrosis. The serum fatty acid variation became more severe with prolonged exposure to a high-fat diet. This variation also correlated significantly with the variation in livers, with the types of fatty acids corresponding to liver steatosis, inflammation, and hepatocellular ballooning scores. Results of this study lead to the following hypothesis: the extent of serum fatty acid variation may be a preliminary biomarker of fatty liver disease caused by high-fat intake. Copyright © 2016. Published by Elsevier B.V.

The Role of Celiac Disease in Severity of Liver Disorders and Effect of a Gluten Free Diet on Diseases Improvement

PubMed Central

Rostami-Nejad, Mohammad; Haldane, Thea; AlDulaimi, David; Alavian, Seyed Moayed; Zali, Mohammad Reza; Rostami, Kamran

2013-01-01

Context Celiac disease (CD) is defined as a permanent intolerance to ingested gluten. The intolerance to gluten results in immune-mediated damage of small intestine mucosa manifested by villous atrophy and crypt hyperplasia. These abnormalities resolve with initiationa gluten-free diet. Evidence Acquisition PubMed, Ovid, and Google were searched for full text articles published between 1963 and 2012. The associated keywords were used, and papers described particularly the impact of celiac disease on severity of liver disorder were identified. Results Recently evidence has emerged revealingthat celiac disease not only is associated with small intestine abnormalities and malabsorption, but is also a multisystem disorder affecting other systems outside gastrointestinal tract, including musculo-skeletal, cardiovascular and nervous systems. Some correlations have been assumed between celiac and liver diseases. In particular, celiac disease is associated with changes in liver biochemistry and linked to alter the prognosis of other disorders. This review will concentrate on the effect of celiac disease and gluten-free diets on the severity of liver disorders. Conclusions Although GFD effect on the progression of CD associated liver diseases is not well defined, it seems that GFD improves liver function tests in patients with a hypertransaminasemia. PMID:24348636

Use of deferiprone for the treatment of hepatic iron storage disease in three hornbills.

PubMed

Sandmeier, Peter; Clauss, Marcus; Donati, Olivio F; Chiers, Koen; Kienzle, Ellen; Hatt, Jean-Michel

2012-01-01

3 hornbills (2 Papua hornbills [Aceros plicatus] and 1 longtailed hornbill [Tockus albocristatus]) were evaluated because of general listlessness and loss of feather glossiness. Because hepatic iron storage disease was suspected, liver biopsy was performed and formalin-fixed liver samples were submitted for histologic examination and quantitative image analysis (QIA). Additional frozen liver samples were submitted for chemical analysis. Birds also underwent magnetic resonance imaging (MRI) under general anesthesia for noninvasive measurement of liver iron content. Serum biochemical analysis and analysis of feed were also performed. Results of diagnostic testing indicated that all 3 hornbills were affected with hepatic iron storage disease. The iron chelator deferiprone was administered (75 mg/kg [34.1 mg/lb], PO, once daily for 90 days). During the treatment period, liver biopsy samples were obtained at regular intervals for QIA and chemical analysis of the liver iron content and follow-up MRI was performed. In all 3 hornbills, a rapid and large decrease in liver iron content was observed. All 3 methods for quantifying the liver iron content were able to verify the decrease in liver iron content. Orally administered deferiprone was found to effectively reduce the liver iron content in these 3 hornbills with iron storage disease. All 3 methods used to monitor the liver iron content (QIA, chemical analysis of liver biopsy samples, and MRI) had similar results, indicating that all of these methods should be considered for the diagnosis of iron storage disease and monitoring of liver iron content during treatment.

Effect of Liver Disease on Hepatic Transporter Expression and Function.

PubMed

Thakkar, Nilay; Slizgi, Jason R; Brouwer, Kim L R

2017-09-01

Liver disease can alter the disposition of xenobiotics and endogenous substances. Regulatory agencies such as the Food and Drug Administration and the European Medicines Evaluation Agency recommend, if possible, studying the effect of liver disease on drugs under development to guide specific dose recommendations in these patients. Although extensive research has been conducted to characterize the effect of liver disease on drug-metabolizing enzymes, emerging data have implicated that the expression and function of hepatobiliary transport proteins also are altered in liver disease. This review summarizes recent developments in the field, which may have implications for understanding altered disposition, safety, and efficacy of new and existing drugs. A brief review of liver physiology and hepatic transporter localization/function is provided. Then, the expression and function of hepatic transporters in cholestasis, hepatitis C infection, hepatocellular carcinoma, human immunodeficiency virus infection, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, and primary biliary cirrhosis are reviewed. In the absence of clinical data, nonclinical information in animal models is presented. This review aims to advance the understanding of altered expression and function of hepatic transporters in liver disease and the implications of such changes on drug disposition. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

[Summary of the practice guideline 'Viral hepatitis and other liver diseases' (second revision) from the Dutch College of General Practitioners].

PubMed

Bouma, M; van Geldrop, W J; Numans, M E; Wiersma, Tj; Goudswaard, A N

2008-12-06

The revised Dutch College of General Practitioners' practice guideline 'Viral hepatitis and other liver diseases' offers advice in the diagnosis and management of viral hepatitis A, B and C and other liver diseases. The guideline is important for general practitioners as well as specialists in internal medicine and gastroenterology. The emphasis is on the management of chronic hepatitis B en C, because the prevalence of these diseases has increased in the Netherlands and, in addition, the treatment options for chronic hepatitis have improved. Consequently, timely recognition and adequate referral of patients with chronic hepatitis B or hepatitis C have become more important. However, many patients with a chronic liver disease have no symptoms. Therefore, the general practitioner should be aware that a patient visiting the practice with fatigue and malaise could have a liver disease if he or she belongs to a high-risk group or has had high-risk contacts. If the general practitioner repeatedly finds increased liver transaminase values during routine examination of asymptomatic patients, additional diagnostic tests should be performed. Further tests should focus on viral hepatitis as well as on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis or, depending on the history-taking, liver damage due to excessive alcohol, medication or drug use.

Fatty Liver Index and Lipid Accumulation Product Can Predict Metabolic Syndrome in Subjects without Fatty Liver Disease

PubMed Central

Cheng, Yuan-Lung; Wang, Yuan-Jen; Lan, Keng-Hsin; Huo, Teh-Ia; Hsieh, Wei-Yao; Hou, Ming-Chih; Lee, Fa-Yauh; Wu, Jaw-Ching; Lee, Shou-Dong

2017-01-01

Background. Fatty liver index (FLI) and lipid accumulation product (LAP) are indexes originally designed to assess the risk of fatty liver and cardiovascular disease, respectively. Both indexes have been proven to be reliable markers of subsequent metabolic syndrome; however, their ability to predict metabolic syndrome in subjects without fatty liver disease has not been clarified. Methods. We enrolled consecutive subjects who received health check-up services at Taipei Veterans General Hospital from 2002 to 2009. Fatty liver disease was diagnosed by abdominal ultrasonography. The ability of the FLI and LAP to predict metabolic syndrome was assessed by analyzing the area under the receiver operating characteristic (AUROC) curve. Results. Male sex was strongly associated with metabolic syndrome, and the LAP and FLI were better than other variables to predict metabolic syndrome among the 29,797 subjects. Both indexes were also better than other variables to detect metabolic syndrome in subjects without fatty liver disease (AUROC: 0.871 and 0.879, resp.), and the predictive power was greater among women. Conclusion. Metabolic syndrome increases the cardiovascular disease risk. The FLI and LAP could be used to recognize the syndrome in both subjects with and without fatty liver disease who require lifestyle modifications and counseling. PMID:28194177

Does hypervascularity of liver metastases as detected on MRI predict disease progression in breast cancer patients?

PubMed

Braga, Larissa; Semelka, Richard C; Pietrobon, Ricardo; Martin, Diego; de Barros, Nestor; Guller, Ulrich

2004-05-01

The aim of our study was to evaluate the association of the vascularity of liver metastases, as characterized by MRI, and disease progression in breast cancer patients. Sixteen breast cancer patients with liver metastases who underwent MRI before and after systemic therapy were retrospectively identified. On the basis of comparison of each MRI examination with the previous examination, disease status of the patients was classified as complete response, partial response, stable disease, or progressive disease. Liver metastases were characterized as hyper- or hypovascular on the basis of the degree of enhancement in the arterial, portal, and interstitial phases of imaging after administration of a contrast agent. Fisher's exact test and ordinal logistic regression models, including the type of systemic therapy, presence of multiple metastases, and hormone receptor status, were used to estimate the unadjusted and risk-adjusted association between the presence of hypervascular liver metastases and disease progression. All patients in our sample (n = 16) were women and most (12/16, 75%) were white. Their median age was 51.5 years. In unadjusted analyses, the association between the presence of hypervascular liver metastases and disease progression was statistically significant (p < 0.0001). In multiple logistic regression analyses, hypervascular liver metastases were found to be an independent predictor of disease progression. Patients with hypervascular liver lesions were 20.5 times more likely to experience disease progression than patients without hypervascular metastases (odds ratio, 20.5; 95% confidence interval, 5.1-83.5; p < 0.0001). Our analysis provides suggestive evidence that disease progression can be predicted through MRI assessment of the vascularity of liver metastases in patients with breast cancer.

Nonalcoholic fatty liver disease in spinal and bulbar muscular atrophy

PubMed Central

Guber, Robert D.; Takyar, Varun; Kokkinis, Angela; Fox, Derrick A.; Alao, Hawwa; Kats, Ilona; Bakar, Dara; Remaley, Alan T.; Hewitt, Stephen M.; Kleiner, David E.; Liu, Chia-Ying; Hadigan, Colleen; Fischbeck, Kenneth H.; Rotman, Yaron

2017-01-01

Objective: To determine the prevalence and features of fatty liver disease in spinal and bulbar muscular atrophy (SBMA). Methods: Two groups of participants with SBMA were evaluated. In the first group, 22 participants with SBMA underwent laboratory analysis and liver imaging. In the second group, 14 participants with SBMA were compared to 13 female carriers and 23 controls. Liver biopsies were done in 4 participants with SBMA. Results: Evidence of fatty liver disease was detected by magnetic resonance spectroscopy in all participants with SBMA in the first group, with an average dome intrahepatic triacylglycerol of 27% (range 6%–66%, ref ≤5.5%). Liver dome magnetic resonance spectroscopy measurements were significantly increased in participants with SBMA in the second group relative to age- and sex-matched controls, with average disease and male control measurements of 17% and 3%, respectively. Liver biopsies were consistent with simple steatosis in 2 participants and nonalcoholic steatohepatitis in 2 others. Conclusions: We observed evidence of nonalcoholic liver disease in nearly all of the participants with SBMA evaluated. These observations expand the phenotypic spectrum of the disease and provide a potential biomarker that can be monitored in future studies. PMID:29142082

Delayed gastric emptying of both the liquid and solid components of a meal in chronic liver disease.

PubMed

Galati, J S; Holdeman, K P; Dalrymple, G V; Harrison, K A; Quigley, E M

1994-05-01

To evaluate gastric emptying in patients with chronic liver disease and portal hypertension. We measured gastric emptying of both the liquid and solid components of a meal in 10 consecutive patients with chronic liver disease and portal hypertension, but free of ascites, and 14 age- and sex-matched healthy controls. In the patients with liver disease, relationships between emptying and liver function were examined. To measure gastric emptying, subjects consumed a test meal that consisted of scrambled eggs labeled with 99mTc-sulfur colloid and 4 oz of water labeled with 111In-diethylene triamine pentacetic acid (DTPA). Patients with liver disease and portal hypertension demonstrated delayed emptying of both the liquid (t1/2, min, mean +/- SE, patients vs. 69.4 +/- 19.4 vs. 31.4 +/- 1.8, p < 0.01) and solid (post-lag phase solid emptying: 141 +/- 32.9 vs. 69.8 +/- 4.6, p < 0.006) components of the meal. We could not identify any correlation between gastric emptying and tests of liver function. Gastric emptying is delayed in patients with liver disease and portal hypertension; this abnormal gastric motor function may contribute to the pathophysiology of foregut complaints in this patient population.

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.

Iron overload and HFE gene mutations in Czech patients with chronic liver diseases.

PubMed

Dostalikova-Cimburova, Marketa; Kratka, Karolina; Stransky, Jaroslav; Putova, Ivana; Cieslarova, Blanka; Horak, Jiri

2012-01-01

The aim of the study was to identify the prevalence of HFE gene mutations in Czech patients with chronic liver diseases and the influence of the mutations on iron status. The presence of HFE gene mutations (C282Y, H63D, and S65C) analyzed by the PCR-RFLP method, presence of cirrhosis, and serum iron indices were compared among 454 patients with different chronic liver diseases (51 with chronic hepatitis B, 122 with chronic hepatitis C, 218 with alcoholic liver disease, and 63 patients with hemochromatosis). Chronic liver diseases patients other than hemochromatics did not have an increased frequency of HFE gene mutations compared to controls. Although 33.3% of patients with hepatitis B, 43% of patients with hepatitis C, and 73.2% of patients with alcoholic liver disease had elevated transferrin saturation or serum ferritin levels, the presence of HFE gene mutations was not significantly associated with iron overload in these patients. Additionally, patients with cirrhosis did not have frequencies of HFE mutations different from those without cirrhosis. This study emphasizes the importance, not only of C282Y, but also of the H63D homozygous genetic constellation in Czech hemochromatosis patients. Our findings show that increased iron indices are common in chronic liver diseases but {\\it HFE} mutations do not play an important role in the pathogenesis of chronic hepatitis B, chronic hepatitis C, and alcoholic liver disease.

Hepatic Lipodystrophy in Galloway Calves.

PubMed

Wieland, M; Mann, S; Hafner-Marx, A; Ignatius, A; Metzner, M

2017-05-01

Hepatic lipodystrophy in Galloway calves is a fatal liver disease affecting a small proportion of the Galloway breed described in different parts of Europe and North America during the past decades. The clinical findings include a diversity of neurological signs. Clinical pathology findings frequently indicate hepatobiliary disease. Postmortem examination reveals an enlarged, pale yellow, and firm liver. Histologic lesions include hepatic fibrosis, hepatic lipidosis, and bile duct hyperplasia. To date, the etiopathogenesis remains obscure. Infectious causes, intoxications, and a hereditary origin have been considered. We describe hepatic lipodystrophy in Galloway calves from an extensively farmed cow-calf operation in southern Germany. Main clinical findings in 6 calves were consistent with hepatic encephalopathy. Clinical pathology findings in 5 of 6 tested animals revealed increased concentration of total bilirubin (maximum value [MV], 54 μmol/l; reference range [RR], <8.5 μmol/l), direct bilirubin (MV, 20 μmol/l; RR, <3.4 μmol/l), increased activity of gamma glutamyl transferase (MV, 162 U/l; RR, <36 U/l) and glutamate dehydrogenase (MV, 420 U/l; RR, <16 U/l). In addition, activity of glutathione peroxidase was decreased in all tested ( n = 5) animals (MV, 61 U/g hemoglobin [Hb]; RR, >250 U/g Hb). Postmortem examination in 6 calves revealed a firm, diffusely enlarged yellow liver with a finely nodular surface. Histologic lesions included hepatic fibrosis, hepatic lipidosis, and bile duct hyperplasia. Our findings add to the existing data on hepatic lipodystrophy in the Galloway breed and outline a protocol to aid in the diagnosis of this disorder.

Rapid Diffusion of Green Fluorescent Protein in the Mitochondrial Matrix

PubMed Central

Partikian, Arthur; Ölveczky, Bence; Swaminathan, R.; Li, Yuxin; Verkman, A.S.

1998-01-01

Abstract. It is thought that the high protein density in the mitochondrial matrix results in severely restricted solute diffusion and metabolite channeling from one enzyme to another without free aqueous-phase diffusion. To test this hypothesis, we measured the diffusion of green fluorescent protein (GFP) expressed in the mitochondrial matrix of fibroblast, liver, skeletal muscle, and epithelial cell lines. Spot photobleaching of GFP with a 100× objective (0.8-μm spot diam) gave half-times for fluorescence recovery of 15–19 ms with >90% of the GFP mobile. As predicted for aqueous-phase diffusion in a confined compartment, fluorescence recovery was slowed or abolished by increased laser spot size or bleach time, and by paraformaldehyde fixation. Quantitative analysis of bleach data using a mathematical model of matrix diffusion gave GFP diffusion coefficients of 2–3 × 10−7 cm2/s, only three to fourfold less than that for GFP diffusion in water. In contrast, little recovery was found for bleaching of GFP in fusion with subunits of the fatty acid β-oxidation multienzyme complex that are normally present in the matrix. Measurement of the rotation of unconjugated GFP by time-resolved anisotropy gave a rotational correlation time of 23.3 ± 1 ns, similar to that of 20 ns for GFP rotation in water. A rapid rotational correlation time of 325 ps was also found for a small fluorescent probe (BCECF, ∼0.5 kD) in the matrix of isolated liver mitochondria. The rapid and unrestricted diffusion of solutes in the mitochondrial matrix suggests that metabolite channeling may not be required to overcome diffusive barriers. We propose that the clustering of matrix enzymes in membrane-associated complexes might serve to establish a relatively uncrowded aqueous space in which solutes can freely diffuse. PMID:9472034

Prediction of high-stage liver fibrosis using ADC value on diffusion-weighted imaging and quantitative enhancement ratio at the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI at 1.5 T.

PubMed

Harada, Taiyo L; Saito, Kazuhiro; Araki, Yoichi; Matsubayashi, Jun; Nagao, Toshitaka; Sugimoto, Katsutoshi; Tokuuye, Koichi

2018-05-01

Background Recently, diffusion-weighted imaging (DWI) and quantitative enhancement ratio measured at the hepatobiliary phase (HBP) of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) has been established as an effective method for evaluating liver fibrosis. Purpose To evaluate which is a more favorable surrogate marker in predicting high-stage liver fibrosis, apparently diffusion coefficient (ADC) value or quantitative enhancement ratio measured on HBP. Material and Methods Eighty-three patients with 99 surgically resected hepatic lesions were enrolled in this study. DWI was performed with b-values of 100 and 800 s/mm 2 . Regions of interest were set on ADC map, and the HBP of Gd-EOB-DTPA-enhanced MRI, to calculate ADC value, liver-to-muscle ratio (LMR), liver-to-spleen ratio (LSR), and contrast enhancement index (CEI) of liver. We compared these parameters between low-stage fibrosis (F0, F1, and F2) and high-stage fibrosis (F3 and F4). Receiver operating characteristic analysis was performed to compare the diagnostic performance when distinguishing low-stage fibrosis from high-stage fibrosis. Results LMR and CEI were significantly lower at high-stage fibrosis than at the low stage ( P < 0.01 and P = 0.04, respectively), whereas LSR did not show a significant difference ( P = 0.053). No significant difference was observed in diagnostic performance between LMR and CEI ( P = 0.185). The best sensitivity and specificity, when an LMR of 2.80 or higher was considered to be low-stage fibrosis, were 82.4% and 75.6%, respectively. ADC value showed no significant differences among fibrosis grades ( P = 0.320). Conclusion LMR and CEI were both adequate surrogate parameters to distinguish high-stage fibrosis from low-stage fibrosis.

Dependence of intravoxel incoherent motion diffusion MR threshold b-value selection for separating perfusion and diffusion compartments and liver fibrosis diagnostic performance.

PubMed

Wáng, Yì Xiáng J; Li, Yáo T; Chevallier, Olivier; Huang, Hua; Leung, Jason Chi Shun; Chen, Weitian; Lu, Pu-Xuan

2018-01-01

Background Intravoxel incoherent motion (IVIM) tissue parameters depend on the threshold b-value. Purpose To explore how threshold b-value impacts PF ( f), D slow ( D), and D fast ( D*) values and their performance for liver fibrosis detection. Material and Methods Fifteen healthy volunteers and 33 hepatitis B patients were included. With a 1.5-T magnetic resonance (MR) scanner and respiration gating, IVIM data were acquired with ten b-values of 10, 20, 40, 60, 80, 100, 150, 200, 400, and 800 s/mm 2 . Signal measurement was performed on the right liver. Segmented-unconstrained analysis was used to compute IVIM parameters and six threshold b-values in the range of 40-200 s/mm 2 were compared. PF, D slow , and D fast values were placed along the x-axis, y-axis, and z-axis, and a plane was defined to separate volunteers from patients. Results Higher threshold b-values were associated with higher PF measurement; while lower threshold b-values led to higher D slow and D fast measurements. The dependence of PF, D slow , and D fast on threshold b-value differed between healthy livers and fibrotic livers; with the healthy livers showing a higher dependence. Threshold b-value = 60 s/mm 2 showed the largest mean distance between healthy liver datapoints vs. fibrotic liver datapoints, and a classification and regression tree showed that a combination of PF (PF < 9.5%), D slow (D slow  < 1.239 × 10 -3 mm 2 /s), and D fast (D fast  < 20.85 × 10 -3 mm 2 /s) differentiated healthy individuals and all individual fibrotic livers with an area under the curve of logistic regression (AUC) of 1. Conclusion For segmented-unconstrained analysis, the selection of threshold b-value = 60 s/mm 2 improves IVIM differentiation between healthy livers and fibrotic livers.

A fourth dimension in decision making in hepatology.

PubMed

Ilan, Yaron

2010-12-01

Today, the assessment of liver function in patients suffering from acute or chronic liver disease is based on liver biopsy and blood tests including synthetic function, liver enzymes and viral load, most of which provide only circumstantial evidence as to the degree of hepatic impairment. Most of these tests lack the degree of sensitivity to be useful for follow-up of these patients at the frequency that is needed for decision making in clinical hepatology. Accurate assessment of liver function is essential to determine both short- and long-term prognosis, and for making decisions about liver and non-liver surgery, TIPS, chemoembolization or radiofrequency ablation in patients with chronic liver disease. Liver function tests can serve as the basis for accurate decision-making regarding the need for liver transplantation in the setting of acute failure or in patients with chronic liver disease. The liver metabolic breath test relies on measuring exhaled (13) C tagged methacetin, which is metabolized only by the liver. Measuring this liver-specific substrate by means of molecular correlation spectroscopy is a rapid, non-invasive method for assessing liver function at the point-of-care. The (13) C methacetin breath test (MBT) is a powerful tool to aid clinical hepatologists in bedside decision-making. Our recent findings regarding the ability of point-of-care (13) C MBT to assess the hepatic functional reserve in patients with acute and chronic liver disease are reviewed along with suggested treatment algorithms for common liver disorders. © 2010 The Japan Society of Hepatology.

Case report: fatal poisoning with Colchicum autumnale.

PubMed

Brvar, Miran; Ploj, Tom; Kozelj, Gordana; Mozina, Martin; Noc, Marko; Bunc, Matjaz

2004-02-01

Colchicum autumnale, commonly known as the autumn crocus, contains alkaloid colchicine with antimitotic properties. A 76-year-old man with a history of alcoholic liver disease and renal insufficiency, who mistakenly ingested Colchicum autumnale instead of wild garlic (Aliium ursinum), presented with nausea, vomiting and diarrhea 12 hours after ingestion. On admission the patient had laboratory signs of dehydration. On the second day the patient became somnolent and developed respiratory insufficiency. The echocardiogram showed heart dilatation with diffuse hypokinesia with positive troponin I. The respiratory insufficiency was further deteriorated by pneumonia, confirmed by chest X-ray and later on by autopsy. Laboratory tests also revealed rhabdomyolysis, coagulopathy and deterioration of renal function and hepatic function. The toxicological analysis disclosed colchicine in the patient's urine (6 microgram/l) and serum (9 microgram/l) on the second day. Therapy was supportive with hydration, vasopressors, mechanical ventilation and antibiotics. On the third day the patient died due to asystolic cardiac arrest. Colchicine poisoning should be considered in patients with gastroenterocolitis after a meal of wild plants. Management includes only intensive support therapy. A more severe clinical presentation should be expected in patients with pre-existing liver and renal diseases. The main reasons for death are cardiovascular collapse, respiratory failure and leukopenia with infection.

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

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.

Multicausality in fatty liver disease: Is there a rationale to distinguish between alcoholic and non-alcoholic origin?

PubMed Central

Völzke, Henry

2012-01-01

Apart from alcohol, there are other factors that may induce complications, which resemble alcohol-related liver disorders. In particular, obesity has been brought into focus as a risk factor for fatty liver disease. The term “non-alcoholic” fatty liver disease is commonly used to distinguish between obesity-related and alcohol-related hepatic steatosis. This review uses the epidemiological perspective to critically assess whether it is necessary and useful to differentiate between alcoholic and “non-alcoholic” fatty liver disease. The MEDLINE database was searched using the PubMed search engine, and a review of reference lists from original research and review articles was conducted. The concept to distinguish between alcoholic and “non-alcoholic” fatty liver disease is mainly based on specific pathomechanisms. This concept has, however, several limitations including the common overlap between alcohol misuse and obesity-related metabolic disorders and the non-consideration of additional causal factors. Both entities share similar histopathological patterns. Studies demonstrating differences in clinical presentation and outcome are often biased by selection. Risk factor reduction is the main principle of prevention and treatment of both disease forms. In conclusion, alcoholic and “non-alcoholic” fatty liver diseases are one and the same disease caused by different risk factors. A shift from artificial categories to a more general approach to fatty liver disease as a multicausal disorder may optimize preventive strategies and help clinicians more effectively treat patients at the individual level. PMID:22826613

Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years.

PubMed

Federico, Alessandro; Dallio, Marcello; Loguercio, Carmelina

2017-01-24

Silymarin is the extract of Silybum marianum , or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver disorders, particularly chronic liver diseases, cirrhosis and hepatocellular carcinoma, because of its antioxidant, anti-inflammatory and antifibrotic power. Indeed, the anti-oxidant and anti-inflammatory effect of silymarin is oriented towards the reduction of virus-related liver damages through inflammatory cascade softening and immune system modulation. It also has a direct antiviral effect associated with its intravenous administration in hepatitis C virus infection. With respect to alcohol abuse, silymarin is able to increase cellular vitality and to reduce both lipid peroxidation and cellular necrosis. Furthermore, silymarin/silybin use has important biological effects in non-alcoholic fatty liver disease. These substances antagonize the progression of non-alcoholic fatty liver disease, by intervening in various therapeutic targets: oxidative stress, insulin resistance, liver fat accumulation and mitochondrial dysfunction. Silymarin is also used in liver cirrhosis and hepatocellular carcinoma that represent common end stages of different hepatopathies by modulating different molecular patterns. Therefore, the aim of this review is to examine scientific studies concerning the effects derived from silymarin/silybin use in chronic liver diseases, cirrhosis and hepatocellular carcinoma.

Circulating Extracellular Vesicles with Specific Proteome and Liver MicroRNAs Are Potential Biomarkers for Liver Injury in Experimental Fatty Liver Disease

PubMed Central

Povero, Davide; Eguchi, Akiko; Li, Hongying; Johnson, Casey D.; Papouchado, Bettina G.; Wree, Alexander; Messer, Karen; Feldstein, Ariel E.

2014-01-01

Background & Aim Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in both adult and children. Currently there are no reliable methods to determine disease severity, monitor disease progression, or efficacy of therapy, other than an invasive liver biopsy. Design Choline Deficient L-Amino Acid (CDAA) and high fat diets were used as physiologically relevant mouse models of NAFLD. Circulating extracellular vesicles were isolated, fully characterized by proteomics and molecular analyses and compared to control groups. Liver-related microRNAs were isolated from purified extracellular vesicles and liver specimens. Results We observed statistically significant differences in the level of extracellular vesicles (EVs) in liver and blood between two control groups and NAFLD animals. Time-course studies showed that EV levels increase early during disease development and reflect changes in liver histolopathology. EV levels correlated with hepatocyte cell death (r2 = 0.64, p<0.05), fibrosis (r2 = 0.66, p<0.05) and pathological angiogenesis (r2 = 0.71, p<0.05). Extensive characterization of blood EVs identified both microparticles (MPs) and exosomes (EXO) present in blood of NAFLD animals. Proteomic analysis of blood EVs detected various differentially expressed proteins in NAFLD versus control animals. Moreover, unsupervised hierarchical clustering identified a signature that allowed for discrimination between NAFLD and controls. Finally, the liver appears to be an important source of circulating EVs in NAFLD animals as evidenced by the enrichment in blood with miR-122 and 192 - two microRNAs previously described in chronic liver diseases, coupled with a corresponding decrease in expression of these microRNAs in the liver. Conclusions These findings suggest a potential for using specific circulating EVs as sensitive and specific biomarkers for the noninvasive diagnosis and monitoring of NAFLD. PMID:25470250

The healthcare burden imposed by liver disease in aging Baby Boomers.

PubMed

Davis, Gary L; Roberts, William L

2010-02-01

The Baby Boomer generation is composed of 78 million Americans who are just beginning to reach their retirement years. Most Boomers have at least one chronic health problem, and these significantly increase the expense of providing medical care. Liver disease is the 12th most common cause of death in the United States, representing a relatively small portion of overall healthcare costs compared with cardiovascular disease and malignancy. Nonetheless, hepatitis C and fatty liver disease are more common in the Boomers and may play a more dominant role as they age. As a consequence, primary liver cancer is likely to become more prevalent. As with most chronic illnesses, prevention rather than disease management is likely to have the greatest impact. For those already afflicted by chronic liver disease, recognition and treatment can reduce the incidence of late complications, as was clearly demonstrated with chronic hepatitis B and C. Perhaps obesity is the greatest threat to our future health, and fatty liver disease, although likely preventable, will probably become the disease that fills the waiting rooms of future hepatologists.

Role of scavenger receptors in the pathophysiology of chronic liver diseases.

PubMed

Armengol, Carolina; Bartolí, Ramon; Sanjurjo, Lucía; Serra, Isabel; Amézaga, Núria; Sala, Margarita; Sarrias, Maria-Rosa

2013-01-01

Scavenger receptors comprise a large family of structurally diverse proteins that are involved in many homeostatic functions. They recognize a wide range of ligands, from pathogen-associated molecular patterns (PAMPs) to endogenous, as well as modified host-derived molecules (DAMPs). The liver deals with blood micro-organisms and DAMPs released from injured organs, thus performing vital metabolic and clearance functions that require the uptake of nutrients and toxins. Many liver cell types, including hepatocytes and Kupffer cells, express scavenger receptors that play key roles in hepatitis C virus entry, lipid uptake, and macrophage activation, among others. Chronic liver disease causes high morbidity and mortality worldwide. Hepatitis virus infection, alcohol abuse, and non-alcoholic fatty liver are the main etiologies associated with this disease. In this context, continuous inflammation as a result of liver damage leads to hepatic fibrosis, which frequently brings about cirrhosis and ultimately hepatocellular carcinoma. In this review, we will summarize the role of scavenger receptors in the pathophysiology of chronic liver diseases. We will also emphasize their potential as biomarkers of advanced liver disease, including cirrhosis and cancer.

Liver diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS): A population-based cohort study of 32,839 one-year survivors.

PubMed

Bonnesen, Trine Gade; Winther, Jeanette F; Andersen, Klaus K; Asdahl, Peter H; de Fine Licht, Sofie; Gudmundsdottir, Thorgerdur; Sällfors Holmqvist, Anna; Madanat-Harjuoja, Laura-Maria; Tryggvadottir, Laufey; Wesenberg, Finn; Heilmann, Carsten; Olsen, Jørgen H; Hasle, Henrik

2018-02-15

Information on late onset liver complications after childhood cancer is scarce. To ensure an appropriate follow-up of childhood cancer survivors and reducing late liver complications, the need for comprehensive and accurate information is presented. We evaluate the risk of liver diseases in a large childhood cancer survivor cohort. We included all 1-year survivors of childhood cancer treated in the five Nordic countries. A Cox proportional hazards model was used to estimate hospitalisation rate (hazard) ratios (HRs) for each liver outcome according to type of cancer. We used the risk among survivors of central nervous system tumour as internal reference. With a median follow-up time of 10 years, 659 (2%) survivors had been hospitalised at least once for a liver disease. The risk for hospitalisation for any liver disease was high after hepatic tumour (HR = 6.9) and leukaemia (HR = 1.7). The Danish sub-cohort of leukaemia treated with haematopoietic stem cell transplantation had a substantially higher risk for hospitalisation for all liver diseases combined (HR = 3.8). Viral hepatitis accounted for 286 of 659 hospitalisations corresponding to 43% of all survivors hospitalised for liver disease. The 20-year cumulative risk of viral hepatitis was 1.8% for survivors diagnosed with cancer before 1990 but only 0.3% for those diagnosed after 1990. The risk of liver disease was low but significantly increased among survivors of hepatic tumours and leukaemia. Further studies with focus on the different treatment modalities are needed to further strengthen the prevention of treatment-induced late liver complications. © 2017 UICC.

De Novo and Recurrence of Nonalcoholic Steatohepatitis After Liver Transplantation.

PubMed

Kappus, Matthew; Abdelmalek, Manal

2017-05-01

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developing countries. Approximately 25% of patients with NAFLD develop nonalcoholic steatohepatitis (NASH). NASH-related cirrhosis is now a leading listing indication for liver transplantation in the United States. Although posttransplant survival for NASH-related cirrhosis is comparable with that of other liver diseases, many patients have features of metabolic syndrome, which can contribute to a recurrence of NAFLD or NASH. This article reviews the epidemiology, pathophysiology, and treatment of de novo and recurrence of NASH after liver transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

Epidemiology and Mortality of Liver Abscess in End-Stage Renal Disease Dialysis Patients: Taiwan National Cohort Study

PubMed Central

Huang, Po-Chang; Wang, Jhi-Joung; Yang, Chun-Ming; Chu, Chin-Chen; Chio, Chung-Ching; Chang, Fu-Lin; Chien, Chih-Chiang

2014-01-01

Background and Objectives To determine the incidence rates and mortality of liver abscess in ESRD patients on dialysis. Design, Setting, Participants, & Measurements Using Taiwan’s National Health Insurance Research Database, we collected data from all ESRD patients who initiated dialysis between 2000 and 2006. Patients were followed until death, end of dialysis, or December 31, 2008. Predictors of liver abscess and mortality were identified using Cox models. Results Of the 53,249 incident dialysis patients identified, 447 were diagnosed as having liver abscesses during the follow-up period (224/100,000 person-years). The cumulative incidence rate of liver abscess was 0.3%, 1.1%, and 1.5% at 1 year, 5 years, and 7 years, respectively. Elderly patients and patients on peritoneal dialysis had higher incidence rates. The baseline comorbidities of diabetes mellitus, polycystic kidney disease, malignancy, chronic liver disease, biliary tract disease, or alcoholism predicted development of liver abscess. Overall in-hospital mortality was 10.1%. Conclusions The incidence of liver abscess is high among ESRD dialysis patients. In addition to the well known risk factors of liver abscess, two other important risk factors, peritoneal dialysis and polycystic kidney disease, were found to predict liver abscess in ESRD dialysis patients. PMID:24551077

The significance of cutaneous spider naevi in children

PubMed Central

Finn, S M; Rowland, M; Lawlor, F; Kinsella, W; Chan, L; Byrne, O; O'Mahony, O; Bourke, B

2006-01-01

Background Cutaneous spider naevi are commonly considered to be a clinical sign of chronic liver disease. Little is known about their occurrence in children. Aim To evaluate the occurrence of spider naevi in children with and without liver disease. Methods The presence of spider naevi was investigated in 460 children, 34 of whom had chronic liver disease. Results Of children without liver involvement, 38% had at least one spider naevus. The prevalence of spider naevi increased with age. Of control patients aged 5 to 15 years, 2.5% had more than five spiders present. Although eight of 10 children with cirrhosis had at least one spider naevus, only four of 34 children with chronic liver disease had five or more spiders present. Most spiders were on the hands and very few were >5 mm in size. Conclusions Children with liver disease rarely have large numbers of spider naevi. Although the finding of five or more spider naevi is more common in liver disease, many normal children also have one or more of these lesions. PMID:16595646

Physicians’ practices for diagnosing liver fibrosis in chronic liver diseases: A nationwide, Canadian survey

PubMed Central

Sebastiani, Giada; Ghali, Peter; Wong, Philip; Klein, Marina B; Deschenes, Marc; Myers, Robert P

2014-01-01

OBJECTIVE: To determine practices among physicians in Canada for the assessment of liver fibrosis in patients with chronic liver diseases. METHODS: Hepatologists, gastroenterologists, infectious diseases specialists, members of the Canadian Gastroenterology Association and/or the Canadian HIV Trials Network who manage patients with liver diseases were invited to participate in a web-based, national survey. RESULTS: Of the 237 physicians invited, 104 (43.9%) completed the survey. Routine assessment of liver fibrosis was requested by the surveyed physicians mostly for chronic hepatitis C (76.5%), followed by autoimmune/cholestatic liver disease (59.6%) and chronic hepatitis B (52.9%). Liver biopsy was the main diagnostic tool for 46.2% of the respondents, Fibroscan (Echosens, France) for 39.4% and Fibrotest (LabCorp, USA) for 7.7%. Etiology-specific differences were observed: noninvasive methods were mostly used for hepatitis C (63% versus 37% liver biopsy) and hepatitis B (62.9% versus 37.1% liver biopsy). For 42.7% of respondents, the use of noninvasive methods reduced the need for liver biopsy by >50%. Physicians’ characteristics associated with higher use of noninvasive methods were older age and being based at a university hospital or in private practice versus community hospital. Physicians’ main concerns regarding noninvasive fibrosis assessment methods were access/availability (42.3%), lack of guidelines for clinical use (26.9%) and cost/lack of reimbursement (14.4%). CONCLUSIONS: Physicians who manage patients with chronic liver diseases in Canada require routine assessment of liver fibrosis stage. Although biopsy remains the primary diagnostic tool for almost one-half of respondents, noninvasive methods, particularly Fibroscan, have significantly reduced the need for liver biopsy in Canada. Limitations in access to and availability of the noninvasive methods represent a significant barrier. Finally, there is a need for clinical guidelines and a better reimbursement policy to implement noninvasive tools to assess liver fibrosis. PMID:24416739

Coping and rehabilitation in alcoholic liver disease patients after hepatic encephalopathy--in interaction with professionals and relatives.

PubMed

Mikkelsen, Maria Rudkjær; Hendriksen, Carsten; Schiødt, Frank Vinholt; Rydahl-Hansen, Susan

2015-12-01

To identify and describe conditions that limit or support patients, with alcoholic liver disease after surviving alcohol-induced hepatic encephalopathy, ability to cope with current and potential physical and psychosocial problems--in interaction with professionals and relatives--and to recommend appropriate interventions. Alcoholic liver disease patients surviving alcohol-induced hepatic encephalopathy have significantly impaired quality of life. Internationally, there is a lack of knowledge about the conditions that affect alcoholic liver disease patients' coping and rehabilitation. A grounded theory study. Semi-structured interviews, conducted with 11 alcoholic liver disease patients who were diagnosed with hepatic encephalopathy. The interview guide was inspired by Richard S. Lazarus's theory of stress and coping. The elements that support or limit alcoholic liver disease patients' ability to cope with physical and psychosocial problems in interaction with professionals and relatives were represented by the core category 'Struggle for preservation of identity as a significant individual'. It was characterised by three categories, which are interrelated and impact upon each other: 'Acknowledgement', 'Struggle to maintain control' and 'Achieving a sense of security'. Alcoholic liver disease patients experience a struggle to preserve their identity as a significant individual. It can be assumed that professionals and relatives in their interaction with, and support of, patients should focus on strengthening and preserving patients' identity in the form of acknowledgement, helping alcoholic liver disease patients maintain self-control and providing a safety net so patients feel a sense of security. It can be assumed that professionals should support alcoholic liver disease patients' appraisal of, and coping with, physical and psychosocial problems based on acknowledgment, understanding and a sympathetic attitude. Professionals should proactively approach patients when they withdraw. It may be useful for professionals to be aware of alcoholic liver disease patients' individual coping strategies and thereby their individual requirements for professional supportive intervention. © 2015 John Wiley & Sons Ltd.

Management of cytomegalovirus infection and disease in liver transplant recipients

PubMed Central

Bruminhent, Jackrapong; Razonable, Raymund R

2014-01-01

Cytomegalovirus (CMV) is one of the most common viral pathogens causing clinical disease in liver transplant recipients, and contributing to substantial morbidity and occasional mortality. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted liver allograft. In addition, CMV has been significantly associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV infection on transplant outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component to the management of liver transplant recipients. Two recently updated guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and such occurrence of late-onset CMV disease was significantly associated with increased all-cause and infection-related mortality after liver transplantation. Therefore, a search for better strategies for prevention, such as prolonged duration of antiviral prophylaxis, a hybrid approach (antiviral prophylaxis followed by preemptive therapy), or the use of immunologic measures to guide antiviral prophylaxis has been suggested to prevent late-onset CMV disease. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, reduction in pharmacologic immunosuppression. In one clinical trial, oral valganciclovir was as effective as intravenous ganciclovir for the treatment of mild to moderate CMV disease in solid organ (including liver) transplant recipients. The aim of this article is to provide a state-of-the art review of the epidemiology, diagnosis, prevention, and treatment of CMV infection and disease after liver transplantation. PMID:25018848

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

Levine, E.; Cook, L.T.; Grantham, J.J.

Hepatic CT findings were analyzed in 44 patients with autosomal-dominant polycystic kidney disease and were correlated with liver and renal function tests and liver, splenic, and renal CT volume measurements. CT showed many large liver cysts in 31.8% of patients, small liver cysts in 25%, and no liver cysts in 43.2%. Patients with many large cysts often showed increased liver volumes. There was no correlation between severity of liver involvement and extent of renal cystic disease as determined from urea nitrogen and creatinine levels and renal volumes. Liver function tests were normal except in two patients, one with a cholangiocarcinoma,more » which may have arisen from a cyst, and the other with an infected liver cyst and chronic active hepatitis. Accordingly, if liver function tests are abnormal, an attempt should be made to identify complications of polycystic liver disease such as tumor cyst infection, and biliary obstruction. CT is a useful method for detecting liver cysts and identifying patients at risk for these complications.« less

Relationship between hepatocellular carcinoma, metabolic syndrome and non-alcoholic fatty liver disease: which clinical arguments?

PubMed

Rosmorduc, Olivier

2013-05-01

Obesity and the metabolic syndrome are growing epidemics associated with an increased risk for many types of cancer. In the liver, inflammatory and angiogenic changes due to insulin resistance and fatty liver disease are associated with an increased incidence of liver cancer. Regardless of underlying liver disease, cirrhosis remains the most important risk factor for hepatocellular carcinoma (HCC) although are cases of HCC arising without cirrhosis raise the possibility of a direct carcinogenesis secondary to Non-alcoholic Fatty Liver Disease (NAFLD). Moreover, metabolic syndrome and its different features may also increase the risk of HCC in the setting of chronic liver diseases of other causes such as viral hepatitis or alcohol abuse. Taking into account all these data, it is necessary to better determine the risk of developing HCC in patients with metabolic syndrome to improve the screening guidelines and develop prophylactic treatments in this setting. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

The parallel universe: microRNAs and their role in chronic hepatitis, liver tissue damage and hepatocarcinogenesis.

PubMed

Haybaeck, Johannes; Zeller, Nicolas; Heikenwalder, Mathias

2011-10-24

In recent years, enormous progress has been made in identifying microRNAs (miRNAs) as important regulators of gene expression and their association with or control of various liver diseases such as fibrosis, hepatitis and hepatocellular carcinoma (HCC). Indeed, many genes encoding miRNAs as well as their targets have been described and their direct or indirect link to the respective liver diseases has been investigated in various experimental systems as well as in human tissue. Here we discuss current knowledge of miRNAs and their involvement in liver diseases, elaborating in particular on the contribution of miRNAs to hepatitis, fibrosis and HCC formation. We also debate possible prognostic, predictive and therapeutic values of respective miRNAs in liver diseases. The discovery of liver disease related miRNAs has constituted a major breakthrough in liver research and will most likely be of high relevance for future therapeutic strategies, especially when dealing with hepatitis, fibrosis and HCC.

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.

Liver fibrosis markers in alcoholic liver disease.

PubMed

Chrostek, Lech; Panasiuk, Anatol

2014-07-07

Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients.

Free-breathing echo-planar imaging based diffusion-weighted magnetic resonance imaging of the liver with prospective acquisition correction.

PubMed

Asbach, Patrick; Hein, Patrick A; Stemmer, Alto; Wagner, Moritz; Huppertz, Alexander; Hamm, Bernd; Taupitz, Matthias; Klessen, Christian

2008-01-01

To evaluate soft tissue contrast and image quality of a respiratory-triggered echo-planar imaging based diffusion-weighted sequence (EPI-DWI) with different b values for magnetic resonance imaging (MRI) of the liver. Forty patients were examined. Quantitative and qualitative evaluation of contrast was performed. Severity of artifacts and overall image quality in comparison with a T2w turbo spin-echo (T2-TSE) sequence were scored. The liver-spleen contrast was significantly higher (P < 0.05) for the EPI-DWI compared with the T2-TSE sequence (0.47 +/- 0.11 (b50); 0.48 +/- 0.13 (b300); 0.47 +/- 0.13 (b600) vs 0.38 +/- 0.11). Liver-lesion contrast strongly depends on the b value of the DWI sequence and decreased with higher b values (b50, 0.47 +/- 0.19; b300, 0.40 +/- 0.20; b600, 0.28 +/- 0.23). Severity of artifacts and overall image quality were comparable to the T2-TSE sequence when using a low b value (P > 0.05), artifacts increased and image quality decreased with higher b values (P < 0.05). Respiratory-triggered EPI-DWI of the liver is feasible because good image quality and favorable soft tissue contrast can be achieved.

Patterns and Timing of Failure for Diffuse Large B-Cell Lymphoma After Initial Therapy in a Cohort Who Underwent Autologous Bone Marrow Transplantation for Relapse

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

Dhakal, Sughosh; Bates, James E.; Casulo, Carla

Purpose: To evaluate the location and timing of initial recurrence in patients with diffuse large B-cell lymphoma (DLBCL) who subsequently underwent high-dose chemotherapy with autologous stem cell transplant (HDC/ASCT), to direct approaches for disease surveillance, elucidate the patterns of failure of contemporary treatment strategies, and guide adjuvant treatment decisions. Methods and Materials: We analyzed consecutive patients with DLBCL who underwent HDC/ASCT between May 1992 and March 2014 at our institution. Of the 187 evaluable patients, 8 had incomplete data, and 79 underwent HDC/ASCT as a component of initial treatment for de novo or refractory DLBCL and were excluded from furthermore » analysis. Results: The median age was 50.8 years; the median time to relapse was 1.3 years. Patients were segregated according to the initial stage at diagnosis, with early stage (ES) defined as stage I/II and advanced stage (AS) defined as stage III/IV. In total, 40.4% of the ES and 75.5% of the AS patients relapsed in sites of initial disease; 68.4% of those with ES disease and 75.0% of those with AS disease relapsed in sites of initial disease only. Extranodal relapses were common (44.7% in ES and 35.9% in AS) and occurred in a variety of organs, although gastrointestinal tract/liver (n=12) was most frequent. Conclusions: Most patients with DLBCL who relapse and subsequently undergo HDC/ASCT initially recur in the previously involved disease site(s). Time to recurrence is brief, suggesting that frequency of screening is most justifiably greatest in the early posttherapy years. © 2016 Elsevier Inc.« less

The Use of Induced Pluripotent Stem Cells for the Study and Treatment of Liver Diseases.

PubMed

Hansel, Marc C; Davila, Julio C; Vosough, Massoud; Gramignoli, Roberto; Skvorak, Kristen J; Dorko, Kenneth; Marongiu, Fabio; Blake, William; Strom, Stephen C

2016-02-01

Liver disease is a major global health concern. Liver cirrhosis is one of the leading causes of death in the world and currently the only therapeutic option for end-stage liver disease (e.g., acute liver failure, cirrhosis, chronic hepatitis, cholestatic diseases, metabolic diseases, and malignant neoplasms) is orthotropic liver transplantation. Transplantation of hepatocytes has been proposed and used as an alternative to whole organ transplant to stabilize and prolong the lives of patients in some clinical cases. Although these experimental therapies have demonstrated promising and beneficial results, their routine use remains a challenge due to the shortage of donor livers available for cell isolation, variable quality of those tissues, the potential need for lifelong immunosuppression in the transplant recipient, and high costs. Therefore, new therapeutic strategies and more reliable clinical treatments are urgently needed. Recent and continuous technological advances in the development of stem cells suggest they may be beneficial in this respect. In this review, we summarize the history of stem cell and induced pluripotent stem cell (iPSC) technology in the context of hepatic differentiation and discuss the potential applications the technology may offer for human liver disease modeling and treatment. This includes developing safer drugs and cell-based therapies to improve the outcomes of patients with currently incurable health illnesses. We also review promising advances in other disease areas to highlight how the stem cell technology could be applied to liver diseases in the future. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

Radiation-induced liver disease as a mimic of liver metastases at serial PET/CT during neoadjuvant chemoradiation of distal esophageal cancer.

PubMed

Grant, Michael J; Didier, Ryne A; Stevens, Jeffrey S; Beyder, Dmitry D; Hunter, John G; Thomas, Charles R; Coakley, Fergus V

2014-10-01

To determine the frequency and appearance of radiation-induced liver disease on PET/CT in patients undergoing serial imaging during neoadjuvant chemoradiation of distal esophageal cancer. In this IRB-approved, HIPAA-compliant retrospective analysis, we identified 112 patients with distal esophageal cancer treated by neoadjuvant chemoradiation who had serial PET/CT imaging available for review. Two readers reviewed all studies in consensus and recorded those cases where new foci of visually detectable increased FDG avidity appeared in the liver during therapy. The etiology of such foci was determined from corresponding findings at CT or MRI, by hepatic biopsy during surgery, by characteristic evolution on post-operative imaging, or by a combination of these methods. New foci of FDG avidity developed in the liver during neoadjuvant therapy in 10 of 112 (9%) patients, of whom nine (8%) were determined to have radiation-induced liver disease based on further imaging and/or biopsy and one of whom had developed interval metastatic disease based on biopsy. In the cases of radiation-induced liver disease, the abnormal foci were found only in the caudate and left hepatic lobes, near the primary tumor, while the patient who developed interval metastatic disease had involvement of the inferior right hepatic lobe, remote from the radiation therapy field. New foci of increased FDG avidity are commonly seen in the caudate and left hepatic lobes of the liver during neoadjuvant chemoradiation of distal esophageal cancer, and these findings generally reflect radiation-induced liver disease rather than metastatic disease.

Toxin-Induced Autoimmune Hepatitis Caused by Raw Cashew Nuts.

PubMed

Crismale, James F; Stueck, Ashley; Bansal, Meena

2016-08-01

A 64-year-old man with no past medical history presented with abnormally elevated liver enzymes 1 year after developing a diffuse rash thought to be related to eating large quantities of raw cashew nuts. Liver biopsy was performed, which revealed features concerning for drug- or toxin-induced autoimmune hepatitis. The patient began treatment with azathioprine and prednisone, and liver enzymes normalized. We describe a unique case of a toxin-induced autoimmune hepatitis precipitated not by a drug or dietary supplement but by a food product.

Association between soil heavy metals and fatty liver disease in men in Taiwan: a cross sectional study.

PubMed

Lin, Yen-Chih; Lian, Ie-Bin; Kor, Chew-Teng; Chang, Chia-Chu; Su, Pei-Yuan; Chang, Wan-Tzu; Liang, Yu-Fen; Su, Wei-Wen; Soon, Maw-Soan

2017-01-23

Metabolic factors are major risk factors for non-alcoholic fatty liver disease although other factors may also contribute to development of fatty liver disease. We explored the association between exposure to soil heavy metals and prevalence of fatty liver disease. We retrospectively analysed data from patients diagnosed with fatty liver disease in 2014 at the Health Evaluation Centre of Chang-Hua Christian Hospital (n=1137). We used residency data provided in the records of the Health Evaluation Centre and data for soil metal concentrations from a nationwide survey conducted by the Environmental Protection Administration of Taiwan. We studied the correlations between the severity of fatty liver disease and concentrations of soil heavy metals (arsenic, mercury, cadmium, chromium, copper, nickel, lead and zinc). The prevalence of moderate to severe fatty liver disease in our study was 26.5%. Using univariate and multivariate analysis, we demonstrated that the presence of soil heavy metals was a significant risk factor for fatty liver disease in men (OR 1.83, 95% CI 1.161 to 2.899, p=0.009). With stratification by body mass index (BMI) and gender, lean men with a BMI <24 kg/m 2 were the most susceptible to soil heavy metals (OR 5.059, 95% CI 1.628 to 15.728, p<0.05). Our study suggested a significant association between exposure to soil heavy metals and fatty liver disease in lean men. 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/.

Influence of age and gender before and after liver transplantation.

PubMed

Burra, Patrizia; De Martin, Eleonora; Gitto, Stefano; Villa, Erica

2013-02-01

Women constitute a particular group among patients with chronic liver disease and in the post-liver transplantation (LT) setting: they are set apart not only by traditional differences with respect to men (ie, body mass index, different etiologies of liver disease, and accessibility to transplantation) but also in increasingly evident ways related to hormonal changes that characterize first the fertile age and subsequently the postmenopausal period (eg, disease course variability and responses to therapy). The aim of this review is, therefore, to evaluate the role of the interplay of factors such as age, gender, and hormones in influencing the natural history of chronic liver disease before and after LT and their importance in determining outcomes after LT. As the population requiring LT ages and the mean age at transplantation increases, older females are being considered for transplantation. Older patients are at greater risk for nonalcoholic steatohepatitis, osteoporosis, and a worse response to antiviral therapy. Female gender per se is associated with a greater risk for osteoporosis because of metabolic changes after menopause, the bodily structure of females, and, in the population of patients with chronic liver disease, the greater prevalence of cholestatic and autoimmune liver diseases. With menopause, the fall of protective estrogen levels can lead to increased fibrosis progression, and this represents a negative turning point for women with chronic liver disease and especially for patients with hepatitis C. Therefore, the notion of gender as a binary female/male factor is now giving way to the awareness of more complex disease processes within the female gender that follow hormonal, social, and age patterns and need to be addressed directly and specifically. Copyright © 2012 American Association for the Study of Liver Diseases.

Risk of Incident Liver Disease in Patients with Psoriasis, Psoriatic Arthritis, and Rheumatoid Arthritis: A Population-Based Study.

PubMed

Ogdie, Alexis; Grewal, Sungat K; Noe, Megan H; Shin, Daniel B; Takeshita, Junko; Chiesa Fuxench, Zelma C; Carr, Rotonya M; Gelfand, Joel M

2018-04-01

Relatively little is known about the risk for incident liver disease in psoriasis (PsO), psoriatic arthritis (PsA), and rheumatoid arthritis (RA). We performed a cohort study among patients with PsO, PsA, or RA and matched controls in The Health Improvement Network from 1994 to 2014. Outcomes of interest were any liver disease, nonalcoholic fatty liver disease, and cirrhosis (any etiology). Among patients with PsO (N = 197,130), PsA (N = 12,308), RA (N = 54,251), and matched controls (N = 1,279,754), the adjusted hazard ratios for any liver disease were elevated among patients with PsO (without systemic therapy [ST] 1.37; with ST 1.97), PsA (without ST 1.38; with ST 1.67), and RA without an ST (1.49) but not elevated in patients with RA prescribed an ST (0.96). Incident nonalcoholic fatty liver disease was highest in patients with PsO prescribed an ST (2.23) and PsA with an ST (2.11). The risk of cirrhosis was highest among patients with PsO with an ST (2.62) and PsA without an ST (3.15). Additionally, the prevalence of liver disease and cirrhosis increased in a stepwise fashion with increasing body surface area affected by PsO (P for trend <0.001). More so than RA, PsO and PsA are associated with liver disease, particularly nonalcoholic fatty liver disease and cirrhosis, and this was true even among patients without ST exposure. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

High incidence of zinc deficiency among Filipino children with compensated and decompensated liver disease.

PubMed

Umusig-Quitain, Perlina; Gregorio, Germana V

2010-02-01

The role of zinc in the nutrition and growth of children with chronic liver disease is poorly defined. The present study determined the serum zinc levels of children with compensated liver disease (CLD) and decompensated liver disease (DLD) and compared this with healthy children. Zinc levels were also correlated with the severity of liver disease as measured by Child-Pugh scores. The study comprised of 60 children 0-10 years of age with chronic liver disease, defined as CLD (n = 30) if the Child-Pugh score was < 6, and DLD (n = 30) if the Child-Pugh score was > or = 6. Thirty healthy children 0-10 years served as controls. Serum zinc levels were measured by atomic absorption spectrometry. The 90 patients included 30 with CLD (mean age: 4.54 years: 21 boys; mean Child-Pugh score: 5.83), 30 with DLD (mean age: 1.39 years; 17 boys; mean Child-Pugh score: 9.53) and 30 healthy children (mean age: 4.6; 16 boys). Zinc levels of patients with CLD were significantly lower compared with the healthy controls (Mean [standard deviation]: 68.07 [31.55]vs 89.9 [25.9]microg/dL, P = 0.000), but significantly higher compared to the patients with DLD (48.8 [26.8]microg/dL). Correlation studies showed that the higher the Child-Pugh score, the lower the zinc levels (r = -0.460) Children with chronic liver disease, whether in a compensated or decompensated state, had lower serum zinc levels compared with the healthy controls. As the severity of liver disease worsened, the zinc levels decreased. The study suggests that zinc supplementation should constitute part of the micronutrient intake of children with chronic liver disease.

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.

Mild Hypothermia and Acute Kidney Injury in Liver Transplantation

ClinicalTrials.gov

2018-06-18

Cirrhosis; End Stage Liver Disease; Acute Kidney Injury; Liver Transplant; Complications; Chronic Kidney Diseases; Hepatitis c; Hepatitis B; NASH - Nonalcoholic Steatohepatitis; Alcoholic Cirrhosis; Hepatocellular Carcinoma

Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques

PubMed Central

Ewers, Evan C.; Pratt, William D.; Twenhafel, Nancy A.; Shamblin, Joshua; Donnelly, Ginger; Esham, Heather; Wlazlowski, Carly; Johnson, Joshua C.; Botto, Miriam; Hensley, Lisa E.; Goff, Arthur J.

2016-01-01

Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine candidates can only be approved through the FDA animal rule—a mechanism requiring well-characterized animal models in which efficacy would be evaluated. Here, we describe a natural history study where rhesus macaques were surgically implanted with telemetry devices and central venous catheters prior to aerosol exposure with Marburg-Angola virus, enabling continuous physiologic monitoring and blood sampling without anesthesia. After a three to four day incubation period, all animals developed fever, viremia, and lymphopenia before developing tachycardia, tachypnea, elevated liver enzymes, decreased liver function, azotemia, elevated D-dimer levels and elevated pro-inflammatory cytokines suggesting a systemic inflammatory response with organ failure. The final, terminal period began with the onset of sustained hypotension, dehydration progressed with signs of major organ hypoperfusion (hyperlactatemia, acute kidney injury, hypothermia), and ended with euthanasia or death. The most significant pathologic findings were marked infection of the respiratory lymphoid tissue with destruction of the tracheobronchial and mediastinal lymph nodes, and severe diffuse infection in the liver, and splenitis. PMID:27043611

Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques.

PubMed

Ewers, Evan C; Pratt, William D; Twenhafel, Nancy A; Shamblin, Joshua; Donnelly, Ginger; Esham, Heather; Wlazlowski, Carly; Johnson, Joshua C; Botto, Miriam; Hensley, Lisa E; Goff, Arthur J

2016-03-30

Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine candidates can only be approved through the FDA animal rule-a mechanism requiring well-characterized animal models in which efficacy would be evaluated. Here, we describe a natural history study where rhesus macaques were surgically implanted with telemetry devices and central venous catheters prior to aerosol exposure with Marburg-Angola virus, enabling continuous physiologic monitoring and blood sampling without anesthesia. After a three to four day incubation period, all animals developed fever, viremia, and lymphopenia before developing tachycardia, tachypnea, elevated liver enzymes, decreased liver function, azotemia, elevated D-dimer levels and elevated pro-inflammatory cytokines suggesting a systemic inflammatory response with organ failure. The final, terminal period began with the onset of sustained hypotension, dehydration progressed with signs of major organ hypoperfusion (hyperlactatemia, acute kidney injury, hypothermia), and ended with euthanasia or death. The most significant pathologic findings were marked infection of the respiratory lymphoid tissue with destruction of the tracheobronchial and mediastinal lymph nodes, and severe diffuse infection in the liver, and splenitis.

Autoimmune hepatitis in children.

PubMed

Mieli-Vergani, Giorgina; Vergani, Diego

2002-08-01

AIH, ASC, and de novo AIH after liver transplantation are childhood liver diseases of an autoimmune nature. The mode of presentation of AIH in childhood is variable, and the disease should be suspected and excluded in all children presenting with symptoms and signs of prolonged or severe acute liver disease. Although corticosteroids are effective in all types of childhood AIH, patients with LKM1 have a higher frequency of acute hepatic failure and relapse after corticosteroid withdrawal than do patients with ANA/SMA. ASC occurs commonly in the absence of inflammatory bowel disease, requires cholangiography for diagnosis, and improves during corticosteroid therapy. The development of AIH de novo in children who undergo liver transplantation for nonautoimmune liver disease may reflect interference with the maturation of T cells by immunosuppressive drugs.

High-throughput T-cell receptor sequencing across chronic liver diseases reveals distinct disease-associated repertoires.

PubMed

Liaskou, Evaggelia; Klemsdal Henriksen, Eva Kristine; Holm, Kristian; Kaveh, Fatemeh; Hamm, David; Fear, Janine; Viken, Marte K; Hov, Johannes Roksund; Melum, Espen; Robins, Harlan; Olweus, Johanna; Karlsen, Tom H; Hirschfield, Gideon M

2016-05-01

Hepatic T-cell infiltrates and a strong genetic human leukocyte antigen association represent characteristic features of various immune-mediated liver diseases. Conceptually the presence of disease-associated antigens is predicted to be reflected in T-cell receptor (TCR) repertoires. Here, we aimed to determine if disease-associated TCRs could be identified in the nonviral chronic liver diseases primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and alcoholic liver disease (ALD). We performed high-throughput sequencing of the TCRβ chain complementarity-determining region 3 of liver-infiltrating T cells from PSC (n = 20), PBC (n = 10), and ALD (n = 10) patients, alongside genomic human leukocyte antigen typing. The frequency of TCRβ nucleotide sequences was significantly higher in PSC samples (2.53 ± 0.80, mean ± standard error of the mean) compared to PBC samples (1.13 ± 0.17, P < 0.0001) and ALD samples (0.62 ± 0.10, P < 0.0001). An average clonotype overlap of 0.85% was detected among PSC samples, significantly higher compared to the average overlap of 0.77% seen within the PBC (P = 0.024) and ALD groups (0.40%, P < 0.0001). From eight to 42 clonotypes were uniquely detected in each of the three disease groups (≥30% of the respective patient samples). Multiple, unique sequences using different variable family genes encoded the same amino acid clonotypes, providing additional support for antigen-driven selection. In PSC and PBC, disease-associated clonotypes were detected among patients with human leukocyte antigen susceptibility alleles. We demonstrate liver-infiltrating disease-associated clonotypes in all three diseases evaluated, and evidence for antigen-driven clonal expansions. Our findings indicate that differential TCR signatures, as determined by high-throughput sequencing, may represent an imprint of distinctive antigenic repertoires present in the different chronic liver diseases; this thereby opens up the prospect of studying disease-relevant T cells in order to better understand and treat liver disease. © 2015 by the American Association for the Study of Liver Diseases.

Nonalcoholic fatty liver disease - A multisystem disease?

PubMed Central

Mikolasevic, Ivana; Milic, Sandra; Turk Wensveen, Tamara; Grgic, Ivana; Jakopcic, Ivan; Stimac, Davor; Wensveen, Felix; Orlic, Lidija

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians. PMID:27920470

Neurologic Manifestations of Chronic Liver Disease and Liver Cirrhosis.

PubMed

Sureka, Binit; Bansal, Kalpana; Patidar, Yashwant; Rajesh, S; Mukund, Amar; Arora, Ankur

2015-01-01

The normal functioning of brain is intimately as well as intricately interrelated with normal functioning of the liver. Liver plays a critical role of not only providing vital nutrients to the brain but also of detoxifying the splanchnic blood. Compromised liver function leads to insufficient detoxification thus allowing neurotoxins (such as ammonia, manganese, and other chemicals) to enter the cerebral circulation. In addition, portosystemic shunts, which are common accompaniments of advanced liver disease, facilitate free passage of neurotoxins into the cerebral circulation. The problem is compounded further by additional variables such as gastrointestinal tract bleeding, malnutrition, and concurrent renal failure, which are often associated with liver cirrhosis. Neurologic damage in chronic liver disease and liver cirrhosis seems to be multifactorial primarily attributable to the following: brain accumulation of ammonia, manganese, and lactate; altered permeability of the blood-brain barrier; recruitment of monocytes after microglial activation; and neuroinflammation, that is, direct effects of circulating systemic proinflammatory cytokines such as tumor necrosis factor, IL-1β, and IL-6. Radiologist should be aware of the conundrum of neurologic complications that can be encountered in liver disease, which include hepatic encephalopathy, hepatocerebral degeneration, hepatic myelopathy, cirrhosis-related parkinsonism, cerebral infections, hemorrhage, and osmotic demyelination. In addition, neurologic complications can be exclusive to certain disorders, for example, Wilson disease, alcoholism (Wernicke encephalopathy, alcoholic cerebellar degeneration, Marchiafava-Bignami disease, etc). Radiologist should be aware of their varied clinical presentation and radiological appearances as the diagnosis is not always straightforward. Copyright © 2015 Mosby, Inc. All rights reserved.

Current Concepts in Diabetes Mellitus and Chronic Liver Disease: Clinical Outcomes, Hepatitis C Virus Association, and Therapy.

PubMed

García-Compeán, Diego; González-González, José Alberto; Lavalle-González, Fernando Javier; González-Moreno, Emmanuel Irineo; Villarreal-Pérez, Jesús Zacarías; Maldonado-Garza, Héctor J

2016-02-01

Hereditary type 2 diabetes mellitus is a risk factor for chronic liver disease, and ~30 % of patients with liver cirrhosis develop diabetes. Diabetes mellitus has been associated with cirrhotic and non-cirrhotic hepatitis C virus liver infection, can aggravate the course the liver infection, and can induce a lower sustained response to antiviral treatment. Evidences that HCV may induce metabolic and autoimmune disturbances leading to hypobetalipoproteinemia, steatosis, insulin resistance, impaired glucose tolerance, thyroid disease, and gonadal dysfunction have been found. Prospective studies have demonstrated that diabetes increases the risk of liver complications and death in patients with cirrhosis. However, treatment of diabetes in these patients is complex, as antidiabetic drugs can promote hypoglycemia and lactic acidosis. There have been few therapeutic studies evaluating antidiabetic treatments in patients with liver cirrhosis published to date; thus, the optimal treatment for diabetes and the impact of treatment on morbidity and mortality are not clearly known. As numbers of patients with chronic liver disease and diabetes mellitus are increasing, largely because of the global epidemics of obesity and nonalcoholic fatty liver disease, evaluation of treatment options is becoming more important. This review discusses new concepts on hepatogenous diabetes, the diabetes mellitus–hepatitis C virus association, and clinical implications of diabetes mellitus in patients with chronic liver disease. In addition, the effectiveness and safety of old and new antidiabetic drugs, including incretin-based therapies, will be described.

Quality of life in patients with nonalcoholic fatty liver disease in combination with essential hypertension considering taste sensitivity to sodium chloride.

PubMed

Mashura, Hanna Y; Hanych, Taras M; Rishko, Alexander A

2016-01-01

Nonalcoholic fatty liver disease and hypertensive disease - is the most common combination of abnormalities that occur in people suffering from metabolic syndrome. Their combination not only causes concurrent damage of the liver and the heart, caused by common pathogenic beginning, and also mutually complicate the disease course of each other. The leading role in the development of nonalcoholic fatty liver disease belongs to abdominal obesity and insulin resistance, and is seen as a manifestation of liver disease in metabolic syndrome. Genetic predisposition, lifestyle, improper nutrition, including excessive use of sodium chloride, lead to excessive formation of visceral adipose tissue with development of abdominal obesity, which is a likely criterion of insulin resistance. The long course of nonalcoholic fatty liver disease in combination with essential hypertension in excessive consumption of sodium chloride may negatively affect their quality of life. The aim of the study is to find out the features of quality of life in patients with nonalcoholic fatty liver disease in combination with hypertensive disease with different taste sensitivity to sodium chloride. We have investigated the quality of life of 65 patients with nonalcoholic fatty liver disease in combination with hypertensive disease II stage with different taste sensitivity to sodium chloride. Salt taste sensitivity threshold to sodium chloride is determined by the method of R. Henkin. Assessment of quality of life was performed using the Ukrainian version of the questionnaire Medical Outcomes Study Short Form 36 (MO S SF-36). Was revealed that in patients with nonalcoholic fatty liver disease in combination with hypertensive disease II stage with high salt taste sensitivity threshold observed the decline in the quality of life that manifests as a decline in physical condition (especially of the physical functioning, physical role functioning and general health perceptions) and mental health (especially social functioning). Also the increased salt intake and salt appetite in patients with high salt taste sensitivity threshold were noted (p <0,05). Reducing the use of sodium chloride can be a preventive measure easier than a decrease in body weight, and one that will reduce the body weight, especially in people with nonalcoholic fatty liver disease in combination with hypertensive disease, can reduce the risk of complications and improve quality of life in patients.

Tuberculous spondylodiscitis in a patient with a sickle-cell disease: CT findings.

PubMed

Krupniewski, Leszek; Palczewski, Piotr; Gołębiowski, Marek; Kosińska-Kaczyńska, Katarzyna

2012-01-01

Although sickle-cell anemia (SCA) is common in black Americans, Sub-Saharan Africa and in the Mediterranean area, the disease is rare in the temperate climate zone. The manifestations of the disease are related mainly to the production of abnormal hemoglobin that leads to organ ischemia and increased susceptibility to infection caused by functional asplenia. The authors present CT findings in a 39-year-old black woman diagnosed due to abdominal pain, lymphadenopathy and fever. CT of the thorax and abdomen demonstrated changes in the liver, spleen, and skeletal system suggestive of SCA complicated with spondylodiscitis in the thoracic spine. Hepatomegaly and small calcified spleen are typical findings in older homozygotic patients with SCA. The lesions in the skeleton may be related either to intramedullary hematopoiesis or osteonecrosis and osteomyelitis. In the latter case, diffuse osteosclerosis and H-shaped vertebrae are most typical. Tuberculous spondylodiscitis is characterized by the location in the thoracic region, preferential involvement of anterior elements, relative sparing of intervertebral discs, and cold abscesses.

HFE gene in primary and secondary hepatic iron overload

PubMed Central

Sebastiani, Giada; Walker, Ann P

2007-01-01

Distinct from hereditary haemochromatosis, hepatic iron overload is a common finding in several chronic liver diseases. Many studies have investigated the prevalence, distribution and possible contributory role of excess hepatic iron in non-haemochromatotic chronic liver diseases. Indeed, some authors have proposed iron removal in liver diseases other than hereditary haemochromatosis. However, the pathogenesis of secondary iron overload remains unclear. The High Fe (HFE) gene has been implicated, but the reported data are controversial. In this article, we summarise current concepts regarding the cellular role of the HFE protein in iron homeostasis. We review the current status of the literature regarding the prevalence, hepatic distribution and possible therapeutic implications of iron overload in chronic hepatitis C, hepatitis B, alcoholic and non-alcoholic fatty liver diseases and porphyria cutanea tarda. We discuss the evidence regarding the role of HFE gene mutations in these liver diseases. Finally, we summarize the common and specific features of iron overload in liver diseases other than haemochromatosis. PMID:17729389

Liver cell-targeted delivery of therapeutic molecules.

PubMed

Kang, Jeong-Hun; Toita, Riki; Murata, Masaharu

2016-01-01

The liver is the largest internal organ in mammals and is involved in metabolism, detoxification, synthesis of proteins and lipids, secretion of cytokines and growth factors and immune/inflammatory responses. Hepatitis, alcoholic or non-alcoholic liver disease, hepatocellular carcinoma, hepatic veno-occlusive disease, and liver fibrosis and cirrhosis are the most common liver diseases. Safe and efficient delivery of therapeutic molecules (drugs, genes or proteins) into the liver is very important to increase the clinical efficacy of these molecules and to reduce their side effects in other organs. Several liver cell-targeted delivery systems have been developed and tested in vivo or ex vivo/in vitro. In this review, we discuss the literature concerning liver cell-targeted delivery systems, with a particular emphasis on the results of in vivo studies.

Inhibition of Experimental Liver Cirrhosis in Mice by Telomerase Gene Delivery

NASA Astrophysics Data System (ADS)

Rudolph, Karl Lenhard; Chang, Sandy; Millard, Melissa; Schreiber-Agus, Nicole; DePinho, Ronald A.

2000-02-01

Accelerated telomere loss has been proposed to be a factor leading to end-stage organ failure in chronic diseases of high cellular turnover such as liver cirrhosis. To test this hypothesis directly, telomerase-deficient mice, null for the essential telomerase RNA (mTR) gene, were subjected to genetic, surgical, and chemical ablation of the liver. Telomere dysfunction was associated with defects in liver regeneration and accelerated the development of liver cirrhosis in response to chronic liver injury. Adenoviral delivery of mTR into the livers of mTR-/- mice with short dysfunctional telomeres restored telomerase activity and telomere function, alleviated cirrhotic pathology, and improved liver function. These studies indicate that telomere dysfunction contributes to chronic diseases of continual cellular loss-replacement and encourage the evaluation of ``telomerase therapy'' for such diseases.

Can paracetamol (acetaminophen) be administered to patients with liver impairment?

PubMed Central

Hayward, Kelly L.; Powell, Elizabeth E.; Irvine, Katharine M.

2015-01-01

Although 60 years have passed since it became widely available on the therapeutic market, paracetamol dosage in patients with liver disease remains a controversial subject. Fulminant hepatic failure has been a well documented consequence of paracetamol overdose since its introduction, while short and long term use have both been associated with elevation of liver transaminases, a surrogate marker for acute liver injury. From these reports it has been assumed that paracetamol use should be restricted or the dosage reduced in patients with chronic liver disease. We review the factors that have been purported to increase risk of hepatocellular injury from paracetamol and the pharmacokinetic alterations in different pathologies of chronic liver disease which may affect this risk. We postulate that inadvertent under‐dosing may result in concentrations too low to enable efficacy. Specific research to improve the evidence base for prescribing paracetamol in patients with different aetiologies of chronic liver disease is needed. PMID:26460177

Assessment of fibrotic liver disease with multimodal nonlinear optical microscopy

NASA Astrophysics Data System (ADS)

Lu, Fake; Zheng, Wei; Tai, Dean C. S.; Lin, Jian; Yu, Hanry; Huang, Zhiwei

2010-02-01

Liver fibrosis is the excessive accumulation of extracellular matrix proteins such as collagens, which may result in cirrhosis, liver failure, and portal hypertension. In this study, we apply a multimodal nonlinear optical microscopy platform developed to investigate the fibrotic liver diseases in rat models established by performing bile duct ligation (BDL) surgery. The three nonlinear microscopy imaging modalities are implemented on the same sectioned tissues of diseased model sequentially: i.e., second harmonic generation (SHG) imaging quantifies the contents of the collagens, the two-photon excitation fluorescence (TPEF) imaging reveals the morphology of hepatic cells, while coherent anti-Stokes Raman scattering (CARS) imaging maps the distributions of fats or lipids quantitatively across the tissue. Our imaging results show that during the development of liver fibrosis (collagens) in BDL model, fatty liver disease also occurs. The aggregated concentrations of collagen and fat constituents in liver fibrosis model show a certain correlationship between each other.

Transient elastography for the diagnosis of liver fibrosis.

PubMed

de Lédinghen, Victor; Vergniol, Julien

2010-11-01

Transient elastography (FibroScan(®)) is a noninvasive method proposed for the assessment of liver fibrosis in patients with chronic liver diseases by measuring liver stiffness. It can be easily performed at the bedside or in the outpatient clinic with immediate results and good reproducibility. FibroScan is validated for the diagnosis of significant fibrosis and cirrhosis in chronic hepatitis C, in recurrence of hepatitis C after liver transplantation, in co-infected HIV-HCV patients, in chronic hepatitis B, in chronic cholestatic diseases, in alcoholic disease and in nonalcoholic fatty liver disease. FibroScan is an excellent tool for the early detection of cirrhosis and for the evaluation of portal hypertension, and may have prognostic value in this setting. FibroScan evaluates liver stiffness, which is related to fibrosis, but also inflammation and portal hypertension. Therefore, FibroScan values have to be interpreted according to clinical, biological and morphological data.

Altered plasma lipidome profile of dairy cows with fatty liver disease.

PubMed

Gerspach, C; Imhasly, S; Gubler, M; Naegeli, H; Ruetten, M; Laczko, E

2017-02-01

Fatty liver disease is a common health problem of dairy cows occurring during the transition from pregnancy to lactation. It is a direct response to fat mobilization due to negative energy balance. Accumulation of lipids in the liver occurs if the uptake of non-esterified fatty acids by the liver exceeds the capacity of lipid oxidation or secretion by the liver. Currently, the diagnosis of fatty liver disease requires confirmation through biopsies to determine the hepatic lipid content. In view of this lack of a practical diagnostic tool, we compared the plasma lipidome of diseased dairy cows using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Multivariate data analysis yielded 20 m/z values that were able to distinguish between dairy cows with no hepatic lipidosis and those exhibiting different stages of the disease. Based on the chromatography retention time and m/z ratios, we identified phosphatidylcholines with reduced plasma abundances in cows with fatty liver disease. The abundances of different bile acids tended to be increased. In addition, we detected two metabolites related to inflammation, resolvin E1 and palmitoyl-ethanolamine (PEA), which need to be further investigated in cattle. These results indicate that the measurement of specific representatives of phosphatidylcholines in plasma may provide a novel diagnostic biomarker of fatty liver disease in dairy cows. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intestinal fungi contribute to development of alcoholic liver disease.

PubMed

Yang, An-Ming; Inamine, Tatsuo; Hochrath, Katrin; Chen, Peng; Wang, Lirui; Llorente, Cristina; Bluemel, Sena; Hartmann, Phillipp; Xu, Jun; Koyama, Yukinori; Kisseleva, Tatiana; Torralba, Manolito G; Moncera, Kelvin; Beeri, Karen; Chen, Chien-Sheng; Freese, Kim; Hellerbrand, Claus; Lee, Serene Ml; Hoffman, Hal M; Mehal, Wajahat Z; Garcia-Tsao, Guadalupe; Mutlu, Ece A; Keshavarzian, Ali; Brown, Gordon D; Ho, Samuel B; Bataller, Ramon; Stärkel, Peter; Fouts, Derrick E; Schnabl, Bernd

2017-06-30

Chronic liver disease with cirrhosis is the 12th leading cause of death in the United States, and alcoholic liver disease accounts for approximately half of all cirrhosis deaths. Chronic alcohol consumption is associated with intestinal bacterial dysbiosis, yet we understand little about the contribution of intestinal fungi, or mycobiota, to alcoholic liver disease. Here we have demonstrated that chronic alcohol administration increases mycobiota populations and translocation of fungal β-glucan into systemic circulation in mice. Treating mice with antifungal agents reduced intestinal fungal overgrowth, decreased β-glucan translocation, and ameliorated ethanol-induced liver disease. Using bone marrow chimeric mice, we found that β-glucan induces liver inflammation via the C-type lectin-like receptor CLEC7A on Kupffer cells and possibly other bone marrow-derived cells. Subsequent increases in IL-1β expression and secretion contributed to hepatocyte damage and promoted development of ethanol-induced liver disease. We observed that alcohol-dependent patients displayed reduced intestinal fungal diversity and Candida overgrowth. Compared with healthy individuals and patients with non-alcohol-related cirrhosis, alcoholic cirrhosis patients had increased systemic exposure and immune response to mycobiota. Moreover, the levels of extraintestinal exposure and immune response correlated with mortality. Thus, chronic alcohol consumption is associated with an altered mycobiota and translocation of fungal products. Manipulating the intestinal mycobiome might be an effective strategy for attenuating alcohol-related liver disease.

Stratifying the risks of oral anticoagulation in patients with liver disease.

PubMed

Efird, Lydia M; Mishkin, Daniel S; Berlowitz, Dan R; Ash, Arlene S; Hylek, Elaine M; Ozonoff, Al; Reisman, Joel I; Zhao, Shibei; Jasuja, Guneet K; Rose, Adam J

2014-05-01

Chronic liver disease presents a relative contraindication to warfarin therapy, but some patients with liver disease nevertheless require long-term anticoagulation. The goal is to identify which patients with liver disease might safely receive warfarin. Among 102 134 patients who received warfarin from the Veterans Affairs from 2007 to 2008, International Classification of Diseases-Ninth Revision codes identified 1763 patients with chronic liver disease. Specific diagnoses and laboratory values (albumin, aspartate aminotransferase, alanine aminotransferase, creatinine, and cholesterol) were examined to identify risk of adverse outcomes, while controlling for available bleeding risk factors. Outcomes included percent time in therapeutic range, a measure of anticoagulation control, and major hemorrhagic events, by International Classification of Diseases-Ninth Revision codes. Patients with liver disease had lower mean time in therapeutic range (53.5%) when compared with patients without (61.7%; P<0.001) and more hemorrhages (hazard ratio, 2.02; P<0.001). Among patients with liver disease, serum albumin and creatinine levels were the strongest predictors of both outcomes. We created a 4-point score system: patients received 1 point each for albumin (2.5-3.49 g/dL) or creatinine (1.01-1.99 mg/dL), and 2 points each for albumin (<2.5 g/dL) or creatinine (≥2 mg/dL). This score predicted both anticoagulation control and hemorrhage. When compared with patients without liver disease, those with a score of zero had modestly lower time in therapeutic range (56.7%) and no increase in hemorrhages (hazard ratio, 1.16; P=0.59), whereas those with the worst score (4) had poor control (29.4%) and high hazard of hemorrhage (hazard ratio, 8.53; P<0.001). Patients with liver disease receiving warfarin have poorer anticoagulation control and more hemorrhages. A simple 4-point scoring system using albumin and creatinine identifies those at risk for poor outcomes. © 2014 American Heart Association, Inc.

Extrahepatic Diseases and NAFLD: The Triangular Relationship between NAFLD, Type 2-Diabetes and Dysbiosis.

PubMed

Scorletti, Eleonora; Byrne, Christopher D

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases from simple steatosis with hepatic lipid accumulation to end-stage liver disease with decompensated cirrhosis, liver failure and hepatocellular carcinoma. Recent data from the USA showed that in 2013, NAFLD was the second most frequent indication for liver transplantation behind hepatitis C. Since there are now effective treatments for hepatitis C and there is currently no licensed treatment for NAFLD, it has been predicted that over the next 10-15 years, NAFLD will replace hepatitis C as the most frequent indication for liver transplantation. Besides, increasing the risk of hepatocellular carcinoma and end-stage liver disease, it has recently become clear that NAFLD also increases risk of extrahepatic diseases such as type 2 diabetes mellitus (T2DM), cardiovascular disease, cardiac diseases and chronic kidney disease, to name but a few. Of each of these extrahepatic diseases, the evidence to date suggests that NAFLD is a strong risk factor for T2DM. When NAFLD occurs in combination with obesity and insulin resistance (as it frequently does), there is a marked increase in risk of incident T2DM with possible synergism occurring between liver fat accumulation, insulin resistance and obesity to further increase risk of development of T2DM. Thus, there is a reciprocal relationship between NAFLD as a risk factor for T2DM, and T2DM as a risk factor for liver disease progression in NAFLD. Moreover, recent evidence now points to the importance of perturbation of the intestinal microbiota (dysbiosis) in both T2DM and NAFLD. Consequently, there is a triangular relationship between dysbiosis and T2DM and NAFLD. This review will focus on T2DM as a key extrahepatic complication of NAFLD and will describe and discuss the triangular relationship between dysbiosis and T2DM and NAFLD and the factors and potential mechanisms underpinning this relationship. © 2016 S. Karger AG, Basel.

Chronic Liver Disease in the Hispanic Population of the United States

PubMed Central

Carrion, Andres F.; Ghanta, Ravi; Carrasquillo, Olveen; Martin, Paul

2014-01-01

Chronic liver disease is a major cause of morbidity and mortality among Hispanic people living in the United States. Environmental, genetic, and behavioral factors, as well as socioeconomic and health care disparities among this ethnic group have emerged as important public health concerns. We review the epidemiology, natural history, and response to therapy of chronic liver disease in Hispanic patients. The review covers nonalcoholic fatty liver disease, viral hepatitis B and C, coinfection of viral hepatitis with human immunodeficiency virus, alcoholic cirrhosis, hepatocellular carcinoma, autoimmune hepatitis, and primary biliary cirrhosis. For most of these disorders, the Hispanic population has a higher incidence and more aggressive pattern of disease and overall worse treatment outcomes than in the non-Hispanic white population. Clinicians should be aware of these differences in caring for Hispanic patients with chronic liver disease. PMID:21628000

Prediction of liver disease in patients whose liver function tests have been checked in primary care: model development and validation using population-based observational cohorts.

PubMed

McLernon, David J; Donnan, Peter T; Sullivan, Frank M; Roderick, Paul; Rosenberg, William M; Ryder, Steve D; Dillon, John F

2014-06-02

To derive and validate a clinical prediction model to estimate the risk of liver disease diagnosis following liver function tests (LFTs) and to convert the model to a simplified scoring tool for use in primary care. Population-based observational cohort study of patients in Tayside Scotland identified as having their LFTs performed in primary care and followed for 2 years. Biochemistry data were linked to secondary care, prescriptions and mortality data to ascertain baseline characteristics of the derivation cohort. A separate validation cohort was obtained from 19 general practices across the rest of Scotland to externally validate the final model. Primary care, Tayside, Scotland. Derivation cohort: LFT results from 310 511 patients. After exclusions (including: patients under 16 years, patients having initial LFTs measured in secondary care, bilirubin >35 μmol/L, liver complications within 6 weeks and history of a liver condition), the derivation cohort contained 95 977 patients with no clinically apparent liver condition. Validation cohort: after exclusions, this cohort contained 11 653 patients. Diagnosis of a liver condition within 2 years. From the derivation cohort (n=95 977), 481 (0.5%) were diagnosed with a liver disease. The model showed good discrimination (C-statistic=0.78). Given the low prevalence of liver disease, the negative predictive values were high. Positive predictive values were low but rose to 20-30% for high-risk patients. This study successfully developed and validated a clinical prediction model and subsequent scoring tool, the Algorithm for Liver Function Investigations (ALFI), which can predict liver disease risk in patients with no clinically obvious liver disease who had their initial LFTs taken in primary care. ALFI can help general practitioners focus referral on a small subset of patients with higher predicted risk while continuing to address modifiable liver disease risk factors in those at lower 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.

Anesthetic management in pediatric orthotopic liver transplant for fulminant hepatic failure and end-stage liver disease.

PubMed

Camkıran, Aynur; Araz, Coşkun; Seyhan Ballı, Sevgi; Torgay, Adnan; Moray, Gökhan; Pirat, Arash; Arslan, Gülnaz; Haberal, Mehmet

2014-03-01

We assessed the anesthetic management and short-term morbidity and mortality in pediatrics patients who underwent an orthotopic liver transplant for fulminant hepatic failure or end-stage liver disease in a university hospital. We retrospectively analyzed the records of children who underwent orthotopic liver transplant from May 2002 to May 2012. Patients were categorized into 2 groups: group fulminant hepatic failure (n=22) and group end-stage liver disease (n=19). Perioperative data related to anesthetic management and intraoperative events were collected along with information related to postoperative course and survival to hospital discharge. Mean age and weight for groups fulminant hepatic failure and end-stage liver disease were 8.6 ± 2.7 years and 10.8 ± 3.8 years (P = .04) and 29.2 ± 11.9 kg and 33.7 ± 16.9 kg (P = .46). There were no differences between the groups regarding length of anhepatic phase (65 ± 21 min vs 73 ± 18 min, P = .13) and operation time (9.1 ± 1.6 h vs 9.5 ± 1.8 h, P = .23). When compared with the patients in group fulminant hepatic failure, those in group end-stage liver disease more commonly had a Glasgow Coma score of 7 or less (32% vs 6%, P = .04). Compared with patients in group fulminant hepatic failure, those in group end-stage liver disease were more frequently extubated in the operating room (31.8% versus 89.5% P < .001). Postoperative duration of mechanical ventilation (2.78 ± 4.02 d vs 2.85 ± 10.21 d, P = .05), and the mortality rates at 1 year after orthotopic liver transplant (7.3% vs 0%, P = .09) were similar between the groups. During pediatric orthotopic liver transplant, those children with fulminant hepatic failure require more intraoperative fluids and more frequent perioperative mechanical ventilation than those with end-stage liver disease.

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

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.

Ammonia toxicity: from head to toe?

PubMed

Dasarathy, Srinivasan; Mookerjee, Rajeshwar P; Rackayova, Veronika; Rangroo Thrane, Vinita; Vairappan, Balasubramaniyan; Ott, Peter; Rose, Christopher F

2017-04-01

Ammonia is diffused and transported across all plasma membranes. This entails that hyperammonemia leads to an increase in ammonia in all organs and tissues. It is known that the toxic ramifications of ammonia primarily touch the brain and cause neurological impairment. However, the deleterious effects of ammonia are not specific to the brain, as the direct effect of increased ammonia (change in pH, membrane potential, metabolism) can occur in any type of cell. Therefore, in the setting of chronic liver disease where multi-organ dysfunction is common, the role of ammonia, only as neurotoxin, is challenged. This review provides insights and evidence that increased ammonia can disturb many organ and cell types and hence lead to dysfunction.

Real-time temperature monitoring with fiber Bragg grating sensor during diffuser-assisted laser-induced interstitial thermotherapy.

PubMed

Pham, Ngot Thi; Lee, Seul Lee; Park, Suhyun; Lee, Yong Wook; Kang, Hyun Wook

2017-04-01

High-sensitivity temperature sensors have been used to validate real-time thermal responses in tissue during photothermal treatment. The objective of the current study was to evaluate the feasible application of a fiber Bragg grating (FBG) sensor for diffuser-assisted laser-induced interstitial thermotherapy (LITT) particularly to treat tubular tissue disease. A 600 - ? m core-diameter diffuser was employed to deliver 980-nm laser light for coagulation treatment. Both a thermocouple and a FBG were comparatively tested to evaluate temperature measurements in ex vivo liver tissue. The degree of tissue denaturation was estimated as a function of irradiation times and quantitatively compared with light distribution as well as temperature development. At the closer distance to a heat source, the thermocouple measured up to 41% higher maximum temperature than the FBG sensor did after 120-s irradiation (i.e., 98.7 ° C ± 6.1 ° C for FBG versus 131.0 ° C ± 5.1 ° C for thermocouple; p < 0.001 ). Ex vivo porcine urethra tests confirmed the real-time temperature measurements of the FBG sensor as well as consistently circumferential tissue denaturation after 72-s irradiation ( coagulation thickness = 2.2 ± 0.3 ?? mm ). The implementation of FBG can be a feasible sensing technique to instantaneously monitor the temperature developments during diffuser-assisted LITT for treatment of tubular tissue structure.

Diffusion-weighted imaging in pediatric body MR imaging: principles, technique, and emerging applications.

PubMed

Chavhan, Govind B; Alsabban, Zehour; Babyn, Paul S

2014-01-01

Diffusion-weighted (DW) imaging is an emerging technique in body imaging that provides indirect information about the microenvironment of tissues and lesions and helps detect, characterize, and follow up abnormalities. Two main challenges in the application of DW imaging to body imaging are the decreased signal-to-noise ratio of body tissues compared with neuronal tissues due to their shorter T2 relaxation time, and image degradation related to physiologic motion (eg, respiratory motion). Use of smaller b values and newer motion compensation techniques allow the evaluation of anatomic structures with DW imaging. DW imaging can be performed as a breath-hold sequence or a free-breathing sequence with or without respiratory triggering. Depending on the mobility of water molecules in their microenvironment, different normal tissues have different signals at DW imaging. Some normal tissues (eg, lymph nodes, spleen, ovarian and testicular parenchyma) are diffusion restricted, whereas others (eg, gallbladder, corpora cavernosa, endometrium, cartilage) show T2 shine-through. Epiphyses that contain fatty marrow and bone cortex appear dark on both DW images and apparent diffusion coefficient maps. Current and emerging applications of DW imaging in pediatric body imaging include tumor detection and characterization, assessment of therapy response and monitoring of tumors, noninvasive detection and grading of liver fibrosis and cirrhosis, detection of abscesses, and evaluation of inflammatory bowel disease. RSNA, 2014

Autoimmune Hepatitis

MedlinePlus

... Living with a Liver Transplant Clinical Trials Nonalcoholic Fatty Liver Disease & NASH Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Nonalcoholic Fatty Liver Disease & NASH in Children Definition & Facts Symptoms & Causes ...

The Association Between Liver and Tumor [18F]FDG Uptake in Patients with Diffuse Large B Cell Lymphoma During Chemotherapy.

PubMed

Wu, Xingchen; Bhattarai, Abhisek; Korkola, Pasi; Pertovaara, Hannu; Eskola, Hannu; Kellokumpu-Lehtinen, Pirkko-Liisa

2017-10-01

The aim of this study was to explore the association between liver, mediastinum and tumor 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) uptake during chemotherapy in diffuse large B cell lymphoma (DLBCL). Nineteen patients with proven DLBCL underwent positron emission tomography (PET)/X-ray computed tomography scan at baseline, 1 week and 2 cycles after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy, and again after chemotherapy completion. The mean and maximal standardized uptake value (SUVmean and SUVmax) of the liver and mediastinum were measured and correlated with the tumor SUVmax, SUVsum, whole-body metabolic tumor volume (MTVwb), and total lesion glycolysis (TLG). At baseline, both the liver and mediastinum SUVmean and SUVmax correlated inversely with the tumor MTVwb or TLG (p < 0.01 or 0.001). The liver SUVmean and SUVmax increased significantly after 1 week of R-CHOP therapy and remained at the high level until chemotherapy completion. The mediastinum SUVmean and SUVmax remained stable during chemotherapy. The tumor SUVmax, SUVsum, MTVwb, and TLG decreased significantly after 1 week of R-CHOP therapy. The change of the liver SUVmean correlated inversely with the change of tumor MTVwb and TLG after 1 week of chemotherapy (p < 0.05, respectively). The intersubject variability of liver and mediastinum [ 18 F]FDG uptake ranged from 11 to 26 %. The liver [ 18 F]FDG uptake increased significantly after R-CHOP therapy. One of the possible reasons is the distribution of a greater fraction of the tracer to healthy tissues rather than tumor after effective chemotherapy. The variability of the liver [ 18 F]FDG uptake during chemotherapy might affect the visual analysis of the interim PET scan and this needs to be confirmed in future studies with a large patient cohort. In addition, the intersubject variability of the liver and mediastinum [ 18 F]FDG uptake should be considered.

Effect of ultrasound frequency on the Nakagami statistics of human liver tissues.

PubMed

Tsui, Po-Hsiang; Zhou, Zhuhuang; Lin, Ying-Hsiu; Hung, Chieh-Ming; Chung, Shih-Jou; Wan, Yung-Liang

2017-01-01

The analysis of the backscattered statistics using the Nakagami parameter is an emerging ultrasound technique for assessing hepatic steatosis and fibrosis. Previous studies indicated that the echo amplitude distribution of a normal liver follows the Rayleigh distribution (the Nakagami parameter m is close to 1). However, using different frequencies may change the backscattered statistics of normal livers. This study explored the frequency dependence of the backscattered statistics in human livers and then discussed the sources of ultrasound scattering in the liver. A total of 30 healthy participants were enrolled to undergo a standard care ultrasound examination on the liver, which is a natural model containing diffuse and coherent scatterers. The liver of each volunteer was scanned from the right intercostal view to obtain image raw data at different central frequencies ranging from 2 to 3.5 MHz. Phantoms with diffuse scatterers only were also made to perform ultrasound scanning using the same protocol for comparisons with clinical data. The Nakagami parameter-frequency correlation was evaluated using Pearson correlation analysis. The median and interquartile range of the Nakagami parameter obtained from livers was 1.00 (0.98-1.05) for 2 MHz, 0.93 (0.89-0.98) for 2.3 MHz, 0.87 (0.84-0.92) for 2.5 MHz, 0.82 (0.77-0.88) for 3.3 MHz, and 0.81 (0.76-0.88) for 3.5 MHz. The Nakagami parameter decreased with the increasing central frequency (r = -0.67, p < 0.0001). However, the effect of ultrasound frequency on the statistical distribution of the backscattered envelopes was not found in the phantom results (r = -0.147, p = 0.0727). The current results demonstrated that the backscattered statistics of normal livers is frequency-dependent. Moreover, the coherent scatterers may be the primary factor to dominate the frequency dependence of the backscattered statistics in a liver.

[Non-alcoholic fatty liver disease, as a component of the metabolic syndrome, and its causal correlations with other extrahepatic diseases].

PubMed

Halmos, Tamás; Suba, Ilona

2017-12-01

Non-alcoholic fatty liver disease is the most common non-infectious chronic liver-disease in our age, and is a spectrum of all the diseases associated with increased fat accumulation in the hepatocytes. Its development is promoted by sedentary life-style, over-feeding, and certain genetic predisposition. Prevalence in the adult population, even in Hungary is ~30%. In a part of cases, this disease may pass into non-alcoholic steatohepatitis, later into fibrosis, rarely into primary hepatocellular cancer. Fatty liver is closely and bidirectionally related to the metabolic syndrome and type 2 diabetes, and nowadays there is a general consensus that fatty liver is the hepatic manifestation of the metabolic sycndrome. The importance of the fatty liver has been highly emphasized recently. In addition to the progression into steatohepatitis, its causal relationship with numerous extrahepatic disorders has been discovered. In our overview, we deal with the epidemiology, pathomechanism of the disease, discuss the possibilities of diagnosis, its relationship with the intestinal microbiota, its recently recognized correlations with bile acids and their receptors, and its supposed correlations with the circadian CLOCK system. Hereinafter, we overview those extrahepatic disorders, which have been shown to be causal link with the non-alcoholic fatty liver disease. Among these, we emphasize the metabolic syndrome/type 2 diabetes, cardiovascular disorders, chronic kidney disease, sleep apnea/hypoventilation syndrome, inflammatory bowel disease, Alzheimer's disease, osteoporosis, and psoriasis, as well. Based on the above, it can be stated, that high risk individuals with non-alcoholic fatty liver disease need systemic care, and require the detection of other components of this systemic pathological condition. While currently specific therapy for the disease is not yet known, life-style changes, adequate use of available medicines can prevent disease progression. Promising research is under way, including drugs, manipulation of the intestinal flora or the possibility of therapeutic use of bile acid receptors, and also bariatric surgery. Orv Hetil. 2017; 158(52): 2051-2061.

Examination of the Spatial Correlation of Statistics Information in the Ultrasonic Echo from Diseased Liver

NASA Astrophysics Data System (ADS)

Yamaguchi, Tadashi; Hachiya, Hiroyuki; Kamiyama, Naohisa; Moriyasu, Fuminori

2002-05-01

To realize a quantitative diagnosis of liver cirrhosis, we have been analyzing the characteristics of echo amplitude in B-mode images. Realizing the distinction between liver diseases such as liver cirrhosis and chronic hepatitis is required in the field of medical ultrasonics. In this study, we examine the spatial correlation, with the coefficient of correlation between the frames and the amplitude characteristics of each frame, using the volumetric data of RF echo signals from normal and diseased liver. It is found that there is a relationship between the tissue structure of liver and the spatial correlation of echo information.

Magnetic resonance imaging and transient elastography in the management of Nonalcoholic Fatty Liver Disease (NAFLD).

PubMed

Han, Ma Ai Thanda; Saouaf, Rola; Ayoub, Walid; Todo, Tsuyoshi; Mena, Edward; Noureddin, Mazen

2017-04-01

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and cirrhosis worldwide and the second most common cause of liver transplantation in major medical centers. Because liver steatosis and fibrosis severity are related to disease morbidity and mortality, the extent of disease, and disease progression, they need to be assessed and monitored. In addition, innovation with new drug developments requires disease staging and monitoring in both phase 2 and 3 clinical trials. Currently, disease assessment in both clinical practice and research is mostly performed by liver biopsy, an invasive, procedure with risks. Noninvasive, highly accurate tests are needed that could be used in clinical trials as surrogate endpoints and in clinical practice for monitoring patients. Area Covered: We discuss noninvasive tests, transient elastography (TE) with controlled attenuation parameter (CAP), magnetic resonance imaging (MRI), and MR elastography (MRE), summarize the available evidence of their usefulness for assessing steatosis and fibrosis. Therefore they could be used as clinical trials outcomes and in disease monitoring in clinical practice. Expert Commentary: TE with CAP, MRI and MRE are highly accurate noninvasive diagnostic tools for quantifying hepatic steatosis and fibrosis. Therefore they could be used as clinical trials outcomes and in disease monitoring in clinical practice.

Liver Transplant: Nutrition

MedlinePlus

... transplant and liver disease patients. Pre-Transplant Protein Malnutrition -- Many patients with end stage liver disease do ... to lose weight sensibly and slowly, without causing malnutrition (especially protein malnutrition). Losing excess weight decreases the ...

Relationship of liver stiffness and controlled attenuation parameter measured by transient elastography with diabetes mellitus in patients with chronic liver disease.

PubMed

Ahn, Jem Ma; Paik, Yong-Han; Kim, So Hyun; Lee, Jun Hee; Cho, Ju Yeon; Sohn, Won; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul

2014-08-01

High prevalence of diabetes mellitus in patients with liver cirrhosis has been reported in many studies. The aim of our study was to evaluate the relationship of hepatic fibrosis and steatosis assessed by transient elastography with diabetes in patients with chronic liver disease. The study population consisted of 979 chronic liver disease patients. Liver fibrosis and steatosis were assessed by liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) on transient elastography. Diabetes was diagnosed in 165 (16.9%) of 979 patients. The prevalence of diabetes had significant difference among the etiologies of chronic liver disease. Higher degrees of liver fibrosis and steatosis, assessed by LSM and CAP score, showed higher prevalence of diabetes (F0/1 [14%], F2/3 [18%], F4 [31%], P<0.001; S0/1 [15%], S2 [17%], S3 [26%], P=0.021). Multivariate analysis showed that the independent predictive risk factors for diabetes were hypertension (OR, 1.98; P=0.001), LSM F4 (OR, 1.86; P=0.010), male gender (OR, 1.60; P=0.027), and age>50 yr (OR, 1.52; P=0.046). The degree of hepatic fibrosis but not steatosis assessed by transient elastography has significant relationship with the prevalence of diabetes in patients with chronic liver disease.

Effects of fatty infiltration in human livers on the backscattered statistics of ultrasound imaging.

PubMed

Wan, Yung-Liang; Tai, Dar-In; Ma, Hsiang-Yang; Chiang, Bing-Hao; Chen, Chin-Kuo; Tsui, Po-Hsiang

2015-06-01

Ultrasound imaging has been widely applied to screen fatty liver disease. Fatty liver disease is a condition where large vacuoles of triglyceride fat accumulate in liver cells, thereby altering the arrangement of scatterers and the corresponding backscattered statistics. In this study, we used ultrasound Nakagami imaging to explore the effects of fatty infiltration in human livers on the statistical distribution of backscattered signals. A total of 107 patients volunteered to participate in the experiments. The livers were scanned using a clinical ultrasound scanner to obtain the raw backscattered signals for ultrasound B-mode and Nakagami imaging. Clinical scores of fatty liver disease for each patient were determined according to a well-accepted sonographic scoring system. The results showed that the Nakagami image can visualize the local backscattering properties of liver tissues. The Nakagami parameter increased from 0.62 ± 0.11 to 1.02 ± 0.07 as the fatty liver disease stage increased from normal to severe, indicating that the backscattered statistics vary from pre-Rayleigh to Rayleigh distributions. A significant positive correlation (correlation coefficient ρ = 0.84; probability value (p value) < 0.0001) exists between the degree of fatty infiltration and the Nakagami parameter, suggesting that ultrasound Nakagami imaging has potentials in future applications in fatty liver disease diagnosis. © IMechE 2015.

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.

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

Radiographic liver size in Pekingese dogs versus other dog breeds.

PubMed

Choi, Jihye; Keh, Seoyeon; Kim, Hyunwook; Kim, Junyoung; Yoon, Junghee

2013-01-01

Differential diagnoses for canine liver disease are commonly based on radiographic estimates of liver size, however little has been published on breed variations. Aims of this study were to describe normal radiographic liver size in Pekingese dogs and to compare normal measurements for this breed with other dog breeds and Pekingese dogs with liver disease. Liver measurements were compared for clinically normal Pekingese (n = 61), normal non-Pekingese brachycephalic (n = 45), normal nonbrachycephalic (n = 71), and Pekingese breed dogs with liver disease (n = 22). For each dog, body weight, liver length, T11 vertebral length, thoracic depth, and thoracic width were measured on right lateral and ventrodorsal abdominal radiographs. Liver volume was calculated using a formula and ratios of liver length/T11 vertebral length and liver volume/body weight ratio were determined. Normal Pekingese dogs had a significantly smaller liver volume/body weight ratio (16.73 ± 5.67, P < 0.05) than normal non-Pekingese brachycephalic breed dogs (19.54 ± 5.03) and normal nonbrachycephalic breed dogs (18.72 ± 6.52). The liver length/T11 vertebral length ratio in normal Pekingese (4.64 ± 0.65) was significantly smaller than normal non-Pekingese brachycephalic breed dogs (5.16 ± 0.74) and normal nonbrachycephalic breed dogs (5.40 ± 0.74). Ratios of liver volume/body weight and liver length/T11 vertebral length in normal Pekingese were significantly different from Pekingese with liver diseases (P < 0.05). Findings supported our hypothesis that Pekingese dogs have a smaller normal radiographic liver size than other breeds. We recommend using 4.64× the length of the T11 vertebra as a radiographic criterion for normal liver length in Pekingese dogs. © 2012 Veterinary Radiology & Ultrasound.

Nonalcoholic fatty liver disease and vascular disease: State-of-the-art

PubMed Central

Fargion, Silvia; Porzio, Marianna; Fracanzani, Anna Ludovica

2014-01-01

Nonalcoholic fatty liver disease (NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis (NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis (increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific life-style modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular disease improving overall prognosis and survival. PMID:25309067

Risk of seizures and status epilepticus in older patients with liver disease.

PubMed

Alkhachroum, Ayham M; Rubinos, Clio; Kummer, Benjamin R; Parikh, Neal S; Chen, Monica; Chatterjee, Abhinaba; Reynolds, Alexandra; Merkler, Alexander E; Claassen, Jan; Kamel, Hooman

2018-06-06

Seizures can be provoked by systemic diseases associated with metabolic derangements, but the association between liver disease and seizures remains unclear. We performed a retrospective cohort study using inpatient and outpatient claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. The primary exposure variable was cirrhosis, and the secondary exposure was mild, noncirrhotic liver disease. The primary outcome was seizure, and the secondary outcome was status epilepticus. Diagnoses were ascertained using validated International Classification of Diseases, Ninth Edition, Clinical Modification codes. Survival statistics were used to calculate incidence rates, and Cox proportional hazards models were used to examine the association between exposures and outcomes while adjusting for seizure risk factors. Among 1 782 402 beneficiaries, we identified 10 393 (0.6%) beneficiaries with cirrhosis and 19 557 (1.1%) with mild, noncirrhotic liver disease. Individuals with liver disease were older and had more seizure risk factors than those without liver disease. Over 4.6 ± 2.2 years of follow-up, 49 843 (2.8%) individuals were diagnosed with seizures and 25 patients (0.001%) were diagnosed with status epilepticus. Cirrhosis was not associated with seizures (hazard ratio [HR] = 1.1, 95% confidence interval [CI] = 1.0-1.3), but there was an association with status epilepticus (HR = 1.9, 95% CI = 1.3-2.8). Mild liver disease was not associated with a higher risk of seizures (HR = 0.8, 95% CI = 0.6-0.9) or status epilepticus (HR = 1.1, 95% CI = 0.7-1.5). In a large, population-based cohort, we found an association between cirrhosis and status epilepticus, but no overall association between liver disease and seizures. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Prevalence of liver diseases as referred by people living in the Santos and São Vicente Estuary.

PubMed

Carvalho, Daniele Fernandes Pena; Guimarães, M T; Ribeiro, T S; Campina, N N; Lobarinhas, M R; Lopes, A L J; Cunha, M G; Souza, I B; Oliveira, V L F; Braga E Braga, L; Martins, L C; Gomes, A; Pereira, L A A; Braga, A L F

2015-10-01

The Santos and São Vicente Estuary has suffered extensively over the years from irregular industrial deposits. The present study aimed to evaluate liver disease prevalence and potential associated risk factors in four of the Estuary's areas (Pilões and Água-Fria, Cubatão Center, Continental São Vicente, and Guarujá) and a reference area (Bertioga). This study consisted of a cross-sectional study design, in which a questionnaire was used to collect information in 820 households at each of the study areas. The proportion of total liver diseases, hepatitis, cirrhosis, and cancer (liver, biliary tract, and pancreas) per area were estimated. Pearson's chi-square test and two proportion differences test were applied in order to evaluate associations between disease occurrence and areas and to test differences between two proportions, respectively. Single and multiple logistic regression models were applied to assess associations between disease prevalence and the different study areas. Liver disease prevalence was 1.5 % among all inhabitants and 1.4 % among those without any type of exposure. Among those who reported the presence of liver disease, a higher percentage of the participants that reported hepatitis (27.7 %) or other liver disease (48.7 %) did not report occupational or alcohol exposures. Hepatitis (77.8 %) was the most reported disease, and a statistical association between living in Pilões and Água-Fria and the occurrence of hepatitis was observed (Pearson's χ (2): z = 18.1; p = 0.001). The consumption of locally-produced groceries (2.88; CI: 1.24-6.70) and water (5.88; CI: 2.24-15.45) were shown to be risk factors for the occurrence of liver disease. Thus, environmental exposure is still a public health problem present in the estuary region.

Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease.

PubMed

Targher, Giovanni; Byrne, Christopher D

2017-05-01

Non-alcoholic fatty liver disease (NAFLD) is caused by an accumulation of fat in the liver; the condition can progress over time to increase the risk of developing cirrhosis, end-stage liver disease and hepatocellular carcinoma. The prevalence of NAFLD is increasing rapidly owing to the global epidemics of obesity and type 2 diabetes mellitus (T2DM), and NAFLD has been predicted to become the most important indication for liver transplantation over the next decade. It is now increasingly clear that NAFLD not only affects the liver but can also increase the risk of developing extra-hepatic diseases, including T2DM, cardiovascular disease and chronic kidney disease (CKD), which have a considerable impact on health-care resources. Accumulating evidence indicates that NAFLD exacerbates insulin resistance, predisposes to atherogenic dyslipidaemia and releases a variety of proinflammatory factors, prothrombotic factors and profibrogenic molecules that can promote vascular and renal damage. Furthermore, communication or 'crosstalk' between affected organs or tissues in these diseases has the potential to further harm function and worsen patient outcomes, and increasing amounts of evidence point to a strong association between NAFLD and CKD. Whether a causal relationship between NAFLD and CKD exists remains to be definitively established.

New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases.

PubMed

Ji, Cheng

2014-01-01

Alcohol-induced liver disease increasingly contributes to human mortality worldwide. Alcohol-induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis have recently been established as a significant mechanism contributing to liver diseases. The alcohol-induced ER stress occurs not only in cultured hepatocytes but also  in vivo  in the livers of several species including mouse, rat, minipigs, zebrafish, and humans. Identified causes for the ER stress include acetaldehyde, oxidative stress, impaired one carbon metabolism, toxic lipid species, insulin resistance, disrupted calcium homeostasis, and aberrant epigenetic modifications. Importance of each of the causes in alcohol-induced liver injury depends on doses, duration and patterns of alcohol exposure, genetic disposition, environmental factors, cross-talks with other pathogenic pathways, and stages of liver disease. The ER stress may occur more or less all the time during alcohol consumption, which interferes with hepatic protein homeostasis, proliferation, and cell cycle progression promoting development of advanced liver diseases. Emerging evidence indicates that long-term alcohol consumption and ER stress may directly be involved in hepatocellular carcinogenesis (HCC). Dissecting ER stress signaling pathways leading to tumorigenesis will uncover potential therapeutic targets for intervention and treatment of human alcoholics with liver cancer.

The antiviral drug tenofovir, an inhibitor of Pannexin-1-mediated ATP release, prevents liver and skin fibrosis by downregulating adenosine levels in the liver and skin

PubMed Central

Corciulo, Carmen; Liu, Hailing; Zhang, Jin; Perez-Aso, Miguel; Picard, Laura; Wilder, Tuere

2017-01-01

Background Fibrosing diseases are a leading cause of morbidity and mortality worldwide and, therefore, there is a need for safe and effective antifibrotic therapies. Adenosine, generated extracellularly by the dephosphorylation of adenine nucleotides, ligates specific receptors which play a critical role in development of hepatic and dermal fibrosis. Results of recent clinical trials indicate that tenofovir, a widely used antiviral agent, reverses hepatic fibrosis/cirrhosis in patients with chronic hepatitis B infection. Belonging to the class of acyclic nucleoside phosphonates, tenofovir is an analogue of AMP. We tested the hypothesis that tenofovir has direct antifibrotic effects in vivo by interfering with adenosine pathways of fibrosis using two distinct models of adenosine and A2AR-mediated fibrosis. Methods Thioacetamide (100mg/kg IP)-treated mice were treated with vehicle, or tenofovir (75mg/kg, SubQ) (n = 5–10). Bleomycin (0.25U, SubQ)-treated mice were treated with vehicle or tenofovir (75mg/kg, IP) (n = 5–10). Adenosine levels were determined by HPLC, and ATP release was quantitated as luciferase-dependent bioluminescence. Skin breaking strength was analysed and H&E and picrosirus red-stained slides were imaged. Pannexin-1expression was knocked down following retroviral-mediated expression of of Pannexin-1-specific or scrambled siRNA. Results Treatment of mice with tenofovir diminished adenosine release from the skin of bleomycin-treated mice and the liver of thioacetamide-treated mice, models of diffuse skin fibrosis and hepatic cirrhosis, respectively. More importantly, tenofovir treatment diminished skin and liver fibrosis in these models. Tenofovir diminished extracellular adenosine concentrations by inhibiting, in a dose-dependent fashion, cellular ATP release but not in cells lacking Pannexin-1. Conclusions These studies suggest that tenofovir, a widely used antiviral agent, could be useful in the treatment of fibrosing diseases. PMID:29145453

Prevalence and severity of non-alcoholic fatty liver disease are underestimated in clinical practice: impact of a dedicated screening approach at a large university teaching hospital.

PubMed

Marjot, T; Sbardella, E; Moolla, A; Hazlehurst, J M; Tan, G D; Ainsworth, M; Cobbold, J F L; Tomlinson, J W

2018-01-01

To define the attitudes and current clinical practice of diabetes specialists with regard to non-alcoholic fatty liver disease and, based on the results, implement an evidenced-based pathway for non-alcoholic fatty liver disease assessment. An online survey was disseminated to diabetes specialists. Based on findings from this survey, we sought a local solution by launching an awareness campaign and implementing a screening algorithm across all diabetes clinics at a secondary/tertiary referral centre. A total of 133 diabetes specialists responded to the survey. Fewer than 5% of responders correctly assessed the prevalence and severity of advanced fibrotic non-alcoholic fatty liver disease in people with diabetes as 50-75%. Whilst most clinicians performed liver function tests, only 5.7% responded stating that they would use, or had used, a non-invasive algorithm to stage the severity of non-alcoholic fatty liver disease. Implementing a local non-alcoholic fatty liver disease awareness campaign and screening strategy using pre-printed blood request forms, we ensured that 100% (n=395) of all people with Type 1 and Type 2 diabetes mellitus attending secondary/tertiary care diabetes clinics over a 6-month period were appropriately screened for advanced fibrotic non-alcoholic fatty liver disease using the Fib-4 index; 17.9% required further investigation or assessment. The prevalence and severity of non-alcoholic fatty liver disease are underestimated among diabetes specialists. The Fib-4 index can easily be incorporated into clinical practice in secondary/tertiary care to identify those individuals at risk of advanced fibrosis who require further assessment and who may benefit from a dedicated multidisciplinary approach to their management. © 2017 Diabetes UK.

Gut microbiota and hepatitis-B-virus-induced chronic liver disease: implications for faecal microbiota transplantation therapy.

PubMed

Kang, Y; Cai, Y

2017-08-01

Hepatitis B is one of the most common infectious diseases globally. It has been estimated that there are 350 million chronic hepatitis B virus (HBV) carriers worldwide. The liver is connected to the small intestine by the bile duct, which carries bile formed in the liver to the intestine. Nearly all of the blood that leaves the stomach and intestines must pass through the liver. Human intestines contain a wide diversity of microbes, collectively termed the 'gut microbiota'. Gut microbiota play a significant role in host metabolic processes and host immune modulation, and influence host development and physiology (organ development). Altered gut microbiota is a common complication in liver disease. Changes in intestinal microbiota seem to play an important role in induction and promotion of HBV-induced chronic liver disease progression, and specific species among the intestinal commensal bacteria may play either a pathogenic or a protective role in the development of HBV-induced chronic liver disease. Thus, the gut microbiome may represent fertile targets for prevention or management of HBV-induced chronic liver disease. Faecal microbiota transplantation (FMT) may be a useful therapy for HBV-related disease in the future. However, the data available in this field remain limited, and relevant scientific work has only just commenced. New technologies have enabled systematic studies of gut microbiota, and provided more realistic information about its composition and pathological variance. This review summarizes the cutting edge of research into the relationship between gut microbiota and HBV-induced chronic liver disease, and the future prospects of FMT therapy. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

How predictive quantitative modelling of tissue organisation can inform liver disease pathogenesis.

PubMed

Drasdo, Dirk; Hoehme, Stefan; Hengstler, Jan G

2014-10-01

From the more than 100 liver diseases described, many of those with high incidence rates manifest themselves by histopathological changes, such as hepatitis, alcoholic liver disease, fatty liver disease, fibrosis, and, in its later stages, cirrhosis, hepatocellular carcinoma, primary biliary cirrhosis and other disorders. Studies of disease pathogeneses are largely based on integrating -omics data pooled from cells at different locations with spatial information from stained liver structures in animal models. Even though this has led to significant insights, the complexity of interactions as well as the involvement of processes at many different time and length scales constrains the possibility to condense disease processes in illustrations, schemes and tables. The combination of modern imaging modalities with image processing and analysis, and mathematical models opens up a promising new approach towards a quantitative understanding of pathologies and of disease processes. This strategy is discussed for two examples, ammonia metabolism after drug-induced acute liver damage, and the recovery of liver mass as well as architecture during the subsequent regeneration process. This interdisciplinary approach permits integration of biological mechanisms and models of processes contributing to disease progression at various scales into mathematical models. These can be used to perform in silico simulations to promote unravelling the relation between architecture and function as below illustrated for liver regeneration, and bridging from the in vitro situation and animal models to humans. In the near future novel mechanisms will usually not be directly elucidated by modelling. However, models will falsify hypotheses and guide towards the most informative experimental design. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Current concepts on cytomegalovirus infection after liver transplantation.

PubMed

Lee, Sang-Oh; Razonable, Raymund R

2010-09-27

Cytomegalovirus (CMV) is the most common viral pathogen that negatively impacts on the outcome of liver transplantation. CMV cause febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted allograft. In addition, CMV has been significantly associated with an increased predisposition to allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV on outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is regarded as an essential component to the medical management of liver transplant patients. Two recent guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and at least in one study, such occurrence of late-onset primary CMV disease was significantly associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention are needed, and aggressive treatment of CMV infection and disease should be pursued. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, one should also reduce the degree of immunosuppression. In one recent controlled clinical trial, valganciclovir was found to be as effective and safe as intravenous ganciclovir for the treatment of mild to moderate CMV disease in solid organ (including liver) transplant recipients. In this article, the authors review the current state and the future perspectives of prevention and treatment of CMV disease after liver transplantation.

Liver disease in Viet Nam: screening, surveillance, management and education: a 5-year plan and call to action.

PubMed

Gish, Robert G; Bui, Tam D; Nguyen, Chuc T K; Nguyen, Duc T; Tran, Huy V; Tran, Diem M T; Trinh, Huy N

2012-02-01

Despite a high prevalence of liver disease in Viet Nam, there has been no nationwide approach to the disease and no systematic screening of at-risk individuals. Risk factors include chronic hepatitis B (estimated prevalence of 12%), chronic hepatitis C (at least 2% prevalence), and heavy consumption of alcohol among men. This combination of factors has resulted in liver cancer being the most common cause of cancer death in Viet Nam. There is a general lack of understanding by both the general public and health-care providers about the major risk to health that liver disease represents. We report here the initial steps taken as part of a comprehensive approach to liver disease that will ultimately include nationwide education for health-care providers, health educators, and the public; expansion of nationwide screening for hepatitis B and C followed by hepatitis B virus vaccination or treatment of chronic hepatitis B and/or hepatitis C; education about alcoholic liver disease; long-term surveillance for liver cancer; reduction of infection transmission related to medical, commercial, and personal re-use of contaminated needles, syringes, sharp instruments, razors, and inadequately sterilized medical equipment; and ongoing collection and analysis of data about the prevalence of all forms of liver disease and the results of the expanded screening, vaccination, and treatment programs. We report the beginning results of our pilot hepatitis B screening program. We believe that this comprehensive nationwide approach could substantially reduce the morbidity and mortality from liver disease and greatly lessen the burden in terms of both lives lost and health-care costs. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children

PubMed Central

Vos, Miriam B.; Abrams, Stephanie H.; Barlow, Sarah E.; Caprio, Sonia; Daniels, Stephen R.; Kohli, Rohit; Mouzaki, Marialena; Sathya, Pushpa; Schwimmer, Jeffrey B.; Sundaram, Shikha S.; Xanthakos, Stavra A.

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease that occurs in the setting of insulin resistance and increased adiposity. It has rapidly evolved into the most common liver disease seen in the pediatric population and is a management challenge for general pediatric practitioners, subspecialists and for health systems. In this guideline, the expert committee on NAFLD (ECON) reviewed and summarized the available literature, formulating recommendations to guide screening and clinical care of children with NAFLD. PMID:28107283

Autoimmune liver disease 2007.

PubMed

Muratori, Paolo; Granito, Alessandro; Pappas, Georgios; Muratori, Luigi; Lenzi, Marco; Bianchi, Francesco B

2008-01-01

Autoimmune liver disease (ALD) includes a spectrum of diseases which comprises both cholestatic and hepatitic forms: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and the so called "overlap" syndromes where hepatitic and cholestatic damage coexists. All these diseases are characterized by an extremely high heterogeneity of presentation, varying from asymptomatic, acute (as in a subset of AIH) or chronic (with aspecific symptoms such as fatigue and myalgia in AIH or fatigue and pruritus in PBC and PSC). The detection and characterization of non organ specific autoantibodies plays a major role in the diagnostic approach of autoimmune liver disease; anti nuclear reactivities (ANA) and anti smooth muscle antibodies (SMA) mark type 1 AIH, liver kidney microsomal antibody type 1 (LKM1) and liver cytosol type 1 (LC1) are the serological markers of type 2 AIH; antimitochondrial antibodies (AMA) are associated with PBC, while no specific marker is found in PSC, since anticytoplasmic neutrophil antibodies with perinuclear pattern (atypical p-ANCA or p-ANNA) are also detected in a substantial proportion of type 1 AIH cases. Treatment options rely on immunosoppressive therapy (steroids and azathioprine) in AIH and on ursodeoxycholic acid in cholestatic conditions; in all these diseases liver transplantation remains the only therapeutical approach for the end stage of liver disease.

Non-invasive Markers of Liver Fibrosis: Adjuncts or Alternatives to Liver Biopsy?

PubMed Central

Chin, Jun L.; Pavlides, Michael; Moolla, Ahmad; Ryan, John D.

2016-01-01

Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an imperfect test and poorly accepted by patients. The development of robust tools to non-invasively assess liver fibrosis has dramatically enhanced clinical decision making in patients with chronic liver disease, allowing a rapid and informed judgment of disease stage and prognosis. Should a liver biopsy be required, the appropriateness is clearer and the diagnostic yield is greater with the use of these adjuncts. While a number of non-invasive liver fibrosis markers are now used in routine practice, a steady stream of innovative approaches exists. With improvement in the reliability, reproducibility and feasibility of these markers, their potential role in disease management is increasing. Moreover, their adoption into clinical trials as outcome measures reflects their validity and dynamic nature. This review will summarize and appraise the current and novel non-invasive markers of liver fibrosis, both blood and imaging based, and look at their prospective application in everyday clinical care. PMID:27378924

Liver transplantation for Wilson's disease in pediatric patients: decision making and timing.

PubMed

Narumi, S; Umehara, M; Toyoki, Y; Ishido, K; Kudo, D; Kimura, N; Kobayashi, T; Sugai, M; Hakamada, K

2012-03-01

Transplantation for Wilson's disease occupies 1/3 of the cases for metabolic diseases in Japan. At the end of 2009, 109 transplantations had been performed including three deceased donor cases in the Japanese registry. We herein discuss problems of transplantation for Wilson's disease as well as its indication, timing, and social care. We retrospectively reviewed four fulminant cases and two chronic cases who underwent living donor liver transplantation. There were two boys and two girls. Four adolescents of average age 11.3 years underwent living donor liver transplantation. Duration from onset to transplantation ranged from 10 to 23 days. Average Model for End-stage Liver Disease (MELD) score was 27.8 (range=24-31). All patients were administrated chelates prior to transplantation. MELD, New Wilson's index, Japanese scoring for liver transplantation, and liver atrophy were useful tools for transplantation decision making; however, none of them was an independent decisive tool. Clinical courses after transplantation were almost uneventful. One girl, however, developed an acute rejection episode due to noncompliance at 3 years after transplantation. All patients currently survive without a graft loss. No disease recurrence had been noted even using living related donors. Two adults evaluated for liver transplantation were listed for deceased donor liver transplantation. Both candidates developed cirrhosis despite long-term medical treatment. There were no appropriate living donors for them. There are many problems in transplantation for Wilson's disease. The indications for liver transplantation should be considered individually using some decision-making tools. The safety of the living donor should be paid the most attention. Copyright © 2012 Elsevier Inc. All rights reserved.

The relationship between liver stiffness measurement and outcome in patients with chronic hepatitis C and cirrhosis: a retrospective longitudinal hospital study.

PubMed

Sultanik, P; Kramer, L; Soudan, D; Bouam, S; Meritet, J-F; Vallet-Pichard, A; Fontaine, H; Bousquet, L; Boueyre, E; Corouge, M; Sogni, P; Pol, S; Mallet, V

2016-09-01

There is a relationship between liver stiffness measurement (LSM) and outcome of HCV patients. To evaluate the performance of LSM to predict outcome of HCV patients at risk of liver-related complication. We established a retrospective longitudinal cohort of 341 HCV patients with unequivocal cirrhosis. All underwent LSM and were followed from September 2006 to July 2015. Outcome measure was a composite end-point of end-stage liver disease (ESLD) and/or hepatocellular carcinoma (HCC). Cox models and areas under receiver operating characteristic (AUROC) curves were used to evaluate independent risk factors of outcome. Overall, LSM was below the 12.5 kPa threshold in 129 (37.8%) patients, including three-fourth and one-third of patients with or without a sustained virological response respectively. Liver disease progressed in 136 (39.9%) patients after a median observational period of 23.5 months. Older age, male gender, alcohol use disorders, metabolic syndrome and LSM were independent risk factors of liver disease progression. Age, alcohol use disorders and LSM were independently associated with ESLD. Age, gender and metabolic syndrome, but not LSM, were associated with HCC. The AUROC curves for disease progression, ESLD and HCC were 0.67, 0.70 and 0.58 respectively. Patients with a liver stiffness >12.5 kPa were at the highest risk of liver disease progression; below 12.5 kPa, liver stiffness was not discriminant. Liver stiffness measurement is not a surrogate of disease progression of HCV patients with cirrhosis. HCV patients with cirrhosis should undergo the recommended follow-up, regardless of liver stiffness measurement. © 2016 John Wiley & Sons Ltd.

Long-term prognosis of patients with chronic hepatitis C who did not receive interferon-based therapy: causes of death and analysis based on the FIB-4 index.

PubMed

Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori; Kiriyama, Seiki; Tanikawa, Makoto; Hisanaga, Yasuhiro; Kanamori, Akira; Kitabatake, Shusuke; Yama, Tsuyoki; Tanaka, Junko

2016-04-01

Interferon (IFN)-based therapy has been reported to reduce the liver-related mortality rate in patients with chronic hepatitis C virus (HCV) infection. However, predictors of survival and causes of death, including non-liver-related causes, have not been sufficiently investigated in chronic HCV patients who have not received IFN-based therapy. A total of 1723 patients with chronic HCV infection who were not treated with IFN-based therapy were enrolled. Survival from liver-related diseases and non-liver-related diseases and causes of death were analyzed on the basis of the fibrosis-4 (FIB-4) index, an index of liver fibrosis. The median follow-up duration was 10.3 years. Of 465 patients who died during the follow-up period, 48.4 % died of liver-related diseases; of the remainder, 51.6 % died of non-liver-related diseases. On the basis of FIB-4 index, the liver-related mortality rate increased as the FIB-4 index increased: 16.1 % in the FIB-4 index < 1.45 group, 36.7 % in the 1.45 ≤ FIB-4 index ≤ 3.25 group, and 58.7 % in the FIB-4 index > 3.25 group (p < 0.001). Conversely, the non-liver-related mortality rate decreased as the FIB-4 index increased: 83.9, 63.3, and 41.3 %, respectively (p = 0.001). In the multivariate analysis, a FIB-4 index greater than 3.25 was identified as a risk factor independently associated with both liver-related death (hazard ratio 13.020; 95 % confidence interval 4.155-40.770) and non-liver-related death (hazard ratio 1.667; 95 % confidence interval 1.188-2.340). Patients with chronic HCV infection and an elevated FIB-4 index may benefit from monitoring not only for the development of liver-related diseases but also for the development of non-liver-related diseases.

MRI diffusion tensor reconstruction with PROPELLER data acquisition.

PubMed

Cheryauka, Arvidas B; Lee, James N; Samsonov, Alexei A; Defrise, Michel; Gullberg, Grant T

2004-02-01

MRI diffusion imaging is effective in measuring the diffusion tensor in brain, cardiac, liver, and spinal tissue. Diffusion tensor tomography MRI (DTT MRI) method is based on reconstructing the diffusion tensor field from measurements of projections of the tensor field. Projections are obtained by appropriate application of rotated diffusion gradients. In the present paper, the potential of a novel data acquisition scheme, PROPELLER (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction), is examined in combination with DTT MRI for its capability and sufficiency for diffusion imaging. An iterative reconstruction algorithm is used to reconstruct the diffusion tensor field from rotated diffusion weighted blades by appropriate rotated diffusion gradients. DTT MRI with PROPELLER data acquisition shows significant potential to reduce the number of weighted measurements, avoid ambiguity in reconstructing diffusion tensor parameters, increase signal-to-noise ratio, and decrease the influence of signal distortion.

Iron overload and HFE gene mutations in Polish patients with liver cirrhosis.

PubMed

Sikorska, Katarzyna; Romanowski, Tomasz; Stalke, Piotr; Iżycka-Świeszewska, Ewa; Bielawski, Krzysztof Piotr

2011-06-01

Increased liver iron stores may contribute to the progression of liver injury and fibrosis, and are associated with a higher risk of hepatocellular carcinoma development. Pre-transplant symptoms of iron overload in patients with liver cirrhosis are associated with higher risk of infectious and malignant complications in liver transplant recipients. HFE gene mutations may be involved in the pathogenesis of liver iron overload and influence the progression of chronic liver diseases of different origins. This study was designed to determine the prevalence of iron overload in relation to HFE gene mutations among Polish patients with liver cirrhosis. Sixty-one patients with liver cirrhosis included in the study were compared with a control group of 42 consecutive patients subjected to liver biopsy because of chronic liver diseases. Liver function tests and serum iron markers were assessed in both groups. All patients were screened for HFE mutations (C282Y, H63D, S65C). Thirty-six of 61 patients from the study group and all controls had liver biopsy performed with semiquantitative assessment of iron deposits in hepatocytes. The biochemical markers of iron overload and iron deposits in the liver were detected with a higher frequency (70% and 47% respectively) in patients with liver cirrhosis. There were no differences in the prevalence of all HFE mutations in both groups. In patients with a diagnosis of hepatocellular carcinoma, no significant associations with iron disorders and HFE gene mutations were found. Iron disorders were detected in patients with liver cirrhosis frequently but without significant association with HFE gene mutations. Only the homozygous C282Y mutation seems to occur more frequently in the selected population of patients with liver cirrhosis. As elevated biochemical iron indices accompanied liver iron deposits more frequently in liver cirrhosis compared to controls with chronic liver disease, there is a need for more extensive studies searching for the possible influence of non-HFE iron homeostasis regulators and their modulation on the course of chronic liver disease and liver cirrhosis.

Effect of Contrast Media on Single Shot EPI: Implications for Abdominal Diffusion Imaging

PubMed Central

Gulani, Vikas; Willatt, Jonathan M.; Blaimer, Martin; Hussain, Hero K.; Duerk, Jeffrey L.; Griswold, Mark A.

2010-01-01

Purpose The goal of this study was to determine the effect of contrast media on the signal behavior of single shot echo planar imaging (ssEPI) used for abdominal diffusion imaging. Materials and Methods The signal of a ssEPI spin echo sequence in a water phantom with varying concentrations of gadolinium was modeled with Bloch equations and the predicted behavior validated on a phantom at 1.5 T. Six volunteers were given gadolinium contrast, and signal intensity (SI) time courses for regions of interest (ROIs) in the liver, pancreas, spleen, renal cortex and medulla were analyzed. The Student's t-test was used to compare pre-contrast SI to 0, 1, 4, 5, 10, and 13 minutes following contrast. Results The results show that following contrast, ssEPI SI goes through a nadir, recovering differently for each organ. Maximal contrast related signal losses relative to pre-contrast signal are 20%, 20%, 53%, and 67%, for the liver, pancreas, renal cortex and medulla respectively. The SIs remain statistically below the pre-contrast values for 5, 4, and 1 minutes for the pancreas, liver, and spleen, and for all times measured for the renal cortex and medulla. Conclusion Abdominal diffusion imaging should be performed prior to contrast due to adverse effects on the signal in ssEPI. PMID:19856456

Crosstalk between the gut and the liver via susceptibility loci: Novel advances in inflammatory bowel disease and autoimmune liver disease.

PubMed

Li, Xinyang; Shen, Jun; Ran, Zhihua

2017-02-01

Inflammatory bowel disease (IBD) is an autoimmune disorder characterized by chronic, relapsing intestinal inflammation. Autoimmune liver disease (AILD) may be involved in IBD as an extra-intestinal manifestation (EIM). Epidemiologic and anatomic evidence have demonstrated an intimate crosstalk between the gut and the liver. In this review, we briefly introduced nine groups of susceptibility loci shared by inflammatory bowel and autoimmune liver disease for the first time. The genome-wide association studies (GWAS) evidence of pathways involving crosstalk between the gut and the liver is clarified and explained. It has been found that HNF4-α, GPR35, MST1R, CARD9, IL2/IL21/IL2R, BACH2, TNFRSF14, MAdCAM-1, and FUT2 are the genes involved in tight junction formation, macrophage function, T helper cell or T reg cell cycle and function, TNF secretion, lymphocyte homing or intestinal dysbiosis, respectively. The intimate crosstalk between the gut and liver in immunity is also highlighted and discussed in this review. Copyright © 2016 Elsevier Inc. All rights reserved.

A report from the European Association for the Study of the Liver's 50th International Liver Congress (April 22-26 - Vienna, Austria).

PubMed

Rabasseda, X

2015-04-01

While Vienna's Prater park offers a varied selection of options, from theme parks to lush gardens and prairies to enjoy the sun, the nearby Messe Wien convention center was the focus of attention in April 2015 for all the scientists, researchers and clinicians interested in viral hepatitis, nonalcoholic steatohepatitis, hepatocellular carcinoma and a variety of other liver diseases. Treatments and potential new therapeutic strategies for these hepatopathies were discussed during the 50th International Liver Congress organized by the European Association for the Study of the Liver. Echoing epidemiological facts and a high social interest for hepatitis C virus infection, new findings with investigational and potential new therapies for the disease centered much of the attention at the conference. Nevertheless, new research was also reported related to potential improvements in how other liver diseases, particularly hepatitis B virus infection, hepatocellular carcinoma and a range of inflammatory and immune-mediated liver diseases, including rare hereditary diseases that should never be forgotten. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

Chronic liver disease in the Hispanic population of the United States.

PubMed

Carrion, Andres F; Ghanta, Ravi; Carrasquillo, Olveen; Martin, Paul

2011-10-01

Chronic liver disease is a major cause of morbidity and mortality among Hispanic people living in the United States. Environmental, genetic, and behavioral factors, as well as socioeconomic and health care disparities among this ethnic group have emerged as important public health concerns. We review the epidemiology, natural history, and response to therapy of chronic liver disease in Hispanic patients. The review covers nonalcoholic fatty liver disease, viral hepatitis B and C, coinfection of viral hepatitis with human immunodeficiency virus, alcoholic cirrhosis, hepatocellular carcinoma, autoimmune hepatitis, and primary biliary cirrhosis. For most of these disorders, the Hispanic population has a higher incidence and more aggressive pattern of disease and overall worse treatment outcomes than in the non-Hispanic white population. Clinicians should be aware of these differences in caring for Hispanic patients with chronic liver disease. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Multi organ assessment of Compensated Cirrhosis Patients using quantitative Magnetic Resonance Imaging.

PubMed

Bradley, Christopher R; Cox, Eleanor F; Scott, Robert A; James, Martin W; Kaye, Phillip; Aithal, Guruprasad P; Francis, Susan T; Guha, Indra Neil

2018-06-07

Advancing liver disease results in deleterious changes in a number of critical organs. The ability to measure structure, blood flow and tissue perfusion within multiple organs in a single scan has implications for determining the balance of benefit versus harm for therapies. Our aim was to establish the feasibility of Magnetic Resonance Imaging to assess changes in compensated cirrhosis (CC), and relate this to disease severity and future liver related outcomes (LROs). 60 CC patients, 40 healthy volunteers and 7 decompensated cirrhotics were recruited. In a single scan session, MRI measures comprised phase-contrast MRI vessel blood flow, arterial spin labelling tissue perfusion, T 1 longitudinal relaxation time and volume assessment of liver, spleen and kidneys, heart rate and cardiac index. We explore MRI parameters with disease severity and differences in baseline MRI parameters in those 11 (18%) of CC patients who had future LROs. In the liver compositional changes were reflected by increased T 1 in progressive disease (p<0.001) and an increase in liver volume in CC (p=0.006), with associated progressive reduction in liver (p < 0.001) and splenic (p<0.001) perfusion. A significant reduction in renal cortex T 1 and increase in cardiac index and superior mesenteric arterial (SMA) blood flow was seen with increasing disease severity. Baseline liver T 1 (p=0.01) and perfusion (p< 0.01), and renal cortex T 1 (p<0.01) were significantly different in CC patients who subsequently developed negative LROs. MRI allows the contemporaneous assessment of organs in liver cirrhosis in a single scan without the requirement of contrast agent. MRI parameters of liver T 1, renal T 1, hepatic and splenic perfusion, and SMA blood flow were related to risk of LROs. This study assesses the changes to structure, blood flow and perfusion that occur in the key organs (liver, spleen and kidney) associated with severe liver disease (compensated cirrhosis). Those MRI measures which change with disease severity and are related to negative liver related clinical outcomes are described. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Effect of liver transplantation on brain magnetic resonance imaging pathology in Wilson disease: a case report.

PubMed

Litwin, T; Dzieżyc, K; Poniatowska, R; Członkowska, A

2013-01-01

The authors present a case report of a 28-year-old patient with hepatic, but no neurological, signs of Wilson disease, with pathological changes in both the globi pallidi and caudate found with routine brain magnetic resonance imaging (MRI). The patient was recommended for liver transplantation by hepatologists, and during the two years of observation after liver transplantation, MRI brain abnormalities due to Wilson disease completely regressed. On the basis of this case, the authors present an argument for the prognostic significance of brain MRI in Wilson disease as well as current recommendations concerning liver transplantation in Wilson disease.

Disease duration and Medsger's severity score are associated with significant liver fibrosis in patients with systemic sclerosis.

PubMed

Lee, Sang-Won; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Song, Jason Jungsik; Park, Yong-Beom; Lee, Soo-Kon; Han, Kwang-Hyub; Kim, Seung Up

2015-01-01

We investigated the prevalence and predictors of significant liver fibrosis in patients with systemic sclerosis (SSc) who had no evidences of liver diseases due to viral infection, drug, and heavy alcohol consumption. A total of 44 SSc patients were recruited. In addition to the clinical and laboratory data, the 2013 College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria score, modified Rodnan skin score (mRSS), and Medsger's severity score (MSS) were analysed. Liver stiffness (LS) was measured using transient elastography to assess the degree of liver fibrosis and 7.4 kPa was adopted as the cut-off value for significant liver fibrosis. The median age of patients (38 women) was 54 years and the median disease duration was 41.0 months. The median LS value was 4.6 kPa. The median mRSS and MSS were 7.0 and 5.0, respectively. Six (13.6%) patients had significant liver fibrosis. Disease duration (standardised β=0.375, p=0.018) and MSS (standardised β=0.398, p=0.047) significantly correlated with LS values. In multivariate analysis, disease duration≥63 months (odds ratio (OR) 19.166, 95% confidence interval 1.090, 336.962, p=0.043) and MSS≥7 (OR 19.796, 95% confidence interval 1.439, 272.252, p=0.026) independently predicted the presence of significant liver fibrosis. The prevalence of significant liver fibrosis was relatively high (13.6%) and its independent predictors were disease duration and MSS.

Evaluation of nonalcoholic fatty liver disease using magnetic resonance in obese children and adolescents.

PubMed

Benetolo, Patrícia O; Fernandes, Maria I M; Ciampo, Ieda R L Del; Elias-Junior, Jorge; Sawamura, Regina

2018-02-10

To determine the frequency of nonalcoholic fatty liver disease using nuclear magnetic resonance as a noninvasive method. This was a cross-sectional study conducted on 50 children and adolescents followed up at an outpatient obesity clinic. The subjects were submitted to physical examination, laboratory tests (transaminases, liver function tests, lipid profile, glycemia, and basal insulin) and abdominal nuclear magnetic resonance (calculation of hepatic, visceral, and subcutaneous fat). Nonalcoholic fatty liver disease was diagnosed in 14 (28%) participants, as a severe condition in eight (percent fat >18%), and as non-severe in four (percent fat from 9% to 18%). Fatty liver was associated with male gender, triglycerides, AST, ALT, AST/ALT ratio, and acanthosis nigricans. Homeostasis model assessment of insulin resistance and metabolic syndrome did not show an association with fatty liver. The frequency of nonalcoholic fatty liver disease in the present population of children and adolescents was lower than that reported in the international literature. It is suggested that nuclear magnetic resonance is an imaging exam that can be applied to children and adolescents, thus representing an effective noninvasive tool for the diagnosis of nonalcoholic fatty liver disease in this age range. However, further national multicenter studies with longitudinal design are needed for a better analysis of the correlation between nonalcoholic fatty liver disease and its risk factors, as well as its consequences. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Cautiously using natural medicine to treat liver problems.

PubMed

Xiong, Fei; Guan, Yong-Song

2017-05-21

Natural medicine is a system of therapy that administrates natural agents and their derivatives to treat human diseases. This medicine has been used to treat many kinds of human diseases for thousands of years. The treatment protocols of natural medicine are integrative in nature, and are required to utilize the most appropriate therapies to address the needs of the individual patient. Because of the relative convenience, safety and efficacy, natural medicine is now increasing worldwide. Naturopathic doctors are licensed in many areas of the world and regulated partly by law in these areas, which is quite different from various other forms of complementary and alternative medicine. Liver diseases, such as hepatitis, liver cirrhosis and liver carcinoma, are serious health problems worldwide. Nearly half of the natural agents used in treatment of liver diseases today are natural products and their derivatives. Although natural medicine is beneficial and safe, physicians should pay close attention to the potential side-effects of the naturopathic agents, which lead to liver injury, interstitial pneumonia and acute respiratory failure. Therefore, when administrating naturopathic protocols to patients for the treatment of liver diseases, we should try our best to prevent and avoid as much as possible the negative impact of these medicines. This article highlights the current practice and recommended improvement of natural medicines in the treatment of liver diseases and gives some specific examples to emphasize the prevention and management of adverse reactions of the natural agents and suggests that natural medicine should be cautiously used to treat liver problems.

Evaluation of liver fat in the presence of iron with MRI using T2* correction: a clinical approach.

PubMed

Henninger, Benjamin; Benjamin, Henninger; Kremser, Christian; Christian, Kremser; Rauch, Stefan; Stefan, Rauch; Eder, Robert; Robert, Eder; Judmaier, Werner; Werner, Judmaier; Zoller, Heinz; Heinz, Zoller; Michaely, Henrik; Henrik, Michaely; Schocke, Michael; Michael, Schocke

2013-06-01

To assess magnetic resonance imaging (MRI) with conventional chemical shift-based sequences with and without T2* correction for the evaluation of steatosis hepatitis (SH) in the presence of iron. Thirty-one patients who underwent MRI and liver biopsy because of clinically suspected diffuse liver disease were retrospectively analysed. The signal intensity (SI) was calculated in co-localised regions of interest (ROIs) using conventional spoiled gradient-echo T1 FLASH in-phase and opposed-phase (IP/OP). T2* relaxation time was recorded in a fat-saturated multi-echo-gradient-echo sequence. The fat fraction (FF) was calculated with non-corrected and T2*-corrected SIs. Results were correlated with liver biopsy. There was significant difference (P < 0.001) between uncorrected and T2* corrected FF in patients with SH and concomitant hepatic iron overload (HIO). Using 5 % as a threshold resulted in eight false negative results with uncorrected FF whereas T2* corrected FF lead to true positive results in 5/8 patients. ROC analysis calculated three threshold values (8.97 %, 5.3 % and 3.92 %) for T2* corrected FF with accuracy 84 %, sensitivity 83-91 % and specificity 63-88 %. FF with T2* correction is accurate for the diagnosis of hepatic fat in the presence of HIO. Findings of our study suggest the use of IP/OP imaging in combination with T2* correction. • Magnetic resonance helps quantify both iron and fat content within the liver • T2* correction helps to predict the correct diagnosis of steatosis hepatitis • "Fat fraction" from T2*-corrected chemical shift-based sequences accurately quantifies hepatic fat • "Fat fraction" without T2* correction underestimates hepatic fat with iron overload.

Health outcomes following liver function testing in primary care: a retrospective cohort study.

PubMed

McLernon, David J; Donnan, Peter T; Ryder, Stephen; Roderick, Paul; Sullivan, Frank M; Rosenberg, William; Dillon, John F

2009-08-01

patients who present with abnormal liver function tests (LFTs) in primary care and no obvious symptoms can be difficult to manage. The objective is to follow-up a cohort of liver function tested patients to determine their outcome. This population-based retrospective cohort study was conducted in Tayside, Scotland, from 1989 to 2003. Subjects were patients with no clinically obvious liver disease at initial liver function testing in primary care. Main outcomes were diagnosed liver disease and mortality. Record linkage of databases ascertained risk factors and outcomes. Measures of performance were calculated and Weibull regression analysis from initial LFT date was performed on all outcomes by level of abnormality. In total, 95 977 patients had 364 194 incident initial LFTs, with median follow-up 3.7 years. A total of 21.7% had at least one abnormal LFT and 1108 (1.15%) developed liver disease. Elevated transaminase was strongly associated with diagnosed liver disease, hazard ratio (HR) = 4.23 (95% confidence interval 3.55, 5.04) for mild levels and HR = 12.67 (95% CI 9.74, 16.47) for severe levels versus normal. For gamma-glutamyl transferase, these hazards were 2.54 (95% CI 2.17, 2.96) and 13.44 (95% CI 10.71, 16.87), respectively. Low albumin was strongly associated with all-cause mortality, HR = 2.65 (95% CI 2.47, 2.85) for mild levels and HR = 4.99 (95% CI 4.26, 5.84) for severe levels. Sensitivity for predicting events over 5 years was low and specificity high. All LFTs were predictive markers for liver disease as well as general ill health, although sensitivity was poor. Most patients with abnormal LFTs had no later formal diagnosis of liver disease within the study period. The time taken to develop liver disease in these patients provides opportunity to intervene.

Living Donor Liver Transplantation for Wilson’s Disease Associated with Fulminant Hepatic Failure: A Case Report

PubMed Central

Huang, Yu; Takatsuki, Mitsuhisa; Soyama, Akihiko; Hidaka, Masaaki; Ono, Shinichiro; Adachi, Tomohiko; Hara, Takanobu; Okada, Satomi; Hamada, Takashi; Eguchi, Susumu

2018-01-01

Patient: Female, 17 Final Diagnosis: Fulminant Wilson’s disease Symptoms: General jaundice • malaise • abdominal pain Medication: — Clinical Procedure: ICU Specialty: Transplantology Objective: Rare disease Background: Liver transplantation is indicated for patients with Wilson’s disease (WD) who present either with acute liver failure or with end-stage liver disease and severe hepatic insufficiency as the first sign of disease. However, almost all reported cases have been treated with death donor liver transplantation. Here we report the case of a patient with WD associated with fulminant hepatic failure (WD-FHF) who underwent living donor liver transplantation (LDLT). Case Report: A 17-year-old female was diagnosed with WD-FHF based on high uric copper (10 603 μg/day, normal <100 μg/day), low serum ceruloplasmin (15 mg/dL, normal >20 mg/dL) and Kayser-Fleischer (K-F) corneal ring, and acute liver failure (ALF), acute renal failure (ARF) and grade 2 hepatic encephalopathy (HE). The model for end-stage liver disease (MELD) score was 35. Due to her critical condition, the patient underwent LDLT utilizing a right liver graft from her 44-year-old mother. The right hepatic vein (RHV) and inferior right hepatic vein (iRHV) were reconstructed. She developed severe liver dysfunction due to a crooked hepatic vein caused by compression from the large graft. To straighten the bend, a reoperation was performed. During the operation, we tried to relieve the compressed hepatic vein by adjusting the graft location, but the benefits were limited. We therefore performed stenting in both the RHV and iRHV on postoperative day 9. The patient gradually improved, exhibiting good liver and renal functions, and was finally discharged on postoperative day 114. Conclusions: When WD-FHF deteriorates too rapidly for conservative management, LDLT is an effective therapeutic strategy. PMID:29549236

Damage to enteric neurons occurs in mice that develop fatty liver disease but not diabetes in response to a high-fat diet.

PubMed

Rivera, L R; Leung, C; Pustovit, R V; Hunne, B L; Andrikopoulos, S; Herath, C; Testro, A; Angus, P W; Furness, J B

2014-08-01

Disorders of gastrointestinal functions that are controlled by enteric neurons commonly accompany fatty liver disease. Established fatty liver disease is associated with diabetes, which itself induces enteric neuron damage. Here, we investigate the relationship between fatty liver disease and enteric neuropathy, in animals fed a high-fat, high-cholesterol diet in the absence of diabetes. Mice were fed a high-fat, high-cholesterol diet (21% fat, 2% cholesterol) or normal chow for 33 weeks. Liver injury was assessed by hematoxylin and eosin, picrosirius red staining, and measurement of plasma alanine aminotransaminase (ALT). Quantitative immunohistochemistry was performed for different types of enteric neurons. The mice developed steatosis, steatohepatitis, fibrosis, and a 10-fold increase in plasma ALT, indicative of liver disease. Oral glucose tolerance was unchanged. Loss and damage to enteric neurons occurred in the myenteric plexus of ileum, cecum, and colon. Total numbers of neurons were reduced by 15-30% and neurons expressing nitric oxide synthase were reduced by 20-40%. The RNA regulating protein, Hu, became more concentrated in the nuclei of enteric neurons after high-fat feeding, which is an indication of stress on the enteric nervous system. There was also disruption of the neuronal cytoskeletal protein, neurofilament medium. Enteric neuron loss and damage occurs in animals with fatty liver disease in the absence of glucose intolerance. The enteric neuron damage may contribute to the gastrointestinal complications of fatty liver disease. © 2014 John Wiley & Sons Ltd.

From the liver to the heart: Cardiac dysfunction in obese children with non-alcoholic fatty liver disease

PubMed Central

Di Sessa, Anna; Umano, Giuseppina Rosaria; Miraglia del Giudice, Emanuele; Santoro, Nicola

2017-01-01

In the last decades the prevalence of non-alcoholic fatty liver disease (NAFLD) has increased as a consequence of the childhood obesity world epidemic. The liver damage occurring in NAFLD ranges from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Recent findings reported that fatty liver disease is related to early atherosclerosis and cardiac dysfunction even in the pediatric population. Moreover, some authors have shown an association between liver steatosis and cardiac abnormalities, including rise in left ventricular mass, systolic and diastolic dysfunction and epicardial adipose tissue thickness. In this editorial, we provide a brief overview of the current knowledge concerning the association between NAFLD and cardiac dysfunction. PMID:28144387

From the liver to the heart: Cardiac dysfunction in obese children with non-alcoholic fatty liver disease.

PubMed

Di Sessa, Anna; Umano, Giuseppina Rosaria; Miraglia Del Giudice, Emanuele; Santoro, Nicola

2017-01-18

In the last decades the prevalence of non-alcoholic fatty liver disease (NAFLD) has increased as a consequence of the childhood obesity world epidemic. The liver damage occurring in NAFLD ranges from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Recent findings reported that fatty liver disease is related to early atherosclerosis and cardiac dysfunction even in the pediatric population. Moreover, some authors have shown an association between liver steatosis and cardiac abnormalities, including rise in left ventricular mass, systolic and diastolic dysfunction and epicardial adipose tissue thickness. In this editorial, we provide a brief overview of the current knowledge concerning the association between NAFLD and cardiac dysfunction.

Alcoholic liver disease patients' perspective of a coping and physical activity-oriented rehabilitation intervention after hepatic encephalopathy.

PubMed

Mikkelsen, Maria Rudkjaer; Hendriksen, Carsten; Schiødt, Frank Vinholt; Rydahl-Hansen, Susan

2016-09-01

To identify and describe the impact of a coping and physical activity-oriented rehabilitation intervention on alcoholic liver disease patients after hepatic encephalopathy in terms of their interaction with professionals and relatives. Patients who have experienced alcohol-induced hepatic encephalopathy have reduced quality of life, multiple complications, and social problems, and rehabilitation opportunities for these patients are limited. A grounded theory study and an evaluation study of a controlled intervention study. Semi-structured interviews were conducted with 10 alcoholic liver disease patients who were diagnosed with hepatic encephalopathy and participated in a coping and physical activity-oriented rehabilitation intervention. Richard S. Lazarus's theory of stress and coping inspired the interview guide. The significance of a coping and physical activity-oriented rehabilitation intervention on alcoholic liver disease patients' ability to cope with problems after surviving alcohol-induced hepatic encephalopathy in terms of their interaction with professionals and relatives was characterised by the core category 'regain control over the diseased body'. This is subdivided into three separate categories: 'the experience of being physically strong', 'togetherness' and 'self-control', and they impact each other and are mutually interdependent. Alcoholic liver disease patients described the strength of the rehabilitation as regaining control over the diseased body. Professionals and relatives of patients with alcoholic liver disease may need to focus on strengthening and preserving patients' control of their diseased body by facilitating the experience of togetherness, self-control and physical strength when interacting with and supporting patients with alcoholic liver disease. A coping and physical activity-oriented rehabilitation intervention may help alcoholic liver disease patients to regain control over their diseased body and give patients the experience of togetherness, self-control and physical strength. Professionals should be aware of giving the patients the experience of togetherness in their interactions, help them perceive self-control and gain physical strength during their rehabilitation. © 2016 John Wiley & Sons Ltd.

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.

Diffusion-Weighted PROPELLER MRI for Quantitative Assessment of Liver Tumor Necrotic Fraction and Viable Tumor Volume in VX2 Rabbits

PubMed Central

Deng, Jie; Virmani, Sumeet; Young, Joseph; Harris, Kathleen; Yang, Guang-Yu; Rademaker, Alfred; Woloschak, Gayle; Omary, Reed A.; Larson, Andrew C.

2010-01-01

Purpose To test the hypothesis that diffusion-weighted (DW)-PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) MRI provides more accurate liver tumor necrotic fraction (NF) and viable tumor volume (VTV) measurements than conventional DW-SE-EPI (spin echo echo-planar imaging) methods. Materials and Methods Our institutional Animal Care and Use Committee approved all experiments. In six rabbits implanted with 10 VX2 liver tumors, DW-PROPELLER and DW-SE-EPI scans were performed at contiguous axial slice positions covering each tumor volume. Apparent diffusion coefficient maps of each tumor were used to generate spatially resolved tumor viability maps for NF and VTV measurements. We compared NF, whole tumor volume (WTV), and VTV measurements to corresponding reference standard histological measurements based on correlation and concordance coefficients and the Bland–Altman analysis. Results DW-PROPELLER generally improved image quality with less distortion compared to DW-SE-EPI. DW-PROPELLER NF, WTV, and VTV measurements were strongly correlated and satisfactorily concordant with histological measurements. DW-SE-EPI NF measurements were weakly correlated and poorly concordant with histological measurements. Bland–Altman analysis demonstrated that DWPROPELLER WTV and VTV measurements were less biased from histological measurements than the corresponding DW-SE-EPI measurements. Conclusion DW-PROPELLER MRI can provide spatially resolved liver tumor viability maps for accurate NF and VTV measurements, superior to DW-SE-EPI approaches. DWPROPELLER measurements may serve as a noninvasive surrogate for pathology, offering the potential for more accurate assessments of therapy response than conventional anatomic size measurements. PMID:18407540

Diabetes mellitus and renal involvement in chronic viral liver disease.

PubMed

Iovanescu, V F; Streba, C T; Ionescu, M; Constantinescu, A F; Vere, C C; Rogoveanu, I; Moța, E

2015-01-01

Chronic viral liver disease is often associated with other conditions. Diabetes mellitus (DM) is frequently reported in this context and may play a role in the progression of the liver disease to hepatocellular carcinoma (HCC). Renal disease is also an important extrahepatic manifestation of hepatitis viral infection and its presence is associated with poor prognosis and management issues. Our study had multiple purposes: to determine the frequency of the association between chronic viral liver disease and diabetes mellitus, evaluate the potential of diabetes mellitus as a risk factor for HCC and assess an eventual renal involvement. We included in our study a number of 246 patients with chronic liver disease, from whom 136 were diagnosed with chronic viral hepatitis and 110 with viral liver cirrhosis. These patients were assessed by using a clinical examination and a series of tests, including serum transaminase levels, serum bilirubin, serum albumin, markers of cholestasis, fasting plasma glucose levels, serum creatinine, urea, albuminuria, Addis-Hamburger test, electrophoresis of urinary proteins, abdominal ultrasound and, in some cases, CT examination. We obtained the following results: diabetes mellitus is often associated with chronic liver disease of viral etiology, having been identified in 18.29% of the patients in our study. Age above 60 in patients with chronic hepatitis (p=0.013<0.05) and presence of hepatitis C virus were particularly correlated with the presence of diabetes mellitus. Renal disease was present in 13.4% of the patients with chronic liver disease and it was especially associated with liver cirrhosis and hepatitis C virus. The most common form of renal injury was glomerulonephritis. Acute kidney injury was diagnosed only in cirrhotic patients as hepatorenal syndrome, occurring in 7.27% of the subjects, while chronic kidney disease was identified only in two cases of chronic viral hepatitis. Four patients in our study were diagnosed with HCC and none of them presented diabetes mellitus. Our study revealed that there is a significant association between diabetes mellitus and chronic viral liver disease induced by hepatitis C virus. Glomerulonephritis was the most common type of renal disease in both hepatitis patients and in those with cirrhosis. Glomerular injury was strongly correlated with the presence of hepatitis C virus than with hepatitis B virus. A connection between diabetes mellitus and hepatocellular carcinoma could not be established.

Characterization of the liver tissue interstitial fluid (TIF) proteome indicates potential for application in liver disease biomarker discovery.

PubMed

Sun, Wei; Ma, Jie; Wu, Songfeng; Yang, Dong; Yan, Yujuan; Liu, Kehui; Wang, Jinglan; Sun, Longqin; Chen, Ning; Wei, Handong; Zhu, Yunping; Xing, Baocai; Zhao, Xiaohang; Qian, Xiaohong; Jiang, Ying; He, Fuchu

2010-02-05

Tissue interstitial fluid (TIF) forms the interface between circulating body fluids and intracellular fluid. Pathological alterations of liver cells could be reflected in TIF, making it a promising source of liver disease biomarkers. Mouse liver TIF was extracted, separated by SDS-PAGE, analyzed by linear ion trap mass spectrometer, and 1450 proteins were identified. These proteins may be secreted, shed from membrane vesicles, or represent cellular breakdown products. They show different profiling patterns, quantities, and possibly modification/cleavage of intracellular proteins. The high solubility and even distribution of liver TIF supports its suitability for proteome analysis. Comparison of mouse liver TIF data with liver tissue and plasma proteome data identified major proteins that might be released from liver to plasma and serve as blood biomarkers of liver origin. This result was partially supported by comparison of human liver TIF data with human liver and plasma proteome data. Paired TIFs from tumor and nontumor liver tissues of a hepatocellular carcinoma patient were analyzed and the profile of subtracted differential proteins supports the potential for biomarker discovery in TIF. This study is the first analysis of the liver TIF proteome and provides a foundation for further application of TIF in liver disease biomarker discovery.

Nonalcoholic Fatty Liver Disease Management: Dietary and Lifestyle Modifications.

PubMed

Nguyen, Vi; George, Jacob

2015-08-01

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of abnormalities that can range from bland liver fat (steatosis), to hepatic inflammation and liver injury (steatohepatitis). It is estimated that NAFLD will become the principal cause of liver disease in Western nations and the leading indication for liver transplantation. Advancements in disease recognition and management are therefore paramount. Although the development of new, reliable drug therapies is vital, lifestyle interventions remain the most effective treatment modality. In addition to weight loss as a primary measure of treatment success, there is growing recognition that other endpoints, including the prevention or delay of diabetes onset, reduced cardiovascular events, prevention of cancer, and improved overall mortality, are equally important outcomes that can be independently modified by lifestyle change. Moreover, NAFLD is inextricably part of a complex, systemic disease process that is linked with deeply entrenched maladaptive lifestyle behaviors. Thus, a holistic, multidisciplinary, and individualized approach to disease management will be the key to achieving any realistic population-level change. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The intersection of nonalcoholic fatty liver disease and obesity.

PubMed

Woo Baidal, Jennifer A; Lavine, Joel E

2016-01-27

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and recently emerged as the most rapidly increasing indication for liver transplant. Although obesity is a risk factor for NAFLD, overlap between these two entities is incompletely understood. We highlight recent insights into the pathogenesis of human NAFLD in relation to obesity and discuss advances in the diagnosis and treatment of NAFLD. Copyright © 2016, American Association for the Advancement of Science.

Festival food coma in cystic fibrosis.

PubMed

Pandit, Chetan; Graham, Christie; Selvadurai, Hiran; Gaskin, Kevin; Cooper, Peter; van Asperen, Peter

2013-07-01

Children with cystic fibrosis liver disease and portal hypertension are at risk of developing acute hepatic encephalopathy. Even in the presence of normal synthetic liver function these children may have porto-systemic shunting. We report a case of an adolosecent who had cystic fibrosis liver disease and presented with life threatening hepatinc encephalopathy. This case illustrates that it is necessary to consider an appropriate dietary regimen in adolosecents with liver disease to prevent hepatic decompensation. Copyright © 2012 Wiley Periodicals, Inc.

Disease progression in Chinese chronic hepatitis C patients with persistently normal alanine aminotransaminase levels.

PubMed

Hui, C-K; Zhang, H-Y; Shek, T; Yao, H; Yueng, Y-H; Leung, K-W; Lai, S-T; Lai, J-Y; Leung, N; Lau, G K

2007-06-01

Although chronic hepatitis C virus-infected patients with persistently normal alanine aminotransaminase levels usually have mild liver disease, disease progression can still occur. However, it is uncertain which group of patients is at risk of disease progression. To examine the severity of liver disease on liver biopsy in Chinese patients with persistently normal alanine aminotransaminase levels, and their disease progression over time. Eighty-two patients with persistently normal alanine aminotransaminase levels were followed up longitudinally. The median time of follow-up was 8.1 years. Forty-seven of the 82 patients (57.3%) had a second liver biopsy. At the time of analysis, six of the 82 patients (7.3%) developed decompensated liver cirrhosis. Patients with an initial fibrosis stage F2 or F3 [6/23 (26.1%) vs. 0/59 (0%), P < 0.0001] or inflammatory grade A2 or A3 [5/40 (12.5%) vs. 1/42 (2.4%), P = 0.04] were more likely to develop decompensated liver cirrhosis. On multivariate analysis, initial fibrosis stage F2 or F3 was independently associated with progression to decompensated liver cirrhosis (relative risk 2.3, 95% confidence interval 0.03-2.5, P = 0.02). Chinese chronic hepatitis C virus patients with persistently normal alanine aminotransaminase levels with moderate to severe fibrosis at initial evaluation are more likely to develop decompensated liver cirrhosis.

Library of molecular associations: curating the complex molecular basis of liver diseases.

PubMed

Buchkremer, Stefan; Hendel, Jasmin; Krupp, Markus; Weinmann, Arndt; Schlamp, Kai; Maass, Thorsten; Staib, Frank; Galle, Peter R; Teufel, Andreas

2010-03-20

Systems biology approaches offer novel insights into the development of chronic liver diseases. Current genomic databases supporting systems biology analyses are mostly based on microarray data. Although these data often cover genome wide expression, the validity of single microarray experiments remains questionable. However, for systems biology approaches addressing the interactions of molecular networks comprehensive but also highly validated data are necessary. We have therefore generated the first comprehensive database for published molecular associations in human liver diseases. It is based on PubMed published abstracts and aimed to close the gap between genome wide coverage of low validity from microarray data and individual highly validated data from PubMed. After an initial text mining process, the extracted abstracts were all manually validated to confirm content and potential genetic associations and may therefore be highly trusted. All data were stored in a publicly available database, Library of Molecular Associations http://www.medicalgenomics.org/databases/loma/news, currently holding approximately 1260 confirmed molecular associations for chronic liver diseases such as HCC, CCC, liver fibrosis, NASH/fatty liver disease, AIH, PBC, and PSC. We furthermore transformed these data into a powerful resource for molecular liver research by connecting them to multiple biomedical information resources. Together, this database is the first available database providing a comprehensive view and analysis options for published molecular associations on multiple liver diseases.

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

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.

Non-alcoholic fatty liver disease: What the clinician needs to know

PubMed Central

Machado, Mariana Verdelho; Cortez-Pinto, Helena

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of liver disease in the Western world. Furthermore, it is increasing worldwide, paralleling the obesity pandemic. Though highly frequent, only about one fifth of affected subjects are at risk of developing the progressive form of the disease, non-alcoholic steatohepatitis with fibrosis. Even in the latter, liver disease is slowly progressive, though, since it is so prevalent, it is already the third cause of liver transplantation in the United States, and it is predicted to get to the top of the ranking in few years. Of relevance, fatty liver is also associated with increased overall mortality and particularly increased cardiovascular mortality. The literature and amount of published papers on NAFLD is increasing as fast as its prevalence, which makes it difficult to keep updated in this topic. This review aims to summarize the latest knowledge on NAFLD, in order to help clinicians understanding its pathogenesis and advances on diagnosis and treatment. PMID:25278691

Emerging roles of SIRT1 in fatty liver diseases

PubMed Central

Ding, Ren-Bo; Bao, Jiaolin; Deng, Chu-Xia

2017-01-01

Fatty liver diseases, which are commonly associated with high-fat/calorie diet, heavy alcohol consumption and/or other metabolic disorder causes, lead to serious medical concerns worldwide in recent years. It has been demonstrated that metabolic homeostasis disruption is most likely to be responsible for this global epidemic. Sirtuins are a group of conserved nicotinamide adenine dinucleotide (NAD+) dependent histone and/or protein deacetylases belonging to the silent information regulator 2 (Sir2) family. Among seven mammalian sirtuins, sirtuin 1 (SIRT 1) is the most extensively studied one and is involved in both alcoholic and nonalcoholic fatty liver diseases. SIRT1 plays beneficial roles in regulating hepatic lipid metabolism, controlling hepatic oxidative stress and mediating hepatic inflammation through deacetylating some transcriptional regulators against the progression of fatty liver diseases. Here we summarize the latest advances of the biological roles of SIRT1 in regulating lipid metabolism, oxidative stress and inflammation in the liver, and discuss the potential of SIRT1 as a therapeutic target for treating alcoholic and nonalcoholic fatty liver diseases. PMID:28808418

[Balneotherapeutics of non-alcoholic fatty liver disease with the use of the Essentuki-type drinking mineral waters].

PubMed

Fedorova, T E; Efimenko, N V; Kaĭsinova, A S

2012-01-01

The objective of the present work was to estimate the effectiveness of combined spa-and-resort treatment with the use of the Essentuki-type drinking mineral waters for the patients presenting with non-alcoholic fatty liver disease. A total of 40 patients presening with non-alcoholic fatty liver disease (NOFLD) were available for the examination. The study has demonstrated positive dynamics of clinical symptoms and results of liver functional tests, characteristics of intrahepatic dynamics, lipid metabolism, antioxidant hemostais, and the hormonal status of the patients with non-alcoholic fatty liver disease. The intake of the Essentuki-type drinking mineral waters promoted normalization of adiponectin and leptin levels in conjunction with the reduction in the degree of insulin resistance, i.e., the key pathogenetic factors responsible for hepatic steatosis and non-alcoholic steatohepatitis. It is concluded that the Essentuki-type drinking mineral waters may be recommended for the inclusion in the combined treatment and prevention of the progression of non-alcoholic fatty liver disease.

Abnormal liver function in common variable immunodeficiency disorders due to nodular regenerative hyperplasia.

PubMed

Ward, C; Lucas, M; Piris, J; Collier, J; Chapel, H

2008-09-01

Patients with common variable immunodeficiency disorders are monitored for liver function test abnormalities. A proportion of patients develop deranged liver function and some also develop hepatomegaly. We investigated the prevalence of abnormalities and types of liver disease, aiming to identify those at risk and determine outcomes. The local primary immunodeficiency database was searched for patients with a common variable immunodeficiency disorder and abnormal liver function and/or a liver biopsy. Patterns of liver dysfunction were determined and biopsies reviewed. A total of 47 of 108 patients had deranged liver function, most commonly raised alkaline phosphatase levels. Twenty-three patients had liver biopsies. Nodular regenerative hyperplasia was found in 13 of 16 with unexplained pathology. These patients were more likely to have other disease-related complications of common variable immunodeficiency disorders, in particular non-coeliac (gluten insensitive) lymphocytic enteropathy. However, five had no symptoms of liver disease and only one died of liver complications. Nodular regenerative hyperplasia is a common complication of common variable immunodeficiency disorders but was rarely complicated by portal hypertension.

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.

Liver Disease and Pulmonary Hypertension

MedlinePlus

... Liver disease can cause what is known as “portal hypertension,” meaning increased blood pressure in the veins that ... diagnosed? A specialist can diagnose POPH by identifying portal hypertension (high pressure in the veins of the liver), ...

Circulating lipocalin 2 is neither related to liver steatosis in patients with non-alcoholic fatty liver disease nor to residual liver function in cirrhosis.

PubMed

Meier, Elisabeth M; Pohl, Rebekka; Rein-Fischboeck, Lisa; Schacherer, Doris; Eisinger, Kristina; Wiest, Reiner; Krautbauer, Sabrina; Buechler, Christa

2016-09-01

Lipocalin 2 (LCN2) is induced in the injured liver and associated with inflammation. Aim of the present study was to evaluate whether serum LCN2 is a non-invasive marker to assess hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) or residual liver function in patients with liver cirrhosis. Therefore, LCN2 was measured by ELISA in serum of 32 randomly selected patients without fatty liver (controls), 24 patients with ultrasound diagnosed NAFLD and 42 patients with liver cirrhosis mainly due to alcohol. Systemic LCN2 was comparable in patients with liver steatosis, those with liver cirrhosis and controls. LCN2 negatively correlated with bilirubin in both cohorts. In cirrhosis, LCN2 was not associated with more advanced liver injury defined by the CHILD-PUGH score and model for end-stage liver disease score. Resistin but not C-reactive protein or chemerin positively correlated with LCN2. LCN2 levels were not increased in patients with ascites or patients with esophageal varices. Consequently, reduction of portal pressure by transjugular intrahepatic portosystemic shunt did not affect LCN2 levels. Hepatic venous blood (HVS), portal venous blood and systemic venous blood levels of LCN2 were similar. HVS LCN2 was unchanged in patients with end-stage liver cirrhosis compared to those with well-compensated disease arguing against increased hepatic release. Current data exclude that serum LCN2 is of any value as steatosis marker in patients with NAFLD and indicator of liver function in patients with alcoholic liver cirrhosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Metabolic phenotyping and systems biology approaches to understanding metabolic syndrome and fatty liver disease.

PubMed

Dumas, Marc-Emmanuel; Kinross, James; Nicholson, Jeremy K

2014-01-01

Metabolic syndrome, a cluster of risk factors for type 2 diabetes mellitus and cardiovascular disease, is becoming an increasing global health concern. Insulin resistance is often associated with metabolic syndrome and also typical hepatic manifestations such as nonalcoholic fatty liver disease. Profiling of metabolic products (metabolic phenotyping or metabotyping) has provided new insights into metabolic syndrome and nonalcoholic fatty liver disease. Data from nuclear magnetic resonance spectroscopy and mass spectrometry combined with statistical modeling and top-down systems biology have allowed us to analyze and interpret metabolic signatures in terms of metabolic pathways and protein interaction networks and to identify the genomic and metagenomic determinants of metabolism. For example, metabolic phenotyping has shown that relationships between host cells and the microbiome affect development of the metabolic syndrome and fatty liver disease. We review recent developments in metabolic phenotyping and systems biology technologies and how these methodologies have provided insights into the mechanisms of metabolic syndrome and nonalcoholic fatty liver disease. We discuss emerging areas of research in this field and outline our vision for how metabolic phenotyping could be used to study metabolic syndrome and fatty liver disease. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Risk stratification in autoimmune cholestatic liver diseases: Opportunities for clinicians and trialists

PubMed Central

Trivedi, Palak J.; Corpechot, Christophe; Pares, Albert

2015-01-01

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are infrequent autoimmune cholestatic liver diseases, that disproportionate to their incidence and prevalence, remain very important causes of morbidity and mortality for patients with liver disease. Mechanistic insights spanning genetic risks and biological pathways to liver injury and fibrosis have led to a renewed interest in developing therapies beyond ursodeoxycholic acid that are aimed at both slowing disease course and improving quality of life. International cohort studies have facilitated a much greater understanding of disease heterogeneity, and in so doing highlight the opportunity to provide patients with a more individualized assessment of their risk of progressive liver disease, based on clinical, laboratory, or imaging findings. This has led to a new approach to patient care that focuses on risk stratification (both high and low risk); and furthermore allows such stratification tools to help identify patient subgroups at greatest potential benefit from inclusion in clinical trials. In this article, we review the applicability and validity of risk stratification in autoimmune cholestatic liver disease, highlighting strengths and weaknesses of current and emergent approaches. (Hepatology 2016;63:644–659) PMID:26290473

Can paracetamol (acetaminophen) be administered to patients with liver impairment?

PubMed

Hayward, Kelly L; Powell, Elizabeth E; Irvine, Katharine M; Martin, Jennifer H

2016-02-01

Although 60 years have passed since it became widely available on the therapeutic market, paracetamol dosage in patients with liver disease remains a controversial subject. Fulminant hepatic failure has been a well documented consequence of paracetamol overdose since its introduction, while short and long term use have both been associated with elevation of liver transaminases, a surrogate marker for acute liver injury. From these reports it has been assumed that paracetamol use should be restricted or the dosage reduced in patients with chronic liver disease. We review the factors that have been purported to increase risk of hepatocellular injury from paracetamol and the pharmacokinetic alterations in different pathologies of chronic liver disease which may affect this risk. We postulate that inadvertent under-dosing may result in concentrations too low to enable efficacy. Specific research to improve the evidence base for prescribing paracetamol in patients with different aetiologies of chronic liver disease is needed. © 2015 The British Pharmacological Society.

RNA interference against stromal interacting molecule-1 (STIM1) ameliorates ethanol-induced hepatotoxicity.

PubMed

Cui, Ruibing; Li, Rong; Guo, Xiaolan; Jia, Xiaoqing; Yan, Ming

2018-06-01

Previously we have demonstrated that stromal interacting molecule-1 (STIM1) was involved in ethanol induced liver injury. However, the exact pathogenic mechanism of STIM1 in alcoholic liver disease (ALD) is still unknown. We constructed plasmid vectors encoding short-hairpin RNA against STIM1 to investigate its role in ALD in the rat liver cell line BRL and in Sprague-Dawley rats. The results showed that STIM1 targeted sh-RNA (Sh-STIM1) significantly ameliorated ethanol-induced BRL cells injury and liver injury in rats with 20 weeks-induced alcoholic liver disease. Inhibition of STIM1 also reduced intracellular calcium ion concentration, reactive oxygen species (ROS) production, lipid peroxidation, NF-kappa B activation and TNF-α production under ethanol exposure. STIM1 may play an important role in the pathogenesis of alcoholic liver disease. Silencing STIM1 may be effective in preventing alcoholic liver disease. Copyright © 2018 Elsevier B.V. All rights reserved.

Hepatic progenitor cells in canine and feline medicine: potential for regenerative strategies

PubMed Central

2014-01-01

New curative therapies for severe liver disease are urgently needed in both the human and veterinary clinic. It is important to find new treatment modalities which aim to compensate for the loss of parenchymal tissue and to repopulate the liver with healthy hepatocytes. A prime focus in regenerative medicine of the liver is the use of adult liver stem cells, or hepatic progenitor cells (HPCs), for functional recovery of liver disease. This review describes recent developments in HPC research in dog and cat and compares these findings to experimental rodent studies and human pathology. Specifically, the role of HPCs in liver regeneration, key components of the HPC niche, and HPC activation in specific types of canine and feline liver disease will be reviewed. Finally, the potential applications of HPCs in regenerative medicine of the liver are discussed and a potential role is suggested for dogs as first target species for HPC-based trials. PMID:24946932

Progress and challenges in the prevention and control of nonalcoholic fatty liver disease.

PubMed

Cai, Jingjing; Zhang, Xiao-Jing; Li, Hongliang

2018-05-30

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide. Individuals with NAFLD have a high frequency of developing progressive liver disease and metabolism-related comorbidities, which result from of a lack of awareness and poor surveillance of the disease and a paucity of approved and effective therapies. Managing the complications of NAFLD has already begun to place a tremendous burden on health-care systems. Although efforts to identify effective therapies are underway, the lack of validated preclinical NAFLD models that represent the biology and outcomes of human disease remains a major barrier. This review summarizes the characteristics and prevalence of the disease and the status of our understanding of its mechanisms and potential therapeutic targets. © 2018 Wiley Periodicals, Inc.

The feasibility of a group stress management Liver SMART intervention for patients with end-stage liver disease: A pilot study.

PubMed

Jutagir, Devika R; Saracino, Rebecca M; Cunningham, Amy; Foran-Tuller, Kelly A; Driscoll, Mary A; Sledge, William H; Emre, Sukru H; Fehon, Dwain C

2018-06-04

Structured, empirically supported psychological interventions are lacking for patients who require organ transplantation. This stage IA psychotherapy development project developed and tested the feasibility, acceptability, tolerability, and preliminary efficacy of an 8-week group cognitive behavioral stress management intervention adapted for patients with end-stage liver disease awaiting liver transplantation. Twenty-nine English-speaking United Network for Organ Sharing-registered patients with end-stage liver disease from a single transplantation center enrolled in 8-week, group cognitive-behavioral liver stress management and relaxation training intervention adapted for patients with end-stage liver disease. Patients completed pre- and postintervention surveys that included the Beck Depression Inventory II and the Beck Anxiety Inventory. Feasibility, acceptability, tolerability, and preliminary efficacy were assessed.ResultAttendance rate was 69.40%. The intervention was rated as "good" to "excellent" by 100% of participants who completed the postintervention survey in teaching them new skills to relax and to cope with stress, and by 94.12% of participants in helping them feel supported while waiting for a liver transplant. No adverse events were recorded over the course of treatment. Attrition was 13.79%. Anxious and depressive symptoms were not statistically different after the intervention.Significance of resultsThe liver stress management and relaxation training intervention is feasible, acceptable, and tolerable to end-stage liver disease patients within a transplant clinic setting. Anxious and depressive symptoms remained stable postintervention. Randomized controlled trials are needed to study the intervention's effectiveness in this population.

Ethnicity and the diagnosis gap in liver disease: a population-based study.

PubMed

Alazawi, William; Mathur, Rohini; Abeysekera, Kushala; Hull, Sally; Boomla, Kambiz; Robson, John; Foster, Graham R

2014-11-01

Liver disease is a major cause of morbidity and mortality worldwide. Large numbers of liver function tests (LFTs) are performed in primary care, with abnormal liver biochemistry a common finding. Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. Metabolic syndrome, common in people from South Asia, is an important risk factor for NAFLD. It is hypothesised that a large gap exists between numbers of patients with abnormal LFTs and those with recorded liver diagnoses, and that NAFLD is more common among adults of South Asian ethnic groups. A cross-sectional study of 690,683 adults in coterminous general practices in a region with high ethnic diversity. Data were extracted on LFTs, liver disease, and process of care measures from computerised primary care medical records. LFTs were performed on 218,032 patients, of whom 31 627 had elevated serum transaminases. The prevalence of abnormal LFTs was highest among individuals of Bangladeshi ethnicity. Of the patients with abnormal LFTs, 88.4% did not have a coded liver diagnosis. NAFLD was the most frequently recorded liver disease and was most common among Bangladeshi patients. In a multivariate analysis, independent risk factors for NAFLD included Bangladeshi ethnicity, diabetes, raised BMI, hypertension, and hypercholesterolaemia. Abnormal LFTs are common in the population, but are underinvestigated and often remain undiagnosed. Bangladeshi ethnicity is an important independent risk factor for NAFLD. © British Journal of General Practice 2014.

Feasibility of detection and intervention for alcohol-related liver disease in the community: the Alcohol and Liver Disease Detection study (ALDDeS)

PubMed Central

Sheron, Nick; Moore, Michael; O’Brien, Wendy; Harris, Scott; Roderick, Paul

2013-01-01

Background In the past 15 years mortality rates from liver disease have doubled in the UK. Brief alcohol advice is cost effective, but clinically meaningful reductions in alcohol consumption only occur in around 1 in 10 individuals. Aim To provide evidence that detecting early liver disease in the community is feasible, practical, and that feedback of liver risk can increase the proportion of subjects reducing alcohol consumption. Design and setting A community feasibility study in nine general practice sites in Hampshire. Method Hazardous and harmful drinkers were identified by WHO AUDIT questionnaire and offered screening for liver fibrosis. Results In total, 4630 individuals responded, of whom 1128 (24%) hazardous or harmful drinkers were offered a liver fibrosis check using the Southampton Traffic Light (STL) test; 393 (38%) attended and test results were returned by post. The STL has a low threshold for liver fibrosis with 45 (11%) red, 157 (40%) amber, and 191 (49%) green results. Follow-up AUDIT data was obtained for 303/393 (77%) and 76/153 (50%) subjects with evidence of liver damage reduced drinking by at least one AUDIT category (harmful to hazardous, or hazardous to low risk) compared with 52/150 (35%, P<0.011) subjects without this evidence; in the subset of harmful drinkers patterns (AUDIT >15), 22/34 (65%) of STL positives, reduced drinking compared with 10/29 (35%, P<0.017) STL negatives. Conclusion Detection of liver disease in the community is feasible, and feedback of liver risk may reduce harmful drinking. PMID:24152485

Feasibility of detection and intervention for alcohol-related liver disease in the community: the Alcohol and Liver Disease Detection study (ALDDeS).

PubMed

Sheron, Nick; Moore, Michael; O'Brien, Wendy; Harris, Scott; Roderick, Paul

2013-10-01

In the past 15 years mortality rates from liver disease have doubled in the UK. Brief alcohol advice is cost effective, but clinically meaningful reductions in alcohol consumption only occur in around 1 in 10 individuals. To provide evidence that detecting early liver disease in the community is feasible, practical, and that feedback of liver risk can increase the proportion of subjects reducing alcohol consumption. A community feasibility study in nine general practice sites in Hampshire. Hazardous and harmful drinkers were identified by WHO AUDIT questionnaire and offered screening for liver fibrosis. In total, 4630 individuals responded, of whom 1128 (24%) hazardous or harmful drinkers were offered a liver fibrosis check using the Southampton Traffic Light (STL) test; 393 (38%) attended and test results were returned by post. The STL has a low threshold for liver fibrosis with 45 (11%) red, 157 (40%) amber, and 191 (49%) green results. Follow-up AUDIT data was obtained for 303/393 (77%) and 76/153 (50%) subjects with evidence of liver damage reduced drinking by at least one AUDIT category (harmful to hazardous, or hazardous to low risk) compared with 52/150 (35%, P<0.011) subjects without this evidence; in the subset of harmful drinkers patterns (AUDIT >15), 22/34 (65%) of STL positives, reduced drinking compared with 10/29 (35%, P<0.017) STL negatives. Detection of liver disease in the community is feasible, and feedback of liver risk may reduce harmful drinking.

In vivo label-free quantification of liver microcirculation using dual-modality microscopy

NASA Astrophysics Data System (ADS)

Yan, Jie; Kang, Yuzhan; Xu, Shuoyu; Ong, Lee-Ling S.; Zhuo, Shuangmu; Bunte, Ralph M.; Chen, Nanguang; Asada, H. Harry; So, Peter T. C.; Wanless, Ian R.; Yu, Hanry

2014-11-01

Microcirculation lesion is a common symptom of chronic liver diseases in the form of vasculature deformation and circulation alteration. In acute to chronic liver diseases such as biliary atresia, microcirculation lesion can have an early onset. Detection of microcirculation lesion is meaningful for studying the progression of liver disease. We have combined wide-field fluorescence microscopy and a laser speckle contrast technique to characterize hepatic microcirculation in vivo without labeling in a bile-duct ligation rat fibrosis model of biliary atresia. Through quantitative image analysis of four microcirculation parameters, we observed significant microcirculation lesion in the early to middle stages of fibrosis. This bimodal imaging method is useful to assess hepatic microcirculation lesion for the study of liver diseases.

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

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.