Lidocaine/monoethylglycinexylidide test, galactose elimination test, and sorbitol elimination test for metabolic assessment of liver cell bioreactors.

PubMed

Gerlach, Jörg C; Brayfield, Candace; Puhl, Gero; Borneman, Reiner; Müller, Christian; Schmelzer, Eva; Zeilinger, Katrin

2010-06-01

Various metabolic tests were compared for the performance characterization of a liver cell bioreactor as a routine function assessment of cultures in a standby for patient application in clinical studies. Everyday quality assessment (QA) is essential to ensure a continuous level of cellular functional capacity in the development of hepatic progenitor cell expansion systems providing cells for regenerative medicine research; it is also of interest to meet safety requirements in bioartificial extracorporeal liver support systems under clinical evaluation. Quality criteria for the description of bioreactor cultures were developed using primary porcine liver cells as a model. Porcine liver cells isolated by collagenase perfusion with an average of 3 x 10(9) primary cells were used in 39 bioreactors for culture periods up to 33 days. Measurements of monoethylglycinexylidide synthesis and elimination of lidocaine, galactose elimination, and sorbitol elimination proved to be useful for routine QA of primary liver cell cultures. We demonstrate two methods for dispensing test substances, bolus administration and continuous, steady-state administration. Bolus test data were grouped in Standard, Therapy, Infection/Contamination, and Cell-free control groups. Statistical analyses show significant differences among all groups for every test substance. Post hoc comparisons indicated significant differences between Standard and Cell-free groups for all elimination parameters. For continuous tests, results were categorized according to number of culture days and time-dependent changes were analyzed. Continuous administration enables a better view of culture health and the time dependency of cellular function, whereas bolus administration is more flexible. Both procedures can be used to define cell function. Assessment of cellular function and bioreactor quality can contribute significantly to the quality of experimental or clinical studies in the field of hepatic bioreactor development.

Effect of commonly used vehicles on gastrointestinal, renal, and liver function in rats.

PubMed

Pestel, Sabine; Martin, Hans-Juergen; Maier, Gerd-Michael; Guth, Brian

2006-01-01

Solubility is often a limiting factor when testing new compounds in animal experiments. Various solubilizing agents may be used, but each have their own pharmacological effects. We investigated the effects of selected vehicles having different chemical characteristics on gastrointestinal, renal, and liver function. Rats were treated orally, intravenously or intraperitoneally and gastric emptying, intestinal transit, renal, and liver function were investigated. Gastrointestinal motility was influenced by hydroxyethylcellulose, hydroxypropyl-beta-cyclodextrin (HPbetaCD), HPgammaCD, DMSO, polyethylene glycol 400 (PEG 400), fat emulsion, and the corresponding emulsifier. Liver function was affected by HPbetaCD, HPgammaCD, DMSO, PEG 400, Polysorbate 80, Cremophor RH 40, and fat emulsion. An increase in liver enzymes was observed after PEG 400 and Polysorbate 80. DMSO interfered with clinical chemistry measurements in serum. Urinary function was modified by HPgammaCD, DMSO, PEG 400, and Polysorbate 80, while enhanced urine enzyme excretion was observed after HPbetaCD, HPgammaCD, DMSO, PEG 400, and Polysorbate 80. Most of the investigated vehicles changed gastrointestinal, renal, and/or liver parameters after application of a certain threshold dose for each assay. No "best" vehicle could be identified that may be used in each test system. Thus, vehicles must be selected not only on their chemical characteristics but also on their potential pharmacological activity in a given test system.

Development of a Convenient In Vivo Hepatotoxin Assay Using a Transgenic Zebrafish Line with Liver-Specific DsRed Expression

PubMed Central

Zhang, Xiaoyan; Li, Caixia; Gong, Zhiyuan

2014-01-01

Previously we have developed a transgenic zebrafish line (LiPan) with liver-specific red fluorescent protein (DsRed) expression under the fabp10a promoter. Since red fluorescence in the liver greatly facilitates the observation of liver in live LiPan fry, we envision that the LiPan zebrafish may provide a useful tool in analyses of hepatotoxicity based on changes of liver red fluorescence intensity and size. In this study, we first tested four well-established hepatotoxins (acetaminophen, aspirin, isoniazid and phenylbutazone) in LiPan fry and demonstrated that these hepatotoxins could significantly reduce both liver red fluorescence and liver size in a dosage-dependent manner, thus the two measurable parameters could be used as indicators of hepatotoxicity. We then tested the LiPan fry with nine other chemicals including environmental toxicants and human drugs. Three (mefenamic acid, lindane, and arsenate) behave like hepatotoxins in reduction of liver red fluorescence, while three others (17β-estradiol, TCDD [2,3,7,8-tetrachlorodibenzo-p-dioxin] and NDMA [N-nitrosodimethylamine]) caused increase of liver red fluorescence and the liver size. Ethanol and two other chemicals, amoxicillin (antibiotics) and chlorphenamine (pain killer) did not resulted in significant changes of liver red fluorescence and liver size. By quantitative RT-PCR analysis, we found that the changes of red fluorescence intensity caused by different chemicals correlated to the changes of endogenous fabp10a RNA expression, indicating that the measured hepatotoxicity was related to fatty acid transportation and metabolism. Finally we tested a mixture of four hepatotoxins and observed a significant reduction of red fluorescence in the liver at concentrations below the lowest effective concentrations of individual hepatotoxins, suggesting that the transgenic zebrafish assay is capable of reporting compound hepatotoxicity effect from chemical mixtures. Thus, the LiPan transgenic fry provide a rapid and convenient in vivo hepatotoxicity assay that should be applicable to high-throughput hepatotoxicity test in drug screening as well as in biomonitoring environmental toxicants. PMID:24626481

First Definition of Reference Intervals of Liver Function Tests in China: A Large-Population-Based Multi-Center Study about Healthy Adults

PubMed Central

Zhang, Chuanbao; Guo, Wei; Huang, Hengjian; Ma, Yueyun; Zhuang, Junhua; Zhang, Jie

2013-01-01

Background Reference intervals of Liver function tests are very important for the screening, diagnosis, treatment, and monitoring of liver diseases. We aim to establish common reference intervals of liver function tests specifically for the Chinese adult population. Methods A total of 3210 individuals (20–79 years) were enrolled in six representative geographical regions in China. Analytes of ALT, AST, GGT, ALP, total protein, albumin and total bilirubin were measured using three analytical systems mainly used in China. The newly established reference intervals were based on the results of traceability or multiple systems, and then validated in 21 large hospitals located nationwide qualified by the National External Quality Assessment (EQA) of China. Results We had been established reference intervals of the seven liver function tests for the Chinese adult population and found there were apparent variances of reference values for the variables for partitioning analysis such as gender(ALT, GGT, total bilirubin), age(ALP, albumin) and region(total protein). More than 86% of the 21 laboratories passed the validation in all subgroup of reference intervals and overall about 95.3% to 98.8% of the 1220 validation results fell within the range of the new reference interval for all liver function tests. In comparison with the currently recommended reference intervals in China, the single side observed proportions of out of range of reference values from our study for most of the tests deviated significantly from the nominal 2.5% such as total bilirubin (15.2%), ALP (0.2%), albumin (0.0%). Most of reference intervals in our study were obviously different from that of other races. Conclusion These used reference intervals are no longer applicable for the current Chinese population. We have established common reference intervals of liver function tests that are defined specifically for Chinese population and can be universally used among EQA-approved laboratories located all over China. PMID:24058449

Review fantastic medical implications of 3D-printing in liver surgeries, liver regeneration, liver transplantation and drug hepatotoxicity testing: A review.

PubMed

Wang, Jing-Zhang; Xiong, Nan-Yan; Zhao, Li-Zhen; Hu, Jin-Tian; Kong, De-Cheng; Yuan, Jiang-Yong

2018-06-07

The epidemiological trend in liver diseases becomes more serious worldwide. Several recent articles published by International Journal of Surgery in 2018 particularly emphasized the encouraging clinical benefits of hepatectomy, liver regeneration and liver transplantation, however, there are still many technical bottlenecks underlying these therapeutic approaches. Remarkably, a few preliminary studies have shown some clues to the role of three-dimensional (3D) printing in improving traditional therapy for liver diseases. Here, we concisely elucidated the curative applications of 3D-printing (no cells) and 3D Bio-printing (with hepatic cells), such as 3D-printed patient-specific liver models and devices for medical education, surgical simulation, hepatectomy and liver transplantation, 3D Bio-printed hepatic constructs for liver regeneration and artificial liver, 3D-printed liver tissues for evaluating drug's hepatotoxicity, and so on. Briefly, 3D-printed liver models and bioactive tissues may facilitate a lot of key steps to cure liver disorders, predictably bringing promising clinical benefits. This work further provides novel insights into facilitating treatment of hepatic carcinoma, promoting liver regeneration both in vivo and in vitro, expanding transplantable liver resources, maximizing therapeutic efficacy as well as minimizing surgical complications, medical hepatotoxicity, operational time, economic costs, etc. Copyright © 2018. Published by Elsevier Ltd.

Surgical Strategy Based on Indocyanine Green Test for Chemotherapy-Associated Liver Injury and Long-Term Outcome in Colorectal Liver Metastases.

PubMed

Takamoto, Takeshi; Hashimoto, Takuya; Ichida, Akihiko; Shimada, Kei; Maruyama, Yoshikazu; Makuuchi, Masatoshi

2018-06-01

It remains unclear whether the presence of chemotherapy-induced liver injury (CALI) or impaired liver functional reserve affects the long-term outcome. This study assessed the applicability and long-term effects of using criteria based on the indocyanine green (ICG) test results in selecting the operative procedure among patients with colorectal liver metastases (CRLM) who had a risk of CALI. CRLM patients who received preoperative chemotherapy including oxaliplatin and/or irinotecan prior to a curative hepatectomy between 2007 and 2017 were included. For each case, the minimum required future remnant liver volume and operative procedure were decided based on the ICG retention rate at 15 min (ICG R15). Patients with an ICG R15 > 10% and who had undergone a major hepatectomy were categorized in a marginal liver functional reserve (MHML) group. Overall, 161 patients were included; 77 of them had an ICG R15 > 10%, and 57 had pathological liver injury (PLI). After the median follow-up time of 30.9 months, the 5-year overall survival rate was 36.1%. The presence of an impaired ICG test result or CALI did not negatively impact the overall and recurrence-free survival outcomes. A multivariate analysis revealed that the presence of four or more nodules of liver metastases was the only independent predictor of a poor overall survival. A significantly larger proportion of patients in the MHML group (n = 37) had a 25% or larger increase in splenic volume (30 vs. 13%; P = 0.024). The presence of an impaired ICG test result or PLI did not affect the long-term outcome after individually selected operative procedure. However, patients undergoing MHML had a higher possibility of developing a > 25% splenic volume increase after hepatectomy.

Fractionated External Beam Radiotherapy as a Suitable Preparative Regimen for Hepatocyte Transplantation After Partial Hepatectomy

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

Krause, Petra; Wolff, Hendrik A.; Rave-Frank, Margret

2011-07-15

Purpose: Hepatocyte transplantation is strongly considered to be a promising option to correct chronic liver failure through repopulation of the diseased organ. We already reported on extensive liver repopulation by hepatocytes transplanted into rats preconditioned with 25-Gy single dose selective external beam irradiation (IR). Herein, we tested lower radiation doses and fractionated protocols, which would be applicable in clinical use. Methods and Material: Livers of dipeptidylpeptidase IV (DPPIV)-deficient rats were preconditioned with partial liver external beam single dose IR at 25 Gy, 8 Gy, or 5 Gy, or fractionated IR at 5 x 5 Gy or 5 x 2 Gy.more » Four days after completion of IR, a partial hepatectomy (PH) was performed to resect the untreated liver section. Subsequently, 12 million wild-type (DPPIV{sup +}) hepatocytes were transplanted via the spleen into the recipient livers. The degree of donor cell integration and liver repopulation was studied 16 weeks after transplantation by means of immunofluorescence and DPPIV-luminescence assay. Results: Donor hepatocyte integration and liver repopulation were more effective in the irradiated livers following pretreatment with the IR doses 1 x 25 Gy and 5 x 5 Gy (formation of large DPPIV-positive cell clusters) than single-dose irradiation at 8 Gy or 5 Gy (DPPIV-positive clusters noticeably smaller and less frequent). Quantitative analysis of extracted DPPIV revealed signals exceeding the control level in all transplanted animals treated with IR and PH. Compared with the standard treatment of 1 x 25 Gy, fractionation with 5 x 5 Gy was equally efficacious, the Mann-Whitney U test disclosing no statistically significant difference (p = 0.146). The lower doses of 1 x 5 Gy, 1 x 8 Gy, and 5 x 2 Gy were significantly less effective with p < 0.05. Conclusion: This study suggests that fractionated radiotherapy in combination with PH is a conceivable pretreatment approach to prime the host liver for hepatocyte transplantation, thus bringing the experimental model a step closer to clinical application.« less

A multimodality imaging-compatible insertion robot with a respiratory motion calibration module designed for ablation of liver tumors: a preclinical study.

PubMed

Li, Dongrui; Cheng, Zhigang; Chen, Gang; Liu, Fangyi; Wu, Wenbo; Yu, Jie; Gu, Ying; Liu, Fengyong; Ren, Chao; Liang, Ping

2018-04-03

To test the accuracy and efficacy of the multimodality imaging-compatible insertion robot with a respiratory motion calibration module designed for ablation of liver tumors in phantom and animal models. To evaluate and compare the influences of intervention experience on robot-assisted and ultrasound-controlled ablation procedures. Accuracy tests on rigid body/phantom model with a respiratory movement simulation device and microwave ablation tests on porcine liver tumor/rabbit liver cancer were performed with the robot we designed or with the traditional ultrasound-guidance by physicians with or without intervention experience. In the accuracy tests performed by the physicians without intervention experience, the insertion accuracy and efficiency of robot-assisted group was higher than those of ultrasound-guided group with statistically significant differences. In the microwave ablation tests performed by the physicians without intervention experience, better complete ablation rate was achieved when applying the robot. In the microwave ablation tests performed by the physicians with intervention experience, there was no statistically significant difference of the insertion number and total ablation time between the robot-assisted group and the ultrasound-controlled group. The evaluation by the NASA-TLX suggested that the robot-assisted insertion and microwave ablation process performed by physicians with or without experience were more comfortable. The multimodality imaging-compatible insertion robot with a respiratory motion calibration module designed for ablation of liver tumors could increase the insertion accuracy and ablation efficacy, and minimize the influence of the physicians' experience. The ablation procedure could be more comfortable with less stress with the application of the robot.

Physiological and biochemical basis of clinical liver function tests: a review.

PubMed

Hoekstra, Lisette T; de Graaf, Wilmar; Nibourg, Geert A A; Heger, Michal; Bennink, Roelof J; Stieger, Bruno; van Gulik, Thomas M

2013-01-01

To review the literature on the most clinically relevant and novel liver function tests used for the assessment of hepatic function before liver surgery. Postoperative liver failure is the major cause of mortality and morbidity after partial liver resection and develops as a result of insufficient remnant liver function. Therefore, accurate preoperative assessment of the future remnant liver function is mandatory in the selection of candidates for safe partial liver resection. A MEDLINE search was performed using the key words "liver function tests," "functional studies in the liver," "compromised liver," "physiological basis," and "mechanistic background," with and without Boolean operators. Passive liver function tests, including biochemical parameters and clinical grading systems, are not accurate enough in predicting outcome after liver surgery. Dynamic quantitative liver function tests, such as the indocyanine green test and galactose elimination capacity, are more accurate as they measure the elimination process of a substance that is cleared and/or metabolized almost exclusively by the liver. However, these tests only measure global liver function. Nuclear imaging techniques ((99m)Tc-galactosyl serum albumin scintigraphy and (99m)Tc-mebrofenin hepatobiliary scintigraphy) can measure both total and future remnant liver function and potentially identify patients at risk for postresectional liver failure. Because of the complexity of liver function, one single test does not represent overall liver function. In addition to computed tomography volumetry, quantitative liver function tests should be used to determine whether a safe resection can be performed. Presently, (99m)Tc-mebrofenin hepatobiliary scintigraphy seems to be the most valuable quantitative liver function test, as it can measure multiple aspects of liver function in, specifically, the future remnant liver.

Modeling Liver-Related Adverse Effects of Drugs Using kNN QSAR Method

PubMed Central

Rodgers, Amie D.; Zhu, Hao; Fourches, Dennis; Rusyn, Ivan; Tropsha, Alexander

2010-01-01

Adverse effects of drugs (AEDs) continue to be a major cause of drug withdrawals both in development and post-marketing. While liver-related AEDs are a major concern for drug safety, there are few in silico models for predicting human liver toxicity for drug candidates. We have applied the Quantitative Structure Activity Relationship (QSAR) approach to model liver AEDs. In this study, we aimed to construct a QSAR model capable of binary classification (active vs. inactive) of drugs for liver AEDs based on chemical structure. To build QSAR models, we have employed an FDA spontaneous reporting database of human liver AEDs (elevations in activity of serum liver enzymes), which contains data on approximately 500 approved drugs. Approximately 200 compounds with wide clinical data coverage, structural similarity and balanced (40/60) active/inactive ratio were selected for modeling and divided into multiple training/test and external validation sets. QSAR models were developed using the k nearest neighbor method and validated using external datasets. Models with high sensitivity (>73%) and specificity (>94%) for prediction of liver AEDs in external validation sets were developed. To test applicability of the models, three chemical databases (World Drug Index, Prestwick Chemical Library, and Biowisdom Liver Intelligence Module) were screened in silico and the validity of predictions was determined, where possible, by comparing model-based classification with assertions in publicly available literature. Validated QSAR models of liver AEDs based on the data from the FDA spontaneous reporting system can be employed as sensitive and specific predictors of AEDs in pre-clinical screening of drug candidates for potential hepatotoxicity in humans. PMID:20192250

Human and rat liver phenol sulfotransferase: structure-activity relationships for phenolic substrates.

PubMed

Campbell, N R; Van Loon, J A; Sundaram, R S; Ames, M M; Hansch, C; Weinshilboum, R

1987-12-01

Phenol sulfotransferase (PST) catalyzes the sulfate conjugation of many phenolic drugs. Human liver contains thermostable (TS) and thermolabile forms of PST. Ion exchange chromatography shows that two isozymes of TS PST (peaks I and II) are present in human liver preparations. Rat liver contains four forms of PST that can be separated by ion exchange chromatography. Quantitative structure-activity relationship (QSAR) analysis was used to study phenolic substrates for both human and rat liver PST. Thirty-six substituted phenols were tested as substrates for partially purified human liver TS PST peak I. QSAR analysis resulted in derivation of the following equation: log 1/Km = 0.92 (+/- 0.18)log P - 1.48 (+/- 0.38)MR'4 - 0.64 (+/- 0.41)MR3 + 1.04 (+/- 0.63)MR2 + 0.67(+/- 0.44) sigma- + 4.03 (+/- 0.42). In this equation Km is the Michaelis constant, P is the octanol-water partition coefficient, MR is the molar refractivity of substituents at the 2-, 3-, and 4-positions, and sigma- is the Hammett constant. Values of log 1/Km calculated with this equation were highly correlated with log 1/Km values (r = 0.950) that were observed experimentally. Nine phenols were also tested as substrates for partially purified human liver TS PST peak II. Log 1/Km values for these compounds were significantly correlated for the two isozymes of TS PST (r = 0.992, p less than 0.001). QSAR analysis was also used to derive equations that described the behavior of phenolic substrates for rat liver PST forms I and II. These equations differed substantially from the equation derived for compounds tested with human liver TS PST peak I. Therefore, the characteristics of the active sites of human liver TS PST peak I and rat liver PST forms I and II appear to differ. Application of these equations may make it possible to predict Km values of phenolic substrates for human liver TS PST and for rat liver PST forms I and II.

Review article: Probiotics in gastrointestinal and liver diseases.

PubMed

Jonkers, D; Stockbrügger, R

2007-12-01

Probiotics, defined as live micro-organisms with beneficial effects for the host, are widely applied in gastrointestinal and liver diseases. To review the available evidence of clinical trials on probiotics in gastrointestinal and liver diseases, with a major focus on irritable bowel syndrome, inflammatory bowel disease, pancreatitis and chronic liver diseases. Evidence for the therapeutic or preventive application of particular probiotic strains is available for antibiotic-associated diarrhoea, rota-virus-associated diarrhoea and pouchitis. Results are encouraging for irritable bowel syndrome, ulcerative colitis and for reducing side effects by Helicobacter pylori eradication therapies, but are less clear for Crohn's disease, lactose intolerance and constipation. In general, for most of these patient groups, more placebo-controlled methodologically well-designed studies that pay attention to both clinical outcome and mechanistic aspects are required. The application in liver disease and pancreatitis is promising, but more human trials have to be awaited. Possible mechanisms of probiotics include modulation of the intestinal microbiota and the immune system, but different bacterial may have different effects. Further insight into disease entities and the functioning of probiotic strains is required to be able to select disease-specific strains, which have to be tested in well-designed placebo-controlled studies.

Laparoscopic versus open liver segmentectomy: prospective, case-matched, intention-to-treat analysis of clinical outcomes and cost effectiveness.

PubMed

Polignano, Francesco M; Quyn, Aaron J; de Figueiredo, Rodrigo S M; Henderson, Nikola A; Kulli, Christoph; Tait, Iain S

2008-12-01

Reduction in hospital stay, blood loss, postoperative pain and complications are common findings after laparoscopic liver resection, suggesting that the laparoscopic approach may be a suitable alternative to open surgery. Some concerns have been raised regarding cost effectiveness of this procedure and potential implications of its large-scale application. Our aim has been to determine cost effectiveness of laparoscopic liver surgery by a case-matched, case-control, intention-to-treat analysis of its costs and short-term clinical outcomes compared with open surgery. Laparoscopic liver segmentectomies and bisegmentectomies performed at Ninewells Hospital and Medical School between 2005 and 2007 were considered. Resections involving more than two Couinaud segments, or involving any synchronous procedure, were excluded. An operation-magnitude-matched control group was identified amongst open liver resections performed between 2004 and 2007. Hospital costs were obtained from the Scottish Health Service Costs Book (ISD Scotland) and average national costs were calculated. Cost of theatre time, disposable surgical devices, hospital stay, and high-dependency unit (HDU) and intensive care unit (ICU) usage were the main endpoints for comparison. Secondary endpoints were morbidity and mortality. Statistical analysis was performed with Student's t-test, chi(2) and Fisher exact test as most appropriate. Twenty-five laparoscopic liver resections were considered, including atypical resection, segmentectomy and bisegmentectomy, and they were compared to 25 matching open resections. The two groups were homogeneous by age, sex, coexistent morbidity, magnitude of resection, prevalence of liver cirrhosis and indications. Operative time (p < 0.03), blood loss (p < 0.0001), Pringle manoeuvre (p < 0.03), hospital stay (p < 0.003) and postoperative complications (p < 0.002) were significantly reduced in the laparoscopic group. Overall hospital cost was significantly lower in the laparoscopic group by an average of 2,571 pounds sterling (p < 0.04). Laparoscopic liver segmentectomy and bisegmentectomy are feasible, safe and cost effective compared to similar open resections. Large-scale application of laparoscopic liver surgery could translate into significant savings to hospitals and health care programmes.

Shape-intensity prior level set combining probabilistic atlas and probability map constrains for automatic liver segmentation from abdominal CT images.

PubMed

Wang, Jinke; Cheng, Yuanzhi; Guo, Changyong; Wang, Yadong; Tamura, Shinichi

2016-05-01

Propose a fully automatic 3D segmentation framework to segment liver on challenging cases that contain the low contrast of adjacent organs and the presence of pathologies from abdominal CT images. First, all of the atlases are weighted in the selected training datasets by calculating the similarities between the atlases and the test image to dynamically generate a subject-specific probabilistic atlas for the test image. The most likely liver region of the test image is further determined based on the generated atlas. A rough segmentation is obtained by a maximum a posteriori classification of probability map, and the final liver segmentation is produced by a shape-intensity prior level set in the most likely liver region. Our method is evaluated and demonstrated on 25 test CT datasets from our partner site, and its results are compared with two state-of-the-art liver segmentation methods. Moreover, our performance results on 10 MICCAI test datasets are submitted to the organizers for comparison with the other automatic algorithms. Using the 25 test CT datasets, average symmetric surface distance is [Formula: see text] mm (range 0.62-2.12 mm), root mean square symmetric surface distance error is [Formula: see text] mm (range 0.97-3.01 mm), and maximum symmetric surface distance error is [Formula: see text] mm (range 12.73-26.67 mm) by our method. Our method on 10 MICCAI test data sets ranks 10th in all the 47 automatic algorithms on the site as of July 2015. Quantitative results, as well as qualitative comparisons of segmentations, indicate that our method is a promising tool to improve the efficiency of both techniques. The applicability of the proposed method to some challenging clinical problems and the segmentation of the liver are demonstrated with good results on both quantitative and qualitative experimentations. This study suggests that the proposed framework can be good enough to replace the time-consuming and tedious slice-by-slice manual segmentation approach.

In situ precision electrospinning as an effective delivery technique for cyanoacrylate medical glue with high efficiency and low toxicity.

PubMed

Dong, R H; Qin, C C; Qiu, X; Yan, X; Yu, M; Cui, L; Zhou, Y; Zhang, H D; Jiang, X Y; Long, Y Z

2015-12-14

The side effects or toxicity of cyanoacrylate used in vivo have been argued since its first application in wound closure. We propose an airflow-assisted in situ precision electrospinning apparatus as an applicator and make a detailed comparison with traditional spraying via in vitro and in vivo experiments. This novel method can not only improve operational performance and safety by precisely depositing cyanoacrylate fibers onto a wound, but significantly reduce the dosage of cyanoacrylate by almost 80%. A white blood cell count, liver function test and histological analysis prove that the in situ precision electrospinning applicator produces a better postoperative outcome, e.g., minor hepatocyte injury, moderate inflammation and the significant ability for liver regeneration. This in situ precision electrospinning method may thus dramatically broaden both civilian and military applications of cyanoacrylates.

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

Long Term Influence of Carbon Nanoparticles on Health and Liver Status in Rats

PubMed Central

Strojny, Barbara; Kurantowicz, Natalia; Sawosz, Ewa; Grodzik, Marta; Jaworski, Sławomir; Kutwin, Marta; Wierzbicki, Mateusz; Hotowy, Anna; Lipińska, Ludwika; Chwalibog, André

2015-01-01

Due to their excellent biocompatibility, carbon nanoparticles have been widely investigated for prospective biomedical applications. However, their impact on an organism with prolonged exposure is still not well understood. Here, we performed an experiment investigating diamond, graphene oxide and graphite nanoparticles, which were repeatedly administrated intraperitoneally into Wistar rats for four weeks. Some of the animals was sacrificed after the last injection, whereas the rest were sacrificed twelve weeks after the last exposure. We evaluated blood morphology and biochemistry, as well as the redox and inflammatory state of the liver. The results show the retention of nanoparticles within the peritoneal cavity in the form of prominent aggregates in proximity to the injection site, as well as the presence of some nanoparticles in the mesentery. Small aggregates were also visible in the liver serosa, suggesting possible transportation to the liver. However, none of the tested nanoparticles affected the health of animals. This lack of toxic effect may suggest the potential applicability of nanoparticles as drug carriers for local therapies, ensuring accumulation and slow release of drugs into a targeted tissue without harmful systemic side effects. PMID:26657282

Long Term Influence of Carbon Nanoparticles on Health and Liver Status in Rats.

PubMed

Strojny, Barbara; Kurantowicz, Natalia; Sawosz, Ewa; Grodzik, Marta; Jaworski, Sławomir; Kutwin, Marta; Wierzbicki, Mateusz; Hotowy, Anna; Lipińska, Ludwika; Chwalibog, André

2015-01-01

Due to their excellent biocompatibility, carbon nanoparticles have been widely investigated for prospective biomedical applications. However, their impact on an organism with prolonged exposure is still not well understood. Here, we performed an experiment investigating diamond, graphene oxide and graphite nanoparticles, which were repeatedly administrated intraperitoneally into Wistar rats for four weeks. Some of the animals was sacrificed after the last injection, whereas the rest were sacrificed twelve weeks after the last exposure. We evaluated blood morphology and biochemistry, as well as the redox and inflammatory state of the liver. The results show the retention of nanoparticles within the peritoneal cavity in the form of prominent aggregates in proximity to the injection site, as well as the presence of some nanoparticles in the mesentery. Small aggregates were also visible in the liver serosa, suggesting possible transportation to the liver. However, none of the tested nanoparticles affected the health of animals. This lack of toxic effect may suggest the potential applicability of nanoparticles as drug carriers for local therapies, ensuring accumulation and slow release of drugs into a targeted tissue without harmful systemic side effects.

Clinical Application of Pluripotent Stem Cells: An Alternative Cell-Based Therapy for Treating Liver Diseases?

PubMed

Tolosa, Laia; Pareja, Eugenia; Gómez-Lechón, Maria José

2016-12-01

The worldwide shortage of donor livers for organ and hepatocyte transplantation has prompted the search for alternative therapies for intractable liver diseases. Cell-based therapy is envisaged as a useful therapeutic option to recover and stabilize the lost metabolic function for acute liver failure, end-stage and congenital liver diseases, or for those patients who are not considered eligible for organ transplantation. In recent years, research to identify alternative and reliable cell sources for transplantation that can be derived by reproducible methods has been encouraged. Human pluripotent stem cells (PSCs), which comprise both embryonic and induced PSCs, may offer many advantages as an alternative to hepatocytes for liver cell therapy. Their capacity for expansion, hepatic differentiation and self-renewal make them a promising source of unlimited numbers of hepatocyte-like cells for treating and repairing damaged livers. Immunogenicity and tumorigenicity of human PSCs remain the bottleneck for successful clinical application. However, recent advances made to develop disease-corrected hepatocyte-like cells from patients' human-induced PSCs by gene editing have opened up many potential gateways for the autologous treatment of hereditary liver diseases, which may likely reduce the risk of rejection and the need for lifelong immunosuppression. Well-defined methods to reduce the expression of oncogenic genes in induced PSCs, including protocols for their complete and safe hepatic differentiation, should be established to minimize the tumorigenicity of transplanted cells. On top of this, such new strategies are currently being rigorously tested and validated in preclinical studies before they can be safely transferred to clinical practice with patients.

Noninvasive models for assessment of liver fibrosis in patients with chronic hepatitis B virus infection

PubMed Central

Zeng, Da-Wu; Dong, Jing; Liu, Yu-Rui; Jiang, Jia-Ji; Zhu, Yue-Yong

2016-01-01

There are approximately 240 million patients with chronic hepatitis B virus (HBV) infection worldwide. Up to 40% of HBV-infected patients can progress to liver cirrhosis, hepatocellular carcinoma or chronic end-stage liver disease during their lifetime. This, in turn, is responsible for around 650000 deaths annually worldwide. Repeated hepatitis flares may increase the progression of liver fibrosis, making the accurate diagnosis of the stage of liver fibrosis critical in order to make antiviral therapeutic decisions for HBV-infected patients. Liver biopsy remains the “gold standard” for diagnosing liver fibrosis. However, this technique has recently been challenged by the development of several novel noninvasive tests to evaluate liver fibrosis, including serum markers, combined models and imaging techniques. In addition, the cost and accessibility of imaging techniques have been suggested as additional limitations for invasive assessment of liver fibrosis in developing countries. Therefore, a noninvasive assessment model has been suggested to evaluate liver fibrosis, specifically in HBV-infected patients, owing to its high applicability, inter-laboratory reproducibility, wide availability for repeated assays and reasonable cost. The current review aims to present the status of knowledge in this new and exciting field, and to highlight the key points in HBV-infected patients for clinicians. PMID:27547009

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/

Application of kidney inhibition swab tests to evaluate penicillin-G residues in sow tissues and body fluids following intramuscular injection

USDA-ARS?s Scientific Manuscript database

Kidney inhibition swab (KIS) tests, recently adapted by the US FSIS for antibiotics on-site screening, were employed to evaluate the depletion of penicillin-G residues from kidney, liver, muscle, serum, and urine of sows after intramuscular (IM) penicillin-G procaine administration. Sows (n=130; 22...

Liver function tests

MedlinePlus

Liver function tests are common tests that are used to see how well the liver is working. Tests include: ... E, Bowne WB, Bluth MH. Evaluation of liver function. In: McPherson RA, Pincus MR, eds. Henry's Clinical ...

Liver Function Tests

MedlinePlus

... food, store energy, and remove poisons. Liver function tests are blood tests that check to see how well your liver ... hepatitis and cirrhosis. You may have liver function tests as part of a regular checkup. Or you ...

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 ...

Application of the combined FibroMeter vibration-controlled transient elastography algorithm in Chinese patients with non-alcoholic fatty liver disease.

PubMed

Loong, Thomson Chi-Wang; Wei, Jeremy Lok; Leung, Jonathan Chung-Fai; Wong, Grace Lai-Hung; Shu, Sally She-Ting; Chim, Angel Mei-Ling; Chan, Anthony Wing-Hung; Choi, Paul Cheung-Lung; Tse, Yee-Kit; Chan, Henry Lik-Yuen; Wong, Vincent Wai-Sun

2017-07-01

The FibroMeter vibration-controlled transient elastography (FM VCTE) is a new formula combining the serum test FM and liver stiffness measurement (LSM) by VCTE. We tested the accuracy and utility of FM VCTE for fibrosis staging in patients with non-alcoholic fatty liver disease (NAFLD). Two hundred fifteen NAFLD patients with LSM, FM NAFLD, FM VCTE, and other serum tests (aspartate aminotransferase-to-platelet ratio index, fibrosis-4 index, BARD score, NAFLD fibrosis score, and aspartate aminotransferase-to-alanine aminotransferase ratio) performed 1 day before liver biopsy were evaluated. Sixty-nine (32.1%) and 43 (20.0%) patients had F2-4 and F3-4, respectively. LSM had higher diagnostic accuracy (area under receiver-operating characteristics curves [AUROC] 0.851 for F2-4, 0.940 for F3-4; Obuchowski index 0.937 ± 0.007) than all evaluated serum tests, while FM NAFLD was the most accurate serum test (AUROC 0.775 and 0.774; Obuchowski index 0.891 ± 0.013). FM VCTE had similar accuracy to LSM (AUROC 0.855 and 0.901; Obuchowski index 0.927 ± 0.009). LSM had excellent negative predictive values of 92.4% and 99.2% to exclude F2-4 and F3-4, but the positive predictive values (PPV) were only 71.4% and 61.0%, respectively. In patients with high LSM, the use of FM VCTE improved the PPV from 71.4% to 84.4% for F2-4 and from 61.0% to 88.9% for F3-4. Liver biopsy could be spared in around 50-65% of patients. Liver stiffness measurement alone can confidently exclude significant and advanced fibrosis in NAFLD patients. Using FM VCTE in patients with high liver stiffness can increase the positive predictive value to rule in F2-4 and F3-4. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Tissue deposition of the insect repellent DEET and the sunscreen oxybenzone from repeated topical skin applications in rats.

PubMed

Fediuk, Daryl J; Wang, Tao; Raizman, Joshua E; Parkinson, Fiona E; Gu, Xiaochen

2010-12-01

Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone are capable of enhancing skin permeation of each other when applied simultaneously. We carried out a cellular study in rat astrocytes and neurons to assess cell toxicity of DEET and oxybenzone and a 30-day study in Sprague-Dawley rats to characterize skin permeation and tissue disposition of the compounds. Cellular toxicity occurred at 1 µg/mL for neurons and 7-day treatment for astrocytes and neurons. DEET and oxybenzone permeated across the skin to accumulate in blood, liver, and brain after repeated topical applications. DEET disappeared from the application site faster than oxybenzone. Combined application enhanced the disposition of DEET in liver. No overt sign of behavioral toxicity was observed from several behavioral testing protocols. It was concluded that despite measurable disposition of the study compounds in vivo, there was no evidence of neurotoxicological deficits from repeated topical applications of DEET, oxybenzone, or both. © The Author(s) 2010

[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.

ASS and SULT2A1 are Novel and Sensitive Biomarkers of Acute Hepatic Injury-A Comparative Study in Animal Models.

PubMed

Prima, Victor; Cao, Mengde; Svetlov, Stanislav I

2013-01-10

Liver and kidney damage associated with polytrauma, endotoxic shock/sepsis, and organ transplantation, are among the leading causes of the multiple organ failure. Development of novel sensitive biomarkers that detect early stages of liver and kidney injury is vital for the effective diagnostics and treatment of these life-threatening conditions. Previously, we identified several hepatic proteins, including Argininosuccinate Synthase (ASS) and sulfotransferases which were degraded in the liver and rapidly released into circulation during Ischemia/Reperfusion (I/R) injury. Here we compared sensitivity and specificity of the newly developed sandwich ELISA assays for ASS and the sulfotransferase isoform SULT2A1 with the standard clinical liver and kidney tests Alanine Aminotransferase (ALT) and Aspartate Transaminase (AST) in various pre-clinical models of acute injury. Our data suggest that ASS and SULT2A1 have superior characteristics for liver and kidney health assessment in endotoxemia, Ischemia/Reperfusion (I/R), chemical and drug-induced liver injury and may be of high potential value for clinical applications.

ASS and SULT2A1 are Novel and Sensitive Biomarkers of Acute Hepatic Injury-A Comparative Study in Animal Models

PubMed Central

Prima, Victor; Cao, Mengde; Svetlov, Stanislav I

2013-01-01

Liver and kidney damage associated with polytrauma, endotoxic shock/sepsis, and organ transplantation, are among the leading causes of the multiple organ failure. Development of novel sensitive biomarkers that detect early stages of liver and kidney injury is vital for the effective diagnostics and treatment of these life-threatening conditions. Previously, we identified several hepatic proteins, including Argininosuccinate Synthase (ASS) and sulfotransferases which were degraded in the liver and rapidly released into circulation during Ischemia/Reperfusion (I/R) injury. Here we compared sensitivity and specificity of the newly developed sandwich ELISA assays for ASS and the sulfotransferase isoform SULT2A1 with the standard clinical liver and kidney tests Alanine Aminotransferase (ALT) and Aspartate Transaminase (AST) in various pre-clinical models of acute injury. Our data suggest that ASS and SULT2A1 have superior characteristics for liver and kidney health assessment in endotoxemia, Ischemia/Reperfusion (I/R), chemical and drug-induced liver injury and may be of high potential value for clinical applications. PMID:23724364

Development of a web-based liver cancer prediction model for type II diabetes patients by using an artificial neural network.

PubMed

Rau, Hsiao-Hsien; Hsu, Chien-Yeh; Lin, Yu-An; Atique, Suleman; Fuad, Anis; Wei, Li-Ming; Hsu, Ming-Huei

2016-03-01

Diabetes mellitus is associated with an increased risk of liver cancer, and these two diseases are among the most common and important causes of morbidity and mortality in Taiwan. To use data mining techniques to develop a model for predicting the development of liver cancer within 6 years of diagnosis with type II diabetes. Data were obtained from the National Health Insurance Research Database (NHIRD) of Taiwan, which covers approximately 22 million people. In this study, we selected patients who were newly diagnosed with type II diabetes during the 2000-2003 periods, with no prior cancer diagnosis. We then used encrypted personal ID to perform data linkage with the cancer registry database to identify whether these patients were diagnosed with liver cancer. Finally, we identified 2060 cases and assigned them to a case group (patients diagnosed with liver cancer after diabetes) and a control group (patients with diabetes but no liver cancer). The risk factors were identified from the literature review and physicians' suggestion, then, chi-square test was conducted on each independent variable (or potential risk factor) for a comparison between patients with liver cancer and those without, those found to be significant were selected as the factors. We subsequently performed data training and testing to construct artificial neural network (ANN) and logistic regression (LR) prediction models. The dataset was randomly divided into 2 groups: a training group and a test group. The training group consisted of 1442 cases (70% of the entire dataset), and the prediction model was developed on the basis of the training group. The remaining 30% (618 cases) were assigned to the test group for model validation. The following 10 variables were used to develop the ANN and LR models: sex, age, alcoholic cirrhosis, nonalcoholic cirrhosis, alcoholic hepatitis, viral hepatitis, other types of chronic hepatitis, alcoholic fatty liver disease, other types of fatty liver disease, and hyperlipidemia. The performance of the ANN was superior to that of LR, according to the sensitivity (0.757), specificity (0.755), and the area under the receiver operating characteristic curve (0.873). After developing the optimal prediction model, we base on this model to construct a web-based application system for liver cancer prediction, which can provide support to physicians during consults with diabetes patients. In the original dataset (n=2060), 33% of diabetes patients were diagnosed with liver cancer (n=515). After using 70% of the original data to training the model and other 30% for testing, the sensitivity and specificity of our model were 0.757 and 0.755, respectively; this means that 75.7% of diabetes patients can be predicted correctly to receive a future liver cancer diagnosis, and 75.5% can be predicted correctly to not be diagnosed with liver cancer. These results reveal that this model can be used as effective predictors of liver cancer for diabetes patients, after discussion with physicians; they also agreed that model can assist physicians to advise potential liver cancer patients and also helpful to decrease the future cost incurred upon cancer treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

In Vitro Hepatic Trans-Differentiation of Human Mesenchymal Stem Cells Using Sera from Congestive/Ischemic Liver during Cardiac Failure

PubMed Central

Bishi, Dillip Kumar; Mathapati, Santosh; Cherian, Kotturathu Mammen; Guhathakurta, Soma; Verma, Rama Shanker

2014-01-01

Cellular therapy for end-stage liver failures using human mesenchymal stem cells (hMSCs)-derived hepatocytes is a potential alternative to liver transplantation. Hepatic trans-differentiation of hMSCs is routinely accomplished by induction with commercially available recombinant growth factors, which is of limited clinical applications. In the present study, we have evaluated the potential of sera from cardiac-failure-associated congestive/ischemic liver patients for hepatic trans-differentiation of hMSCs. Results from such experiments were confirmed through morphological changes and expression of hepatocyte-specific markers at molecular and cellular level. Furthermore, the process of mesenchymal-to-epithelial transition during hepatic trans-differentiation of hMSCs was confirmed by elevated expression of E-Cadherin and down-regulation of Snail. The functionality of hMSCs-derived hepatocytes was validated by various liver function tests such as albumin synthesis, urea release, glycogen accumulation and presence of a drug inducible cytochrome P450 system. Based on these findings, we conclude that sera from congestive/ischemic liver during cardiac failure support a liver specific microenvironment for effective hepatic trans-differentiation of hMSCs in vitro. PMID:24642599

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.

Guidelines on the management of abnormal liver blood tests

PubMed Central

Cramb, Rob; Davison, Suzanne M; Dillon, John F; Foulerton, Mark; Godfrey, Edmund M; Hall, Richard; Harrower, Ulrike; Hudson, Mark; Langford, Andrew; Mackie, Anne; Mitchell-Thain, Robert; Sennett, Karen; Sheron, Nicholas C; Verne, Julia; Walmsley, Martine; Yeoman, Andrew

2018-01-01

These updated guidelines on the management of abnormal liver blood tests have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines, which this document supersedes, were written in 2000 and have undergone extensive revision by members of the Guidelines Development Group (GDG). The GDG comprises representatives from patient/carer groups (British Liver Trust, Liver4life, PBC Foundation and PSC Support), elected members of the BSG liver section (including representatives from Scotland and Wales), British Association for the Study of the Liver (BASL), Specialist Advisory Committee in Clinical Biochemistry/Royal College of Pathology and Association for Clinical Biochemistry, British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN), Public Health England (implementation and screening), Royal College of General Practice, British Society of Gastrointestinal and Abdominal Radiologists (BSGAR) and Society of Acute Medicine. The quality of evidence and grading of recommendations was appraised using the AGREE II tool. These guidelines deal specifically with the management of abnormal liver blood tests in children and adults in both primary and secondary care under the following subheadings: (1) What constitutes an abnormal liver blood test? (2) What constitutes a standard liver blood test panel? (3) When should liver blood tests be checked? (4) Does the extent and duration of abnormal liver blood tests determine subsequent investigation? (5) Response to abnormal liver blood tests. They are not designed to deal with the management of the underlying liver disease. PMID:29122851

The combination of indocyanine green clearance test and model for end-stage liver disease score predicts early graft outcome after liver transplantation.

PubMed

Yunhua, Tang; Weiqiang, Ju; Maogen, Chen; Sai, Yang; Zhiheng, Zhang; Dongping, Wang; Zhiyong, Guo; Xiaoshun, He

2018-06-01

Early allograft dysfunction (EAD) and early postoperative complications are two important clinical endpoints when evaluating clinical outcomes of liver transplantation (LT). We developed and validated two ICGR15-MELD models in 87 liver transplant recipients for predicting EAD and early postoperative complications after LT by incorporating the quantitative liver function tests (ICGR15) into the MELD score. Eighty seven consecutive patients who underwent LT were collected and divided into a training cohort (n = 61) and an internal validation cohort (n = 26). For predicting EAD after LT, the area under curve (AUC) for ICGR15-MELD score was 0.876, with a sensitivity of 92.0% and a specificity of 75.0%, which is better than MELD score or ICGR15 alone. The recipients with a ICGR15-MELD score ≥0.243 have a higher incidence of EAD than those with a ICGR15-MELD score <0.243 (P <0.001). For predicting early postoperative complications, the AUC of ICGR15-MELD score was 0.832, with a sensitivity of 90.9% and a specificity of 71.0%. Those recipients with an ICGR15-MELD score ≥0.098 have a higher incidence of early postoperative complications than those with an ICGR15-MELD score <0.098 (P < 0.001). Finally, application of the two ICGR15-MELD models in the validation cohort still gave good accuracy (AUC, 0.835 and 0.826, respectively) in predicting EAD and early postoperative complications after LT. The combination of quantitative liver function tests (ICGR15) and the preoperative MELD score is a reliable and effective predictor of EAD and early postoperative complications after LT, which is better than MELD score or ICGR15 alone.

Hepatic (Liver) Function Panel

MedlinePlus

... Educators Search English Español Blood Test: Hepatic (Liver) Function Panel KidsHealth / For Parents / Blood Test: Hepatic (Liver) ... kidneys ) is working. What Is a Hepatic (Liver) Function Panel? A liver function panel is a blood ...

[Correlation between red blood cell count and liver function status].

PubMed

Xie, Xiaomeng; Wang, Leijie; Yao, Mingjie; Wen, Xiajie; Chen, Xiangmei; You, Hong; Jia, Jidong; Zhao, Jingmin; Lu, Fengmin

2016-02-01

To investigate the changes in red blood cell count in patients with different liver diseases and the correlation between red blood cell count and degree of liver damage. The clinical data of 1427 patients with primary liver cancer, 172 patients with liver cirrhosis, and 185 patients with hepatitis were collected, and the Child-Pugh class was determined for all patients. The differences in red blood cell count between patients with different liver diseases were retrospectively analyzed, and the correlation between red blood cell count and liver function status was investigated. The Mann-Whitney U test, Kruskal-Wallis H test, rank sum test, Spearman rank sum correlation test, and chi-square test were performed for different types of data. Red blood cell count showed significant differences between patients with chronic hepatitis, liver cancer, and liver cirrhosis and was highest in patients with chronic hepatitis and lowest in patients with liver cirrhosis (P < 0.05). In the patients with liver cirrhosis, red blood cell count tended to decrease in patients with a higher Child-Pugh class (P < 0.05). For patients with liver cirrhosis, red blood cell count can reflect the degree of liver damage, which may contribute to an improved liver function prediction model for these patients.

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

Automatic liver contouring for radiotherapy treatment planning

NASA Astrophysics Data System (ADS)

Li, Dengwang; Liu, Li; Kapp, Daniel S.; Xing, Lei

2015-09-01

To develop automatic and efficient liver contouring software for planning 3D-CT and four-dimensional computed tomography (4D-CT) for application in clinical radiation therapy treatment planning systems. The algorithm comprises three steps for overcoming the challenge of similar intensities between the liver region and its surrounding tissues. First, the total variation model with the L1 norm (TV-L1), which has the characteristic of multi-scale decomposition and an edge-preserving property, is used for removing the surrounding muscles and tissues. Second, an improved level set model that contains both global and local energy functions is utilized to extract liver contour information sequentially. In the global energy function, the local correlation coefficient (LCC) is constructed based on the gray level co-occurrence matrix both of the initial liver region and the background region. The LCC can calculate the correlation of a pixel with the foreground and background regions, respectively. The LCC is combined with intensity distribution models to classify pixels during the evolutionary process of the level set based method. The obtained liver contour is used as the candidate liver region for the following step. In the third step, voxel-based texture characterization is employed for refining the liver region and obtaining the final liver contours. The proposed method was validated based on the planning CT images of a group of 25 patients undergoing radiation therapy treatment planning. These included ten lung cancer patients with normal appearing livers and ten patients with hepatocellular carcinoma or liver metastases. The method was also tested on abdominal 4D-CT images of a group of five patients with hepatocellular carcinoma or liver metastases. The false positive volume percentage, the false negative volume percentage, and the dice similarity coefficient between liver contours obtained by a developed algorithm and a current standard delineated by the expert group are on an average 2.15-2.57%, 2.96-3.23%, and 91.01-97.21% for the CT images with normal appearing livers, 2.28-3.62%, 3.15-4.33%, and 86.14-93.53% for the CT images with hepatocellular carcinoma or liver metastases, and 2.37-3.96%, 3.25-4.57%, and 82.23-89.44% for the 4D-CT images also with hepatocellular carcinoma or liver metastases, respectively. The proposed three-step method can achieve efficient automatic liver contouring for planning CT and 4D-CT images with follow-up treatment planning and should find widespread applications in future treatment planning systems.

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.

Augmenter of liver regeneration protects against carbon tetrachloride-induced liver injury by promoting autophagy in mice

PubMed Central

Shi, Hongbo; Han, Weijia; Shi, Honglin; Ren, Feng; Chen, Dexi; Chen, Yu; Duan, Zhongping

2017-01-01

Background Augmenter of liver regeneration (ALR) exerts strong hepatoprotective properties in various animal models of liver injury, but its protective mechanisms have not yet been explored. Autophagy is a recently recognized rudimentary cellular response to inflammation and injury. The aim of this study was to test the hypothesis that ALR may protect against acute liver injury through the autophagic pathway. Methods The level and role of ALR in liver injury were studied in a mouse model of acute liver injury induced by carbon tetrachloride (CCl4). The effect of ALR on autophagy was analyzed in vitro and in vivo. After autophagy was inhibited by 3-methyladenine (3-MA), apoptosis and proliferation were detected in the mouse model with acute liver injury. The ALR and autophagic levels were measured in patients with liver cirrhosis (LC) and acute liver failure (ALF), respectively. Results During the progression of acute liver injury, the ALR levels increased slightly in early stage and significantly decreased in late stage in mice Treatment with an ALR plasmid via tail vein injection protected mice against acute liver injury. The protective effect of ALR relied on the induction of autophagy, which was supported by the following evidence: (1) ALR overexpression directly induced autophagy flux in vitro and in vivo; and (2) ALR treatment suppressed apoptosis and promoted proliferation in mice exposed to CCl4, but the inhibition of autophagy reversed these effects. More importantly, the ALR levels decreased in patients with LC and ALF compared with normal controls. Conclusion We demonstrated that ALR ameliorated liver injury via an autophagic mechanism, which indicates a potential therapeutic application for liver injury. PMID:28061452

Measurement of hepatic functional mass by means of 13C-methacetin and 13C-phenylalanine breath tests in chronic liver disease: Comparison with Child-Pugh score and serum bile acid levels

PubMed Central

Festi, D.; Capodicasa, S.; Sandri, L.; Colaiocco-Ferrante, L.; Staniscia, T.; Vitacolonna, E.; Vestito, A.; Simoni, P.; Mazzella, G.; Portincasa, P.; Roda, E.; Colecchia, A.

2005-01-01

AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels. METHODS: One hundred and forty patients (50 HCV- related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated. RESULTS: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids. Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test. CONCLUSION: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients. PMID:15609414

Systemic administration of a novel human umbilical cord mesenchymal stem cells population accelerates the resolution of acute liver injury

PubMed Central

2012-01-01

Background Hepatocytes and stem cells transplantation may be an alternative to liver transplantation in acute or chronic liver disease. We aimed to evaluate the therapeutic potential of mesenchymal stem cells from human umbilical cord (UCMSCs), a readily available source of mesenchymal stem cells, in the CCl4-induced acute liver injury model. Methods Mesenchymal stem cells profile was analyzed by flow cytometry. In order to evaluate the capability of our UCMSCs to differentiate in hepatocytes, cells were seeded on three different supports, untreated plastic support, MatrigelTM and human liver acellular matrix. Cells were analyzed by immunocitochemistry for alpha-fetoprotein and albumin expression, qPCR for hepatocyte markers gene expression, Periodic Acid-Schiff staining for glycogen storage, ELISA for albumin detection and colorimetric assay for urea secretion. To assess the effects of undifferentiated UCMSCs in hepatic regeneration after an acute liver injury, we transplanted them via tail vein in mice injected intraperitoneally with a single dose of CCl4. Livers were analyzed by histological evaluation for damage quantification, immunostaining for Kupffer and stellate cells/liver myofibroblasts activation and for UCMSCs homing. Pro- and anti-inflammatory cytokines gene expression was evaluated by qPCR analysis and antioxidant enzyme activity was measured by catalase quantification. Data were analyzed by Mann–Whitney U-test, Kruskal-Wallis test and Cuzick’s test followed by Bonferroni correction for multiple comparisons. Results We have standardized the isolation procedure to obtain a cell population with hepatogenic properties prior to in vivo transplantation. When subjected to hepatogenic differentiation on untreated plastic support, UCMSCs differentiated in hepatocyte-like cells as demonstrated by their morphology, progressive up-regulation of mature hepatocyte markers, glycogen storage, albumin and urea secretion. However, cells seeded on 3D-supports showed a minor or negligible differentiation capacity. UCMSCs-transplanted mice showed a more rapid damage resolution, as shown by histological analysis, with a lower inflammation level and an increased catalase activity compared to CCl4-treated mice. Conclusions Our findings show that UCMSCs can be reliably isolated, have hepatogenic properties and following systemic administration are able to accelerate the resolution of an acute liver injury without any differentiation and manipulation. These features make UCMSCs strong candidates for future application in regenerative medicine for human acute liver disease. PMID:22788801

Prediction of postoperative outcome after hepatectomy with a new bedside test for maximal liver function capacity.

PubMed

Stockmann, Martin; Lock, Johan F; Riecke, Björn; Heyne, Karsten; Martus, Peter; Fricke, Michael; Lehmann, Sina; Niehues, Stefan M; Schwabe, Michael; Lemke, Arne-Jörn; Neuhaus, Peter

2009-07-01

To validate the LiMAx test, a new bedside test for the determination of maximal liver function capacity based on C-methacetin kinetics. To investigate the diagnostic performance of different liver function tests and scores including the LiMAx test for the prediction of postoperative outcome after hepatectomy. Liver failure is a major cause of mortality after hepatectomy. Preoperative prediction of residual liver function has been limited so far. Sixty-four patients undergoing hepatectomy were analyzed in a prospective observational study. Volumetric analysis of the liver was carried out using preoperative computed tomography and intraoperative measurements. Perioperative factors associated with morbidity and mortality were analyzed. Cutoff values of the LiMAx test were evaluated by receiver operating characteristic. Residual LiMAx demonstrated an excellent linear correlation with residual liver volume (r = 0.94, P < 0.001) after hepatectomy. The multivariate analysis revealed LiMAx on postoperative day 1 as the only predictor of liver failure (P = 0.003) and mortality (P = 0.004). AUROC for the prediction of liver failure and liver failure related death by the LiMAx test was both 0.99. Preoperative volume/function analysis combining CT volumetry and LiMAx allowed an accurate calculation of the remnant liver function capacity prior to surgery (r = 0.85, P < 0.001). Residual liver function is the major factor influencing the outcome of patients after hepatectomy and can be predicted preoperatively by a combination of LiMAx and CT volumetry.

Artificial Neural Network Application in the Diagnosis of Disease Conditions with Liver Ultrasound Images

PubMed Central

Lele, Ramachandra Dattatraya; Joshi, Mukund; Chowdhary, Abhay

2014-01-01

The preliminary study presented within this paper shows a comparative study of various texture features extracted from liver ultrasonic images by employing Multilayer Perceptron (MLP), a type of artificial neural network, to study the presence of disease conditions. An ultrasound (US) image shows echo-texture patterns, which defines the organ characteristics. Ultrasound images of liver disease conditions such as “fatty liver,” “cirrhosis,” and “hepatomegaly” produce distinctive echo patterns. However, various ultrasound imaging artifacts and speckle noise make these echo-texture patterns difficult to identify and often hard to distinguish visually. Here, based on the extracted features from the ultrasonic images, we employed an artificial neural network for the diagnosis of disease conditions in liver and finding of the best classifier that distinguishes between abnormal and normal conditions of the liver. Comparison of the overall performance of all the feature classifiers concluded that “mixed feature set” is the best feature set. It showed an excellent rate of accuracy for the training data set. The gray level run length matrix (GLRLM) feature shows better results when the network was tested against unknown data. PMID:25332717

Mapping of the circulating metabolome reveals α-ketoglutarate as a predictor of morbid obesity-associated non-alcoholic fatty liver disease.

PubMed

Rodríguez-Gallego, E; Guirro, M; Riera-Borrull, M; Hernández-Aguilera, A; Mariné-Casadó, R; Fernández-Arroyo, S; Beltrán-Debón, R; Sabench, F; Hernández, M; del Castillo, D; Menendez, J A; Camps, J; Ras, R; Arola, L; Joven, J

2015-02-01

Obesity severely affects human health, and the accompanying non-alcoholic fatty liver disease (NAFLD) is associated with high morbidity and mortality. Rapid and non-invasive methods to detect this condition may substantially improve clinical care. We used liquid and gas chromatography-quadruple time-of-flight-mass spectrometry (LC/GC-QTOF-MS) analysis in a non-targeted metabolomics approach on the plasma from morbidly obese patients undergoing bariatric surgery to gain a comprehensive measure of metabolite levels. On the basis of these findings, we developed a method (GC-QTOF-MS) for the accurate quantification of plasma α-ketoglutarate to explore its potential as a novel biomarker for the detection of NAFLD. Plasma biochemical differences were observed between patients with and without NAFLD indicating that the accumulation of lipids in hepatocytes decreased β-oxidation energy production, reduced liver function and altered glucose metabolism. The results obtained from the plasma analysis suggest pathophysiological insights that link lipid and glucose disturbances with α-ketoglutarate. Plasma α-ketoglutarate levels are significantly increased in obese patients compared with lean controls. Among obese patients, the measurement of this metabolite differentiates between those with or without NAFLD. Data from the liver were consistent with data from plasma. Clinical utility was assessed, and the results revealed that plasma α-ketoglutarate is a fair-to-good biomarker in patients (n=230). Other common laboratory liver tests used in routine application did not favourably compare. Plasma α-ketoglutarate is superior to common liver function tests in obese patients as a surrogate biomarker of NAFLD. The measurement of this biomarker may potentiate the search for a therapeutic approach, may decrease the need for liver biopsy and may be useful in the assessment of disease progression.

Transient oxidative stress and inflammation after intraperitoneal administration of multiwalled carbon nanotubes functionalized with single strand DNA in rats

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

Clichici, Simona, E-mail: simonaclichici@yahoo.com; Biris, Alexandru Radu; Tabaran, Flaviu

2012-03-15

Multi-walled carbon nanotubes (MWCNTs) are widely used for nanotechnology. Their impact on living organisms is, however, not entirely clarified. Oxidative stress and inflammation seem to be the key mechanisms involved in MWCNTs' cytotoxicity. Until present, pulmonary and skin models were the main tested experimental designs to assess carbon nanotubes' toxicity. The systemic administration of MWCNTs is essential, with respect for future medical applications. Our research is performed on Wistar rats and is focused on the dynamics of oxidative stress parameters in blood and liver and pro-inflammatory cytokines in liver, after single dose (270 mg l{sup −1}) ip administration of MWCNTsmore » (exterior diameter 15–25 nm, interior diameter 10–15 nm, surface 88 m{sup 2} g{sup −1}) functionalized with single strand DNA (ss-DNA). The presence of MWCNTs in blood was assessed by Raman spectroscopy, while in liver histological examination and confocal microscopy were used. It was found that ss-DNA-MWCNTs induce oxidative stress in plasma and liver, with the return of the tested parameters to normal values, 6 h after ip injection of nanotubes, with the exception of reduced glutathione in plasma. The inflammatory cytokines (TNF-α, IL-1β) had a similar pattern of evolution. We also assessed the level of ERK1/2 and the phosphorylation of p65 subunit of NF-kB in liver that had a transient increase and returned to normal at the end of the tested period. Our results demonstrate that ss-DNA-MWCNTs produce oxidative stress and inflammation, but with a transient pattern. Given the fact that antioxidants modify the profile not only for oxidative stress, but also of inflammation, the dynamics of these alterations may be of practical importance for future protective strategies. -- Highlights: ► ss-DNA-MWCNTs ip administration induce oxidative stress in plasma and liver. ► ss-DNA-MWCNTs ip administration determine liver inflammation. ► ERK1/2 and p65 phosphorylated NF-KB increase in liver after MWCNTs ip injection. ► All the alterations, except plasma GSH, return to normal within 6 days.« less

Toxicokinetics and biodistribution of dextran stabilized iron oxide nanoparticles in rats

NASA Astrophysics Data System (ADS)

Easo, S. L.; Neelima, R.; Mohanan, P. V.

2015-07-01

Dextran stabilized iron oxide nanoparticles (DIONPs) synthesized and characterized for hyperthermia application were tested for toxicokinetics and biodistribution in order to analyze the prospect of safety and biocompatibility of these particles for advanced use. Rats were administered a single dose of DIONPs at a concentration of 10 mg kg-1 by intravenous injection with a post-exposure period of 1, 7, 14 and 28 days. Liver, spleen, kidney, blood, urine and feces were examined for iron content by inductively coupled plasma atomic emission spectroscopy. At 24 h, greater amounts of nanoparticles were deposited in liver and spleen. Maximum absorption of iron in blood occurred at day 7 and excess iron appeared to be eliminated by liver, seemingly via biliary excretion. Serum hematology and biochemistry analysis revealed an overall lack of systemic toxicity due to metabolism of DIONPs. Additionally, pathological changes associated with repeated exposure to DIONPs with a post exposure period of 28 days were also assessed. Although no significant pathological alterations were seen in spleen or kidney, slight morphological deviations from normal were observed in liver. Further progression in the analysis of biological response towards DIONPs will be determined in long-term studies in the presence of an alternating magnetic field in the context of hyperthermia application.

Clinical Application of Vibration Controlled Transient Elastography in Patients with Chronic Hepatitis B

PubMed Central

Liang, Xie-Er; Chen, Yong-Peng

2017-01-01

Abstract Evaluation of the extent and progression of liver fibrosis and cirrhosis is of critical importance in the management and prognosis of patients with chronic hepatitis B. Due to the limitation of liver biopsy, non-invasive methods, especially liver stiffness measurement (LSM) by vibration controlled transient elastography, have been developed and widely applied for liver fibrosis assessment. LSM aims to reduce, but not to substitute, the need for liver biopsy for fibrosis/cirrhosis diagnosis. While LSM may have potential utility in monitoring treatment response, its applications in prediction of liver complications in terms of portal hypertension and esophageal varices, as well as disease prognosis, have been gradually validated. Here, we review the latest clinical applications of LSM in patients with chronic hepatitis B. PMID:29226103

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

PubMed

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

2010-06-01

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

Microphysiological systems meet hiPSC technology - New tools for disease modeling of liver infections in basic research and drug development.

PubMed

Raasch, Martin; Fritsche, Enrico; Kurtz, Andreas; Bauer, Michael; Mosig, Alexander S

2018-06-14

Complex cell culture models such as microphysiological models (MPS) mimicking human liver functionality in vitro are in the spotlight as alternative to conventional cell culture and animal models. Promising techniques like microfluidic cell culture or micropatterning by 3D bioprinting are gaining increasing importance for the development of MPS to address the needs for more predictivity and cost efficiency. In this context, human induced pluripotent stem cells (hiPSCs) offer new perspectives for the development of advanced liver-on-chip systems by recreating an in vivo like microenvironment that supports the reliable differentiation of hiPSCs to hepatocyte-like cells (HLC). In this review we will summarize current protocols of HLC generation and highlight recently established MPS suitable to resemble physiological hepatocyte function in vitro. In addition, we are discussing potential applications of liver MPS for disease modeling related to systemic or direct liver infections and the use of MPS in testing of new drug candidates. Copyright © 2018. Published by Elsevier B.V.

Nor-Ursodeoxycholic Acid as a Novel Therapeutic Approach for Cholestatic and Metabolic Liver Diseases.

PubMed

Halilbasic, Emina; Steinacher, Daniel; Trauner, Michael

2017-01-01

Norursodeoxycholic acid (norUDCA) is a side-chain-shortened derivative of ursodeoxycholic acid with relative resistance to amidation, which enables its cholehepatic shunting. Based on its specific pharmacologic properties, norUDCA is a promising drug for a range of cholestatic liver and bile duct disorders. Recently, norUDCA has been successfully tested clinically in patients with primary sclerosing cholangitis (PSC) as first application in patients. Moreover, hepatic enrichment of norUDCA facilitates direct therapeutic effects on both parenchymal and non-parenchymal liver cells, thereby counteracting cholestasis, steatosis, hepatic inflammation and fibrosis, inhibiting hepatocellular proliferation, and promoting autophagy. This may open its therapeutic use to other non-cholestatic and metabolic liver diseases. This review article is a summary of a lecture given at the XXIV International Bile Acid Meeting (Falk Symposium 203) on "Bile Acids in Health and Disease" held in Düsseldorf, on June 17-18, 2016 and summarizes the recent progress of norUDCA as novel therapeutic approach in cholestatic and metabolic liver disorders with a specific focus on PSC. © 2017 S. Karger AG, Basel.

Combination of blood tests for significant fibrosis and cirrhosis improves the assessment of liver-prognosis in chronic hepatitis C.

PubMed

Boursier, J; Brochard, C; Bertrais, S; Michalak, S; Gallois, Y; Fouchard-Hubert, I; Oberti, F; Rousselet, M-C; Calès, P

2014-07-01

Recent longitudinal studies have emphasised the prognostic value of noninvasive tests of liver fibrosis and cross-sectional studies have shown their combination significantly improves diagnostic accuracy. To compare the prognostic accuracy of six blood fibrosis tests and liver biopsy, and evaluate if test combination improves the liver-prognosis assessment in chronic hepatitis C (CHC). A total of 373 patients with compensated CHC, liver biopsy (Metavir F) and blood tests targeting fibrosis (APRI, FIB4, Fibrotest, Hepascore, FibroMeter) or cirrhosis (CirrhoMeter) were included. Significant liver-related events (SLRE) and liver-related deaths were recorded during follow-up (started the day of biopsy). During the median follow-up of 9.5 years (3508 person-years), 47 patients had a SLRE and 23 patients died from liver-related causes. For the prediction of first SLRE, most blood tests allowed higher prognostication than Metavir F [Harrell C-index: 0.811 (95% CI: 0.751-0.868)] with a significant increase for FIB4: 0.879 [0.832-0.919] (P = 0.002), FibroMeter: 0.870 [0.812-0.922] (P = 0.005) and APRI: 0.861 [0.813-0.902] (P = 0.039). Multivariate analysis identified FibroMeter, CirrhoMeter and sustained viral response as independent predictors of first SLRE. CirrhoMeter was the only independent predictor of liver-related death. The combination of FibroMeter and CirrhoMeter classifications into a new FM/CM classification improved the liver-prognosis assessment compared to Metavir F staging or single tests by identifying five subgroups of patients with significantly different prognoses. Some blood fibrosis tests are more accurate than liver biopsy for determining liver prognosis in CHC. A new combination of two complementary blood tests, one targeted for fibrosis and the other for cirrhosis, optimises assessment of liver-prognosis. © 2014 John Wiley & Sons Ltd.

Adult Liver Cancer Symptoms, Tests, Prognosis, and Stages (PDQ®)—Patient Version

Cancer.gov

Hepatocellular carcinoma is the most common type of adult primary liver cancer. The Barcelona Clinical Liver Cancer (BCLC) Staging System is used to stage liver cancer. Learn more about risk factors, signs and symptoms, tests to diagnose, prognosis, and stages of adult primary liver cancer.

Alanine transaminase (ALT) blood test

MedlinePlus

... the levels of substances checked by other liver blood tests have also increased. An increased ALT level may be due to any of the following: Scarring of the liver ( cirrhosis ) Death of liver tissue Swollen and inflamed liver ( ...

Application of low-frequency sonophoresis and reduction of antibiotics in the aquatic systems.

PubMed

Cobo Labarca, C; Radinger, J; Schöning, V; Ariav, R; Jung, R; Thompson, K D; Kloas, W; Knopf, K

2017-11-01

A major concern in aquaculture is the use of chemical therapeutics, such as antibiotics, because of their impact on the environment as well as on the fish product. As a potential tool for reducing antibiotic use, we tested the application of low-frequency ultrasound as a method for enhancing antibiotic uptake. Rainbow trout juveniles (Oncorhynchus mykiss) were exposed to two different concentrations of oxytetracycline (OTC), flumequine (FLU) and florfenicol (FLO), administered by bath after the application of ultrasound. After exposure, concentrations of these substances were measured in the liver and blood of treated fish. Results showed that the ultrasound treatment can significantly increase the uptake for all three antibiotics. The uptake of OTC for example, in fish exposed to an OTC concentration of 20 mg L -1 after prior treatment with ultrasound, was similar to the OTC concentrations in their liver and blood to fish exposed to 100 mg L -1 without sonication. For FLU and FLO, the use of ultrasound caused significant differences of uptake in the liver at high antibiotic concentrations. This suggests that the use of ultrasound as a technique to deliver antibiotics to fish can ultimately reduce the amount of antibiotics discharged into the aquatic environment. © 2017 John Wiley & Sons Ltd.

Thinking outside the liver: Induced pluripotent stem cells for hepatic applications

PubMed Central

Subba Rao, Mekala; Sasikala, Mitnala; Reddy, D Nageshwar

2013-01-01

The discovery of induced pluripotent stem cells (iPSCs) unraveled a mystery in stem cell research, after identification of four re-programming factors for generating pluripotent stem cells without the need of embryos. This breakthrough in generating iPSCs from somatic cells has overcome the ethical issues and immune rejection involved in the use of human embryonic stem cells. Hence, iPSCs form a great potential source for developing disease models, drug toxicity screening and cell-based therapies. These cells have the potential to differentiate into desired cell types, including hepatocytes, under in vitro as well as under in vivo conditions given the proper microenvironment. iPSC-derived hepatocytes could be useful as an unlimited source, which can be utilized in disease modeling, drug toxicity testing and producing autologous cell therapies that would avoid immune rejection and enable correction of gene defects prior to cell transplantation. In this review, we discuss the induction methods, role of reprogramming factors, and characterization of iPSCs, along with hepatocyte differentiation from iPSCs and potential applications. Further, we discuss the location and detection of liver stem cells and their role in liver regeneration. Although tumor formation and genetic mutations are a cause of concern, iPSCs still form a promising source for clinical applications. PMID:23801830

Thinking outside the liver: induced pluripotent stem cells for hepatic applications.

PubMed

Subba Rao, Mekala; Sasikala, Mitnala; Nageshwar Reddy, D

2013-06-14

The discovery of induced pluripotent stem cells (iPSCs) unraveled a mystery in stem cell research, after identification of four re-programming factors for generating pluripotent stem cells without the need of embryos. This breakthrough in generating iPSCs from somatic cells has overcome the ethical issues and immune rejection involved in the use of human embryonic stem cells. Hence, iPSCs form a great potential source for developing disease models, drug toxicity screening and cell-based therapies. These cells have the potential to differentiate into desired cell types, including hepatocytes, under in vitro as well as under in vivo conditions given the proper microenvironment. iPSC-derived hepatocytes could be useful as an unlimited source, which can be utilized in disease modeling, drug toxicity testing and producing autologous cell therapies that would avoid immune rejection and enable correction of gene defects prior to cell transplantation. In this review, we discuss the induction methods, role of reprogramming factors, and characterization of iPSCs, along with hepatocyte differentiation from iPSCs and potential applications. Further, we discuss the location and detection of liver stem cells and their role in liver regeneration. Although tumor formation and genetic mutations are a cause of concern, iPSCs still form a promising source for clinical applications.

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

Chronic hepatitis C virus infection: Serum biomarkers in predicting liver damage

PubMed Central

Valva, Pamela; Ríos, Daniela A; De Matteo, Elena; Preciado, Maria V

2016-01-01

Currently, a major clinical challenge in the management of the increasing number of hepatitis C virus (HCV) infected patients is determining the best means for evaluating liver impairment. Prognosis and treatment of chronic hepatitis C (CHC) are partly dependent on the assessment of histological activity, namely cell necrosis and inflammation, and the degree of liver fibrosis. These parameters can be provided by liver biopsy; however, in addition to the risks related to an invasive procedure, liver biopsy has been associated with sampling error mostly due to suboptimal biopsy size. To avoid these pitfalls, several markers have been proposed as non-invasive alternatives for the diagnosis of liver damage. Distinct approaches among the currently available non-invasive methods are (1) the physical ones based on imaging techniques; and (2) the biological ones based on serum biomarkers. In this review, we discuss these approaches with special focus on currently available non-invasive serum markers. We will discuss: (1) class I serum biomarkers individually and as combined panels, particularly those that mirror the metabolism of liver extracellular matrix turnover and/or fibrogenic cell changes; (2) class II biomarkers that are indirect serum markers and are based on the evaluation of common functional alterations in the liver; and (3) biomarkers of liver cell death, since hepatocyte apoptosis plays a significant role in the pathogenesis of HCV infection. We highlight in this review the evidence behind the use of these markers and assess the diagnostic accuracy as well as advantages, limitations, and application in clinical practice of each test for predicting liver damage in CHC. PMID:26819506

A multi-residue method for 17 anticoccidial drugs and ractopamine in animal tissues by liquid chromatography-tandem mass spectrometry and time-of-flight mass spectrometry.

PubMed

Matus, Johanna L; Boison, Joe O

2016-05-01

A new and sensitive multi-residue liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-quadrupole time-of-flight-mass spectrometry (LC-QToF-MS) method was developed and validated for the determination and confirmation of residues of 17 anticoccidials, plus free ractopamine in poultry muscle and liver, and bovine muscle, liver, and kidney tissues. The 17 anticoccidials are lasalocid, halofuginone, narasin, monensin, semduramicin, ethopabate, robenidine, buquinolate, toltrazuril as its sulfone metabolite, maduramicin, salinomycin, diclazuril, amprolium, decoquinate, dinitolmide, clopidol, and the nicarbazin metabolite DNC (N,N1-bis(4-nitrophenyl)urea). The analytes were extracted and cleaned up within a 3-hour period by simply extracting the analytes into a solvent mixture with salts followed by centrifugation, dilution, and filtration. The validated method was used in a pilot study for the analysis of 173 samples that included quail liver, bovine kidney, liver, muscle, and horse muscle. The predominant residues found in this study were monensin, ractopamine, and lasalocid. The results of this pilot study showed that this new method is applicable to real samples, and is fit for use in a regulatory testing programme. © 2016 Her Majesty the Queen in Right of Canada. Drug Testing and Analysis. © 2016 John Wiley & Sons, Ltd. © 2016 Her Majesty the Queen in Right of Canada. Drug Testing and Analysis. © 2016 John Wiley & Sons, Ltd.

Fibrosis assessment in patients with chronic hepatitis B virus (HBV) infection

PubMed Central

Parikh, Pathik; Ryan, John D.

2017-01-01

Chronic hepatitis B virus (HBV) infection is a major cause of liver morbidity and mortality worldwide. While a proportion of the 250 million individuals chronically infected with HBV will not come to significant harm or require therapy, many others risk developing complications of the end-stage liver disease such as decompensated cirrhosis and hepatocellular carcinoma (HCC), without intervention. Due to the complex natural history of HBV infection, patients require an expert assessment to interpret biochemistry, viral serology and appropriately stage the disease, and to initiate monitoring and/or therapy where indicated. The detection and quantification of liver fibrosis is a key factor for disease management and prognostication for an individual with HBV. The reliance on invasive liver biopsy to stage disease is diminishing with the advent of robust non-invasive blood- and imaging-based algorithms which can reliably stage disease in many cases. These tests are now incorporated into International guidelines for HBV management and relied upon daily to inform clinical judgement. Both blood- and imaging-based approaches have advantages over liver biopsy, including minimal risks, lower cost, better patient acceptance and speed of results, while disadvantages include lower diagnostic accuracy in intermediate disease stages and variability with co-existing hepatic inflammation or steatosis. This review outlines the methods of fibrosis assessment in chronic HBV infection and focuses on the most commonly used blood- and imaging-based non-invasive tests, reviewing their diagnostic performance and applicability to patient care. PMID:28251119

Drug and herb induced liver injury: Council for International Organizations of Medical Sciences scale for causality assessment

PubMed Central

Teschke, Rolf; Wolff, Albrecht; Frenzel, Christian; Schwarzenboeck, Alexander; Schulze, Johannes; Eickhoff, Axel

2014-01-01

Causality assessment of suspected drug induced liver injury (DILI) and herb induced liver injury (HILI) is hampered by the lack of a standardized approach to be used by attending physicians and at various subsequent evaluating levels. The aim of this review was to analyze the suitability of the liver specific Council for International Organizations of Medical Sciences (CIOMS) scale as a standard tool for causality assessment in DILI and HILI cases. PubMed database was searched for the following terms: drug induced liver injury; herb induced liver injury; DILI causality assessment; and HILI causality assessment. The strength of the CIOMS lies in its potential as a standardized scale for DILI and HILI causality assessment. Other advantages include its liver specificity and its validation for hepatotoxicity with excellent sensitivity, specificity and predictive validity, based on cases with a positive reexposure test. This scale allows prospective collection of all relevant data required for a valid causality assessment. It does not require expert knowledge in hepatotoxicity and its results may subsequently be refined. Weaknesses of the CIOMS scale include the limited exclusion of alternative causes and qualitatively graded risk factors. In conclusion, CIOMS appears to be suitable as a standard scale for attending physicians, regulatory agencies, expert panels and other scientists to provide a standardized, reproducible causality assessment in suspected DILI and HILI cases, applicable primarily at all assessing levels involved. PMID:24653791

Prognostic durability of liver fibrosis tests and improvement in predictive performance for mortality by combining tests.

PubMed

Bertrais, Sandrine; Boursier, Jérôme; Ducancelle, Alexandra; Oberti, Frédéric; Fouchard-Hubert, Isabelle; Moal, Valérie; Calès, Paul

2017-06-01

There is currently no recommended time interval between noninvasive fibrosis measurements for monitoring chronic liver diseases. We determined how long a single liver fibrosis evaluation may accurately predict mortality, and assessed whether combining tests improves prognostic performance. We included 1559 patients with chronic liver disease and available baseline liver stiffness measurement (LSM) by Fibroscan, aspartate aminotransferase to platelet ratio index (APRI), FIB-4, Hepascore, and FibroMeter V2G . Median follow-up was 2.8 years during which 262 (16.8%) patients died, with 115 liver-related deaths. All fibrosis tests were able to predict mortality, although APRI (and FIB-4 for liver-related mortality) showed lower overall discriminative ability than the other tests (differences in Harrell's C-index: P < 0.050). According to time-dependent AUROCs, the time period with optimal predictive performance was 2-3 years in patients with no/mild fibrosis, 1 year in patients with significant fibrosis, and <6 months in cirrhotic patients even in those with a model of end-stage liver disease (MELD) score <15. Patients were then randomly split in training/testing sets. In the training set, blood tests and LSM were independent predictors of all-cause mortality. The best-fit multivariate model included age, sex, LSM, and FibroMeter V2G with C-index = 0.834 (95% confidence interval, 0.803-0.862). The prognostic model for liver-related mortality included the same covariates with C-index = 0.868 (0.831-0.902). In the testing set, the multivariate models had higher prognostic accuracy than FibroMeter V2G or LSM alone for all-cause mortality and FibroMeter V2G alone for liver-related mortality. The prognostic durability of a single baseline fibrosis evaluation depends on the liver fibrosis level. Combining LSM with a blood fibrosis test improves mortality risk assessment. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Automatic 3D liver segmentation based on deep learning and globally optimized surface evolution

NASA Astrophysics Data System (ADS)

Hu, Peijun; Wu, Fa; Peng, Jialin; Liang, Ping; Kong, Dexing

2016-12-01

The detection and delineation of the liver from abdominal 3D computed tomography (CT) images are fundamental tasks in computer-assisted liver surgery planning. However, automatic and accurate segmentation, especially liver detection, remains challenging due to complex backgrounds, ambiguous boundaries, heterogeneous appearances and highly varied shapes of the liver. To address these difficulties, we propose an automatic segmentation framework based on 3D convolutional neural network (CNN) and globally optimized surface evolution. First, a deep 3D CNN is trained to learn a subject-specific probability map of the liver, which gives the initial surface and acts as a shape prior in the following segmentation step. Then, both global and local appearance information from the prior segmentation are adaptively incorporated into a segmentation model, which is globally optimized in a surface evolution way. The proposed method has been validated on 42 CT images from the public Sliver07 database and local hospitals. On the Sliver07 online testing set, the proposed method can achieve an overall score of 80.3+/- 4.5 , yielding a mean Dice similarity coefficient of 97.25+/- 0.65 % , and an average symmetric surface distance of 0.84+/- 0.25 mm. The quantitative validations and comparisons show that the proposed method is accurate and effective for clinical application.

The effect of nanofibrous galactosylated chitosan scaffolds on the formation of rat primary hepatocyte aggregates and the maintenance of liver function.

PubMed

Feng, Zhang-Qi; Chu, Xuehui; Huang, Ning-Ping; Wang, Tao; Wang, Yichun; Shi, Xiaolei; Ding, Yitao; Gu, Zhong-Ze

2009-05-01

Liver tissue engineering requires a perfect extracellular matrix (ECM) for primary hepatocytes culture to maintain high level of liver-specific functions and desirable mechanical stability. The aim of this study was to develop a novel natural nanofibrous scaffold with surface-galactose ligands to enhance the bioactivity and mechanical stability of primary hepatocytes in culture. The nanofibrous scaffold was fabricated by electrospinning a natural material, galactosylated chitosan (GC), into nanofibers with an average diameter of approximately 160 nm. The GC nanofibrous scaffolds displayed slow degradation and suitable mechanical properties as an ECM for hepatocytes according to the evaluation of disintegration and Young's modulus testing. The results of morphology characterization, double-staining fluorescence assay and function detection showed that hepatocytes cultured on GC nanofibrous scaffold formed stably immobilized 3D flat aggregates and exhibited superior cell bioactivity with higher levels of liver-specific function maintenance in terms of albumin secretion, urea synthesis and cytochrome P-450 enzyme than 3D spheroid aggregates formed on GC films. These spheroid aggregates could be detached easily during culture period from the flat GC films. We suggest such GC-based nanofibrous scaffolds could be useful for various applications such as bioartificial liver-assist devices and tissue engineering for liver regeneration as primary hepatocytes culture substrates.

Autoimmune hepatitis-specific antibodies against soluble liver antigen and liver cytosol type 1 in patients with chronic viral hepatitis.

PubMed

Rigopoulou, Eirini I; Mytilinaiou, Maria; Romanidou, Ourania; Liaskos, Christos; Dalekos, George N

2007-02-04

Non-organ specific autoantibodies are highly prevalent in patients with chronic hepatitis C (HCV). Among them, anti-liver kidney microsomal type 1 (LKM1) antibody--the serological marker of type 2 autoimmune hepatitis (AIH-2)--is detected in up to 11% of the HCV-infected subjects. On the other hand, anti-liver cytosol type 1 antibodies (anti-LC1)--either in association with anti-LKM1, or in isolation--and anti-soluble liver antigen antibodies (anti-SLA) have been considered as useful and specific diagnostic markers for AIH. However, their specificity for AIH has been questioned by some recent studies, which have shown the detection of anti-LC1 and anti-SLA by immunoprecipitation assays in HCV patients irrespective of their anti-LKM1 status. The aim of the present study was to test the anti-LC1 and anti-SLA presence by specific enzyme linked immunosorbent assays (ELISAs), in a large group of Greek HCV-infected patients with or without anti-LKM1 reactivity as firstly, immunoprecipitation assays are limited to few specialized laboratories worldwide and cannot be used routinely and secondly, to assess whether application of such tests has any relevance in the context of patients with viral hepatitis since antibody detection based on such ELISAs has not been described in detail in large groups of HCV patients. One hundred and thirty eight consecutive HCV patients (120 anti-LKM1 negative and 18 anti-LKM1 positive) were investigated for the presence of anti-LC1 and anti-SLA by commercial ELISAs. A similar number (120) of chronic hepatitis B virus (HBV) infected patients seronegative for anti-LKM1 was also tested as pathological controls. Six out of 18 (33%) anti-LKM(pos)/HCV(pos) patients tested positive for anti-LC1 compared to 1/120 (0.83%) anti-LKM(neg)/HCV(pos) patients and 0/120 (0%) of the anti-LKM1(neg)/HBV(pos) patients (p < 0.001 for both comparisons). Anti-SLA antibodies were not present in any of the HCV (with or without anti-LKM1) or HBV-infected patients. We showed that anti-LC1 and anti-SLA autoantibodies are not detected by conventional assays in a large group of anti-LKM1 negative patients with chronic hepatitis B and C infections. Based on these results we cannot find any justification for the application of anti-LC1 and anti-SLA tests in the routine laboratory testing of viral hepatitis-related autoantibody serology with the only potential exception being the anti-LC1 screening in anti-LKM1(pos)/HCV(pos) patients.

Autoimmune hepatitis-specific antibodies against soluble liver antigen and liver cytosol type 1 in patients with chronic viral hepatitis

PubMed Central

Rigopoulou, Eirini I; Mytilinaiou, Maria; Romanidou, Ourania; Liaskos, Christos; Dalekos, George N

2007-01-01

Background Non-organ specific autoantibodies are highly prevalent in patients with chronic hepatitis C (HCV). Among them, anti-liver kidney microsomal type 1 (LKM1) antibody – the serological marker of type 2 autoimmune hepatitis (AIH-2)- is detected in up to 11% of the HCV-infected subjects. On the other hand, anti-liver cytosol type 1 antibodies (anti-LC1) – either in association with anti-LKM1, or in isolation- and anti-soluble liver antigen antibodies (anti-SLA) have been considered as useful and specific diagnostic markers for AIH. However, their specificity for AIH has been questioned by some recent studies, which have shown the detection of anti-LC1 and anti-SLA by immunoprecipitation assays in HCV patients irrespective of their anti-LKM1 status. The aim of the present study was to test the anti-LC1 and anti-SLA presence by specific enzyme linked immunosorbent assays (ELISAs), in a large group of Greek HCV-infected patients with or without anti-LKM1 reactivity as firstly, immunoprecipitation assays are limited to few specialized laboratories worldwide and cannot be used routinely and secondly, to assess whether application of such tests has any relevance in the context of patients with viral hepatitis since antibody detection based on such ELISAs has not been described in detail in large groups of HCV patients. Methods One hundred and thirty eight consecutive HCV patients (120 anti-LKM1 negative and 18 anti-LKM1 positive) were investigated for the presence of anti-LC1 and anti-SLA by commercial ELISAs. A similar number (120) of chronic hepatitis B virus (HBV) infected patients seronegative for anti-LKM1 was also tested as pathological controls. Results Six out of 18 (33%) anti-LKMpos/HCVpos patients tested positive for anti-LC1 compared to 1/120 (0.83%) anti-LKMneg/HCVpos patients and 0/120 (0%) of the anti-LKM1neg/HBVpos patients (p < 0.001 for both comparisons). Anti-SLA antibodies were not present in any of the HCV (with or without anti-LKM1) or HBV-infected patients. Conclusion We showed that anti-LC1 and anti-SLA autoantibodies are not detected by conventional assays in a large group of anti-LKM1 negative patients with chronic hepatitis B and C infections. Based on these results we cannot find any justification for the application of anti-LC1 and anti-SLA tests in the routine laboratory testing of viral hepatitis-related autoantibody serology with the only potential exception being the anti-LC1 screening in anti-LKM1pos/HCVpos patients. PMID:17274827

Serum Fetuin-A levels in obese children with biopsy proven nonalcoholic fatty liver disease.

PubMed

Pampanini, V; Inzaghi, E; Germani, D; Alterio, A; Puglianiello, A; Alisi, A; Nobili, V; Cianfarani, S

2018-01-01

Fetuin-A has been proposed as a marker of liver damage in adults with obesity-related NAFLD. The aim of this study was to test serum fetuin-A concentrations in obese children with NAFLD diagnosed either by ultrasonography or by liver biopsy and to determine its applicability as predictive tool in pediatric NAFLD. Metabolic parameters and fetuin-A levels were investigated in 81 obese children with NAFLD diagnosed by biopsy, 79 obese children with NAFLD defined by liver ultrasonography and 23 lean subjects. Serum fetuin-A correlated significantly with age, waist circumference, systolic blood pressure, fasting insulin and 2-h postload insulin during OGTT, HOMA-IR, ISI, CRP, and apo B levels. Obese children with NAFLD detected by ultrasonography had significantly higher fetuin-A levels compared to those with normal liver. In obese children who underwent liver biopsy, no significant differences were detected in fetuin-A levels between subject with nonalcoholic steatohepatitis and those with simple steatosis. Fetuin-A was not different between obese and lean children. Fetuin-A is not related with the degree of liver damage in obese children with NAFLD and its routine measurement as marker of liver disease severity is therefore not recommended. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease.

PubMed

Boursier, Jérôme; Vergniol, Julien; Guillet, Anne; Hiriart, Jean-Baptiste; Lannes, Adrien; Le Bail, Brigitte; Michalak, Sophie; Chermak, Faiza; Bertrais, Sandrine; Foucher, Juliette; Oberti, Frédéric; Charbonnier, Maude; Fouchard-Hubert, Isabelle; Rousselet, Marie-Christine; Calès, Paul; de Lédinghen, Victor

2016-09-01

NAFLD is highly prevalent but only a small subset of patients develop advanced liver fibrosis with impaired liver-related prognosis. We aimed to compare blood fibrosis tests and liver stiffness measurement (LSM) by FibroScan for the diagnosis of liver fibrosis and the evaluation of prognosis in NAFLD. Diagnostic accuracy was evaluated in a cross-sectional study including 452 NAFLD patients with liver biopsy (NASH-CRN fibrosis stage), LSM, and eight blood fibrosis tests (BARD, NAFLD fibrosis score, FibroMeter(NAFLD), aspartate aminotransferase to platelet ratio index (APRI), FIB4, FibroTest, Hepascore, FibroMeter(V2G)). Prognostic accuracy was evaluated in a longitudinal study including 360 NAFLD patients. LSM and FibroMeter(V2G) were the two best-performing tests in the cross-sectional study: AUROCs for advanced fibrosis (F3/4) were, respectively, 0.831±0.019 and 0.817±0.020 (p⩽0.041 vs. other tests); rates of patients with ⩾90% negative/positive predictive values for F3/4 were 56.4% and 46.7% (p<0.001 vs. other tests); Obuchowski indexes were 0.834±0.014 and 0.798±0.016 (p⩽0.036 vs. other tests). Two fibrosis classifications were developed to precisely estimate the histological fibrosis stage from LSM or FibroMeter(V2G) results without liver biopsy (diagnostic accuracy, respectively: 80.8% vs. 77.4%, p=0.190). Kaplan-Meier curves in the longitudinal study showed that both classifications categorised NAFLD patients into subgroups with significantly different prognoses (p<0.001): the higher was the class of the fibrosis classification, the worse was the prognosis. LSM and FibroMeter(V2G) were the most accurate of nine evaluated tests for the non-invasive diagnosis of liver fibrosis in NAFLD. LSM and FibroMeter(V2G) fibrosis classifications help physicians estimate both fibrosis stage and patient prognosis in clinical practice. The amount of liver fibrosis is the main determinant of the liver-related prognosis in patients with non-alcoholic fatty liver disease (NAFLD). We evaluated eight blood tests and FibroScan in a cross-sectional diagnostic study and found that FibroScan and the blood test FibroMeter(V2G) were the two most accurate tests for the non-invasive evaluation of liver fibrosis in NAFLD. A longitudinal prognostic study showed these two tests initially developed for the diagnosis are also prognostic markers as they allow for the stratification of NAFLD patients in several subgroups with significantly different prognosis. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Serum-Free Medium and Mesenchymal Stromal Cells Enhance Functionality and Stabilize Integrity of Rat Hepatocyte Spheroids

PubMed Central

Bao, Ji; Fisher, James E.; Lillegard, Joseph B.; Wang, William; Amiot, Bruce; Yu, Yue; Dietz, Allan B.; Nahmias, Yaakov; Nyberg, Scott L.

2013-01-01

Long-term culture of hepatocyte spheroids with high ammonia clearance is valuable for therapeutic applications, especially the bioartificial liver. However, the optimal conditions are not well studied. We hypothesized that liver urea cycle enzymes can be induced by high protein diet and maintain on a higher expression level in rat hepatocyte spheroids by serum-free medium (SFM) culture and coculture with mesenchymal stromal cells (MSCs). Rats were feed normal protein diet (NPD) or high protein diet (HPD) for 7 days before liver digestion and isolation of hepatocytes. Hepatocyte spheroids were formed and maintained in a rocked suspension culture with or without MSCs in SFM or 10% serum-containing medium (SCM). Spheroid viability, kinetics of spheroid formation, hepatic functions, gene expression, and biochemical activities of rat hepatocyte spheroids were tested over 14 days of culture. We observed that urea cycle enzymes of hepatocyte spheroids can be induced by high protein diet. SFM and MSCs enhanced ammonia clearance and ureagenesis and stabilized integrity of hepatocyte spheroids compared to control conditions over 14 days. Hepatocytes from high protein diet-fed rats formed spheroids and maintained a high level of ammonia detoxification for over 14 days in a novel SFM. Hepatic functionality and spheroid integrity were further stabilized by coculture of hepatocytes with MSCs in the spheroid microenvironment. These findings have direct application to development of the spheroid reservoir bioartificial liver. PMID:23006214

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.

Development and application of a rat PBPK model to elucidate kidney and liver effects induced by ETBE and tert-butanol.

PubMed

Salazar, Keith D; Brinkerhoff, Christopher J; Lee, Janice S; Chiu, Weihsueh A

2015-11-01

Subchronic and chronic studies in rats of the gasoline oxygenates ethyl tert-butyl ether (ETBE) and tert-butanol (TBA) report similar noncancer kidney and liver effects but differing results with respect to kidney and liver tumors. Because TBA is a major metabolite of ETBE, it is possible that TBA is the active toxic moiety in all these studies, with reported differences due simply to differences in the internal dose. To test this hypothesis, a physiologically-based pharmacokinetic (PBPK) model was developed for ETBE and TBA to calculate internal dosimetrics of TBA following either TBA or ETBE exposure. This model, based on earlier PBPK models of methyl tert-butyl ether (MTBE), was used to evaluate whether kidney and liver effects are consistent across routes of exposure, as well as between ETBE and TBA studies, on the basis of estimated internal dose. The results demonstrate that noncancer kidney effects, including kidney weight changes, urothelial hyperplasia, and chronic progressive nephropathy (CPN), yielded consistent dose-response relationships across routes of exposure and across ETBE and TBA studies using TBA blood concentration as the dose metric. Relative liver weights were also consistent across studies on the basis of TBA metabolism, which is proportional to TBA liver concentrations. However, kidney and liver tumors were not consistent using any dose metric. These results support the hypothesis that TBA mediates the noncancer kidney and liver effects following ETBE administration; however, additional factors besides internal dose are necessary to explain the induction of liver and kidney tumors. Published by Elsevier Inc.

Bioengineered humanized livers as better three-dimensional drug testing model system.

PubMed

Vishwakarma, Sandeep Kumar; Bardia, Avinash; Lakkireddy, Chandrakala; Nagarapu, Raju; Habeeb, Md Aejaz; Khan, Aleem Ahmed

2018-01-27

To develop appropriate humanized three-dimensional ex-vivo model system for drug testing. Bioengineered humanized livers were developed in this study using human hepatic stem cells repopulation within the acellularized liver scaffolds which mimics with the natural organ anatomy and physiology. Six cytochrome P-450 probes were used to enable efficient identification of drug metabolism in bioengineered humanized livers. The drug metabolism study in bioengineered livers was evaluated to identify the absorption, distribution, metabolism, excretion and toxicity responses. The bioengineered humanized livers showed cellular and molecular characteristics of human livers. The bioengineered liver showed three-dimensional natural architecture with intact vasculature and extra-cellular matrix. Human hepatic cells were engrafted similar to the human liver. Drug metabolism studies provided a suitable platform alternative to available ex-vivo and in vivo models for identifying cellular and molecular dynamics of pharmacological drugs. The present study paves a way towards the development of suitable humanized preclinical model systems for pharmacological testing. This approach may reduce the cost and time duration of preclinical drug testing and further overcomes on the anatomical and physiological variations in xenogeneic systems.

A clinical study of the LiVac laparoscopic liver retractor system.

PubMed

Gan, Philip; Bingham, Judy

2016-02-01

All retractors for laparoscopic operations on the gallbladder or stomach apply an upward force to the under-surface of the liver or gallbladder, most requiring an additional skin incision. The LiVac laparoscopic liver retractor system (LiVac retractor) comprises a soft silicone ring attached to suction tubing and connected to a regulated source of suction. The suction tubing extends alongside existing ports. When placed between the liver and diaphragm, and suction applied, a vacuum is created within the ring, keeping these in apposition. Following successful proof-of-concept animal testing, a clinical study was conducted to evaluate the performance and safety of the retractor in patients. The study was a dual-centre, single-surgeon, open-label study and recruited ten patients scheduled to undergo routine upper abdominal laparoscopic surgery including cholecystectomy, primary gastric banding surgery or fundoplication. The study was conducted at two sites and was approved by the institutions' ethics committees. The primary objective of the study was to evaluate the performance of the LiVac retractor in patients undergoing upper abdominal single- or multi-port laparoscopic surgery. Performance was measured by the attainment of milestones for the retractor and accessory bevel, where used, and safety outcomes through the recording of adverse events, physical parameters, pain scales, blood tests and a post-operative liver ultrasound. The LiVac retractor achieved both primary and secondary performance and safety objectives in all patients. No serious adverse events and no device-related adverse events or device deficiencies were reported. The LiVac retractor achieved effective liver retraction without clinically significant trauma and has potential application in multi- or single-port laparoscopic upper abdominal surgery. As a separate incision is not required, the use of the LiVac retractor in multi-port surgery therefore reduces the number of incisions.

A web-based computer aided system for liver surgery planning: initial implementation on RayPlus

NASA Astrophysics Data System (ADS)

Luo, Ming; Yuan, Rong; Sun, Zhi; Li, Tianhong; Xie, Qingguo

2016-03-01

At present, computer aided systems for liver surgery design and risk evaluation are widely used in clinical all over the world. However, most systems are local applications that run on high-performance workstations, and the images have to processed offline. Compared with local applications, a web-based system is accessible anywhere and for a range of regardless of relative processing power or operating system. RayPlus (http://rayplus.life.hust.edu.cn), a B/S platform for medical image processing, was developed to give a jump start on web-based medical image processing. In this paper, we implement a computer aided system for liver surgery planning on the architecture of RayPlus. The system consists of a series of processing to CT images including filtering, segmentation, visualization and analyzing. Each processing is packaged into an executable program and runs on the server side. CT images in DICOM format are processed step by to interactive modeling on browser with zero-installation and server-side computing. The system supports users to semi-automatically segment the liver, intrahepatic vessel and tumor from the pre-processed images. Then, surface and volume models are built to analyze the vessel structure and the relative position between adjacent organs. The results show that the initial implementation meets satisfactorily its first-order objectives and provide an accurate 3D delineation of the liver anatomy. Vessel labeling and resection simulation are planned to add in the future. The system is available on Internet at the link mentioned above and an open username for testing is offered.

Non-rigid registration between 3D ultrasound and CT images of the liver based on intensity and gradient information

NASA Astrophysics Data System (ADS)

Lee, Duhgoon; Nam, Woo Hyun; Lee, Jae Young; Ra, Jong Beom

2011-01-01

In order to utilize both ultrasound (US) and computed tomography (CT) images of the liver concurrently for medical applications such as diagnosis and image-guided intervention, non-rigid registration between these two types of images is an essential step, as local deformation between US and CT images exists due to the different respiratory phases involved and due to the probe pressure that occurs in US imaging. This paper introduces a voxel-based non-rigid registration algorithm between the 3D B-mode US and CT images of the liver. In the proposed algorithm, to improve the registration accuracy, we utilize the surface information of the liver and gallbladder in addition to the information of the vessels inside the liver. For an effective correlation between US and CT images, we treat those anatomical regions separately according to their characteristics in US and CT images. Based on a novel objective function using a 3D joint histogram of the intensity and gradient information, vessel-based non-rigid registration is followed by surface-based non-rigid registration in sequence, which improves the registration accuracy. The proposed algorithm is tested for ten clinical datasets and quantitative evaluations are conducted. Experimental results show that the registration error between anatomical features of US and CT images is less than 2 mm on average, even with local deformation due to different respiratory phases and probe pressure. In addition, the lesion registration error is less than 3 mm on average with a maximum of 4.5 mm that is considered acceptable for clinical applications.

Halofuginone can worsen liver fibrosis in bile duct obstructed rats.

PubMed

Van de Casteele, Marc; Roskams, Tania; Van der Elst, Ingrid; van Pelt, Jos F; Fevery, Johan; Nevens, Frederik

2004-10-01

Halofuginone (HF) is an antifibrotic agent in rat models of liver fibrosis caused by repetitive intoxications. A beneficial effect of HF on a biliary type of liver fibrosis has not been proven yet. Bile duct-obstructed rats were given HF from the moment of obstruction onwards and compared with no treatment. After 3 weeks, respectively, 6 weeks, aminopyrine breath test (ABT) and haemodynamic measurements including of portal pressure were carried out. Liver pieces were taken for Sirius red quantitative scoring, as well as for semiquantitative determinations of collagen type I and III RNA levels. ABT was significantly worse in HF-treated rats as compared with no treatment (P=0.02). Haemodynamic data and collagen type I and III determinations were not significantly different between groups. Biliary fibrosis scores were significantly higher in HF-treated rats as compared with no treatment (P=0.03). More Sirius red staining was associated with more proliferation of bile ductules. HF may worsen biliary fibrosis. This contrasts sharply with antifibrotic effects in other models of liver fibrosis. Distinctive cellular mechanisms in biliary fibrosis may explain this discrepancy. One should be cautious for chronic application of HF in man with cholestasis.

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

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.

Liver Transplant

MedlinePlus

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Assessment of the accuracy of an ultrasound elastography liver scanning system using a PVA-cryogel phantom with optimal acoustic and mechanical properties

NASA Astrophysics Data System (ADS)

Cournane, S.; Cannon, L.; Browne, J. E.; Fagan, A. J.

2010-10-01

The accuracy of a transient elastography liver-scanning ultrasound system was assessed using a novel application of PVA-cryogel as a tissue-mimicking material with acoustic and shear elasticity properties optimized to best represent those of liver tissue. Although the liver-scanning system has been shown to offer a safer alternative for diagnosing liver cirrhosis through stiffness measurement, as compared to the liver needle biopsy exam, the scanner's accuracy has not been fully established. Young's elastic modulus values of 5-6 wt% PVA-cryogel phantoms, also containing glycerol and 0.3 µm Al2O3 and 3 µm Al2O3, were measured using a 'gold standard' mechanical testing technique and transient elastography. The mechanically measured values and acoustic velocities of the phantoms ranged between 1.6 and 16.1 kPa and 1540 and 1570 m s-1, respectively, mimicking those observed in liver tissue. The values reported by the transient elastography system overestimated Young's elastic modulus values representative of the progressive stages of liver fibrosis by up to 32%. These results were attributed to the relative rather than absolute nature of the measurement arising from the single-point acoustic velocity calibration of the system, rendering the measurements critically dependent on the speed of sound of the sample under investigation. Given the wide range of acoustic velocities which exist in the liver, spanning healthy tissue to cirrhotic pathology, coupled with the system's assumption that the liver is approximately elastic when it is rather highly viscoelastic, care should be exercised when interpreting the results from this system in patient groups.

A Portal Vein Injection Model to Study Liver Metastasis of Breast Cancer.

PubMed

Goddard, Erica T; Fischer, Jacob; Schedin, Pepper

2016-12-26

Breast cancer is the leading cause of cancer-related mortality in women worldwide. Liver metastasis is involved in upwards of 30% of cases with breast cancer metastasis, and results in poor outcomes with median survival rates of only 4.8 - 15 months. Current rodent models of breast cancer metastasis, including primary tumor cell xenograft and spontaneous tumor models, rarely metastasize to the liver. Intracardiac and intrasplenic injection models do result in liver metastases, however these models can be confounded by concomitant secondary-site metastasis, or by compromised immunity due to removal of the spleen to avoid tumor growth at the injection site. To address the need for improved liver metastasis models, a murine portal vein injection method that delivers tumor cells firstly and directly to the liver was developed. This model delivers tumor cells to the liver without complications of concurrent metastases in other organs or removal of the spleen. The optimized portal vein protocol employs small injection volumes of 5 - 10 μl, ≥ 32 gauge needles, and hemostatic gauze at the injection site to control for blood loss. The portal vein injection approach in Balb/c female mice using three syngeneic mammary tumor lines of varying metastatic potential was tested; high-metastatic 4T1 cells, moderate-metastatic D2A1 cells, and low-metastatic D2.OR cells. Concentrations of ≤ 10,000 cells/injection results in a latency of ~ 20 - 40 days for development of liver metastases with the higher metastatic 4T1 and D2A1 lines, and > 55 days for the less aggressive D2.OR line. This model represents an important tool to study breast cancer metastasis to the liver, and may be applicable to other cancers that frequently metastasize to the liver including colorectal and pancreatic adenocarcinomas.

Effects of gadolinium-based MRI contrast agents on liver tissue.

PubMed

Mercantepe, Tolga; Tümkaya, Levent; Çeliker, Fatma Beyazal; Topal Suzan, Zehra; Çinar, Seda; Akyildiz, Kerimali; Mercantepe, Filiz; Yilmaz, Adnan

2018-04-01

MRI with contrast is often used clinically. However, recent studies have reported a high accumulation of gadolinium-based contrast agents (GBCAs) in kidney, liver, and spleen tissues in several mouse models. To compare the effects on liver tissue of gadolinium-based MRI contrast agents in the light of biochemical and histopathological evaluation. Institutional Review Board (IRB)-approved controlled longitudinal study. In all, 32 male Sprague-Dawley rats were divided into a healthy control group subjected to no procedure (Group 1), a sham group (Group 2), a gadodiamide group (Group 3), and a gadoteric acid group (Group 4). Not applicable. Liver tissues removed at the end of the fifth week and evaluated pathologically (scored Knodell's histological activity index [HAI] method by two histopathologists) immunohistochemical (caspase-3 and biochemical tests (AST, ALT, TAS, TOS, and OSI method by Erel et al) were obtained. Differences between groups were analyzed using the nonparametric Kruskal-Wallis test followed by the Tamhane test, and one-way analysis of variance (ANOVA) followed by Turkey's HSD test. An increase was observed in histological activity scores in sections from rats administered gadodiamide and gadoteric acid, and in caspase-3, AST and ALT values (P < 0.05). In contrast, we determined no change in TOS (P = 0.568 and P = 0.094, respectively), TAS (P = 0.151 and P = 0.055, respectively), or OSI (P = 0.949 and P = 0.494, respectively) values. These data suggest that gadodiamide and gadoteric acid trigger hepatocellular necrosis and apoptosis by causing damage in hepatocytes, although no change occurs in total antioxidant and antioxidant capacity. 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Incidence of abnormal liver biochemical tests in hyperthyroidism.

PubMed

Lin, Tiffany Y; Shekar, Anshula O; Li, Ning; Yeh, Michael W; Saab, Sammy; Wilson, Mark; Leung, Angela M

2017-05-01

Abnormal serum liver function tests are common in patients with untreated thyrotoxicosis, even prior to the initiation of antithyroidal medications that may worsen the severity of the abnormal serum liver biochemistries. There is a wide range of the incidence of these abnormalities in the published literature. The aim of this study was to assess the risks factors and threshold of thyrotoxicosis severity for developing an abnormal liver biochemical test upon the diagnosis of new thyrotoxicosis. Single-institution retrospective cohort study. Patients of ≥18 years old receiving medical care at a large, academic, urban US medical centre between 2002-2016. Inclusion criteria were a serum thyroid stimulating hormone (TSH) concentration of <0·3 mIU/l or ICD-9 code for thyrotoxicosis, with thyrotoxicosis confirmed by either a concurrent elevated serum triiodothyronine (T3) or thyroxine (T4) concentration ([total or free] within 3 months), and an available liver biochemical test(s) within 6 months of thyrotoxicosis. The biochemical liver tests assessed were serum aspartate transaminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma-glutamyltransferase (GGT), total bilirubin, and conjugated bilirubin concentrations. In this cohort of 1514 subjects, the overall incidence of any biochemical liver test abnormality within 6 months of thyrotoxicosis was 39%. An initial serum TSH concentration <0·02 mIU/l, male gender, and African-American race were significant predictors of an abnormal serum liver biochemical test within 6 months of the diagnosis of new-onset untreated thyrotoxicosis. This study identifies risk factors for patients who develop an abnormal serum liver biochemical test result within 6 months of a diagnosis of untreated thyrotoxicosis. © 2017 John Wiley & Sons Ltd.

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 ...

Childhood Liver Cancer Symptoms, Tests, Prognosis, and Stages (PDQ®)—Patient Version

Cancer.gov

Liver cancer is rare in children and adolescents. There are two main types of childhood liver cancer. Hepatoblastoma usually affects children 3 years and younger, and hepatocellular carcinoma occurs in older children and teenagers. Learn about risk factors, tests to diagnose, and stages of childhood liver cancer.

Prevalence and factors associated with the presence of abnormal function liver tests in patients with ulcerative colitis.

PubMed

Yamamoto-Furusho, Jesús K; Sánchez-Osorio, Magdalena; Uribe, Misael

2010-01-01

To investigate the prevalence of abnormal function liver tests and risk factors associated with their development in Mexican patients with UC. A total of 200 patients with confirmed diagnosis of UC were evaluated prospectively during a one year period from January 1, 2007 to December 31, 2008. A total of 94 females and 106 males patients with UC were analyzed. The age at diagnosis was 31.4 ± 13.2 years and the mean of disease duration was 6.7 ± 5.2 years. We found a high prevalence of abnormal function livers tests in 40% of UC patients. The pattern of abnormal function liver test was hepatitis in 70%, cholestatic (20%) and mixed (10%). The most common cause of abnormal function liver test was transient elevation in 50 patients (63%) followed by fatty liver disease (11.2%), primary sclerosing cholangitis (6.3%), drug-toxicity (6%) and others (13.5%) including chronic hepatitis C, total parenteral nutrition, granulomatous and ischemic hepatitis. In the multivariate logistic regression model, active disease, colectomy and abdominal sepsis were factors that persisted associated with the development of abnormal liver tests in UC patients. A high prevalence of abnormal function liver tests (40%) was found in Mexican UC patients is likely to be related to active disease, colectomy and the presence of sepsis.

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 ...

Accuracy of the Enhanced Liver Fibrosis Test vs FibroTest, Elastography, and Indirect Markers in Detection of Advanced Fibrosis in Patients With Alcoholic Liver Disease.

PubMed

Thiele, Maja; Madsen, Bjørn Stæhr; Hansen, Janne Fuglsang; Detlefsen, Sönke; Antonsen, Steen; Krag, Aleksander

2018-04-01

Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3). We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day. Patients were recruited from primary centers (municipal alcohol rehabilitation, n = 128; 6% with advanced fibrosis) and secondary health care centers (hospital outpatient clinics, n = 161; 36% with advanced fibrosis) in the Region of Southern Denmark from 2013 through 2016. Biopsy-verified fibrosis stage was used as the reference standard. The primary aim was to validate ELF in detection of advanced fibrosis in patients with alcoholic liver disease recruited from primary and secondary health care centers, using the literature-based cutoff value of 10.5. Secondary aims were to assess the diagnostic accuracy of ELF for significant fibrosis and cirrhosis and to determine whether combinations of fibrosis markers increase diagnostic yield. The ELF identified patients with advanced liver fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% confidence interval 0.89-0.96); findings did not differ significantly between patients from primary vs secondary care (P = .917). ELF more accurately identified patients with advanced liver fibrosis than indirect marker tests, but ELF and FibroTest had comparable diagnostic accuracies (AUROC of FibroTest, 0.90) (P = .209 for comparison with ELF). Results from the ELF and FibroTest did not differ significantly from those of liver stiffness measurement in intention-to-diagnose analyses (AUROC for transient elastography, 0.90), but did differ in the per-protocol analysis (AUROC for transient elastography, 0.97) (P = .521 and .004 for comparison with ELF). Adding a serum marker to transient elastography analysis did not increase accuracy. For patients in primary care, ELF values below 10.5 and FibroTest values below 0.58 had negative predictive values for advanced liver fibrosis of 98% and 94%, respectively. In a prospective, direct comparison of tests, ELF and FibroTest identified advanced liver fibrosis in alcoholic patients from primary and secondary care with high diagnostic accuracy (AUROC values of 0.90 or higher using biopsy as reference). Advanced fibrosis can be ruled out in primary health care patients based on an ELF value below 10.5 or a FibroTest value below 0.58. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Gd-EOB-DTPA-Enhanced MR Guidance in Thermal Ablation of Liver Malignancies

PubMed Central

Rosenberg, Christian; Jahn, Andrea; Pickartz, Tilman; Wahnschaffe, Ulrich; Patrzyk, Maciej; Hosten, Norbert

2014-01-01

Objective To evaluate the potency of Gd-EOB-DTPA to support hepatic catheter placement in laser ablation procedures by quantifying time-dependent delineation effects for instrumentation and target tumor within liver parenchyma. Monitoring potential influence on online MR thermometry during the ablation procedure is a secondary aim. Materials and Methods 30 cases of MR-guided laser ablation were performed after i.v. bolus injection of gadoxetic acid (0.025 mmol/Kg Gd-EOB-DTPA; Bayer Healthcare, Berlin, Germany). T1-weighted GRE sequences were used for applicator guidance (FLASH 3D) in the catheter placement phase and for therapy monitoring (FLASH 2D) in the therapy phase. SNR and consecutive CNR values were measured for elements of interest plotted over time both for catheter placement and therapy phase and compared with a non-contrast control group of 19 earlier cases. Statistical analysis was realized using the paired Wilcoxon test. Results Sustainable signal elevation of liver parenchyma in the contrast-enhanced group was sufficient to silhouette both target tumor and applicator against the liver. Differences in time dependent CNR alteration were highly significant between contrast-enhanced and non-contrast interventions for parenchyma and target on the one hand (p = 0.020) and parenchyma and instrument on the other hand (p = 0.002). Effects lasted for the whole procedure (monitoring up to 60 min) and were specific for the contrast-enhanced group. Contrasting maxima were seen after median 30 (applicator) and 38 (tumor) minutes, in the potential core time of a multineedle procedure. Contrast influence on T1 thermometry for real-time monitoring of thermal impact was not significant (p = 0.068–0.715). Conclusion Results strongly support anticipated promotive effects of Gd-EOB-DTPA for MR-guided percutaneous liver interventions by proving and quantifying the delineating effects for therapy-relevant elements in the procedure. Time benefit, cost effectiveness and oncologic outcome of the described beneficiary effects will have to be part of further investigations. PMID:25541950

Gd-EOB-DTPA-enhanced MR guidance in thermal ablation of liver malignancies.

PubMed

Rosenberg, Christian; Jahn, Andrea; Pickartz, Tilman; Wahnschaffe, Ulrich; Patrzyk, Maciej; Hosten, Norbert

2014-01-01

To evaluate the potency of Gd-EOB-DTPA to support hepatic catheter placement in laser ablation procedures by quantifying time-dependent delineation effects for instrumentation and target tumor within liver parenchyma. Monitoring potential influence on online MR thermometry during the ablation procedure is a secondary aim. 30 cases of MR-guided laser ablation were performed after i.v. bolus injection of gadoxetic acid (0.025 mmol/Kg Gd-EOB-DTPA; Bayer Healthcare, Berlin, Germany). T1-weighted GRE sequences were used for applicator guidance (FLASH 3D) in the catheter placement phase and for therapy monitoring (FLASH 2D) in the therapy phase. SNR and consecutive CNR values were measured for elements of interest plotted over time both for catheter placement and therapy phase and compared with a non-contrast control group of 19 earlier cases. Statistical analysis was realized using the paired Wilcoxon test. Sustainable signal elevation of liver parenchyma in the contrast-enhanced group was sufficient to silhouette both target tumor and applicator against the liver. Differences in time dependent CNR alteration were highly significant between contrast-enhanced and non-contrast interventions for parenchyma and target on the one hand (p = 0.020) and parenchyma and instrument on the other hand (p = 0.002). Effects lasted for the whole procedure (monitoring up to 60 min) and were specific for the contrast-enhanced group. Contrasting maxima were seen after median 30 (applicator) and 38 (tumor) minutes, in the potential core time of a multineedle procedure. Contrast influence on T1 thermometry for real-time monitoring of thermal impact was not significant (p = 0.068-0.715). Results strongly support anticipated promotive effects of Gd-EOB-DTPA for MR-guided percutaneous liver interventions by proving and quantifying the delineating effects for therapy-relevant elements in the procedure. Time benefit, cost effectiveness and oncologic outcome of the described beneficiary effects will have to be part of further investigations.

Ultrasound elastographic techniques in focal liver lesions

PubMed Central

Conti, Clara Benedetta; Cavalcoli, Federica; Fraquelli, Mirella; Conte, Dario; Massironi, Sara

2016-01-01

Elastographic techniques are new ultrasound-based imaging techniques developed to estimate tissue deformability/stiffness. Several ultrasound elastographic approaches have been developed, such as static elastography, transient elastography and acoustic radiation force imaging methods, which include point shear wave and shear wave imaging elastography. The application of these methods in clinical practice aims at estimating the mechanical tissues properties. One of the main settings for the application of these tools has been liver stiffness assessment in chronic liver disease, which has been studied mainly using transient elastography. Another field of application for these techniques is the assessment of focal lesions, detected by ultrasound in organs such as pancreas, prostate, breast, thyroid, lymph nodes. Considering the frequency and importance of the detection of focal liver lesions through routine ultrasound, some studies have also aimed to assess the role that elestography can play in studying the stiffness of different types of liver lesions, in order to predict their nature and thus offer valuable non-invasive methods for the diagnosis of liver masses. PMID:26973405

Ultrasound elastographic techniques in focal liver lesions.

PubMed

Conti, Clara Benedetta; Cavalcoli, Federica; Fraquelli, Mirella; Conte, Dario; Massironi, Sara

2016-03-07

Elastographic techniques are new ultrasound-based imaging techniques developed to estimate tissue deformability/stiffness. Several ultrasound elastographic approaches have been developed, such as static elastography, transient elastography and acoustic radiation force imaging methods, which include point shear wave and shear wave imaging elastography. The application of these methods in clinical practice aims at estimating the mechanical tissues properties. One of the main settings for the application of these tools has been liver stiffness assessment in chronic liver disease, which has been studied mainly using transient elastography. Another field of application for these techniques is the assessment of focal lesions, detected by ultrasound in organs such as pancreas, prostate, breast, thyroid, lymph nodes. Considering the frequency and importance of the detection of focal liver lesions through routine ultrasound, some studies have also aimed to assess the role that elestography can play in studying the stiffness of different types of liver lesions, in order to predict their nature and thus offer valuable non-invasive methods for the diagnosis of liver masses.

Depletion of penicillin G residues in heavy sows after intramuscular injection. Part II: application of kidney inhibition swab tests.

PubMed

Shelver, Weilin L; Lupton, Sara J; Newman, David J; Larsen, Steven; Smith, David J

2014-07-30

Sows (n = 126; 228 ± 30.1 kg) were administered daily IM doses of penicillin G procaine (33 000 IU/kg bw; 5× the label dose) for 3 consecutive days using three different administration patterns. Within treatment, six sows each were slaughtered on withdrawal day 5, 10, 15, 20, 25, 32, and 39. Tissues (injection site, kidney, liver, skeletal muscle) or body fluids (serum and urine) were screened for penicillin G using the KIS test, recently adopted by the USDA Food Safety and Inspection Service. The IM administration patterns had no discernible effect on penicillin G depletion. Residues were depleted more rapidly from liver and skeletal muscle and more slowly from kidney and urine. Kidney was the most sensitive and suitable tissue for detecting penicillin G residues on-site, with two positive results after a 39-day withdrawal period. Urine was the most suitable ante-mortem surrogate to predict the results of kidney tests.

Primary biliary cirrhosis

MedlinePlus

... stools Itching Poor appetite and weight loss As liver function worsens, symptoms may include: Fluid buildup in the ... your liver is working properly: Albumin blood test Liver function tests (serum alkaline phosphatase is most important) Prothrombin ...

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.

Filipendula ulmaria extracts attenuate cisplatin-induced liver and kidney oxidative stress in rats: In vivo investigation and LC-MS analysis.

PubMed

Katanić, Jelena; Matić, Sanja; Pferschy-Wenzig, Eva-Maria; Kretschmer, Nadine; Boroja, Tatjana; Mihailović, Vladimir; Stanković, Vesna; Stanković, Nevena; Mladenović, Milan; Stanić, Snežana; Mihailović, Mirjana; Bauer, Rudolf

2017-01-01

Filipendula ulmaria, known as meadowsweet, is a perennial herb found in wild and cultivated habitats in Europe and Asia. Usage of F. ulmaria in traditional medicine is based on diuretic, astringent, antirheumatic, and anti-inflammatory properties of this plant. Exposure to cisplatin at a dose of 7.5 mg/kg caused significant increase in serum parameters of liver and kidneys function and tissue oxidative stress markers along with some histopathological changes in liver and kidney tissues of experimental rats, as well as high level of genotoxicity. Administration of F. ulmaria extracts in three different concentrations (100, 200, and 400 mg/kg/day) for 10 days resulted in a reduction of oxidative stress in tissues and decrease of serum parameters. Moreover, tested extracts attenuated the genotoxicity of cisplatin in reverse dose-dependent manner. F. ulmaria extracts had no in vitro cytotoxic activity at all applied concentrations (IC 50  > 50 μg/mL). Tested extracts, rich in polyphenolic compounds, attenuate cisplatin-induced liver and kidney oxidative stress, reduce tissue damage, and enhance the antioxidative status of experimental animals during cisplatin application. Therefore, F. ulmaria extracts may be used as supportive agent for the prevention and amelioration of cisplatin side effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Composite Configuration Interventional Therapy Robot for the Microwave Ablation of Liver Tumors

NASA Astrophysics Data System (ADS)

Cao, Ying-Yu; Xue, Long; Qi, Bo-Jin; Jiang, Li-Pei; Deng, Shuang-Cheng; Liang, Ping; Liu, Jia

2017-11-01

The existing interventional therapy robots for the microwave ablation of liver tumors have a poor clinical applicability with a large volume, low positioning speed and complex automatic navigation control. To solve above problems, a composite configuration interventional therapy robot with passive and active joints is developed. The design of composite configuration reduces the size of the robot under the premise of a wide range of movement, and the robot with composite configuration can realizes rapid positioning with operation safety. The cumulative error of positioning is eliminated and the control complexity is reduced by decoupling active parts. The navigation algorithms for the robot are proposed based on solution of the inverse kinematics and geometric analysis. A simulation clinical test method is designed for the robot, and the functions of the robot and the navigation algorithms are verified by the test method. The mean error of navigation is 1.488 mm and the maximum error is 2.056 mm, and the positioning time for the ablation needle is in 10 s. The experimental results show that the designed robot can meet the clinical requirements for the microwave ablation of liver tumors. The composite configuration is proposed in development of the interventional therapy robot for the microwave ablation of liver tumors, which provides a new idea for the structural design of medical robots.

Request of laboratory liver tests in primary care in Spain: potential savings if appropriateness indicator targets were achieved.

PubMed

Salinas, Maria; López-Garrigós, Maite; Flores, Emilio; Uris, Joaquín; Leiva-Salinas, Carlos

2015-10-01

Liver laboratory tests are used to screen for liver disease, suggest the underlying cause, estimate the severity, assess prognosis, and monitor the efficacy of therapy. The aim of this study was to compare the liver laboratory tests requesting patterns by GPs in Spain, according to geographic and hospital characteristics, to investigate the degree of requesting appropriateness. One hundred and forty-one clinical laboratories were invited to participate from diverse regions across Spain. They filed out the number of laboratory liver tests requested by GPs for the year 2012. Two types of appropriateness indicators were calculated: every test request per 1000 inhabitants or ratios of related tests requests. The indicator results obtained were compared between the different hospitals, according to their setting, location, and management. The savings generated, if each area would have achieved indicator targets, were calculated. We recruited 76 laboratories covering a population of 17,679,195 inhabitants. GPs requested 20,916,780 laboratory liver tests in the year 2012. No differences were obtained according to their setting. Lactate dehydrogenase and direct bilirubin per 1000 inhabitants were significantly higher in institutions with private management. Largest differences were observed between communities. Nine, 31, 0, and 13 laboratories, respectively, achieved the aspartate aminotransferase, lactate dehydrogenase, γ-glutamyl transpeptidase, and total bilirubin-related alanine aminotransferase indicator targets. Reaching ratios would have resulted in savings of €1,028,468. There was a high variability in the request of liver tests. This emphasizes the need to implement interventions to improve appropriate use of liver tests.

Incidence of Abnormal Liver Biochemical Tests in Hyperthyroidism

PubMed Central

Lin, Tiffany Y.; Shekar, Anshula O.; Li, Ning; Yeh, Michael W.; Saab, Sammy; Wilson, Mark; Leung, Angela M.

2017-01-01

Objective Abnormal serum liver function tests are common in patients with untreated thyrotoxicosis, even prior to the initiation of antithyroidal medications that may worsen their severity. There is a wide range of the incidence of these abnormalities in the published literature. The aim of this study was to assess the risks factors and threshold of thyrotoxicosis severity for developing an abnormal liver biochemical test upon the diagnosis of new thyrotoxicosis. Design Single-institution retrospective cohort study. Patients Patients ≥18 years old receiving medical care at a large, academic, urban U.S. medical center between 2002–2016. Measurements Inclusion criteria were a serum thyroid stimulating hormone [TSH] concentration < 0.3 mIU/L or ICD-9 code for thyrotoxicosis, with thyrotoxicosis confirmed by either a concurrent elevated serum triiodothyronine (T3) and/or thyroxine (T4) concentration [total or free] within 3 months), and an available liver biochemical test(s) within 6 months of thyrotoxicosis. The biochemical liver tests assessed were serum aspartate transaminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma-glutamyltransferase (GGT), total bilirubin, and conjugated bilirubin concentrations. Results In this cohort of 1,514 subjects, the overall incidence of any biochemical liver test abnormality within 6 months of thyrotoxicosis was 39%. An initial serum TSH concentration <0.02 mIU/L, male gender, and African-American race were significant predictors of an abnormal serum liver biochemical test within 6 months of the diagnosis of new-onset untreated thyrotoxicosis. Conclusions This study identifies risk factors for patients who develop an abnormal serum liver biochemical test result within 6 months of a diagnosis of untreated thyrotoxicosis. PMID:28199740

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

PubMed

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

2018-02-27

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

Study of Abnormal Liver Function Test during Pregnancy in a Tertiary Care Hospital in Chhattisgarh.

PubMed

Mishra, Nalini; Mishra, V N; Thakur, Parineeta

2016-10-01

Abnormal liver function tests (LFTs) in pregnancy require proper interpretation in order to avoid pitfalls in the diagnosis. The underlying disorder can have a significant effect on the outcome of both mother and foetus. The present study was done with the objective to study the clinical profile, incidence and possible causes of derangements of liver function tests. Eighty pregnant women with abnormal liver dysfunction were studied prospectively. Women with chronic liver disease and drug-induced abnormal liver function test were excluded. All available LFTs including LDH were studied along with some more definitive tests to aid identification of underlying cause. Foetomaternal outcome was noted in all. The incidence of abnormal LFT was 0.9 %. 13/80 (16.75 %) women had liver disorder not specific to pregnancy, whereas 67/80 (83.25 %) women had pregnancy-specific liver dysfunction. Of these, 65(81.25 %) women with liver dysfunction had pre-eclampsia including 11 (13.75 %) with HELLP and six women with eclampsia. 48/65 (60 %) women had pre-eclampsia in the absence of HELLP syndrome or eclampsia. The mean value for bilirubin (mg %) in hypertensive disorders of pregnancy ranged from 1.64 to 3.8, between 5 and 10 for ICP and AFLP and >10 in infective hepatitis. Transaminases were highest in infective hepatitis, whereas alkaline phosphate was highest in ICP. Total 27 (33.75 %) women suffered from adverse outcome with four (5 %) maternal deaths and 23 (28.75 %) major maternal morbidities. 33/80 (41.25 %) women had intrauterine death. 26.25 % babies were small for date. Pregnancy-specific disorders are the leading cause of abnormal liver function test during pregnant state particularly in the third trimester. Pre-eclampsia-related disorder is the commonest. Gestational age of pregnancy and relative values of various liver function tests in different pregnancy-specific and pregnancy nonspecific disorders appear to be the best guide to clinch the diagnosis.

Development and application of a rat PBPK model to elucidate kidney and liver effects induced by ETBE and tert-butanol

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

Salazar, Keith D., E-mail: Salazar.keith@epa.gov; Brinkerhoff, Christopher J., E-mail: Brinkerhoff.Chris@epa.gov; Lee, Janice S., E-mail: Lee.JaniceS@epa.gov

Subchronic and chronic studies in rats of the gasoline oxygenates ethyl tert-butyl ether (ETBE) and tert-butanol (TBA) report similar noncancer kidney and liver effects but differing results with respect to kidney and liver tumors. Because TBA is a major metabolite of ETBE, it is possible that TBA is the active toxic moiety in all these studies, with reported differences due simply to differences in the internal dose. To test this hypothesis, a physiologically-based pharmacokinetic (PBPK) model was developed for ETBE and TBA to calculate internal dosimetrics of TBA following either TBA or ETBE exposure. This model, based on earlier PBPKmore » models of methyl tert-butyl ether (MTBE), was used to evaluate whether kidney and liver effects are consistent across routes of exposure, as well as between ETBE and TBA studies, on the basis of estimated internal dose. The results demonstrate that noncancer kidney effects, including kidney weight changes, urothelial hyperplasia, and chronic progressive nephropathy (CPN), yielded consistent dose–response relationships across routes of exposure and across ETBE and TBA studies using TBA blood concentration as the dose metric. Relative liver weights were also consistent across studies on the basis of TBA metabolism, which is proportional to TBA liver concentrations. However, kidney and liver tumors were not consistent using any dose metric. These results support the hypothesis that TBA mediates the noncancer kidney and liver effects following ETBE administration; however, additional factors besides internal dose are necessary to explain the induction of liver and kidney tumors. - Highlights: • We model two metabolically-related fuel oxygenates to address toxicity data gaps. • Kidney and liver effects are compared on an internal dose basis. • Noncancer kidney effects are consistent using TBA blood concentration. • Liver weight changes are consistent using TBA metabolic rate. • Kidney and liver tumors are not consistent using any internal dose metric.« less

Superpixel-based and boundary-sensitive convolutional neural network for automated liver segmentation

NASA Astrophysics Data System (ADS)

Qin, Wenjian; Wu, Jia; Han, Fei; Yuan, Yixuan; Zhao, Wei; Ibragimov, Bulat; Gu, Jia; Xing, Lei

2018-05-01

Segmentation of liver in abdominal computed tomography (CT) is an important step for radiation therapy planning of hepatocellular carcinoma. Practically, a fully automatic segmentation of liver remains challenging because of low soft tissue contrast between liver and its surrounding organs, and its highly deformable shape. The purpose of this work is to develop a novel superpixel-based and boundary sensitive convolutional neural network (SBBS-CNN) pipeline for automated liver segmentation. The entire CT images were first partitioned into superpixel regions, where nearby pixels with similar CT number were aggregated. Secondly, we converted the conventional binary segmentation into a multinomial classification by labeling the superpixels into three classes: interior liver, liver boundary, and non-liver background. By doing this, the boundary region of the liver was explicitly identified and highlighted for the subsequent classification. Thirdly, we computed an entropy-based saliency map for each CT volume, and leveraged this map to guide the sampling of image patches over the superpixels. In this way, more patches were extracted from informative regions (e.g. the liver boundary with irregular changes) and fewer patches were extracted from homogeneous regions. Finally, deep CNN pipeline was built and trained to predict the probability map of the liver boundary. We tested the proposed algorithm in a cohort of 100 patients. With 10-fold cross validation, the SBBS-CNN achieved mean Dice similarity coefficients of 97.31  ±  0.36% and average symmetric surface distance of 1.77  ±  0.49 mm. Moreover, it showed superior performance in comparison with state-of-art methods, including U-Net, pixel-based CNN, active contour, level-sets and graph-cut algorithms. SBBS-CNN provides an accurate and effective tool for automated liver segmentation. It is also envisioned that the proposed framework is directly applicable in other medical image segmentation scenarios.

Acoustic accessibility investigation for ultrasound mediated treatment of glycogen storage disease type Ia patients.

PubMed

Wang, Shutao; Raju, Balasundar I; Leyvi, Evgeniy; Weinstein, David A; Seip, Ralf

2011-09-01

Glycogen storage disease type Ia (GSDIa) is caused by an inherited defect in the glucose-6-phosphatase gene. The recent advent of targeted ultrasound-mediated delivery (USMD) of plasmid DNA (pDNA) to the liver in conjunction with microbubbles may provide an alternative treatment option. This study focuses on determining the acoustically accessible liver volume in GSDIa patients using transducer models of various geometries with an image-based geometry-driven approach. Results show that transducers with longer focal lengths and smaller apertures (up to an f/number of 2) are able to access larger liver volumes in GSDIa patients while still being capable of delivering the required ultrasound dose in situ (2.5 MPa peak negative pressure at the focus). With sufficiently large acoustic windows and the ability to use glucose to easily assess efficacy, GSD appears to be a good model for testing USMD as proof of principle as a potential therapy for liver applications in general. Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

A stepwise algorithm using an at-a-glance first-line test for the non-invasive diagnosis of advanced liver fibrosis and cirrhosis.

PubMed

Boursier, Jérôme; de Ledinghen, Victor; Leroy, Vincent; Anty, Rodolphe; Francque, Sven; Salmon, Dominique; Lannes, Adrien; Bertrais, Sandrine; Oberti, Frederic; Fouchard-Hubert, Isabelle; Calès, Paul

2017-06-01

Chronic liver diseases (CLD) are common, and are therefore mainly managed by non-hepatologists. These physicians lack access to the best non-invasive tests of liver fibrosis, and consequently cannot accurately determine the disease severity. Referral to a hepatologist is then needed. We aimed to implement an algorithm, comprising a new first-line test usable by all physicians, for the detection of advanced liver fibrosis in all CLD patients. Diagnostic study: 3754 CLD patients with liver biopsy were 2:1 randomized into derivation and validation sets. Prognostic study: longitudinal follow-up of 1275 CLD patients with baseline fibrosis tests. Diagnostic study: the easy liver fibrosis test (eLIFT), an "at-a-glance" sum of points attributed to age, gender, gamma-glutamyl transferase, aspartate aminotransferase (AST), platelets and prothrombin time, was developed for the diagnosis of advanced fibrosis. In the validation set, eLIFT and fibrosis-4 (FIB4) had the same sensitivity (78.0% vs. 76.6%, p=0.470) but eLIFT gave fewer false positive results, especially in patients ≥60years old (53.8% vs. 82.0%, p<0.001), and was thus more suitable as screening test. FibroMeter with vibration controlled transient elastography (VCTE) was the most accurate among the eight fibrosis tests evaluated. The sensitivity of the eLIFT-FM VCTE algorithm (first-line eLIFT, second-line FibroMeter VCTE ) was 76.1% for advanced fibrosis and 92.1% for cirrhosis. Prognostic study: patients diagnosed as having "no/mild fibrosis" by the algorithm had excellent liver-related prognosis with thus no need for referral to a hepatologist. The eLIFT-FM VCTE algorithm extends the detection of advanced liver fibrosis to all CLD patients and reduces unnecessary referrals of patients without significant CLD to hepatologists. Blood fibrosis tests and transient elastography accurately diagnose advanced liver fibrosis in the large population of patients having chronic liver disease, but these non-invasive tests are only currently available in specialized centers. We have developed an algorithm including the easy liver fibrosis test (eLIFT), a new simple and widely available blood test. It is used as a first-line procedure that selects at-risk patients who need further evaluation with the FibroMeter VCTE , an accurate fibrosis test combining blood markers and transient elastography result. This new algorithm, called the eLIFT-FM VCTE , accurately identifies the patients with advanced chronic liver disease who need referral to a specialist, and those with no or mild liver lesions who can remain under the care of their usual physician. No registration (analysis of pooled data from previously published diagnostic studies). Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Tracking fuzzy borders using geodesic curves with application to liver segmentation on planning CT

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

Yuan, Yading, E-mail: yading.yuan@mssm.edu; Chao, Ming; Sheu, Ren-Dih

Purpose: This work aims to develop a robust and efficient method to track the fuzzy borders between liver and the abutted organs where automatic liver segmentation usually suffers, and to investigate its applications in automatic liver segmentation on noncontrast-enhanced planning computed tomography (CT) images. Methods: In order to track the fuzzy liver–chestwall and liver–heart borders where oversegmentation is often found, a starting point and an ending point were first identified on the coronal view images; the fuzzy border was then determined as a geodesic curve constructed by minimizing the gradient-weighted path length between these two points near the fuzzy border.more » The minimization of path length was numerically solved by fast-marching method. The resultant fuzzy borders were incorporated into the authors’ automatic segmentation scheme, in which the liver was initially estimated by a patient-specific adaptive thresholding and then refined by a geodesic active contour model. By using planning CT images of 15 liver patients treated with stereotactic body radiation therapy, the liver contours extracted by the proposed computerized scheme were compared with those manually delineated by a radiation oncologist. Results: The proposed automatic liver segmentation method yielded an average Dice similarity coefficient of 0.930 ± 0.015, whereas it was 0.912 ± 0.020 if the fuzzy border tracking was not used. The application of fuzzy border tracking was found to significantly improve the segmentation performance. The mean liver volume obtained by the proposed method was 1727 cm{sup 3}, whereas it was 1719 cm{sup 3} for manual-outlined volumes. The computer-generated liver volumes achieved excellent agreement with manual-outlined volumes with correlation coefficient of 0.98. Conclusions: The proposed method was shown to provide accurate segmentation for liver in the planning CT images where contrast agent is not applied. The authors’ results also clearly demonstrated that the application of tracking the fuzzy borders could significantly reduce contour leakage during active contour evolution.« less

"Artificial micro organs"--a microfluidic device for dielectrophoretic assembly of liver sinusoids.

PubMed

Schütte, Julia; Hagmeyer, Britta; Holzner, Felix; Kubon, Massimo; Werner, Simon; Freudigmann, Christian; Benz, Karin; Böttger, Jan; Gebhardt, Rolf; Becker, Holger; Stelzle, Martin

2011-06-01

In order to study possible toxic side effects of potential drug compounds in vitro a reliable test system is needed. Predicting liver toxicity presents a major challenge of particular importance as liver cells grown in a cell culture suffer from a rapid loss of their liver specific functions. Therefore we are developing a new microfluidic test system for liver toxicity. This test system is based on an organ-like liver 3D co-culture of hepatocytes and endothelial cells. We devised a microfluidic chip featuring cell culture chambers with integrated electrodes for the assembly of liver sinusoids by dielectrophoresis. Fluid channels enable an organ-like perfusion with culture media and test compounds. Different chamber designs were studied and optimized with regard to dielectrophoretic force distribution, hydrodynamic flow profile, and cell trapping rate using numeric simulations. Based on simulation results a microchip was injection-moulded from COP. This chip allowed the assembly of viable hepatocytes and endothelial cells in a sinusoid-like fashion.

Hemochromatosis

MedlinePlus

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Galactosemia

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Diagnostic tests for hepatitis C: Recent trends in electrochemical immunosensor and genosensor analysis

PubMed Central

Uliana, Carolina V; Riccardi, Carla S; Yamanaka, Hideko

2014-01-01

Hepatitis C is a liver disease that is transmitted through contact with the blood of an infected person. An estimated 150 million individuals worldwide have been chronically infected with the hepatitis C virus (HCV). Hepatitis C shows significant genetic variation in the global population, due to the high rate of viral RNA mutation. There are six variants of the virus (HCV genotypes 1, 2, 3, 4, 5, and 6), with 15 recorded subtypes that vary in prevalence across different regions of the world. A variety of devices are used to diagnose hepatitis C, including HCV antibody test, HCV viral load test, HCV genotype test and liver biopsy. Rapid, inexpensive, sensitive, and robust analytical devices are therefore essential for effective diagnosis and monitoring of disease treatment. This review provides an overview of current electrochemical immunosensor and genosensor technologies employed in HCV detection. There are a limited number of publications showing electrochemical biosensors being used for the detection of HCV. Due to their simplicity, specificity, and reliability, electrochemical biosensor devices have potential clinical applications in several viral infections. PMID:25400433

Toxicity testing of four silver nanoparticle-coated dental castings in 3-D LO2 cell cultures.

PubMed

Zhao, Yi-Ying; Chu, Qiang; Shi, Xu-Er; Zheng, Xiao-Dong; Shen, Xiao-Ting; Zhang, Yan-Zhen

To address the controversial issue of the toxicity of dental alloys and silver nanoparticles in medical applications, an in vivo-like LO2 3-D model was constructed within polyvinylidene fluoride hollow fiber materials to mimic the microenvironment of liver tissue. The use of microscopy methods and the measurement of liver-specific functions optimized the model for best cell performances and also proved the superiority of the 3-D LO2 model when compared with the traditional monolayer model. Toxicity tests were conducted using the newly constructed model, finding that four dental castings coated with silver nanoparticles were toxic to human hepatocytes after cell viability assays. In general, the toxicity of both the castings and the coated silver nanoparticles aggravated as time increased, yet the nanoparticles attenuated the general toxicity by preventing metal ion release, especially at high concentrations.

Alagille Syndrome

MedlinePlus

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Newborn Jaundice

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Reye Syndrome

MedlinePlus

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Herb-Induced Liver Injuries in Developing Nations: An Update.

PubMed

Amadi, Cecilia Nwadiuto; Orisakwe, Orish Ebere

2018-04-17

The last few decades have seen a rise in the use of herbal supplements, natural products, and traditional medicines. However, there are growing concerns related to the safety and toxicities of these medicines. These herbal medicines are associated with complications such as liver damage with a high incidence of mortalities and morbidities. Clinical manifestations range from asymptomatic cases with abnormal liver functions tests to sudden and severe liver failure necessitating liver transplantation. This work aimed to review the etiology, risk factors, diagnosis, clinical manifestations and selected clinical case reports of herbal hepatotoxicity in developing nations. PubMed and Google Scholar searches were undertaken to identify relevant literature. Furthermore, we scanned the reference lists of the primary and review articles to identify publications not retrieved by electronic searches. Little data exists on clinical cases of herb-induced liver injury in some developing countries such as Nigeria, as most incidences are either not reported to health care providers or reports from hospitals go unpublished. Studies in Nigeria have highlighted a possible correlation between use of herbs and liver disease. In Uganda, and association between the use of traditional herbal medicine with liver fibrosis in HIV-infected and non-HIV patients was demonstrated. Reports from China have revealed incidences of acute liver failure as a result of herbal medicine use. The actual incidence and prevalence of HILI in developing nations remain largely unknown due to both poor pharmacovigilance programs and non-application of emerging technologies. Improving education and public awareness of the potential risks of herbals and herbal products is desirable to ensure that suspected adverse effects are formally reported. There is need for stricter regulations and pre-clinical studies necessary for efficacy and safety.

Microbiology of liver abscesses and the predictive value of abscess gram stain and associated blood cultures.

PubMed

Chemaly, Roy F; Hall, Gerri S; Keys, Thomas F; Procop, Gary W

2003-08-01

Although rare, pyogenic liver abscesses are potentially fatal. We evaluated the predictive value of Gram stain of liver abscess aspirates and temporally associated blood cultures. Gram stains detected bacteria in 79% of the liver abscesses tested. The sensitivity and specificity of Gram stain of the liver abscesses were 90% and 100% for Gram-positive cocci (GPC) and 52% and 94% for Gram-negative bacilli (GNB). The sensitivities of the blood cultures for any GPC and GNB present in the liver abscess were 30% and 39%, respectively. Although, Gram stains and blood cultures offer incomplete detection of the microbial contents of pyogenic liver abscesses, both tests should always accompany liver abscess cultures.

Characterization of hepatic markers in human Wharton's Jelly-derived mesenchymal stem cells.

PubMed

Buyl, Karolien; De Kock, Joery; Najar, Mehdi; Lagneaux, Laurence; Branson, Steven; Rogiers, Vera; Vanhaecke, Tamara

2014-02-01

Stem cell technology could offer a unique tool to develop human-based in vitro liver models that are applicable for testing of potential liver toxicity early during drug development. In this context, recent research has indicated that human Wharton's Jelly-derived mesenchymal stem cells (hWJs) represent an interesting stem cell population to develop human hepatocyte-like cells. Here, an in-depth analysis of the expression of liver-specific transcription factors and other key hepatic markers in hWJs is evaluated at both the mRNA and protein level. Our results reveal that transcription factors that are mandatory to acquire and maintain an adult hepatic phenotype (HNF4A and HNF1A), as well as adult hepatic markers (ALB, CX32, CYP1A1, CYP1A2, CYP2B6 and CYP3A4) are not expressed in hWJs with the exception of K18. On the contrary, transcription factors involved in liver development (GATA4, GATA6, SOX9 and SOX17) and liver progenitor markers (DKK1, DPP4, DSG2, CX43 and K19) were found to be highly expressed in hWJs. These findings provide additional indication that hWJs could be a promising stem cell source to generate hepatocyte-like cells necessary for the development of a functional human-based in vitro liver model. Copyright © 2013 Elsevier Ltd. All rights reserved.

Determination of Selected Amino Acids in Serum of Patients with Liver Disease.

PubMed

Kanďár, Roman; Drábková, Petra; Toiflová, Tereza; Čegan, Alexander

2016-01-01

The determination of amino acids can be a reliable approach for extended diagnosis of liver diseases. This is because liver disease can be a cause of impaired amino acid metabolism. Therefore, a method for the determination of serum amino acids, applicable for clinical purposes, is necessary. The aim of this study was to find differences in the levels of selected amino acids between patients with liver disease and a control group. Samples of peripheral venous blood were obtained from a group of patients with liver disease (n = 131, 59 women at an average age of 60 years and 72 men at an average age of 52 years) and a control group (n = 105, 47 women at an average age of 62 years and 58 men at an average age of 58 years). Before the separation, the amino acids were derivatized with naphthalene-2,3-dicarboxaldehyde. For the separation, reverse phase column was used. The effluent was monitored with a fluorescence detector. There were significant differences in the concentrations of some amino acids between the patients and the control group, but also between women and men. Correlations between some amino acids and markers of liver blood tests and lipid metabolism were observed. A simple, relatively rapid and selective HPLC method with fluorescence detection for the determination of selected amino acids in serum has been developed.

HEPATOKIN1 is a biochemistry-based model of liver metabolism for applications in medicine and pharmacology.

PubMed

Berndt, Nikolaus; Bulik, Sascha; Wallach, Iwona; Wünsch, Tilo; König, Matthias; Stockmann, Martin; Meierhofer, David; Holzhütter, Hermann-Georg

2018-06-19

The epidemic increase of non-alcoholic fatty liver diseases (NAFLD) requires a deeper understanding of the regulatory circuits controlling the response of liver metabolism to nutritional challenges, medical drugs, and genetic enzyme variants. As in vivo studies of human liver metabolism are encumbered with serious ethical and technical issues, we developed a comprehensive biochemistry-based kinetic model of the central liver metabolism including the regulation of enzyme activities by their reactants, allosteric effectors, and hormone-dependent phosphorylation. The utility of the model for basic research and applications in medicine and pharmacology is illustrated by simulating diurnal variations of the metabolic state of the liver at various perturbations caused by nutritional challenges (alcohol), drugs (valproate), and inherited enzyme disorders (galactosemia). Using proteomics data to scale maximal enzyme activities, the model is used to highlight differences in the metabolic functions of normal hepatocytes and malignant liver cells (adenoma and hepatocellular carcinoma).

Cholangiocarcinoma

MedlinePlus

... microscope Blood tests that may be done include: Liver function tests (especially alkaline phosphatase or bilirubin levels) Complete blood count (CBC) Treatment ... and may result in a cure. If the tumor is large, the entire liver may need to be removed and a liver ...

Extensive testing or focused testing of patients with elevated liver enzymes.

PubMed

Tapper, Elliot B; Saini, Sameer D; Sengupta, Neil

2017-02-01

Many patients have elevated serum aminotransferases reflecting many underlying conditions, both common and rare. Clinicians generally apply one of two evaluative strategies: testing for all diseases at once (extensive) or just common diseases first (focused). We simulated the evaluation of 10,000 adult outpatients with elevated with alanine aminotransferase to compare both testing strategies. Model inputs employed population-based data from the US (National Health and Nutrition Examination Survey) and Britain (Birmingham and Lambeth Liver Evaluation Testing Strategies). Patients were followed until a diagnosis was provided or a diagnostic liver biopsy was considered. The primary outcome was US dollars per diagnosis. Secondary outcomes included doctor visits per diagnosis, false-positives per diagnosis and confirmatory liver biopsies ordered. The extensive testing strategy required the lowest monetary cost, yielding diagnoses for 54% of patients at $448/patient compared to 53% for $502 under the focused strategy. The extensive strategy also required fewer doctor visits (1.35 vs. 1.61 visits/patient). However, the focused strategy generated fewer false-positives (0.1 vs. 0.19/patient) and more biopsies (0.04 vs. 0.08/patient). Focused testing becomes the most cost-effective strategy when accounting for pre-test probabilities and prior evaluations performed. This includes when the respective prevalence of alcoholic, non-alcoholic and drug-induced liver disease exceeds 51.1%, 53.0% and 13.0%. Focused testing is also the most cost-effective strategy in the referral setting where assessments for viral hepatitis, alcoholic and non-alcoholic fatty liver disease have already been performed. Testing for elevated liver enzymes should be deliberate and focused to account for pre-test probabilities if possible. Many patients have elevated liver enzymes reflecting one of many possible liver diseases, some of which are very common and some of which are rare. Tests are widely available for most causes but it is unclear whether clinicians should order them all at once or direct testing based on how likely a given disease may be given the patient's history and physical exam. The tradeoffs of both approaches involve the money spent on testing, number of office visits needed, and false positive results generated. This study shows that if there are no clues available at the time of evaluation, testing all at once saves time and money while causing more false positives. However, if there are strong clues regarding the likelihood of a particular disease, limited testing saves time, money and prevents false positives. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Primary Sclerosing Cholangitis (PSC)

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Type I Glycogen Storage Disease

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Accuracy of indocyanine green pulse spectrophotometry clearance test for liver function prediction in transplanted patients

PubMed Central

Hsieh, Chung-Bao; Chen, Chung-Jueng; Chen, Teng-Wei; Yu, Jyh-Cherng; Shen, Kuo-Liang; Chang, Tzu-Ming; Liu, Yao-Chi

2004-01-01

AIM: To investigate whether the non-invasive real-time Indocynine green (ICG) clearance is a sensitive index of liver viability in patients before, during, and after liver transplantation. METHODS: Thirteen patients were studied, two before, three during, and eight following liver transplantation, with two patients suffering acute rejection. The conventional invasive ICG clearance test and ICG pulse spectrophotometry non-invasive real-time ICG clearance test were performed simultaneously. Using linear regression analysis we tested the correlation between these two methods. The transplantation condition of these patients and serum total bilirubin (T. Bil), alanine aminotransferase (ALT), and platelet count were also evaluated. RESULTS: The correlation between these two methods was excellent (r2 = 0.977). CONCLUSION: ICG pulse spectrophotometry clearance is a quick, non-invasive, and reliable liver function test in transplantation patients. PMID:15285026

 Usefulness of acoustic radiation force impulse and fibrotest in liver fibrosis assessment after liver transplant.

PubMed

Bignulin, Sara; Falleti, Edmondo; Cmet, Sara; Cappello, Dario; Cussigh, Annarosa; Lenisa, Ilaria; Dissegna, Denis; Pugliese, Fabio; Vivarelli, Cinzia; Fabris, Carlo; Fabris, Carlo; Toniutto, Pierluigi

2016-01-01

 Background and rationale. Acoustic radiation force impulse (ARFI) is a non-invasive tool used in the evaluation of liver fibrosis in HCV positive immune-competent patients. This study aimed to assess the accuracy of ARFI in discriminating liver transplanted patients with different graft fibrosis severity and to verify whether ARFI, eventually combined with non-invasive biochemical tests, could spare liver biopsies. This prospective study included 51 HCV positive liver transplanted patients who consecutively underwent to annual liver biopsy concomitantly with ARFI and blood chemistry tests measurements needed to calculate several non-invasive liver fibrosis tests. Overall ARFI showed an AUC of 0.885 in discriminating between patients without or with significant fibrosis (Ishak score 0-2vs. 3-6). Using a cut-off of 1.365 m/s, ARFI possesses a negative predictive value of 100% in identifying patients without significant fibrosis. AUC for Fibrotest was 0.848 in discriminating patients with Ishak fibrosis score 0-2 vs. 3-6. The combined assessment of ARFI and Fibro-test did not improve the results obtained by ARFI alone. ARFI measurement in HCV positive liver transplanted patients can be considered an easy and accurate non-invasive tool in identify patients with a benign course of HCV recurrence.

Development of a decision support tool to facilitate primary care management of patients with abnormal liver function tests without clinically apparent liver disease [HTA03/38/02]. Abnormal Liver Function Investigations Evaluation (ALFIE).

PubMed

Donnan, Peter T; McLernon, David; Steinke, Douglas; Ryder, Stephen; Roderick, Paul; Sullivan, Frank M; Rosenberg, William; Dillon, John F

2007-04-16

Liver function tests (LFTs) are routinely performed in primary care, and are often the gateway to further invasive and/or expensive investigations. Little is known of the consequences in people with an initial abnormal liver function (ALF) test in primary care and with no obvious liver disease. Further investigations may be dangerous for the patient and expensive for Health Services. The aims of this study are to determine the natural history of abnormalities in LFTs before overt liver disease presents in the population and identify those who require minimal further investigations with the potential for reduction in NHS costs. A population-based retrospective cohort study will follow up all those who have had an incident liver function test (LFT) in primary care to subsequent liver disease or mortality over a period of 15 years (approx. 2.3 million tests in 99,000 people). The study is set in Primary Care in the region of Tayside, Scotland (pop approx. 429,000) between 1989 and 2003. The target population consists of patients with no recorded clinical signs or symptoms of liver disease and registered with a GP. The health technologies being assessed are LFTs, viral and auto-antibody tests, ultrasound, CT, MRI and liver biopsy. The study will utilise the Epidemiology of Liver Disease In Tayside (ELDIT) database to determine the outcomes of liver disease. These are based on hospital admission data (Scottish Morbidity Record 1), dispensed medication records, death certificates, and examination of medical records from Tayside hospitals. A sample of patients (n = 150) with recent initial ALF tests or invitation to biopsy will complete questionnaires to obtain quality of life data and anxiety measures. Cost-effectiveness and cost utility Markov model analyses will be performed from health service and patient perspectives using standard NHS costs. The findings will also be used to develop a computerised clinical decision support tool. The results of this study will be widely disseminated to primary care, as well as G.I. hospital specialists through publications and presentations at local and national meetings and the project website. This will facilitate optimal decision-making both for the benefit of the patient and the National Health Service.

Fibromax-based nonalcoholic fatty liver disease in chronic obstructive pulmonary disease patients with obstructive sleep apnea: Methodological considerations

PubMed Central

Monneret, Denis

2017-01-01

The relationship between nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) has been well demonstrated, but remains to be evidenced in chronic obstructive pulmonary disease (COPD). Recently, Viglino et al. (Eur Respir J, 2017) attempted to determine the prevalence of liver fibrosis, steatosis and nonalcoholic steatohepatitis (NASH) in COPD patients, some of whom had OSA, basing the NAFLD diagnostic on three circulating biomarker-based liver scores: the FibroTest, SteatoTest and NashTest, from the Fibromax® panel. Among the main findings, the absence of OSA treatment emerged as independently associated with liver fibrosis and steatosis, when compared to effective treatment. However, besides the low number of treated patients, no polysomnographic respiratory data was provided, making it difficult to differentiate the impact of OSA from that of COPD in NAFLD prevalence. Furthermore, NAFLD diagnosis relied exclusively on circulating biomarker-based liver scores, without histological, imagery or other liver exploratory methods. Therefore, in this article, some methodological points are reminded and discussed, including the choice of OSA measurements, and the significance of ActiTest and AshTest scores from Fibromax® in this pathophysiological context. PMID:29225775

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.

Significance testing of clinical data using virus dynamics models with a Markov chain Monte Carlo method: application to emergence of lamivudine-resistant hepatitis B virus.

PubMed Central

Burroughs, N J; Pillay, D; Mutimer, D

1999-01-01

Bayesian analysis using a virus dynamics model is demonstrated to facilitate hypothesis testing of patterns in clinical time-series. Our Markov chain Monte Carlo implementation demonstrates that the viraemia time-series observed in two sets of hepatitis B patients on antiviral (lamivudine) therapy, chronic carriers and liver transplant patients, are significantly different, overcoming clinical trial design differences that question the validity of non-parametric tests. We show that lamivudine-resistant mutants grow faster in transplant patients than in chronic carriers, which probably explains the differences in emergence times and failure rates between these two sets of patients. Incorporation of dynamic models into Bayesian parameter analysis is of general applicability in medical statistics. PMID:10643081

Three-dimensional Cell Culture Devices for Cancer Migration and Drug Testing

NASA Astrophysics Data System (ADS)

Ma, Liang

Porous polymeric materials are widely used to mimic the extracellular matrix (ECM) environment for applications such as 3D cell culturing and tissue engineering. A series of comparative experiments on 3D cell cultures both in PLA porous scaffolds and alginate gels were conducted to create an in vitro tumor model. A novel 3D cell culture device based on porous polymeric material was developed to study cancer migration. Significant cell migration was observed through the porous channel within 1--2 weeks induced by 20% fetal bovine serum (FBS). A three-dimensional micro-scale perfusion-based two-chamber (3D-muPTC) tissue model system was developed to test the cytotoxicity of anticancer drugs by emulating liver metabolism effects in vitro. Hepatoma cells and glioblastoma multiforme (GBM) cancer cells were cultured in porous polymeric scaffolds in two separate chambers, representing the liver and tumor, respectively. The cytotoxic effect of temozolomide (TMZ) was first tested using this system. It was found that the GBM cells showed a much higher viability under the TMZ treatment with liver cells in the system, suggesting that the drug metabolism in liver is affecting the efficacy of the drug. The favorable metabolism effect of cytochrome P450 (CYP) was tested using a prodrug ifosfamide (IFO). Without the liver cells, IFO showed only slight toxicity to GBM cells. Moreover, it was shown that different expression levels of CYP 3A4, a major drug metabolizing enzyme, in liver cells caused significantly different levels of GBM cell viability. Simulation of the flow characteristics in the 3D-muPTC system was conducted using the finite-element analysis approach. The shear stress was predicted in the porous scaffolds under different flow rate conditions. The predicted shear stress effects agreed well with an experimental cell viability study. A low cost organic solvent free approach to fabricating tissue engineering scaffolds was developed by combining the twin-screw extrusion and particulate leaching. High porosity and interconnected porous PLA scaffolds with the pore size 50 to 200μm were fabricated with this immiscible polymer blending method. This combined extrusion and particulate leaching method provides a new technique to fabricate tissue engineering scaffolds that can be used in the 3D-muPTC device.

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

PubMed Central

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

2018-01-01

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

Idiopathic liver function test abnormality in pregnancy is associated with assisted reproduction techniques.

PubMed

Kopylov, Uri; Avidan, Benjamin; Papageorgiou, Neofytos P; Katz, Lior H; Sivan, Eyal; Zimlichman, Eyal; Hussein, Haya; Maor, Yaakov

2013-02-01

To examine the prevalence, etiology, risk factors, and outcomes of liver abnormality in pregnancy, in a tertiary medical center, and to study the potential impact of artificial reproduction techniques (ART) on the incidence and the outcome of pregnancy-related liver abnormality. A retrospective case-control study using an electronic database and patients' files. Tertiary referral center. Women in the third trimester of pregnancy who were hospitalized for delivery. None. Development of significant elevation of alanine aminotransferase (ALT ≥ 100 IU/L). Secondary outcomes included development of maternal and fetal complications. The upper limit of normal of ALT was ≥ 1.5 times and it occurred in 440 (1.6%) pregnancies; of those, 228 (0.8%) had ALT ≥ 100 IU/L. The etiology of significant liver test abnormality was idiopathic in 47% of patients. Compared with spontaneous pregnancies (295/23,793), ART was significantly associated with liver test abnormality (145/4, 520). The presence of ALT ≥ 100 IU/L in the third trimester was associated with higher rates of cesarean sections, prematurity, low birthweight, and fetal complications. A definite etiology was not determined in about half of pregnancy-associated liver test abnormality. The ART was significantly associated with liver test elevation. Significant liver test abnormality in the third trimester may have an impact on maternal and fetal/neonatal outcomes. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

FibroMeters: a family of blood tests for liver fibrosis.

PubMed

Calès, P; Boursier, J; Oberti, F; Hubert, I; Gallois, Y; Rousselet, M-C; Dib, N; Moal, V; Macchi, L; Chevailler, A; Michalak, S; Hunault, G; Chaigneau, J; Sawadogo, A; Lunel, F

2008-09-01

FibroMeters are blood tests for liver fibrosis with several specificities: two main diagnostic targets (fibrosis stage and area of fibrosis); adaptation to specific causes; and results confirmed by an expert system. Thus, FibroMeters comprise six different tests: one for staging and one for quantitation of liver fibrosis in each of the three main causes of chronic liver disease-chronic viral hepatitis, alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). FibroMeters display a high overall diagnostic accuracy and are the only tests to correctly classify 100% of HCV patients without fibrosis or with cirrhosis. They have 90% predictive values in a higher proportion of patients than with other usual blood tests. A 90% correct classification is available in 100% of HCV patients with the following reliable diagnostic intervals: F0/1, F1/2, F2+/-1, F3+/-1. In real-life conditions, the reproducibility of FibroMeters is higher than that of liver biopsy or ultrasonographic elastometry. FibroMeters are robust tests with the most stable diagnostic performance across different centers. Optional tests are also available, such as a specific one for cirrhosis, which has a diagnostic accuracy of 93.0% (AUROC: 0.92) and a 100% positive predictive value for diagnosis of HCV cirrhosis. Determination by FibroMeters of the area of fibrosis - the only direct, non-invasive, quantitative measurement of liver fibrosis - are especially useful for following-up cirrhosis as it correlates well with clinical events. FibroMeters are also very accurate in HVB or HIV-HCV co-infected patients. The tests specific for ALD and NAFLD also have a high diagnostic accuracy (AUROCs: 0.96 and 0.94, respectively, for significant fibrosis).

A bioartificial liver to treat severe acute liver failure.

PubMed Central

Rozga, J; Podesta, L; LePage, E; Morsiani, E; Moscioni, A D; Hoffman, A; Sher, L; Villamil, F; Woolf, G; McGrath, M

1994-01-01

OBJECTIVE: To test the safety and efficacy of a bioartificial liver support system in patients with severe acute liver failure. SUMMARY BACKGROUND DATA: The authors developed a bioartificial liver using porcine hepatocytes. The system was tested in vitro and shown to have differentiated liver functions (cytochrome P450 activity, synthesis of liver-specific proteins, bilirubin synthesis, and conjugation). When tested in vivo in experimental animals with liver failure, it gave substantial metabolic and hemodynamic support. METHODS: Seven patients with severe acute liver failure received a double lumen catheter in the saphenous vein; blood was removed, plasma was separated and perfused through a cartridge containing 4 to 6 x 10(9) porcine hepatocytes, and plasma and blood cells were reconstituted and reinfused. Each treatment lasted 6 to 7 hours. RESULTS: All patients tolerated the procedure(s) well, with neurologic improvement, decreased intracranial pressure (23.0 +/- 2.3 to 7.8 +/- 1.7 mm Hg; p < 0.005) associated with an increase in cerebral perfusion pressure, decreased plasma ammonia (163.3 +/- 21.3 to 112.2 +/- 9.8 microMoles/L; p < 0.01), and increased encephalopathy index (0.60 +/- 0.17 to 1.24 +/- 0.22; p < 0.03). All patients survived, had a liver transplant, and were discharged from the hospital. CONCLUSIONS: This bioartificial liver is safe and serves as an effective "bridge" to liver transplant in some patients. Images Figure 2. Figure 3. PMID:8185403

Liver (Hepatocellular) Cancer Screening (PDQ®)—Patient Version

Cancer.gov

Liver (hepatocellular) cancer screening is not currently recommended as a routine part of cancer screening. Not all screening tests are helpful, and many have risks. Learn more about liver cancer and the tests used to detect it in this expert-reviewed summary.

Monitoring of Total and Regional Liver Function after SIRT.

PubMed

Bennink, Roelof J; Cieslak, Kasia P; van Delden, Otto M; van Lienden, Krijn P; Klümpen, Heinz-Josef; Jansen, Peter L; van Gulik, Thomas M

2014-01-01

Selective internal radiation therapy (SIRT) is a promising treatment modality for advanced hepatocellular carcinoma or metastatic liver cancer. SIRT is usually well tolerated. However, in most patients, SIRT will result in a (temporary) decreased liver function. Occasionally patients develop radioembolization-induced liver disease (REILD). In case of a high tumor burden of the liver, it could be beneficial to perform SIRT in two sessions enabling the primary untreated liver segments to guarantee liver function until function in the treated segments has recovered or functional hypertrophy has occurred. Clinically used liver function tests provide evidence of only one of the many liver functions, though all of them lack the possibility of assessment of segmental (regional) liver function. Hepatobiliary scintigraphy (HBS) has been validated as a tool to assess total and regional liver function in liver surgery. It is also used to assess segmental liver function before and after portal vein embolization. HBS is considered as a valuable quantitative liver function test enabling assessment of segmental liver function recovery after regional intervention and determination of future remnant liver function. We present two cases in which HBS was used to monitor total and regional liver function in a patient after repeated whole liver SIRT complicated with REILD and a patient treated unilaterally without complications.

Clamp-crushing vs. radiofrequency-assisted liver resection:changes in liver function tests.

PubMed

Palibrk, Ivan; Milicic, Biljana; Stojiljkovic, Ljuba; Manojlovic, Nebojsa; Dugalic, Vladimir; Bumbasirevic, Vesna; Kalezic, Nevena; Zuvela, Marinko; Milicevic, Miroslav

2012-05-01

Liver resection is the gold standard in managing patients with metastatic or primary liver cancer. The aim of our study was to compare the traditional clamp-crushing technique to the radiofrequency- assisted liver resection technique in terms of postoperative liver function. Liver function was evaluated preoperatively and on postoperative days 3 and 7. Liver synthetic function parameters (serum albumin level, prothrombin time and international normalized ratio), markers of hepatic injury and necrosis (serum alanine aminotransferase, aspartate aminotransferase and total bilirubin level) and microsomal activity (quantitative lidocaine test) were compared. Forty three patients completed the study (14 had clamp-crushing and 29 had radiofrequency assisted liver resection). The groups did not differ in demographic characteristics, pre-operative liver function, operative time and perioperative transfusion rate. In postoperative period, there were similar changes in monitored parameters in both groups except albumin levels, that were higher in radiofrequency-assisted liver resection group (p=0.047). Both, traditional clamp-crushing technique and radiofrequency assisted liver resection technique, result in similar postoperative changes of most monitored liver function parameters.

Comparison of rapid diagnostic tests to detect Mycobacterium avium subsp. paratuberculosis disseminated infection in bovine liver.

PubMed

Zarei, Mehdi; Ghorbanpour, Masoud; Tajbakhsh, Samaneh; Mosavari, Nader

2017-08-01

Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne's disease, a chronic enteritis in cattle and other domestic and wild ruminants. The presence of MAP in tissues other than intestines and associated lymph nodes, such as meat and liver, is a potential public health concern. In the present study, the relationship between the results of rapid diagnostic tests of the Johne's disease, such as serum ELISA, rectal scraping PCR, and acid-fast staining, and the presence of MAP in liver was evaluated. Blood, liver, and rectal scraping samples were collected from 200 slaughtered cattle with unknown Johne's disease status. ELISA was performed to determine the MAP antibody activity in the serum. Acid-fast staining was performed on rectal scraping samples, and PCR was performed on rectal scraping and liver samples. PCR-positive liver samples were used for mycobacterial culture. Overall, the results of this study demonstrated that MAP can be detected and cultured from liver of slaughtered cattle and rapid diagnostic tests of Johne's disease have limited value in detecting cattle with MAP infection in liver. These findings show that the presence of MAP in liver tissue may occur in cows with negative results for rapid diagnostic tests and vice versa. Hence, liver might represent another possible risk of human exposure to MAP. Given concerns about a potential zoonotic role for MAP, these results show the necessity to find new methods for detecting cattle with MAP disseminated infection.

Microwaves create larger ablations than radiofrequency when controlled for power in ex vivo tissue.

PubMed

Andreano, A; Huang, Yu; Meloni, M Franca; Lee, Fred T; Brace, Christopher

2010-06-01

To compare ablation zones created with equal amounts of 2.45 GHz microwave and 480 kHz radiofrequency (RF) energy in ex vivo liver and lung. A total of 38 ablations were performed in ex vivo liver and lung for 10 min each. Nineteen RF ablations (nine liver, ten lung) were performed with a 480 kHz system (200 W max, impedance-based pulsing) and cooled electrode while measuring the average RF power applied. Nineteen microwave ablations (nine liver, ten lung) were then created using a cooled triaxial antenna to deliver 2.45 GHz at the same power level as in RF experiments. Ablation zones were then sectioned and measured for minimum, maximum and mean diameters, and circularity. Measurements were compared using t-tests, with P < 0.05 indicating statistical significance. Mean diameters of microwave ablations were greater than RF ablations in both liver and lung (4.4 +/- 0.3 vs 3.3 +/- 0.2 cm in liver; 2.45 +/- 0.3 vs 1.6 +/- 0.5 cm in lungs; P < 0.0005 all comparisons). There was no significant difference in the mean power applied during microwave or RF ablations in either organ (54.44 +/- 1.71 W vs 56.4 +/- 6.7 W in liver, P > 0.05; 40 +/- 0.95 W vs 44.9 +/- 7.1 W in lung, P > 0.05). Using a single cooled applicator, microwave energy at 2.45 GHz produces larger ablations than an equivalent amount of 480 kHz RF energy in normal liver and lung. This was more apparent in lung, likely due to the high baseline impedance which limits RF, but not microwave power delivery.

Non-Invasive Assessment of Liver Function

PubMed Central

Helmke, Steve; Colmenero, Jordi; Everson, Gregory T.

2015-01-01

Purpose of review It is our opinion that there is an unmet need in Hepatology for a minimally- or noninvasive test of liver function and physiology. Quantitative liver function tests (QLFTs) define the severity and prognosis of liver disease by measuring the clearance of substrates whose uptake or metabolism is dependent upon liver perfusion or hepatocyte function. Substrates with high affinity hepatic transporters exhibit high “first-pass” hepatic extraction and their clearance measures hepatic perfusion. In contrast, substrates metabolized by the liver have low first-pass extraction and their clearance measures specific drug metabolizing pathways. Recent Findings We highlight one QLFT, the dual cholate test, and introduce the concept of a disease severity index (DSI) linked to clinical outcome that quantifies the simultaneous processes of hepatocyte uptake, clearance from the systemic circulation, clearance from the portal circulation, and portal-systemic shunting. Summary It is our opinion that dual cholate is a relevant test for defining disease severity, monitoring the natural course of disease progression, and quantifying the response to therapy. PMID:25714706

Portal Vein Embolization with Contralateral Application of Stem Cells Facilitates Increase of Future Liver Remnant Volume in Patients with Liver Metastases

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

Ludvík, Jaroslav, E-mail: ludvikj@fnplzen.cz; Duras, Petr; Třeška, Vladislav

ObjectivesThis study aimed to evaluate the progress of future liver remnant volume (FLRV) in patients with liver metastases after portal vein embolization (PVE) with the application of hematopoietic stem cells (HSCs) and compare it with a patients control group after PVE only.MethodsTwenty patients (group 1) underwent PVE with contralateral HSC application. Subsequently, CT volumetry with the determination of FLRV was performed at weekly intervals, in total three weeks. A sample of twenty patients (group 2) who underwent PVE without HSC application was used as a control group.ResultsThe mean of FLRV increased by 173.2 mL during three weeks after the PVE/HSC procedure,more » whereas by 98.9 mL after PVE only (p = 0.015). Furthermore, the mean daily growth of FLRV by 7.6 mL in group 1 was significantly higher in comparison with 4.1 mL in group 2 (p = 0.007).ConclusionsPVE with the application of HSC significantly facilitates growth of FLRV in comparison with PVE only. This method could be one of the new suitable approaches to increase the resectability of liver tumours.« less

Discrimination of liver cancer in cellular level based on backscatter micro-spectrum with PCA algorithm and BP neural network

NASA Astrophysics Data System (ADS)

Yang, Jing; Wang, Cheng; Cai, Gan; Dong, Xiaona

2016-10-01

The incidence and mortality rate of the primary liver cancer are very high and its postoperative metastasis and recurrence have become important factors to the prognosis of patients. Circulating tumor cells (CTC), as a new tumor marker, play important roles in the early diagnosis and individualized treatment. This paper presents an effective method to distinguish liver cancer based on the cellular scattering spectrum, which is a non-fluorescence technique based on the fiber confocal microscopic spectrometer. Combining the principal component analysis (PCA) with back propagation (BP) neural network were utilized to establish an automatic recognition model for backscatter spectrum of the liver cancer cells from blood cell. PCA was applied to reduce the dimension of the scattering spectral data which obtained by the fiber confocal microscopic spectrometer. After dimensionality reduction by PCA, a neural network pattern recognition model with 2 input layer nodes, 11 hidden layer nodes, 3 output nodes was established. We trained the network with 66 samples and also tested it. Results showed that the recognition rate of the three types of cells is more than 90%, the relative standard deviation is only 2.36%. The experimental results showed that the fiber confocal microscopic spectrometer combining with the algorithm of PCA and BP neural network can automatically identify the liver cancer cell from the blood cells. This will provide a better tool for investigating the metastasis of liver cancers in vivo, the biology metabolic characteristics of liver cancers and drug transportation. Additionally, it is obviously referential in practical application.

Hepatobiliary magnetic resonance imaging in patients with liver disease: correlation of liver enhancement with biochemical liver function tests.

PubMed

Kukuk, Guido M; Schaefer, Stephanie G; Fimmers, Rolf; Hadizadeh, Dariusch R; Ezziddin, Samer; Spengler, Ulrich; Schild, Hans H; Willinek, Winfried A

2014-10-01

To evaluate hepatobiliary magnetic resonance imaging (MRI) using Gd-EOB-DTPA in relation to various liver function tests in patients with liver disorders. Fifty-one patients with liver disease underwent Gd-EOB-DTPA-enhanced liver MRI. Based on region-of-interest (ROI) analysis, liver signal intensity was calculated using the spleen as reference tissue. Liver-spleen contrast ratio (LSCR) and relative liver enhancement (RLE) were calculated. Serum levels of total bilirubin, gamma glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), serum albumin level (AL), prothrombin time (PT), creatinine (CR) as well as international normalised ratio (INR) and model for end-stage liver disease (MELD) score were tested for correlation with LSCR and RLE. Pre-contrast LSCR values correlated with total bilirubin (r = -0.39; p = 0.005), GGT (r = -0.37; p = 0.009), AST (r = -0.38; p = 0.013), ALT (r = -0.29; p = 0.046), PT (r = 0.52; p < 0.001), GLDH (r = -0.55; p = 0.044), INR (r = -0.42; p = 0.003), and MELD Score (r = -0.53; p < 0.001). After administration of Gd-EOB-DTPA bilirubin (r = -0.45; p = 0.001), GGT (r = -0.40; p = 0.004), PT (r = 0.54; p < 0.001), AST (r = -0.46; p = 0.002), ALT (r = -0.31; p = 0.030), INR (r = -0.45; p = 0.001) and MELD Score (r = -0.56; p < 0.001) significantly correlated with LSCR. RLE correlated with bilirubin (r = -0.40; p = 0.004), AST (r = -0.38; p = 0.013), PT (r = 0.42; p = 0.003), GGT (r = -0.33; p = 0.020), INR (r = -0.36; p = 0.011) and MELD Score (r = -0.43; p = 0.003). Liver-spleen contrast ratio and relative liver enhancement using Gd-EOB-DTPA correlate with a number of routinely used biochemical liver function tests, suggesting that hepatobiliary MRI may serve as a valuable biomarker for liver function. The strongest correlation with liver enhancement was found for the MELD Score. • Relative enhancement (RLE) of Gd-EOB-DTPA is related to biochemical liver function tests. • Correlation of RLE with bilirubin, ALT, AST, GGT, INR and MELD Score is reverse. • The correlation of relative liver enhancement with prothrombin time is positive. • AST, ALT, GLDH, prothrombin time, INR and MELD Score correlate with pre-contrast liver-spleen contrast ratio. • Such biomarkers may help to evaluate liver function.

A Portal Vein Injection Model to Study Liver Metastasis of Breast Cancer

PubMed Central

Goddard, Erica T.; Fischer, Jacob; Schedin, Pepper

2016-01-01

Breast cancer is the leading cause of cancer-related mortality in women worldwide. Liver metastasis is involved in upwards of 30% of cases with breast cancer metastasis, and results in poor outcomes with median survival rates of only 4.8 - 15 months. Current rodent models of breast cancer metastasis, including primary tumor cell xenograft and spontaneous tumor models, rarely metastasize to the liver. Intracardiac and intrasplenic injection models do result in liver metastases, however these models can be confounded by concomitant secondary-site metastasis, or by compromised immunity due to removal of the spleen to avoid tumor growth at the injection site. To address the need for improved liver metastasis models, a murine portal vein injection method that delivers tumor cells firstly and directly to the liver was developed. This model delivers tumor cells to the liver without complications of concurrent metastases in other organs or removal of the spleen. The optimized portal vein protocol employs small injection volumes of 5 - 10 μl, ≥ 32 gauge needles, and hemostatic gauze at the injection site to control for blood loss. The portal vein injection approach in Balb/c female mice using three syngeneic mammary tumor lines of varying metastatic potential was tested; high-metastatic 4T1 cells, moderate-metastatic D2A1 cells, and low-metastatic D2.OR cells. Concentrations of ≤ 10,000 cells/injection results in a latency of ~ 20 - 40 days for development of liver metastases with the higher metastatic 4T1 and D2A1 lines, and > 55 days for the less aggressive D2.OR line. This model represents an important tool to study breast cancer metastasis to the liver, and may be applicable to other cancers that frequently metastasize to the liver including colorectal and pancreatic adenocarcinomas. PMID:28060292

Preliminary study on liver function changes after trisectionectomy with versus without prior portal vein embolization.

PubMed

Malinowski, Maciej; Lock, Johan Friso; Seehofer, Daniel; Gebauer, Bernhard; Schulz, Antje; Demirel, Lina; Bednarsch, Jan; Stary, Victoria; Neuhaus, Peter; Stockmann, Martin

2016-09-01

Post-hepatectomy liver failure (PHLF) is the major risk factor for mortality after hepatectomy. Preoperative planning of the future liver remnant volume reduces PHLF rates; however, future liver remnant function (FLR-F) might have an even stronger predictive value. In this preliminary study, we used a new method to calculate FLR-F by the LiMAx test and computer tomography-assisted volumetric-analysis to visualize liver function changes after portal vein embolization (PVE) before extended hepatectomy. The subjects included patients undergoing extended right hepatectomy either directly (NO-PVE group) or after PVE (PVE group). Computed tomography (CT) scan and liver function tests (LiMAx) were done before PVE and preoperatively. FLR-F was calculated and correlated with the postoperative liver function. There were 12 patients in the NO-PVE group and 19 patients in the PVE group. FLR-F and postoperative liver function correlated significantly in both groups (p = 0.036, p = 0.011), although postoperative liver function was slightly overestimated, at 32 and 45 µg/kg/min, in the NO-PVE and PVE groups, respectively. LiMAx value did not change after PVE. Volume-function analysis using LiMAx and CT scan enables us to reliably predict early postoperative liver function. Global enzymatic liver function measured by the LiMAx test did not change after PVE, confirming that liver function distribution in the liver stays constant after PVE. An overestimation of FLR-F is needed to compensate for the intraoperative liver injury that occurs in patients undergoing extended hepatectomy.

Fibrosis Assessment in Nonalcoholic Fatty Liver Disease (NAFLD) in 2016.

PubMed

Kaswala, Dharmesh H; Lai, Michelle; Afdhal, Nezam H

2016-05-01

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver pathologies characterized by hepatic steatosis with a history of little to no alcohol consumption or secondary causes of hepatic steatosis. The prevalence of NAFLD is 20-25 % of the general population in the Western countries and is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. The spectrum of disease ranges from simple steatosis to nonalcoholic steatohepatitis, fibrosis, and cirrhosis. Advanced fibrosis is the most significant predictor of mortality in NAFLD. It is crucial to assess for the presence and degree of hepatic fibrosis in order to make therapeutic decisions and predict clinical outcomes. Liver biopsy, the current gold standard to assess the liver fibrosis, has a number of drawbacks such as invasiveness, sampling error, cost, and inter-/intra-observer variability. There are currently available a number of noninvasive tests as an alternative to liver biopsy for fibrosis staging. These noninvasive fibrosis tests are increasingly used to rule out advanced fibrosis and help guide disease management. While these noninvasive tests perform relatively well for ruling out advanced fibrosis, they also have limitations. Understanding the strengths and limitations of liver biopsy and the noninvasive tests is necessary for deciding when to use the appropriate tests in the evaluation of patients with NAFLD.

Liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfection: Diagnostic methods and clinical impact

PubMed Central

Sagnelli, Caterina; Martini, Salvatore; Pisaturo, Mariantonietta; Pasquale, Giuseppe; Macera, Margherita; Zampino, Rosa; Coppola, Nicola; Sagnelli, Evangelista

2015-01-01

Several non-invasive surrogate methods have recently challenged the main role of liver biopsy in assessing liver fibrosis in hepatitis C virus (HCV)-monoinfected and human immunodeficiency virus (HIV)/HCV-coinfected patients, applied to avoid the well-known side effects of liver puncture. Serological tests involve the determination of biochemical markers of synthesis or degradation of fibrosis, tests not readily available in clinical practice, or combinations of routine tests used in chronic hepatitis and HIV/HCV coinfection. Several radiologic techniques have also been proposed, some of which commonly used in clinical practice. The studies performed to compare the prognostic value of non-invasive surrogate methods with that of the degree of liver fibrosis assessed on liver tissue have not as yet provided conclusive results. Each surrogate technique has shown some limitations, including the risk of over- or under-estimating the extent of liver fibrosis. The current knowledge on liver fibrosis in HIV/HCV-coinfected patients will be summarized in this review article, which is addressed in particular to physicians involved in this setting in their clinical practice. PMID:26523204

Radiation-Induced Liver Injury in Three-Dimensional Conformal Radiation Therapy (3D-CRT) for Postoperative or Locoregional Recurrent Gastric Cancer: Risk Factors and Dose Limitations.

PubMed

Li, Guichao; Wang, Jiazhou; Hu, Weigang; Zhang, Zhen

2015-01-01

This study examined the status of radiation-induced liver injury in adjuvant or palliative gastric cancer radiation therapy (RT), identified risk factors of radiation-induced liver injury in gastric cancer RT, analysed the dose-volume effects of liver injury, and developed a liver dose limitation reference for gastric cancer RT. Data for 56 post-operative gastric cancer patients and 6 locoregional recurrent gastric cancer patients treated with three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) from Sep 2007 to Sep 2009 were analysed. Forty patients (65%) were administered concurrent chemotherapy. Pre- and post-radiation chemotherapy were given to 61 patients and 43 patients, respectively. The radiation dose was 45-50.4 Gy in 25-28 fractions. Clinical parameters, including gender, age, hepatic B virus status, concurrent chemotherapy, and the total number of chemotherapy cycles, were included in the analysis. Univariate analyses with a non-parametric rank test (Mann-Whitney test) and logistic regression test and a multivariate analysis using a logistic regression test were completed. We also analysed the correlation between RT and the changes in serum chemistry parameters [including total bilirubin, (TB), direct bilirubin (D-TB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum albumin (ALB)] after RT. The Child-Pugh grade progressed from grade A to grade B after radiotherapy in 10 patients. A total of 16 cases of classic radiation-induced liver disease (RILD) were observed, and 2 patients had both Child-Pugh grade progression and classic RILD. No cases of non-classic radiation liver injury occurred in the study population. Among the tested clinical parameters, the total number of chemotherapy cycles correlated with liver function injury. V35 and ALP levels were significant predictive factors for radiation liver injury. In 3D-CRT for gastric cancer patients, radiation-induced liver injury may occur and affect the overall treatment plan. The total number of chemotherapy cycles correlated with liver function injury, and V35 and ALP are significant predictive factors for radiation-induced liver injury. Our dose limitation reference for liver protection is feasible.

Albumin Apheresis for Artificial Liver Support: In Vitro Testing of a Novel Filter.

PubMed

Piatek, Tomasz; Giebultowicz, Joanna; Rüth, Marieke; Lemke, Horst-Dieter; Bonn, Florian; Wroczynski, Piotr; Malkowski, Piotr; Rozga, Jacek

2018-05-16

Currently there is no direct therapy for liver failure. We have previously described selective plasma exchange therapy using a hemofilter permeable to substances that have a molecular mass of up to 100 kDa. The proof-of-concept studies and a Phase I study in patients with decompensated cirrhosis demonstrated that hemofiltration using an albumin-leaking membrane is safe and effective in removing target molecules, alleviating severe encephalopathy and improving blood chemistry. In this study a novel large-pore filter for similar clinical application is described. The performance of the filter was studied in vitro; it was found to effectively remove a wide spectrum of pathogenic factors implicated in the pathophysiology of hepatic failure, including protein bound toxins and defective forms of circulating albumin. Data on mass transport characteristics and functionality using various modes of filtration and dialysis provide rationale for clinical evaluation of the filter for artificial liver support using albumin apheresis. © 2018 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Herbal Compound Songyou Yin and Moderate Swimming Suppress Growth and Metastasis of Liver Cancer by Enhancing Immune Function.

PubMed

Zhang, Quan-Bao; Meng, Xiang-Ting; Jia, Qing-An; Bu, Yang; Ren, Zheng-Gang; Zhang, Bo-Heng; Tang, Zhao-You

2016-09-01

Objective Both the Chinese herbal compound Songyou Yin (SYY) and swimming exercise have been shown to have protective effects against liver cancer in animal models. In this study, we investigated whether SYY and moderate swimming (MS) have enhanced effect on suppressing progression of liver cancer by immunomodulation. Methods C57BL/6 mice were transplanted with Hepa1-6 murine liver cancer cell lines and received treatment with SYY alone or SYY combined with MS. The green fluorescent protein (GFP)-positive metastatic foci in lungs were imaged with a stereoscopic fluorescence microscope. Flow cytometry was used to test the proportion of CD4 +, CD8 + T cells in peripheral blood and the proportions of CD4 + CD25 + Foxp3 + Treg cells in peripheral blood, spleen, and tumor tissues. Cytokine transforming growth factor (TGF)-β1 level in serum was detected by ELISA. Results SYY plus MS significantly suppressed the growth and lung metastasis of liver cancer and prolonged survival in tumor-burdened mice. SYY plus MS markedly raised the CD4 to CD8 ratio in peripheral blood and lowered the serum TGF-β1 level and the proportions of Treg cells in peripheral blood, spleen, and tumor tissue. The effects of the combined intervention were significantly superior to SYY or MS alone. Conclusion The combined application of SYY and MS exerted an enhanced effect on suppressing growth and metastasis of liver cancer by strengthening immunity. © The Author(s) 2015.

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.

Evaluation of liver functional reserve by combining D-sorbitol clearance rate and CT measured liver volume

PubMed Central

Li, Yi-Ming; Lv, Fan; Xu, Xin; Ji, Hong; Gao, Wen-Tao; Lei, Tuan-Jie; Ren, Gui-Bing; Bai, Zhi-Lan; Li, Qiang

2003-01-01

AIM: Our research attempted to evaluate the overall functional reserve of cirrhotic liver by combination of hepatic functional blood flow, liver volume, and Child-Pugh’s classification, and to discuss its value of clinical application. METHODS: Ninety two patients with portal hypertension due to hepatic cirrhosis were investigated. All had a history of haematemesis and hematochezia, esophageal and gastric fundus varices, splenomegaly and hypersplenia. A 2-year follow-up was routinely performed and no one was lost. Twenty two healthy volunteers were used as control group. Blood and urine samples were collected 4 times before and after intravenous D-sorbitol infusion. The hepatic clearance (CLH) of D-sorbitol was then calculated according to enzymatic spectrophotometric method while the total blood flow (QTOTAL) and intrahepatic shunt (RINS) were detected by multicolor Doppler ultrasound, and the liver volume was measured by spiral CT. Data were estimated by t-test, variance calculation and chi-squared test. The relationships between all these parameters and different groups were investigated according to Child-Pugh classification and postoperative complications respectively. RESULTS: Steady blood concentration was achieved 120 mins after D-sorbitol intravenous infusion, which was (0.358 ± 0.064) mmol·L-1 in cirrhotic group and (0.189 ± 0.05) mmol·L-1 in control group (P < 0.01). CLH = (812.7 ± 112.4) mL·min-1, QTOTAL = (1280.6 ± 131.4) mL·min-1, and RINS = (36.54 ± 10.65)% in cirrhotic group and CLH = (1248.3 ± 210.5) mL·min-1, QTOTAL = (1362.4 ± 126.9) mL·min-1, and RINS = (8.37 ± 3.32)% in control group (P < 0.01). The liver volume of cirrhotic group was 1057 ± 249 cm3, 851 ± 148 cm3 and 663 ± 77 cm3 in Child A, B and C group respectively with significant difference (P < 0.001). The average volume of cirrhotic liver in Child B, C group was significantly reduced in comparison with that in control group (P < 0.001). The patient, whose liver volume decreased by 40% with the CLH below 600 mL·min-1, would have a higher incidence of postoperative complications. There was no strict correspondent relationship between CLH, liver volume and Child-Pugh’s classification. CONCLUSION: The hepatic clearance of D-sorbitol, CT measured liver volume can be reliably used for the evaluation of hepatic functional blood flow and liver metabolic volume. Combined with the Child-Pugh’s classification, it could be very useful for further understanding the liver functional reserve, therefore help determine reasonable therapeutic plan, choose surgical procedures and operating time. PMID:12970913

Comparison of nine blood tests and transient elastography for liver fibrosis in chronic hepatitis C: the ANRS HCEP-23 study.

PubMed

Zarski, Jean-Pierre; Sturm, Nathalie; Guechot, Jérôme; Paris, Adeline; Zafrani, Elie-Serge; Asselah, Tarik; Boisson, Renée-Claude; Bosson, Jean-Luc; Guyader, Dominique; Renversez, Jean-Charles; Bronowicki, Jean-Pierre; Gelineau, Marie-Christine; Tran, Albert; Trocme, Candice; De Ledinghen, Victor; Lasnier, Elisabeth; Poujol-Robert, Armelle; Ziegler, Frédéric; Bourliere, Marc; Voitot, Hélène; Larrey, Dominique; Rosenthal-Allieri, Maria Alessandra; Fouchard Hubert, Isabelle; Bailly, François; Vaubourdolle, Michel

2012-01-01

Blood tests and transient elastography (Fibroscan™) have been developed as alternatives to liver biopsy. This ANRS HCEP-23 study compared the diagnostic accuracy of nine blood tests and transient elastography (Fibroscan™) to assess liver fibrosis, vs. liver biopsy, in untreated patients with chronic hepatitis C (CHC). This was a multicentre prospective independent study in 19 French University hospitals of consecutive adult patients having simultaneous liver biopsy, biochemical blood tests (performed in a centralized laboratory) and Fibroscan™. Two experienced pathologists independently reviewed the liver biopsies (mean length=25±8.4 mm). Performance was assessed using ROC curves corrected by Obuchowski's method. Fibroscan™ was not interpretable in 113 (22%) patients. In the 382 patients having both blood tests and interpretable Fibroscan™, Fibroscan™ performed similarly to the best blood tests for the diagnosis of significant fibrosis and cirrhosis. Obuchowski's measure showed Fibrometer® (0.86), Fibrotest® (0.84), Hepascore® (0.84), and interpretable Fibroscan™ (0.84) to be the most accurate tests. The combination of Fibrotest®, Fibrometer®, or Hepascore® with Fibroscan™ or Apri increases the percentage of well classified patients from 70-73% to 80-83% for significant fibrosis, but for cirrhosis a combination offers no improvement. For the 436 patients having all the blood tests, AUROC's ranged from 0.82 (Fibrometer®) to 0.75 (Hyaluronate) for significant fibrosis, and from 0.89 (Fibrometer® and Hepascore®) to 0.83 (FIB-4) for cirrhosis. Contrarily to blood tests, performance of Fibroscan™ was reduced due to uninterpretable results. Fibrotest®, interpretable Fibroscan™, Fibrometer®, and Hepascore® perform best and similarly for diagnosis of significant fibrosis and cirrhosis. Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The application of antitumor drug-targeting models on liver cancer.

PubMed

Yan, Yan; Chen, Ningbo; Wang, Yunbing; Wang, Ke

2016-06-01

Hepatocarcinoma animal models, such as the induced tumor model, transplanted tumor model, gene animal model, are significant experimental tools for the evaluation of targeting drug delivery system as well as the pre-clinical studies of liver cancer. The application of antitumor drug-targeting models not only furnishes similar biological characteristics to human liver cancer but also offers guarantee of pharmacokinetic indicators of the liver-targeting preparations. In this article, we have reviewed some kinds of antitumor drug-targeting models of hepatoma and speculated that the research on this field would be capable of attaining a deeper level and expecting a superior achievement in the future.

Gamma-glutamyl transpeptidase (GGT) blood test

MedlinePlus

... test is used to detect diseases of the liver or bile ducts. It is also done with other tests (such ... and bilirubin tests) to tell the difference between liver or bile duct disorders and bone disease. It may also be ...

Printing Technologies for Medical Applications.

PubMed

Shafiee, Ashkan; Atala, Anthony

2016-03-01

Over the past 15 years, printers have been increasingly utilized for biomedical applications in various areas of medicine and tissue engineering. This review discusses the current and future applications of 3D bioprinting. Several 3D printing tools with broad applications from surgical planning to 3D models are being created, such as liver replicas and intermediate splints. Numerous researchers are exploring this technique to pattern cells or fabricate several different tissues and organs, such as blood vessels or cardiac patches. Current investigations in bioprinting applications are yielding further advances. As one of the fastest areas of industry expansion, 3D additive manufacturing will change techniques across biomedical applications, from research and testing models to surgical planning, device manufacturing, and tissue or organ replacement. Copyright © 2016. Published by Elsevier Ltd.

The Predictive Value of the Maximal Liver Function Capacity Test for the Isolation of Primary Human Hepatocytes.

PubMed

Major, Rebeka D; Kluge, Martin; Jara, Maximilian; Nösser, Maximilian; Horner, Rosa; Gassner, Joseph; Struecker, Benjamin; Tang, Peter; Lippert, Steffen; Reutzel-Selke, Anja; Geisel, Dominik; Denecke, Timm; Stockmann, Martin; Pratschke, Johann; Sauer, Igor M; Raschzok, Nathanael

2018-03-01

The need for primary human hepatocytes is constantly growing for basic research, as well as for therapeutic applications. However, the isolation outcome strongly depends on the quality of liver tissue, and we are still lacking a preoperative test that allows the prediction of the hepatocyte isolation outcome. In this study, we evaluated the "maximal liver function capacity test" (LiMAx) as predictive test for the quantitative and qualitative outcome of hepatocyte isolation. This test is already used in clinical routine to measure preoperative and to predict postoperative liver function. The patient's preoperative mean LiMAx was obtained from the patient records, and preoperative computed tomography and magnetic resonance images were used to calculate the whole liver volume to adjust the mean LiMAx. The outcome parameters of the hepatocyte isolation procedures were analyzed in correlation with the adjusted mean LiMAx. Primary human hepatocytes were isolated from partial hepatectomies (n = 64). From these 64 hepatectomies we included 48 to our study and correlated their isolation outcome parameters with volume corrected LiMAx values. From a total of 11 hepatocyte isolation procedures, metabolic parameters (albumin, urea, and aspartate aminotransferase or AST) were assessed during the hepatocyte cultivation period of 5 days. The volume adjusted mean LiMAx showed a significant positive correlation with the total cell yield (p = 0.049; r = 0.242; n = 48). The correlations of volume adjusted LiMAx values with viable cell yield and cell viability did not reach statistical significance. To create a more homogenous study group regarding tumor entities, subgroup analyses were performed. A subgroup analysis of isolations from patients with colorectal metastasis revealed a significant correlation between volume adjusted mean LiMAx and total cell yield (p = 0.012; r = 0.488; n = 21) and viable cell yield (p = 0.034; r = 0.405; n = 21), whereas a subgroup analysis of isolations of patients with carcinoma of the biliary tree showed significant correlations of volume adjusted mean LiMAx with cell viability (r = 0.387; p = 0.046; n = 20) and lacked significant correlations with total cell yield (r = -0.060; p = 0.401; n = 20) and viable cell yield (r = 0.012; p = 0.480; n = 20). The volume-adjusted mean LiMAx did not show a significant correlation with any of the metabolic parameters. In conclusion, the LiMAx test might be a useful tool to predict the quantitative outcome of hepatocyte isolation, as long as underlying liver disease is taken into consideration.

Radiation-force-based Estimation of Acoustic Attenuation Using Harmonic Motion Imaging (HMI) in Phantoms and in vitro Livers Before and After HIFU Ablation

PubMed Central

Chen, Jiangang; Hou, Gary Y.; Marquet, Fabrice; Han, Yang; Camarena, Francisco

2015-01-01

Acoustic attenuation represents the energy loss of the propagating wave through biological tissues and plays a significant role in both therapeutic and diagnostic ultrasound applications. Estimation of acoustic attenuation remains challenging but critical for tissue characterization. In this study, an attenuation estimation approach was developed using the radiation-force-based method of Harmonic Motion Imaging (HMI). 2D tissue displacement maps were acquired by moving the transducer in a raster-scan format. A linear regression model was applied on the logarithm of the HMI displacements at different depths in order to estimate the acoustic attenuation. Commercially available phantoms with known attenuations (n=5) and in vitro canine livers (n=3) were tested, as well as HIFU lesions in in vitro canine livers (n=5). Results demonstrated that attenuations obtained from the phantoms showed a good correlation (R2=0.976) with the independently obtained values reported by the manufacturer with an estimation error (compared to the values independently measured) varying within the range of 15-35%. The estimated attenuation in the in vitro canine livers was equal to 0.32±0.03 dB/cm/MHz, which is in good agreement with the existing literature. The attenuation in HIFU lesions was found to be higher (0.58±0.06 dB/cm/MHz) than that in normal tissues, also in agreement with the results from previous publications. Future potential applications of the proposed method include estimation of attenuation in pathological tissues before and after thermal ablation. PMID:26371501

A study of cryogenic tissue-engineered liver slices in calcium alginate gel for drug testing.

PubMed

Chen, Ruomeng; Wang, Bo; Liu, Yaxiong; Lin, Rong; He, Jiankang; Li, Dichen

2018-06-01

To address issues such as transportation and the time-consuming nature of tissue-engineered liver for use as an effective drug metabolism and toxicity testing model, "ready-to-use" cryogenic tissue-engineered liver needs to be studied. The research developed a cryogenic tissue-engineered liver slice (TELS), which comprised of HepG2 cells and calcium alginate gel. Cell viability and liver-specific functions were examined after different cryopreservation and recovery culture times. Then, cryogenic TELSs were used as a drug-testing model and treated with Gefitinib. Cryogenic TELSs were stored at -80 °C to ensure high cell viability. During recovery in culture, the cells in the cryogenic TELS were evenly distributed, massively proliferated, and then formed spheroid-like aggregates from day 1 to day 13. The liver-specific functions in the cryogenic TELS were closely related to cryopreservation time and cell proliferation. As a reproducible drug-testing model, the cryogenic TELS showed an obvious drug reaction after treatment with the Gefitinib. The present study shows that the cryopreservation techniques can be used in drug-testing models. Copyright © 2018 Elsevier Inc. All rights reserved.

Liver CT image processing: a short introduction of the technical elements.

PubMed

Masutani, Y; Uozumi, K; Akahane, Masaaki; Ohtomo, Kuni

2006-05-01

In this paper, we describe the technical aspects of image analysis for liver diagnosis and treatment, including the state-of-the-art of liver image analysis and its applications. After discussion on modalities for liver image analysis, various technical elements for liver image analysis such as registration, segmentation, modeling, and computer-assisted detection are covered with examples performed with clinical data sets. Perspective in the imaging technologies is also reviewed and discussed.

Influence of jute (Corchorus olitorius) seed protein enriched diet on some enzymes and liver lipids of albino rats (Rattus norvegicus).

PubMed

Laskar, S; Majumdar, S G; Basak, B; Dey, C D

1986-01-01

The effect of protein, isolated from Jute (Corchorus olitorius) seed was studied upon albino rats with respect to some of their serum, liver and intestinal enzymes and liver lipids. An increase in the body weight (including the weight of the liver) was noted in test animals after feeding with a Jute seed protein enriched diet. It was also observed that AST, ALT and total lipid of liver increased significantly whereas AST and ALT of serum were decreased. An increase in the concentration of lipids in the liver was found and this may be due to excess of the seed protein in the diet. An overall observation reveals that there is slight fatty infiltration in the liver of test animals.

Noninvasive Assessment of Liver Fibrosis Stage Using Ultrasound-Based Shear Wave Velocity Measurements and Serum Algorithms in Patients With Viral Hepatitis B: A Retrospective Cohort Study.

PubMed

Liu, Jianxue; Zhao, Junzhi; Zhang, Yaoren; Ji, Yonghao; Lin, Shumei; Dun, Guoliang; Guo, Sujuan

2017-02-01

Liver biopsy remains the reference standard for the assessment of liver fibrosis, but this procedure is invasive and can lead to complications. Thus, studies to determine the optimal noninvasive test are warranted. This study compared several noninvasive tests and their combinations for evaluating liver fibrosis stages in patients with chronic hepatitis B. The shear wave velocity (SWV) and laboratory indicators were collected from 174 patients with chronic hepatitis B. Formulas were applied to calculate the serum fibrosis model, including the aspartate aminotransaminase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4) and aspartate aminotransferase-to-alanine aminotransferase ratio (AAR). The diagnostic performance of all noninvasive tests was assessed in comparison with percutaneous liver biopsy, based on a receiver operating characteristic curve analysis. The SWV (area under the receiver operating characteristic curve [AUC], 0.82) and APRI (AUC = 0.77) performed better than the FIB-4 (AUC = 0.62), and the AAR (AUC = 0.47) was not suitable for evaluating substantial liver fibrosis (stage ≥F2). The SWV (AUC = 0.96) was the best indicator, being superior to the APRI (AUC = 0.75) and FIB-4 (AUC = 0.74), and the AAR (AUC = 0.45) was not suitable for assessing cirrhosis (F4). Combining the SWV and APRI, the AUC improved to 0.85 for substantial liver fibrosis, and the sensitivity increased to 100% for cirrhosis. The SWV, APRI, and FIB-4 were valid tests for evaluating substantial liver fibrosis and cirrhosis. The combination of these tests with several noninvasive indicators is expected to enhance the assessment of liver fibrosis stages. © 2016 by the American Institute of Ultrasound in Medicine.

Intraperitoneal administration of apigenin in liver ischemia/reperfusion injury protective effects.

PubMed

Tsaroucha, Alexandra K; Tsiaousidou, Anastasia; Ouzounidis, Nikolaos; Tsalkidou, Evanthia; Lambropoulou, Maria; Giakoustidis, Dimitrios; Chatzaki, Ekaterini; Simopoulos, Constantinos

2016-11-01

Hepatic injury caused by ischemia/reperfusion (I/R) is a clinical problem associated with major liver surgery. Among other flavonoids, apigenin has shown a promising effect on I/R cases. In this study, we have investigated the effects of apigenin after liver I/R injury in rats. Forty eight rats were randomized into the following eight groups: (1) Control-sham group: rats subjected to the surgical procedure, except for liver I/R; (2) DMSO group: rats subjected to surgery, except for liver I/R given the apigenin solvent dimethyl-sulfoxide intraperitoneally; (3) C60 group; (4) C120 group; (5) C240 group: rats underwent liver ischemia for 45 min followed by reperfusion for 60 min, 120 min, and 240 min; (6) AP60 group; (7) AP120 group; (8) AP240 group: rats underwent liver ischemia for 45 min, and then given apigenin (5 mg) intraperitoneally followed by reperfusion for 60 min, 120 min, and 240 min. Reverse transcription polymerase chain reaction was performed on liver tissues to measure BCL-2/BAX expression, enzyme-linked immunosorbent assay to measure M30/M65 and ICAM-1. Immunohistochemistry was used to identify M30 biomarker in liver tissues. Quantitative variables were tested by Kolmogorov-Smirnov test, repeated measures analysis of variance/Friedman test. Gene levels were assessed by Student's t-test/Mann-Whitney U-test. BCL-2 levels were significantly higher in I/R apigenin groups than in I/R control groups. BAX levels were lower in the AP240 group than in C240 group. Prolongation of reperfusion resulted in increased activation of M30. ICAM-1 levels were lower in the AP240 group than in C240 group. Apigenin seems to inhibit the process of apoptosis and ameliorate the hepatic I/R injury.

An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure.

PubMed

Roberts, Dean W; Lee, William M; Hinson, Jack A; Bai, Shasha; Swearingen, Christopher J; Stravitz, R Todd; Reuben, Adrian; Letzig, Lynda; Simpson, Pippa M; Rule, Jody; Fontana, Robert J; Ganger, Daniel; Reddy, K Rajender; Liou, Iris; Fix, Oren; James, Laura P

2017-04-01

A rapid and reliable point-of-care assay to detect acetaminophen protein adducts in the serum of patients with acute liver injury could improve diagnosis and management. AcetaSTAT is a competitive immunoassay used to measure acetaminophen protein adducts formed by toxic metabolites in serum samples from patients. We compared the accuracy of AcetaSTAT vs high-pressure liquid chromatography with electrochemical detection (HPLC-EC; a sensitive and specific quantitative analytic assay) to detect acetaminophen protein adducts. We collected serum samples from 19 healthy individuals (no liver injury, no recent acetaminophen use), 29 patients without acetaminophen-associated acute liver injury, and 33 patients with acetaminophen-associated acute liver injury participating in the Acute Liver Failure Study Group registry. Each serum sample was analyzed by AcetaSTAT (reported as test band amplitude) and HPLC-EC (the reference standard). We also collected data on patient age, sex, weight, level of alanine aminotransferase on test day and peak values, concentration of acetaminophen, diagnoses (by site investigator and causality review committee), and outcome after 21 days. Differences between groups were analyzed using the Fisher exact test for categoric variables and the Kruskal-Wallis test or rank-sum test for continuous variables. AcetaSTAT discriminated between patients with and without acetaminophen-associated acute liver injury; the median AcetaSTAT test band amplitude for patients with acetaminophen-associated acute liver injury was 584 (range, 222-1027) vs 3678 (range, 394-8289) for those without (P < .001). AcetaSTAT identified patients with acetaminophen-associated acute liver injury with 100% sensitivity, 86.2% specificity, a positive predictive value of 89.2%, and a negative predictive value of 100%. Results from AcetaSTAT were positive in 4 subjects who received a causality review committee diagnosis of non-acetaminophen-associated acute liver injury; HPLC-EC and biochemical profiles were consistent with acetaminophen-associated acute liver injury in 3 of these cases. The competitive immunoassay AcetaSTAT shows a high degree of concordance with HPLC-EC results in identifying patients with acetaminophen-associated acute liver injury. This rapid and simple assay could increase early detection of this disorder and aid clinical management. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients with Acute Liver Injury or Failure

PubMed Central

Roberts, Dean W.; Lee, William M.; Hinson, Jack A.; Bai, Shasha; Swearingen, Christopher J.; Stravitz, R. Todd; Reuben, Adrian; Letzig, Lynda; Simpson, Pippa M.; Rule, Jody; Fontana, Robert J.; Ganger, Daniel; Reddy, K. Rajender; Liou, Iris; Fix, Oren; James, Laura P.

2017-01-01

Background & Aims A rapid, reliable point-of-care assay to detect acetaminophen protein adducts in serum of patients with acute liver injury could improve diagnosis and management. AcetaSTAT is a competitive immunoassay used to measure acetaminophen protein adducts formed by toxic metabolites in serum samples from patients. We compared the accuracy of AcetaSTAT vs high-pressure liquid chromatography with electrochemical detection (HPLC-EC, a sensitive and specific quantitative analytical assay) to detect acetaminophen protein adducts. Methods We collected serum samples from 19 healthy individuals (no liver injury, no recent acetaminophen use), 29 patients without acetaminophen-associated acute liver injury, and 33 patients with acetaminophen-associated acute liver injury participating in the Acute Liver Failure Study Group registry. Each serum sample was analyzed by AcetaSTAT (reported as test band amplitude) and HPLC-EC (the reference standard). We also collected data on patient age, sex, weight, level of alanine aminotransferase on test day and peak values, concentration of acetaminophen, diagnoses (by site investigator and causality review committee), and outcome after 21 days. Differences between groups were analyzed using Fisher’s Exact for categorical variables and Kruskal-Wallis Test or Rank-Sum test for continuous variables. Results AcetaSTAT discriminated between patients with and without acetaminophen-associated acute liver injury; the median (and range) AcetaSTAT test band amplitude for patients with acetaminophen-associated acute liver injury was 584 (range, 222–1027) vs 3678 (range, 394–8289) for those without (P<.001). AcetaSTAT identified patients with acetaminophen-associated acute liver injury with 100% sensitivity, 86.2% specificity, a positive-predictive value of 89.2%, and a negative-predictive value of 100%. Results from AcetaSTAT were positive in 4 subjects who received a causality review committee diagnosis of non-acetaminophen–associated acute liver injury; HPLC-EC and biochemical profiles were consistent with acetaminophen-associated acute liver injury in 3 of these cases. Conclusion The competitive immunoassay AcetaSTAT demonstrates a high degree of concordance with HPLC-EC results in identifying patients with acetaminophen-associated acute liver injury. This rapid and simple assay could increase early detection of this disorder and aid clinical management. PMID:27641661

Impact of beta-blockers on cardiopulmonary exercise testing in patients with advanced liver disease.

PubMed

Wallen, M P; Hall, A; Dias, K A; Ramos, J S; Keating, S E; Woodward, A J; Skinner, T L; Macdonald, G A; Arena, R; Coombes, J S

2017-10-01

Patients with advanced liver disease may develop portal hypertension that can result in variceal haemorrhage. Beta-blockers reduce portal pressure and minimise haemorrhage risk. These medications may attenuate measures of cardiopulmonary performance, such as the ventilatory threshold and peak oxygen uptake measured via cardiopulmonary exercise testing. To determine the effect of beta-blockers on cardiopulmonary exercise testing variables in patients with advanced liver disease. This was a cross-sectional analysis of 72 participants who completed a cardiopulmonary exercise test before liver transplantation. All participants remained on their usual beta-blocker dose and timing prior to the test. Variables measured during cardiopulmonary exercise testing included the ventilatory threshold, peak oxygen uptake, heart rate, oxygen pulse, the oxygen uptake efficiency slope and the ventilatory equivalents for carbon dioxide slope. Participants taking beta-blockers (n = 28) had a lower ventilatory threshold (P <.01) and peak oxygen uptake (P = .02), compared to participants not taking beta-blockers. After adjusting for age, the model of end-stage liver-disease score, liver-disease aetiology, presence of refractory ascites and ventilatory threshold remained significantly lower in the beta-blocker group (P = .04). The oxygen uptake efficiency slope was not impacted by beta-blocker use. Ventilatory threshold is reduced in patients with advanced liver disease taking beta-blockers compared to those not taking the medication. This may incorrectly risk stratify patients on beta-blockers and has implications for patient management before and after liver transplantation. The oxygen uptake efficiency slope was not influenced by beta-blockers and may therefore be a better measure of cardiopulmonary performance in this patient population. © 2017 John Wiley & Sons Ltd.

Methods for Improving the Curvature of Steerable Needles in Biological Tissue

PubMed Central

Adebar, Troy K.; Greer, Joseph D.; Laeseke, Paul F.; Hwang, Gloria L.; Okamura, Allison M.

2016-01-01

Robotic needle steering systems have the potential to improve percutaneous interventions such as radiofrequency ablation of liver tumors, but steering techniques described to date have not achieved sufficiently small radius of curvature in biological tissue to be relevant to this application. In this work, the impact of tip geometry on steerable needle curvature is examined. Finite-element simulations and experiments with bent-tip needles in ex vivo liver tissue demonstrate that selection of tip length and angle can greatly improve curvature, with radius of curvature below 5 cm in liver tissue possible through judicious selection of these parameters. Motivated by the results of this analysis, a new articulated-tip steerable needle is described, in which a distal section is actively switched by a robotic system between a straight tip (resulting in a straight path) and a bent tip (resulting in a curved path). This approach allows the tip length and angle to be increased, while the straight configuration allows the needle tip to still pass through an introducer sheath and rotate inside the body. Validation testing in liver tissue shows that the new articulated-tip steerable needle achieves smaller radius of curvature compared to bent-tip needles described in previous work. Steerable needles with optimized tip parameters, which can generate tight curves in liver tissue, increase the clinical relevance of needle steering to percutaneous interventions. PMID:26441438

The effect of riboflavin/UVA cross-linking on anti-degeneration and promoting angiogenic capability of decellularized liver matrix.

PubMed

Xiang, Junxi; Liu, Peng; Zheng, Xinglong; Dong, Dinghui; Fan, Shujuan; Dong, Jian; Zhang, Xufeng; Liu, Xuemin; Wang, Bo; Lv, Yi

2017-10-01

Weak mechanical property and unstable degradation rate limited the application of decellularized liver matrix in tissue engineering. The aim of this study was to explore a new method for improving the mechanical properties, anti-degeneration and angiogenic capability of decellularized liver matrix. This was achieved by a novel approach using riboflavin/ultraviolet A treatment to induce collagen cross-linking of decellularized matrix. Histological staining and scanning electron microscope showed that the diameter of cross-linked fibers significantly increased compared with the control group. The average peak load and Young's modulus of decellularized matrix were obviously improved after cross-linking. Then we implanted the modified matrix into the rat hepatic injury model to test the anti-degeneration and angiogenic capability of riboflavin/UVA cross-linked decellularized liver scaffolds in vivo. The results indicated that cross-linked scaffolds degrade more slowly than those in the control group. In the experiment group, average microvessel density in the implanted matrix was higher than that in the control group since the first week after implantation. In conclusion, we initiated the method to improve the biomechanical properties of decellularized liver scaffolds by riboflavin/UVA cross-linking, and more importantly, its improvement on anti-degeneration and angiogenesis was identified. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2662-2669, 2017. © 2017 Wiley Periodicals, Inc.

Hepatitis C prevalence and the significance of liver enzyme elevations in the insurance population.

PubMed

Stout, R L

1997-01-01

Liver enzyme elevation(s) are a common finding in the insurance applicant population. Hepatitis C infection results in histological and functional changes in the liver with both short and long term changes in serum liver enzyme levels. The prevalence of antibodies to HCV in the general population is estimated to be 4%. This paper reports on the prevalence of antibodies to HCV in the insurance applicant population and their relationship to the liver enzyme(s). Antibodies to HCV are present in 1.8% of a random sampling of insurance applicants. Alanine aminotransferase (ALT) elevations occur in 95.4% of all samples positive for antibodies to HCV. More than half of positive samples (56.7%) have ALT elevations of less than two time the upper range of normal. Antibody prevalence is lowest in samples with single enzyme elevation, 4.2%. In comparison, the prevalence is 16.4% in samples with all three enzymes, ALT, AST, and GGT, elevated. For maximal specificity two immunoassays, configured with different HCV antigens, should be performed sequentially on all positive applicant samples. HCV is the most prevalent, chronic viral infection in the insurance population. HCV prevalence is 40 times HIV prevalence. In an evaluation of enzyme reflex markers ALT was positive for antibodies to HCV 8.6% of the time while identifying 95.4% of HCV antibody positive applicants.

Non-invasive diagnostic assessment tools for the detection of liver fibrosis in patients with suspected alcohol-related liver disease: a systematic review and economic evaluation.

PubMed

Stevenson, M; Lloyd-Jones, M; Morgan, M Y; Wong, R

2012-01-01

Excessive alcohol consumption may lead to the development of alcohol-related liver disease (ALD). Liver biopsy may be used in patients with suspected ALD to confirm the diagnosis, exclude other or additional liver pathologies, and provide accurate staging of the degree of liver injury in order to enable the prediction of prognosis and inform treatment decisions. However, as it is an invasive procedure that carries the risk of morbidity and mortality, current UK guidance recommends that biopsy is not required to confirm the diagnosis in patients with a high clinical suspicion of ALD in whom blood tests have excluded other causes of liver disease, unless it is necessary to confirm a diagnosis of acute alcoholic hepatitis in order to inform specific treatment decisions. To evaluate the diagnostic accuracy, cost-effectiveness, and effect on patient outcomes of four non-invasive tests for liver fibrosis [the Enhanced Liver Fibrosis (ELF™) test (Siemens Healthcare Diagnostic Inc., Tarrytown, NY, USA), FibroTest (BioPredictive, Paris, France), FibroMAX (BioPredictive, Paris, France) and transient elastography (FibroScan(®); produced by EchoSens, Paris, France and distributed in the UK by Artemis Medical Ltd, Kent, UK)] in patients suspected of having ALD. A systematic review was undertaken to identify studies reporting the diagnostic and prognostic accuracy of the ELF test, FibroTest, FibroMAX, and FibroScan for the identification of liver fibrosis and associated conditions in patients with suspected ALD. The following databases were searched in January 2010: MEDLINE (from 1950 to January 2010), MEDLINE In-Process & Other Non-Indexed Citations (from 1950 to January 2010), EMBASE (from 1980 to January 2010), Cochrane Database of Systematic Reviews (from 1996 to January 2010), Cochrane Central Register of Controlled Trials (from 1898 to January 2010), Cochrane Methodology Register (from 1904 to January 2010), Database of Abstracts of Reviews of Effects (from 1995 to January 2010), HTA Database (from 1995 to January 2010), NHS Economic Evaluation Database (from 1995 to January 2010), Cumulative Index to Nursing and Allied Health Literature (from 1982 to January 2010), Web of Knowledge and Science Citation Index (from 1969 to January 2010). Study quality was assessed using the QUADAS (Quality Assessment of Diagnostic Accuracy Studies) checklist. Owing to the heterogeneity of the studies, no formal meta-analysis was undertaken. A de novo mathematical model was constructed to estimate the incremental costs and incremental quality-adjusted life-years (QALYs) associated with alternative strategies compared with a biopsy-all strategy. The tests are assessed first as a replacement for liver biopsy, and secondly as an additional test prior to liver biopsy. Thirty-six scenarios were assessed for each non-invasive test strategy, which varied the sensitivity of biopsy, the anxiety associated with biopsy, sensitivity and specificity values and whether or not the biopsy was percutaneous or transjugular. For each scenario, threshold levels were reported where biopsying all patients was more cost-effective than the strategy for two parameters (the decreased level of abstinence associated with the strategy compared with biopsying all and the level of incidental QALY gain associated with biopsy). No studies were identified that specifically assessed the ELF test, although a study was identified that evaluated the diagnostic accuracy of the European Liver Fibrosis Test (essentially, the ELF test with the addition of age to the algorithm) compared with biopsy. Three studies of FibroTest, no relevant studies of FibroMax, and six studies of FibroScan assessing accuracy compared with biopsy in patients with known or suspected alcohol-related liver disease were identified. In all studies, the number of patients with suspected ALD was small, meaning that the estimated sensitivities and specificities were not robust. No conclusive estimate of the cost per QALY of each non-invasive test could be provided. Scenarios exist in which each of the strateg

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

A comprehensive review of noninvasive liver fibrosis tests in pediatric nonalcoholic Fatty liver disease.

PubMed

Mansoor, Sana; Collyer, Elizabeth; Alkhouri, Naim

2015-06-01

Nonalcoholic fatty liver disease (NAFLD) and its spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and fibrosis have been increasing in the pediatric population. The presence and severity of fibrosis in patients with NAFLD are important prognostic factors for the risk of disease progression to cirrhosis. The gold standard for staging liver fibrosis is a liver biopsy. However, given the risks of this procedure, especially in the pediatric population, the development of noninvasive markers to diagnose and monitor progression of NAFLD is desirable. This paper will review recently developed noninvasive methods for diagnosing liver fibrosis in children with NAFLD. These include simple fibrosis scores, advanced biochemical markers, and radiologic imaging studies. Simple fibrosis scores use readily available laboratory tests; available one include AST/ALT ratio, AST to platelet ratio index (APRI), fibrosis (FIB)-4 index, NAFLD fibrosis score (NFS), pediatric NAFLD fibrosis index (PNFI), and pediatric NALFD fibrosis score (PNFS). Advanced biochemical markers include biomarkers of hepatocyte cell death such as cytokeratin 18 fragment levels, and markers of extracellular matrix turnover such as the Enhanced Liver Fibrosis (ELF) test and hyaluronic acid. Radiologic imaging studies estimate liver stiffness as a surrogate for liver fibrosis; these include transient elastography (TE), magnetic resonance elastography (MRE), and acoustic radiation force impulse imaging (ARFI).

Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus.

PubMed

Shigefuku, Ryuta; Takahashi, Hideaki; Nakano, Hiroyasu; Watanabe, Tsunamasa; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Kato, Masaki; Morita, Ryo; Michikawa, Yousuke; Tamura, Tomohiro; Hiraishi, Tetsuya; Hattori, Nobuhiro; Noguchi, Yohei; Nakahara, Kazunari; Ikeda, Hiroki; Ishii, Toshiya; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

2016-09-14

The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.

Characteristics of liver fibrosis with different etiologies using a fully quantitative fibrosis assessment tool.

PubMed

Wu, Q; Zhao, X; You, H

2017-05-18

This study aimed to test the diagnostic performance of a fully quantitative fibrosis assessment tool for liver fibrosis in patients with chronic hepatitis B (CHB), primary biliary cirrhosis (PBC) and non-alcoholic steatohepatitis (NASH). A total of 117 patients with liver fibrosis were included in this study, including 50 patients with CHB, 49 patients with PBC and 18 patients with NASH. All patients underwent liver biopsy (LB). Fibrosis stages were assessed by two experienced pathologists. Histopathological images of LB slices were processed by second harmonic generation (SHG)/two-photon excited fluorescence (TPEF) microscopy without staining, a system called qFibrosis (quantitative fibrosis) system. Altogether 101 quantitative features of the SHG/TPEF images were acquired. The parameters of aggregated collagen in portal, septal and fibrillar areas increased significantly with stages of liver fibrosis in PBC and CHB (P<0.05), but the same was not found for parameters of distributed collagen (P>0.05). There was a significant correlation between parameters of aggregated collagen in portal, septal and fibrillar areas and stages of liver fibrosis from CHB and PBC (P<0.05), but no correlation was found between the distributed collagen parameters and the stages of liver fibrosis from those patients (P>0.05). There was no significant correlation between NASH parameters and stages of fibrosis (P>0.05). For CHB and PBC patients, the highest correlation was between septal parameters and fibrosis stages, the second highest was between portal parameters and fibrosis stages and the lowest correlation was between fibrillar parameters and fibrosis stages. The correlation between the septal parameters of the PBC and stages is significantly higher than the parameters of the other two areas (P<0.05). The qFibrosis candidate parameters based on CHB were also applicable for quantitative analysis of liver fibrosis in PBC patients. Different parameters should be selected for liver fibrosis assessment in different stages of PBC compared with CHB.

Characteristics of liver fibrosis with different etiologies using a fully quantitative fibrosis assessment tool

PubMed Central

Wu, Q.; Zhao, X.; You, H.

2017-01-01

This study aimed to test the diagnostic performance of a fully quantitative fibrosis assessment tool for liver fibrosis in patients with chronic hepatitis B (CHB), primary biliary cirrhosis (PBC) and non-alcoholic steatohepatitis (NASH). A total of 117 patients with liver fibrosis were included in this study, including 50 patients with CHB, 49 patients with PBC and 18 patients with NASH. All patients underwent liver biopsy (LB). Fibrosis stages were assessed by two experienced pathologists. Histopathological images of LB slices were processed by second harmonic generation (SHG)/two-photon excited fluorescence (TPEF) microscopy without staining, a system called qFibrosis (quantitative fibrosis) system. Altogether 101 quantitative features of the SHG/TPEF images were acquired. The parameters of aggregated collagen in portal, septal and fibrillar areas increased significantly with stages of liver fibrosis in PBC and CHB (P<0.05), but the same was not found for parameters of distributed collagen (P>0.05). There was a significant correlation between parameters of aggregated collagen in portal, septal and fibrillar areas and stages of liver fibrosis from CHB and PBC (P<0.05), but no correlation was found between the distributed collagen parameters and the stages of liver fibrosis from those patients (P>0.05). There was no significant correlation between NASH parameters and stages of fibrosis (P>0.05). For CHB and PBC patients, the highest correlation was between septal parameters and fibrosis stages, the second highest was between portal parameters and fibrosis stages and the lowest correlation was between fibrillar parameters and fibrosis stages. The correlation between the septal parameters of the PBC and stages is significantly higher than the parameters of the other two areas (P<0.05). The qFibrosis candidate parameters based on CHB were also applicable for quantitative analysis of liver fibrosis in PBC patients. Different parameters should be selected for liver fibrosis assessment in different stages of PBC compared with CHB. PMID:28538834

Hypocholesterolemia in Patients with an Amebic Liver Abscess

PubMed Central

Flores, María S.; Obregón-Cárdenas, Adriana; Tamez, Eva; Rodríguez, Elba; Arévalo, Katiushka; Quintero, Isela; Tijerina, Rolando; Bosques, Francisco; Galán, Luis

2014-01-01

Background/Aims Many parasites induce changes in the lipid profiles of the host. Cholesterol increases the virulence of Entamoeba histolytica in animal models and in vitro culture. This study aimed to determine, in patients with an amebic liver abscess, the correlation between cholesterol and other features, such as the size and number of abscesses, standard hematological and serum chemistry profiles, liver tests, and duration of hospital stay. Methods A total of 108 patients with an amebic liver abscess and 140 clinically healthy volunteers were investigated. Cholesterol and triglycerides were measured in the sera. The data from medical observations and laboratory tests were obtained from the clinical records. Results A total of 93% of patients with an amebic liver abscess showed hypocholesterolemia not related to any of the studied parameters. Liver function tests correlated with the size of the abscess. The most severe cases of amebic liver disease or death were found in patients whose cholesterol levels continued to decrease despite receiving antiamebic treatment and hospital care. Conclusions Our results show that the hypocholesterolemia observed in patients with an amebic liver abscess is not related to any of the clinical and laboratory features analyzed. This is the first study relating hypocholesterolemia to severity of hepatic amebiasis. PMID:25071907

Thymoquinone restores liver fibrosis and improves oxidative stress status in a lipopolysaccharide-induced inflammation model in rats.

PubMed

Asgharzadeh, Fereshteh; Bargi, Rahimeh; Beheshti, Farimah; Hosseini, Mahmoud; Farzadnia, Mehdi; Khazaei, Majid

2017-01-01

Liver fibrosis is the primary sign of chronic liver injury induced by various causes. Thymoquinone (TQ) is the major ingredient of Nigella sativa with several beneficial effects on the body. In the present study, we aimed to investigate the effect of TQ on liver fibrosis in a lipopolysaccharide (LPS)-induced inflammation in male rats. Fifty male Wistar rats were randomly divided into five groups (n=10 in each group) as follow: (1) control; (2) LPS (1 mg/kg/day; i.p); (3) LPS+TQ 2 mg/kg/day (i.p) (LPs+TQ2); (4) LPS+TQ 5 mg/kg/day (LPS+TQ5); (5) LPS+ TQ 10 mg/kg/day (LPS+ TQ10). After three weeks, blood samples were taken for evaluation of liver function tests. Then, the livers were harvested for histological evaluation of fibrosis and collagen content and measurement of oxidative stress markers including malondialdehyde (MDA), total thiol groups, superoxide dismutase (SOD) and catalase activity in tissue homogenates. LPS group showed higher levels of fibrosis and collagen content stained by Masson's trichrome in liver tissue with impaired liver function test and increased oxidative stress markers (p<0.05). Treatment by TQ restored liver fibrosis, improved liver function tests and increased the levels of anti-oxidative enzymes (SOD and catalase), while reduced MDA concentration (p<0.05). Treatment by TQ restores inflammation-induced liver fibrosis possibly through affecting oxidative stress status. It seems that administration of TQ can be considered as a part of liver fibrosis management.

Comparison of fatty liver index with noninvasive methods for steatosis detection and quantification

PubMed Central

Zelber-Sagi, Shira; Webb, Muriel; Assy, Nimer; Blendis, Laurie; Yeshua, Hanny; Leshno, Moshe; Ratziu, Vlad; Halpern, Zamir; Oren, Ran; Santo, Erwin

2013-01-01

AIM: To compare noninvasive methods presently used for steatosis detection and quantification in nonalcoholic fatty liver disease (NAFLD). METHODS: Cross-sectional study of subjects from the general population, a subgroup from the First Israeli National Health Survey, without excessive alcohol consumption or viral hepatitis. All subjects underwent anthropometric measurements and fasting blood tests. Evaluation of liver fat was performed using four noninvasive methods: the SteatoTest; the fatty liver index (FLI); regular abdominal ultrasound (AUS); and the hepatorenal ultrasound index (HRI). Two of the noninvasive methods have been validated vs liver biopsy and were considered as the reference methods: the HRI, the ratio between the median brightness level of the liver and right kidney cortex; and the SteatoTest, a biochemical surrogate marker of liver steatosis. The FLI is calculated by an algorithm based on triglycerides, body mass index, γ-glutamyl-transpeptidase and waist circumference, that has been validated only vs AUS. FLI < 30 rules out and FLI ≥ 60 rules in fatty liver. RESULTS: Three hundred and thirty-eight volunteers met the inclusion and exclusion criteria and had valid tests. The prevalence rate of NAFLD was 31.1% according to AUS. The FLI was very strongly correlated with SteatoTest (r = 0.91, P < 0.001) and to a lesser but significant degree with HRI (r = 0.55, P < 0.001). HRI and SteatoTest were significantly correlated (r = 0.52, P < 0.001). The κ between diagnosis of fatty liver by SteatoTest (≥ S2) and by FLI (≥ 60) was 0.74, which represented good agreement. The sensitivity of FLI vs SteatoTest was 85.5%, specificity 92.6%, positive predictive value (PPV) 74.7%, and negative predictive value (NPV) 96.1%. Most subjects (84.2%) with FLI < 60 had S0 and none had S3-S4. The κ between diagnosis of fatty liver by HRI (≥ 1.5) and by FLI (≥ 60) was 0.43, which represented only moderate agreement. The sensitivity of FLI vs HRI was 56.3%, specificity 86.5%, PPV 57.0%, and NPV 86.1%. The diagnostic accuracy of FLI for steatosis > 5%, as predicted by SteatoTest, yielded an area under the receiver operating characteristic curve (AUROC) of 0.97 (95% CI: 0.95-0.98). The diagnostic accuracy of FLI for steatosis > 5%, as predicted by HRI, yielded an AUROC of 0.82 (95% CI: 0.77-0.87). The κ between diagnosis of fatty liver by AUS and by FLI (≥ 60) was 0.48 for the entire sample. However, after exclusion of all subjects with an intermediate FLI score of 30-60, the κ between diagnosis of fatty liver by AUS and by FLI either ≥ 60 or < 30 was 0.65, representing good agreement. Excluding all the subjects with an intermediate FLI score, the sensitivity of FLI was 80.3% and the specificity 87.3%. Only 8.5% of those with FLI < 30 had fatty liver on AUS, but 27.8% of those with FLI ≥ 60 had normal liver on AUS. CONCLUSION: FLI has striking agreement with SteatoTest and moderate agreements with AUS or HRI. However, if intermediate values are excluded FLI has high diagnostic value vs AUS. PMID:23326163

Approach to the patient with abnormal liver tests.

PubMed

Mahl, T C

1998-01-01

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

The influence of TLR4 agonist lipopolysaccharides on hepatocellular carcinoma cells and the feasibility of its application in treating liver cancer.

PubMed

Gu, Junsheng; Sun, Ranran; Shen, Shen; Yu, Zujiang

2015-01-01

This study was designed to explore the influence of Toll-like receptor 4 (TLR4) agonist lipopolysaccharides (LPS) on liver cancer cell and the feasibility to perform liver cancer adjuvant therapy. Human liver cancer cell lines HepG2, H7402, and PLC/PRF/5 were taken as models, and the expression of TLRs mRNA was detected by real time-polymerase chain reaction method semiquantitatively. WST-1 method was used to detect the influence of LPS on the proliferation ability of liver cancer cells; propidium iodide (PI) single staining and Annexin V/PI double staining were used to test the influence of LPS on the cell cycle and apoptosis, respectively, on human liver cancer cell line H7402. Fluorescent quantitative polymerase chain reaction and Western blot method were used to determine the change of expression of Cyclin D1. The results demonstrated that most TLRs were expressed in liver cancer cells; stimulating TLR4 by LPS could upregulate TLR4 mRNA and the protein level, activate NF-κB signaling pathway downstream of TLR4, and mediate the generation of inflammatory factors IL-6, IL-8, and TNF-α; LPS was found to be able to strengthen the proliferation ability of liver cancer cells, especially H7402 cells; the expression of Cyclin D1 rose and H7402 cells were promoted to transit from G1 stage to S stage under the stimulation of LPS, but cell apoptosis was not affected. It was also found that LPS was able to activate signal transducer and activator of transcription -3 (STAT3) signaling pathway in H7402 cells and meanwhile significantly increase the initiation activity of STAT3; proliferation promoting effect of LPS to liver cancer cells remarkably lowered once STAT3 was blocked or inhibited. Thus, TLR4 agonist LPS is proved to be able to induce liver cancer cells to express inflammation factors and mediate liver cancer cell proliferation and generation of multidrug resistance by activating the cyclooxygenase-2/prostaglandin signal axis as well as the STAT3 pathway.

[Expression of ATAD2 in different liver lesions and its clinical significance].

PubMed

Liu, F; Zhou, X; Ji, H H; Li, H; Xiang, F G

2017-05-20

Objective: To examine the expression of ATAD2 in different liver lesions and its clinical significance. Methods: ATAD2 expression in 60 hepatocellular carcinoma (HCC) surgical specimens (49 of which have concurrent liver cirrhosis), 43 HCC biopsy specimens, 2 high-grade liver dysplastic nodule specimens, 3 low-grade liver dysplastic nodule specimens, 50 liver cirrhosis tissue samples, and 20 normal liver tissue samples were measured using immunohistochemistry. The F-test, q-test, t-test, and chi-square test were used for statistical analysis of data. Results: ATAD2 was expressed in 56 HCC surgical specimens (93.33%), 35 HCC biopsy specimens (81.40%), and 2 high-grade liver dysplastic nodule specimens (2/2), but not in the low-grade liver dysplastic nodule, liver cirrhosis tissue, and normal liver tissue samples. The mean expression of ATAD2 was significantly higher in HCC tissues than in high-grade and low-grade liver dysplastic nodule tissues, liver cirrhosis tissue, and normal liver tissue ( F = 22.96, q = 3.138, 3.972, 12.272, and 9.101, respectively, all P < 0.01). There were no significant differences in the mean expression and positive expression rate of ATAD2 between HCC surgical and biopsy specimens ( t = 1.40, P > 0.05; χ ² = 3.47, P >0.05). Of the 35 HCC biopsy specimens that expressed ATAD2, the mean ATAD2 expression was ≥1% in 35 specimens (100%), ≥3% in 27 specimens (77.14%), and ≥5 % in 23 specimens (65.71%). In addition, among the pathological grade I-II HCC biopsy specimens, the mean ATAD2 expression was ≥1% in 28 specimens (100%), ≥3% in 22 specimens (62.86%), and ≥5% in 19 specimens (54.29%). Moreover, ATAD2 expression in HCC was associated with serum alpha-fetoprotein level, presence of hepatitis B virus surface antigen (HBsAg), and presence of concurrent liver cirrhosis ( t = 2.09, 2.30, and 2.18, respectively, all P < 0.05). Conclusion: ATAD2 may play an important role in HCC tumorigenesis, and may be involved in malignant transformation of cells. ATAD2 expression can be a valuable marker for differentiating the nature of lesions in liver biopsy tissues during clinical practice.

Stem cell-derived models to improve mechanistic understanding and prediction of human drug-induced liver injury.

PubMed

Goldring, Christopher; Antoine, Daniel J; Bonner, Frank; Crozier, Jonathan; Denning, Chris; Fontana, Robert J; Hanley, Neil A; Hay, David C; Ingelman-Sundberg, Magnus; Juhila, Satu; Kitteringham, Neil; Silva-Lima, Beatriz; Norris, Alan; Pridgeon, Chris; Ross, James A; Young, Rowena Sison; Tagle, Danilo; Tornesi, Belen; van de Water, Bob; Weaver, Richard J; Zhang, Fang; Park, B Kevin

2017-02-01

Current preclinical drug testing does not predict some forms of adverse drug reactions in humans. Efforts at improving predictability of drug-induced tissue injury in humans include using stem cell technology to generate human cells for screening for adverse effects of drugs in humans. The advent of induced pluripotent stem cells means that it may ultimately be possible to develop personalized toxicology to determine interindividual susceptibility to adverse drug reactions. However, the complexity of idiosyncratic drug-induced liver injury means that no current single-cell model, whether of primary liver tissue origin, from liver cell lines, or derived from stem cells, adequately emulates what is believed to occur during human drug-induced liver injury. Nevertheless, a single-cell model of a human hepatocyte which emulates key features of a hepatocyte is likely to be valuable in assessing potential chemical risk; furthermore, understanding how to generate a relevant hepatocyte will also be critical to efforts to build complex multicellular models of the liver. Currently, hepatocyte-like cells differentiated from stem cells still fall short of recapitulating the full mature hepatocellular phenotype. Therefore, we convened a number of experts from the areas of preclinical and clinical hepatotoxicity and safety assessment, from industry, academia, and regulatory bodies, to specifically explore the application of stem cells in hepatotoxicity safety assessment and to make recommendations for the way forward. In this short review, we particularly discuss the importance of benchmarking stem cell-derived hepatocyte-like cells to their terminally differentiated human counterparts using defined phenotyping, to make sure the cells are relevant and comparable between labs, and outline why this process is essential before the cells are introduced into chemical safety assessment. (Hepatology 2017;65:710-721). © 2016 by the American Association for the Study of Liver Diseases.

Novel Bioimaging Techniques of Metals by Laser Ablation Inductively Coupled Plasma Mass Spectrometry for Diagnosis Of Fibrotic and Cirrhotic Liver Disorders

PubMed Central

Gassler, Nikolaus; Bosserhoff, Anja K.; Becker, J. Sabine

2013-01-01

Background and Aims Hereditary disorders associated with metal overload or unwanted toxic accumulation of heavy metals can lead to morbidity and mortality. Patients with hereditary hemochromatosis or Wilson disease for example may develop severe hepatic pathology including fibrosis, cirrhosis or hepatocellular carcinoma. While relevant disease genes are identified and genetic testing is applicable, liver biopsy in combination with metal detecting techniques such as energy-dispersive X-ray spectroscopy (EDX) is still applied for accurate diagnosis of metals. Vice versa, several metals are needed in trace amounts for carrying out vital functions and their deficiency due to rapid growth, pregnancy, excessive blood loss, and insufficient nutritional or digestive uptake results in organic and systemic shortcomings. Established in situ techniques, such as EDX-ray spectroscopy, are not sensitive enough to analyze trace metal distribution and the quantification of metal images is difficult. Methods In this study, we developed a quantitative biometal imaging technique of human liver tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) in order to compare the distribution of selected metals in cryo-sections of healthy and fibrotic/cirrhotic livers. Results Most of the metals are homogeneous distributed within the normal tissue, while they are redirected within fibrotic livers resulting in significant metal deposits. Moreover, total iron and copper concentrations in diseased liver were found about 3-5 times higher than in normal liver samples. Conclusions Biometal imaging via LA-ICP-MS is a sensitive innovative diagnostic tool that will impact clinical practice in identification and evaluation of hepatic metal disorders and to detect subtle metal variations during ongoing hepatic fibrogenesis. PMID:23505552

Magnetic resonance cholangiopancreatography (MRCP) using new negative per-oral contrast agent based on superparamagnetic iron oxide nanoparticles for extrahepatic biliary duct visualization in liver cirrhosis.

PubMed

Polakova, Katerina; Mocikova, Ingrid; Purova, Dana; Tucek, Pavel; Novak, Pavel; Novotna, Katerina; Izak, Niko; Bielik, Radoslav; Zboril, Radek; Miroslav, Herman

2016-12-01

Magnetic resonance cholangiopancreatography (MRCP) is often used for imaging of the biliary tree and is required by surgeons before liver transplantation. Advanced liver cirrhosis and ascites in patients however present diagnostic problems for MRCP. The aim of this study was to find out if the use of our negative per-oral contrast agent containing superparamagnetic iron oxide nanoparticles (SPIO) in MRCP is helpful for imaging of hepatobiliary tree in patients with liver cirrhosis. Forty patients with liver cirrhosis were examined on a 1.5 T MR unit using standard MRCP protocol. Twenty patients (group A) underwent MRCP after administration of per-oral SPIO contrast agent 30 min before examination. In group B, twenty patients were examined without per-oral bowel preparation. Ascites was present in eleven patients from group A and in thirteen patients in group B. Four radiologists analyzed MR images for visibility and delineation of the biliary tree. χ 2 tests were used for comparison of the visibility of intrahepatic and extrahepatic biliary ducts in patients with and without ascites. Better extrahepatic biliary duct visualization and visibility of extraluminal pathologies in patients with ascites was proved after administration of SPIO contrast agent. No statistically significant difference between group A and B was found for visualization of extrahepatic biliary ducts in patients without ascites. Delineation of intrahepatic biliary ducts was independent on bowel preparation. Application of our negative per-oral SPIO contrast agent before MRCP improves the visualization of extrahepatic biliary ducts in patients with ascites which is helpful during the liver surgery, mainly in liver transplantation.

Redox-Dependent HMGB1 Isoforms as Pivotal Co-Ordinators of Drug-Induced Liver Injury: Mechanistic Biomarkers and Therapeutic Targets.

PubMed

Lea, Jonathan D; Clarke, Joanna I; McGuire, Niamh; Antoine, Daniel J

2016-04-20

High-mobility group box 1 (HMGB1) is a critical protein in the coordination of the inflammatory response in drug-induced liver injury (DILI). HMGB1 is released from necrotic hepatocytes and activated immune cells. The extracellular function of HMGB1 is dependent upon redox modification of cysteine residues that control chemoattractant and cytokine-inducing properties. Existing biomarkers of DILI such as alanine aminotransferase (ALT) have limitations such as lack of sensitivity and tissue specificity that can adversely affect clinical intervention. HMGB1 isoforms have been shown to be more sensitive biomarkers than ALT for predicting DILI development and the requirement for liver transplant following acetaminophen (APAP) overdose. Hepatocyte-specific conditional knockout of HMGB1 has demonstrated the pivotal role of HMGB1 in DILI and liver disease. Tandem mass spectrometry (MS/MS) enables the characterization and quantification of different mechanism-dependent post-translationally modified isoforms of HMGB1. HMGB1 shows great promise as a biomarker of DILI. However, current diagnostic assays are either too time-consuming to be clinically applicable (MS/MS) or are unable to distinguish between different redox and acetyl isoforms of HMGB1 (ELISA). Additionally, HMGB1 is not liver specific, so while it outperforms ALT (also not liver specific) as a biomarker for the prediction of DILI development, it should be used in a biomarker panel along with liver-specific markers such as miR-122. A point-of-care test for HMGB1 and the development of redox and acetyl isoform-targeting antibodies will advance clinical utility. Work is ongoing to validate baseline levels of circulating HMGB1 in healthy volunteers.

Liver enzyme abnormalities in taking traditional herbal medicine in Korea: A retrospective large sample cohort study of musculoskeletal disorder patients.

PubMed

Lee, Jinho; Shin, Joon-Shik; Kim, Me-Riong; Byun, Jang-Hoon; Lee, Seung-Yeol; Shin, Ye-Sle; Kim, Hyejin; Byung Park, Ki; Shin, Byung-Cheul; Lee, Myeong Soo; Ha, In-Hyuk

2015-07-01

The objective of this study is to report the incidence of liver injury from herbal medicine in musculoskeletal disease patients as large-scale studies are scarce. Considering that herbal medicine is frequently used in patients irrespective of liver function in Korea, we investigated the prevalence of liver injury by liver function test results in musculoskeletal disease patients. Of 32675 inpatients taking herbal medicine at 7 locations of a Korean medicine hospital between 2005 and 2013, we screened for liver injury in 6894 patients with liver function tests (LFTs) at admission and discharge. LFTs included t-bilirubin, AST, ALT, and ALP. Liver injury at discharge was assessed by LFT result classifications at admission (liver injury, liver function abnormality, and normal liver function). In analyses for risk factors of liver injury at discharge, we adjusted for age, sex, length of stay, conventional medicine intake, HBs antigen/antibody, and liver function at admission. A total 354 patients (prevalence 5.1%) had liver injury at admission, and 217 (3.1%) at discharge. Of the 354 patients with liver injury at admission, only 9 showed a clinically significant increase after herbal medicine intake, and 225 returned to within normal range or showed significant liver function recovery. Out of 4769 patients with normal liver function at admission, 27 (0.6%) had liver injury at discharge. In multivariate analyses for risk factors, younger age, liver function abnormality at admission, and HBs antigen positive were associated with injury at discharge. The prevalence of liver injury in patients with normal liver function taking herbal medicine for musculoskeletal disease was low, and herbal medicine did not exacerbate liver injury in most patients with injury prior to intake. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Endoscopic ultrasound description of liver segmentation and anatomy.

PubMed

Bhatia, Vikram; Hijioka, Susumu; Hara, Kazuo; Mizuno, Nobumasa; Imaoka, Hiroshi; Yamao, Kenji

2014-05-01

Endoscopic ultrasound (EUS) can demonstrate the detailed anatomy of the liver from the transgastric and transduodenal routes. Most of the liver segments can be imaged with EUS, except the right posterior segments. The intrahepatic vascular landmarks include the major hepatic veins, portal vein radicals, hepatic arterial branches, and the inferior vena cava, and the venosum and teres ligaments are other important intrahepatic landmarks. The liver hilum and gallbladder serve as useful surface landmarks. Deciphering liver segmentation and anatomy by EUS requires orienting the scan planes with these landmarkstructures, and is different from the static cross-sectional radiological images. Orientation during EUS requires appreciation of the numerous scan planes possible in real-time, and the direction of scanning from the stomach and duodenal bulb. We describe EUS imaging of the liver with a curved linear probe in a step-by-step approach, with the relevant anatomical details, potential applications, and pitfalls of this novel EUS application. © 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.

Living Donor Liver Transplantation Using a Liver Graft With Congenital Intrahepatic Portosystemic Shunt

PubMed Central

Kamei, Hideya; Imai, Hisashi; Onishi, Yasuharu; Sugimoto, Hiroyuki; Suzuki, Kojiro; Ogura, Yasuhiro

2016-01-01

Background Despite of recent development of imaging modalities, congenital intrahepatic portosystemic shunt (IPSS) is rarely diagnosed. Therefore, living donor liver transplantation using a liver graft with IPSS has not been previously published. Materials and Methods We report a 28-year-old male patient with end-stage liver disease secondary to Wilson disease. His 26-year-old brother was a potential living donor, who had an IPSS of 25 mm in diameter at segment 6 as shown by computed tomography. Liver function tests were normal, and blood ammonia concentration was in the upper limit of normal. Results Living donor liver transplantation was uneventfully performed. After surgery, a recipient liver function tests showed a quick recovery, and serum ammonia levels were consistently normal. Although thrombosis inside the IPSS was confirmed by computed tomography on postoperative day 21, this thrombosis disappeared at 3 months posttransplant with anticoagulants. Currently (12 months posttransplant), the patient has fully recovered, and the IPSS is still the same size. Conclusions Based on our experience, liver allografts with IPSS can be accepted as potential liver allografts. PMID:27500240

Methodology on quantification of sonication duration for safe application of MR guided focused ultrasound for liver tumour ablation.

PubMed

Mihcin, Senay; Karakitsios, Ioannis; Le, Nhan; Strehlow, Jan; Demedts, Daniel; Schwenke, Michael; Haase, Sabrina; Preusser, Tobias; Melzer, Andreas

2017-12-01

Magnetic Resonance Guided Focused Ultrasound (MRgFUS) for liver tumour ablation is a challenging task due to motion caused by breathing and occlusion due the ribcage between the transducer and the tumour. To overcome these challenges, a novel system for liver tumour ablation during free breathing has been designed. The novel TRANS-FUSIMO Treatment System (TTS, EUFP7) interacts with a Magnetic Resonance (MR) scanner and a focused ultrasound transducer to sonicate to a moving target in liver. To meet the requirements of ISO 13485; a quality management system for medical device design, the system needs to be tested for certain process parameters. The duration of sonication and, the delay after the sonication button is activated, are among the parameters that need to be quantified for efficient and safe ablation of tumour tissue. A novel methodology is developed to quantify these process parameters. A computerised scope is programmed in LabVIEW to collect data via hydrophone; where the coordinates of fiber-optic sensor assembly was fed into the TRANS-FUSIMO treatment software via Magnetic Resonance Imaging (MRI) to sonicate to the tip of the sensor, which is synchronised with the clock of the scope, embedded in a degassed water tank via sensor assembly holder. The sonications were executed for 50 W, 100 W, 150 W for 10 s to quantify the actual sonication duration and the delay after the emergency stop by two independent operators for thirty times. The deviation of the system from the predefined specs was calculated. Student's-T test was used to investigate the user dependency. The duration of sonication and the delay after the sonication were quantified successfully with the developed method. TTS can sonicate with a maximum deviation of 0.16 s (Std 0.32) from the planned duration and with a delay of 14 ms (Std 0.14) for the emergency stop. Student's T tests indicate that the results do not depend on operators (p > .05). The evidence obtained via this protocol is crucial for translation- of-research into the clinics for safe application of MRgFUS. The developed protocol could be used for system maintenance in compliance with quality systems in clinics for daily quality assurance routines. Copyright © 2017 Elsevier B.V. All rights reserved.

Small-Animal SPECT/CT of the Progression and Recovery of Rat Liver Fibrosis by Using an Integrin αvβ3-targeting Radiotracer.

PubMed

Yu, Xinhe; Wu, Yue; Liu, Hao; Gao, Liquan; Sun, Xianlei; Zhang, Chenran; Shi, Jiyun; Zhao, Huiyun; Jia, Bing; Liu, Zhaofei; Wang, Fan

2016-05-01

To assess the potential utility of an integrin αvβ3-targeting radiotracer, technetium 99m-PEG4-E[PEG4-cyclo(arginine-glycine-aspartic acid-D-phenylalanine-lysine)]2 ((99m)Tc-3PRGD2), for single photon emission computed tomography (SPECT)/computed tomography (CT) for monitoring of the progression and prognosis of liver fibrosis in a rat model. All animal experiments were performed by following the protocol approved by the institutional animal care and use committee. (99m)Tc-3PRGD2 was prepared and longitudinal SPECT/CT was performed to monitor the progression (n = 8) and recovery (n = 5) of liver fibrosis induced in a rat model by means of thioacetamide (TAA) administration. The mean liver-to-background radioactivity per unit volume ratio was analyzed for comparisons between the TAA and control (saline) groups at different stages of liver fibrosis. Data were compared by using Student t and Mann-Whitney tests. Results:of SPECT/CT were compared with those of ex vivo biodistribution analysis (n = 5). Accumulation of (99m)Tc-3PRGD2 in the liver increased in proportion to the progression of fibrosis and TAA exposure time; accumulation levels were significantly different between the TAA and control groups as early as week 4 of TAA administration (liver-to-background ratio: 32.30 ± 3.39 vs 19.01 ± 3.31; P = .0002). Results of ex vivo immunofluorescence staining demonstrated the positive expression of integrin αvβ3 on the activated hepatic stellate cells, and the integrin αvβ3 levels in the liver corresponded to the results of SPECT/CT (R(2) = 0.75, P < .0001). (99m)Tc-3PRGD2 uptake in the fibrotic liver decreased after antifibrotic therapy with interferon α2b compared with that in the control group (relative liver-to-background ratio: 0.45 ± 0.05 vs 1.01 ± 0.05; P < .0001) or spontaneous recovery (relative liver-to-background ratio: 0.56 ± 0.06 vs 1.01 ± 0.05; P < .0001). (99m)Tc-3PRGD2 SPECT/CT was successfully used to monitor the progression and recovery of liver fibrosis and shows potential applications for noninvasive diagnosis of early stage liver fibrosis. (©) RSNA, 2015 Online supplemental material is available for this article.

Evaluating Diagnostic Accuracy of Noninvasive Tests in Assessment of Significant Liver Fibrosis in Chronic Hepatitis C Egyptian Patients.

PubMed

Omran, Dalia; Zayed, Rania A; Nabeel, Mohammed M; Mobarak, Lamiaa; Zakaria, Zeinab; Farid, Azza; Hassany, Mohamed; Saif, Sameh; Mostafa, Muhammad; Saad, Omar Khalid; Yosry, Ayman

2018-05-01

Stage of liver fibrosis is critical for treatment decision and prediction of outcomes in chronic hepatitis C (CHC) patients. We evaluated the diagnostic accuracy of transient elastography (TE)-FibroScan and noninvasive serum markers tests in the assessment of liver fibrosis in CHC patients, in reference to liver biopsy. One-hundred treatment-naive CHC patients were subjected to liver biopsy, TE-FibroScan, and eight serum biomarkers tests; AST/ALT ratio (AAR), AST to platelet ratio index (APRI), age-platelet index (AP index), fibrosis quotient (FibroQ), fibrosis 4 index (FIB-4), cirrhosis discriminant score (CDS), King score, and Goteborg University Cirrhosis Index (GUCI). Receiver operating characteristic curves were constructed to compare the diagnostic accuracy of these noninvasive methods in predicting significant fibrosis in CHC patients. TE-FibroScan predicted significant fibrosis at cutoff value 8.5 kPa with area under the receiver operating characteristic (AUROC) 0.90, sensitivity 83%, specificity 91.5%, positive predictive value (PPV) 91.2%, and negative predictive value (NPV) 84.4%. Serum biomarkers tests showed that AP index and FibroQ had the highest diagnostic accuracy in predicting significant liver fibrosis at cutoff 4.5 and 2.7, AUROC was 0.8 and 0.8 with sensitivity 73.6% and 73.6%, specificity 70.2% and 68.1%, PPV 71.1% and 69.8%, and NPV 72.9% and 72.3%, respectively. Combined AP index and FibroQ had AUROC 0.83 with sensitivity 73.6%, specificity 80.9%, PPV 79.6%, and NPV 75.7% for predicting significant liver fibrosis. APRI, FIB-4, CDS, King score, and GUCI had intermediate accuracy in predicting significant liver fibrosis with AUROC 0.68, 0.78, 0.74, 0.74, and 0.67, respectively, while AAR had low accuracy in predicting significant liver fibrosis. TE-FibroScan is the most accurate noninvasive alternative to liver biopsy. AP index and FibroQ, either as individual tests or combined, have good accuracy in predicting significant liver fibrosis, and are better combined for higher specificity.

Yogi Detox Tea: A Potential Cause of Acute Liver Failure.

PubMed

Kesavarapu, Keerthana; Kang, Mitchell; Shin, Jaewook James; Rothstein, Kenneth

2017-01-01

We present a case of acute fulminant liver failure from a liver detoxification tea. We present a 60-year-old female with weakness, lethargy, scleral icterus, jaundice, and worsening mental status. She drank herbal tea three times a day for 14 days prior to symptom development. Liver tests were elevated. Remaining laboratory tests and imaging were negative for other etiologies. An ultrasound-guided liver biopsy showed submassive necrosis. A literature search on the ingredients shows six ingredients as having hepatotoxic effects and remaining ingredients as having very sparse hepatoprotective data. Healthcare professionals should discuss herbal medication and tea use and report adverse effects.

Yogi Detox Tea: A Potential Cause of Acute Liver Failure

PubMed Central

Kang, Mitchell; Shin, Jaewook James; Rothstein, Kenneth

2017-01-01

We present a case of acute fulminant liver failure from a liver detoxification tea. We present a 60-year-old female with weakness, lethargy, scleral icterus, jaundice, and worsening mental status. She drank herbal tea three times a day for 14 days prior to symptom development. Liver tests were elevated. Remaining laboratory tests and imaging were negative for other etiologies. An ultrasound-guided liver biopsy showed submassive necrosis. A literature search on the ingredients shows six ingredients as having hepatotoxic effects and remaining ingredients as having very sparse hepatoprotective data. Healthcare professionals should discuss herbal medication and tea use and report adverse effects. PMID:29204300

Evaluation of the aspartate aminotransferase/platelet ratio index and enhanced liver fibrosis tests to detect significant fibrosis due to chronic hepatitis C.

PubMed

Petersen, John R; Stevenson, Heather L; Kasturi, Krishna S; Naniwadekar, Ashutosh; Parkes, Julie; Cross, Richard; Rosenberg, William M; Xiao, Shu-Yuan; Snyder, Ned

2014-04-01

The assessment of liver fibrosis in chronic hepatitis C patients is important for prognosis and making decisions regarding antiviral treatment. Although liver biopsy is considered the reference standard for assessing hepatic fibrosis in patients with chronic hepatitis C, it is invasive and associated with sampling and interobserver variability. Serum fibrosis markers have been utilized as surrogates for a liver biopsy. We completed a prospective study of 191 patients in which blood draws and liver biopsies were performed on the same visit. Using liver biopsies the sensitivity, specificity, and negative and positive predictive values for both aspartate aminotransferase/platelet ratio index (APRI) and enhanced liver fibrosis (ELF) were determined. The patients were divided into training and validation patient sets to develop and validate a clinically useful algorithm for differentiating mild and significant fibrosis. The area under the ROC curve for the APRI and ELF tests for the training set was 0.865 and 0.880, respectively. The clinical sensitivity in separating mild (F0-F1) from significant fibrosis (F2-F4) was 80% and 86.0% with a clinical specificity of 86.7% and 77.8%, respectively. For the validation sets the area under the ROC curve for the APRI and ELF tests was, 0.855 and 0.780, respectively. The clinical sensitivity of the APRI and ELF tests in separating mild (F0-F1) from significant (F2-F4) fibrosis for the validation set was 90.0% and 70.0% with a clinical specificity of 73.3% and 86.7%, respectively. There were no differences between the APRI and ELF tests in distinguishing mild from significant fibrosis for either the training or validation sets (P=0.61 and 0.20, respectively). Using APRI as the primary test followed by ELF for patients in the intermediate zone, would have decreased the number of liver biopsies needed by 40% for the validation set. Overall, use of our algorithm would have decreased the number of patients who needed a liver biopsy from 95 to 24-a 74.7% reduction. This study has shown that the APRI and ELF tests are equally accurate in distinguishing mild from significant liver fibrosis, and combining them into a validated algorithm improves their performance in distinguishing mild from significant fibrosis.

Bioprinting of Micro-Organ Tissue Analog for Drug Metabolism Study

NASA Astrophysics Data System (ADS)

Sun, Wei

An evolving application of tissue engineering is to develop in vitro 3D cell/tissue models for drug screening and pharmacological study. In order to test in space, these in vitro models are mostly manufactured through micro-fabrication techniques and incorporate living cells with MEMS or microfluidic devices. These cell-integrated microfluidic devices, or referred as microorgans, are effective in furnishing reliable and inexpensive drug metabolism and toxicity studies [1-3]. This paper will present an on-going research collaborated between Drexel University and NASA JSC Radiation Physics Laboratory for applying a direct cell printing technique to freeform fabrication of 3D liver tissue analog in drug metabolism study. The paper will discuss modeling, design, and solid freeform fabrication of micro-fluidic flow patterns and bioprinting of 3D micro-liver chamber that biomimics liver physiological microenvironment for enhanced drug metabolization. Technical details to address bioprinting of 3D liver tissue analog, integration with a microfluidic device, and basic drug metabolism study for NASA's interests will presented. 1. Holtorf H. Leslie J. Chang R, Nam J, Culbertson C, Sun W, Gonda S, "Development of a Three-Dimensional Tissue-on-a-Chip Micro-Organ Device for Pharmacokinetic Analysis", the 47th Annual Meeting of the American Society for Cell Biology, Washington, DC, December 1-5, 2007. 2. Chang, R., Nam, J., Culbertson C., Holtorf, H., Jeevarajan, A., Gonda, S. and Sun, W., "Bio-printing and Modeling of Flow Patterns for Cell Encapsulated 3D Liver Chambers For Pharmacokinetic Study", TERMIS North America 2007 Conference and Exposition, Westin Harbour Castle, Toronto, Canada, June 13-16, 2007. 3.Starly, B., Chang, R., Sun, W., Culbertson, C., Holtorf, H. and Gonda, S., "Bioprinted Tissue-on-chip Application for Pharmacokinetic Studies", Proceedings of World Congress on Tissue Engineering and Regenerative Medicine, Pittsburgh, PA, USA, April 24-27, 2006.

A Single Test Combining Blood Markers and Elastography is More Accurate Than Other Fibrosis Tests in the Main Causes of Chronic Liver Diseases.

PubMed

Ducancelle, Alexandra; Leroy, Vincent; Vergniol, Julien; Sturm, Nathalie; Le Bail, Brigitte; Zarski, Jean Pierre; Nguyen Khac, Eric; Salmon, Dominique; de Ledinghen, Victor; Calès, Paul

2017-08-01

International guidelines suggest combining a blood test and liver stiffness measurement (LSM) to stage liver fibrosis in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). Therefore, we compared the accuracies of these tests between the main etiologies of chronic liver diseases. Overall, 1968 patients were included in 5 etiologies: CHC: 698, chronic hepatitis B: 152, human immunodeficiency virus/CHC: 628, NAFLD: 225, and alcoholic liver disease (ALD): 265. Sixteen tests [13 blood tests, LSM (Fibroscan), 2 combined: FibroMeters] were evaluated. References were Metavir staging and CHC etiology. Accuracy was evaluated mainly with the Obuchowski index (OI) and accessorily with area under the receiver operating characteristics (F≥2, F≥3, cirrhosis). OIs in CHC were: FibroMeters: 0.812, FibroMeters: 0.785 to 0.797, Fibrotest: 0.762, CirrhoMeters: 0.756 to 0.771, LSM: 0.754, Hepascore: 0.752, FibroMeter: 0.750, aspartate aminotransferase platelet ratio index: 0.742, Fib-4: 0.741. In other etiologies, most tests had nonsignificant changes in OIs. In NAFLD, CHC-specific tests were more accurate than NAFLD-specific tests. The combined FibroMeters had significantly higher accuracy than their 2 constitutive tests (FibroMeters and LSM) in at least 1 diagnostic target in all etiologies, except in ALD where LSM had the highest OI, and in 3 diagnostic targets (OIs and 2 area under the receiver operating characteristics) in CHC and NAFLD. Some tests developed in CHC outperformed other tests in their specific etiologies. Tests combining blood markers and LSM outperformed single tests, validating recent guidelines and extending them to main etiologies. Noninvasive fibrosis evaluation can thus be simplified in the main etiologies by using a unique test: either LSM alone, especially in ALD, or preferably combined to blood markers.

Side Effects of HIV Medicines: HIV and Hepatotoxicity

MedlinePlus

... provider tells you to. How is hepatotoxicity detected? Liver function tests (LFTs) are a group of blood tests ... Laboratory Testing From the Department of Veterans Affairs: Primary Care of Veterans with HIV: Liver Disease and Cirrhosis From the National Institutes of ...

HCV-RNA quantification in liver bioptic samples and extrahepatic compartments, using the abbott RealTime HCV assay.

PubMed

Antonucci, FrancescoPaolo; Cento, Valeria; Sorbo, Maria Chiara; Manuelli, Matteo Ciancio; Lenci, Ilaria; Sforza, Daniele; Di Carlo, Domenico; Milana, Martina; Manzia, Tommaso Maria; Angelico, Mario; Tisone, Giuseppe; Perno, Carlo Federico; Ceccherini-Silberstein, Francesca

2017-08-01

We evaluated the performance of a rapid method to quantify HCV-RNA in the hepatic and extrahepatic compartments, by using for the first time the Abbott RealTime HCV-assay. Non-tumoral (NT), tumoral (TT) liver samples, lymph nodes and ascitic fluid from patients undergoing orthotopic-liver-transplantation (N=18) or liver resection (N=4) were used for the HCV-RNA quantification; 5/22 patients were tested after or during direct acting antivirals (DAA) treatment. Total RNA and DNA quantification from tissue-biopsies allowed normalization of HCV-RNA concentrations in IU/μg of total RNA and IU/10 6 liver-cells, respectively. HCV-RNA was successfully quantified with high reliability in liver biopsies, lymph nodes and ascitic fluid samples. Among the 17 untreated patients, a positive and significant HCV-RNA correlation between serum and NT liver-samples was observed (Pearson: rho=0.544, p=0.024). Three DAA-treated patients were HCV-RNA "undetectable" in serum, but still "detectable" in all tested liver-tissues. Differently, only one DAA-treated patient, tested after sustained-virological-response, showed HCV-RNA "undetectability" in liver-tissue. HCV-RNA was successfully quantified with high reliability in liver bioptic samples and extrahepatic compartments, even when HCV-RNA was "undetectable" in serum. Abbott RealTime HCV-assay is a good diagnostic tool for HCV quantification in intra- and extra-hepatic compartments, whenever a bioptic sample is available. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

An improved stereologic method for three-dimensional estimation of particle size distribution from observations in two dimensions and its application.

PubMed

Xu, Yi-Hua; Pitot, Henry C

2003-09-01

Single enzyme-altered hepatocytes; altered hepatic foci (AHF); and nodular lesions have been implicated, respectively in the processes of initiation, promotion, and progression in rodent hepatocarcinogenesis. Qualitative and quantitative analyses of such lesions have been utilized both to identify and to determine the potency of initiating, promoting, and progressor agents in rodent liver. Of a number of possible parameters determined in the study of such lesions, estimation of the number of foci or nodules in the liver is very important. The method of Saltykov has been used for estimating the number of AHF in rat liver. However, in practice, the Saltykov calculation has at least two weak points: (a) the size class range is limited to 12, which in many instances is too narrow to cover the range of AHF data obtained; and (b) under some conditions, the Saltykov equation generates negative values in several size classes, an obvious impossibility in the real world. In order to overcome these limitations in the Saltykov calculations, a study of the particle size distribution in a wide-range, polydispersed sphere system was performed. A stereologic method, termed the 25F Association method, was developed from this study. This method offers 25 association factors that are derived from the frequency of different-sized transections obtained from transecting a spherical particle, thus expanding the size class range to be analyzed up to 25, which is sufficiently wide to encompass all rat AHF found in most cases. This method exhibits greater flexibility, which allows adjustments to be made within the calculation process when NA((k,k)), the net number of transections from the same size spheres, was found to be a negative value, which is not possible in real situations. The reliability of the 25F Association method was tested thoroughly by computer simulation in both monodispersed and polydispersed sphere systems. The test results were compared with the original Saltykov method. We found that the 25F Association method yielded a better estimate of the total number of spheres in the three-dimensional tissue sample as well as the detailed size distribution information. Although the 25F Association method was derived from the study of a polydispersed sphere system, it can be used for continuous size distribution sphere systems. Application of this method to the estimation of parameters of preneoplastic foci in rodent liver is presented as an example of its utility. An application software program, 3D_estimation.exe, which uses the 25F Association method to estimate the number of AHF in rodent liver, has been developed and is now available at the website of this laboratory.

Comparison of FibroTest-ActiTest with histopathology in demonstrating fibrosis and necroinflammatory activity in chronic hepatitis B and C.

PubMed

Uyar, Cemile; Akcam, Fusun Zeynep; Ciris, Metin; Kaya, Onur; Kockar, Cem; Isler, Mehmet

2010-01-01

FibroTest and ActiTest are noninvasive tests used in determining the level of fibrosis and the degree of necroinflammatory activity in the liver. In our study, we aimed to investigate whether these tests could be alternative to liver biopsy. Fifty patients were included in the study. Serum samples were obtained and liver needle biopsy was performed on the same day. Levels of fibrosis in FibroTest and levels of activity in ActiTest, both determined via serum biochemical markers, were compared with levels of fibrosis and activity in histopathological examination. For statistical analyses, Mc Nemar chi square test and Spearman's correlation tests were used. There was a significant positive correlation between fibrosis in biopsy and the level of fibrosis in FibroTest in patients with hepatitis B virus (HBV) (rho: 0.67, P < 0.0001). However, no significant correlation was determined between the activity in biopsy and the degree of activity in ActiTest (rho: 0.29, P < 0.05). No significant correlation was determined between both fibrosis and activity established in biopsy and the results of FibroTest and ActiTest in the group of patients with hepatitis C virus (HCV) (rho: 0.22, P < 0.05 and rho: 0.15, P < 0.05, respectively). Our results suggest that novel and safer noninvasive biochemical tests are needed as an alternative to histopathology in patients infected with HBV and HCV. Consequently, we believe that liver biopsy maintains its place as a gold standard in determining the histopathological condition of the liver.

Rating of CCl(4)-induced rat liver fibrosis by blood serum glycomics.

PubMed

Desmyter, Liesbeth; Fan, Ye-Dong; Praet, Marleen; Jaworski, Tomasz; Vervecken, Wouter; De Hemptinne, Bernard; Contreras, Roland; Chen, Cuiying

2007-07-01

Non-invasive staging of human liver fibrosis is a desirable objective that remains under extensive evaluation. Animal model systems are often used for studying human liver disease and screening antifibrotic compounds. The aim of the present study was to investigate the potential use of serum N-glycan profiles to evaluate liver fibrosis in a rat model. Liver fibrosis and cirrhosis were induced in rats by oral administration of CCl(4). Liver injury was assessed biochemically (alanine aminotransferase [ALT] activity, aspartate aminotransferase [AST] activity and total bilirubin) and histologically. The N-glycan profile (GlycoTest) was performed using DNA sequencer-assisted-fluorophore-assisted carbohydrate electrophoresis technology. In parallel, the effect of cotreatment with antifibrotic interferon-gamma (IFN-gamma) was studied. The biopsy scoring system showed that CCl(4) induced early fibrosis (F < 1-2) in rats after 3 weeks of treatment, and cirrhosis (F4) after 12 weeks. Significant increases in ALT activity, AST activity and total bilirubin levels were detected only after 12 weeks of CCl(4) treatment. GlycoTest showed three glycans were significantly altered in the CCl(4)-goup. Peak 3 started at week 6, at an early stage in fibrosis development (F < 1-2), whereas peaks 4 and 5 occurred at week 9, at which time mild liver fibrosis (F = 1-2) had developed. The changes in the CCl(4)-IFN-gamma group were intermediate between the CCl(4)- and the control groups. The GlycoTest is much more sensitive than biochemical tests for evaluating liver fibrosis/cirrhosis in the rat model. The test can also be used as a non-invasive marker for screening and monitoring the antifibrotic activity of potential therapeutic compounds.

A new veno-venous bypass type for ex-vivo liver resection in dogs.

PubMed

Lei, Peng; Liu, Shi-Qi; Cui, Xiao-Hai; Lv, Yi; Zhao, Ge; Li, Jian-Hui

2013-08-01

Ex-vivo liver resection is a procedure in which the liver is completely removed, perfused and after bench surgery, the liver is autotransplanted to the original site. Ex-vivo liver resection is an important treatment for unresectable liver tumors. This surgical procedure requires long operation time, during which blood flow must be carefully maintained to avoid venous congestion. An effective veno-venous bypass (VVB) may meet this requirement. The present study was to test our new designed VVB device which comprised one heparinized polyvinylchloride tube and three magnetic rings. The efficacy of this device was tested in five dogs. A VVB was established in 6-10 minutes. There was no leakage during the procedure. Hemodynamics was stable at anhepatic phase, which indicated that the bypass was successful. This newly-developed VVB device maintained circulation stability during ex-vivo liver resection in our dog model and thus, this VVB device significantly shortened the operation time.

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

PubMed

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

2018-03-01

Liver fibrosis (LF) is a chronic disease, associated with many collateral diseases including reproductive dysfunction. Although the normal liver has a large regenerative capacity the complications of LF could be severe and irreversible. Hormone and sex-related issues of LF development and interactions with male reproductive have not been finally studied. The aim was to study the reproductive function of male rats in experimental CCl 4 -induced liver fibrosis rat model, and the capability for restoration of both the liver and male reproduction system. Studies were conducted on 20 3-month old Wistar male rats. The experimental animals were injected with freshly prepared 50% olive oil solution of carbohydrate tetrachloride (CCl 4 ). On the 8th week after injection we noted the manifestations of liver fibrosis. The rats were left to self-healing of the liver for 8 weeks. All male rats underwent ultrasound and biopsy of the liver and testes on the 8th and 16th weeks. The male rats were mated with healthy females before CCl 4 injection, after modeling LF on the 8th week, and after self-healing of the liver. Pregnancy was monitored on ultrasound. On the 8th week of experiment we observed ultrasound manifestation of advanced liver fibrosis, including hepatosplenomegaly, portal hypertension. Ultrasound exam of the rat testes showed testicular degeneration, hydrocele, fibrosis, scarring, petrifications, size reduction, and restriction of testicular descent; testes size decreased from 1.24 ± 0.62 ml to 0.61 ± 0.13, p  < 0.01. Liver histology showed granular dystrophy of hepatocytes, necrotic areas, lipid inclusions in parenchyma. Rats with liver fibrosis demonstrated severe injury of the reproductive system and altering of fertility: the offspring of male rats with advanced LF was 4.71 ± 0.53 born alive vs 9.55 ± 0.47 born from mating with healthy males, p  < 0.001. Eight weeks after last CCl 4 injection, we revealed signs of liver regeneration, significant recovery of its structure. The ALT and AST levels significantly decreased and reached background measurements. As a result of the second interbreeding after liver self-healing no significant difference was found vs previous mating. Carbohydrate tetrachloride induces injury of liver parenchyma evoking fast and severe liver fibrosis, and is associated with irreversible structural and functional changes in testes, reducing fertility, decreasing potential pregnancy rate, and affecting its development. Liver showed high potential to regenerate, however the self-restoring after liver fibrosis was not accompanied with recovery of the reproductive system.

Application of an in silico liver model to determine nuclear receptor mediated pathways in liver cancer

EPA Science Inventory

Nuclear receptors (NRs) are ligand-activated transcription factors that control diverse cellular processes. Chronic stimulation of some NRs in rodents can result in increased incidence of liver tumors. These are generally thought to develop through a non-genotoxic mechanism with...

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.

Toxicology of a Peruvian botanical remedy to support healthy liver function.

PubMed

Semple, Hugh A; Sloley, B Duff; Cabanillas, José; Chiu, Andrea; Aung, Steven K H; Green, Francis H Y

2016-06-01

The purpose of these studies was to determine the safety of a botanical treatment for supporting healthy liver function developed in Peru. The formulation, A4+, contains extracts of Curcuma longa L. rhizome (A4R), Cordia lutea Lam. flower (A4F) and Annona muricata L. leaf (A4L). The tests were used to support an application for a non-traditional Natural Health Product Licence from the Natural Health Product Directorate of Health Canada and future clinical trials. Besides reviewing the scientific and clinical information from Peru on the ingredients and conducting an initial Ames test for mutagenicity, we analysed A4+ for its chemical profile and tested genotoxicity (micronucleus test) and general toxicity (28-day repeated dose). A4+ and extracts from the three plants provided distinctive chemical fingerprints. A4L contained acetogenins, requiring a second chromatographic method to produce a specific fingerprint. The Ames test proved positive at the highest concentration (5,000 μg/mL) but A4+ showed no evidence of genotoxicity in the more specific mouse micronucleus test. The 28-day repeated dose (general toxicity) study in rats showed no toxicity at 2,000 mg/kg. We conclude that under the conditions of these studies, A4+ shows no evidence of toxicity at the levels indicated. A no observed adverse effect level (NOAEL) of 2,000 mg/kg was assigned.

13C-methacetin and 13C-galactose breath tests can assess restricted liver function even in early stages of primary biliary cirrhosis.

PubMed

Holtmeier, Julia; Leuschner, Maria; Schneider, Arne; Leuschner, Ulrich; Caspary, Wolfgang F; Braden, Barbara

2006-11-01

The 13C-methacetin breath test quantitatively evaluates cytochrome P450-dependent liver function. The 13C-galactose breath test non-invasively measures the galactose oxidation capacity of the liver. The aim of this study was to find out whether these breath tests are sensitive parameters also in non-cirrhotic patients with primary biliary cirrhosis. Nineteen patients with early-stage primary biliary cirrhosis (no cirrhotic alterations in the liver biopsy, Ludwig stage I-III) and 20 healthy controls underwent the 13C-methacetin and 13C-galactose breath tests. Patients with primary biliary cirrhosis metabolized less 13C-methacetin than controls (cumulative recovery within 30 min 7.5+/-2.4% versus 14.0+/-2.6%; p < 0.001). When a cut-off > 9.8% was used for the cumulative recovery after 30 min, the methacetin breath test reached 84.2% sensitivity and 95.0 specificity. In the 13C-galactose breath test, the percentage recovery at 60 min in patients was 3.1+/-1.3%/h, and 6.3+/-1.1%/h in controls (p < 0.001). Using a cut-off > 4.7%/h, the galactose breath test reached 89.5% sensitivity and 95.0 specificity. In non-cirrhotic, early-stage, primary biliary cirrhosis the 13C-methacetin breath test and the 13C-galactose breath test reliably indicate decreased liver function. The 13C-galactose breath test can also predict the histological score.

Corticosteroid therapy in a case of severe cholestasic hepatitis associated with amoxicillin-clavulanate.

PubMed

Herrero-Herrero, José-Ignacio; García-Aparicio, Judit

2010-12-01

Amoxicillin-clavulanate is the most common drug involved in drug-induced liver injury and the single most frequently prescribed product leading to hospitalization for drug-induced liver disease in Spain. The liver damage most frequently associated with amoxicillin-clavulanate is cholestasic type. The latency period between first intake and onset of symptoms is 3-4 weeks on average. A 76-year-old man developed fever, pruritus, and jaundice 3 weeks after having completed treatment with amoxicillin-clavulanate. Liver function tests showed cholestasic hepatitis (up to 50.75 mg/dL of total serum bilirubin level). The ultrasound-guided liver biopsy revealed severe canalicular cholestasis and portal and lobular eosinophilic infiltrates. Prednisone and ursodeoxycholic acid therapy were then prescribed. The patient became symptom-free with normal liver function tests. Amoxicillin-clavulanate can cause hepatocellular, cholestasic, or mixed liver injury. The presence of eosinophilic infiltrates in the liver biopsy and the clinical signs of hypersensitivity in some of the cholestasic cases suggest a pathophysiological immunoallergic mechanism. For this reason, corticosteroid treatment should be considered for patients with severe cholestasic liver injury.

Unraveling cellular pathways contributing to drug-induced liver injury by dynamical modeling.

PubMed

Kuijper, Isoude A; Yang, Huan; Van De Water, Bob; Beltman, Joost B

2017-01-01

Drug-induced liver injury (DILI) is a significant threat to human health and a major problem in drug development. It is hard to predict due to its idiosyncratic nature and which does not show up in animal trials. Hepatic adaptive stress response pathway activation is generally observed in drug-induced liver injury. Dynamical pathway modeling has the potential to foresee adverse effects of drugs before they go in trial. Ordinary differential equation modeling can offer mechanistic insight, and allows us to study the dynamical behavior of stress pathways involved in DILI. Areas covered: This review provides an overview on the progress of the dynamical modeling of stress and death pathways pertinent to DILI, i.e. pathways relevant for oxidative stress, inflammatory stress, DNA damage, unfolded proteins, heat shock and apoptosis. We also discuss the required steps for applying such modeling to the liver. Expert opinion: Despite the strong progress made since the turn of the century, models of stress pathways have only rarely been specifically applied to describe pathway dynamics for DILI. We argue that with minor changes, in some cases only to parameter values, many of these models can be repurposed for application in DILI research. Combining both dynamical models with in vitro testing might offer novel screening methods for the harmful side-effects of drugs.

Radiation-force-based estimation of acoustic attenuation using harmonic motion imaging (HMI) in phantoms and in vitro livers before and after HIFU ablation

NASA Astrophysics Data System (ADS)

Chen, Jiangang; Hou, Gary Y.; Marquet, Fabrice; Han, Yang; Camarena, Francisco; Konofagou, Elisa

2015-10-01

Acoustic attenuation represents the energy loss of the propagating wave through biological tissues and plays a significant role in both therapeutic and diagnostic ultrasound applications. Estimation of acoustic attenuation remains challenging but critical for tissue characterization. In this study, an attenuation estimation approach was developed using the radiation-force-based method of harmonic motion imaging (HMI). 2D tissue displacement maps were acquired by moving the transducer in a raster-scan format. A linear regression model was applied on the logarithm of the HMI displacements at different depths in order to estimate the acoustic attenuation. Commercially available phantoms with known attenuations (n=5 ) and in vitro canine livers (n=3 ) were tested, as well as HIFU lesions in in vitro canine livers (n=5 ). Results demonstrated that attenuations obtained from the phantoms showed a good correlation ({{R}2}=0.976 ) with the independently obtained values reported by the manufacturer with an estimation error (compared to the values independently measured) varying within the range of 15-35%. The estimated attenuation in the in vitro canine livers was equal to 0.32   ±   0.03 dB cm-1 MHz-1, which is in good agreement with the existing literature. The attenuation in HIFU lesions was found to be higher (0.58   ±   0.06 dB cm-1 MHz-1) than that in normal tissues, also in agreement with the results from previous publications. Future potential applications of the proposed method include estimation of attenuation in pathological tissues before and after thermal ablation.

Radiation-force-based estimation of acoustic attenuation using harmonic motion imaging (HMI) in phantoms and in vitro livers before and after HIFU ablation.

PubMed

Chen, Jiangang; Hou, Gary Y; Marquet, Fabrice; Han, Yang; Camarena, Francisco; Konofagou, Elisa

2015-10-07

Acoustic attenuation represents the energy loss of the propagating wave through biological tissues and plays a significant role in both therapeutic and diagnostic ultrasound applications. Estimation of acoustic attenuation remains challenging but critical for tissue characterization. In this study, an attenuation estimation approach was developed using the radiation-force-based method of harmonic motion imaging (HMI). 2D tissue displacement maps were acquired by moving the transducer in a raster-scan format. A linear regression model was applied on the logarithm of the HMI displacements at different depths in order to estimate the acoustic attenuation. Commercially available phantoms with known attenuations (n = 5) and in vitro canine livers (n = 3) were tested, as well as HIFU lesions in in vitro canine livers (n = 5). Results demonstrated that attenuations obtained from the phantoms showed a good correlation (R² = 0.976) with the independently obtained values reported by the manufacturer with an estimation error (compared to the values independently measured) varying within the range of 15-35%. The estimated attenuation in the in vitro canine livers was equal to 0.32   ±   0.03 dB cm(-1) MHz(-1), which is in good agreement with the existing literature. The attenuation in HIFU lesions was found to be higher (0.58   ±   0.06 dB cm(-1) MHz(-1)) than that in normal tissues, also in agreement with the results from previous publications. Future potential applications of the proposed method include estimation of attenuation in pathological tissues before and after thermal ablation.

Weight loss and severe jaundice in a patient with hyperthyroidism.

PubMed

Breidert, M; Offensperger, S; Blum, H E; Fischer, R

2011-09-01

Thyrotoxicosis may significantly alter hepatic function and is associated with autoimmune disorders of the liver. We report the case of a thyrotoxic patient with Graves' disease and histologically established cholestatic hepatitis. Medical treatment of hyperthyroidism normalized liver function tests. In patients with elevated liver function parameters and jaundice of unknown origin, thyroid function should generally be tested. Moreover, medical treatment of hyperthyroidism with thyrostatics may cause severe hepatitis whereas untreated hyperthyroid patients are at risk of developing chronic liver failure. © Georg Thieme Verlag KG Stuttgart · New York.

Alpha fetoprotein - series (image)

MedlinePlus

... normal levels of AFP may be due to: Cancer in testes, ovaries, biliary (liver secretion) tract, stomach, or pancreas Cirrhosis of the liver Liver cancer Malignant teratoma Recovery from hepatitis Problems during pregnancy ...

Physical activity as a protective factor for development of non-alcoholic fatty liver in men

PubMed Central

Pinto, Carla Giuliano de Sá; Marega, Marcio; de Carvalho, José Antonio Maluf; Carmona, Felipe Gambetta; Lopes, Carlos Eduardo Felix; Ceschini, Fabio Luis; Bocalini, Danilo Sales; Figueira, Aylton José

2015-01-01

Objective To determine the impact of physical activity on the prevalence of fatty liver, metabolic and cardiovascular disease in adult men. Methods This study evaluated 1,399 men (40.7±8.18 years) with body mass index of 26.7kg/m2 (±3.4) who participated in the Protocol of Preventive Health Check-up at Hospital Israelita Albert Einstein from January to October 2011. We conducted tests of serum blood glucose, total cholesterol, LDL, HDL, triglycerides, reactive c-protein, aspartate transaminase, alanine transaminase and gamma-glutamyl transpeptidase. The statistical analysis comprised in the comparison of mean and standard deviation. The analysis of variance was based in two paths of two way ANOVA, Student’s t-test, Mann Whitney U test, Wald test and χ2. We considered a significance level at p<0.05 and correlation of univariate Poison with 95% confidence interval. Results :Fatty liver was diagnosed in 37.0% of the sample. Triglyceride levels of active men with fatty liver were 148.2±77.6mg/dL while inactive men with fatty liver had 173.4±15.6mg/dL. The remaining serum levels were normal. Inactive individuals showed higher values than active. In addition, inactive individuals have 10.68 times higher risk of developing fatty liver compared with active. Conclusion Physical activity improves metabolic parameters such as triglycerides, weight control, HDL, which interfere in the development of fatty liver. Physically active individuals had lower fatty liver prevalence regardless of values of body composition and lipid profile, leading the conclusion that physical activity has a protective role against development of fatty liver. PMID:25993066

Non-invasive assessment of liver fibrosis

PubMed Central

Papastergiou, Vasilios; Tsochatzis, Emmanuel; Burroughs, Andrew K.

2012-01-01

The presence and degree of hepatic fibrosis is crucial in order to make therapeutic decisions and predict clinical outcomes. Currently, the place of liver biopsy as the standard of reference for assessing liver fibrosis has been challenged by the increasing awareness of a number of drawbacks related to its use (invasiveness, sampling error, inter-/intraobserver variability). In parallel with this, noninvasive assessment of liver fibrosis has experienced explosive growth in recent years and a wide spectrum of noninvasive methods ranging from serum assays to imaging techniques have been developed. Some are validated methods, such as the Fibrotest/ Fibrosure and transient elastography in Europe, and are gaining a growing role in routine clinical practice, especially in chronic hepatitis C. Large-scale validation is awaited in the setting of other chronic liver diseases. However, noninvasive tests used to detect significant fibrosis and cirrhosis, the two major clinical endpoints, are not yet at a level of performance suitable for routine diagnostic tests, and there is still no perfect surrogate or method able to completely replace an optimal liver biopsy. This article aims to review current noninvasive tests for the assessment of liver fibrosis and the perspectives for their rational use in clinical practice. PMID:24714123

Proliferative human cell sources applied as biocomponent in bioartificial livers: a review.

PubMed

Nibourg, Geert A A; Chamuleau, Robert A F M; van Gulik, Thomas M; Hoekstra, Ruurdtje

2012-07-01

Bioartificial livers (BALs) are urgently needed to bridge severe liver failure patients to liver transplantation or liver regeneration. When based on primary hepatocytes, their efficacy has been shown in animal experiments and their safety was confirmed in clinical trials. However, a proliferative human cell source with therapeutic functionality is needed to secure availability and move BAL application forward. This review compares the performance of BALs based on proliferative human biocomponents and primary hepatocytes. This review evaluates relevant studies identified by searching the MEDLINE database until July 2011 and some of our own unpublished data. All the discussed hepatocyte-like biocomponents show deficiencies in their hepatic functionality compared with primary hepatocytes, particularly functions occurring late in liver development. Nonetheless, the HepaRG, HepG2-GS-CYP3A4, and mesenchymal stem cells show efficacy in a statistically well-powered animal model of acute liver failure, when applied in a BAL device. Various methods to gain higher functionality of BALs, including genetic modification, the usage of combinatory cell sources, and improvement of culture methods, have scarcely been applied, but may further pave the path for BAL application. Clinical implementation of a BAL based on a human proliferative biocomponent is still several years away.

Muscular exercise can cause highly pathological liver function tests in healthy men

PubMed Central

Pettersson, Jonas; Hindorf, Ulf; Persson, Paula; Bengtsson, Thomas; Malmqvist, Ulf; Werkström, Viktoria; Ekelund, Mats

2008-01-01

Aim To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men. Methods Fifteen healthy men, used to moderate physical activity not including weightlifting, performed an 1 h long weightlifting programme. Blood was sampled for clinical chemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), gamma-glutamyl transferase (γGT), alkaline phosphatase (ALP), bilirubin, creatine kinase (CK) and myoglobin] at repeated intervals during 7 days postexercise and at a follow-up examination 10–12 days postexercise. Results Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P < 0.01) and remained increased for at least 7 days postexercise. Bilirubin, γGT and ALP remained within the normal range. Conclusion The liver function parameters, AST and ALT, were significantly increased for at least 7 days after the exercise. In addition, LD and, in particular, CK and myoglobin showed highly elevated levels. These findings highlight the importance of imposing restrictions on weightlifting prior to and during clinical studies. Intensive muscular exercise, e.g. weightlifting, should also be considered as a cause of asymptomatic elevations of liver function tests in daily clinical practice. What is already known about this subject The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the leading cause of postmarketing warnings and withdrawals.Physical exercise can result in transient elevations of liver function tests.There is no consensus in the literature on which forms of exercise may cause changes in liver function tests and to what extent. What this study adds Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including weightlifting.Liver function tests are significantly increased for at least 7 days after weightlifting.It is important to impose relevant restrictions on heavy muscular exercise prior to and during clinical studies. PMID:17764474

Muscular exercise can cause highly pathological liver function tests in healthy men.

PubMed

Pettersson, Jonas; Hindorf, Ulf; Persson, Paula; Bengtsson, Thomas; Malmqvist, Ulf; Werkström, Viktoria; Ekelund, Mats

2008-02-01

The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the leading cause of postmarketing warnings and withdrawals. Physical exercise can result in transient elevations of liver function tests. There is no consensus in the literature on which forms of exercise may cause changes in liver function tests and to what extent. Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including weightlifting. Liver function tests are significantly increased for at least 7 days after weightlifting. It is important to impose relevant restrictions on heavy muscular exercise prior to and during clinical studies. To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men. Fifteen healthy men, used to moderate physical activity not including weightlifting, performed an 1 h long weightlifting programme. Blood was sampled for clinical chemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), gamma-glutamyl transferase (gamma GT), alkaline phosphatase (ALP), bilirubin, creatine kinase (CK) and myoglobin] at repeated intervals during 7 days postexercise and at a follow-up examination 10-12 days postexercise. Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P < 0.01) and remained increased for at least 7 days postexercise. Bilirubin, gamma GT and ALP remained within the normal range. The liver function parameters, AST and ALT, were significantly increased for at least 7 days after the exercise. In addition, LD and, in particular, CK and myoglobin showed highly elevated levels. These findings highlight the importance of imposing restrictions on weightlifting prior to and during clinical studies. Intensive muscular exercise, e.g. weightlifting, should also be considered as a cause of asymptomatic elevations of liver function tests in daily clinical practice.

Indocyanine green plasma disappearance rate during the anhepatic phase of orthotopic liver transplantation.

PubMed

Bruegger, Lukas; Studer, Peter; Schmid, Stefan W; Pestel, Gunther; Reichen, Juerg; Seiler, Christian; Candinas, Daniel; Inderbitzin, Daniel

2008-01-01

Non-invasive pulse spectrophotometry to measure indocyanine green (ICG) elimination correlates well with the conventional invasive ICG clearance test. Nevertheless, the precision of this method remains unclear for any application, including small-for-size liver remnants. We therefore measured ICG plasma disappearance rate (PDR) during the anhepatic phase of orthotopic liver transplantation using pulse spectrophotometry. Measurements were done in 24 patients. The median PDR after exclusion of two outliers and two patients with inconstant signal was 1.55%/min (95% confidence interval [CI]=0.8-2.2). No correlation with patient age, gender, body mass, blood loss, administration of fresh frozen plasma, norepinephrine dose, postoperative albumin (serum), or difference in pre and post transplant body weight was detected. In conclusion, we found an ICG-PDR different from zero in the anhepatic phase, an overestimation that may arise in particular from a redistribution into the interstitial space. If ICG pulse spectrophotometry is used to measure functional hepatic reserve, the verified average difference from zero (1.55%/min) determined in our study needs to be taken into account.

[Contrast-enhanced ultrasound (CEUS) and image fusion for procedures of liver interventions].

PubMed

Jung, E M; Clevert, D A

2018-06-01

Contrast-enhanced ultrasound (CEUS) is becoming increasingly important for the detection and characterization of malignant liver lesions and allows percutaneous treatment when surgery is not possible. Contrast-enhanced ultrasound image fusion with computed tomography (CT) and magnetic resonance imaging (MRI) opens up further options for the targeted investigation of a modified tumor treatment. Ultrasound image fusion offers the potential for real-time imaging and can be combined with other cross-sectional imaging techniques as well as CEUS. With the implementation of ultrasound contrast agents and image fusion, ultrasound has been improved in the detection and characterization of liver lesions in comparison to other cross-sectional imaging techniques. In addition, this method can also be used for intervention procedures. The success rate of fusion-guided biopsies or CEUS-guided tumor ablation lies between 80 and 100% in the literature. Ultrasound-guided image fusion using CT or MRI data, in combination with CEUS, can facilitate diagnosis and therapy follow-up after liver interventions. In addition to the primary applications of image fusion in the diagnosis and treatment of liver lesions, further useful indications can be integrated into daily work. These include, for example, intraoperative and vascular applications as well applications in other organ systems.

[Medical assessments and measurements in ELSA-Brasil].

PubMed

Mill, Jose Geraldo; Pinto, Karina; Griep, Rosane Härter; Goulart, Alessandra; Foppa, Murilo; Lotufo, Paulo A; Maestri, Marcelo K; Ribeiro, Antonio Luiz; Andreão, Rodrigo Varejão; Dantas, Eduardo Miranda; Oliveira, Ilka; Fuchs, Sandra C; Cunha, Roberto de Sá; Bensenor, Isabela M

2013-06-01

The article describes assessments and measurements performed in the Brazilian Longitudinal Study for Adult Health (ELSA-Brasil). Some assessments including anthropometric assessment, casual blood pressure measurement, and ankle-brachial index have an established clinical application while others including pulse wave velocity, heart rate variability, and carotid intima-media thickness have no established application and do not have reference values for healthy Brazilian population but may be important predictors of cardiovascular outcomes. Blood pressure measurement following postural change maneuver was included in the ELSA-Brasil because it has not been much tested in epidemiological studies. Innovative approaches were developed for assessing the ankle-brachial index using an automatic device instead of the mercury column to measure blood pressure and for assessing the anterior-posterior diameter of the right lobe of the liver by ultrasound for quantitative assessment of nonalcoholic fatty liver disease. All ELSA-Brasil subjects were younger (35 years or more) than those included in other cohorts studying subclinical atherosclerosis. The inclusion of younger individuals and a variety of assessments make the ELSA-Brasil a relevant epidemiology study nationwide and worldwide.

Delivery of RNAi reagents in murine models of obesity and diabetes.

PubMed

Wilcox, Denise M; Yang, Ruojing; Morgan, Sherry J; Nguyen, Phong T; Voorbach, Martin J; Jung, Paul M; Haasch, Deanna L; Lin, Emily; Bush, Eugene N; Opgenorth, Terry J; Jacobson, Peer B; Collins, Christine A; Rondinone, Cristina M; Surowy, Terry; Landschulz, Katherine T

2006-11-29

RNA interference (RNAi) is an exciting new tool to effect acute in vivo knockdown of genes for pharmacological target validation. Testing the application of this technology to metabolic disease targets, three RNAi delivery methods were compared in two frequently utilized preclinical models of obesity and diabetes, the diet-induced obese (DIO) and B6.V-Lep/J (ob/ob) mouse. Intraperitoneal (i.p.) and high pressure hydrodynamic intravenous (i.v.) administration of naked siRNA, and low pressure i.v. administration of shRNA-expressing adenovirus were assessed for both safety and gene knockdown efficacy using constructs targeting cJun N-terminal kinase 1 (JNK1). Hydrodynamic delivery of siRNA lowered liver JNK1 protein levels 40% in DIO mice, but was accompanied by iatrogenic liver damage. The ob/ob model proved even more intolerant of this technique, with hydrodynamic delivery resulting in severe liver damage and death of most animals. While well-tolerated, i.p. injections of siRNA in DIO mice did not result in any knockdown or phenotypic changes in the mice. On the other hand, i.v. injected adenovirus expressing shRNA potently reduced expression of JNK1 in vivo by 95% without liver toxicity. In conclusion, i.p. and hydrodynamic injections of siRNA were ineffective and/or inappropriate for in vivo gene targeting in DIO and ob/ob mice, while adenovirus-mediated delivery of shRNA provided a relatively benign and effective method for exploring liver target silencing.

Development of experimental fibrotic liver diseases animal model by Carbon Tetracholoride.

PubMed

Gitiara, Atoosa; Tokhanbigli, Samaneh; Mazhari, Sogol; Baghaei, Kaveh; Hatami, Behzad; Hashemi, Seyed Mahmoud; Asadi Rad, Ali; Moradi, Afshin; Nasiri, Meyam; Zarrabi Ahrabi, Nakisa; Zali, Mohammad Reza

2017-01-01

This study is presenting an effective method of inducing liver fibrosis by CCL4 as a toxin in two different breeds of rat models. Liver fibrosis is a result of inflammation and liver injury caused by wound healing responses which ultimately lead to liver failure. Consequently, after liver fibrosis, the progression will be continued to liver cirrhosis and at the end stage hepatocellular carcinoma (HCC). Many studies have demonstrated that one of the most important causes of liver fibrosis is Non-alcoholic steatohepatitis (NASH). Fibrotic Liver is affected by an excessive accumulation of extracellular matrix (ECM) proteins like collagen and α-SMA. In two different experiments, male Vistar, and Sprague Dawley Rat models ranging from 200±60, corresponding to an age of approximately 10 weeks were utilized in order to induce CCL4 treated liver fibrosis. After 6 weeks of CCL4 injection, different tests have been carried out to verify the liver fibrosis including serum markers such as Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT), molecular tests containing, laminin and α-SMA and also pathological observation by Hematoxylin and eosin staining in both fibrosis and control group. The results of Pathology and Real-time PCR showed that fibrosis was induced much more effectively in Sprague Dawley rat model compared with Wistar rats.

Impact of UCSF criteria according to pre- and post-OLT tumor features: analysis of 479 patients listed for HCC with a short waiting time.

PubMed

Decaens, Thomas; Roudot-Thoraval, Françoise; Hadni-Bresson, Solange; Meyer, Carole; Gugenheim, Jean; Durand, Francois; Bernard, Pierre-Henri; Boillot, Olivier; Sulpice, Laurent; Calmus, Yvon; Hardwigsen, Jean; Ducerf, Christian; Pageaux, Georges-Philippe; Dharancy, Sebastien; Chazouilleres, Olivier; Cherqui, Daniel; Duvoux, Christophe

2006-12-01

Orthotopic liver transplantation (OLT) indication for hepatocellular carcinoma (HCC) is currently based on the Milan criteria. The University of California, San Francisco (UCSF) recently proposed an expansion of the selection criteria according to tumors characteristics on the explanted liver. This study: 1) assessed the validity of these criteria in an independent large series and 2) tested for the usefulness of these criteria when applied to pre-OLT tumor evaluation. Between 1985 and 1998, 479 patients were listed for liver transplantation (LT) for HCC and 467 were transplanted. According to pre-OLT (imaging at date of listing) or post-OLT (explanted liver) tumor characteristics, patients were retrospectively classified according to both the Milan and UCSF criteria. The 5-yr survival statistics were assessed by the Kaplan-Meier method and compared by the log-rank test. Pre-OLT UCSF criteria were analyzed according to an intention-to-treat principle. Based on the pre-OLT evaluation, 279 patients were Milan+, 44 patients were UCSF+ but Milan- (subgroup of patients that might benefit from the expansion), and 145 patients were UCSF- and Milan-. With a short median waiting time of 4 months, 5-yr survival was 60.1 +/- 3.0%, 45.6 +/- 7.8%, and 34.7 +/- 4.0%, respectively (P < 0.001). The 5-yr survival was arithmetically lower in UCSF+ Milan- patients compared to Milan+ but this difference was not significant (P = 0.10). Based on pathological features of the explanted liver, 5-yr survival was 70.4 +/- 3.4%, 63.6 +/- 7.8%, and 34.1 +/- 3.1%, in Milan+ patients (n = 184), UCSF+ Milan- patients (n = 39), and UCSF- Milan- patients (n = 238), respectively (P < 0.001). However, the 5-yr survival did not differ between Milan+ and UCSF+ Milan- patients (P = 0.33). In conclusion, these results show that when applied to pre-OLT evaluation, the UCSF criteria are associated with a 5-yr survival below 50%. Their applicability is therefore limited, despite similar survival rates compared to the Milan criteria, when the explanted liver is taken into account.

Thallium-201 per rectum for the diagnosis of cirrhosis in patients with asymptomatic chronic hepatitis

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

D'Arienzo, A.; Celentano, L.; Scuotto, A.

1988-07-01

In normal subjects, thallium-201, administered per rectum, is taken up mainly by the liver (heart/liver ratio in normal subjects: 0.04 to 0.12). It has been claimed that an increased heart/liver ratio is suggestive of portal-caval shunting and portal hypertension. To evaluate the possibility of using thallium-201 as a test to diagnose cirrhosis, we administered this substance per rectum to 33 patients with biochemical evidence, but no clinical symptoms, of liver disease. Laparoscopy and liver biopsy revealed chronic active hepatitis without cirrhosis in 18 patients, and chronic active hepatitis with cirrhosis in the others. The results of conventional liver function testsmore » were similar in both groups. A significant difference, however, was found between the means of fasting serum bile acid concentrations (9.8 +/- 3.2 and 18.3 +/- 4.2 microM per liter) in chronic active hepatitis without cirrhosis and cirrhotic patients, and between the means of the heart/liver ratios 20 min after thallium-201 administration (heart/liver: 0.09 +/- 0.03 and 0.54 +/- 0.13, respectively). Unlike the serum bile acid concentration which gave some overlapping values, the thallium-201 test clearly distinguished the chronic active hepatitis without cirrhosis group from the cirrhotics. In the cirrhotic group, there was a significant correlation between the heart/liver ratio and signs of portal hypertension such as esophageal varices, increased diameter of the vena porta and hypersplenism. The thallium-201 test is therefore useful in discriminating between chronic active hepatitis with and without cirrhosis in clinically asymptomatic subjects with biochemical evidence of moderate liver function impairment. A heart/liver uptake ratio much higher than normal (above 0.30) strongly suggests the development of hepatic cirrhosis.« less

Japanese quail acute exposure to methamidophos: experimental design, lethal, sub-lethal effects and cholinesterase biochemical and histochemical expression.

PubMed

Foudoulakis, Manousos; Balaskas, Christos; Csato, Attila; Szentes, Csaba; Arapis, Gerassimos

2013-04-15

We exposed the Japanese quail (Coturnix coturnix japonica) to the organophosphate methamidophos using acute oral test. Mortality and sub-lethal effects were recorded in accordance to internationally accepted protocols. In addition cholinesterases were biochemically estimated in tissues of the quail: brain, liver and plasma. Furthermore, brain, liver and duodenum cryostat sections were processed for cholinesterase histochemistry using various substrates and inhibitors. Mortalities occurred mainly in the first 1-2h following application. Sub-lethal effects, such as ataxia, ruffled feathers, tremor, salivation and reduced or no reaction to external stimuli were observed. Biochemical analysis in the brain, liver and plasma indicates a strong cholinesterase dependent inhibition with respect to mortality and sub-lethal effects of the quail. The histochemical staining also indicated a strong cholinesterase inhibition in the organs examined and the analysis of the stained sections allowed for an estimation and interpretation of the intoxication effects of methamidophos, in combination with tissue morphology visible by Haematoxylin and Eosin staining. We conclude that the use of biochemistry and histochemistry for the biomarker cholinesterase, may constitute a significantly novel approach for understanding the results obtained by the acute oral test employed in order to assess the effects of methamidophos and other chemicals known to inhibit this very important nervous system enzyme. Copyright © 2012 Elsevier B.V. All rights reserved.

Ultrasound Elastography and MR Elastography for Assessing Liver Fibrosis: Part 2, Diagnostic Performance, Confounders, and Future Directions

PubMed Central

Tang, An; Cloutier, Guy; Szeverenyi, Nikolaus M.; Sirlin, Claude B.

2016-01-01

OBJECTIVE The purpose of the article is to review the diagnostic performance of ultrasound and MR elastography techniques for detection and staging of liver fibrosis, the main current clinical applications of elastography in the abdomen. CONCLUSION Technical and instrument-related factors and biologic and patient-related factors may constitute potential confounders of stiffness measurements for assessment of liver fibrosis. Future developments may expand the scope of elastography for monitoring liver fibrosis and predict complications of chronic liver disease. PMID:25905762

Spectrum of pathogens in native liver, bile, and blood during pediatric liver transplantation.

PubMed

Schukfeh, Nagoud; Doerner, Judith M; Heintschel von Heinegg, Evelyn; Steinmann, Joerg; Metzelder, Martin L; Kathemann, Simone; Hoyer, Peter F; Paul, Andreas; Gerner, Patrick

2014-05-01

During LTX, there may be a risk that pathogens of the native liver are released into the systemic circulation. No investigations on incidence/spectrum of pathogens in native livers have been published. We hypothesized that pathogens are found in the native liver of a large proportion of pediatric patients during LTX and investigated the microbiology of native livers. These data may help optimize antibiotic therapy. Twenty-two consecutive pediatric patients (median age 14 months, range, 5 months-15 yr) receiving LTX in our department from October 2010 to October 2011 were included in this prospective study. Tissue and bile were collected from the explanted liver and were cultivated on different media. All liver tissues were investigated using a broad-range PCR (SepsiTest(®)). In 16 patients, blood cultures were collected post-transplantation. Eleven patients (50%) had at least one pathogen detected; nine of these patients had an underlying diagnosis of biliary atresia. SepsiTest(®) was positive in seven patients. In four patients it was the only test detecting any pathogen. In detail, the positivity rate for liver tissue in all patients was 41% (n = 9); for bile 25% (n = 3); and for blood 25% (n = 4). Thirteen different pathogens (69% bacterial, 31% fungal) were isolated. A highly-sensitive broad-range PCR appears to be an effective method to detect pathogens in native livers of patients undergoing LTX. A high number and variety of microbes, including a high proportion of fungal pathogens, were detected. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Do older patients utilize excess health care resources after liver transplantation?

PubMed

Shankar, Neil; AlBasheer, Mamoun; Marotta, Paul; Wall, William; McAlister, Vivian; Chandok, Natasha

2011-01-01

Liver transplantation is a highly effective treatment for end-stage liver disease. However, there is debate over the practice of liver transplantation in older recipients (age ≥ 60 years) given the relative shortage of donor grafts, worse post-transplantation survival, and concern that that older patients may utilize excess resources postoperatively, thus threatening the economic feasibility of the procedure. To determine if patients ≥ 60 years of age utilize more health resources following liver transplantation compared with younger patients. Consecutive adult patients who underwent primary liver transplantation (n = 208) at a single center were studied over a 2.5-year period. Data were collected on clinico-demographic characteristics and resource utilization. Descriptive statistics, including means, standard deviations, or frequencies were obtained for baseline variables. Patients were stratified into 2 groups: age ≥ 60 years (n = 51) and < 60 years (n = 157). The Chi-Square Test, Mantel-Haenszel Test, 2-sample test and odds ratios were calculated to ascertain associations between age and resource utilization parameters. Regression analyses were adjusted for model for end-stage liver disease score, location before surgery, diabetes mellitus, donor age, cold ischemia time, albumin, and diagnosis of hepatitis C. Recipients ≥ 60 years of age have similar lengths of hospitalization, re-operative rates, need for consultative services and readmission rates following liver transplantation, but have longer lengths of stay in the intensive care (hazard ratio 1.97, p = 0.03). Overall, liver transplant recipients ≥ 60 years of age utilize comparable resources following LT vs. younger recipients. Our findings have implications on cost-containment policies for liver transplantation.

Effects of purified eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: results from the Welcome* study.

PubMed

Scorletti, Eleonora; Bhatia, Lokpal; McCormick, Keith G; Clough, Geraldine F; Nash, Kathryn; Hodson, Leanne; Moyses, Helen E; Calder, Philip C; Byrne, Christopher D

2014-10-01

There is no licensed treatment for non-alcoholic fatty liver disease (NAFLD), a condition that increases risk of chronic liver disease, type 2 diabetes and cardiovascular disease. We tested whether 15-18 months treatment with docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA) (Omacor/Lovaza) (4 g/day) decreased liver fat and improved two histologically-validated liver fibrosis biomarker scores (primary outcomes). Patients with NAFLD were randomised in a double blind placebo-controlled trial [DHA+EPA(n=51), placebo(n=52)]. We quantified liver fat percentage (%) by magnetic resonance spectroscopy in three liver zones. We measured liver fibrosis using two validated scores. We tested adherence to the intervention (Omacor group) and contamination (with DHA and EPA) (placebo group) by measuring erythrocyte percentage DHA and EPA enrichment (gas chromatography). We undertook multivariable linear regression to test effects of: a) DHA+EPA treatment (ITT analyses) and b) erythrocyte DHA and EPA enrichment (secondary analysis). Median (IQR) baseline and end of study liver fat% were 21.7 (19.3) and 19.7 (18.0) (placebo), and 23.0 (36.2) and 16.3 (22.0), (DHA+EPA). In the fully adjusted regression model there was a trend towards improvement in liver fat% with DHA+EPA treatment (β=-3.64 (95%CI -8.0,0.8); p=0.1) but there was evidence of contamination in the placebo group and variable adherence to the intervention in the Omacor group. Further regression analysis showed that DHA enrichment was independently associated with a decrease in liver fat% (for each 1% enrichment, β=-1.70 (95%CI -2.9,-0.5); p=0.007). No improvement in the fibrosis scores occurred. Conclusion. Erythrocyte DHA enrichment with DHA+EPA treatment is linearly associated with decreased liver fat%. Substantial decreases in liver fat% can be achieved with high percentage erythrocyte DHA enrichment in NAFLD. (Hepatology 2014;).

Validating New Software for Semiautomated Liver Volumetry--Better than Manual Measurement?

PubMed

Noschinski, L E; Maiwald, B; Voigt, P; Wiltberger, G; Kahn, T; Stumpp, P

2015-09-01

This prospective study compared a manual program for liver volumetry with semiautomated software. The hypothesis was that the semiautomated software would be faster, more accurate and less dependent on the evaluator's experience. Ten patients undergoing hemihepatectomy were included in this IRB approved study after written informed consent. All patients underwent a preoperative abdominal 3-phase CT scan, which was used for whole liver volumetry and volume prediction for the liver part to be resected. Two different types of software were used: 1) manual method: borders of the liver had to be defined per slice by the user; 2) semiautomated software: automatic identification of liver volume with manual assistance for definition of Couinaud segments. Measurements were done by six observers with different experience levels. Water displacement volumetry immediately after partial liver resection served as the gold standard. The resected part was examined with a CT scan after displacement volumetry. Volumetry of the resected liver scan showed excellent correlation to water displacement volumetry (manual: ρ = 0.997; semiautomated software: ρ = 0.995). The difference between the predicted volume and the real volume was significantly smaller with the semiautomated software than with the manual method (33% vs. 57%, p = 0.002). The semiautomated software was almost four times faster for volumetry of the whole liver (manual: 6:59 ± 3:04 min; semiautomated: 1:47 ± 1:11 min). Both methods for liver volumetry give an estimated liver volume close to the real one. The tested semiautomated software is faster, more accurate in predicting the volume of the resected liver part, gives more reproducible results and is less dependent on the user's experience. Both tested types of software allow exact volumetry of resected liver parts. Preoperative prediction can be performed more accurately with the semiautomated software. The semiautomated software is nearly four times faster than the tested manual program and less dependent on the user's experience. © Georg Thieme Verlag KG Stuttgart · New York.

Carcinogenicity of by-products of disinfection in mouse and rat liver

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

Herren-Freund, S.L.; Pereira, M.A.

1986-11-01

By-products of disinfection were tested for initiating and/or promoting activity in rat liver by using the rat liver foci bioassay. The assay uses an increased incidence of ..gamma..-glutamyltranspeptidase-positive foci (GGT foci) as an indicator of carcinogenicity. The by-products of disinfection, including chloramine, halogenated humic acids, halogenated ethanes, halogenated acetonitriles, halogenated methanes, halogenated ethylene, and N-Cl piperidine, did not initiate GGT foci, which would indicate that they are not capable of initiating carcinogenesis. Chloroform and halogenated benzenes were tested in this assay for their ability to promote the occurrence of GGT foci and tumors initiated by diethylnitrosamine (DENA). Chloroform either hadmore » no effect or inhibited the occurrence of GGT foci when administered subsequent to a single dose of DENA. However, when the chloroform was administered in drinking water concurrently with weekly doses of DENA, it enhanced the formation of liver tumors. Of 20 halogenated benzenes tested, only 1,2,4,5-tetrachlorobenzene and hexachlorobenzene promoted the occurrence of DENA-initiated GGT foci. Thus in rat liver, the tested by-products of drinking water disinfection did not demonstrate tumor-initiating activity, although a few appeared to possess tumor-promoting activity. Chloroform was also tested for tumor-promoting activity in 15-days-old Swiss mice initiated with ethylnitrosourea (ENU). ENU at 5 and 20 ..mu..g/g caused a dose-dependent increase in liver tumors. In male mice, chloroform inhibited both spontaneous and ENU-induced liver tumors. When administered in the drinking water, chloroform inhibited, whereas phenobarbital promoted, hepatocarcinogenesis in mice.« less

Non-invasive fibrosis tests are correlated with necroinflammatory actvity of liver in patients with chronic hepatitis B.

PubMed

Ozyalvacli, G; Kucukbayrak, A; Kurt, M; Gurel, K; Gunes, O; Ustun, C; Akdeniz, H

2014-01-01

The gold standarda method used for assessing necroinflammatory activity and fibrosis in the liver is a liver biopsy which has many disadvantages. Therefore, many investigators have been trying to develop non-invasive tests for predicting liver fibrosis score (LFS) of these patients. The aim of this study is to describe the relationship between certain non-invasive fibrosis markers with LFS and histological activity index (HAI) detected histopathologically by liver biopsy in chronic hepatitis B patients. A total of 54 patients who had undergone a liver biopsy with the diagnosis of chronic HBV infection were included in the study. Ishak scoring was used for the evaluation of liver fibrosis, and a modified Knodell HAI was used for demonstration of necroinflammation. In this study, non-invasive fibrosis tests were calculated as described in previous studies. Histological acitivity index was positively correlated with age, age/platelet index, cirrhosis discriminant score (CDS), AST/platelet ratio index (APRI), AST/platelet/GGT/AFP index (APGA), fibro-quotient (Fibro-Q), Goteburg University Cirrhosis Index (Guci), and Platelet/Age/Phosphatase/AFP/AST index (PAPAS). When divided into two groups according to HAI, Guci and APGA were found significantly different both in >4 and >4 HAI groups than the other group. In ROC analysis performed for LFS; PAPAS, APGA, FFI and APRI were the markers having the highest AUC levels, and in ROC analysis performed for HAI; Guci, APRI and APGA were the markers with the highest AUC levels. APRI, APGA and GUCI tests may be helpful in prediction of necroinflammatory scores in the liver.

Fulminant liver failure resulting from massive hepatic infarction associated with hemolysis, elevated liver enzymes, and low platelets syndrome.

PubMed

Yoshihara, Masato; Mayama, Michinori; Ukai, Mayu; Tano, Sho; Kishigami, Yasuyuki; Oguchi, Hidenori

2016-10-01

Hepatic infarction is an extremely rare and fatal complication associated with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. It can develop into fulminant liver failure, which increases both maternal and neonatal mortality rates. A 34-year-old woman with no remarkable past medical history developed eclampsia after delivery at 40 weeks of gestation. Imaging indicated massive hepatic infarction and rupture followed by cardiac arrest and fulminant liver failure. Despite liver replacement therapy with plasma exchange and continuous hemodiafiltration, the patient gradually deteriorated with persistent bacterial infection until death at 98 days after delivery. The management of fulminant liver failure complicated with HELLP syndrome should be multidisciplinary. Liver transplantation, the only radical treatment for fulminant liver failure, is worth attempting, if applicable. © 2016 Japan Society of Obstetrics and Gynecology.

Reducing liver function tests for statin monitoring: an observational comparison of two clinical commissioning groups.

PubMed

Homer, Kate; Robson, John; Solaiman, Susannah; Davis, Abigail; Khan, Saima Zubeda; McCoy, David; Mathur, Rohini; Hull, Sally; Boomla, Kambiz

2017-03-01

Current liver function testing for statin monitoring is largely unnecessary and costly. Statins do not cause liver disease. Both reduction in test frequency and use of a single alanine transaminase (ALT) rather than a full seven analyte liver function test (LFT) array would reduce cost and may benefit patients. To assess LFT testing in relation to statin use and evaluate an intervention to reduce full-array LFTs ordered by GPs for statin monitoring. Two-year cross-sectional time series in two east London clinical commissioning groups (CCGs) with 650 000 patients. One CCG received the intervention; the other did not. The intervention comprised local guidance on LFTs for statin monitoring and access to a single ALT rather than full LFT array. Of the total population, 17.6% were on statins, accounting for 43.2% of total LFTs. In the population without liver disease, liver function tests were 3.6 times higher for those on statins compared with those who were not. Following intervention there was a significant reduction in the full LFT array per 1000 people on statins, from 70.3 (95% confidence interval [CI] = 66.3 to 74.6) in the pre-intervention year, to 58.1 (95% CI = 55.5 to 60.7) in the post-intervention year ( P <0.001). In the final month, March 2016, the rate was 53.2, a 24.3% reduction on the pre-intervention rate. This simple and generalisable intervention, enabling ordering of a single ALT combined with information recommending prudent rather than periodic testing, reduced full LFT testing by 24.3% in people on statins. This is likely to have patient benefit at reduced cost. © British Journal of General Practice 2017.

Study of FibroTest and hyaluronic acid biological variation in healthy volunteers and comparison of serum hyaluronic acid biological variation between chronic liver diseases of different etiology and fibrotic stage using confidence intervals.

PubMed

Istaces, Nicolas; Gulbis, Béatrice

2015-07-01

Personalized ranges of liver fibrosis serum biomarkers such as FibroTest or hyaluronic acid could be used for early detection of fibrotic changes in patients with progressive chronic liver disease. Our aim was to generate reliable biological variation estimates for these two biomarkers with confidence intervals for within-subject biological variation and reference change value. Nine fasting healthy volunteers and 66 chronic liver disease patients were included. Biological variation estimates were calculated for FibroTest in healthy volunteers, and for hyaluronic acid in healthy volunteers and chronic liver disease patients stratified by etiology and liver fibrosis stage. In healthy volunteers, within-subject biological coefficient of variation (with 95% confidence intervals) and index of individuality were 20% (16%-28%) and 0.6 for FibroTest and 34% (27%-47%) and 0.79 for hyaluronic acid, respectively. Overall hyaluronic acid within-subject biological coefficient of variation was similar among non-alcoholic fatty liver disease and chronic hepatitis C with 41% (34%-52%) and 45% (39%-55%), respectively, in contrast to chronic hepatitis B with 170% (140%-215%). Hyaluronic acid within-subject biological coefficients of variation were similar between F0-F1, F2 and F3 liver fibrosis stages in non-alcoholic fatty liver disease with 34% (25%-49%), 41% (31%-59%) and 34% (23%-62%), respectively, and in chronic hepatitis C with 34% (27%-47%), 33% (26%-45%) and 38% (27%-65%), respectively. However, corresponding hyaluronic acid indexes of individuality were lower in the higher fibrosis stages. Non-overlapping confidence intervals of biological variation estimates allowed us to detect significant differences regarding hyaluronic acid biological variation between chronic liver disease subgroups. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Liver maximum capacity (LiMAx) test as a helpful prognostic tool in acute liver failure with sepsis: a case report.

PubMed

Buechter, Matthias; Gerken, Guido; Hoyer, Dieter P; Bertram, Stefanie; Theysohn, Jens M; Thodou, Viktoria; Kahraman, Alisan

2018-06-20

Acute liver failure (ALF) is a life-threatening entity particularly when infectious complications worsen the clinical course. Urgent liver transplantation (LT) is frequently the only curative treatment. However, in some cases, recovery is observed under conservative treatment. Therefore, prognostic tools for estimating course of the disease are of great clinical interest. Since laboratory parameters sometimes lack sensitivity and specificity, enzymatic liver function measured by liver maximum capacity (LiMAx) test may offer novel and valuable additional information in this setting. We here report the case of a formerly healthy 20-year old male caucasian patient who was admitted to our clinic for ALF of unknown origin in December 2017. Laboratory parameters confirmed the diagnosis with an initial MELD score of 28 points. Likewise, enzymatic liver function was significantly impaired with a value of 147 [> 315] μg/h/kg. Clinical and biochemical analyses for viral-, autoimmune-, or drug-induced hepatitis were negative. Liver synthesis parameters further deteriorated reaching a MELD score of 40 points whilst clinical course was complicated by septic pneumonia leading to severe hepatic encephalopathy grade III-IV, finally resulting in mechanical ventilation of the patient. Interestingly, although clinical course and laboratory data suggested poor outcome, serial LiMAx test revealed improvement of the enzymatic liver function at this time point increasing to 169 μg/h/kg. Clinical condition and laboratory data slowly improved likewise, however with significant time delay of 11 days. Finally, the patient could be dismissed from our clinic after 37 days. Estimating prognosis in patients with ALF is challenging by use of the established scores. In our case, improvement of enzymatic liver function measured by the LiMAx test was the first parameter predicting beneficial outcome in a patient with ALF complicated by sepsis.

Design and implementation of handheld and desktop software for the structured reporting of hepatic masses using the LI-RADS schema.

PubMed

Clark, Toshimasa J; McNeeley, Michael F; Maki, Jeffrey H

2014-04-01

The Liver Imaging Reporting and Data System (LI-RADS) can enhance communication between radiologists and clinicians if applied consistently. We identified an institutional need to improve liver imaging report standardization and developed handheld and desktop software to serve this purpose. We developed two complementary applications that implement the LI-RADS schema. A mobile application for iOS devices written in the Objective-C language allows for rapid characterization of hepatic observations under a variety of circumstances. A desktop application written in the Java language allows for comprehensive observation characterization and standardized report text generation. We chose the applications' languages and feature sets based on the computing resources of target platforms, anticipated usage scenarios, and ease of application installation, deployment, and updating. Our primary results are the publication of the core source code implementing the LI-RADS algorithm and the availability of the applications for use worldwide via our website, http://www.liradsapp.com/. The Java application is free open-source software that can be integrated into nearly any vendor's reporting system. The iOS application is distributed through Apple's iTunes App Store. Observation categorizations of both programs have been manually validated to be correct. The iOS application has been used to characterize liver tumors during multidisciplinary conferences of our institution, and several faculty members, fellows, and residents have adopted the generated text of Java application into their diagnostic reports. Although these two applications were developed for the specific reporting requirements of our liver tumor service, we intend to apply this development model to other diseases as well. Through semiautomated structured report generation and observation characterization, we aim to improve patient care while increasing radiologist efficiency. Published by Elsevier Inc.

[The curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning].

PubMed

Liu, Jing; Wang, Qiu-ying; Wang, Bei; Xuan, Xiao-qiang; Chen, Qiong; Xu, Dong-wei; Cheng, Ning

2011-02-01

To assess the curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning. In present study 220 SD rats were divided into control group (10 rats), carbonyl nickel group (10 rats), 20 mg/kg methylprednisolone group (40 rats), 100 mg/kg DDC group (40 rats), 10 µmol/kg sodium selenite group (40 rats), 0.25 ml shenfuhuiyangtang group (40 rats) and 20 mg/kg methylprednisolone with 100 mg/kg DDC group (40 rats). All rats except for control group inhaled passively 250 mg/m(3) carbonyl nickel for 30 minutes. At 4h and 30h after exposure, the drugs were given intraperitoneally to the rats. On the 3rd and 7th days after exposure, the liver samples were taken from 10 rats each group. The DNA damage of liver cells was detected using comet assay, the ultrastructure changes in liver cells were examined under an electronmicroscope. Compared to carbonyl nickel group, the tail lengths of liver cells in 5 groups administrated at 4 h or 30 h and tested on the 3rd or 7th day after exposure decreased significantly (P < 0.05). Compared to the control group, the tail lengths of liver cells in sodium selenite and shenfuhuiyangtang groups administrated at 4h after exposure or sodium selenite, shenfuhuiyangtang and methylprednisolone with DDC groups administrated at 30h after exposure increased significantly (P < 0.05 or P < 0.01), when tested on the 3rd day after exposure. Except from methylprednisolone sub-group administrated at 4h and tested on the 7th day after exposure, the tail lengths of liver cells in other groups administrated at 4 h or 30 h and tested on the 7th day after exposure increased significantly (P < 0.05). Compared to carbonyl nickel group, the Olive moment of liver cells in 5 groups administrated at 4 h or 30 h tested on the 3rd or 7th day after exposure decreased significantly (P < 0.05 or P < 0.01). Compared to the control group, the Olive moment of liver cells in following groups (selenite and shenfuhuiyangtang groups administrated at 4 h or 30 h and tested on the 3rd or 7th day after exposure, DDC group administrated at 4 h or 30 h and tested on the 7th day after exposure, DDC group administrated at 30h and tested on the 3rd day after exposure, and methylprednisolone with DDC group administrated at 30 h and tested on the 7th day after exposure) increased significantly (P < 0.05 or P < 0.01). As compared with carbonyl nickel group, the ultrastructure observation indicated that the nucleus and other organelles of liver cells in methylprednisolone, DDC and methylprednisolone with DDC groups administrated at 4h and tested on the 3rd day were access to normal levels. The results of present study showed that methylprednisolone, DDC and methylprednisolone with DDC could improve obviously the repair of rat liver cell damage induced by acute carbonyl nickel poisoning, and the curative effects of early treatment were better than those of later treatment.

77 FR 35878 - Establishment of User Fees for Filovirus Testing of Nonhuman Primate Liver Samples

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-15

... Establishment of User Fees for Filovirus Testing of Nonhuman Primate Liver Samples AGENCY: Centers for Disease... comment on the establishment of user fees for filovirus testing of all nonhuman primates that die during... nonhuman primates. HHS/CDC took this action because (1) testing is no longer being offered by the only...

High prevalence of asymptomatic Leishmania spp. infection among liver transplant recipients and donors from an endemic area of Brazil.

PubMed

Clemente, W T; Rabello, A; Faria, L C; Peruhype-Magalhães, V; Gomes, L I; da Silva, T A M; Nunes, R V P; Iodith, J B; Protil, K Z; Fernandes, H R; Cortes, J R G; Lima, S S S; Lima, A S; Romanelli, R M C

2014-01-01

Visceral leishmaniasis is an uncommon disease in transplant recipients; however, if left untreated, the mortality can be high. If an organ donor or recipient is known to be an asymptomatic Leishmania spp. carrier,monitoring is advised. This study proposes to assess the prevalence of asymptomatic Leishmania spp.infection in liver transplant donors and recipients from an endemic area. A total of 50 liver recipients and 17 liver donors were evaluated by direct parasite search, indirect fluorescent antibody test (IFAT), anti-Leishmania rK39 rapid test and Leishmania spp.DNA detection by polymerase chain reaction (PCR).Leishmania spp. amastigotes were not observed in liver or spleen tissues. Of the 67 serum samples, IFAT was reactive in 1.5% and indeterminate for 17.9%, and the anti-Leishmania rK39 rapid test was negative for all samples. The PCR test was positive for 7.5%, 8.9%, and 5.9% of blood, liver and spleen samples, respectively(accounting for 23.5% of the donors and 8% of the recipients). Leishmania infantum-specific PCR confirmed all positive samples. In conclusion, a high prevalence of asymptomatic L. infantum was observed in donors and recipients from an endemic area, and PCR was the most sensitive method for screening these individuals.

Influence of Prescribed Herbal and Western Medicine on Patients with Abnormal Liver Function Tests: A Retrospective Quasi-Experimental Study

PubMed Central

Lee, Ah-Ram; Yim, Je-Min; Kim, Won-Il

2012-01-01

Objectives: The aim of this study was to investigate the safety and the efficacy of Korean herbal, western and combination medicine use in patients with abnormal liver function tests. Methods: We investigated nerve disease patients with abnormal liver function tests who were treated with Korean herbal, western and combination medicine at Dong-Eui University Oriental Hospital from January 2011 to August 2011. We compared aspartic aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (T-bil) levels before and after taking medicine and excluded patients who had liver-related disease when admitted. Results: AST and ALT were decreased significantly in patients who had taken herbal, western medicine. AST, ALT and ALP were decreased significantly in patients who had taken combination medicine. Compare to herbal medicine, AST, ALT and ALP were decreased significantly in patients who had taken western medicine, and ALT and ALP were decreased significantly in patients who had taken combination medicine. There were no significant differences between western and combination medicine. Conclusions: This study suggests that prescribed Korean herbal medicine, at least, does not injure liver function for patients’, moreover, it was shown to be effective in patients with abnormal liver function tests. PMID:25780634

The PAPAS index: a novel index for the prediction of hepatitis C-related fibrosis.

PubMed

Ozel, Banu D; Poyrazoğlu, Orhan K; Karaman, Ahmet; Karaman, Hatice; Altinkaya, Engin; Sevinç, Eylem; Zararsiz, Gökmen

2015-08-01

Several noninvasive tests have been developed to determine the degree of hepatic fibrosis in patients with chronic hepatitis C (CHC) without performing liver biopsy. This study aimed to determine the performance of the PAPAS (Platelet/Age/Phosphatase/AFP/AST) index in patients with CHC for the prediction of significant fibrosis and cirrhosis and to compare it with other noninvasive tests. To date, no study has evaluated the application of the PAPAS index in CHC-associated liver fibrosis. This retrospective study included 137 consecutive patients with CHC who had undergone a percutaneous liver biopsy before treatment. The aspartate aminotransferase/platelet ratio (APRI), aspartate aminotransferase/alanine transaminase ratio (AAR), age-platelet index (API), FIB4, cirrhosis discriminate score (CDS), the Göteborg University cirrhosis index (GUCI), and PAPAS were calculated and compared with the diagnostic accuracies of all fibrosis indices between the groups F0-F2 (no-mild fibrosis) versus F3-F6 (significant fibrosis) and F0-F4 (no cirrhosis) versus F5-F6 (cirrhosis). To predict significant fibrosis, the area under curve (95% confidence interval) for FIB4 was 0.727 followed by GUCI (0.721), PAPAS≈APRI≈CDS (0.716), and API (0.68). To predict cirrhosis, the area under curve (95% confidence interval) for FIB4 was calculated to be 0.735, followed by GUCI (0.723), PAPAS≈APRI≈CDS≈(0.71), and API (0.66). No statistically significant difference was observed among these predictors to exclude both significant fibrosis and cirrhosis (P>0.05). The diagnostic capability of the PAPAS index has moderate efficiency and was not superior to other fibrosis markers for the identification of fibrosis in CHC patients. There is a need for more comprehensive prospective studies to help determine the diagnostic value of PAPAS for liver fibrosis.

 Albumin dialysis with MARS for the treatment of anabolic steroid-induced cholestasis.

PubMed

Díaz, Francia C; Sáez-González, Esteban; Benlloch, Salvador; Álvarez-Sotomayor, Diego; Conde, Isabel; Polo, Begoña; García, María; Rodríguez, María; Prieto, Martín

 Background and aims. Steroid-related hepatotoxicity has become one of the most relevant causes of drug induced liver cholestasis. Some patients do not improve after standard medical treatment (SMT) and may therefore require other approaches, like extracorporeal liver support. We report four cases of patients with pruritus, abnormal liver function tests and biopsy-proven anabolic steroid-induced cholestasis who were unresponsive to SMT. They underwent treatment with albumin dialysis (Molecular Adsorbent Recirculating System -MARS®-). A minimum of two MARS sessions were performed. After MARS® procedure, patients' symptoms improved, as well as liver function tests, thus avoiding liver transplantation. Albumin dialysis appears as a valuable therapeutic option for the management of anabolic steroid-induced cholestasis in patients that are unresponsive to SMT.

Campylobacter in chicken livers and their destruction by pan frying.

PubMed

Whyte, R; Hudson, J A; Graham, C

2006-12-01

To enumerate Campylobacter spp. on the external surface and internal portions of chicken livers, and to assess the cooking required to inactivate naturally present cells. Of 30 livers tested all yielded Campylobacter spp. on their surfaces and 90% were found to contain the organism in internal tissue. Four (13%) livers contained >10(4) MPN campylobacters, and an additional seven (23%) contained >10(3) MPN campylobacters per liver. The internal temperature of pan-fried livers under the conditions used reached a maximum of 70-80 degrees C, and maintaining this temperature for 2-3 min was necessary to inactivate naturally occurring Campylobacter spp. All isolates identified were either C. jejuni or C. coli. Chicken livers represent a potential source of human campylobacteriosis as they contained >10(4) MPN per liver in 13% of the samples tested. Pan-frying can produce an acceptable product that is safe to eat. SIGNIFICANCE AND IMPACT OF THIS STUDY: The data provided can be used in exposure assessments of Campylobacter in poultry products in terms of both quantitative data and assessing pan-frying and its ability to destroy campylobacters.

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

PubMed

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

2014-08-01

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

Effect of oral D-tagatose on liver volume and hepatic glycogen accumulation in healthy male volunteers.

PubMed

Boesch, C; Ith, M; Jung, B; Bruegger, K; Erban, S; Diamantis, I; Kreis, R; Bär, A

2001-04-01

Standard toxicity tests with high levels of D-tagatose showed a reversible enlargement of the liver in Sprague-Dawley rats without increase of liver enzymes. The present study tests the hypotheses that partial substitution of dietary sucrose by D-tagatose for 28 days increases the volume of human liver and the concentration of liver glycogen. Twelve healthy, male volunteers were studied in a double-blind crossover study with ingestion of D-tagatose (3x15 g daily) and placebo (sucrose, 3x15 g daily) for periods of 28 days each. Liver volume and glycogen concentration have been determined by magnetic resonance (MR) imaging and spectroscopy, which were accompanied by routine medical examinations. MR examinations before and after the treatments revealed no effects (P>0.05) of treatment, period, or subject for changes in liver volume or glycogen concentration. A steady increase of liver volumes, independent of the D-tagatose or placebo intake, has been observed over the study in parallel with a slight increase in body weight. The treatment with D-tagatose was not associated with clinically relevant changes of the examined clinico-chemical and hematological parameters, including liver enzymes and uric acid. Copyright 2001 Academic Press.

LIVER DAMAGE IN MICE TREATED WITH 4-(p-DIMETHYLAMINOSTYRYL) QUINOLINE, A RADIOMIMETIC AGENT

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

Davis, M.L.; Gude, W.D.; Asano, M.

1963-10-01

The effects of intravenous injections of the radiomimetic agent 4-(p- dimethylaminostyryl)quinoline on the liver were studied in mice of the RF/Up and (101 x C3H) F/sub 1/ strains. The effects were assessed by use of the Bromsulphalcin (BSP) liver function test and histologic examimation of liver sections. Liver cell lipoid vacuolation was noted within 1 hour after injection of 4 mg of the drug and was very severe before 24 hours had elapsed. BSP testing on succeeding days indicated progressive liver damage that reached a peak on the sixth day in the RF/Up mice and on the third day inmore » the (101 x C3H) F/sub 1/ mice. This was accompanied by extensive liver cell necrosis, especially in the central part of the lobule. Resolution of the lesions occurred gradually over the 17-day observation period, but residual cytologic changes were still present at the end of this time. (P.C.H.)« less

Comparison of non-invasive assessment to diagnose liver fibrosis in chronic hepatitis B and C patients.

PubMed

Stibbe, Krista J M; Verveer, Claudia; Francke, Jan; Hansen, Bettina E; Zondervan, Pieter E; Kuipers, Ernst J; de Knegt, Robert J; van Vuuren, Anneke J

2011-07-01

Chronic viral hepatitis B and C cause liver fibrosis, leading to cirrhosis. Fibrosis assessment is essential to establish prognosis and treatment indication. We compared seven non-invasive tests, separately and in combination, in chronic hepatitis patients to detect early stages of fibrosis according to the Metavir score in liver biopsy. Galactose and methacetin breath tests (GBT and MBT), biomarkers (hyaluronic acid (HA), aspartate aminotransferase platelet ratio index (APRI), FibroTest, and Fib-4) and transient elastography (TE) were evaluated in 89 patients. Additionally, 31 healthy controls were included for evaluation of breath tests and biomarkers. Serum markers (HA, APRI, FibroTest, and Fib-4) and elastography significantly distinguished non-cirrhotic (F0123) from cirrhotic (F4) patients (p < 0.001, p = 0.015, p < 0.001, p = 0.005, p = 0.006, respectively). GBT, HA, APRI, FibroTest, Fib-4, and TE detected F01 from F234 (p = 0.04, p = 0.011, p = 0.009, p < 0.001, p < 0.001, and p < 0.001, respectively). A combination of different tests (TE, HA, and FibroTest) improved the performance statistically, area under the curve (AUC) = 0.87 for F234, 0.92 for F34, and 0.90 for F4. HA, APRI, FibroTest, Fib-4, and TE reliably distinguish non-cirrhotic and cirrhotic patients. Except for MBT, all tests discriminate between mild and moderate fibrosis. As single tests: FibroTest, Fib-4, and TE were the most accurate for detecting early fibrosis; combining different non-invasive tests increased the accuracy for detection of liver fibrosis to such an extent and thus might be acceptable to replace liver biopsy.

Prediction of Nonalcoholic Fatty Liver Disease Via a Novel Panel of Serum Adipokines

PubMed Central

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

2016-01-01

Abstract Considering limitations of liver biopsy for diagnosis of nonalcoholic liver disease (NAFLD), biomarkers’ panels were proposed. The aims of this study were to establish models based on serum adipokines for discriminating NAFLD from healthy individuals and nonalcoholic steatohepatitis (NASH) from simple steatosis. This case-control study was conducted in patients with persistent elevated serum aminotransferase levels and fatty liver on ultrasound. Individuals with evidence of alcohol consumption, hepatotoxic medication, viral hepatitis, and known liver disease were excluded. Liver biopsy was performed in the remaining patients to distinguish NAFLD/NASH. Histologic findings were interpreted using “nonalcoholic fatty liver activity score.” Control group consisted of healthy volunteers with normal physical examination, liver function tests, and liver ultrasound. Binary logistic regression analysis was applied to ascertain the effects of independent variables on the likelihood that participants have NAFLD/NASH. Decreased serum adiponectin and elevated serum visfatin, IL-6, TNF-a were associated with an increased likelihood of exhibiting NAFLD. NAFLD discriminant score was developed as the following: [(−0.298 × adiponectin) + (0.022 × TNF-a) + (1.021 × Log visfatin) + (0.709 × Log IL-6) + 1.154]. In NAFLD discriminant score, 86.4% of original grouped cases were correctly classified. Discriminant score threshold value of (−0.29) yielded a sensitivity and specificity of 91% and 83% respectively, for discriminating NAFLD from healthy controls. Decreased serum adiponectin and elevated serum visfatin, IL-8, TNF-a were correlated with an increased probability of NASH. NASH discriminant score was proposed as the following: [(−0.091 × adiponectin) + (0.044 × TNF-a) + (1.017 × Log visfatin) + (0.028 × Log IL-8) − 1.787] In NASH model, 84% of original cases were correctly classified. Discriminant score threshold value of (−0.22) yielded a sensitivity and specificity of 90% and 66% respectively, for separating NASH from simple steatosis. New discriminant scores were introduced for differentiating NAFLD/NASH patients with a high accuracy. If verified by future studies, application of suggested models for screening of NAFLD/NASH seems reasonable. PMID:26844476

Laboratory-Based Biomarkers and Liver Metastases in Metastatic Castration-Resistant Prostate Cancer.

PubMed

Cotogno, Patrick M; Ranasinghe, Lahiru K; Ledet, Elisa M; Lewis, Brian E; Sartor, Oliver

2018-04-26

Metastatic castrate-resistant prostate cancer (mCRPC) patients with liver metastases have a poor prognosis. No large studies have investigated the clinical and biochemical parameters associated with liver metastases in this population. Patient data made available via Project Data Sphere were collected from 1,281 men with mCRPC who were enrolled on to three phase III clinical trials for the treatment of their disease. Multiple logistic regression was performed on eight clinical and biochemical baseline variables to test their association with the presence of liver metastases on baseline radiographic imaging. Variables of interest included prior docetaxel exposure, Eastern Cooperative Oncology Group performance status, albumin, alkaline phosphatase, alanine transaminase, aspartate transaminase (AST), hemoglobin (HGB), lactate dehydrogenase (LDH), prostate-specific antigen, and total bilirubin. Final models were compared when treating the variables as either continuous or categorized. Multiple variable analysis demonstrated that an increasing serum AST or LDH or a decreasing HGB was associated with an increased probability of having documented radiographic liver metastases ( p  < .0001). The area under the curve for the continuous model was 0.6842 and 0.6890 for the categorical one, with the latter model containing a dichotomized AST and LDH based on the upper limit of normal and tertile ranges of HGB based on the distribution of the outcome. Our analysis demonstrated a significant association between the presence of liver metastases and laboratory levels of AST, LDH, and HGB. These have implications for patient management. More research is needed to validate these biomarkers and prospectively determine their application in the clinical setting. The purpose of this study was to evaluate biochemical and clinical biomarkers associated with the presence of liver metastases in men diagnosed with metastatic castrate-resistant prostate cancer. The results indicate that quantitative assessments of aspartate transaminase, lactate dehydrogenase, and hemoglobin are significantly associated with an increased probability of having documented radiographic liver metastases. Analysis of these simple variables can alert clinicians to those at high risk for prostate cancer that has spread to the liver, a finding of clear importance for clinical management. © AlphaMed Press 2018.

Elevated red blood cell distribution width is associated with liver function tests in patients with primary hepatocellular carcinoma.

PubMed

Wei, Ting-Ting; Tang, Qing-Qin; Qin, Bao-Dong; Ma, Ning; Wang, Li-Li; Zhou, Lin; Zhong, Ren-Qian

2016-11-25

Red blood cell distribution width (RDW), a routinely tested parameter of the complete blood count (CBC), has been reported to be increased in various cancers and correlated with the patients' clinical characteristics. However, the significance of RDW in primary hepatocellular carcinoma (pHCC) is largely unknown. The aim of this study was to evaluate the associations between RDW and the clinical characteristics of pHCC patients. Medical records of 110 treatment-naive pHCC patients were retrospectively reviewed. Their clinical characteristics on admission, including RDW, liver function tests and tumor stage, were extracted, and their relationships were analyzed using Spearman correlation and Kruskal-Wallis test. Sixty-eight healthy individuals were set as controls. RDW was significantly increased in pHCC patients and correlated with the liver function tests. However, no correlation between RDW and tumor stage was found. RDW may be used to assess the liver function, but not the tumor stage in pHCC patients.

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.

Synthesis and toxicity test of magnetic nanoparticle via biocompatible microemulsion system as template for application in targeted drug delivery

NASA Astrophysics Data System (ADS)

Kader, Razinah Abdul; Rose, Laili Che; Suhaimi, Hamdan; Manickam, Mariessa Soosai

2017-09-01

This work reports the preparation of magnetic nanoparticles (FeNPs) using biocompatible W/O microemulsion for biomedical applications. W/O microemulsion was formed using decane as oil phase, water, tween 80 as non-ionic surfactant and hexanol as organic solvent. The synthesized FeNPs were characterised by using Fourier Transform Infrared Resonance Spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and X-Ray Diffraction (XRD). The FTIR showed that Fe-O bond exist on 581cm-1 having strong magnetic strength whereas SEM showed the morphology surface of magnetic nanoparticles (FeNPs). Furthermore, analysis of XRD pattern magnetic nanoparticles (FeNPs) reveals a cubic iron oxide phase with good crystallize structure. Furthermore, toxicity test on human liver cells proved that it is 70% safe on human and proved to be a safety nanomedicine.

[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.

Perioperative Non-Invasive Indocyanine Green-Clearance Testing to Predict Postoperative Outcome after Liver Resection

PubMed Central

Haegele, Stefanie; Reiter, Silvia; Wanek, David; Offensperger, Florian; Pereyra, David; Stremitzer, Stefan; Fleischmann, Edith; Brostjan, Christine; Gruenberger, Thomas; Starlinger, Patrick

2016-01-01

Background Postoperative liver dysfunction may lead to morbidity and mortality after liver resection. Preoperative liver function assessment is critical to identify preexisting liver dysfunction in patients prior to resection. The aim of this study was to evaluate the predictive potential of perioperative indocyanine green (ICG)-clearance testing to prevent postoperative liver dysfunction and morbidity using standardized outcome parameters in a routine Western-clinical-setting. Study Design 137 patients undergoing partial hepatectomy between 2011 and 2013, at the general hospital of Vienna, were included. ICG-clearance was recorded one day prior to surgery as well as on the first and fifth postoperative day. Postoperative liver dysfunction was defined according to the International Study Group of Liver Surgery and evaluation of morbidity was based on the Dindo-Clavien classification. Statistical analyses were based on non-parametric tests. Results Preoperative reduced ICG—plasma disappearance rate (PDR) as well as increased ICG—retention rate at 15 min (R15) were able to significantly predict postoperative liver dysfunction (Area under the curve = PDR: 0.716, P = 0.018; R15: 0.719, P = 0.016). Furthermore, PDR <17%/min. or R15 >8%, were able to accurately predict postoperative complications prior to surgery. In addition to this, ICG-clearance on postoperative day 1 comparably predicted postoperative liver dysfunction (Area under the curve = PDR: 0.895; R15: 0.893; both P <0.001), specifically, PDR <10%/min or R15 >20% on postoperative day 1 predicted poor postoperative outcome. Conclusion PDR and R15 may represent useful parameters to distinguish preoperative high and low risk patients in a Western collective as well as on postoperative day 1, to identify patients who require closer monitoring for potential complications. PMID:27812143

Development of experimental fibrotic liver diseases animal model by Carbon Tetracholoride

PubMed Central

Gitiara, Atoosa; Tokhanbigli, Samaneh; Mazhari, Sogol; Baghaei, Kaveh; Hatami, Behzad; Hashemi, Seyed Mahmoud; Asadi Rad, Ali; Moradi, Afshin; Nasiri, Meyam; Zarrabi Ahrabi, Nakisa; Zali, Mohammad Reza

2017-01-01

Aim: This study is presenting an effective method of inducing liver fibrosis by CCL4 as a toxin in two different breeds of rat models. Background: Liver fibrosis is a result of inflammation and liver injury caused by wound healing responses which ultimately lead to liver failure. Consequently, after liver fibrosis, the progression will be continued to liver cirrhosis and at the end stage hepatocellular carcinoma (HCC). Many studies have demonstrated that one of the most important causes of liver fibrosis is Non-alcoholic steatohepatitis (NASH). Fibrotic Liver is affected by an excessive accumulation of extracellular matrix (ECM) proteins like collagen and α-SMA. Methods: In two different experiments, male Vistar, and Sprague Dawley Rat models ranging from 200±60, corresponding to an age of approximately 10 weeks were utilized in order to induce CCL4 treated liver fibrosis. Results: After 6 weeks of CCL4 injection, different tests have been carried out to verify the liver fibrosis including serum markers such as Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT), molecular tests containing, laminin and α-SMA and also pathological observation by Hematoxylin and eosin staining in both fibrosis and control group. Conclusion: The results of Pathology and Real-time PCR showed that fibrosis was induced much more effectively in Sprague Dawley rat model compared with Wistar rats. PMID:29511482

Open-Porous Hydroxyapatite Scaffolds for Three-Dimensional Culture of Human Adult Liver Cells

PubMed Central

Schmelzer, Eva; Over, Patrick; Nettleship, Ian; Gerlach, Joerg C.

2016-01-01

Liver cell culture within three-dimensional structures provides an improved culture system for various applications in basic research, pharmacological screening, and implantable or extracorporeal liver support. Biodegradable calcium-based scaffolds in such systems could enhance liver cell functionality by providing endothelial and hepatic cell support through locally elevated calcium levels, increased surface area for cell attachment, and allowing three-dimensional tissue restructuring. Open-porous hydroxyapatite scaffolds were fabricated and seeded with primary adult human liver cells, which were embedded within or without gels of extracellular matrix protein collagen-1 or hyaluronan. Metabolic functions were assessed after 5, 15, and 28 days. Longer-term cultures exhibited highest cell numbers and liver specific gene expression when cultured on hydroxyapatite scaffolds in collagen-1. Endothelial gene expression was induced in cells cultured on scaffolds without extracellular matrix proteins. Hydroxyapatite induced gene expression for cytokeratin-19 when cells were cultured in collagen-1 gel while culture in hyaluronan increased cytokeratin-19 gene expression independent of the use of scaffold in long-term culture. The implementation of hydroxyapatite composites with extracellular matrices affected liver cell cultures and cell differentiation depending on the type of matrix protein and the presence of a scaffold. The hydroxyapatite scaffolds enable scale-up of hepatic three-dimensional culture models for regenerative medicine applications. PMID:27403430

Three-dimensional growth dynamics of the liver in the human fetus.

PubMed

Szpinda, Michał; Paruszewska-Achtel, Monika; Woźniak, Alina; Badura, Mateusz; Mila-Kierzenkowska, Celestyna; Wiśniewski, Marcin

2015-07-01

The fetal liver is indubitably the earliest and the most severely affected organ by abnormal fetal growth. The size of the fetal liver assessed by three-dimensional ultrasonography is indispensable in determining the status of fetal growth, nutrition and maturity, and in the early recognition and monitoring fetal micro- and macrosomias. The aim of the present study was to measure the human fetal liver length, transverse and sagittal diameters to establish their age-specific reference intervals, the 3rd, 10th, 50th, 90th, and 97th smoothed centile curves, and the relative growth of the liver calculated for the 50th centile. Using anatomical, digital (NIS-Elements AR 3.0, Nikon) and statistical methods (one-way ANOVA test for paired data and post hoc RIR Tukey test, Shapiro-Wilk test, Fisher's test, Student's t test, the Altman-Chitty method), length, transverse and sagittal diameters of the liver for the 3rd, 10th, 50th, 90th, and 97th centiles were assessed in 69 human fetuses of both sexes (32 males and 37 females) aged 18-30 weeks, derived from spontaneous abortions or stillbirths. No male-female differences (P > 0.05) concerning the three parameters studied were found. During the study period, the fetal liver increased tri-dimensionally: in length from 19.51 ± 1.02 to 39.65 ± 7.05 mm, in transverse diameter from 29.44 ± 3.73 to 53.13 ± 5.31 mm, and in sagittal diameter from 22.97 ± 3.79 to 43.22 ± 5.49 mm. The natural logarithmic models were found to fit the data with gestational age (P < 0.001) in the following five cutoff points: 3rd, 10th, 50th, 90th and 97th centiles. The values of liver parameters in relation to gestational age in weeks were calculated by the following logarithmic regressions: y = -82.778 + 35.752 × ln(age) ± Z × (-2.778 + 0.308 × age) for liver length, y = -123.06 + 52.668 × ln(age) ± Z × (3.156 + 0.049 × age) for liver transverse diameter, and y = -108.94 + 46.052 × ln(age) ± Z × (-0.541 + 0.188 × age) for liver sagittal diameter. For the 50th centile, at the range of 18-30 weeks, the growth rates per week were gradually decreasing from 1.93 to 1.21 mm for length, from 2.85 to 1.79 mm for transverse diameter, and from 2.49 to 1.56 mm for sagittal diameter of the liver (P < 0.05). During the study period both the length-to-transverse diameter ratio and the sagittal-to-transverse diameter ratio of the liver changed little, attaining the values of 0.71 ± 0.11 and 0.87 ± 0.12, respectively. The fetal liver does not reveal sex differences in its length, transverse and sagittal diameters. The fetal liver length, transverse and sagittal diameters grow logarithmically. The regression equations for the estimation of the mean and standard deviation of liver length, transverse and sagittal diameters allow for calculating any desired centiles according to gestational age. The three-dimensional evolution of the fetal liver follows proportionately. The age-specific reference intervals for evolving liver length, transverse and sagittal diameters constitute the normative values of potential relevance in monitoring normal fetal development and screening for disturbances in fetal growth.

Surgical anatomy of segmental liver transplantation.

PubMed

Deshpande, R R; Heaton, N D; Rela, M

2002-09-01

The emergence of split and living donor liver transplantation has necessitated re-evaluation of liver anatomy in greater depth and from a different perspective than before. Early attempts at split liver transplantation were met with significant numbers of vascular and biliary complications. Technical innovations in this field have evolved largely by recognizing anatomical anomalies and variations at operation, and devising novel ways of dealing with them. This has led to increasing acceptance of these procedures and decreased morbidity and mortality rates, similar to those observed with whole liver transplantation. The following review is based on clinical experience of more than 180 split and living related liver transplantations in adults and children, performed over a 7-year period from 1994 to 2001. A comprehensive understanding and application of surgical anatomy of the liver is essential to improve and maintain the excellent results of segmental liver transplantation.

Analysis of LIF-Raman spectroscopy for the diagnosis of normal and liver diseases

NASA Astrophysics Data System (ADS)

Li, Xiaozhou; Yang, Tianyue; Yu, Ting; Sun, Ruomin; Li, Siqi

2011-07-01

In this paper, 514.5nm argon ion laser induced human serum Raman and auto-fluorescence spectra of normal, liver cirrhosis and liver cancer were measured and analyzed. The spectral differences between these three types of serums were observed and given brief explanations. Three parameters α, φ and Δλ were introduced to describe characteristics of each type of spectrum. Experimental results showed that these parameters might be applicable for discrimination of normal, liver cirrhosis and liver cancer, which will provide some reference values to explore the method of laser spectral diagnosis of cancer.

Recent Progress of Nano-drug Delivery System for Liver Cancer Treatment.

PubMed

Zhou, Feilong; Teng, Fangfang; Deng, Peizong; Meng, Ning; Song, Zhimei; Feng, Runliang

2018-02-07

Liver cancer is one of serious diseases which threaten human life and health. Studies on the treatment of liver cancer have attracted widespread attention. Application of nano-drug delivery system (NDDS) can not only improve selective drug delivery to liver tissue and improve the bioavailability of drug, but also can reduce the side effects of drugs when it is specially modified in the respects of structure modification or specific target molecules decoration. This review will address the latest development of liver-targeted drug delivery system. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Variation of Metallothionein I and II Gene Expression in the Bank Vole (Clethrionomys glareolus) Under Environmental Zinc and Cadmium Exposure.

PubMed

Mikowska, Magdalena; Dziublińska, Barbara; Świergosz-Kowalewska, Renata

2018-07-01

The main idea of the study was to assess how environmental metal pollution activates defence responses at transcription levels in the tissues of bank voles (Clethrionomys glareolus). For this purpose, the metallothioneine (MT) genes expression (a well known biomarker of exposure and response to various metals) was measured. The real-time PCR method was used for relative quantification of metallothionein I and metallothionein II expressions in the livers, kidneys and testes of bank voles from six populations exposed to different contaminants, mainly zinc, cadmium and iron. The assessment of Zn, Cu and Fe concentrations in the tissues allowed to study the MTs gene expression responses to these metals. ANOVA analysis showed differences between populations in terms of metal concentration in tissues, livers and kidneys. Student T test showed significant differences in metal concentration between unpolluted and polluted sites only for the liver tissue: significantly lower Zn levels and significantly higher Fe levels in the unpolluted sites. Kruskal-Wallis test performed on C T data shows differences in the gene expressions between populations for both MT genes for liver and testes. In the liver metallothionein I gene expression was upregulated in populations considered as more polluted (up to 7.5 higher expression in Miasteczko Śląskie comparing to Mikołajki). Expression of metallothionein II revealed a similar pattern. In kidneys, differences in expression of both MT genes were not that evident. In testes, MT upregulation in polluted sites was noted for metallothionein II. For metallothionein however, we found downregulation in populations from more contaminated sites. The expressions of both MTs were positively influenced by cadmium in kidney (concentration data from the previous study) and zinc and copper in liver, while cadmium had effects only on the liver MT II gene expression. Positive relationship was obtained for lead and metallothionein II expression in the liver.

Distribution of Ca, Fe, Cu and Zn in primary colorectal cancer and secondary colorectal liver metastases

NASA Astrophysics Data System (ADS)

Al-Ebraheem, A.; Mersov, A.; Gurusamy, K.; Farquharson, M. J.

2010-07-01

A microbeam synchrotron X-ray fluorescence (μSRXRF) technique has been used to determine the localization and the relative concentrations of Zn, Cu, Fe and Ca in primary colorectal cancer and secondary colorectal liver metastases. 24 colon and 23 liver samples were examined, all of which were formalin fixed tissues arranged as microarrays of 1.0 mm diameter and 10 μm thickness. The distribution of these metals was compared with light transmission images of adjacent sections that were H and E stained to reveal the location of the cancer cells. Histological details were provided for each sample which enable concentrations of all elements in different tissue types to be compared. In the case of liver, significant differences have been found for all elements when comparing tumour, normal, necrotic, fibrotic, and blood vessel tissues (Kruskal Wallis Test, P<0.0001). The concentrations of all elements have also been found to be significantly different among tumour, necrotic, fibrotic, and mucin tissues in the colon samples (Kruskal Wallis Test, P<0.0001). The concentrations of all elements have been compared between primary colorectal samples and colorectal liver metastases. Concentration of Zn, Cu, Fe and Ca are higher in all types of liver tissues compared to those in the colon tissues. Comparing liver tumour and colon tumour samples, significant differences have been found for all elements (Mann Whitney, P<0.0001). For necrotic tissues, significant increase has been found for Zn, Ca, Cu and Fe (Mann Whitney, P<0.0001 for Fe and Zn, 0.014 for Ca, and 0.001 for Cu). The liver fibrotic levels of Zn, Ca, Cu and Fe were higher than the fibrotic colon areas (independent T test, P=0.007 for Zn and Mann Whitney test P<0.0001 for Cu, Fe and Ca). For the blood vessel tissue, the analysis revealed that the difference was only significant for Fe ( P=0.009) from independent T test.

In vivo assessment of diet-induced rat hepatic steatosis development by percutaneous single-fiber spectroscopy detects scattering spectral changes due to fatty infiltration

NASA Astrophysics Data System (ADS)

Piao, Daqing; Sultana, Nigar; Holyoak, G. Reed; Ritchey, Jerry W.; Wall, Corey R.; Murray, Jill K.; Bartels, Kenneth E.

2015-11-01

This study explores percutaneous single-fiber spectroscopy (SfS) of rat livers undergoing fatty infiltration. Eight test rats were fed a methionine-choline-deficient (MCD) diet, and four control rats were fed a normal diet. Two test rats and one control rat were euthanized on days 12, 28, 49, and 77 following initiation of the diet, after percutaneous SfS of the liver under transabdominal ultrasound guidance. Histology of each set of the two euthanized test rats showed mild and mild hepatic lipid accumulations on day 12, moderate and severe on day 28, severe and mild on day 49, and moderate and mild on day 77. Livers with moderate or higher lipid accumulation generally presented higher spectral reflectance intensity when compared to lean livers. Livers of the eight test rats on day 12, two of which had mild lipid accumulation, revealed an average scattering power of 0.37±0.14 in comparison to 0.07±0.14 for the four control rats (p<0.01). When livers of the test rats with various levels of fatty infiltration were combined, the average scattering power was 0.36±0.15 in comparison to 0.14±0.24 of the control rats (0.05

The Acute Toxicity Test of Methanolic Extract of Hyptis pectinata Poit on Liver Balb/c Mice

NASA Astrophysics Data System (ADS)

Suzery, M.; Cahyono, B.; Astuti, P.

2017-02-01

Plants from Lamiaceae family has almost entirely reported having physiological activities. One of them is Hyptis pectinata Poit plant. Research on the toxicity of Hyptis pectinata needs to be done to protect people from the possibility of its harmful effects. This study aim to know the acute toxicity effects of Hyptis pectinata extract (HPE) on liver of Balb/c mice. This research was a laboratory experimental study using the post test only controlled group design. Balb/c mice were randomly divided into 4 groups. K (control group), P1, P2 and P3 (treatment groups; given HPE 200mg/kgBW, 1000 mg/kgBW, and 5000 mg/kgBW, respectively). The extract was orally given with gastric tube on the first day and the mice were terminated at the 8th day then the livers were observed. The Kruskal-Wallis test for macroscopic morphological and volume of the liver showed there were no significant difference with p=0.406 and p=0.054. The highest liver histopathological score was in P3 group. The Kruskal-Wallis test showed significantly difference (p=0.000). Continued with Mann-Withney test that showed a significant difference in K-P1 (p=0.009), K-P2 (p=0.009), K-P3 (p=0.009), P1-P2 (p=0.028), and P1-P3 (p=0.009). In conclusion, the HPE is safe to use which has no complication with liver of mice.

Impact of effective versus sham continuous positive airway pressure on liver injury in obstructive sleep apnoea: Data from randomized trials.

PubMed

Jullian-Desayes, Ingrid; Tamisier, Renaud; Zarski, Jean-Pierre; Aron-Wisnewsky, Judith; Launois-Rollinat, Sandrine H; Trocme, Candice; Levy, Patrick; Joyeux-Faure, Marie; Pepin, Jean-Louis

2016-02-01

Obstructive sleep apnoea (OSA) could be an independent risk factor for non-alcoholic fatty liver disease (NAFLD) occurrence and progression. The impact of continuous positive airway pressure (CPAP) treatment on non-invasive markers of NAFLD has not been studied. The aim of this study was to evaluate the effect of 6-12 weeks of effective CPAP on the FibroMax test (comprising components including the SteatoTest, NashTest and FibroTest) through three randomized sham controlled studies. The FibroMax test was performed in 103 obstructive sleep apnoea patients (apnoea + hypopnoea index > 15/h) enrolled in a randomized study comparing sham versus effective CPAP. At baseline, 40.4% of patients in the sham CPAP group and 45.5% in the CPAP group exhibited liver steatosis. Furthermore, 39.6% of patients in the sham CPAP group and 58.4% in the CPAP group displayed borderline or possible non-alcoholic steatohepatitis (NASH). Six to twelve weeks of effective CPAP did not demonstrate any impact on reducing steatosis, NASH or liver fibrosis even after adjustment for gender, BMI, baseline apnoea + hypopnoea index and severity of liver injury. A number of non-invasive markers of liver damage are increased in untreated obstructive sleep apnoea patients, potentially contributing to cardiometabolic risk, but they do not improve after 6-12 weeks of effective CPAP treatment. NCT01196845 (ADISAS), NCT00464659 (MneSAS) and NCT00669695 (StatinflaSAS) at ClinicalTrials.gov. © 2015 Asian Pacific Society of Respirology.

77 FR 7109 - Establishment of User Fees for Filovirus Testing of Nonhuman Primate Liver Samples

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-10

... assay (ELISA) or other appropriate methodology. Each specimen will be held for six months. After six... loss of the only commercially available antigen-detection ELISA filovirus testing facility. Currently... current methodology (ELISA) used to test NHP liver samples. This cost determines the amount of the user...

Evaluation of living liver transplant donors: method for precise anatomic definition by using a dedicated contrast-enhanced MR imaging protocol.

PubMed

Sahani, Dushyant; D'souza, Roy; Kadavigere, Rajagopal; Hertl, Martin; McGowan, Jennifer; Saini, Sanjay; Mueller, Peter R

2004-01-01

Liver transplantation from a living donor involves removal of part of the donor liver in a fashion that does not endanger its vascular supply or metabolic function. The radiologist plays an important role in evaluation of the living donor to define the conditions under which graft donation is contraindicated and to identify anatomic variations that may alter the surgical approach. In the past, diagnostic work-up of the donor involved costly and invasive tests. Currently, dynamic contrast material-enhanced computed tomography and magnetic resonance (MR) imaging are the imaging tests performed, each of which has advantages and limitations. MR imaging performed with liver-specific and extravascular contrast agents may be used as a single imaging test for comprehensive noninvasive evaluation of living liver transplant donors. MR imaging provides valuable information about variations in the vascular and biliary anatomy and allows evaluation of the hepatic parenchyma for diffuse or focal abnormalities. Copyright RSNA, 2004

Diagnosis of cirrhosis and portal hypertension: imaging, non-invasive markers of fibrosis and liver biopsy

PubMed Central

Procopet, Bogdan

2017-01-01

Abstract The concept of ‘cirrhosis’ is evolving and it is now clear that compensated and decompensated cirrhosis are completely different in terms of prognosis. Furthermore, the term ‘advanced chronic liver disease (ACLD)’ better reflects the continuum of histological changes occurring in the liver, which continue to progress even after cirrhosis has developed, and might regress after removing the etiological factor causing the liver disease. In compensated ACLD, portal hypertension marks the progression to a stage with higher risk of clinical complication and requires an appropriate evaluation and treatment. Invasive tests to diagnose cirrhosis (liver biopsy) and portal hypertension (hepatic venous pressure gradient measurement and endoscopy) remain of crucial importance in several difficult clinical scenarios, but their need can be reduced by using different non-invasive tests in standard cases. Among non-invasive tests, the accepted use, major limitations and major benefits of serum markers of fibrosis, elastography and imaging methods are summarized in the present review. PMID:28533906

Prognostic value of enzymatic liver function for the estimation of short-term survival of liver transplant candidates: a prospective study with the LiMAx test.

PubMed

Jara, Maximilian; Malinowski, Maciej; Lüttgert, Katja; Schott, Eckart; Neuhaus, Peter; Stockmann, Martin

2015-01-01

LiMAx has been recently proposed as a new quantitative liver function test. Thus, we aimed to evaluate the diagnostic ability of LiMAx to assess short-term survival in liver transplant candidates and compare its performance to the model for end-stage liver disease (MELD) and indocyanine green plasma disappearance rate (ICG-PDR). Liver function of 167 chronic liver failure patients without hepatocellular carcinoma was prospectively investigated when they were evaluated for liver transplantation. Primary study endpoints were liver-related death within 6 months of follow-up. Within 6 months of follow-up, 18 patients died and 36 underwent liver transplantation. Median LiMAx results on evaluation day were significantly lower in patients who died (99 μg/kg/h vs. 55 μg/kg/h; P = 0.024), while median ICG-PDR results did not differ within both groups (4.4%/min vs. 3.5%/min; P = 0.159). LiMAx showed a higher negative predictive value (NPV: 0.93) as compared with ICG-PDR (NPV: 0.90) and the MELD (NPV: 0.91) in predicting risk of death within 6 months. In conclusion, LiMAx provides good prognostic information of liver transplant candidates. In particular, patients who are not at risk of death can be identified reliably by measuring actual enzymatic liver function capacity. © 2014 Steunstichting ESOT.

Liver transplantation for hepatocellular carcinoma: the Hong Kong experience.

PubMed

Ng, Kelvin K; Lo, Chung Mau; Chan, See Ching; Chok, Kenneth S; Cheung, Tan-To; Fan, Sheung Tat

2010-09-01

Orthotopic liver transplantation (OLT) is the best treatment option for selected patients with hepatocellular carcinoma (HCC) with the background of cirrhosis since this treatment modality can cure both diseases at once. Over the years, the applicability of OLT for HCC has evolved. In Asia, including Hong Kong, a shortage of deceased donor liver grafts is a universal problem having to be faced in all transplant centers. Living-donor liver transplant (LDLT) has therefore been developed to counteract organ shortage and the high prevalence of HCC. The application of LDLT for HCC is a complex process involving donor voluntarism, selection criteria for the recipient and justification with respect to long-term survival in comparison to the result of deceased donor liver transplant. This article reviews the authors' experience with OLT for HCC patients in Hong Kong, with emphasis on the applicability and outcome of LDLT for HCC. Donor voluntarism has a significant impact on the application of LDLT. "Fast-track" LDLT in the setting of recurrence following curative treatment carries a high risk of recurrence even though the tumor stage fulfills the standard criteria. Although the survival outcome may be worse following LDLT than DDLT for HCC, LDLT is still the main treatment option for patients with transplantable HCC in Hong Kong, and a reasonable survival outcome can be achieved in selected patients with extended indications. It is particularly true that LDLT provides the only hope for patients with advanced HCC under the constricting problem of organ shortage.

Bile leakage test in liver resection: A systematic review and meta-analysis

PubMed Central

Wang, Hai-Qing; Yang, Jian; Yang, Jia-Yin; Yan, Lu-Nan

2013-01-01

AIM: To assess systematically the safety and efficacy of bile leakage test in liver resection. METHODS : Randomized controlled trials and controlled clinical trials involving the bile leakage test were included in a systematic literature search. Two authors independently assessed the studies for inclusion and extracted the data. A meta-analysis was conducted to estimate postoperative bile leakage, intraoperative positive bile leakage, and complications. We used either the fixed-effects or random-effects model. RESULTS: Eight studies involving a total of 1253 patients were included and they all involved the bile leakage test in liver resection. The bile leakage test group was associated with a significant reduction in bile leakage compared with the non-bile leakage test group (RR = 0.39, 95%CI: 0.23-0.67; I2 = 3%). The white test had superiority for detection of intraoperative bile leakage compared with the saline solution test (RR = 2.38, 95%CI: 1.24-4.56, P = 0.009). No significant intergroup differences were observed in total number of complications, ileus, liver failure, intraperitoneal hemorrhage, pulmonary disorder, abdominal infection, and wound infection. CONCLUSION: The bile leakage test reduced postoperative bile leakage and did not increase incidence of complications. Fat emulsion is the best choice of solution for the test. PMID:24363535

Bile leakage test in liver resection: a systematic review and meta-analysis.

PubMed

Wang, Hai-Qing; Yang, Jian; Yang, Jia-Yin; Yan, Lu-Nan

2013-12-07

To assess systematically the safety and efficacy of bile leakage test in liver resection. Randomized controlled trials and controlled clinical trials involving the bile leakage test were included in a systematic literature search. Two authors independently assessed the studies for inclusion and extracted the data. A meta-analysis was conducted to estimate postoperative bile leakage, intraoperative positive bile leakage, and complications. We used either the fixed-effects or random-effects model. Eight studies involving a total of 1253 patients were included and they all involved the bile leakage test in liver resection. The bile leakage test group was associated with a significant reduction in bile leakage compared with the non-bile leakage test group (RR = 0.39, 95%CI: 0.23-0.67; I (2) = 3%). The white test had superiority for detection of intraoperative bile leakage compared with the saline solution test (RR = 2.38, 95%CI: 1.24-4.56, P = 0.009). No significant intergroup differences were observed in total number of complications, ileus, liver failure, intraperitoneal hemorrhage, pulmonary disorder, abdominal infection, and wound infection. The bile leakage test reduced postoperative bile leakage and did not increase incidence of complications. Fat emulsion is the best choice of solution for the test. © 2013 Baishideng Publishing Group Co., Limited. All rights reserved.

The Effects of Lasiocarpine, Retrorsine and Retronecine Pyrrole on Human Embryo Lung and Liver Cells in Culture

PubMed Central

Armstrong, Sylvia J.; Zuckerman, A. J.

1972-01-01

Retronecine pyrrole induces toxic changes both in human liver and lung cells. Lasiocarpine and retrorsine are toxic to liver cells but not to lung cells, which are unable to metabolize the pyrrolizidine alkaloids to pyrroles. The application of lasiocarpine to human liver cells in culture is followed by inhibition of DNA, RNA and protein synthesis; vacuolation of the cells, the prevention of mitosis and the formation of giant cells (“megalocytes”). PMID:5032089

Correlation between plasma endothelin-1 levels and severity of septic liver failure quantified by maximal liver function capacity (LiMAx test). A prospective study.

PubMed

Kaffarnik, Magnus F; Ahmadi, Navid; Lock, Johan F; Wuensch, Tilo; Pratschke, Johann; Stockmann, Martin; Malinowski, Maciej

2017-01-01

To investigate the relationship between the degree of liver dysfunction, quantified by maximal liver function capacity (LiMAx test) and endothelin-1, TNF-α and IL-6 in septic surgical patients. 28 septic patients (8 female, 20 male, age range 35-80y) were prospectively investigated on a surgical intensive care unit. Liver function, defined by LiMAx test, and measurements of plasma levels of endothelin-1, TNF-α and IL-6 were carried out within the first 24 hours after onset of septic symptoms, followed by day 2, 5 and 10. Patients were divided into 2 groups (group A: LiMAx ≥100 μg/kg/h, moderate liver dysfunction; group B: LiMAx <100 μg/kg/h, severe liver dysfunction) for analysis and investigated regarding the correlation between endothelin-1 and the severity of liver failure, quantified by LiMAx test. Group B showed significant higher results for endothelin-1 than patients in group A (P = 0.01, d5; 0.02, d10). For TNF-α, group B revealed higher results than group A, with a significant difference on day 10 (P = 0.005). IL-6 showed a non-significant trend to higher results in group B. The Spearman's rank correlation coefficient revealed a significant correlation between LiMAx and endothelin-1 (-0.434; P <0.001), TNF-α (-0.515; P <0.001) and IL-6 (-0.590; P <0.001). Sepsis-related hepatic dysfunction is associated with elevated plasma levels of endothelin-1, TNF-α and IL-6. Low LiMAx results combined with increased endothelin-1 and TNF-α and a favourable correlation between LiMAx and cytokine values support the findings of a crucial role of Endothelin-1 and TNF-α in development of septic liver failure.

Correlation between plasma endothelin-1 levels and severity of septic liver failure quantified by maximal liver function capacity (LiMAx test). A prospective study

PubMed Central

Kaffarnik, Magnus F.; Ahmadi, Navid; Lock, Johan F.; Wuensch, Tilo; Pratschke, Johann; Stockmann, Martin; Malinowski, Maciej

2017-01-01

Aim To investigate the relationship between the degree of liver dysfunction, quantified by maximal liver function capacity (LiMAx test) and endothelin-1, TNF-α and IL-6 in septic surgical patients. Methods 28 septic patients (8 female, 20 male, age range 35–80y) were prospectively investigated on a surgical intensive care unit. Liver function, defined by LiMAx test, and measurements of plasma levels of endothelin-1, TNF-α and IL-6 were carried out within the first 24 hours after onset of septic symptoms, followed by day 2, 5 and 10. Patients were divided into 2 groups (group A: LiMAx ≥100 μg/kg/h, moderate liver dysfunction; group B: LiMAx <100 μg/kg/h, severe liver dysfunction) for analysis and investigated regarding the correlation between endothelin-1 and the severity of liver failure, quantified by LiMAx test. Results Group B showed significant higher results for endothelin-1 than patients in group A (P = 0.01, d5; 0.02, d10). For TNF-α, group B revealed higher results than group A, with a significant difference on day 10 (P = 0.005). IL-6 showed a non-significant trend to higher results in group B. The Spearman's rank correlation coefficient revealed a significant correlation between LiMAx and endothelin-1 (-0.434; P <0.001), TNF-α (-0.515; P <0.001) and IL-6 (-0.590; P <0.001). Conclusions Sepsis-related hepatic dysfunction is associated with elevated plasma levels of endothelin-1, TNF-α and IL-6. Low LiMAx results combined with increased endothelin-1 and TNF-α and a favourable correlation between LiMAx and cytokine values support the findings of a crucial role of Endothelin-1 and TNF-α in development of septic liver failure. PMID:28542386

Hepatic artery pseudoaneurysm with hemobilia following angioplasty after liver transplantation.

PubMed

Narumi, S; Osorio, R W; Freise, C E; Stock, P G; Roberts, J P; Ascher, N L

1998-12-01

A 58-yr-old female with primary biliary cirrhosis underwent an uncomplicated orthotopic liver transplantation. Elevated liver function tests 2 months post-transplantation were evaluated with Doppler ultrasound and a hepatic artery stricture was documented. The hepatic artery stenosis was treated with angioplasty. She developed hemobilia 1 d after the procedure, which was confirmed by angiography. Emergent exploratory laparotomy revealed a pseudoaneurysm at the hepatic artery anastomosis. The pseudoaneurysm was resected and the proper hepatic artery of the graft was anastomosed to the splenic artery of the host using preserved homograft. Her post-operative course was uneventful and liver function tests returned to normal quickly after the surgery. This report will discuss the unusual nature of this complication, and review the problem of hemobilia and pseudoaneurysms in liver transplant recipients.

Evaluation of the COBAS AMPLICOR CMV MONITOR test for detection of viral DNA in specimens taken from patients after liver transplantation.

PubMed

Sia, I G; Wilson, J A; Espy, M J; Paya, C V; Smith, T F

2000-02-01

Detection of cytomegalovirus (CMV) DNA in blood by PCR is a sensitive method for the detection of infection in patients posttransplantation. The test, however, has low specificity for the identification of overt CMV disease. Quantitative CMV PCR has been shown to overcome this shortcoming. The COBAS AMPLICOR CMV MONITOR test was evaluated by using consecutive serum and peripheral blood mononuclear cell (PBMN) samples from liver transplant patients. Twenty-five patients had CMV viremia (by shell vial cell culture assay) and/or tissue-invasive disease (by biopsy); 20 had no active infection. A total of 262 serum and 62 PBMN specimens were tested. Of 159 serum specimens from patients with overt CMV infection, the COBAS assay detected CMV DNA in 21 patients (sensitivity, 84%). Only 1 of 103 samples from patients with no evidence of active infection had detectable CMV DNA (341 copies/ml). By comparison of 62 matching serum and PBMN samples by the same assay, 12 PBMN samples were exclusively positive, whereas only 2 serum samples were exclusively positive (P < 0.05). At the time of clinical CMV infection, viral copy numbers were higher in PBMNs than serum from four of five patients. The COBAS AMPLICOR CMV MONITOR test is a sensitive and specific test for the quantitative detection of CMV DNA in blood. Clinical applications of the assay will require further validation with samples from a larger population of transplant patients.

Evaluation of the COBAS AMPLICOR CMV MONITOR Test for Detection of Viral DNA in Specimens Taken from Patients after Liver Transplantation

PubMed Central

Sia, Irene G.; Wilson, Jennie A.; Espy, Mark J.; Paya, Carlos V.; Smith, Thomas F.

2000-01-01

Detection of cytomegalovirus (CMV) DNA in blood by PCR is a sensitive method for the detection of infection in patients posttransplantation. The test, however, has low specificity for the identification of overt CMV disease. Quantitative CMV PCR has been shown to overcome this shortcoming. The COBAS AMPLICOR CMV MONITOR test was evaluated by using consecutive serum and peripheral blood mononuclear cell (PBMN) samples from liver transplant patients. Twenty-five patients had CMV viremia (by shell vial cell culture assay) and/or tissue-invasive disease (by biopsy); 20 had no active infection. A total of 262 serum and 62 PBMN specimens were tested. Of 159 serum specimens from patients with overt CMV infection, the COBAS assay detected CMV DNA in 21 patients (sensitivity, 84%). Only 1 of 103 samples from patients with no evidence of active infection had detectable CMV DNA (341 copies/ml). By comparison of 62 matching serum and PBMN samples by the same assay, 12 PBMN samples were exclusively positive, whereas only 2 serum samples were exclusively positive (P < 0.05). At the time of clinical CMV infection, viral copy numbers were higher in PBMNs than serum from four of five patients. The COBAS AMPLICOR CMV MONITOR test is a sensitive and specific test for the quantitative detection of CMV DNA in blood. Clinical applications of the assay will require further validation with samples from a larger population of transplant patients. PMID:10655353

Modeling correction of severe urea cycle defects in the growing murine liver using a hybrid recombinant adeno-associated virus/piggyBac transposase gene delivery system.

PubMed

Cunningham, Sharon C; Siew, Susan M; Hallwirth, Claus V; Bolitho, Christine; Sasaki, Natsuki; Garg, Gagan; Michael, Iacovos P; Hetherington, Nicola A; Carpenter, Kevin; de Alencastro, Gustavo; Nagy, Andras; Alexander, Ian E

2015-08-01

Liver-targeted gene therapy based on recombinant adeno-associated viral vectors (rAAV) shows promising therapeutic efficacy in animal models and adult-focused clinical trials. This promise, however, is not directly translatable to the growing liver, where high rates of hepatocellular proliferation are accompanied by loss of episomal rAAV genomes and subsequently a loss in therapeutic efficacy. We have developed a hybrid rAAV/piggyBac transposon vector system combining the highly efficient liver-targeting properties of rAAV with stable piggyBac-mediated transposition of the transgene into the hepatocyte genome. Transposition efficiency was first tested using an enhanced green fluorescent protein expression cassette following delivery to newborn wild-type mice, with a 20-fold increase in stably gene-modified hepatocytes observed 4 weeks posttreatment compared to traditional rAAV gene delivery. We next modeled the therapeutic potential of the system in the context of severe urea cycle defects. A single treatment in the perinatal period was sufficient to confer robust and stable phenotype correction in the ornithine transcarbamylase-deficient Spf(ash) mouse and the neonatal lethal argininosuccinate synthetase knockout mouse. Finally, transposon integration patterns were analyzed, revealing 127,386 unique integration sites which conformed to previously published piggyBac data. Using a hybrid rAAV/piggyBac transposon vector system, we achieved stable therapeutic protection in two urea cycle defect mouse models; a clinically conceivable early application of this technology in the management of severe urea cycle defects could be as a bridging therapy while awaiting liver transplantation; further improvement of the system will result from the development of highly human liver-tropic capsids, the use of alternative strategies to achieve transient transposase expression, and engineered refinements in the safety profile of piggyBac transposase-mediated integration. © 2015 by the American Association for the Study of Liver Diseases.

Occult hepatitis C virus infection in patients in whom the etiology of persistently abnormal results of liver-function tests is unknown.

PubMed

Castillo, Inmaculada; Pardo, Margarita; Bartolomé, Javier; Ortiz-Movilla, Nuria; Rodríguez-Iñigo, Elena; de Lucas, Susana; Salas, Clara; Jiménez-Heffernan, Jose A; Pérez-Mota, Arturo; Graus, Javier; López-Alcorocho, Juan Manuel; Carreño, Vicente

2004-01-01

There are patients in whom the etiology of long-standing abnormal results of liver-function tests is unknown (ALF-EU) after exclusion of all known causes of liver diseases. We analyzed the presence of hepatitis C virus (HCV) RNA in liver-biopsy specimens from 100 patients who were negative for anti-HCV antibodies and for serum HCV RNA and who had ALF-EU. HCV RNA status was tested by reverse-transcription polymerase chain reaction (RT-PCR) and by in situ hybridization, in liver and peripheral-blood mononuclear cells (PBMCs). HCV RNA was detected in liver-biopsy specimens from 57 of 100 patients negative for anti-HCV antibodies and for serum HCV RNA (i.e., who had occult HCV infection). HCV RNA of negative polarity was found in the liver of 48 (84.2%) of these 57 patients with occult HCV infection. Nucleotide-sequence analysis confirmed the specificity of detection of HCV RNA and that patients were infected with the HCV 1b genotype. Of these 57 patients with intrahepatic HCV RNA, 40 (70%) had viral RNA in their PBMCs. With regard to liver histology, patients with occult HCV infection were more likely to have necroinflammatory activity (P=.017) and fibrosis (P=.022) than were patients without intrahepatic HCV RNA. Patients with ALF-EU may have intrahepatic HCV RNA in the absence of anti-HCV antibodies and of serum HCV RNA.

Influence of Fasciola hepatica on Serum Biochemical Parameters and Vascular and Biliary System of Sheep Liver

PubMed Central

Hodžić, A; Zuko, A; Avdić, R; Alić, A; Omeragić, J; Jažić, A

2013-01-01

Background The aim of this study was to evaluate the functional capacity of the liver based on the activity of specific enzymes and bilirubin in serum and also to investigate the influence of mechanical and toxic effects of Fasciola hepatica on the structures of the blood vessels and biliary tract in the sheep liver. Methods Blood samples and liver of 63 indigenous sheep of Pramenka breed, slaughtered in the period from March to December 2009 were used. Based on parasitological findings in the liver, all animals were divided into two groups: control (n = 34) and infected group (n = 29). For investigation and description of pathological changes in sheep liver, naturally infected with F. hepatica, corrosion cast technique was used. Results Biochemical analysis of tested parameters showed a significant elevation (P≤0.05) of serum gamma-glutamyl transferase (GGT), total bilirubin (TBIL) and direct bilirubin (DBIL) in infected sheep group comparing with the control group. No significant differences were observed for activity of aspartate aminotranferase (AST) between groups. Vascular and biliary systems of the liver were found to be affected. Conclusion Results of biochemical analysis are consistent with pathological findings and measuring of tested parameters could be used in early diagnosis of sheep fasciolosis and to test the effectiveness of anthelmintic therapy. Corrosion cast technique is very useful for investigation of pathological changes and neoangiogenesis of vascular and biliary system in sheep liver, caused by mechanical and toxic effects of F. hepatica. PMID:23682266

Non-operative management (NOM) of blunt hepatic trauma: 80 cases.

PubMed

Özoğul, Bünyami; Kısaoğlu, Abdullah; Aydınlı, Bülent; Öztürk, Gürkan; Bayramoğlu, Atıf; Sarıtemur, Murat; Aköz, Ayhan; Bulut, Özgür Hakan; Atamanalp, Sabri Selçuk

2014-03-01

Liver is the most frequently injured organ upon abdominal trauma. We present a group of patients with blunt hepatic trauma who were managed without any invasive diagnostic tools and/or surgical intervention. A total of 80 patients with blunt liver injury who were hospitalized to the general surgery clinic or other clinics due to the concomitant injuries were followed non-operatively. The normally distributed numeric variables were evaluated by Student's t-test or one way analysis of variance, while non-normally distributed variables were analyzed by Mann-Whitney U-test or Kruskal-Wallis variance analysis. Chi-square test was also employed for the comparison of categorical variables. Statistical significance was assumed for p<0.05. There was no significant relationship between patients' Hgb level and liver injury grade, outcome, and mechanism of injury. Also, there was no statistical relationship between liver injury grade, outcome, and mechanism of injury and ALT levels as well as AST level. There was no mortality in any of the patients. During the last quarter of century, changes in the diagnosis and treatment of liver injury were associated with increased survival. NOM of liver injury in patients with stable hemodynamics and hepatic trauma seems to be the gold standard.

The effects of sulforaphane on the liver and remote organ damage in hepatic ischemia-reperfusion model formed with pringle maneuver in rats.

PubMed

Oguz, Abdullah; Kapan, Murat; Kaplan, Ibrahim; Alabalik, Ulas; Ulger, Burak Veli; Uslukaya, Omer; Turkoglu, Ahmet; Polat, Yilmaz

2015-06-01

The purpose of this study was to investigate the effect of Sulforaphane on ischemia/ reperfusion (IR) injury of the liver and distant organs resulting from liver blood flow arrest. Fourty Wistar rats were assigned into four groups, each included 10 rats were used. Group I as only laparatomy, Group II laparatomy and Sulforaphane application, Group III hepatic IR; and Group IV as hepatic IR and Sulforaphane application group. Animals were subjected to liver ischemia for 30 min and then reperfusion is started. 5 mg/kg Sulforaphane was applied via oral lavage 15 minutes before initiating the experimental study. Blood samples were taken from the animals for biochemical analysis at 60th minutes of the experiment in the first and second groups; 30 minutes after beginning reperfusion in the third and forth groups. Simultaneously, liver, lung and kidney tissues were sampled for biochemical and histopathological examinations. The administration of sulforaphane significantly reduced the serum TOA and liver TOA levels, increased the serum TAC and liver TAC levels and also decreased The OSI and liver OSI levels. In the histopathologic examination, the injury was reduced by the administration of sulforaphane. Administration of sulforaphane did not lead to any significant changes in any parameter including histopathological parameters in both the kidney and the lung. Sulforaphane reduced the liver oxidative stress from I/R injury. A histological injury in liver was reduced by sulforaphane administration. However, there were no significant effects of sulforaphane on the remote organ injuries induced by IR. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Tangeretin Alleviates Cisplatin-Induced Acute Hepatic Injury in Rats: Targeting MAPKs and Apoptosis.

PubMed

Omar, Hany A; Mohamed, Wafaa R; Arab, Hany H; Arafa, El-Shaimaa A

2016-01-01

Despite its broad applications, cisplatin affords considerable nephro- and hepatotoxicity through triggering inflammatory and oxidative stress cascades. The aim of the current investigation was to study the possible protective effects of tangeretin on cisplatin-induced hepatotoxicity. The impact of tangeretin on cisplatin-evoked hepatic dysfunction and histopathologic changes along with oxidative stress, inflammatory and apoptotic biomarkers were investigated compared to silymarin. Tangeretin pre-treatment significantly improved liver function tests (ALT and AST), inhibited cisplatin-induced lipid profile aberrations (total cholesterol and triglycerides) and diminished histopathologic structural damage in liver tissues. Tangeretin also attenuated cisplatin-induced hepatic inflammatory events as indicated by suppression of tumor necrosis factor-α (TNF-α) and enhancement of interleukin-10 (IL-10). Meanwhile, it lowered malondialdehyde (MDA), nitric oxide (NO) and nuclear factor erythroid 2-related factor 2 (NRF-2) levels with restoration of glutathione (GSH), and glutathione peroxidase (GPx). Regarding mitogen-activated protein kinase (MAPK) pathway, tangeretin attenuated cisplatin-induced increase in phospho-p38, phospho-c-Jun N-terminal kinase (p-JNK) and phospho-extracellular signal-regulated kinase (p-ERK1/2) in liver tissues. In addition, tangeretin downregulated Bax expression with augmentation of Bcl-2 promoting liver cell survival. Our results highlight the protective effects of tangeretin against cisplatin-induced acute hepatic injury via the concerted modulation of inflammation, oxidative stress, MAPKs and apoptotic pathways.

Expression of Innate Immune Response Genes in Liver and Three Types of Adipose Tissue in Cloned Pigs

PubMed Central

Rødgaard, Tina; Skovgaard, Kerstin; Stagsted, Jan

2012-01-01

Abstract The pig has been proposed as a relevant model for human obesity-induced inflammation, and cloning may improve the applicability of this model. We tested the assumptions that cloning would reduce interindividual variation in gene expression of innate immune factors and that their expression would remain unaffected by the cloning process. We investigated the expression of 40 innate immune factors by high-throughput quantitative real-time PCR in samples from liver, abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and neck SAT in cloned pigs compared to normal outbred pigs. The variation in gene expression was found to be similar for the two groups, and the expression of a small number of genes was significantly affected by cloning. In the VAT and abdominal SAT, six out of seven significantly differentially expressed genes were downregulated in the clones. In contrast, most differently expressed genes in both liver and neck SAT were upregulated (seven out of eight). Remarkably, acute phase proteins (APPs) dominated the upregulated genes in the liver, whereas APP expression was either unchanged or downregulated in abdominal SAT and VAT. The general conclusion from this work is that cloning leads to subtle changes in specific subsets of innate immune genes. Such changes, even if minor, may have phenotypic effects over time, e.g., in models of long-term inflammation related to obesity. PMID:22928970

Nadolol for lithium tremor in the presence of liver damage.

PubMed

Dave, M; Langbart, M M

1994-03-01

Lithium-induced tremor classically responds to treatment with propranolol. Since it is metabolized in the liver, propranolol may not be the drug of choice in those patients who have compromised liver function or who are recovering from prior liver diseases. Another nonselective beta-adrenergic blocker, nadolol, has no hepatic biotransformation. We present here the first case report of successful treatment of lithium-induced tremor with nadolol, which was selected because the patient had compromised liver function. The patient's liver function tests remained stable with the therapy.

Liver fibrosis: a compilation on the biomarkers status and their significance during disease progression

PubMed Central

Nallagangula, Krishna Sumanth; Nagaraj, Shashidhar Kurpad; Venkataswamy, Lakshmaiah; Chandrappa, Muninarayana

2018-01-01

Liver fibrosis occurs in response to different etiologies of chronic liver injury. Diagnosing degree of liver fibrosis is a crucial step in evaluation of severity of the disease. An invasive liver biopsy is the gold standard method associated with pain and complications. Biomarkers to detect liver fibrosis include direct markers of extracellular matrix turnover and indirect markers as a reflection of liver dysfunction. Although a single marker may not be useful for successful management, a mathematical equation combining tests might be effective. The main purpose of this review is to understand the diagnostic accuracy of biomarkers and scoring systems for liver fibrosis. Advances in -omics approach have generated clinically significant biomarker candidates for liver fibrosis that need further evaluation. PMID:29255622

The SHH/Gli axis regulates CD90-mediated liver cancer stem cell function by activating the IL6/JAK2 pathway.

PubMed

Zhang, Ketao; Che, Siyao; Pan, Chuzhi; Su, Zheng; Zheng, Shangyou; Yang, Shanglin; Zhang, Huayao; Li, Wenda; Wang, Weidong; Liu, Jianping

2018-05-02

The cell surface antigen CD90 has recently been established as a promising marker for liver cancer stem cells. This study aimed to investigate potential implications of SHH/Gli signalling in CD90+ liver cancer stem cells. Correlation of the expression of SHH signalling components and CD90 in liver cancer cells and clinical tissues, as well as in enriched CD90+ liver cancer stem cells and the TCGA database, were analysed by quantitative RT-PCR, Western blotting and flow cytometry. Functional analysis was conducted by siRNA-mediated CD90, Gli1 and Gli3 gene knockdown, SHH treatment and application of the JAK2 inhibitor AZD1480 and IL6 neutralizing antibody in CD90+ liver cancer stem cells, followed by cell proliferation, migration, sphere formation and tumorigenicity assays. CD90 expression exhibited a high positive correlation with Gli1 and Gli3 in multiple liver cancer cell lines and human cancerous liver tissues, both of which showed a significant increase in liver cancer. Analysis of TCGA data revealed an association of CD90, Gli1 and Gli3 with a short overall survival and positive correlation between CD90 expression and Gli3 expression level. The stem cell potentials of CD90+ 97L liver cancer cells were greatly impaired by Gli1/3 knockdown with siRNA but enhanced by SHH treatment. Application of the JAK2 inhibitor AZD1480 and IL6 neutralizing antibody showed the CD90 and SHH/Gli-regulated liver cancer stem cell functions were mediated by the IL6/JAK2/STAT3 pathway. The stem cell properties of CD90+ liver cancer cells are regulated by the downstream SHH/Gli and IL6/JAK2/STAT3 signalling pathways. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Percutaneous intraportal application of adipose tissue-derived mesenchymal stem cells using a balloon occlusion catheter in a porcine model of liver fibrosis.

PubMed

Avritscher, Rony; Abdelsalam, Mohamed E; Javadi, Sanaz; Ensor, Joe; Wallace, Michael J; Alt, Eckhard; Madoff, David C; Vykoukal, Jody V

2013-12-01

To investigate the safety and effectiveness of a novel endovascular approach for therapeutic cell delivery using a balloon occlusion catheter in a large animal model of liver fibrosis. Transcatheter arterial embolization with ethiodized oil (Ethiodol) and ethanol was used to induce liver damage in 11 pigs. Mesenchymal stem cells (MSCs) were harvested from adipose tissue and engineered to express green fluorescent protein (GFP). A balloon occlusion catheter was positioned in the bilateral first-order portal vein branches 2 weeks after embolization to allow intraportal application of MSCs in six experimental animals. MSCs were allowed to dwell for 10 minutes using prolonged balloon inflation. Five control animals received a sham injection of normal saline in a similar fashion. Hepatic venous pressure gradient (HVPG) was measured immediately before necropsy. Specimens from all accessible lobes were obtained with ultrasound-guided percutaneous 18-gauge biopsy 2 hours after cell application. All animals were euthanized within 4 weeks. Fluorescent microscopy was used to assess the presence and distribution of cells. Liver injury and fibrosis were successfully induced in all animals. MSCs (6-10 × 10(7)) were successfully delivered into the portal vein in the six experimental animals. Cell application was not associated with vascular complications. HVPG showed no instances of portal hypertension. GFP-expressing MSCs were visualized in biopsy specimens and were distributed primarily within the sinusoidal spaces; however, 4 weeks after implantation, MSCs could not be identified in histologic specimens. A percutaneous endovascular approach for cell delivery using a balloon occlusion catheter proved safe for intraportal MSC application in a large animal model of liver fibrosis. © 2013 SIR Published by SIR All rights reserved.

Can the biliary enhancement of Gd-EOB-DTPA predict the degree of liver function?

PubMed

Okada, Masahiro; Ishii, Kazunari; Numata, Kazushi; Hyodo, Tomoko; Kumano, Seishi; Kitano, Masayuki; Kudo, Masatoshi; Murakami, Takamichi

2012-06-01

Excretion of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) in the bile may be related to liver function, because of elimination from the liver after preferential uptake by hepatocytes. The purpose of this study was to investigate the relation between liver and biliary enhancement in patients with or without liver dysfunction, and to compare the tumor-to-liver contrast in these patients. Forty patients [group 1: normal liver and Child-Pugh class A in 20 patients, group 2: Child-Pugh class B in 18 patients and Child-Pugh C in 2] were evaluated. All patients underwent MR imaging of the liver using a 1.5-Tesla system. T1-weighted 3D images were obtained at 5, 10, 15 and 20 minutes after Gd-EOB-DTPA injection. The relation between group 3 (total bilirubin <1.8 mg/dL) and group 4 (total bilirubin ≥1.8 mg/dL) was investigated at 20 minutes. Liver and biliary signals were measured, and compared between groups 1 and 2 or groups 3 and 4. Tumor-to-liver ratio was also evaluated between groups 1 and 2. Scheffe's post-hoc test after two-way repeated-measures ANOVA and Pearson's correlation test were used for statistical analysis. Liver enhancement showed significant difference at all time points between groups 1 and 2. Biliary enhancement did not show a significant difference between groups 1 and 2 at 5 minutes, but did at 10, 15 and 20 minutes. At 20 minutes, significant differences between groups 3 and 4 were seen for liver and biliary enhancement. At all time points, liver enhancement correlated with biliary enhancement in both groups. At 5 minutes and 20 minutes, statistical differences between groups 1 and 2 were seen for tumor-to-liver ratio. The degree of biliary enhancement has a close correlation to that of liver enhancement. It is especially important that insufficient liver enhancement causes lower tumor-to-liver contrast in the hepatobiliary phase of Gd-EOB-DTPA.

Nonselective inhibition of prostaglandin-endoperoxide synthase by naproxen ameliorates hepatic injury in animals with acute or chronic liver injury

PubMed Central

Bahde, Ralf; Kapoor, Sorabh; Gupta, Sanjeev

2014-01-01

The rising prevalence of hepatic injury due to toxins, metabolites, viruses, etc., necessitates development of further mechanisms for protecting the liver and for treating acute or chronic liver diseases. To examine whether inhibition of inflammation directed by cyclo-oxygenase pathways, we performed animal studies with naproxen, which inhibits prostaglandin-endoperoxide synthases 1 and 2 and is in extensive clinical use. We administered carbon tetrachloride to induce acute liver injury and ligated the common bile duct to induce chronic liver injury in adult rats. These experimental manipulations produced abnormalities in liver tests, tissue necrosis, compensatory hepatocyte or biliary proliferation, and onset of fibrosis, particularly after bile duct ligation. After carbon tetrachloride-induced acute injury, naproxen decreased liver test abnormalities, tissue necrosis and compensatory hepatocellular proliferation. After bile duct ligation-induced chronic injury, naproxen decreased liver test abnormalities, tissue injury and compensatory biliary hyperplasia. Moreover, after bile duct ligation, naproxen-treated rats showed more periductular oval liver cells, which have been classified as hepatic progenitor cells. In naproxen-treated rats, we found greater expression in hepatic stellate cells and mononuclear cells of cytoprotective factors, such as vascular endothelial growth factor. The ability of naproxen to induce expression of vascular endothelial growth factor was verified in cell culture studies with CFSC-8B clone of rat hepatic stellate cells. Whereas assays for carbon tetrachloride toxicity using cultured primary hepatocytes established that naproxen was not directly cytoprotective, we found conditioned medium containing vascular endothelial growth factor from naproxen-treated CFSC-8B cells protected hepatocytes from carbon tetrachloride toxicity. Therefore, naproxen was capable of ameliorating toxic liver injury, which involved naproxen-induced release of physiological cytoprotective factors in nonparenchymal liver cells. Such drug-induced release of endogenous cytoprotectants will advance therapeutic development for hepatic injury. PMID:24220607

Non-Invasive markers for hepatic fibrosis

PubMed Central

2011-01-01

With great advancements in the therapeutic modalities used for the treatment of chronic liver diseases, the accurate assessment of liver fibrosis is a vital need for successful individualized management of disease activity in patients. The lack of accurate, reproducible and easily applied methods for fibrosis assessment has been the major limitation in both the clinical management and for research in liver diseases. However, the problem of the development of biomarkers capable of non-invasive staging of fibrosis in the liver is difficult due to the fact that the process of fibrogenesis is a component of the normal healing response to injury, invasion by pathogens, and many other etiologic factors. Current non-invasive methods range from serum biomarker assays to advanced imaging techniques such as transient elastography and magnetic resonance imaging (MRI). Among non-invasive methods that gain strongest clinical foothold are FibroScan elastometry and serum-based APRI and FibroTest. There are many other tests that are not yet widely validated, but are none the less, promising. The rate of adoption of non-invasive diagnostic tests for liver fibrosis differs from country to country, but remains limited. At the present time, use of non-invasive procedures could be recommended as pre-screening that may allow physicians to narrow down the patients' population before definitive testing of liver fibrosis by biopsy of the liver. This review provides a systematic overview of these techniques, as well as both direct and indirect biomarkers based approaches used to stage fibrosis and covers recent developments in this rapidly advancing area. PMID:21849046

Evaluation of liver function using gadoxetate disodium (Gd-EOB-DTPA) enhanced MR imaging

NASA Astrophysics Data System (ADS)

Yamada, Akira; Hara, Takeshi; Li, Feng; Doi, Kunio

2010-03-01

Indocyanine green (ICG) is widely used for its clearance test in the evaluation of liver function. Gadoxetate disodium (Gd-EOB-DTPA) is a targeted MR contrast agent partially taken up by hepatocytes. The objective of this study was to evaluate the feasibility of an estimation of the liver function corresponding to plasma disappearance rate of indocyanine green (ICG-PDR) by use of the signal intensity of the liver alone in Gd-EOB-DTPA enhanced MR imaging (EOB-MRI). We evaluated fourteen patients who had EOB-MRI and ICG clearance test within 1 month. 2D-GRE T1 weighted images were obtained at pre contrast, 3 min (equilibrium phase) and 20 min (hepatobiliary phase) after the intravenous administration of Gd-EOB-DTPA, and the mean signal intensity of the liver was measured. The correlation between ICG-PDR and many parameters derived from the signal intensity of the liver in EOB-MRI was evaluated. The correlation coefficient between ICG-PDR and many parameters derived from the signal intensity of the liver in EOBMRI was low and not significant. The estimation of the liver function corresponding to ICG-PDR by use of the signal intensity of the liver alone in EOB-MRI would not be reliable.

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.

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

The binding of decomposition products of UDP-galactose to the microsomes and polyribosomes isolated from rat liver.

PubMed

Kopacz-Jodczyk, T; Gałasiński, W

1987-10-01

UDP-D-[U-14C]galactose is decomposed to [U-14C]galactose-1-phosphate and [U-14C]galactose by rat liver microsomal and crude polyribosomal fractions, under conditions commonly used to assay of glycosyltransferase activities. UDP-D-[U-14C]galactose, at neutral pH, is also chemically degraded to the [U-14C]galactose-1,2-cyclic phosphate. The 1,2-cyclic phosphate derivative of galactose also exists in the commercial UDP-D-[U-14C]galactose. It is a very important finding that products of the UDP-D-[U-14C]galactose decomposition are tightly, although nonenzymatically, bound to tested subcellular fractions and may create a false impression of protein glycosylation. The application of controls containing all radioactive substances present in suitable samples is recommended in order to avoid incorrect interpretations of the results.

Binding of decomposition products of UDP-galactose to the microsomes and polyribosomes isolated from rat liver

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

Kopacz-Jodczyk, T.; Galasinski, W.

1987-10-01

UDP-D-(U-/sup 14/C)galactose is decomposed to (U-/sup 14/C)galactose-1-phosphate and (U-/sup 14/C)galactose by rat liver microsomal and crude polyribosomal fractions, under conditions commonly used to assay of glycosyltransferase activities. UDP-D-(U-/sup 14/C)galactose, at neutral pH, is also chemically degraded to the (U-/sup 14/C)galactose-1,2-cyclic phosphate. The 1,2-cyclic phosphate derivative of galactose also exists in the commercial UDP-D-(U-/sup 14/C)galactose. It is a very important finding that products of the UDP-D-(U-/sup 14/C)galactose decomposition are tightly, although nonenzymatically, bound to tested subcellular fractions and may create a false impression of protein glycosylation. The application of controls containing all radioactive substances present in suitable samples is recommended inmore » order to avoid incorrect interpretations of the results.« less

Fatty acid methyl esters are detectable in the plasma and their presence correlates with liver dysfunction.

PubMed

Aleryani, Samir Lutf; Cluette-Brown, Joanne E; Khan, Zia A; Hasaba, Hasan; Lopez de Heredia, Luis; Laposata, Michael

2005-09-01

Methanol is a component of certain alcoholic beverages and is also an endogenously formed product. On this basis, we have proposed that methanol may promote synthesis of fatty acid methyl esters (FAMEs) in the same way that ethanol promotes fatty acid ethyl ester (FAEE) synthesis. We tested the hypothesis that FAMEs appear in the blood after ethanol intake. Patient plasma samples obtained from our laboratory (n=78) were grouped according to blood ethanol concentrations (intoxicated, blood ethanol >800 mg/l) and non-intoxicated. These samples were further subdivided into groups based on whether the patient had normal or abnormal liver function tests (abnormal, defined as > or =1 abnormality of plasma alanine and aspartate aminotransferase, albumin, total bilirubin, and alkaline phosphatase). A separate set of plasma samples were also divided into normal and abnormal groups based on pancreatic function tests (amylase and lipase). There were no patients with detectable ethanol in this group. Patients with abnormalities in pancreatic function tests were included upon recognition of endogenously produced FAMEs by patients with liver function test abnormalities. FAMEs were extracted from plasma and individual species of FAMEs quantified by gas chromatography-mass spectrometry (GC/MS). Increased concentrations of FAME were found in patient samples with evidence of liver dysfunction, regardless of whether or not they were intoxicated (n=21, p=0.01). No significant differences in plasma FAME concentrations were found between patients with normal (n=15) versus abnormal pancreatic function tests (n=22, p=0.72). The presence of FAMEs in human plasma may be related to the existence of liver disease, and not to blood ethanol concentrations or pancreatic dysfunction. The metabolic pathways associated with FAME production in patients with impaired liver function remain to be identified.

New experimental model for single liver lobe hyperthermia in small animals using non-directional microwaves.

PubMed

Tudorancea, Ionuț; Porumb, Vlad; Trandabăţ, Alexandru; Neaga, Decebal; Tamba, Bogdan; Iliescu, Radu; Dimofte, Gabriel M

2017-01-01

Our aim was to develop a new experimental model for in vivo hyperthermia using non-directional microwaves, applicable to small experimental animals. We present an affordable approach for targeted microwave heat delivery to an isolated liver lobe in rat, which allows rapid, precise and stable tissue temperature control. A new experimental model is proposed. We used a commercial available magnetron generating 2450 MHz, with 4.4V and 14A in the filament and 4500V anodic voltage. Modifications were required in order to adjust tissue heating such as to prevent overheating and to allow for fine adjustments according to real-time target temperature. The heating is controlled using a virtual instrument application implemented in LabView® and responds to 0.1° C variations in the target. Ten healthy adult male Wistar rats, weighing 250-270 g were used in this study. The middle liver lobe was the target for controlled heating, while the rest of the living animal was protected. In vivo microwave delivery using our experimental setting is safe for the animals. Target tissue temperature rises from 30°C to 40°C with 3.375°C / second (R2 = 0.9551), while the increment is lower it the next two intervals (40-42°C and 42-44°C) with 0.291°C/ s (R2 = 0.9337) and 0.136°C/ s (R2 = 0.7894) respectively, when testing in sequences. After reaching the desired temperature, controlled microwave delivery insures a very stable temperature during the experiments. We have developed an inexpensive and easy to manufacture system for targeted hyperthermia using non-directional microwave radiation. This system allows for fine and stable temperature adjustments within the target tissue and is ideal for experimental models testing below or above threshold hyperthermia.

New experimental model for single liver lobe hyperthermia in small animals using non-directional microwaves

PubMed Central

Iliescu, Radu; Dimofte, Gabriel M.

2017-01-01

Purpose Our aim was to develop a new experimental model for in vivo hyperthermia using non-directional microwaves, applicable to small experimental animals. We present an affordable approach for targeted microwave heat delivery to an isolated liver lobe in rat, which allows rapid, precise and stable tissue temperature control. Materials and methods A new experimental model is proposed. We used a commercial available magnetron generating 2450 MHz, with 4.4V and 14A in the filament and 4500V anodic voltage. Modifications were required in order to adjust tissue heating such as to prevent overheating and to allow for fine adjustments according to real-time target temperature. The heating is controlled using a virtual instrument application implemented in LabView® and responds to 0.1° C variations in the target. Ten healthy adult male Wistar rats, weighing 250–270 g were used in this study. The middle liver lobe was the target for controlled heating, while the rest of the living animal was protected. Results In vivo microwave delivery using our experimental setting is safe for the animals. Target tissue temperature rises from 30°C to 40°C with 3.375°C / second (R2 = 0.9551), while the increment is lower it the next two intervals (40–42°C and 42–44°C) with 0.291°C/ s (R2 = 0.9337) and 0.136°C/ s (R2 = 0.7894) respectively, when testing in sequences. After reaching the desired temperature, controlled microwave delivery insures a very stable temperature during the experiments. Conclusions We have developed an inexpensive and easy to manufacture system for targeted hyperthermia using non-directional microwave radiation. This system allows for fine and stable temperature adjustments within the target tissue and is ideal for experimental models testing below or above threshold hyperthermia PMID:28934251

The Coagulation Profile of End-Stage Liver Disease and Considerations for Intraoperative Management.

PubMed

Forkin, Katherine T; Colquhoun, Douglas A; Nemergut, Edward C; Huffmyer, Julie L

2018-01-01

The coagulopathy of end-stage liver disease results from a complex derangement in both anticoagulant and procoagulant processes. With even minor insults, cirrhotic patients experience either inappropriate bleeding or clotting, or even both simultaneously. The various phases of liver transplantation along with fluid and blood product administration may contribute to additional disturbances in coagulation. Thus, anesthetic management of patients undergoing liver transplantation to improve hemostasis and avoid inappropriate thrombosis in the perioperative environment can be challenging. To add to this challenge, traditional laboratory tests of coagulation are difficult to interpret in patients with end-stage liver disease. Viscoelastic coagulation tests such as thromboelastography (Haemonetics Corporation, Braintree, MA) and rotational thromboelastometry (TEM International, Munich, Germany) have helped to reduce transfusion of allogeneic blood products, especially fresh frozen plasma, but have also lead to the increased use of fibrinogen-containing products. In general, advancements in surgical techniques and anesthetic management have led to significant reduction in blood transfusion requirements during liver transplantation. Targeted transfusion protocols and pharmacologic prevention of fibrinolysis may further aid in the management of the complex coagulopathy of end-stage liver disease.

Detection and characterization of infectious Hepatitis E virus from commercial pig livers sold in local grocery stores in the USA.

PubMed

Feagins, A R; Opriessnig, T; Guenette, D K; Halbur, P G; Meng, X-J

2007-03-01

Hepatitis E virus (HEV) is a zoonotic pathogen of which pigs are reservoirs. To determine the presence of HEV RNA in commercial pig livers sold in local grocery stores in the USA, 127 packages of commercial pig liver were purchased and tested by a universal RT-PCR assay capable of detecting all four known HEV genotypes. Among the 127 livers tested, 14 were positive for HEV RNA. Sequence and phylogenetic analyses revealed that the 14 isolates all belonged to genotype 3. An animal study was subsequently conducted in pigs to determine whether the PCR-positive pig livers still contained infectious virus. The results showed that pigs inoculated with two of the three PCR-positive pig-liver homogenates became infected, as evidenced by the detection of faecal virus shedding, viraemia and seroconversion. The data demonstrated that commercial pig livers sold in grocery stores are contaminated by HEV and that the contaminating virus remains infectious, thus raising a public-health concern for food-borne HEV infection.

Optimizing the pre-referral workup for gastroenterology and hepatology specialty care: consensus using the Delphi method.

PubMed

Ho, Chanda K; Boscardin, Christy K; Gleason, Nathaniel; Collado, Don; Terdiman, Jonathan; Terrault, Norah A; Gonzales, Ralph

2016-02-01

Specialty care referrals have doubled in the last decade. Optimization of the pre-referral workup by a primary care doctor can lead to a more efficient first specialty visit with the patient. Guidance regarding pre-referral laboratory testing is a first step towards improving the specialty referral process. Our aim was to establish consensus regarding appropriate pre-referral workup for common gastrointestinal and liver conditions. The Delphi method was used to establish local consensus for recommending certain laboratory tests prior to specialty referral for 13 clinical conditions. Seven conditions from The University of Michigan outpatient referral guidelines were used as a baseline. An expert panel of three PCPs and nine gastroenterologists from three academic hospitals participated in three iterative rounds of electronic surveys. Each panellist ranked each test using a 5-point Likert scale (strongly disagree to strongly agree). Local panellists could recommend additional tests for the initial diagnoses, and also recommended additional diagnoses needing guidelines: iron deficiency anaemia, abdominal pain, irritable bowel syndrome, fatty liver disease, liver mass and cirrhosis. Consensus was defined as ≥70% of experts scoring ≥4 (agree or strongly agree). Applying Delphi methodology to extrapolate externally developed referral guidelines for local implementation resulted in considerable modifications. For some conditions, many tests from the external group were eliminated by the local group (abdominal bloating; iron deficiency anaemia; irritable bowel syndrome). In contrast, for chronic diarrhoea, abnormal liver enzymes and viral hepatitis, all/most original tests were retained with additional tests added. For liver mass, fatty liver disease and cirrhosis, there was high concordance among the panel with few tests added or eliminated. Consideration of externally developed referral guidelines using a consensus-building process leads to significant local tailoring and adaption. Our next steps include implementation and dissemination of these guidelines and evaluating their impact on care efficiency in clinical practice. © 2015 John Wiley & Sons, Ltd.

COMPARISON OF BLOOD PROTEIN AND TARGET ORGAN DNA AND PROTEIN BINDING FOLLOWING TOPICAL APPLICATION OF BENZO[A]PYRENE AND 7H-DIBENZO[C,G]CARBAZOLE TO MICE

EPA Science Inventory

7H-Dibenzo[c,g]carbazole (DBC) induces skin and liver tumors in mice following topical application, whereas benzo[a]pyrene (BP) induces only skin tumors. DBC also binds to liver DNA to a much greater extent than does BP. The present study examined factors that might account for t...

Evaluation of fatty proportion in fatty liver using least squares method with constraints.

PubMed

Li, Xingsong; Deng, Yinhui; Yu, Jinhua; Wang, Yuanyuan; Shamdasani, Vijay

2014-01-01

Backscatter and attenuation parameters are not easily measured in clinical applications due to tissue inhomogeneity in the region of interest (ROI). A least squares method(LSM) that fits the echo signal power spectra from a ROI to a 3-parameter tissue model was used to get attenuation coefficient imaging in fatty liver. Since fat's attenuation value is higher than normal liver parenchyma, a reasonable threshold was chosen to evaluate the fatty proportion in fatty liver. Experimental results using clinical data of fatty liver illustrate that the least squares method can get accurate attenuation estimates. It is proved that the attenuation values have a positive correlation with the fatty proportion, which can be used to evaluate the syndrome of fatty liver.

Study of Silymarin and Vitamin E Protective Effects on Silver Nanoparticle Toxicity on Mice Liver Primary Cell Culture.

PubMed

Faedmaleki, Firouz; Shirazi, Farshad H; Ejtemaeimehr, Shahram; Anjarani, Soghra; Salarian, Amir-Ahmad; Ahmadi Ashtiani, Hamidreza; Rastegar, Hossein

2016-02-01

Nanotechnology is a most promising field for generating new applications in medicine, although, only few nano products are currently in use for medical purposes. A most prominent nanoproduct is nanosilver. Nano-silver has biological properties which are significant for consumer products, food technology, textiles, and medical applications (e.g. wound care products, implantable medical devices, in diagnosis, drug delivery, and imaging). For their antibacterial activity, silver nanoparticles (Ag NPs) are largely used in various commercially available products. The use of nano-silver is becoming more and more widespread in medicine and related applications, and due to its increasing exposure, toxicological and environmental issues need to be raised. Cytotoxicity induced by silver nanoparticles (AgNPs) and the role that oxidative stress plays in this process were demonstrated in human hepatoma cells AgNPs agglomerated in the cytoplasm and nuclei of treated cells, and they induced intracellular oxidative stress. AgNP reduced ATP content of the cell and caused damage to mitochondria and increased production of reactive oxygen species (ROS) in a dose-dependent manner. Silymarin was known as a hepatoprotective agent that is used in the treatment of hepatic diseases including viral hepatitis, alcoholic liver diseases, Amanita mushroom poisoning, liver cirrhosis, toxic and drug-induced liver diseases. It promotes protein synthesis, helps in regenerating liver tissue, controls inflammation, enhances glucuronidation, and protects against glutathione depletion. Vitamin E is a well-known antioxidant and has hepatoprotective effect in liver diseases. In this study, we investigated the cytotoxic effects of Ag NPs on primary liver cells of mice. Cell viability (cytotoxicity) was examined with MTT assay after primary liver cells of mice exposure to AgNPs at 1, 10, 50, 100, 150, 200, 400 ppm for 24h. AgNPs caused a concentration- dependent decrease of cell viability (IC50 value = 121.7 ppm or µg/ml). Then the hepatoprotective effect of silymarin and vitamin E were experimented on silver nanoparticle toxicity on mice liver primary cell culture. The results showed that silymarin at 600 µg/ml and vitamin E at 2500 µmol/l have protective effects on silver nanoparticle toxicity on mice liver primary cell culture. Viability percentage of the primary liver cell of the mouse were exposed to silver nanoparticles at 121.7 ppm and co-treatment of silymarin, and vitamin E is more than viability percentage of the primary liver cell of the mouse were exposed to silver nanoparticles and silymarin or silver nanoparticles and vitamin E.

[Establishment of a D-galactosamine/lipopolysaccharide induced acute-on-chronic liver failure model in rats].

PubMed

Liu, Xu-hua; Chen, Yu; Wang, Tai-ling; Lu, Jun; Zhang, Li-jie; Song, Chen-zhao; Zhang, Jing; Duan, Zhong-ping

2007-10-01

To establish a practical and reproducible animal model of human acute-on-chronic liver failure for further study of the pathophysiological mechanism of acute-on-chronic liver failure and for drug screening and evaluation in its treatment. Immunological hepatic fibrosis was induced by human serum albumin in Wistar rats. In rats with early-stage cirrhosis (fibrosis stage IV), D-galactosamine and lipopolysaccharide were administered. Mortality and survival time were recorded in 20 rats. Ten rats were sacrificed at 4, 8, and 12 hours. Liver function tests and plasma cytokine levels were measured after D-galactosamine/lipopolysaccharide administration and liver pathology was studied. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Most of the rats treated with human albumin developed cirrhosis and fibrosis, and 90% of them died from acute liver failure after administration of D-galactosamine/lipopolysaccharide, with a mean survival time of (16.1+/-3.7) hours. Liver histopathology showed massive or submassive necrosis of the regenerated nodules, while fibrosis septa were intact. Liver function tests were compatible with massive necrosis of hepatocytes. Plasma level of TNFalpha increased significantly, parallel with the degree of the hepatocytes apoptosis. Plasma IL-10 levels increased similarly as seen in patients with acute-on-chronic liver failure. We established an animal model of acute-on-chronic liver failure by treating rats with human serum albumin and later with D-galactosamine and lipopolysaccharide. TNFalpha-mediated liver cell apoptoses plays a very important role in the pathogenesis of acute liver failure.

Does adjuvant radiotherapy suppress liver regeneration after partial hepatectomy?

PubMed

Choi, Jin-Hwa; Kim, Kyubo; Chie, Eui Kyu; Jang, Jin-Young; Kim, Sun Whe; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue; Ha, Sung W

2009-05-01

To analyze the influence of the adjuvant radiotherapy (RT) on the liver regeneration and liver function after partial hepatectomy (PH). Thirty-four patients who underwent PH for biliary tract cancer between October 2003 and July 2005 were reviewed. Hemihepatectomy was performed in 14 patients and less extensive surgery in 20. Of the patients, 19 patients had no adjuvant therapy (non-RT group) and 15 underwent adjuvant RT by a three-dimensional conformal technique (RT group). Radiation dose range was 40 to 50 Gy (median, 40 Gy). Liver volume on computed tomography and the results of liver function tests at 1, 4, 12, 24, and 52 weeks after PH were compared between the RT and non-RT groups. The preoperative characteristics were identical for both groups. During the interval between Weeks 4 and 12 when adjuvant RT was delivered in the RT group, the increase in liver volume was significantly smaller in the RT group than non-RT group (22.9 +/- 38.3cm(3) and 81.5 +/- 75.6cm(3), respectively, p = 0.007). However, the final liver volume measured at 1 year after PH did not differ between the two groups (p = 0.878). Liver function tests were comparable for both groups. The resection extent and original liver volume was independent factors for final liver volume measured at 1 year after PH. In this study, adjuvant RT delayed the liver regeneration process after PH, but the volume difference between the two study groups became nonsignificant after 1 year. Adjuvant RT had no additional adverse effect on liver function after PH.

Assessment of Liver Function in Patients With Hepatocellular Carcinoma: A New Evidence-Based Approach—The ALBI Grade

PubMed Central

Johnson, Philip J.; Berhane, Sarah; Kagebayashi, Chiaki; Satomura, Shinji; Teng, Mabel; Reeves, Helen L.; O'Beirne, James; Fox, Richard; Skowronska, Anna; Palmer, Daniel; Yeo, Winnie; Mo, Frankie; Lai, Paul; Iñarrairaegui, Mercedes; Chan, Stephen L.; Sangro, Bruno; Miksad, Rebecca; Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori

2015-01-01

Purpose Most patients with hepatocellular carcinoma (HCC) have associated chronic liver disease, the severity of which is currently assessed by the Child-Pugh (C-P) grade. In this international collaboration, we identify objective measures of liver function/dysfunction that independently influence survival in patients with HCC and then combine these into a model that could be compared with the conventional C-P grade. Patients and Methods We developed a simple model to assess liver function, based on 1,313 patients with HCC of all stages from Japan, that involved only serum bilirubin and albumin levels. We then tested the model using similar cohorts from other geographical regions (n = 5,097) and other clinical situations (patients undergoing resection [n = 525] or sorafenib treatment for advanced HCC [n = 1,132]). The specificity of the model for liver (dys)function was tested in patients with chronic liver disease but without HCC (n = 501). Results The model, the Albumin-Bilirubin (ALBI) grade, performed at least as well as the C-P grade in all geographic regions. The majority of patients with HCC had C-P grade A disease at presentation, and within this C-P grade, ALBI revealed two classes with clearly different prognoses. Its utility in patients with chronic liver disease alone supported the contention that the ALBI grade was indeed an index of liver (dys)function. Conclusion The ALBI grade offers a simple, evidence-based, objective, and discriminatory method of assessing liver function in HCC that has been extensively tested in an international setting. This new model eliminates the need for subjective variables such as ascites and encephalopathy, a requirement in the conventional C-P grade. PMID:25512453

Building shared experience to advance practical application of pathway-based toxicology: liver toxicity mode-of-action.

PubMed

Willett, Catherine; Caverly Rae, Jessica; Goyak, Katy O; Minsavage, Gary; Westmoreland, Carl; Andersen, Melvin; Avigan, Mark; Duché, Daniel; Harris, Georgina; Hartung, Thomas; Jaeschke, Hartmut; Kleensang, Andre; Landesmann, Brigitte; Martos, Suzanne; Matevia, Marilyn; Toole, Colleen; Rowan, Andrew; Schultz, Terry; Seed, Jennifer; Senior, John; Shah, Imran; Subramanian, Kalyanasundaram; Vinken, Mathieu; Watkins, Paul

2014-01-01

A workshop sponsored by the Human Toxicology Project Consortium (HTPC), "Building Shared Experience to Advance Practical Application of Pathway-Based Toxicology: Liver Toxicity Mode-of-Action" brought together experts from a wide range of perspectives to inform the process of pathway development and to advance two prototype pathways initially developed by the European Commission Joint Research Center (JRC): liver-specific fibrosis and steatosis. The first half of the workshop focused on the theory and practice of pathway development; the second on liver disease and the two prototype pathways. Participants agreed pathway development is extremely useful for organizing information and found that focusing the theoretical discussion on a specific AOP is extremely helpful. In addition, it is important to include several perspectives during pathway development, including information specialists, pathologists, human health and environmental risk assessors, and chemical and product manufacturers, to ensure the biology is well captured and end use is considered.

[3D evaluation model for drug hepatotoxicity testing on HepG2 cells and its application in drug safety evaluation].

PubMed

Li, Dan-Dan; Tang, Xiang-Lin; Tan, Hong-Ling; Liang, Qian-de; Wang, Yu-Guang; Ma, Zeng-Chun; Xiao, Cheng-Rong; Gao, Yue

2016-04-01

3D in vitro toxicity testing model was developed by magnetic levitation method for culture of the human hepatoma cell line HepG2 and applied to evaluate the drug hepatotoxicity. After formation of stable 3D structure for HepG2 cells, their glycogen storage capacity under 2D and 3D culture conditions were detected by immunohistochemistry technology, and the mRNA expression levels of phase Ⅰ and Ⅱ drug metabolism enzymes, drug transporters, nuclear receptors and liver-specific marker albumin(ALB) were compared between 2D and 3D culture conditions by using RT-PCR method. Immunohistochemistry results showed that HepG2 cells had abundant glycogen storage capacity under 3D culture conditions, which was similar to human liver tissues. The mRNA expression levels of major drug metabolism enzymes, drug transporters, nuclear receptors and ALB in HepG2 cells under 3D culture conditions were up-regulated as compared with 2D culture conditions. For drug hepatotoxicity evaluation, the typical hepatotoxic drug acetaminophen(APAP), and most reported drugs Polygonum multiflorum Thunb.(Chinese name He-shou-wu) and Psoraleae corylifolia L.(Chinese name Bu-gu-zhi) were selected for single dose and repeated dose(7 d) exposure. In the repeated dose exposure test, 3D HepG2 cells showed higher sensitivity. This established 3D HepG2 cells model with magnetic levitation 3D culture techniques was more close to the human liver tissues both in morphology and functions, so it was a better 3D hepatotoxicity evaluation model. Copyright© by the Chinese Pharmaceutical Association.

Hydrodynamic rupture of liver in combat patient: a case of successful application of "damage control" tactic in area of the hybrid war in East Ukraine.

PubMed

Khomenko, Igor; Shapovalov, Vitalii; Tsema, Ievgen; Makarov, Georgii; Palytsia, Roman; Zavodovskyi, Ievgen; Ishchenko, Ivan; Dinets, Andrii; Mishalov, Vladimir

2017-08-15

The hybrid war of Russia against Ukraine has been started in certain districts of Donetsk and Luhansk oblasts within the Donbas area in 2014. We report a clinical case of a combat patient who was injured after the multiple launcher rocket system "Grad" shelling, diagnosed with hydrodynamic liver rupture followed by medical management with application of damage control (DC) tactic in conditions of hybrid war. The patient underwent relaparatomy, liver resection, endoscopic papillosphincterotomy, endoscopic retrograde cholecystopancreatography, stenting of the common bile duct, and VAC-therapy. Applied treatment modalities were effective; the patient was discharged on the 49th day after injury. To our best knowledge, this is the first report describing a successful application of DC tactic in the hybrid war in East Ukraine. From this case, we suggest that application of DC tactic at all levels of combat medical care could save more lives.

High Efficient Differentiation of Functional Hepatocytes from Porcine Induced Pluripotent Stem Cells

PubMed Central

Ao, Ying; Mich-Basso, Jocelyn Danielle; Lin, Bo; Yang, Lei

2014-01-01

Hepatocyte transplantation is considered to be a promising therapy for patients with liver diseases. Induced pluripotent stem cells (iPSCs) provide an unlimited source for the generation of functional hepatocytes. In this study, we generated iPSCs from porcine ear fibroblasts (PEFs) by overexpressing Sox2, Klf4, Oct4, and c-Myc (SKOM), and developed a novel strategy for the efficient differentiation of hepatocyte-like cells from porcine iPSCs by following the processes of early liver development. The differentiated cells displayed the phenotypes of hepatocytes, exhibited classic hepatocyte-associated bio-functions, such as LDL uptake, glycogen storage and urea secretion, as well as possessed the metabolic activities of cytochrome P-450 (CYP) 3A and 2C. Furthermore, we compared the hepatocyte differentiation efficacy of our protocol with another published method, and the results demonstrated that our differentiation strategy could significantly improve the generation of morphological and functional hepatocyte-like cells from porcine iPSCs. In conclusion, this study establishes an efficient method for in vitro generation of functional hepatocytes from porcine iPSCs, which could represent a promising cell source for preclinical testing of cell-based therapeutics for liver failure and for pharmacological applications. PMID:24949734

Perfluorooctanoic acid exposure for 28 days affects glucose homeostasis and induces insulin hypersensitivity in mice

NASA Astrophysics Data System (ADS)

Yan, Shengmin; Zhang, Hongxia; Zheng, Fei; Sheng, Nan; Guo, Xuejiang; Dai, Jiayin

2015-06-01

Perfluoroalkyl acids (PFAAs) are widely used in many applications due to their unique physical and chemical characteristics. Because of the increasing prevalence of metabolic syndromes, including obesity, dyslipidemia and insulin resistance, concern has arisen about the roles of environmental pollutants in such diseases. Earlier epidemiologic studies showed a potential association between perfluorooctanoic acid (PFOA) and glucose metabolism, but how PFOA influences glucose homeostasis is still unknown. Here, we report on the modulation of the phosphatidylinositol 3-kinase-serine/threonine protein kinase (PI3K-AKT) signaling pathway in the livers of mice after 28 d of exposure to PFOA. Compared with normal mice, PFOA exposure significantly decreased the expression of the phosphatase and tensin homologue (PTEN) protein and affected the PI3K-AKT signaling pathway in the liver. Tolerance tests further indicated that PFOA exposure induced higher insulin sensitivity and glucose tolerance in mice. Biochemical analysis revealed that PFOA exposure reduced hepatic glycogen synthesis, which might be attributed to gluconeogenesis inhibition. The levels of several circulating proteins were altered after PFOA exposure, including proteins potentially related to diabetes and liver disease. Our results suggest that PFOA affected glucose metabolism and induced insulin hypersensitivity in mice.

Evolution of the Food and Drug Administration approach to liver safety assessment for new drugs: current status and challenges.

PubMed

Senior, John R

2014-11-01

Prompted by approval in 1997 of troglitazone and bromfenac, two drugs that promptly began to show serious and sometimes fatal liver toxicity, we began at the Food and Drug Administration (FDA) a series of annual conferences in 1999 to consider issues of drug-induced liver injury (DILI). First inviting reviewers of new drug applications we opened the audiences in 2001 to pharmaceutical industry and academic consultants to industry and FDA, and slides shown at the meetings were posted on the internet to be available at the website of the American Association for the Study of Liver Diseases (AASLD)-go to ( http://www.aasld.org/dili/Pages/default.aspx ). Observations by Dr. Hyman J. Zimmerman that "drug-induced hepatocellular jaundice is a serious lesion" with possible mortality formed a basis for developing a computer program to plot peak serum values for alanine aminotransferase (ALT) and total bilirubin (TBL) in an x-y log-log graph for all subjects enrolled in clinical trials. This program had the capability to show the time course of all liver tests for individuals who had both hepatocellular injury and reduced whole liver function, plus clinical narratives to diagnose the severity and most likely cause of the abnormalities. We called the program eDISH (for evaluation of Drug-Induced Serious Hepatotoxicity), and began in 2004 to use it to assess DILI in clinical trial subjects. From 2008, comments made by the presenters at the conferences about their slides and ensuing discussions have been added to the website. All this has raised awareness of the problem, and since 1997, the FDA has not had to withdraw a single drug because of post-marketing hepatotoxicity. Many issues still remain to be resolved; among the most controversial is the best method to estimate likelihood that a given liver injury was actually caused by the drug in question. On November 9, 2012, a workshop was convened to discuss the best practices for the assessment of drug-induced liver injury (DILI) in clinical trials.

Nutrition and Liver Health.

PubMed

Jackson, Alan A

2017-01-01

Good clinical practice is based on a secure and accurate diagnosis. Poor nutrition is frequently associated with disorders of the liver, and a specific nutrition diagnosis is needed for providing best care and experiencing successful outcome. There is opportunity for better-structured approaches to making secure and consistent nutritional diagnoses in patients with liver disease. Nutrition is the set of integrated processes by which cells, tissues, organs and the whole body acquire the energy and nutrients to retain normal structure and perform the required functions. At the level of the whole body, this is achieved through dietary supply and the capacity of the body to transform the substrates and cofactors necessary for metabolism. All of these domains (diet, metabolic capacity, activity of the microbiome, body composition and the level of demand for energy and nutrients) are influenced by levels of physical activity and can vary according to physiological and pathological disease states. The liver plays a central role in establishing and maintaining these regulated processes. Its capacity to achieve and maintain these functional capabilities is established during one's early life. When these capabilities are exceeded and the ability to maintain the milieu interieur is compromised, ill-health supervenes. Stress tests that assess flow through gateway pathways can be used to determine the maximal capacity and functional reserve for critical functions. The inability of the liver to reliably integrate body lipid metabolism and the accumulation of abnormal lipid are obvious manifestations of impaired regulation both in situations of weight loss, for example, the fatty liver of severe malnutrition, and in situations of energy excess, as in non-alcoholic fatty liver disease. The use of stable isotopic probes and the more recent definition of the variability in the metabolome in different nutritional and pathological states indicate the great potential for clinical tools that would enable a more precise nutritional diagnosis, but these require systematic investigation and application. For the present, approaches that place emphasis on being able to control the metabolic state without exposing the liver to unnecessary metabolic stress remain the basis for successful nutritional support. © 2017 S. Karger AG, Basel.

Percutaneous absorption of topically applied DTIC-14C (NSC-45388) in Yorkshire white pigs. Final report, 14 September-14 November 1976

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

Skierkowski, P.; Murphy, J.C.; Watson, E.S.

1978-03-01

The absorption of topically applied DTIC (5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide-2-14C) (NSC-45388) was studied in female, weanling, Yorkshire white pigs. After 48 hours, an average of 9.61% of the topically applied dose was excreted in the urine of the test animals. Liver and kidney showed the most consistent uptake of radioactivity with heart and adrenal samples also showing significant uptake. Radioactivity was detected in random muscle samples at 6 hours after application, and in bone after 48 hours. A significant percentage of the applied dose was generally detected at and near the site of application.

Hepatitis A, B, C, D, E, G: an update.

PubMed

Hall, Gairy F

2007-01-01

Acute and chronic liver diseases are an assortment of disorders brought to the clinician's attention by abnormal liver function tests or specific signs and symptoms. The differential diagnosis includes disorders that have primary or secondary liver involvement. This paper will be limited to the epidemiology, clinical manifestations, diagnosis, treatment, and prevention of the different viral liver diseases: A, B, C, D, E and G.

Intraarterial Liver-Directed Therapies: The Role of Interventional Oncology

PubMed Central

Ma, Jenson; Sandow, Tyler; Devun, Daniel; Kirsch, David; Gulotta, Paul; Gilbert, Patrick; Kay, Dennis

2017-01-01

Background: Since the early 1990s, the minimally invasive image-guided therapies used in interventional oncology to treat hepatocellular carcinoma have continued to evolve. Additionally, the range of applications has been expanded to the treatment of hepatic metastases from colorectal cancer, neuroendocrine tumors, cholangiocarcinoma, breast cancer, melanoma, and sarcoma. Methods: We searched the literature to identify publications from 1990 to the present on various image-guided intraarterial therapies and their efficacy, as well as their role in the management of primary and secondary liver malignancies. Results: Chemoembolization and radioembolization are considered a standard of care in treating, delaying progression of disease, and downstaging to bridge to liver transplantation. Progression-free survival and overall survival outcomes are promising in patients with colorectal cancer and neuroendocrine tumors with liver metastases. Applications in the treatment of hepatic metastases from cholangiocarcinoma, breast cancer, melanoma, and sarcoma also show potential. Conclusion: Interventional oncology and its image-guided intraarterial therapies continue to gain recognition as treatment options for primary and secondary liver cancers. Growing evidence supports their role as a standard of care alongside medical oncology, surgery, and radiation oncology. PMID:29230127

Establishment of an Effective Radioiodide Thyroid Ablation Protocol in Mice.

PubMed

Schmohl, Kathrin A; Müller, Andrea M; Schwenk, Nathalie; Knoop, Kerstin; Rijntjes, Eddy; Köhrle, Josef; Heuer, Heike; Bartenstein, Peter; Göke, Burkhard; Nelson, Peter J; Spitzweg, Christine

2015-09-01

Due to the high variance in available protocols on iodide-131 ((131)I) ablation in rodents, we set out to establish an effective method to generate a thyroid-ablated mouse model that allows the application of the sodium iodide symporter (NIS) as a reporter gene without interference with thyroidal NIS. We tested a range of (131)I doses with and without prestimulation of thyroidal radioiodide uptake by a low-iodine diet and thyroid-stimulating hormone (TSH) application. Efficacy of induction of hypothyroidism was tested by measurement of serum T4 concentrations, pituitary TSHβ and liver deiodinase type 1 (DIO1) mRNA expression, body weight analysis, and (99m)Tc-pertechnetate scintigraphy. While 200 µCi (7.4 MBq) (131)I alone was not sufficient to abolish thyroidal T4 production, 500 µCi (18.5 MBq) (131)I combined with 1 week of a low-iodine diet decreased serum concentrations below the detection limit. However, the high (131)I dose resulted in severe side effects. A combination of 1 week of a low-iodine diet followed by injection of bovine TSH before the application of 150 µCi (5.5 MBq) (131)I decreased serum T4 concentrations below the detection limit and significantly increased pituitary TSHβ concentrations. The systemic effects of induced hypothyroidism were shown by growth arrest and a decrease in liver DIO1 expression below the detection limit. (99m)Tc-pertechnetate scintigraphy revealed absence of thyroidal (99m)Tc-pertechnetate uptake in ablated mice. In summary, we report a revised protocol for radioiodide ablation of the thyroid gland in the mouse to generate an in vivo model that allows the study of thyroid hormone action using NIS as a reporter gene.

Establishment of an Effective Radioiodide Thyroid Ablation Protocol in Mice

PubMed Central

Schmohl, Kathrin A.; Müller, Andrea M.; Schwenk, Nathalie; Knoop, Kerstin; Rijntjes, Eddy; Köhrle, Josef; Heuer, Heike; Bartenstein, Peter; Göke, Burkhard; Nelson, Peter J.; Spitzweg, Christine

2015-01-01

Due to the high variance in available protocols on iodide-131 (131I) ablation in rodents, we set out to establish an effective method to generate a thyroid-ablated mouse model that allows the application of the sodium iodide symporter (NIS) as a reporter gene without interference with thyroidal NIS. We tested a range of 131I doses with and without prestimulation of thyroidal radioiodide uptake by a low-iodine diet and thyroid-stimulating hormone (TSH) application. Efficacy of induction of hypothyroidism was tested by measurement of serum T4 concentrations, pituitary TSHβ and liver deiodinase type 1 (DIO1) mRNA expression, body weight analysis, and 99mTc-pertechnetate scintigraphy. While 200 µCi (7.4 MBq) 131I alone was not sufficient to abolish thyroidal T4 production, 500 µCi (18.5 MBq) 131I combined with 1 week of a low-iodine diet decreased serum concentrations below the detection limit. However, the high 131I dose resulted in severe side effects. A combination of 1 week of a low-iodine diet followed by injection of bovine TSH before the application of 150 µCi (5.5 MBq) 131I decreased serum T4 concentrations below the detection limit and significantly increased pituitary TSHβ concentrations. The systemic effects of induced hypothyroidism were shown by growth arrest and a decrease in liver DIO1 expression below the detection limit. 99mTc-pertechnetate scintigraphy revealed absence of thyroidal 99mTc-pertechnetate uptake in ablated mice. In summary, we report a revised protocol for radioiodide ablation of the thyroid gland in the mouse to generate an in vivo model that allows the study of thyroid hormone action using NIS as a reporter gene. PMID:26601076

Local application of osteoprotegerin-chitosan gel in critical-sized defects in a rabbit model

PubMed Central

2017-01-01

Background Osteoprotegerin (OPG) is used for the systemic treatment of bone diseases, although it has many side effects. The aim of this study was to investigate a newly formulated OPG-chitosan gel for local application to repair bone defects. Recent studies have reported that immunodetection of osteopontin (OPN) and osteocalcin (OC) can be used to characterise osteogenesis and new bone formation. Methods The osteogenic potential of the OPG-chitosan gel was evaluated in rabbits. Critical-sized defects were created in the calvarial bone, which were either left unfilled (control; group I), or filled with chitosan gel (group II) or OPG-chitosan gel (group III), with rabbits sacrificed at 6 and 12 weeks. Bone samples from the surgical area were decalcified and treated with routine histological and immunohistochemical protocols using OC, OPN, and cathepsin K (osteoclast marker) antibodies. The toxicity of the OPG-chitosan gel was evaluated by biochemical assays (liver and kidney function tests). Results The mean bone growth in defects filled with the OPG-chitosan gel was significantly higher than those filled with the chitosan gel or the unfilled group (p < 0.05). At 6 and 12 weeks, the highest levels of OC and OPN markers were found in the OPG-chitosan gel group, followed by the chitosan gel group. The number of osteoclasts in the OPG-chitosan gel group was lower than the other groups. The results of the liver and kidney functional tests indicated no signs of harmful systemic effects of treatment. In conclusion, the OPG-chitosan gel has many characteristics that make it suitable for bone repair and regeneration, highlighting its potential benefits for tissue engineering applications. PMID:28674665

Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome.

PubMed

Vootla, Vamshidhar R; Daniel, Myrta

2015-01-01

Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome.

A D-D/D-T fusion reaction based neutron generator system for liver tumor BNCT

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

Koivunoro, H.; Lou, T.P.; Leung, K. N.

2003-04-02

Boron-neutron capture therapy (BNCT) is an experimental radiation treatment modality used for highly malignant tumor treatments. Prior to irradiation with low energetic neutrons, a 10B compound is located selectively in the tumor cells. The effect of the treatment is based on the high LET radiation released in the {sup 10}B(n,{alpha}){sup 7}Li reaction with thermal neutrons. BNCT has been used experimentally for brain tumor and melanoma treatments. Lately applications of other severe tumor type treatments have been introduced. Results have shown that liver tumors can also be treated by BNCT. At Lawrence Berkeley National Laboratory, various compact neutron generators based onmore » D-D or D-T fusion reactions are being developed. The earlier theoretical studies of the D-D or D-T fusion reaction based neutron generators have shown that the optimal moderator and reflector configuration for brain tumor BNCT can be created. In this work, the applicability of 2.5 MeV neutrons for liver tumor BNCT application was studied. The optimal neutron energy for external liver treatments is not known. Neutron beams of different energies (1eV < E < 100 keV) were simulated and the dose distribution in the liver was calculated with the MCNP simulation code. In order to obtain the optimal neutron energy spectrum with the D-D neutrons, various moderator designs were performed using MCNP simulations. In this article the neutron spectrum and the optimized beam shaping assembly for liver tumor treatments is presented.« less

Applicability of a gene expression based prediction method to SD and Wistar rats: an example of CARCINOscreen®.

PubMed

Matsumoto, Hiroshi; Saito, Fumiyo; Takeyoshi, Masahiro

2015-12-01

Recently, the development of several gene expression-based prediction methods has been attempted in the fields of toxicology. CARCINOscreen® is a gene expression-based screening method to predict carcinogenicity of chemicals which target the liver with high accuracy. In this study, we investigated the applicability of the gene expression-based screening method to SD and Wistar rats by using CARCINOscreen®, originally developed with F344 rats, with two carcinogens, 2,4-diaminotoluen and thioacetamide, and two non-carcinogens, 2,6-diaminotoluen and sodium benzoate. After the 28-day repeated dose test was conducted with each chemical in SD and Wistar rats, microarray analysis was performed using total RNA extracted from each liver. Obtained gene expression data were applied to CARCINOscreen®. Predictive scores obtained by the CARCINOscreen® for known carcinogens were > 2 in all strains of rats, while non-carcinogens gave prediction scores below 0.5. These results suggested that the gene expression based screening method, CARCINOscreen®, can be applied to SD and Wistar rats, widely used strains in toxicological studies, by setting of an appropriate boundary line of prediction score to classify the chemicals into carcinogens and non-carcinogens.

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.

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

Imaging-based quantification of hepatic fat: methods and clinical applications.

PubMed

Ma, Xiaozhou; Holalkere, Nagaraj-Setty; Kambadakone R, Avinash; Mino-Kenudson, Mari; Hahn, Peter F; Sahani, Dushyant V

2009-01-01

Fatty liver disease comprises a spectrum of conditions (simple hepatic steatosis, steatohepatitis with inflammatory changes, and end-stage liver disease with fibrosis and cirrhosis). Hepatic steatosis is often associated with diabetes and obesity and may be secondary to alcohol and drug use, toxins, viral infections, and metabolic diseases. Detection and quantification of liver fat have many clinical applications, and early recognition is crucial to institute appropriate management and prevent progression. Histopathologic analysis is the reference standard to detect and quantify fat in the liver, but results are vulnerable to sampling error. Moreover, it can cause morbidity and complications and cannot be repeated often enough to monitor treatment response. Imaging can be repeated regularly and allows assessment of the entire liver, thus avoiding sampling error. Selection of appropriate imaging methods demands understanding of their advantages and limitations and the suitable clinical setting. Ultrasonography is effective for detecting moderate or severe fatty infiltration but is limited by lack of interobserver reliability and intraobserver reproducibility. Computed tomography allows quantitative and qualitative evaluation and is generally highly accurate and reliable; however, the results may be confounded by hepatic parenchymal changes due to cirrhosis or depositional diseases. Magnetic resonance (MR) imaging with appropriate sequences (eg, chemical shift techniques) has similarly high sensitivity, and MR spectroscopy provides unique advantages for some applications. However, both are expensive and too complex to be used to monitor steatosis. (c) RSNA, 2009.

Tailoring microfluidic systems for organ-like cell culture applications using multiphysics simulations

NASA Astrophysics Data System (ADS)

Hagmeyer, Britta; Schütte, Julia; Böttger, Jan; Gebhardt, Rolf; Stelzle, Martin

2013-03-01

Replacing animal testing with in vitro cocultures of human cells is a long-term goal in pre-clinical drug tests used to gain reliable insight into drug-induced cell toxicity. However, current state-of-the-art 2D or 3D cell cultures aiming at mimicking human organs in vitro still lack organ-like morphology and perfusion and thus organ-like functions. To this end, microfluidic systems enable construction of cell culture devices which can be designed to more closely resemble the smallest functional unit of organs. Multiphysics simulations represent a powerful tool to study the various relevant physical phenomena and their impact on functionality inside microfluidic structures. This is particularly useful as it allows for assessment of system functions already during the design stage prior to actual chip fabrication. In the HepaChip®, dielectrophoretic forces are used to assemble human hepatocytes and human endothelial cells in liver sinusoid-like structures. Numerical simulations of flow distribution, shear stress, electrical fields and heat dissipation inside the cell assembly chambers as well as surface wetting and surface tension effects during filling of the microchannel network supported the design of this human-liver-on-chip microfluidic system for cell culture applications. Based on the device design resulting thereof, a prototype chip was injection-moulded in COP (cyclic olefin polymer). Functional hepatocyte and endothelial cell cocultures were established inside the HepaChip® showing excellent metabolic and secretory performance.

Liver regenerative medicine: advances and challenges.

PubMed

Chistiakov, Dimitry A

2012-01-01

Liver transplantation is the standard care for many end-stage liver diseases. However, donor organs are scarce and some people succumb to liver failure before a donor is found. Liver regenerative medicine is a special interdisciplinary field of medicine focused on the development of new therapies incorporating stem cells, gene therapy and engineered tissues in order to repair or replace the damaged organ. In this review we consider the emerging progress achieved in the hepatic regenerative medicine within the last decade. The review starts with the characterization of liver organogenesis, fetal and adult stem/progenitor cells. Then, applications of primary hepatocytes, embryonic and adult (mesenchymal, hematopoietic and induced pluripotent) stem cells in cell therapy of liver diseases are considered. Current advances and challenges in producing mature hepatocytes from stem/progenitor cells are discussed. A section about hepatic tissue engineering includes consideration of synthetic and natural biomaterials in engineering scaffolds, strategies and achievements in the development of 3D bioactive matrices and 3D hepatocyte cultures, liver microengineering, generating bioartificial liver and prospects for fabrication of the bioengineered liver. Copyright © 2012 S. Karger AG, Basel.

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

PubMed

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

2014-04-01

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

Deep Learning with Convolutional Neural Network for Differentiation of Liver Masses at Dynamic Contrast-enhanced CT: A Preliminary Study.

PubMed

Yasaka, Koichiro; Akai, Hiroyuki; Abe, Osamu; Kiryu, Shigeru

2018-03-01

Purpose To investigate diagnostic performance by using a deep learning method with a convolutional neural network (CNN) for the differentiation of liver masses at dynamic contrast agent-enhanced computed tomography (CT). Materials and Methods This clinical retrospective study used CT image sets of liver masses over three phases (noncontrast-agent enhanced, arterial, and delayed). Masses were diagnosed according to five categories (category A, classic hepatocellular carcinomas [HCCs]; category B, malignant liver tumors other than classic and early HCCs; category C, indeterminate masses or mass-like lesions [including early HCCs and dysplastic nodules] and rare benign liver masses other than hemangiomas and cysts; category D, hemangiomas; and category E, cysts). Supervised training was performed by using 55 536 image sets obtained in 2013 (from 460 patients, 1068 sets were obtained and they were augmented by a factor of 52 [rotated, parallel-shifted, strongly enlarged, and noise-added images were generated from the original images]). The CNN was composed of six convolutional, three maximum pooling, and three fully connected layers. The CNN was tested with 100 liver mass image sets obtained in 2016 (74 men and 26 women; mean age, 66.4 years ± 10.6 [standard deviation]; mean mass size, 26.9 mm ± 25.9; 21, nine, 35, 20, and 15 liver masses for categories A, B, C, D, and E, respectively). Training and testing were performed five times. Accuracy for categorizing liver masses with CNN model and the area under receiver operating characteristic curve for differentiating categories A-B versus categories C-E were calculated. Results Median accuracy of differential diagnosis of liver masses for test data were 0.84. Median area under the receiver operating characteristic curve for differentiating categories A-B from C-E was 0.92. Conclusion Deep learning with CNN showed high diagnostic performance in differentiation of liver masses at dynamic CT. © RSNA, 2017 Online supplemental material is available for this article.

Brainstem evoked response audiometry: an investigatory tool in detecting hepatic encephalopathy in decompensated chronic liver disease.

PubMed

Kabali, Balasubramanian; Velayutham, Gowri; Kapali, Suresh Chander

2014-01-01

It is estimated that globally there is a marked increase in liver disease with reports of rising morbidity and mortality, particularly in younger age groups. Brainstem auditory evoked potential (BAEP) was recorded in 60 decompensated chronic liver disease (DCLD) subjects who fulfilled the selection criteria and compared to 60 age and gender matched healthy subjects with normal liver functions. DCLD subjects were divided into two inter groups based on presence or absence of hepatic encephalopathy (HE). Group 1 comprises of 30 subjects of grade- I HE and Group 2 included 30 subjects without hepatic encephalopathy (NHE). Absolute and interpeak wave latencies were measured. Results were analysed by student independent t- test using SPSS software 11 version. Statistical significance was tested using P value. From the present study it can be concluded that the central nervous system is involved in liver cirrhosis evidenced by an abnormal BAEP latencies parameters. This shows that there may be progressive demyelination occurring along with axonal loss or dysfunction in liver cirrhosis HE. This study suggests that periodic evaluation of cirrhotic individuals to such test will help in monitoring the progress of encephalopathy. The prime goal of this study is early diagnosis and initiation of treatment before the onset of coma can reduce the fatality rate.

Assessment of School Readiness in Chronic Cholestatic Liver Disease: A Pilot Study Examining Children with and without Liver Transplantation.

PubMed

Gold, Anna; Rogers, Alaine; Cruchley, Elizabeth; Rankin, Stephanie; Parmar, Arpita; Kamath, Binita M; Avitzur, Yaron; Ng, Vicky Lee

2017-01-01

Background. Assessment of school readiness evaluates physical, social-emotional, and neuropsychological domains essential for educational success. Cognitive testing of preschool aged children with chronic liver disease may guide more timely interventions and focused efforts by health care providers. Patients and Methods. Children with chronic cholestatic liver disease diagnosed as an infant and still with their native liver (NL) and children who received a liver transplant (LT) before age of 2 years underwent testing with a battery of well-validated pediatric psychometric measures. Results. Eighteen (13 LT, 5 NL) patients (median age of 4.45 and 4.05 years, resp.) were tested. Median Full-Scale IQ was 98 (range 102-116) for LT and 116 [(range 90-106), p = 0.35, NS] for NL subjects. LT recipients had significantly greater visual based difficulties, poorer caregiver rated daily living skills ( p = 0.04), and higher levels of executive function based difficulties (e.g., inattention, inhibition). Conclusion. This pilot study highlights the risk of neuropsychological difficulties in early school age children who were under 2 years of age at time of LT. Comprehensive early school age assessment should integrate psychometric measures to identify children at greatest risk, thus allowing for proactive educational intervention.

Dental postoperative bleeding complications in patients with suspected and documented liver disease.

PubMed

Hong, C H; Scobey, M W; Napenas, J J; Brennan, M T; Lockhart, P B

2012-10-01

The aims of this study were to determine the frequency of bleeding complications following dental procedures in patients with known or suspected chronic liver disease and whether international normalized ratio (INR) determination could aid in predicting bleeding complications in these patients. We identified 90 patients (mean age: 51 ± 9 years) in this retrospective chart review. Sixty-nine patients had a known history of chronic liver disease and 21 had suspected chronic liver disease. Descriptive statistics were determined. Independent sample t-test and one-way variance test were utilized for continuous variables and chi-square test for dichotomous variables. The mean INR value for all patients was 1.2 ± 0.3. The INR value was significantly associated with the diagnosis of liver cirrhosis, the diagnoses of Hepatitis B and C together, the presence of ascites alone, and the number of clinical signs and symptoms (i.e. ascites, jaundice and encephalopathy) present. Nine patients with INR values between 1.5 and 2 underwent invasive dental procedures without postoperative bleeding complications. There were no episodes of postoperative bleeding in patients. The findings suggest that clinicians should not rely solely on an INR value to predict post-procedure bleeding in patients with liver disease. © 2012 John Wiley & Sons A/S.

Representative Sinusoids for Hepatic Four-Scale Pharmacokinetics Simulations

PubMed Central

Schwen, Lars Ole; Schenk, Arne; Kreutz, Clemens; Timmer, Jens; Bartolomé Rodríguez, María Matilde; Kuepfer, Lars; Preusser, Tobias

2015-01-01

The mammalian liver plays a key role for metabolism and detoxification of xenobiotics in the body. The corresponding biochemical processes are typically subject to spatial variations at different length scales. Zonal enzyme expression along sinusoids leads to zonated metabolization already in the healthy state. Pathological states of the liver may involve liver cells affected in a zonated manner or heterogeneously across the whole organ. This spatial heterogeneity, however, cannot be described by most computational models which usually consider the liver as a homogeneous, well-stirred organ. The goal of this article is to present a methodology to extend whole-body pharmacokinetics models by a detailed liver model, combining different modeling approaches from the literature. This approach results in an integrated four-scale model, from single cells via sinusoids and the organ to the whole organism, capable of mechanistically representing metabolization inhomogeneity in livers at different spatial scales. Moreover, the model shows circulatory mixing effects due to a delayed recirculation through the surrounding organism. To show that this approach is generally applicable for different physiological processes, we show three applications as proofs of concept, covering a range of species, compounds, and diseased states: clearance of midazolam in steatotic human livers, clearance of caffeine in mouse livers regenerating from necrosis, and a parameter study on the impact of different cell entities on insulin uptake in mouse livers. The examples illustrate how variations only discernible at the local scale influence substance distribution in the plasma at the whole-body level. In particular, our results show that simultaneously considering variations at all relevant spatial scales may be necessary to understand their impact on observations at the organism scale. PMID:26222615

What is the best strategy for investigating abnormal liver function tests in primary care? Implications from a prospective study.

PubMed

Lilford, Richard J; Bentham, Louise M; Armstrong, Matthew J; Neuberger, James; Girling, Alan J

2013-06-20

Evaluation of predictive value of liver function tests (LFTs) for the detection of liver-related disease in primary care. A prospective observational study. 11 UK primary care practices. Patients (n=1290) with an abnormal eight-panel LFT (but no previously diagnosed liver disease). Patients were investigated by recording clinical features, and repeating LFTs, specific tests for individual liver diseases, and abdominal ultrasound scan. Patients were characterised as having: hepatocellular disease; biliary disease; tumours of the hepato-biliary system and none of the above. The relationship between LFT results and disease categories was evaluated by stepwise regression and logistic discrimination, with adjustment for demographic and clinical factors. True and False Positives generated by all possible LFT combinations were compared with a view towards optimising the choice of analytes in the routine LFT panel. Regression methods showed that alanine aminotransferase (ALT) was associated with hepatocellular disease (32 patients), while alkaline phosphatase (ALP) was associated with biliary disease (12 patients) and tumours of the hepatobiliary system (9 patients). A restricted panel of ALT and ALP was an efficient choice of analytes, comparing favourably with the complete panel of eight analytes, provided that 48 False Positives can be tolerated to obtain one additional True Positive. Repeating a complete panel in response to an abnormal reading is not the optimal strategy. The LFT panel can be restricted to ALT and ALP when the purpose of testing is to exclude liver disease in primary care.

Liver enzyme monitoring in patients treated with troglitazone.

PubMed

Graham, D J; Drinkard, C R; Shatin, D; Tsong, Y; Burgess, M J

2001-08-15

Soon after initial marketing in March 1997, troglitazone, the first thiazolidinedione antidiabetic agent, was found to cause life-threatening acute liver failure. The drug was removed from the market in March 2000. To evaluate the effect of US Food and Drug Administration (FDA) risk management efforts, including repeated labeling changes and "Dear Healthcare Professional" letters, on periodic liver enzyme monitoring of patients taking troglitazone. Claims data from a large, multistate managed care organization were used to establish 4 cohorts of patients (N = 7603) with at least 90 days of health plan enrollment before first troglitazone prescription during 4 consecutive periods spanning April 1997 to September 1999 and representing 4 progressively stringent liver monitoring recommendations. Percentage of eligible troglitazone users in each cohort with baseline, monthly (for up to 6 months of continuous use), and complete (baseline and monthly) enzyme monitoring, based on computerized records of laboratory claims. Baseline testing increased from 15% before any FDA monitoring recommendations (cohort 1) to 44.6% following 4 separate FDA interventions (cohort 4; P<.001). In cohort 4, 33.4% of users had follow-up testing after 1 month of therapy, falling to 13% after 5 months of continuous use. In all cohorts, less than 5% received all recommended liver enzyme tests by the third month of continuous use. The FDA risk management efforts did not achieve meaningful or sustained improvement in liver enzyme testing. Evaluation of the impact of regulatory actions is needed before such actions can be regarded as effective or sufficient.

Orlistat-induced fulminant hepatic failure.

PubMed

Sall, D; Wang, J; Rashkin, M; Welch, M; Droege, C; Schauer, D

2014-12-01

Orlistat was approved by the Food and Drug Administration in 1998 and has been shown to be superior to placebo in achieving weight loss. It is generally well tolerated. However, severe liver injury has been reported. We present a case of hepatic failure in a patient taking orlistat. A 54-year-old African-American woman with hypertension presented with hepatic failure. She had noticed increasing fatigue, jaundice and confusion. She used alcohol sparingly and denied tobacco or illicit drug use, but had been taking over-the-counter orlistat for the past two months. Physical examination revealed scleral icterus, jaundice, asterixis and slow speech. Laboratory testing showed markedly abnormal liver function tests with coagulopathy. Acute viral and autoimmune serologies were negative, as was toxicology screen. Liver biopsy showed necrotic hepatic parenchyma likely secondary to drug toxicity. Based upon her clinical presentation and time course, the pattern of liver injury seen on liver biopsy and lack of an alternative plausible explanation, her liver failure was most likely associated with orlistat use. She continued to deteriorate and ultimately underwent orthotopic liver transplantation. Fourteen cases of severe liver injury associated with orlistat use have been reported, four of which are detailed in the literature. This is the second published case of liver failure associated with over-the-counter orlistat usage. Clinicians should be aware of the growing number of cases associating liver injury and orlistat use and carefully monitor their patients on this medication for signs of hepatic dysfunction. © 2014 The Authors. Clinical Obesity © 2014 World Obesity.

Ammonia blood test

MedlinePlus

Serum ammonia; Encephalopathy - ammonia; Cirrhosis - ammonia; Liver failure - ammonia ... Ammonia (NH3) is produced by cells throughout the body, especially the intestines, liver, and kidneys. Most of ...

Effect of Topically Applied Diisopropylfluorophosphate on Glucose Metabolism in the Rat.

DTIC Science & Technology

1982-12-01

intermediary metabolism, * liver , adipose tissue topical application. DFP - diisopropylfluorophosphate OL AIISTRACT’MOMNomrse sft NOMNY Ol~ dulp lekib) .1A...skin, liver and adipose tissue preparations were determined. DFP had no demonstratable effect on glucose oxidation. In contrast, DFP enhanced fatty...acid synthesis by 70% over the control values in the skin and by 56 and 92% in the liver and adipose tissue, respectively. DFP stimulated synthesis. of

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

Relation of Insulin Resistance and Liver Fibrosis Progression in Patients with Chronic Hepatitis C Virus Infection

PubMed Central

Mohamed, Hassan R; Abdel-Azziz, Mohamed Yaqoot; Zalata, Kkaled Refaat; Abdel-Razik, Ahmed M M

2009-01-01

Background: Hepatitis C virus (HCV) infection can predispose to the development of insulin resistance before diabetes occurs. Such a potential link is particularly cogent in light of recent data indicate that diabetes may be associated with increased hepatic fibrosis progression in patients with chronic HCV infection. The aim of the study is to determine the prevalence of insulin resistance in non diabetic patients with chronic hepatitis C and its relation to liver fibrosis. Methods: Thirty eight patients with chronic liver diseases. They subdivided into 2 groups; chronic hepatitis C (CHC) with elevated liver enzymes and CHC with normal liver enzymes. Age and sex matched 12 healthy subjects as control group. All subjects were subjected to Careful history and copmlete examination with stress upon symptoms and signs of chronic liver diseases. Investigations include liver function tests; viral markers (Anti HCV antibodies & PCR for HCV). Serum fasting glucose; serum fasting insulin; homeostasis model assessment (HOMA), liver biopsy and abdominal ultrasound. Results: No correlation between viral load and hepatic fibrosis in HCV infected patients. Liver fibrosis is considerably higher among HCV patients with elevated serum transaminase levels. Insulin resistance is present in HCV infected cases compared with control group and it is positively correlated with liver fibrosis. Conclusion: The present data support the hypothesis that insulin resistance may increase the rate of fibrosis progression in non diabetic patients with chronic HCV. Follow up of hyperinsulinemia by serial measurement of HOMA test in non diabetic HCV infected patients may be a biochemical indicator for progression of liver fibrosis. PMID:21475535

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.

Current status and perspectives in split liver transplantation

PubMed Central

Lauterio, Andrea; Di Sandro, Stefano; Concone, Giacomo; De Carlis, Riccardo; Giacomoni, Alessandro; De Carlis, Luciano

2015-01-01

Growing experience with the liver splitting technique and favorable results equivalent to those of whole liver transplant have led to wider application of split liver transplantation (SLT) for adult and pediatric recipients in the last decade. Conversely, SLT for two adult recipients remains a challenging surgical procedure and outcomes have yet to improve. Differences in organ shortages together with religious and ethical issues related to cadaveric organ donation have had an impact on the worldwide distribution of SLT. Despite technical refinements and a better understanding of the complex liver anatomy, SLT remains a technically and logistically demanding surgical procedure. This article reviews the surgical and clinical advances in this field of liver transplantation focusing on the role of SLT and the issues that may lead a further expansion of this complex surgical procedure. PMID:26494957

The role of serum hyaluronic acid determination in the diagnosis of liver fibrosis.

PubMed

Gudowska, Monika; Cylwik, Bogdan; Chrostek, Lech

2017-01-01

The common pathway leading to liver fibrosis and cirrhosis is growing deposition of extracellular matrix (ECM). It results from molecular and histological rearrangement of collagens, glycoproteins and hyaluronans. Hyaluronic acid is a chief component of the extracellular matrix of connective tissues and plays the main structural role in the formation of ECM. The most important organ involved in the synthesis of hyaluronic acid is the liver. In this paper the meaning of hyaluronic acid in the diagnostics of liver diseases is discussed. Here, we focus on the described changes of hyaluronic acid concentration in the pathological processes of the liver, including alcoholic and non-alcoholic liver diseases. The results of published clinical studies have shown its high diagnostic sensitivity, which probably enables its application in laboratory diagnosis.

The role of ultrasound elastographic techniques in chronic liver disease: current status and future perspectives.

PubMed

Piscaglia, Fabio; Marinelli, Sara; Bota, Simona; Serra, Carla; Venerandi, Laura; Leoni, Simona; Salvatore, Veronica

2014-03-01

This review illustrates the state of the art clinical applications and the future perspectives of ultrasound elastographic methods for the evaluation of chronic liver diseases, including the most widely used and validated technique, transient elastography, followed by shear wave elastography and strain imaging elastography. Liver ultrasound elastography allows the non-invasive evaluation of liver stiffness, providing information regarding the stage of fibrosis, comparable to liver biopsy which is still considered the gold standard; in this way, it can help physicians in managing patients, including the decision as to when to start antiviral treatment. The characterization of focal liver lesions and the prognostic role of the elastographic technique in the prediction of complications of cirrhosis are still under investigation. Copyright © 2013 Elsevier Ireland Ltd. 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.

Laparoscopic management of liver metastases from uveal melanoma.

PubMed

Akyuz, Muhammet; Yazici, Pınar; Dural, Cem; Yigitbas, Hakan; Okoh, Alexis; Bucak, Emre; McNamara, Michael; Singh, Arun; Berber, Eren

2016-06-01

Although uveal melanoma is a rare disease, its metastasis to the liver is associated with a poor survival. The aim of this study is to analyze the survival after surgical treatment of uveal melanoma metastases to the liver. Within 15 years, 44 patients with uveal melanoma metastases to the liver were managed at a single center. Medical records were reviewed to identify patients who underwent surgical treatment of their liver disease. Clinical and oncologic results were compared to those patients who were managed otherwise. T test, Chi-square test, and Kaplan-Meier survival analyses were performed. There were 16 patients who underwent surgical treatment (laparoscopic liver resection, n = 2 and laparoscopic radiofrequency ablation, n = 14), compared to 28 patients who received systemic therapy. The groups were similar regarding demographics and size of primary tumor. The interval between diagnoses of primary tumor and liver metastases was longer for the surgical group (58 vs 22 months, respectively, p = 0.010). Although the dominant liver tumor size was similar, the average number of liver tumors was 4 in the surgical group and 10 in the systemic therapy group (p < 0.0001). The median survival after diagnosis of liver metastases was 35 months in the surgical group and 15 months in the systemic therapy group (p ≤ 0.0001). Five-year survival was zero in the systemic therapy group and 22 % in the surgical group. This study shows that surgical treatment of liver metastases in selected patients with uveal melanoma, who have limited liver tumor burden and a long interval to metastases development, may result in long-term survival.

Neutrophil-cytokine interactions in a rat model of sulindac-induced idiosyncratic liver injury.

PubMed

Zou, Wei; Roth, Robert A; Younis, Husam S; Malle, Ernst; Ganey, Patricia E

2011-12-18

Previous studies indicated that lipopolysaccharide (LPS) interacts with the nonsteroidal anti-inflammatory drug sulindac (SLD) to produce liver injury in rats. In the present study, the mechanism of SLD/LPS-induced liver injury was further investigated. Accumulation of polymorphonuclear neutrophils (PMNs) in the liver was greater in SLD/LPS-cotreated rats compared to those treated with SLD or LPS alone. In addition, PMN activation occurred specifically in livers of rats cotreated with SLD/LPS. The hypothesis that PMNs and proteases released from them play critical roles in the hepatotoxicity was tested. SLD/LPS-induced liver injury was attenuated by prior depletion of PMNs or by treatment with the PMN protease inhibitor, eglin C. Previous studies suggested that tumor necrosis factor-α (TNF) and the hemostatic system play critical roles in the pathogenesis of liver injury induced by SLD/LPS. TNF and plasminogen activator inhibitor-1 (PAI-1) can contribute to hepatotoxicity by affecting PMN activation and fibrin deposition. Therefore, the role of TNF and PAI-1 in PMN activation and fibrin deposition in the SLD/LPS-induced liver injury model was tested. Neutralization of TNF or inhibition of PAI-1 attenuated PMN activation. TNF had no effect on PAI-1 production or fibrin deposition. In contrast, PAI-1 contributed to fibrin deposition in livers of rats treated with SLD/LPS. In summary, PMNs, TNF and PAI-1 contribute to the liver injury induced by SLD/LPS cotreatment. TNF and PAI-1 independently contributed to PMN activation, which is critical to the pathogenesis of liver injury. Moreover, PAI-1 contributed to liver injury by promoting fibrin deposition. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Acetaminophen-induced acute liver injury in HCV transgenic mice

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

Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle

2013-01-15

The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wildmore » type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.« less

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

PubMed

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

2015-03-01

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

 Rapid identification system of frontal dysfunction in subclinical hepatic encephalopathy.

PubMed

Moretti, Rita; Gazzin, Silvia; Crocè, Lory Saveria; Baso, Beatrice; Masutti, Flora; Bedogni, Giorgio; Tiribelli, Claudio

2016-01-01

 Introduction and aim. Liver disease is associated with cognitive dysfunction also at early stages, and minimal hepatic encephalopathy, affecting 20-70% of patients, is frequently under-recognized. The main purpose of this work was to demonstrate that a substantial number of patients, enrolled due to an acute confusional state in absence of a diagnosis of liver disease, suffers of hepatic encephalopathy. Before a diagnosis of a well-compensated liver diseases was performed, 410 patients with an acute confusional state were enrolled in this study. Even in the presence of minimal alterations of hepatic function, the psychometric tests applied demonstrated early signs of cerebral frontal alteration. The alteration was associated with the severity of liver disease, paralleling the progression of the patient to minimal hepatic failure or chronic liver disease. These psychometric tests are essential to detect early and subclinical frontal failure. Frontal dysfunction may be a useful tool in the follow-up of these patients.

Reasons for compliance or noncompliance with advice to test for hepatitis C via an internet-mediated blood screening service: a qualitative study.

PubMed

Zuure, Freke R; Heijman, Titia; Urbanus, Anouk T; Prins, Maria; Kok, Gerjo; Davidovich, Udi

2011-05-10

Hepatitis C virus (HCV) is mainly transmitted by exposure to infected blood, and can lead to liver cirrhosis and liver cancer. Since the onset of HCV and the development of liver cirrhosis usually are asymptomatic, many HCV-infected individuals are still undiagnosed. To identify individuals infected with HCV in the general population, a low threshold, internet-mediated blood testing service was set up. We performed a qualitative study examining reasons for compliance and noncompliance with advice to test for HCV via the online blood testing service. Semistructured telephone interviews were conducted with 33 website visitors who had been advised to test for HCV (18 testers, 15 non-testers). Transcribed interviews were analyzed qualitatively and interpreted using psychosocial theories of health behavior. Reasons for testing pertaining to the online service were: the testing procedure is autonomous, personalized test advice is provided online, reminder emails are sent, and there is an online planning tool. Reasons for testing not specific to the online service were: knowing one's status can prevent liver disease and further transmission of HCV, HCV is curable, testing can provide reassurance, physical complaints are present, and there is liver disease in one's social environment. Service-related reasons for not testing pertained to inconvenient testing facilities, a lack of commitment due to the low threshold character of the service, computer/printing problems, and incorrectly interpreting an online planning tool. The reasons for not testing that are not specific to the online service were: the belief that personal risk is low, the absence of symptoms, low perceived urgency for testing and treatment, fear of the consequences of a positive test result, avoiding threatening information, and a discouraging social environment. Features specific to the online service played a significant role in motivation to test for HCV above and beyond the more conventional perceived health benefits of HCV testing. However, some online specific features were considered problematic and need to be adapted. Methods and strategies for dealing with these impeding factors and for improving compliance with testing via the online service are outlined.

Reasons for compliance or noncompliance with advice to test for hepatitis C via an internet-mediated blood screening service: a qualitative study

PubMed Central

2011-01-01

Background Hepatitis C virus (HCV) is mainly transmitted by exposure to infected blood, and can lead to liver cirrhosis and liver cancer. Since the onset of HCV and the development of liver cirrhosis usually are asymptomatic, many HCV-infected individuals are still undiagnosed. To identify individuals infected with HCV in the general population, a low threshold, internet-mediated blood testing service was set up. We performed a qualitative study examining reasons for compliance and noncompliance with advice to test for HCV via the online blood testing service. Methods Semistructured telephone interviews were conducted with 33 website visitors who had been advised to test for HCV (18 testers, 15 non-testers). Transcribed interviews were analyzed qualitatively and interpreted using psychosocial theories of health behavior. Results Reasons for testing pertaining to the online service were: the testing procedure is autonomous, personalized test advice is provided online, reminder emails are sent, and there is an online planning tool. Reasons for testing not specific to the online service were: knowing one's status can prevent liver disease and further transmission of HCV, HCV is curable, testing can provide reassurance, physical complaints are present, and there is liver disease in one's social environment. Service-related reasons for not testing pertained to inconvenient testing facilities, a lack of commitment due to the low threshold character of the service, computer/printing problems, and incorrectly interpreting an online planning tool. The reasons for not testing that are not specific to the online service were: the belief that personal risk is low, the absence of symptoms, low perceived urgency for testing and treatment, fear of the consequences of a positive test result, avoiding threatening information, and a discouraging social environment. Conclusions Features specific to the online service played a significant role in motivation to test for HCV above and beyond the more conventional perceived health benefits of HCV testing. However, some online specific features were considered problematic and need to be adapted. Methods and strategies for dealing with these impeding factors and for improving compliance with testing via the online service are outlined. PMID:21569224

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

Metabolic profile of liver damage in non-cirrhotic virus C and autoimmune hepatitis: A proton decoupled 31P-MRS study.

PubMed

Hakkarainen, Antti; Puustinen, Lauri; Kivisaari, Reetta; Boyd, Sonja; Nieminen, Urpo; Arkkila, Perttu; Lundbom, Nina

2017-05-01

To study liver 31 P MRS, histology, transient elastography, and liver function tests in patients with virus C hepatitis (HCV) or autoimmune hepatitis (AIH) to test the hypothesis that 31 P MR metabolic profile of these diseases differ. 25 patients with HCV (n=12) or AIH (n=13) underwent proton decoupled 31 P MRS spectroscopy performed on a 3.0T MR imager. Intensities of phosphomonoesters (PME) of phosphoethanolamine (PE) and phosphocholine (PC), phosphodiesters (PDE) of glycerophosphoethanolamine (GPE) and glycerophosphocholine (GPC), and γ, α and β resonances of adenosine triphosphate (ATP), and nicotinamide adenine dinucleotide phosphate (NADPH) were determined. Liver stiffness was measured by transient elastography. Inflammation and fibrosis were staged according to METAVIR from biopsy samples. Activities of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALT) and thromboplastin time (TT) were determined from serum samples. PME had a stronger correlation with AST (z=1.73, p=0.04) and ALT (z=1.77, p=0.04) in HCV than in AIH patients. PME, PME/PDE, PE/GPE correlated positively and PDE negatively with inflammatory activity. PE, PC and PME correlated positively with liver function tests. 31 P-MRS suggests a more serious liver damage in HCV than in AIH with similar histopathological findings. 31 P-MRS is more sensitive in detecting inflammation than fibrosis in the liver. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhanced liver fibrosis test using ELISA assay accurately discriminates advanced stage of liver fibrosis as determined by transient elastography fibroscan in treatment naïve chronic HCV patients.

PubMed

Omran, Dalia; Yosry, Ayman; Darweesh, Samar K; Nabeel, Mohammed M; El-Beshlawey, Mohammed; Saif, Sameh; Fared, Azza; Hassany, Mohamed; Zayed, Rania A

2018-02-01

Evaluation of liver fibrosis stage is crucial in the assessment of chronic HCV patients, regarding decision to start treatment and during follow-up. Our aim was to assess the validity of the enhanced liver fibrosis (ELF) score in discrimination of advanced stage of liver fibrosis in naïve chronic HCV patients. We prospectively evaluated liver fibrosis stage in one hundred eighty-one naïve chronic HCV Egyptian patients by transient elastography (TE)-FibroScan. Patients were categorized into mild to moderate fibrosis (≤F2) group and advanced fibrosis (≥F3) group. The ELF score components, hyaluronic acid (HA), amino-terminal propeptide of type-III-procollagen (PIIINP) and tissue inhibitor of metalloproteinase type-1 (TIMP-1), were done using ELISA test. The mean values of ELF and its individual components significantly correlated with the hepatic fibrosis stage as measured by TE-FibroScan (P value 0.001). ELF cutoff value of 9.8 generated a sensitivity of 77.8%, specificity of 67.1%, area under the receiver operator characteristic curve (AUROC) of 0.76 with 95% confidence interval [CI] (0.68-0.83) for detecting advanced fibrosis (F ≥ 3). ELF panel is a good, reliable noninvasive test and showed comparable results to TE-FibroScan in detecting liver fibrosis stage in treatment naïve chronic HCV patients.

A comparison of liver function after hepatectomy with inflow occlusion between sevoflurane and propofol anesthesia.

PubMed

Song, J C; Sun, Y M; Yang, L Q; Zhang, M Z; Lu, Z J; Yu, W F

2010-10-01

In this study, we compared liver function tests after hepatectomy with inflow occlusion as a function of propofol versus sevoflurane anesthesia. One hundred patients undergoing elective liver resection with inflow occlusion were randomized into a sevoflurane group or a propofol group. General anesthesia was induced with 3 μg/kg fentanyl, 0.2 mg/kg cisatracurium, and target-controlled infusion of propofol, set at a plasma target concentration of 4 to 6 μg/mL, or sevoflurane initially started at 8%. Anesthesia was maintained with target-controlled infusion of propofol (2-4 μg/mL) or sevoflurane (1.5%-2.5%). The primary end point was postoperative liver injury assessed by peak values of liver transaminases. Transaminase levels peaked between the first and the third postoperative day. Peak alanine aminotransferase was 504 and 571 U/L in the sevoflurane group and the propofol group, respectively. Peak aspartate aminotransferase was 435 U/L after sevoflurane and 581 U/L in the propofol group. There were no significant differences in peak alanine aminotransferase or peak aspartate aminotransferase between groups. Other liver function tests including bilirubin and alkaline phosphatase, and peak values of white blood cell counts and creatinine, were also not different between groups. Sevoflurane and propofol anesthetics resulted in similar patterns of liver function tests after hepatectomy with inflow occlusion. These data suggest that the 2 anesthetics are equivalent in this clinical context.

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.

Liver Rapid Reference Set Application: Hemken - Abbott (2015) — EDRN Public Portal

Cancer.gov

The aim for this testing is to find a small panel of biomarkers (n=2-5) that can be tested on the Abbott ARCHITECT automated immunoassay platform for the early detection of hepatocellular carcinoma (HCC). This panel of biomarkers should perform significantly better than alpha-fetoprotein (AFP) alone based on multivariate statistical analysis. This testing of the EDRN reference set will help expedite the selection of a small panel of ARCHITECT biomarkers for the early detection of HCC. The panel of ARCHITECT biomarkers Abbott plans to test include: AFP, protein induced by vitamin K absence or antagonist-II (PIVKA-II), golgi protein 73 (GP73), hepatocellular growth factor (HGF), dipeptidyl peptidase 4 (DPP4) and DPP4/seprase (surface expressed protease) heterodimer hybrid. PIVKA-II is abnormal des-carboxylated prothrombin (DCP) present in vitamin K deficiency.

Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver.

PubMed

Kaifi, Jussuf T; Kunkel, Miriam; Dicker, David T; Joude, Jamal; Allen, Joshua E; Das, Avisnata; Zhu, Junjia; Yang, Zhaohai; Sarwani, Nabeel E; Li, Guangfu; Staveley-O'Carroll, Kevin F; El-Deiry, Wafik S

2015-01-01

Metastatic spread is the most common cause of cancer-related death in colorectal cancer (CRC) patients, with the liver being the mostly affected organ. Circulating tumor cells (CTCs) are a prognostic marker in stage IV CRC. We hypothesized that tumor burden in the liver correlates with CTC quantity. Blood (7.5 ml) was prospectively collected from 24 patients with novel stage IV CRC diagnosis. Baseline EpCAM+ CTCs were analyzed with the FDA-approved CellSearch® system. Clinicopathological data were collected, and hepatic tumor burden was determined by radiographic liver volumetry with contrast-enhanced CT scans. CRC primary tumors were immunohistochemically stained for EpCAM expression with BerEP4 monoclonal antibody. Statistical analyses were performed using 2-sample T-test, non-parametric Wilcoxon Rank-Sum test, and Fisher's exact test. CTCs were detected n 17 (71%) of 24 patients. The overall mean CTC number as determined by EpCAM-based CellSearch® detection was 6.3 (SEM 2.9). High baseline CTC numbers (≥3) correlated significantly with a high tumor/liver ratio (≥30%), and with high serum CEA levels, as determined by two-sample T-test on log-transformed data and by Fisher's Exact test on categorical data analysis (P < 0.05). The CRC primary tumors were consistently expressing EpCAM by immunostaining. High tumor burden in the liver and high baseline serum CEA levels are associated with high number of baseline CTCs in stage IV CRC patients. Future studies should further investigate the biological role and expression patterns of single CTCs in cancer patients to further improve personalized treatment strategies.

A model of the health and economic impact of posttransfusion hepatitis C: application to cost-effectiveness analysis of further expansion of HCV screening protocols.

PubMed

Pereira, A; Sanz, C

2000-10-01

Cost-effectiveness analyses are needed to decide the value of further expansion of the screening protocols for HCV in blood donors. However, such analyses are hampered by imperfect knowledge of the health and economic repercussions of posttransfusion hepatitis C (PTHC). A Monte Carlo simulation of a Markov model representing the outcomes of patients transfused with HCV-infective blood was used to estimate the health and economic impact of PTHC and to calculate the cost-effectiveness ratio of various HCV screening methods. Median survival for hypothetical patients with PTHC and for controls without hepatitis was 11.25 and 11.75 years, respectively. Overall, 12.3 percent of patients receiving HCV-infective blood will develop chronic hepatitis, 9.3 percent will progress to liver failure, and 9. 25 percent will eventually die of liver disease after a median time of 20.75 years (range, 6-70). Ninety-one percent of the infected blood recipients had no reduction in life expectancy due to PTHC, and the average loss per patient was 0.754 years. The present value of the lifetime health costs incurred by patients with PTHC is $6330 per case. HCV antibody testing increases the patients' life expectancy by 20.4 hours per blood collection tested, and it results in net savings by decreasing the number of patients that will require treatment for liver disease in the future. Adding HCV NAT increases the patients' life expectancy by 0.08 hours per blood collection tested, at a cost-effectiveness ratio of $1,829,611 per QALY gained. PTHC has low health benefits because of the advanced age of many blood recipients. Testing donors for HCV antibodies results in net savings for the health care system, despite low health benefits. Adding HCV NAT would produce little additional gain at a very high cost.

Pretreatment data is highly predictive of liver chemistry signals in clinical trials.

PubMed

Cai, Zhaohui; Bresell, Anders; Steinberg, Mark H; Silberg, Debra G; Furlong, Stephen T

2012-01-01

The goal of this retrospective analysis was to assess how well predictive models could determine which patients would develop liver chemistry signals during clinical trials based on their pretreatment (baseline) information. Based on data from 24 late-stage clinical trials, classification models were developed to predict liver chemistry outcomes using baseline information, which included demographics, medical history, concomitant medications, and baseline laboratory results. Predictive models using baseline data predicted which patients would develop liver signals during the trials with average validation accuracy around 80%. Baseline levels of individual liver chemistry tests were most important for predicting their own elevations during the trials. High bilirubin levels at baseline were not uncommon and were associated with a high risk of developing biochemical Hy's law cases. Baseline γ-glutamyltransferase (GGT) level appeared to have some predictive value, but did not increase predictability beyond using established liver chemistry tests. It is possible to predict which patients are at a higher risk of developing liver chemistry signals using pretreatment (baseline) data. Derived knowledge from such predictions may allow proactive and targeted risk management, and the type of analysis described here could help determine whether new biomarkers offer improved performance over established ones.

Normothermic ex-situ liver preservation: the new gold standard.

PubMed

Laing, Richard W; Mergental, Hynek; Mirza, Darius F

2017-06-01

Normothermic machine perfusion of the liver (NMP-L) is a novel technology recently introduced into the practice of liver transplantation. This review recapitulates benefits of normothermic perfusion over conventional static cold storage and summarizes recent publications in this area. The first clinical trials have demonstrated both safety and feasibility of NMP-L. They have shown that machine perfusion can entirely replace cold storage or be commenced following a period of cold ischaemia. The technology currently allows transplant teams to extend the period of organ preservation for up to 24 h. Results from the first randomized control trial comparing NMP-L with static cold storage will be available soon. One major advantage of NMP-L technology over other parallel technologies is the potential to assess liver function during NMP-L. Several case series have suggested parameters usable for liver viability testing during NMP-L including bile production and clearance of lactic acidosis. NMP-L allows viability testing of high-risk livers. It has shown the potential to increase utilization of donor organs and improve transplant procedure logistics. NMP-L is likely to become an important technology that will improve organ preservation as well as have the potential to improve utilization of extended criteria donor livers.

Toxocariasis masquerading as liver and lung metastatic nodules in patents with gastrointestinal cancer: clinicopathologic study of five cases.

PubMed

Park, Sanghui; Kim, Yun Soo; Kim, Yu Jin; Kyung, Sun Young; Park, Jeong-Woong; Jeong, Sung Hwan; Lee, Sang Pyo

2012-01-01

There are sporadic reports in the literature in which radiologic liver and lung lesions found incidentally during follow-up metastatic surveillance were shown to be caused by toxocariasis. The objective of the work discussed in this report was to identify common clinical and histopathological features of toxocariasis resembling metastatic nodules in five patients with gastrointestinal cancer. We retrospectively analyzed clinical features of five gastrointestinal cancer patients with liver or lung nodules mimicking metastasis. Serologic tests for parasitic infestations and pathologic examinations were performed. All five patients were males and three patients had gastric cancer and two had colorectal cancer. All the cases of toxocariasis were confirmed serologically. On follow-up imaging, the lesions improved or resolved, suggestive of the phenomenon of visceral larva migrans. In two patients, liver biopsy was performed and showed eosinophilic abscess. Serologic tests and liver or lung biopsy should be performed aggressively to exclude toxocariasis when patients with underlying gastrointestinal cancer present with hepatic or pulmonary nodules associated with eosinophilia, particularly if the patients have a clinical history of raw animal liver ingestion. Curative surgical intervention should not be excluded just because of multiple nodules in the liver or the lungs.

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.

[The Application of Gold-immunochromatographic Test Strip Reader in Serum Antibody Detection in Echinococcosis].

PubMed

Xie, Gui-lin; Yin, Jun-xia; Duan, Xin-yu; Feng, Xiao-hui; Wang, Yang; Jiang, Kai; Chen, Xin-mei

2015-06-01

One hundred and fifty-nine serum samples from hydatid disease patients and 80 serum samples from patients with other liver diseases were detected by gold-immunochromatographic assay, and read by naked eyes and the gold-immunochromatographic test strip reader. The sensitivity, specificity, and accuracy of eye-based method was 92.4% (147/159), 85.0% (68/80), and 89.9% (215/239), which was lower than that of the reader detection (95.6%, 93.7%, 95.0%, respectively). While, its false negative rate (7.5%, 12/159) and false positive rate (15.0%, 12/80) was higher than that of the reader detection (4.4% and 6.3%, respectively).

Immortalized Human Hepatic Cell Lines for In Vitro Testing and Research Purposes.

PubMed

Ramboer, Eva; Vanhaecke, Tamara; Rogiers, Vera; Vinken, Mathieu

2015-01-01

The ubiquitous shortage of primary human hepatocytes has urged the scientific community to search for alternative cell sources, such as immortalized hepatic cell lines. Over the years, several human hepatic cell lines have been produced, whether or not using a combination of viral oncogenes and human telomerase reverse transcriptase protein. Conditional approaches for hepatocyte immortalization have also been established and allow generation of growth-controlled cell lines. A variety of immortalized human hepatocytes have already proven useful as tools for liver-based in vitro testing and fundamental research purposes. The present chapter describes currently applied immortalization strategies and provides an overview of the actually available immortalized human hepatic cell lines and their in vitro applications.

A novel method of mouse ex utero transplantation of hepatic progenitor cells into the fetal liver

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

Shikanai, Mima; Asahina, Kinji; Iseki, Sachiko

2009-04-03

Avoiding the limitations of the adult liver niche, transplantation of hepatic stem/progenitor cells into fetal liver is desirable to analyze immature cells in a hepatic developmental environment. Here, we established a new monitor tool for cell fate of hepatic progenitor cells transplanted into the mouse fetal liver by using ex utero surgery. When embryonic day (ED) 14.5 hepatoblasts were injected into the ED14.5 fetal liver, the transplanted cells expressed albumin abundantly or {alpha}-fetoprotein weakly, and contained glycogen in the neonatal liver, indicating that transplanted hepatoblasts can proliferate and differentiate in concord with surrounding recipient parenchymal cells. The transplanted cells becamemore » mature in the liver of 6-week-old mice. Furthermore, this method was applicable to transplantation of hepatoblast-like cells derived from mouse embryonic stem cells. These data indicate that this unique technique will provide a new in vivo experimental system for studying cell fate of hepatic stem/progenitor cells and liver organogenesis.« less

Herbal and Dietary Supplement Induced Liver Injury

PubMed Central

de Boer, Ynto S.; Sherker, Averell H.

2016-01-01

Summary The increase in the use of herbal and dietary supplements (HDS) over the last decades has been accompanied with an increase in the reports of HDS associated hepatotoxicity. The spectrum of HDS induced liver injury is diverse and the outcome may vary from transient liver test elevations to fulminant hepatic failure resulting in death or requiring liver transplantation. There are no validated standardized tools to establish the diagnosis, but some HDS products do have a typical clinical signature that may help to identify HDS induced liver injury. PMID:27842768

Alpha-1 antitrypsin blood test

MedlinePlus

... the lungs ( bronchiectasis ) Scarring of the liver ( cirrhosis ) Chronic obstructive pulmonary disease (COPD) Liver tumors Yellowing of the skin and eyes due to blocked bile flow ( obstructive ...

Evolution of noninvasive tests of liver fibrosis is associated with prognosis in patients with chronic hepatitis C.

PubMed

Vergniol, Julien; Boursier, Jérôme; Coutzac, Clélia; Bertrais, Sandrine; Foucher, Juliette; Angel, Camille; Chermak, Faiza; Hubert, Isabelle Fouchard; Merrouche, Wassil; Oberti, Frédéric; de Lédinghen, Victor; Calès, Paul

2014-07-01

No data are available about the prediction of long-term survival using repeated noninvasive tests of liver fibrosis in chronic hepatitis C (CHC). We aimed to assess the prognostic value of 3-year liver stiffness measurement (LSM), aspartate aminotransferase to platelet ratio index (APRI), and fibrosis 4 (FIB-4) evolution in CHC. CHC patients with two LSM (1,000-1,500 days interval) were prospectively included. Blood fibrosis tests APRI and FIB-4 were calculated the day of baseline (bLSM) and follow-up (fLSM) LSM. Evolution of fibrosis tests was expressed as delta: (follow-up-baseline results)/duration. Date and cause of death were recorded during follow-up that started the day of fLSM. In all, 1,025 patients were included. Median follow-up after fLSM was 38.0 months (interquartile range [IQR]: 27.7-46.1) during which 35 patients died (14 liver-related death) and seven had liver transplantation. Prognostic accuracy (Harrell C-index) of multivariate models including baseline and delta results was not significantly different between LSM and FIB-4 (P ≥ 0.24), whereas FIB-4 provided more accurate prognostic models than APRI (P = 0.03). By multivariate analysis including LSM variables, overall survival was independently predicted by bLSM, delta (dLSM), and sustained virological response (SVR). Prognosis was excellent in patients having bLSM <7 kPa, SVR, or no increase (<1 kPa/year) in 7-14 kPa bLSM. Prognosis was significantly impaired in patients with an increase (≥ 1 kPa/year) in 7-14 kPa bLSM, or decrease (≤ 0 kPa/year) in ≥ 14 kPa bLSM (P = 0.949 between these two groups). Patients with an increase (>0 kPa/year) in ≥ 14 kPa bLSM had the worst prognosis. Baseline and delta FIB-4 also identified patient subgroups with significantly different prognosis. Three-year evolution of noninvasive tests of liver fibrosis has a strong prognostic value in CHC patients. These tests should be repeated to monitor patients and predict their outcome. © 2014 by the American Association for the Study of Liver Diseases.

Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome

PubMed Central

Vootla, Vamshidhar R.; Daniel, Myrta

2015-01-01

Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome. PMID:26351414

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

Molecularly imprinted polymer solid-phase extraction coupled to square wave voltammetry at carbon fibre microelectrodes for the determination of fenbendazole in beef liver.

PubMed

Guzmán-Vázquez de Prada, A; Loaiza, Oscar A; Serra, B; Morales, D; Martínez-Ruiz, P; Reviejo, A J; Pingarrón, J M

2007-05-01

A molecularly imprinted polymer was developed and used for solid-phase extraction (MISPE) of the antihelmintic fenbendazole in beef liver samples. Detection of the analyte was accomplished using square wave voltammetry (SWV) at a cylindrical carbon fibre microelectrode (CFME). A mixture of MeOH/HAc (9:1) was employed both as eluent in the MISPE system and as working medium for electrochemical detection of fenbendazole. The limit of detection was 1.9x10(-7) mol L-1 (57 microg L-1), which was appropriate for the determination of fenbendazole at the maximum residue level permitted by the European Commission (500 microg kg-1 in liver). Given that the SW voltammetric analysis could not be directly performed in the sample extract as a consequence of interference from some sample components, a sample clean-up with a MIP for selectively retaining fenbendazole was performed. The MIP was synthesized using a 1:8:22 template/methacrylic acid/ethylene glycol dimethacrylate ratio. A Britton-Robinson Buffer of pH 9.0 was selected for retaining fenbendazole in the MIP cartridges, and an eluent volume of 5.0 mL at a flow rate of 2.0 mL min-1 was chosen in the elution step. Cross-reactivity with the MIP was observed for other benzimidazoles. The synthesized MIP exhibited a good selectivity for benzimidazoles with respect to other veterinary drugs. The applicability of the MISPE-SWV method was tested with beef liver samples, spiked with fenbendazole at 5,000 and 500 microg kg-1. Results obtained for ten different liver samples yielded mean recoveries of (95+/-12)% and (96+/-11)% for the upper and lower concentration level, respectively.

Anti-soluble liver antigen/liver-pancreas (SLA/LP) antibodies in pediatric patients with autoimmune hepatitis.

PubMed

Vitozzi, Susana; Djilali-Saiah, Idriss; Lapierre, Pascal; Alvarez, Fernando

2002-12-01

Antibodies against soluble liver antigen/liver-pancreas (SLA/LP) have been associated with severe autoimmune hepatitis (AIH) and poor outcome, but most of these reports have focused on adult patients. The aim of this study was to assess the prevalence and clinical significance of anti-SLA/LP antibodies in a pediatric population with AIH. We developed a quantitative enzyme-linked immunoassay (ELISA), a Western blot (WB) and an immunoprecipitation assay (IPA) based on recombinant cDNA from activated Jurkat cells. The specificity of these tests was validated by testing 200 serum samples from healthy subjects, and from patients with liver and non-liver diseases. Anti-SLA/LP antibodies were found in patients with type 1 and type 2 AIH. The prevalence of these antibodies in patients with type 1 AIH was: 42% when tested by ELISA, 15% by WB and 50% by IPA. In patients with type 2 AIH, the prevalence rates were 42% by ELISA, 18% by WB and 44% by IPA. The mean titer values for anti-SLA/LP antibodies was significantly higher in type 2 AIH (1:1,300 +/- 339) than in type 1 AIH (1:600 +/- 71; p < 0.0001) and closely associated with higher titers of anti-liver kidney microsome type 1 (LKM1) and anti-liver cytosol type 1 (LC1) antibodies in sera. The presence of anti-SLA/LP showed a significant female preponderance in type 1 and 2 AIH patients (p = 0.0003 and p = 0.003, respectively), and was significantly correlated with a lower age at diagnosis (p = 0.05) in type 1 AIH patients. In conclusion, anti-SLA/LP antibodies in pediatric patients are associated with both type 1 and 2 AIH.

Underappreciation of non-alcoholic fatty liver disease by primary care clinicians: limited awareness of surrogate markers of fibrosis.

PubMed

Patel, Preya J; Banh, Xuan; Horsfall, Leigh U; Hayward, Kelly L; Hossain, Fabrina; Johnson, Tracey; Stuart, Katherine A; Brown, Nigel N; Saad, Nivene; Clouston, Andrew; Irvine, Katharine M; Russell, Anthony W; Valery, Patricia C; Williams, Suzanne; Powell, Elizabeth E

2018-02-01

Non-alcoholic fatty liver disease (NAFLD) is a common cause of incidental liver test abnormalities. General practitioners (GP) have a key role in identifying people with NAFLD at risk of significant liver disease. Recent specialist guidelines emphasise the use of fibrosis algorithms or serum biomarkers rather than routine liver tests, to assess advanced fibrosis. To evaluate primary care clinicians' current approach to diagnosis, management and referral of NAFLD. A cross-sectional survey of primary care clinicians was undertaken through a structured questionnaire about NAFLD. A convenience sample of general practice clinics and general practice conferences in Metropolitan Brisbane and regional south east Queensland was selected. A total of 108 primary care clinicians completed the survey (participation rate 100%). Fifty-one percent of respondents considered the prevalence of NAFLD in the general population to be ≤10%. Twenty-four percent of respondents felt that liver enzymes were sufficiently sensitive to detect underlying NAFLD. Most respondents were unsure whether the Fibrosis 4 score (62.7% unsure) or Enhanced Liver Fibrosis score (63.7% unsure) could help to identify advanced fibrosis or cirrhosis. Although 47% of respondents said they would refer a patient to a Gastroenterologist/Hepatologist if they suspect the patient has NAFLD, 44.1% do not make any referrals. Of concern, 70.6% of clinicians said they were unlikely to refer a patient to Hepatology unless liver function tests are abnormal. Our findings demonstrate that many primary care clinicians underestimate the prevalence of NAFLD and under-recognise the clinical spectrum of NAFLD and how this is assessed. © 2017 Royal Australasian College of Physicians.

Clinical Characteristics and Outcome of Hepatic Sarcoidosis: A Population-Based Study 1976-2013.

PubMed

Ungprasert, Patompong; Crowson, Cynthia S; Simonetto, Douglas A; Matteson, Eric L

2017-10-01

Data on clinical manifestations and outcome of hepatic sarcoidosis are scarce. This study aimed to use a population-based cohort of patients with incident sarcoidosis to better describe the characteristics of hepatic sarcoidosis. A cohort of incident cases of sarcoidosis in Olmsted County, MN, USA, from 1976 to 2013 was identified from the database. Diagnosis was verified by individual medical record review. Confirmed cases of sarcoidosis were then reviewed for liver involvement. Data on clinical manifestations, imaging study, liver biochemical tests, treatment, and outcome were collected. Cumulative incidence of cirrhosis adjusted for the competing risk of death was estimated. A total of 345 cases of incident sarcoidosis were identified. Of these, 19 cases (6%) had liver involvement (mean age 46.1 years, 53% female and 79% Caucasian). Most patients had asymptomatic liver disease and were discovered in pursuit of abnormal biochemical tests and imaging studies. Alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were elevated in the majority of patients (88 and 90%, respectively). Elevated transaminases were less common and less severe. About half of patients had abnormal imaging study with hypodense nodular lesions being the most common abnormality (six patients) followed by hepatomegaly (three patients). Liver biopsy revealed non-caseating granuloma in 88% (14 of 16 patients). A total of four patients developed cirrhosis. Involvement of the liver by sarcoidosis was seen in 6% of patients with sarcoidosis. The majority of patients were asymptomatic. Elevated ALP and GGT were the most common abnormal biochemical tests. Liver biopsy revealed non-caseating granuloma in almost all cases. Cirrhosis was seen in a significant number of patients. Generalizability of the observations to other populations may be limited, as the studied population was predominantly Caucasian. The prevalence of liver disease may be higher in more diverse populations.

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.

Integration of technologies for hepatic tissue engineering.

PubMed

Nahmias, Yaakov; Berthiaume, Francois; Yarmush, Martin L

2007-01-01

The liver is the largest internal organ in the body, responsible for over 500 metabolic, regulatory, and immune functions. Loss of liver function leads to liver failure which causes over 25,000 deaths/year in the United States. Efforts in the field of hepatic tissue engineering include the design of bioartificial liver systems to prolong patient's lives during liver failure, for drug toxicity screening and for the study of liver regeneration, ischemia/reperfusion injury, fibrosis, viral infection, and inflammation. This chapter will overview the current state-of-the-art in hepatology including isolated perfused liver, culture of liver slices and tissue explants, hepatocyte culture on collagen "sandwich" and spheroids, coculture of hepatocytes with non-parenchymal cells, and the integration of these culture techniques with microfluidics and reactor design. This work will discuss the role of oxygen and medium composition in hepatocyte culture and present promising new technologies for hepatocyte proliferation and function. We will also discuss liver development, architecture, and function as they relate to these culture techniques. Finally, we will review current opportunities and major challenges in integrating cell culture, bioreactor design, and microtechnology to develop new systems for novel applications.

The need for venovenous bypass in liver transplantation

PubMed Central

Fonouni*, Hamidreza; Soleimani, Mehrdad; Müller, Sascha A.; Büchler, Markus W.; Schmidt, Jan

2008-01-01

Since introduction of the conventional liver transplantation (CLTx) by Starzl, which was based on the resection of recipient inferior vena cava (IVC) along the liver, the procedure has undergone several refinements. Successful use of venovenous bypass (VVB) was first introduced by Shaw et al., although in recent decades there has been controversy regarding the routine use of VVB during CLTx. With development of piggyback liver transplantation (PLTx), the use of caval clamping and VVB is avoided, leading to fewer complications related to VVB. However, some authors still advocate VVB in PLTx. The great diversity among centers in their use of VVB during CLTx, or even along the PLTx technique, has led to confusion regarding the indication setting for VVB. For this reason, we present an overview of the use of VVB in CLTx, the target of patients for whom VVB could be beneficial, and the needs assessment of VVB for patients undergoing PLTx. Recent studies have shown that with the advancement of surgical skills, refinement of surgical techniques, and improvements in anesthesiology, there are only limited indications for doing CLTx with VVB routinely. PLTx with preservation of IVC can be performed in almost all primary transplants and in the majority of re-transplantations without the need for VVB. Nevertheless, in a few selective cases with severe intra-operative hemodynamic instability, or with a failed test of transient IVC occlusion, the application of VVB is still justifiable. These indications should be judged intra-operatively and the decision is based on each center's preference. PMID:18773054

Adenoviral Gene Transfer of Hepatic Stimulator Substance Confers Resistance Against Hepatic Ischemia–Reperfusion Injury by Improving Mitochondrial Function

PubMed Central

Jiang, Shu-Jun; Li, Wen

2013-01-01

Abstract Hepatic stimulator substance (HSS) has been suggested to protect liver cells from various toxins. However, the precise role of HSS in hepatic ischemia–reperfusion (I/R) injury remains unknown. This study aims to elucidate whether overexpression of HSS could attenuate hepatic ischemia–reperfusion injury and its possible mechanisms. Both in vivo hepatic I/R injury in mice and in vitro hypoxia–reoxygenation (H/R) in a cell model were used to evaluate the effect of HSS protection after adenoviral gene transfer. Moreover, a possible mitochondrial mechanism of HSS protection was investigated. Efficient transfer of the HSS gene into liver inhibited hepatic I/R injury in mice, as evidenced by improvement in liver function tests, the preservation of hepatic morphology, and a reduction in hepatocyte apoptosis. HSS overexpression also inhibited H/R-induced cell death, as detected by cell viability and cell apoptosis assays. The underlying mechanism of this hepatic protection might involve the attenuation of mitochondrial dysfunction and mitochondrial-dependent cell apoptosis, as shown by the good preservation of mitochondrial ultrastructure, mitochondrial membrane potential, and the inhibition of cytochrome c leakage and caspase activity. Moreover, the suppression of H/R-induced mitochondrial ROS production and the maintenance of mitochondrial respiratory chain complex activities may participate in this mechanism. This new function of HSS expands the possibility of its application for the prevention of I/R injury, such as hepatic resection and liver transplantation in clinical practice. PMID:23461564

Evaluating Drug-Induced Liver Injury and Its Remission via Discrimination and Imaging of HClO and H2S with a Two-Photon Fluorescent Probe.

PubMed

Jiao, Xiaoyun; Xiao, Yongsheng; Li, Yong; Liang, Muwen; Xie, Xilei; Wang, Xu; Tang, Bo

2018-06-19

Drug-induced liver injury (DILI) has aroused wide concern. Finding new markers or indicators as well as detoxification molecules for DILI is of great significance and good application prospect, which can help develop effective preclinical screening methodology and corresponding treatment protocols. Herein, in this article, DILI caused by antidepressant drugs of duloxetine and fluoxetine and its remission were evaluated by a two-photon fluorescent probe, RPC-1, through discriminating and imaging HClO and H 2 S simultaneously. By being applied both in vitro and in vivo, RPC-1 revealed slight up-regulation of HClO and negligible liver damage after administration of either of the two drugs. In contrast, an apparent up-regulation of HClO and obvious liver damage was observed after combined administration of the drugs. Meanwhile, the pretreatment of N-acetyl cysteine (NAC) resulted in the increasing of endogenous H 2 S level, which contributed to the remission of DILI. The histological analysis and serological test both gave good consistency with the imaging results. These findings demonstrate that HClO may be an appropriate indicator of DILI, and H 2 S plays an important role in the antidotal effect of NAC. We envision that RPC-1 can be used as a powerful tool to predict clinical DILI and study the effect of antidote, as well as explore the molecular mechanisms involved.

Liver Transplantation Outcomes Using Grafts From Donors Older Than the Age of 80 Years.

PubMed

Rabelo, A V; Alvarez, M J; Méndez, C S M; Villegas, M T; MGraneroa, K; Becerra, A; Dominguez, M; Raya, A M; Exposito, M; Suárez, Y F

2015-11-01

We performed a retrospective cohort study between 2002 and 2014 to compare liver transplantation outcomes between recipients of grafts from donors older than and younger than the age of 80 years. Numerical variables were compared with the Student t test when their distribution was normal and the Mann-Whitney test when it was not, whereas categorical variables were compared with Pearson chi-squared test or Fisher test, as appropriate; P < .05 was considered significant. The study included 312 patients with organs from donors younger than 80 years of age and 17 with organs from older donors. The 2 recipient groups did not significantly differ in weight, height, gender, body mass index (BMI), CHILD or MELD score, intensive care unit (ICU) or hospital stay, need for intraoperative hemoderivatives, postreperfusion syndrome, biliary or vascular complications, ischemic cholangiopathy, number of repeat surgeries, graft rejection, retransplantation, or survival at 6 months. Although earlier studies considered livers from elderly donors to be suboptimal, our results support the proposition that octogenarian donors can be an excellent source of liver grafts. Copyright © 2015 Elsevier Inc. All rights reserved.

Interleukin-1 inhibition facilitates recovery from liver injury and promotes regeneration of hepatocytes in alcoholic hepatitis in mice.

PubMed

Iracheta-Vellve, Arvin; Petrasek, Jan; Gyogyosi, Benedek; Bala, Shashi; Csak, Timea; Kodys, Karen; Szabo, Gyongyi

2017-07-01

Inflammation and impaired hepatocyte regeneration contribute to liver failure in alcoholic hepatitis (AH). Interleukin (IL)-1 is a key inflammatory cytokine in the pathobiology of AH. The role of IL-1 in liver regeneration in the recovery phase of alcohol-induced liver injury is unknown. In this study, we tested IL-1 receptor antagonist to block IL-1 signalling in a mouse model of acute-on-chronic liver injury on liver inflammation and hepatocyte regeneration in AH. We observed that inhibition of IL-1 signalling decreased liver inflammation and neutrophil infiltration, and resulted in enhanced regeneration of hepatocytes and increased rate of recovery from liver injury in AH. Our novel findings suggest that IL-1 drives sustained liver inflammation and impaired hepatocyte regeneration even after cessation of ethanol exposure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Non-invasive diagnosis of non-alcoholic fatty liver disease. A critical appraisal.

PubMed

Machado, Mariana V; Cortez-Pinto, Helena

2013-05-01

Non-alcoholic fatty liver disease (NAFLD) affects one in every three subjects in the occidental world. The vast majority will not progress, but a relevant minority will develop liver cirrhosis and its complications. The classical gold standard for diagnosing and staging NAFLD and assessing fibrosis is liver biopsy (LB). However, it has important sample error issues and subjectivity in the interpretation, apart from a small but real risk of complications. The decision to perform an LB is even harder in a condition so prevalent such as NAFLD, in which the probability of finding severe liver injury is low. In an attempt to overcome LB and to subcategorize patients with NAFLD in different prognoses allowing better management decisions, several non-invasive methods have been studied in the last decade. The literature is vast and confusing. This review will summarize which methods have been tested and how they perform, which tests are adequate for clinical practice and how they can change the management of these patients. Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Lead effects on body composition and organ size of wintering canvasbacks Aythya valisineria in Louisiana

USGS Publications Warehouse

Pace, R.M.; Hohman, W.L.; Custer, T.W.

1999-01-01

We tested whether lead exposure, as evidenced by liver lead concentration, affected body composition and organ sizes of canvasback ducks Aythya valisineria in Louisiana during winter 1987-88. After adjusting for body size, sex, age, and site and month of collection, we found decreases in ingesta-free body mass; breast, leg, and body protein; body fat; intestine length; and liver and gizzard masses associated with increased liver lead concentrations. There were no apparent associations between liver lead concentrations and testes and body ash masses, or caecal length. We used the concentration of 26.7 ppm of liver lead on a dry matter (dm) basis as indicative of lead toxicosis. We predicted that a canvasback with 26.7 ppm dm liver lead would weigh 209 g less and have 105 g less fat than an unexposed individual. Whereas many lead exposed canvasbacks may survive through winter, their subsequent survival, ability to reproduce and perform other annual cycle events may be compromised. We recommend management to make lead unavailable to waterfowl at major concentration areas and periodic monitoring of lead contamination in waterfowl populations.

The clinical value of 201Tl per rectum scintigraphy in the work-up of patients with alcoholic liver disease.

PubMed

Urbain, D; Reding, P; Georges, B; Thys, O; Ham, H R

1986-01-01

The clinical value of thallium 201 per rectum scintigraphy in the work-up of patients with alcoholic liver disease was evaluated using data obtained in 104 patients. The 25th min ratio of heart to liver activities was used as an index of portal systemic shunting. This ratio was found to be normal in alcoholic patients with normal liver biopsy and also in those presenting only steatosis. It was slightly higher in patients with liver fibrosis and significantly higher values were observed in patients with liver cirrhosis. High values of the ratio were associated with a higher risk of portal systemic encephalopathy and/or gastrointestinal bleeding. The prognostic value of the test was supported by the fact that good correlations were observed between the ratio and widely accepted prognostic scores such as the Child score or the Orrego index. Moreover, high ratios were associated with an increased mortality risk at one year. We conclude that this simple test is interesting in the screening of cirrhotics at risk of encephalopathy, gastrointestinal hemorrhage, or early death.

Water Quality for Hexachlorethane

DTIC Science & Technology

1988-03-01

50,000 to 100,000 bacterial cells/mL; therefore, the teat organisms wete provided with a food source during testing . Two replicates of five animals ...liver weight was significantly in- creased. Two animals died, one each during weeks 4 and 5. Dermal sensitization tests performed on guinea pigs...absolute body waights starting at week 4 in animals exposed to 260 ppm than in control rats, Relative liver, lung, kidney, and testes weights were increased

A CONSORT-Compliant, Randomized, Double-Blind, Placebo-Controlled Pilot Trial of Purified Anthocyanin in Patients With Nonalcoholic Fatty Liver Disease

PubMed Central

Zhang, Pei-Wen; Chen, Feng-Xia; Li, Di; Ling, Wen-Hua; Guo, Hong-Hui

2015-01-01

Abstract Nonalcoholic fatty liver disease (NAFLD) is a common liver disease that can progress to cirrhosis and liver failure. Anthocyanin, a member of the flavonoid family, has been shown to ameliorate NAFLD-associated pathologies in rodents. The aim of this CONSORT-compliant pilot study is to evaluate the effects of anthocyanin supplementation on insulin resistance and liver injury biomarkers in patients with NAFLD. A total of 74 subjects with NAFLD were divided into 2 groups in this double-blind, randomized study. Patients received either purified anthocyanin (320 mg/d) derived from bilberry and black currant or placebo for 12 weeks. Diet, physical activity, anthropometric parameters, glucose tolerance, and a set of biomarkers related to NAFLD were evaluated before and after intervention. No significant differences were observed in nutrient intake, physical activity, anthropometric parameters, or plasma lipid profile between patients receiving anthocyanin or placebo. Compared to controls, the anthocyanin group exhibited significant decreases (P < 0.05, all comparisons) in plasma alanine aminotransferase (−19.1% vs 3.1%), cytokeratin-18 M30 fragment (−8.8% vs 5.6%) and myeloperoxidase (−75.0% vs −44.8%). Significant decreases from baseline in fasting blood glucose and homeostasis model assessment for insulin resistance were observed in the anthocyanin group; however, these differences were not significant relative to placebo controls. In addition, the oral glucose tolerance test indicated that anthocyanin supplementation significantly decreased the 2-hour loading glucose level compared to control (−18.7% vs −3.8%, P = 0.02). A 12-week supplement of purified anthocyanin improved insulin resistance, indicators of liver injury, and clinical evolution in NAFLD patients. Further studies are warranted to determine the clinical applications of anthocyanin in NAFLD. This trial was registered at clinicaltrials.gov as NCT01940263. PMID:25997043

[Use of fish oil lipid emulsions in hospitalized patients under 18 years old with abnormal results in liver tests associated with total parental nutrition].

PubMed

Giraldo Villa, Adriana; Henao Roldan, Catherine; García Loboguerrero, Fanny; Martínez Volkmar, María Isabel; Contreras Ramírez, Mónica María; Ruiz Navas, Patricia

2014-04-01

Prolonged Total Parental Nutrition (TPN) is associated with life-threatening complications in the pediatric population, being cholestasis one of the most important ones. The source of fatty acids, the amount of phytosterols and the dose of lipids in the nutritional support, have been linked to the development of this complication. To describe the behavior of liver function tests in pediatric patients with TPN where lipid based omega 3 fatty acids (OmegavenR) were used. A retrospective research was made in a population of children under 18 years old where omega 3 fatty acids were used for a minimum of 8 days. Patients were initially classified into two groups: cholestasis and abnormal liver tests. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), direct bilirubin (DB) gamma glutamyl transferase (GGT) and alkaline phosphatase (AP) before and after treatment with OmegavenR was evaluated. 33 patients met the inclusion criteria. At the end of treatment with OmegavenR, 82.4% of patients who initially presented cholestasis showed resolution or improvement. The group of patients with abnormal liver tests 18.8% progressed to cholestasis. Our study suggests that the use of OmegavenR in pediatric patients with TPN and DB ≥ 2 mg/dL, seem to reverse or improve cholestasis while in patients with abnormal liver tests we still don't have clear effect. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Design and rationale of the WELCOME trial: A randomised, placebo controlled study to test the efficacy of purified long chainomega-3 fatty acid treatment in non-alcoholic fatty liver disease [corrected].

PubMed

Scorletti, E; Bhatia, L; McCormick, K G; Clough, G F; Nash, K; Calder, P C; Byrne, C D

2014-03-01

Non-alcoholic fatty liver disease (NAFLD) represents a range of liver conditions from simple fatty liver to progressive end stage liver disease requiring liver transplantation. NAFLD is common in the population and in certain sub groups (e.g. type 2 diabetes) up to 70% of patients may be affected. NAFLD is not only a cause of end stage liver disease and hepatocellular carcinoma, but is also an independent risk factor for type 2 diabetes and cardiovascular disease. Consequently, effective treatments for NAFLD are urgently needed. The WELCOME study is testing the hypothesis that treatment with high dose purified long chain omega-3 fatty acids will have a beneficial effect on a) liver fat percentage and b) two histologically validated algorithmically-derived biomarker scores for liver fibrosis. In a randomised double blind placebo controlled trial, 103 participants with NAFLD were randomised to 15-18months treatment with either 4g/day purified long chain omega-3 fatty acids (Omacor) or 4g/day olive oil as placebo. Erythrocyte percentage DHA and EPA enrichment (a validated proxy for hepatic enrichment) was determined by gas chromatography. Liver fat percentage was measured in three discrete liver zones by magnetic resonance spectroscopy (MRS). We also measured body fat distribution, physical activity and a range of cardiometabolic risk factors. Recruitment started in January 2010 and ended in June 2011. We identified 178 potential participants, and randomised 103 participants who met the inclusion criteria. The WELCOME study was approved by the local ethics committee (REC: 08/H0502/165; www.clinicalTrials.gov registration number NCT00760513). Copyright © 2014 Elsevier Inc. All rights reserved.

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.

Herbal Hepatotoxicity: Clinical Characteristics and Listing Compilation

PubMed Central

Frenzel, Christian; Teschke, Rolf

2016-01-01

Herb induced liver injury (HILI) and drug induced liver injury (DILI) share the common characteristic of chemical compounds as their causative agents, which were either produced by the plant or synthetic processes. Both, natural and synthetic chemicals are foreign products to the body and need metabolic degradation to be eliminated. During this process, hepatotoxic metabolites may be generated causing liver injury in susceptible patients. There is uncertainty, whether risk factors such as high lipophilicity or high daily and cumulative doses play a pathogenetic role for HILI, as these are under discussion for DILI. It is also often unclear, whether a HILI case has an idiosyncratic or an intrinsic background. Treatment with herbs of Western medicine or traditional Chinese medicine (TCM) rarely causes elevated liver tests (LT). However, HILI can develop to acute liver failure requiring liver transplantation in single cases. HILI is a diagnosis of exclusion, because clinical features of HILI are not specific as they are also found in many other liver diseases unrelated to herbal use. In strikingly increased liver tests signifying severe liver injury, herbal use has to be stopped. To establish HILI as the cause of liver damage, RUCAM (Roussel Uclaf Causality Assessment Method) is a useful tool. Diagnostic problems may emerge when alternative causes were not carefully excluded and the correct therapy is withheld. Future strategies should focus on RUCAM based causality assessment in suspected HILI cases and more regulatory efforts to provide all herbal medicines and herbal dietary supplements used as medicine with strict regulatory surveillance, considering them as herbal drugs and ascertaining an appropriate risk benefit balance. PMID:27128912

Computed tomography findings in liver fibrosis and cirrhosis.

PubMed

Huber, A; Ebner, L; Montani, M; Semmo, N; Roy Choudhury, K; Heverhagen, J; Christe, A

2014-02-19

Computed tomography (CT) is inferior to the fibroscan and laboratory testing in the noninvasive diagnosis of liver fibrosis. On the other hand, CT is a frequently used diagnostic tool in modern medicine. The auxiliary finding of clinically occult liver fibrosis in CT scans could result in an earlier diagnosis. The aim of this study was to analyse quantifiable direct signs of liver remodelling in CT scans to depict liver fibrosis in a precirrhotic stage. Retrospective review of 148 abdominal CT scans (80 liver cirrhosis, 35 precirrhotic fibrosis and 33 control patients). Fibrosis and cirrhosis were histologically proven. The diameters of the three main hepatic veins were measured 1-2 cm before their aperture into the inferior caval vein. The width of the caudate and the right hepatic lobe were divided, and measured horizontally at the level of the first bifurcation of the right portal vein in axial planes (caudate-right-lobe ratio). A combination of both (sum of liver vein diameters divided by the caudate-right lobe ratio) was defined as the ld/crl ratio. These metrics were analysed for the detection of liver fibrosis and cirrhosis. An ld/crl-r <24 showed a sensitivity of 83% and a specificity of 76% for precirrhotic liver fibrosis. Liver cirrhosis could be detected with a sensitivity of 88% and a specificity of 82% if ld/crl-r <20. An ld/crl-r <24 justifies laboratory testing and a fibroscan. This could bring forward the diagnosis and patients would profit from early treatment in a potentially reversible stage of disease.

Diagnosis and Management of Alcoholic Liver Disease.

PubMed

Dugum, Mohannad; McCullough, Arthur

2015-06-28

Alcohol is a leading cause of liver disease and is associated with significant morbidity and mortality. Several factors, including the amount and duration of alcohol consumption, affect the development and progression of alcoholic liver disease (ALD). ALD represents a spectrum of liver pathology ranging from fatty change to fibrosis to cirrhosis. Early diagnosis of ALD is important to encourage alcohol abstinence, minimize the progression of liver fibrosis, and manage cirrhosis-related complications including hepatocellular carcinoma. A number of questionnaires and laboratory tests are available to screen for alcohol intake. Liver biopsy remains the gold-standard diagnostic tool for ALD, but noninvasive accurate alternatives, including a number of biochemical tests as well as liver stiffness measurement, are increasingly being utilized in the evaluation of patients with suspected ALD. The management of ALD depends largely on complete abstinence from alcohol. Supportive care should focus on treating alcohol withdrawal and providing enteral nutrition while managing the complications of liver failure. Alcoholic hepatitis (AH) is a devastating acute form of ALD that requires early recognition and specialized tertiary medical care. Assessment of AH severity using defined scoring systems is important to allocate resources and initiate appropriate therapy. Corticosteroids or pentoxifylline are commonly used in treating AH but provide a limited survival benefit. Liver transplantation represents the ultimate therapy for patients with alcoholic cirrhosis, with most transplant centers mandating a 6 month period of abstinence from alcohol before listing. Early liver transplantation is also emerging as a therapeutic measure in specifically selected patients with severe AH. A number of novel targeted therapies for ALD are currently being evaluated in clinical trials.

Data Mining in the U.S. National Toxicology Program (NTP) Database Reveals a Potential Bias Regarding Liver Tumors in Rodents Irrespective of the Test Agent

PubMed Central

Ring, Matthias; Eskofier, Bjoern M.

2015-01-01

Long-term studies in rodents are the benchmark method to assess carcinogenicity of single substances, mixtures, and multi-compounds. In such a study, mice and rats are exposed to a test agent at different dose levels for a period of two years and the incidence of neoplastic lesions is observed. However, this two-year study is also expensive, time-consuming, and burdensome to the experimental animals. Consequently, various alternatives have been proposed in the literature to assess carcinogenicity on basis of short-term studies. In this paper, we investigated if effects on the rodents’ liver weight in short-term studies can be exploited to predict the incidence of liver tumors in long-term studies. A set of 138 paired short- and long-term studies was compiled from the database of the U.S. National Toxicology Program (NTP), more precisely, from (long-term) two-year carcinogenicity studies and their preceding (short-term) dose finding studies. In this set, data mining methods revealed patterns that can predict the incidence of liver tumors with accuracies of over 80%. However, the results simultaneously indicated a potential bias regarding liver tumors in two-year NTP studies. The incidence of liver tumors does not only depend on the test agent but also on other confounding factors in the study design, e.g., species, sex, type of substance. We recommend considering this bias if the hazard or risk of a test agent is assessed on basis of a NTP carcinogenicity study. PMID:25658102

Progression of Liver Fibrosis in HIV/HCV Co-Infection: A Comparison between Non-Invasive Assessment Methods and Liver Biopsy

PubMed Central

Schmid, Patrick; Bregenzer, Andrea; Huber, Milo; Rauch, Andri; Jochum, Wolfram; Müllhaupt, Beat; Vernazza, Pietro; Opravil, Milos; Weber, Rainer

2015-01-01

Objectives To evaluate the diagnostic performance of seven non-invasive tests (NITs) of liver fibrosis and to assess fibrosis progression over time in HIV/HCV co-infected patients. Methods Transient elastography (TE) and six blood tests were compared to histopathological fibrosis stage (METAVIR). Participants were followed over three years with NITs at yearly intervals. Results Area under the receiver operating characteristic curve (AUROC) for significant fibrosis (> = F2) in 105 participants was highest for TE (0.85), followed by FIB-4 (0.77), ELF-Test (0.77), APRI (0.76), Fibrotest (0.75), hyaluronic acid (0.70), and Hepascore (0.68). AUROC for cirrhosis (F4) was 0.97 for TE followed by FIB-4 (0.91), APRI (0.89), Fibrotest (0.84), Hepascore (0.82), ELF-Test (0.82), and hyaluronic acid (0.79). A three year follow-up was completed by 87 participants, all on antiretroviral therapy and in 20 patients who completed HCV treatment (9 with sustained virologic response). TE, APRI and Fibrotest did not significantly change during follow-up. There was weak evidence for an increase of FIB-4 (mean increase: 0.22, p = 0.07). 42 participants had a second liver biopsy: Among 38 participants with F0-F3 at baseline, 10 were progessors (1-stage increase in fibrosis, 8 participants; 2-stage, 1; 3-stage, 1). Among progressors, mean increase in TE was 3.35 kPa, in APRI 0.36, and in FIB-4 0.75. Fibrotest results did not change over 3 years. Conclusion TE was the best NIT for liver fibrosis staging in HIV/HCV co-infected patients. APRI-Score, FIB-4 Index, Fibrotest, and ELF-Test were less reliable. Routinely available APRI and FIB-4 performed as good as more expensive tests. NITs did not change significantly during a follow-up of three years, suggesting slow liver disease progression in a majority of HIV/HCV co-infected persons on antiretroviral therapy. PMID:26418061

Progression of Liver Fibrosis in HIV/HCV Co-Infection: A Comparison between Non-Invasive Assessment Methods and Liver Biopsy.

PubMed

Schmid, Patrick; Bregenzer, Andrea; Huber, Milo; Rauch, Andri; Jochum, Wolfram; Müllhaupt, Beat; Vernazza, Pietro; Opravil, Milos; Weber, Rainer

2015-01-01

To evaluate the diagnostic performance of seven non-invasive tests (NITs) of liver fibrosis and to assess fibrosis progression over time in HIV/HCV co-infected patients. Transient elastography (TE) and six blood tests were compared to histopathological fibrosis stage (METAVIR). Participants were followed over three years with NITs at yearly intervals. Area under the receiver operating characteristic curve (AUROC) for significant fibrosis (> = F2) in 105 participants was highest for TE (0.85), followed by FIB-4 (0.77), ELF-Test (0.77), APRI (0.76), Fibrotest (0.75), hyaluronic acid (0.70), and Hepascore (0.68). AUROC for cirrhosis (F4) was 0.97 for TE followed by FIB-4 (0.91), APRI (0.89), Fibrotest (0.84), Hepascore (0.82), ELF-Test (0.82), and hyaluronic acid (0.79). A three year follow-up was completed by 87 participants, all on antiretroviral therapy and in 20 patients who completed HCV treatment (9 with sustained virologic response). TE, APRI and Fibrotest did not significantly change during follow-up. There was weak evidence for an increase of FIB-4 (mean increase: 0.22, p = 0.07). 42 participants had a second liver biopsy: Among 38 participants with F0-F3 at baseline, 10 were progessors (1-stage increase in fibrosis, 8 participants; 2-stage, 1; 3-stage, 1). Among progressors, mean increase in TE was 3.35 kPa, in APRI 0.36, and in FIB-4 0.75. Fibrotest results did not change over 3 years. TE was the best NIT for liver fibrosis staging in HIV/HCV co-infected patients. APRI-Score, FIB-4 Index, Fibrotest, and ELF-Test were less reliable. Routinely available APRI and FIB-4 performed as good as more expensive tests. NITs did not change significantly during a follow-up of three years, suggesting slow liver disease progression in a majority of HIV/HCV co-infected persons on antiretroviral therapy.

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.

Periportal fibrosis and other liver ultrasonography findings in vinyl chloride workers

PubMed Central

Maroni, M; Mocci, F; Visentin, S; Preti, G; Fanetti, A

2003-01-01

Aims: To investigate the presence of liver lesions and their relation with vinyl chloride monomer (VCM) exposure or other personal risk factors, in workers involved in the production of VCM and polyvinyl chloride (PVC). Methods: A liver ultrasonography examination was conducted in 757 workers, some of whom had long standing service in the production of VCM and PVC. The study involved: assessment of individual past and present VCM exposure of each worker; collection of past personal health history, lifestyle and personal data; routine liver function tests; and liver ultrasonography. Results: No cases of liver malignancies were detected. Angiomas and liver cysts were found with a frequency of occurrence within the expected range of the general population. The main findings consisted of hepatomegaly (34.7%), steatosis (31.8%), and periportal fibrosis (16.0%). A logistic regression analysis indicated that hepatomegaly and steatosis were associated with obesity and lipid metabolism disturbances and not with VCM exposure. Periportal fibrosis, in addition to constitutional or dietary factors, was shown to be associated with VCM exposure, but only when maximum exposure in the subject's history had been at least 200 ppm as a yearly average; no effects were observed at 50 ppm or below. Conclusions: Workers exposed to 200 ppm VCM for at least one year have a fourfold increased risk of developing periportal liver fibrosis. Liver ultrasonography is a suitable and important diagnostic test for the medical surveillance of vinyl chloride workers. PMID:12499459

Building Shared Experience to Advance Practical Application of Pathway-Based Toxicology: Liver Toxicity Mode-of-Action

PubMed Central

Willett, Catherine; Rae, Jessica Caverly; Goyak, Katy O.; Minsavage, Gary; Westmoreland, Carl; Andersen, Melvin; Avigan, Mark; Duché, Daniel; Harris, Georgina; Hartung, Thomas; Jaeschke, Hartmut; Kleensang, Andre; Landesmann, Brigitte; Martos, Suzanne; Matevia, Marilyn; Toole, Colleen; Rowan, Andrew; Schultz, Terry; Seed, Jennifer; Senior, John; Shah, Imran; Subramanian, Kalyanasundaram; Vinken, Mathieu; Watkins, Paul

2016-01-01

Summary A workshop sponsored by the Human Toxicology Project Consortium (HTPC), “Building Shared Experience to Advance Practical Application of Pathway-Based Toxicology: Liver Toxicity Mode-of-Action” brought together experts from a wide range of perspectives to inform the process of pathway development and to advance two prototype pathways initially developed by the European Commission Joint Research Center (JRC): liver-specific fibrosis and steatosis. The first half of the workshop focused on the theory and practice of pathway development; the second on liver disease and the two prototype pathways. Participants agreed pathway development is extremely useful for organizing information and found that focusing the theoretical discussion on a specific AOP is helpful. It is important to include several perspectives during pathway development, including information specialists, pathologists, human health and environmental risk assessors, and chemical and product manufacturers, to ensure the biology is well captured and end use is considered. PMID:24535319

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

PubMed Central

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

1984-01-01

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

Association of liver enzymes and computed tomography markers of liver steatosis with familial longevity.

PubMed

Sala, Michiel; Kroft, Lucia J M; Röell, Boudewijn; van der Grond, Jeroen; Slagboom, P Eline; Mooijaart, Simon P; de Roos, Albert; van Heemst, Diana

2014-01-01

Familial longevity is marked by enhanced peripheral but not hepatic insulin sensitivity. The liver has a critical role in the pathogenesis of hepatic insulin resistance. Therefore we hypothesized that the extent of liver steatosis would be similar between offspring of long-lived siblings and control subjects. To test our hypothesis, we investigated the extent of liver steatosis in non-diabetic offspring of long-lived siblings and age-matched controls by measuring liver enzymes in plasma and liver fat by computed tomography (CT). We measured nonfasting alanine transaminase (ALT), aspartate aminotransferase (AST), and Υ-glutamyl transferase (GGT) in 1625 subjects (736 men, mean age 59.1 years) from the Leiden Longevity Study, comprising offspring of long-lived siblings and partners thereof. In a random subgroup, fasting serum samples (n = 230) were evaluated and CT was performed (n = 268) for assessment of liver-spleen (L/S) ratio and the prevalence of moderate-to-severe non-alcoholic fatty liver disease (NAFLD). Linear mixed model analysis was performed adjusting for age, gender, body mass index, smoking, use of alcohol and hepatotoxic medication, and correlation of sibling relationship. Offspring of long-lived siblings had higher nonfasting ALT levels as compared to control subjects (24.3 mmol/L versus 23.2 mmol/L, p = 0.03), while AST and GGT levels were similar between the two groups. All fasting liver enzyme levels were similar between the two groups. CT L/S ratio and prevalence of moderate-to-severe NAFLD was similar between groups (1.12 vs 1.14, p = 0.25 and 8% versus 8%, p = 0.91, respectively). Except for nonfasting levels of ALT, which were slightly higher in the offspring of long-lived siblings compared to controls, no differences were found between groups in the extent of liver steatosis, as assessed with liver biochemical tests and CT. Thus, our data indicate that the extent of liver steatosis is similar between offspring of long-lived siblings and control subjects.

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

PubMed Central

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

2016-01-01

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

[Comparative studies on the toxicity of various dieelectrics, kerosene derivatives, used in the electroerosion technic. I. Morphological, cytoenzymatic and biochemical changes in the liver of rats chronically exposed to kerosene hydrocarbons].

PubMed

Starek, A; Kamiński, M

1982-01-01

Rats exposed to cosmetic kerosene mists (odourless kerosene), concentration of 75 and 300 mg/m3 for 14 days, underwent morphological and cytoenzymatic liver tests and biochemical tests of lipids composition in this organ. In addition, lipids concentration and activity of test--enzymes in blood serum were determined. The findings were: passive congestion, fine--droplet fatty degeneration in I zones of clusters and increased number of Browicz--Kupffer's phagocytes near liver triads. Those changes were accompanied by: decreased activity of succinic dehydrogenese (SDH), tetrazolic NADPH--reductase (NADPH-r.t.) and glucose-6-phosphatase (G-6-P-ase) and increased activity of adenosine triphosphatase (Mg++-ATP-ase) and acid phosphatase (AcP). In blood serum medium increase of base phosphatase (AP), 5-nucleotidase (5-Nt) and leucyloaminepeptidase (LAP) and decreased activity of prothrombin (Pt) were found. In addition, it was demonstrated that liver steatosis was characterized by cumulation of free fatty acids, phospholipids and cholesterol esters with simultaneous decrease in triglycerides content in this organ. The obtained results indicate that changes induced by kerosene hydrocarbons in liver are focal and cumulate in I zones of liver clusters. The degree of lesion varies with the extent of exposure, and results from toxic effects of this preparation on hepatic cells lypoproteid membranes.

Predictive factors of short term outcome after liver transplantation: A review

PubMed Central

Bolondi, Giuliano; Mocchegiani, Federico; Montalti, Roberto; Nicolini, Daniele; Vivarelli, Marco; De Pietri, Lesley

2016-01-01

Liver transplantation represents a fundamental therapeutic solution to end-stage liver disease. The need for liver allografts has extended the set of criteria for organ acceptability, increasing the risk of adverse outcomes. Little is known about the early postoperative parameters that can be used as valid predictive indices for early graft function, retransplantation or surgical reintervention, secondary complications, long intensive care unit stay or death. In this review, we present state-of-the-art knowledge regarding the early post-transplantation tests and scores that can be applied during the first postoperative week to predict liver allograft function and patient outcome, thereby guiding the therapeutic and surgical decisions of the medical staff. Post-transplant clinical and biochemical assessment of patients through laboratory tests (platelet count, transaminase and bilirubin levels, INR, factor V, lactates, and Insulin Growth Factor 1) and scores (model for end-stage liver disease, acute physiology and chronic health evaluation, sequential organ failure assessment and model of early allograft function) have been reported to have good performance, but they only allow late evaluation of patient status and graft function, requiring days to be quantified. The indocyanine green plasma disappearance rate has long been used as a liver function assessment technique and has produced interesting, although not univocal, results when performed between the 1th and the 5th day after transplantation. The liver maximal function capacity test is a promising method of metabolic liver activity assessment, but its use is limited by economic cost and extrahepatic factors. To date, a consensual definition of early allograft dysfunction and the integration and validation of the above-mentioned techniques, through the development of numerically consistent multicentric prospective randomised trials, are necessary. The medical and surgical management of transplanted patients could be greatly improved by using clinically reliable tools to predict early graft function. PMID:27468188

Predictive factors of short term outcome after liver transplantation: A review.

PubMed

Bolondi, Giuliano; Mocchegiani, Federico; Montalti, Roberto; Nicolini, Daniele; Vivarelli, Marco; De Pietri, Lesley

2016-07-14

Liver transplantation represents a fundamental therapeutic solution to end-stage liver disease. The need for liver allografts has extended the set of criteria for organ acceptability, increasing the risk of adverse outcomes. Little is known about the early postoperative parameters that can be used as valid predictive indices for early graft function, retransplantation or surgical reintervention, secondary complications, long intensive care unit stay or death. In this review, we present state-of-the-art knowledge regarding the early post-transplantation tests and scores that can be applied during the first postoperative week to predict liver allograft function and patient outcome, thereby guiding the therapeutic and surgical decisions of the medical staff. Post-transplant clinical and biochemical assessment of patients through laboratory tests (platelet count, transaminase and bilirubin levels, INR, factor V, lactates, and Insulin Growth Factor 1) and scores (model for end-stage liver disease, acute physiology and chronic health evaluation, sequential organ failure assessment and model of early allograft function) have been reported to have good performance, but they only allow late evaluation of patient status and graft function, requiring days to be quantified. The indocyanine green plasma disappearance rate has long been used as a liver function assessment technique and has produced interesting, although not univocal, results when performed between the 1(th) and the 5(th) day after transplantation. The liver maximal function capacity test is a promising method of metabolic liver activity assessment, but its use is limited by economic cost and extrahepatic factors. To date, a consensual definition of early allograft dysfunction and the integration and validation of the above-mentioned techniques, through the development of numerically consistent multicentric prospective randomised trials, are necessary. The medical and surgical management of transplanted patients could be greatly improved by using clinically reliable tools to predict early graft function.

Left Lobe Auxiliary Liver Transplantation for End-stage Hepatitis B Liver Cirrhosis.

PubMed

Wang, S-F; Chen, X-P; Chen, Z-S; Wei, L; Dong, S-L; Guo, H; Jiang, J-P; Teng, W-H; Huang, Z-Y; Zhang, W-G

2017-06-01

Auxiliary liver transplantation (ALT) for hepatitis B virus (HBV)-related liver cirrhosis previously showed poor results, because the native liver was a significant source of HBV recurrence and the graft could be rapidly destroyed by HBV infection in an immunosuppressive condition. Four patients with HBV-related liver cirrhosis were unable to undergo orthotopic liver transplantation because the only available grafts of left lobe were too small. Under entecavir-based anti-HBV treatment, they underwent ALT in which the recipient left liver was removed and the small left lobe graft was implanted in the corresponding space. The mean graft weight/recipient weight was 0.49% (range, 0.38%-0.55%). One year after transplantation, the graft sizes were increased to 273% and the remnant livers were decreased to 44%. Serum HBV DNA was persistently undetectable. Periodic graft biopsy showed no signs of tissue injury and negative immunostaining for hepatitis B surface antigen and hepatitis B core antigen. After a mean follow-up period of 21 months, all patients live well with normal graft function. Our study suggests that ALT for HBV-related liver cirrhosis is feasible under entecavir-based anti-HBV treatment. Successful application of small left livers in end-stage liver cirrhosis may significantly increase the pool of left liver grafts for adult patients. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

21 CFR 862.1535 - Ornithine carbamyl transferase test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... and treatment of liver diseases, such as infectious hepatitis, acute cholecystitis (inflammation of the gall bladder), cirrhosis, and liver metastases. (b) Classification. Class I (general controls...

Percutaneous management of postoperative bile leaks with an ethylene vinyl alcohol copolymer (Onyx).

PubMed

Uller, W; Müller-Wille, R; Loss, M; Hammer, S; Schleder, S; Goessmann, H; Wiggermann, P; Stroszczynski, C; Wohlgemuth, W A

2013-12-01

The management of postoperative bile leakage is challenging especially if the leak rises from the cut surface of the liver and endoscopic treatment fails. Percutaneous transhepatic treatment of bile leaks with biliary drainage is accepted but often requires long-term placement of the drains and is associated with treatment failures. This series evaluates selective embolization of bile ducts with an ethylene vinyl alcohol copolymer (Onyx) in patients with postoperative bile leaks as an alternative treatment option. Between January and September 2012, five consecutive patients with persistent postoperative bile leaks underwent percutaneous transhepatic Onyx application and were analyzed regarding procedural management, complications and success rates. The persistent bile leaks were situated at the cystic stump (after cholecystectomy, n = 2), at the cut surface of the liver (after extended liver resection, n = 2) and at the surface of the liver after surgical exploration and perihepatic abscess (n = 1). Bile drainage alone (endoscopic or percutaneous) failed in all patients and open redo-surgery was deemed potentially harmful. Bilomas were externally drained in all patients before Onyx application. For the closure of bile leaks, Onyx was injected through a microcatheter in a previously built coil nest to keep Onyx in place. All bile leaks were initially closed immediately. In the 2nd week after Onyx embolization, 2 patients showed recurrent small bile leaks without clinical symptoms. In the 4th week after Onyx application, all leaks were closed. No complications occurred. All leaking bile ducts were initially closed immediately after Onyx application. In the 2nd week after Onyx application, 2 patients showed small bile leaks without clinical symptoms. All leaks were closed in the 4th week after Onyx application. © Georg Thieme Verlag KG Stuttgart · New York.

EFSUMB guidelines 2011: comment on emergent indications and visions.

PubMed

Dietrich, C F; Cui, X W; Barreiros, A P; Hocke, M; Ignee, A

2012-07-01

The focus of this article is the emergent and potential indications of contrast-enhanced ultrasound (CEUS). Emergent applications of CEUS techniques include extravascular and intracavitary contrast-enhanced ultrasound, quantitative assessment of microvascular circulation for tumor response assessment, and tumor characterization using dynamic contrast-enhanced ultrasound (DCE-US). Potential indications for microbubble agents include novel molecular imaging and drug and gene delivery techniques, which have been successfully tested in animal models. "Comments and Illustrations of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Non-Liver Guidelines 2011" which focus more on established applications are published in the same supplement to Ultraschall in der Medizin (European Journal of Ultrasound). © Georg Thieme Verlag KG Stuttgart · New York.

Over-dose insulin and stable gastric pentadecapeptide BPC 157. Attenuated gastric ulcers, seizures, brain lesions, hepatomegaly, fatty liver, breakdown of liver glycogen, profound hypoglycemia and calcification in rats.

PubMed

Ilic, S; Brcic, I; Mester, M; Filipovic, M; Sever, M; Klicek, R; Barisic, I; Radic, B; Zoricic, Z; Bilic, V; Berkopic, L; Brcic, L; Kolenc, D; Romic, Z; Pazanin, L; Seiwerth, S; Sikiric, P

2009-12-01

We focused on over-dose insulin (250 IU/kg i.p.) induced gastric ulcers and then on other disturbances that were concomitantly induced in rats, seizures (eventually fatal), severely damaged neurons in cerebral cortex and hippocampus, hepatomegaly, fatty liver, increased AST, ALT and amylase serum values, breakdown of liver glycogen with profound hypoglycemia and calcification development. Calcium deposits were present in the blood vessel walls, hepatocytes surrounding blood vessels and sometimes even in parenchyma of the liver mainly as linear and only occasionally as granular accumulation. As an antidote after insulin, we applied the stable gastric pentadecapeptide BPC 157 (10 microg/kg) given (i) intraperitoneally or (ii) intragastrically immediately after insulin. Controls received simultaneously an equivolume of saline (5 ml/kg). Those rats that survived till the 180 minutes after over-dose application were further assessed. Interestingly, pentadecapeptide BPC 157, as an antiulcer peptide, may besides stomach ulcer consistently counteract all insulin disturbances and fatal outcome. BPC 157 rats showed no fatal outcome, they were mostly without hypoglycemic seizures with apparently higher blood glucose levels (glycogen was still present in hepatocytes), less liver pathology (i.e., normal liver weight, less fatty liver), decreased ALT, AST and amylase serum values, markedly less damaged neurons in brain and they only occasionally had small gastric lesions. BPC 157 rats exhibited mostly only dot-like calcium presentation. In conclusion, the success of BPC 157 therapy may indicate a likely role of BPC 157 in insulin controlling and BPC 157 may influence one or more causative process(es) after excessive insulin application.

Thermodiffusion for continuous quantification of hepatic microcirculation--validation and potential in liver transplantation.

PubMed

Klar, E; Kraus, T; Bleyl, J; Newman, W H; Bowman, H F; Hofmann, W J; Kummer, R; Bredt, M; Herfarth, C

1999-09-01

Hepatic microcirculation is a main determinant of reperfusion injury and graft quality in liver transplantation. Methods available for the quantification of hepatic microcirculation are indirect, are invasive, or preclude postoperative application. The aim of this study was the validation of thermodiffusion in a new modification allowing long-term use in the clinical setting. In six pigs Doppler flowmeters were positioned around the hepatic artery and portal vein for the measurement of total liver blood flow. Liver perfusion was quantified by thermodiffusion and compared to H(2) clearance as an established technique under baseline conditions, during different degrees of portal venous obstruction and during occlusion of the hepatic artery. Thermodiffusion measurements were recorded for five days postoperatively followed by histological evaluation of the hepatic puncture site. Perfusion data obtained by thermodiffusion were significantly correlated to H(2) clearance (r = 0.94, P < 0. 001) and to liver blood flow (r = 0.9, P < 0.05). The agreement between thermodiffusion and H(2) clearance was excellent (mean difference -2.1 ml/100 g/min; limits of agreement -12.5 and 8.3 ml/100 g/min). Occlusion of the portal vein or hepatic artery was immediately detected by thermodiffusion, indicating a decrease of perfusion by 64 +/- 7% or 27 +/- 5% of baseline, respectively. Perfusion values at baseline and during vascular occlusion were reproducible during the entire observation period. Histological changes of the liver tissue adjacent to the thermodiffusion probes were minute and did not influence long-term measurements. In vivo validation proved that enhanced thermodiffusion is a minimally invasive technique for the continuous, real-time quantification of hepatic microcirculation. Changes in liver perfusion can be safely detected over several days postoperatively. The implication for liver transplantation has led to the clinical application of thermodiffusion. Copyright 1999 Academic Press.

Non-invasive assessment of liver fibrosis: Between prediction/prevention of outcomes and cost-effectiveness.

PubMed

Stasi, Cristina; Milani, Stefano

2016-01-28

The assessment of the fibrotic evolution of chronic hepatitis has always been a challenge for the clinical hepatologist. Over the past decade, various non-invasive methods have been proposed to detect the presence of fibrosis, including the elastometric measure of stiffness, panels of clinical and biochemical parameters, and combinations of both methods. The aim of this review is to analyse the most recent data on non-invasive techniques for the evaluation of hepatic fibrosis with particular attention to cost-effectiveness. We searched for relevant studies published in English using the PubMed database from 2009 to the present. A large number of studies have suggested that elastography and serum markers are useful techniques for diagnosing severe fibrosis and cirrhosis and for excluding significant fibrosis in hepatitis C virus patients. In addition, hepatic stiffness may also help to prognosticate treatment response to antiviral therapy. It has also been shown that magnetic resonance elastography has a high accuracy for staging and differentiating liver fibrosis. Finally, studies have shown that non-invasive methods are becoming increasingly precise in either positively identifying or excluding liver fibrosis, thus reducing the need for liver biopsy. However, both serum markers and transient elastography still have "grey area" values of lower accuracy. In this case, liver biopsy is still required to properly assess liver fibrosis. Recently, the guidelines produced by the World Health Organization have suggested that the AST-to-platelet ratio index or FIB-4 test could be utilised for the evaluation of liver fibrosis rather than other, more expensive non-invasive tests, such as elastography or FibroTest.

Non-invasive assessment of liver fibrosis: Between prediction/prevention of outcomes and cost-effectiveness

PubMed Central

Stasi, Cristina; Milani, Stefano

2016-01-01

The assessment of the fibrotic evolution of chronic hepatitis has always been a challenge for the clinical hepatologist. Over the past decade, various non-invasive methods have been proposed to detect the presence of fibrosis, including the elastometric measure of stiffness, panels of clinical and biochemical parameters, and combinations of both methods. The aim of this review is to analyse the most recent data on non-invasive techniques for the evaluation of hepatic fibrosis with particular attention to cost-effectiveness. We searched for relevant studies published in English using the PubMed database from 2009 to the present. A large number of studies have suggested that elastography and serum markers are useful techniques for diagnosing severe fibrosis and cirrhosis and for excluding significant fibrosis in hepatitis C virus patients. In addition, hepatic stiffness may also help to prognosticate treatment response to antiviral therapy. It has also been shown that magnetic resonance elastography has a high accuracy for staging and differentiating liver fibrosis. Finally, studies have shown that non-invasive methods are becoming increasingly precise in either positively identifying or excluding liver fibrosis, thus reducing the need for liver biopsy. However, both serum markers and transient elastography still have “grey area” values of lower accuracy. In this case, liver biopsy is still required to properly assess liver fibrosis. Recently, the guidelines produced by the World Health Organization have suggested that the AST-to-platelet ratio index or FIB-4 test could be utilised for the evaluation of liver fibrosis rather than other, more expensive non-invasive tests, such as elastography or FibroTest. PMID:26819535

Isolation of a novel thermophilic Campylobacter from cases of spotty liver disease in laying hens and experimental reproduction of infection and microscopic pathology.

PubMed

Crawshaw, Tim R; Chanter, Jeremy I; Young, Stuart C L; Cawthraw, Shaun; Whatmore, Adrian M; Koylass, Mark S; Vidal, Ana B; Salguero, Francisco J; Irvine, Richard M

2015-09-30

The condition known as spotty liver disease or spotty liver syndrome can cause significant mortality in free range laying hen flocks. It has been described in Europe and Australia but the aetiology has not been established. There are similarities between spotty liver disease and avian vibrionic hepatitis, a condition which was reported in the 1950s. A Vibrio-like organism was suspected to be the cause of avian vibrionic hepatitis, although this organism was never fully characterised. We report the isolation of a novel Campylobacter from five separate outbreaks of spotty liver disease. The conditions required for culture, the growth characteristics, electron microscopical morphology and results of the phenotypic tests used in the identification of this novel Campylobacter sp. are described. The novel Campylobacter is slow growing and fastidious and does not grow on media routinely used for isolating Campylobacter sp. The morphology is typical for a Campylobacter sp. and phenotypic tests and a duplex real time PCR test differentiate the novel Campylobacter from other members of the genus. 16S rRNA analysis of 19 isolates showed an identical sequence which appears to represent a hitherto unknown sub lineage within the genus Campylobacter. Experimental intraperitoneal infection of four week old SPF chickens produced microscopic liver pathology indistinguishable from natural disease and the novel Campylobacter was recovered from the experimentally infected chicks. The isolates described appear to be a possible causal organism for spotty liver disease. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

[IMPORTANCE OF SHEAR WAVE ELASTOGRAPHY OF LIVERS IN PRACTICALLY HEALTHY PREGNANT WOMEN].

PubMed

Sariyeva, E; Salahova, S; Bayramov, N

2017-01-01

Pulse-wave elastography (SWE) that is one of the mostly used methods in the recent years holds important place in assessment of liver fibrosis. However there is no exact information on the results of liver elastography in healthy pregnant women in the world literature. The aim of the study was to investigate theSWE parameters of liver elastography in practically healthy pregnant women. The subject of the research was 50 practically healthy pregnant women within 18-45 years old (mean age 27.7±0.7). The pregnant women with genital and extragenital diseases were not included to the research. The research work was executed in the II Department of Obstetrics and Gynecology of Azerbaijan Medical University. SWE of liver in pregnant women was conducted in the I Department of Surgical Diseases of Azerbaijan Medical University through Supersonic Aixplorer Multi Wave device presented by the Scientific Development Foundation under the President of the Azerbaijan Republic. The obtained tissue hardness indicators are assessed under METAVIR scale. The results of the research showed that the measures of liver in practically healthy pregnant women are normal, edges flat, its echogenicity mainly normal, echostructure of its parenchyma homogenous, hardness was F0-F1 (normal) under METAVIR scale, fibrosis not observed. The obtained results were processed by variational (power average, percentile distribution) and correlation (ρ-Spearman) analyzes using the statistical package SPSS-20. A statistical study of the distribution of liver density in healthy women showed that the average density was 4,43±0,01 with 95% confidence interval (4,23 - 4,63). The histogram of distribution of liver density in practically healthy women belongs to the family of normal distributions with coefficients of variation coefficient (16.3%), asymmetry (-0.861±0.337) and excess (-0.068±0.662). Correlation analysis in healthy women did not reveal a reliable relationship between age and liver density (ρ=0.082, p=0.571), but a significant inverse correlation was found between the body mass index (BMI) and liver density (ρ=-0.317; p=0.025). Easy application, non-invasiveness, maximum exactness within the real time, repeatedly application of procedure and no risk to fetus by Shear Wave elastography of liver allow applying this method in pregnant women. Study of liver elasticity in pregnant women allows assessing the grades of hepatic fibrosis and differentiating liver disease.

Donor Indocyanine Green Clearance Test Predicts Graft Quality and Early Graft Prognosis After Liver Transplantation.

PubMed

Tang, Yunhua; Han, Ming; Chen, Maogen; Wang, Xiaoping; Ji, Fei; Zhao, Qiang; Zhang, Zhiheng; Ju, Weiqiang; Wang, Dongping; Guo, Zhiyong; He, Xiaoshun

2017-11-01

Transplantation centers have given much attention to donor availability. However, no reliable quantitative methods have been employed to accurately assess graft quality before transplantation. Here, we report that the indocyanine green (ICG) clearance test is a valuable index for liver grafts. We performed the ICG clearance test on 90 brain-dead donors within 6 h before organ procurement between March 2015 and November 2016. We also analyzed the relationship between graft liver function and early graft survival after liver transplantation (LT). Our results suggest that the ICG retention rate at 15 min (ICGR15) of donors before procurement was independently associated with 3-month graft survival after LT. The best donor ICGR15 cutoff value was 11.0%/min, and we observed a significant increase in 3-month graft failure among patients with a donor ICGR15 above this value. On the other hand, a donor ICGR15 value of ≤ 11.0%/min could be used as an early assessment index of graft quality because it provides additional information to the transplant surgeon or organ procurement organization members who must maintain or improve organ function to adapt the LT. An ICG clearance test before liver procurement might be an effective quantitative method to predict graft availability and improve early graft prognosis after LT.

Hepatocerebral degeneration

MedlinePlus

... Liver damage can lead to the buildup of ammonia and other toxic materials in the body. This ... Walking instability Laboratory tests may show a high ammonia level in the bloodstream and abnormal liver function. ...

Technical Note: Validation and implementation of a wireless transponder tracking system for gated stereotactic ablative radiotherapy of the liver

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

James, Joshua, E-mail: joshua.james@louisville.edu; Dunlap, Neal E.; Nguyen, Vi Nhan

Purpose: Tracking soft-tissue targets has recently been cleared as a new application of Calypso, an electromagnetic wireless transponder tracking system, allowing for gated treatment of the liver based on the motion of the target volume itself. The purpose of this study is to describe the details of validating the Calypso system for wireless transponder tracking of the liver and to present the clinical workflow for using it to deliver gated stereotactic ablative radiotherapy (SABR). Methods: A commercial 3D diode array motion system was used to evaluate the dynamic tracking accuracy of Calypso when tracking continuous large amplitude motion. It wasmore » then used to perform end-to-end tests to evaluate the dosimetric accuracy of gated beam delivery for liver SABR. In addition, gating limits were investigated to determine how large the gating window can be while still maintaining dosimetric accuracy. The gating latency of the Calypso system was also measured using a customized motion phantom. Results: The average absolute difference between the measured and expected positional offset was 0.3 mm. The 2%/2 mm gamma pass rates for the gated treatment delivery were greater than 97%. When increasing the gating limits beyond the known extent of planned motion, the gamma pass rates decreased as expected. The 2%/2 mm gamma pass rate for a 1, 2, and 3 mm increase in gating limits was measured to be 97.8%, 82.9%, and 61.4%, respectively. The average gating latency was measured to be 63.8 ms for beam-hold and 195.8 ms for beam-on. Four liver patients with 17 total fractions have been successfully treated at our institution. Conclusions: Wireless transponder tracking was validated as a dosimetrically accurate way to provide gated SABR of the liver. The dynamic tracking accuracy of the Calypso system met manufacturer’s specification, even for continuous large amplitude motion that can be encountered when tracking liver tumors close to the diaphragm. The measured beam-hold gating latency was appropriate for targets that will traverse the gating limit each respiratory cycle causing the beam to be interrupted constantly throughout treatment delivery.« less

Jaundice in a pregnant woman.

PubMed

Ibrahimi, Sophiane; Mroué, Abbas Ali; Francois, Erik; Jagodzinski, Robert

2017-01-01

A 34-year-old woman in the 22nd week of gestation presented with generalized pruritis and weight loss since the first trimester of pregnancy. Physical examination revealed cutaneous scratch lesions, jaundice, and hepatomegaly. Blood tests revealed cholestasis with elevated direct bilirubinemia. Auto-antibody and viral hepatitis tests were negative. Liver ultrasound was normal. The initial diagnosis was cholestasis of pregnancy. However despite treatment with ursodeoxycholic acid, the patient did not improve. Delivery was by cesarean section at the 26th week of pregnancy for obstetrical reasons. A new liver ultrasound showed a heterogeneous nodular mass. Nuclear magnetic resonance (NMR) of the liver showed an 11-cm mass centered on the hilum, dilated intrahepatic bile ducts, involvement of the hepatic veins, and hilar adenopathy. A liver biopsy revealed fibrolamellar hepatocellular carcinoma (FHC). © Acta Gastro-Enterologica Belgica.

Liver function in workers exposed of the cosmetics industry.

PubMed

Casale, T; Caciari, T; Rosati, M V; Biagi, M; De Sio, S; Andreozzi, G; Schifano, M P; Capozzella, A; Pimpinella, B; Tomei, G; Tomei, F

2013-01-01

The purpose of this study is to assess whether occupational exposure to substances used in the cosmetic factories may cause effects on the liver and blood counts in exposed workers. The study included 48 exposed workers and 86 unexposed controls. All workers included in the study underwent blood count, white blood count, total, direct and indirect bilirubin, transaminases, alkaline phosphatase and cholinesterase. The differences between the means and frequencies were compared using the Student's t-test and chi-square test with Yates correction and were considered significant when the p value was <0.05. The analysis of the results shows that 35.4% of workers in the cosmetics industry had liver test values above the range. We noted a statistically significant higher prevalence of GPT (p <0.05) and total bilirubin (p <0.05) in the workers of the cosmetics industry compared with the control group. The results obtained suggest that occupational exposure to low doses of substances used in the cosmetic industry is able to influence some liver parameters in occupationally exposed workers.

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

PubMed

Veeravahu, M

1985-01-01

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

Two Cases of Lethal Complications Following Ultrasound-Guided Percutaneous Fine-Needle Biopsy of the Liver

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

Drinkovic, Ivan; Brkljacic, Boris

1996-09-15

Two cases with lethal complications are reported among 1750 ultrasound (US)-guided percutaneous fine-needle liver biopsies performed in our department. The first patient had angiosarcoma of the liver which was not suspected after computed tomography (CT) and US studies had been performed. The other patient had hepatocellular carcinoma in advanced hepatic cirrhosis. Death was due to bleeding in both cases. Pre-procedure laboratory tests did not reveal the existence of major bleeding disorders in either case. Normal liver tissue was interposed in the needle track between the liver capsule and the lesions which were targeted.

Liver function tests abnormality and clinical severity of dengue infection in adult patients.

PubMed

Kittitrakul, Chatporn; Silachamroon, Udomsak; Phumratanaprapin, Weerapong; Krudsood, Srivicha; Wilairatana, Polrat; Treeprasertsuk, Sombat

2015-01-01

The clinical manifestations of dengue infection in the adult are different from those in children, i.e. having less prevalence to bleeding, and more commonly, abnormal liver function tests. The primary objective is to describe the clinical manifestations of dengue infection in adult patients. The secondary objective is to compare the clinical manifestations of dengue infection between the groups of normal and abnormal liver function tests in adult patients. Retrospective study was done in adults (age 15 years) dengue patients admitted at the Hospital for Tropical Diseases from 2000-2002. Dengue infection diagnosed by WHO clinical criteria 1997 with serological tests confirmed by ELISA test or Rapid Immunochromatographic test. Liver function test was recorded by day of fever. There were 127 adult dengue patients with mean age 26.4 ± 11.5 years. Classifications of dengue infection by WHO criteria were DF 4.7%, DHF grade 126.0%, DHF grade 2 63.0% and DHF grade 3 6.3%. Mean duration of fever clearance time was 6.0 ± 1.9 days but the fever lasted longer in cases of high-level transaminases (> 10 folds). The common presenting symptoms and signs were myalgia (95.9%), nausea/vomiting (87.7%), positive tourniquet test (77.2%), abdominal pain (42.7%), hepatomegaly (34.6%), and bleeding (20.5%). The ratio of AST and ALTwas 1.8:1. Abnormal AST and ALT were found in 88.2% and 69.3% of the patients, respectively. Patients with nausea/vomiting, petechiae or duration of fever > 7 days more frequently had abnormal transaminases. Abnormal AST during the febrile stage was associated with bleeding. High-level AST and ALT occurred in 11.0% and 7.0%, respectively. Shock was associated with high-level ALT during the febrile stage. Adult dengue patients commonly showed abnormal liver function tests and accounted for at least two-thirds of them. High-level ALT during the febrile stage showed association with shock.

What is the Real Function of the Liver ‘Function’ Tests?

PubMed Central

Hall, Philip; Cash, Johnny

2012-01-01

Liver enzymes are commonly used in the evaluation of patients with a range of diseases. Classically they are used to give information on whether a patient’s primary disorder is hepatitic or cholestatic in origin. However, knowledge of enzyme ratios and pattern recognition allow much more information to be derived from these simple tests. PMID:23536736

GENE EXPRESSION PROFILING IN THE LIVER OF CD-1 MICE TO CHARACTERIZE THE HEPATOTOXICITY OF TRIAZOLE FUNGICIDES.

EPA Science Inventory

Four triazole fungicides used in agricultural or pharmaceutical applications were examined for hepatotoxic effects in mouse liver. Besides organ weight, histopathology, and cytochrome P450 (CYP) enzyme induction, DNA microarrays were used to generate gene expression profiles and ...

GENE EXPRESSION PROFILING IN THE LIVER OF CD-1 MICE TO CHARACTERIZE THE HEPATOTOXICITY OF TRIAZOLE FUNGICIDES

EPA Science Inventory

Four triazole fungicides used in agricultural or pharmaceutical applications were examined for hepatotoxic effects in mouse liver. Besides organ weight, histopathology, and cytochrome P450 (CYP) enzyme induction, DNA microarrays were used to generate gene expression profiles and ...

Shared liver-like transcriptional characteristics in liver metastases and corresponding primary colorectal tumors.

PubMed

Cheng, Jun; Song, Xuekun; Ao, Lu; Chen, Rou; Chi, Meirong; Guo, You; Zhang, Jiahui; Li, Hongdong; Zhao, Wenyuan; Guo, Zheng; Wang, Xianlong

2018-01-01

Background & Aims : Primary tumors of colorectal carcinoma (CRC) with liver metastasis might gain some liver-specific characteristics to adapt the liver micro-environment. This study aims to reveal potential liver-like transcriptional characteristics associated with the liver metastasis in primary colorectal carcinoma. Methods: Among the genes up-regulated in normal liver tissues versus normal colorectal tissues, we identified "liver-specific" genes whose expression levels ranked among the bottom 10% ("unexpressed") of all measured genes in both normal colorectal tissues and primary colorectal tumors without metastasis. These liver-specific genes were investigated for their expressions in both the primary tumors and the corresponding liver metastases of seven primary CRC patients with liver metastasis using microdissected samples. Results: Among the 3958 genes detected to be up-regulated in normal liver tissues versus normal colorectal tissues, we identified 12 liver-specific genes and found two of them, ANGPTL3 and CFHR5 , were unexpressed in microdissected primary colorectal tumors without metastasis but expressed in both microdissected liver metastases and corresponding primary colorectal tumors (Fisher's exact test, P < 0.05). Genes co-expressed with ANGPTL3 and CFHR5 were significantly enriched in metabolism pathways characterizing liver tissues, including "starch and sucrose metabolism" and "drug metabolism-cytochrome P450". Conclusions: For primary CRC with liver metastasis, both the liver metastases and corresponding primary colorectal tumors may express some liver-specific genes which may help the tumor cells adapt the liver micro-environment.

Modeling the mechanical properties of liver fibrosis in rats.

PubMed

Zhu, Ying; Chen, Xin; Zhang, Xinyu; Chen, Siping; Shen, Yuanyuan; Song, Liang

2016-06-14

The progression of liver fibrosis changes the biomechanical properties of liver tissue. This study characterized and compared different liver fibrosis stages in rats in terms of viscoelasticity. Three viscoelastic models, the Voigt, Maxwell, and Zener models, were applied to experimental data from rheometer tests and then the elasticity and viscosity were estimated for each fibrosis stage. The study found that both elasticity and viscosity are correlated with the various stages of liver fibrosis. The study revealed that the Zener model is the optimal model for describing the mechanical properties of each fibrosis stage, but there is no significant difference between the Zener and Voigt models in their performance on liver fibrosis staging. Therefore the Voigt model can still be effectively used for liver fibrosis grading. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tests and Procedures

MedlinePlus

... Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid ... Tumor Liver Cancer Lymphoma (Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma ...

Haptoglobin blood test

MedlinePlus

... Chronic liver disease Blood buildup under the skin (hematoma) Liver disease Transfusion reaction Higher-than-normal levels ... may include: Excessive bleeding Fainting or feeling lightheaded Hematoma (blood accumulating under the skin) Infection (a slight ...

Pretreatment data is highly predictive of liver chemistry signals in clinical trials

PubMed Central

Cai, Zhaohui; Bresell, Anders; Steinberg, Mark H; Silberg, Debra G; Furlong, Stephen T

2012-01-01

Purpose The goal of this retrospective analysis was to assess how well predictive models could determine which patients would develop liver chemistry signals during clinical trials based on their pretreatment (baseline) information. Patients and methods Based on data from 24 late-stage clinical trials, classification models were developed to predict liver chemistry outcomes using baseline information, which included demographics, medical history, concomitant medications, and baseline laboratory results. Results Predictive models using baseline data predicted which patients would develop liver signals during the trials with average validation accuracy around 80%. Baseline levels of individual liver chemistry tests were most important for predicting their own elevations during the trials. High bilirubin levels at baseline were not uncommon and were associated with a high risk of developing biochemical Hy’s law cases. Baseline γ-glutamyltransferase (GGT) level appeared to have some predictive value, but did not increase predictability beyond using established liver chemistry tests. Conclusion It is possible to predict which patients are at a higher risk of developing liver chemistry signals using pretreatment (baseline) data. Derived knowledge from such predictions may allow proactive and targeted risk management, and the type of analysis described here could help determine whether new biomarkers offer improved performance over established ones. PMID:23226004

Liver Transplantation With Older Donors: A Comparison With Younger Donors in a Context of Organ Shortage.

PubMed

Barbier, Louise; Cesaretti, Manuela; Dondero, Federica; Cauchy, François; Khoy-Ear, Linda; Aoyagi, Takeshi; Weiss, Emmanuel; Roux, Olivier; Dokmak, Safi; Francoz, Claire; Paugam-Burtz, Catherine; Sepulveda, Ailton; Belghiti, Jacques; Durand, François; Soubrane, Olivier

2016-11-01

Older liver grafts have been considered in the past decade due to organ shortage. The aim was to compare outcomes after liver transplantation with either younger or older donors. Patients transplanted in our center between 2004 and 2014 with younger donors (younger than 60 years; n = 253) were compared with older donors (older than 75 years; n = 157). Multiorgan transplantations, split grafts, or non-heart-beating donors were not included. Donors in the older group were mostly women deceased from stroke, and only 3 patients had experienced cardiac arrest. Liver tests were significantly better in the older group than in the younger group. There was no difference regarding cold ischemia time, model for end-stage liver disease score, and steatosis. There was no significant difference regarding primary nonfunction and dysfunction, hepatic artery and biliary complications, and retransplantation rates. Graft survival was not different (65% and 64% in the older and younger groups, P = 0.692). Within the older group, hepatitis C infection, retransplantation, and emergency transplantation were associated with poor graft survival. Provided normal liver tests and the absence of cardiac arrest in donors, older liver grafts (>75 years) may be safely attributed to non-hepatitis C-infected recipients in the setting of a first and nonurgent transplantation.

Transient elastography (FibroScan®) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease - Where do we stand?

PubMed Central

Mikolasevic, Ivana; Orlic, Lidija; Franjic, Neven; Hauser, Goran; Stimac, Davor; Milic, Sandra

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Currently, the routinely used modalities are unable to adequately determine the levels of steatosis and fibrosis (laboratory tests and ultrasonography) or cannot be applied as a screening procedure (liver biopsy). Among the non-invasive tests, transient elastography (FibroScan®, TE) with controlled attenuation parameter (CAP) has demonstrated good accuracy in quantifying the levels of liver steatosis and fibrosis in patients with NAFLD, the factors associated with the diagnosis and NAFLD progression. The method is fast, reliable and reproducible, with good intra- and interobserver levels of agreement, thus allowing for population-wide screening and disease follow-up. The initial inability of the procedure to accurately determine fibrosis and steatosis in obese patients has been addressed with the development of the obese-specific XL probe. TE with CAP is a viable alternative to ultrasonography, both as an initial assessment and during follow-up of patients with NAFLD. Its ability to exclude patients with advanced fibrosis may be used to identify low-risk NAFLD patients in whom liver biopsy is not needed, therefore reducing the risk of complications and the financial costs. PMID:27621571

Marked elevation of hepatic transaminases in recipients of an orthotopic liver transplant from a brain-dead donor receiving extracorporeal membrane oxygenation.

PubMed

Teng-Wei, Chen; Chung-Bao, Hsieh; Chan, De-Chuan; Yu, Jyh-Cherng; Kuo, Shih-Ming; Tsai, Chien-Sung; Fan, Hsiu-Lung

2014-12-29

Hemodynamic instability can lead to failure of donor organ procurement in brain-dead donors. Extracorporeal membrane oxygenation (ECMO) has been used in non-heart-beating donors to increase the donor pool, but the use of ECMO to salvage donor organs has been rarely used. We aimed to analyze postoperative liver function test results in patients receiving orthotopic liver transplants from ECMO-supported brain-dead donors. We retrospectively reviewed the records of 43 recipients of orthotopic liver transplantation from May 2009 to June 2012. Six recipients received liver grafts from ECMO-maintained donors designated as the ECMO group (n=6). The remaining patients were assigned to the non-ECMO group (n=37). Complication and mortality rates and liver function test results on postoperative days 1, 3, 5, 7, and 14 were compared between the 2 groups. Serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase levels were significantly elevated on postoperative Day 1 in the ECMO group. There were no significant differences in the complication and overall survival rates between the 2 groups (P=0.411). Although serum transaminases markedly elevated on postoperative Day 1, ECMO successfully preserved potential liver grafts in hemodynamically unstable brain-dead donors.

Application of the BAR score as a predictor of short- and long-term survival in liver transplantation patients.

PubMed

de Campos Junior, Ivan Dias; Stucchi, Raquel Silveira Bello; Udo, Elisabete Yoko; Boin, Ilka de Fátima Santana Ferreira

2015-01-01

The balance of risk (BAR) is a prediction system after liver transplantation. To assess the BAR system, a retrospective observational study was performed in 402 patients who had transplant surgery between 1997 and 2012. The BAR score was computed for each patient. Receiver operating characteristic curve analysis with the Hosmer-Lemeshow test was used to calculate sensitivity, specificity, and model calibration. The cutoff value with the best Youden index was selected. Statistical analysis employed the Kaplan-Meier method (log-rank test) for survival, the Mann-Whitney test for group comparison, and multiple logistic regression analysis. 3-month survival was 46% for BAR ≥ 11 and 77% for BAR <11 (p = 0.001); 12-month survival was 44% for BAR ≥ 11 and 69% for BAR <11 (p = 0.001). Factors of survival <3 months were BAR ≥ 11 [odds ratio (OR) 3.08; 95% confidence interval (CI) 1.75-5.42; p = 0.001] and intrasurgical use of packed red blood cells (RBC) above 6 units (OR 4.49; 95% CI 2.73-7.39; p = 0.001). For survival <12 months, factors were BAR ≥ 11 (OR 2.94; 95% CI 1.67-5.16; p = 0.001) and RBC >6 units (OR 2.99; 95% CI 1.92-4.64; p = 0.001). Our study contributes to the incorporation of the BAR system into Brazilian transplantation centers.

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

PubMed

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

2016-12-14

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

Novel circulating biomarkers for non-alcoholic fatty liver disease: A systematic review.

PubMed

Sahebkar, Amirhossein; Sancho, Elena; Abelló, David; Camps, Jordi; Joven, Jorge

2018-02-01

Currently, a liver biopsy remains the only reliable way to precisely diagnose non-alcoholic fatty liver disease (NAFLD) and establish the severity of liver injury, presence of fibrosis, and architecture remodeling. However, the cost and the intrinsic invasive procedure of a liver biopsy rules it out as a gold standard diagnostic test, and the imaging test are not the best choice due to the price, and currently is being refined. The lack of a biomarker of NAFLD pushes to develop this new line of research. The aim of the present systematic review is to clarify and update all the NAFLD biomarkers described in the literature until recently. We highlight α-ketoglutarate and CK18-F as currently the best potential biomarker of NAFLD. However, due to methodological differences, we propose the implementation of international, multicenter, multiethnic studies with larger population size, and biopsy proven NAFLD diagnosis to analyze and compare α-ketoglutarate and CK18-F as potential biomarkers of the silent evolution of NAFLD. © 2017 Wiley Periodicals, Inc.

Bendiocarb induced histopathological and biochemical alterations in rat liver and preventive role of vitamins C and E.

PubMed

Apaydin, Fatma Gökçe; Baş, Hatice; Kalender, Suna; Kalender, Yusuf

2017-01-01

In this study, biochemical changes and histological structure of rat liver after bendiocarb administration and possible preventive effects of vitamins C and E were studied. The animals were given with bendiocarb, vitamin C and vitamin E, daily 0,8mg/kg of body weight (bw), 100mg/kg-bw and 100mg/kg-bw for 28days, respectively. Lipid peroxidation, antioxidant enzyme activities, histological alterations and antioxidant capacity assays of liver and also liver function tests and lipid profile were measured. Bendiocarb treatment decreased the antioxidant enzyme activities, FRAP and TEAC values and increased malondialdehyde levels compared to control. Also, there were statistically significant alterations in liver function tests, lipid profile parameters and histopathological changes in bendiocarb treated groups. Vitamins C and E showed protective effects against examining parameters. According to results we can say that co-treatment of vitamin C and vitamin E may be more effective than use of them alone. Copyright © 2016 Elsevier B.V. All rights reserved.

Pathogenesis of Zika Virus-Associated Embryopathy.

PubMed

Mawson, Anthony R

2016-01-01

A strong causal association has become evident between Zika virus (ZIKV) infection during pregnancy and the occurrence of fetal growth restriction, microcephaly and eye defects. Circumstantial evidence is presented in this paper in support of the hypothesis that these effects, as well as the Guillain-Barré syndrome, are due to an endogenous form of hypervitaminosis A resulting from ZIKV infection-induced damage to the liver and the spillage of stored vitamin A compounds ("retinoids") into the maternal and fetal circulation in toxic concentrations. Retinoids are mainly stored in the liver (about 80%) and are essential for numerous biological functions. In higher concentration, retinoids are potentially cytotoxic, pro-oxidant, mutagenic and teratogenic, especially if sudden shifts occur in their bodily distribution. Although liver involvement has not been mentioned specifically in recent reports, conventional liver enzyme tests underestimate the true extent of liver dysfunction. The proposed model could be tested by comparing retinoid concentration and expression profiles in microcephalic newborns of ZIKV-infected mothers and nonmicrocephalic newborn controls, and by correlating these profiles with measures of clinical severity.

[Effect of clinical doses of Realgar-Indigo Naturalis formula and large-dose of realgar on CYP450s of rat liver].

PubMed

Xu, Huan-Hua; Wang, Mei-Xi; Tan, Hong-Ling; Wang, Yu-Guang; Tang, Xiang-Lin; Xiao, Cheng-Rong; Li, Hua; Gao, Yue; Ma, Zeng-Chun

2017-02-01

To investigate the effect of clinical dose of Realgar-Indigo Naturais formula (RIF) and large-dose of Realgar on main drug-metabolizing enzymes CYP450s of rat liver, as well as its regulatory effect on mRNA expression. Wistar rats were administrated orally with tested drugs for 14 days. A Cocktail method combined with HPLC-MS/MS was used in the determination of 4 cytochrome P450 isozymes (CYP1A2, CYP2B, CYP3A and CYP2C) in liver of the rats, and the mRNA expression levels of the above subtypes were detected by real-time fluorescent quantitative PCR. The results showed that RIF can significantly induce CYP1A2 and CYP2B enzyme activity, and inhibit CYP3A enzyme activity. This result was consistent with the mRNA expression. However, its single compound showed weaker or even contrary phenomenon. Different doses of Realgar also showed significant inconsistencies on CYP450 enzymes activity and mRNA expression. These phenomena may be relevant with RIF compatibility synergies or toxicity reduction. The results can also prompt drug interactions when RIF is combined with other medicines in application. Copyright© by the Chinese Pharmaceutical Association.

Self-assessment of postoperative scars in living liver donors.

PubMed

Imamura, Hajime; Soyama, Akihiko; Takatsuki, Mitsuhisa; Muraoka, Izumi; Hara, Takanobu; Yamaguchi, Izumi; Tanaka, Takayuki; Kinoshita, Ayaka; Kuroki, Tamotsu; Eguchi, Susumu

2013-01-01

The application of less invasive techniques for liver surgery in patients undergoing living donor hepatectomy (LDH) has been reported. The objective of this study was to evaluate physical status according to type of incision in donors. One hundred and forty-seven living liver donors underwent hepatectomy using three types of incisions: (i) Mercedes-Benz incision (M.B.), (ii) right subcostal incision with midline up to xiphoid incision (S.C.), and (iii) short upper midline incision (U.M.). A total of 100 donors answered the questionnaires, and 87 had sufficient data for the analyses. An original questionnaire designed to evaluate the physical status concerning postoperative scars. The questionnaire consisted of three major categories: appearance, sensation, and daily activities. The univariate analysis was performed using the chi-square test. Numbness of the abdominal wall was reported more frequently by the donor with M.B.s and right subcostal incisions up to xiphoid incisions. In terms of appearance, sensation, and daily activities, LDH with a U.M. was found to have a good self-assessment compared with that performed using other types of incisions. LDH with a U.M. is a preferable procedure in terms of physical status and safety. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Guidelines for the sociomedical assessment of performance in patients suffering from chronic non-malignant diseases of the liver and the bile ducts--for the Medical Assessment Services of the German Pension Fund].

PubMed

Horn, S; Irle, H; Knorr, I; Pottins, I; Rohwetter, M; Schuhknecht, P; Timner, K; Becker, E

2009-06-01

The following guidelines were developed for the medical assessment services of the German pension fund. Starting from day-to-day practice, criteria and attributes to guide decisions for a systematisation of the sociomedical assessment of performance in diseases of the liver and the bile ducts were compiled. The guidelines aim at standardising the sociomedical assessment of performance and help to make the decision-making process more transparent, e. g., for the assessment of applications for decreased earning capacity benefits. The guidelines summarise the typical manifestations of diseases of the liver and the bile ducts and describe the necessary medical information for the sociomedical assessment of performance. Relevant assessment criteria for the medical history, clinical examination, and for diagnostic tests are illustrated. The assessment of the individual's capacity is outlined, taking occupational factors into account. Following the determination of dysfunctions, the remaining abilities and disabilities, respectively, are deduced and compared with occupational demands. Finally, inferences are drawn regarding the occupational capacity of the individual. The guidelines followed from an extended procedure to attain a wide consensus in the setting of the German Pension Fund and an upgraded evidence base.

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.

Biotechnology Challenges to In Vitro Maturation of Hepatic Stem Cells.

PubMed

Chen, Chen; Soto-Gutierrez, Alejandro; Baptista, Pedro M; Spee, Bart

2018-04-01

The incidence of liver disease is increasing globally. The only curative therapy for severe end-stage liver disease, liver transplantation, is limited by the shortage of organ donors. In vitro models of liver physiology have been developed and new technologies and approaches are progressing rapidly. Stem cells might be used as a source of liver tissue for development of models, therapies, and tissue-engineering applications. However, we have been unable to generate and maintain stable and mature adult liver cells ex vivo. We review factors that promote hepatocyte differentiation and maturation, including growth factors, transcription factors, microRNAs, small molecules, and the microenvironment. We discuss how the hepatic circulation, microbiome, and nutrition affect liver function, and the criteria for considering cells derived from stem cells to be fully mature hepatocytes. We explain the challenges to cell transplantation and consider future technologies for use in hepatic stem cell maturation, including 3-dimensional biofabrication and genome modification. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Visualizing liver anatomy, physiology and pharmacology using multiphoton microscopy.

PubMed

Wang, Haolu; Liang, Xiaowen; Gravot, Germain; Thorling, Camilla A; Crawford, Darrell H G; Xu, Zhi Ping; Liu, Xin; Roberts, Michael S

2017-01-01

Multiphoton microscopy (MPM) has become increasingly popular and widely used in both basic and clinical liver studies over the past few years. This technology provides insights into deep live tissues with less photobleaching and phototoxicity, which helps us to better understand the cellular morphology, microenvironment, immune responses and spatiotemporal dynamics of drugs and therapeutic cells in the healthy and diseased liver. This review summarizes the principles, opportunities, applications and limitations of MPM in hepatology. A key emphasis is on the use of fluorescence lifetime imaging (FLIM) to add additional quantification and specificity to the detection of endogenous fluorescent species in the liver as well as exogenous molecules and nanoparticles that are applied to the liver in vivo. We anticipate that in the near future MPM-FLIM will advance our understanding of the cellular and molecular mechanisms of liver diseases, and will be evaluated from bench to bedside, leading to real-time histology of human liver diseases. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Extraction of liver volumetry based on blood vessel from the portal phase CT dataset

NASA Astrophysics Data System (ADS)

Maklad, Ahmed S.; Matsuhiro, Mikio; Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Utsunomiya, Tohru; Shimada, Mitsuo

2012-02-01

At liver surgery planning stage, the liver volumetry would be essential for surgeons. Main problem at liver extraction is the wide variability of livers in shapes and sizes. Since, hepatic blood vessels structure varies from a person to another and covers liver region, the present method uses that information for extraction of liver in two stages. The first stage is to extract abdominal blood vessels in the form of hepatic and nonhepatic blood vessels. At the second stage, extracted vessels are used to control extraction of liver region automatically. Contrast enhanced CT datasets at only the portal phase of 50 cases is used. Those data include 30 abnormal livers. A reference for all cases is done through a comparison of two experts labeling results and correction of their inter-reader variability. Results of the proposed method agree with the reference at an average rate of 97.8%. Through application of different metrics mentioned at MICCAI workshop for liver segmentation, it is found that: volume overlap error is 4.4%, volume difference is 0.3%, average symmetric distance is 0.7 mm, Root mean square symmetric distance is 0.8 mm, and maximum distance is 15.8 mm. These results represent the average of overall data and show an improved accuracy compared to current liver segmentation methods. It seems to be a promising method for extraction of liver volumetry of various shapes and sizes.

Noninvasive detection of hepatic lipidosis in dairy cows with calibrated ultrasonographic image analysis.

PubMed

Starke, A; Haudum, A; Weijers, G; Herzog, K; Wohlsein, P; Beyerbach, M; de Korte, C L; Thijssen, J M; Rehage, J

2010-07-01

The aim was to test the accuracy of calibrated digital analysis of ultrasonographic hepatic images for diagnosing fatty liver in dairy cows. Digital analysis was performed by means of a novel method, computer-aided ultrasound diagnosis (CAUS), previously published by the authors. This method implies a set of pre- and postprocessing steps to normalize and correct the transcutaneous ultrasonographic images. Transcutaneous hepatic ultrasonography was performed before surgical correction on 151 German Holstein dairy cows (mean +/- standard error of the means; body weight: 571+/-7 kg; age: 4.9+/-0.2 yr; DIM: 35+/-5) with left-sided abomasal displacement. Concentration of triacylglycerol (TAG) was biochemically determined in liver samples collected via biopsy and values were considered the gold standard to which ultrasound estimates were compared. According to histopathologic examination of biopsies, none of the cows suffered from hepatic disorders other than hepatic lipidosis. Hepatic TAG concentrations ranged from 4.6 to 292.4 mg/g of liver fresh weight (FW). High correlations were found between the hepatic TAG and mean echo level (r=0.59) and residual attenuation (ResAtt; r=0.80) obtained in ultrasonographic imaging. High correlation existed between ResAtt and mean echo level (r=0.76). The 151 studied cows were split randomly into a training set of 76 cows and a test set of 75 cows. Based on the data from the training set, ResAtt was statistically selected by means of stepwise multiple regression analysis for hepatic TAG prediction (R(2)=0.69). Then, using the predicted TAG data of the test set, receiver operating characteristic analysis was performed to summarize the accuracy and predictive potential of the differentiation between various measured hepatic TAG values, based on TAG predicted from the regression formula. The area under the curve values of the receiver operating characteristic based on the regression equation were 0.94 (<50 vs. >or=50mg of TAG/g of FW), 0.83 (<100 vs. >or=100mg of TAG/g of FW), and 0.97 (<50 vs. >or=100mg of TAG/g of FW). The CAUS methodology and software for digitally analyzing liver ultrasonographic images is considered feasible for noninvasive screening of fatty liver in dairy herd health programs. Using the single parameter linear regression equation might be ideal for practical applications. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Abacavir-induced liver toxicity.

PubMed

Pezzani, Maria Diletta; Resnati, Chiara; Di Cristo, Valentina; Riva, Agostino; Gervasoni, Cristina

2016-01-01

Abacavir-induced liver toxicity is a rare event almost exclusively occurring in HLA B*5701-positive patients. Herein, we report one case of abnormal liver function tests occurring in a young HLA B*5701-negative woman on a stable nevirapine-based regimen with no history of liver problems or alcohol abuse after switching to abacavir from tenofovir. We also investigated the reasons for abacavir discontinuation in a cohort of patients treated with abacavir-lamivudine-nevirapine. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Can we prevent ischemic-type biliary lesions in donation after circulatory determination of death liver transplantation?

PubMed

Hessheimer, Amelia J; Cárdenas, Andrés; García-Valdecasas, Juan C; Fondevila, Constantino

2016-07-01

The pool of livers for transplantation consists of an increasingly greater proportion of marginal grafts, in particular those arising through donation after circulatory determination of death (DCD). However, a primary factor limiting the use of marginal livers, and, thereby, the applicability of liver transplantation in general, is concern over the subsequent development of ischemic-type biliary lesion (ITBL). ITBL is a devastating complication of liver transplantation; in its most severe forms, recipients suffer frequent infectious complications that require repeated invasive biliary procedures and ultimately result in either retransplantation or death. In the present review article, we discuss our current understanding of ITBL pathogenesis as it pertains to DCD, in particular. We discuss the most relevant theories regarding its development and provide a comprehensive overview of the most promising strategies we have available today to prevent the appearance of ITBL, strategies that may, furthermore, allow us to transplant a greater proportion of marginal livers in the future. Liver Transplantation 22 1025-1033 2016 AASLD. © 2016 American Association for the Study of Liver Diseases.

21 CFR 862.1440 - Lactate dehydrogenase test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... dehydrogenase measurements are used in the diagnosis and treatment of liver diseases such as acute viral hepatitis, cirrhosis, and metastatic carcinoma of the liver, cardiac diseases such as myocardial infarction...

Advances in bioartificial liver assist devices.

PubMed

Patzer, J F

2001-11-01

Rapid advances in development of bioartificial liver assist devices (BLADs) are exciting clinical interest in the application of BLAD technology for support of patients with acute liver failure. Four devices (Circe Biomedical HepatAssist, Vitagen ELAD, Gerlach BELS, and Excorp Medical BLSS) that rely on hepatocytes cultured in hollow-fiber membrane technology are currently in various stages of clinical evaluation. Several alternative approaches for culture and perfusion of hepatocytes have been evaluated in preclinical, large animal models of liver failure, or at a laboratory scale. Engineering design issues with respect to xenotransplantation, BLAD perfusion, hepatocyte functionality and culture maintenance, and ultimate distribution of a BLAD to a clinical site are delineated.

Accuracy of simple biochemical tests in identifying liver fibrosis in patients co-infected with human immunodeficiency virus and hepatitis C virus.

PubMed

Tural, Cristina; Tor, Jordi; Sanvisens, Arantza; Pérez-Alvarez, Núria; Martínez, Elisenda; Ojanguren, Isabel; García-Samaniego, Javier; Rockstroh, Juergen; Barluenga, Eva; Muga, Robert; Planas, Ramon; Sirera, Guillem; Rey-Joly, Celestino; Clotet, Bonaventura

2009-03-01

We assessed the ability of 3 simple biochemical tests to stage liver fibrosis in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). We analyzed liver biopsy samples from 324 consecutive HIV/HCV-positive patients (72% men; mean age, 38 y; mean CD4+ T-cell counts, 548 cells/mm(3)). Scheuer fibrosis scores were as follows: 30% had F0, 22% had F1, 19% had F2, 23% had F3, and 6% had F4. Logistic regression analyses were used to predict the probability of significant (>or=F2) or advanced (>or=F3) fibrosis, based on numeric scores from the APRI, FORNS, or FIB-4 tests (alone and in combination). Area under the receiver operating characteristic curves were analyzed to assess diagnostic performance. Area under the receiver operating characteristic curves analyses indicated that the 3 tests had similar abilities to identify F2 and F3; the ability of APRI, FORNS, and FIB-4 were as follows: F2 or greater: 0.72, 0.67, and 0.72, respectively; F3 or greater: 0.75, 0.73, and 0.78, respectively. The accuracy of each test in predicting which samples were F3 or greater was significantly higher than for F2 or greater (APRI, FORNS, and FIB-4: >or=F3: 75%, 76%, and 76%, respectively; >or=F2: 66%, 62%, and 68%, respectively). By using the lowest cut-off values for all 3 tests, F3 or greater was ruled out with sensitivity and negative predictive values of 79% to 94% and 87% to 91%, respectively, and 47% to 70% accuracy. Advanced liver fibrosis (>or=F3) was identified using the highest cut-off value, with specificity and positive predictive values of 90% to 96% and 63% to 73%, respectively, and 75% to 77% accuracy. Simple biochemical tests accurately predicted liver fibrosis in more than half the HIV/HCV co-infected patients. The absence and presence of liver fibrosis are predicted fairly using the lowest and highest cut-off levels, respectively.

Correlation of Body Mass Index and Serum Parameters With Ultrasonographic Grade of Fatty Change in Non-alcoholic Fatty Liver Disease

PubMed Central

Abangah, Ghobad; Yousefi, Atefeh; Asadollahi, Rouhangiz; Veisani, Yousef; Rahimifar, Paria; Alizadeh, Sajjad

2014-01-01

Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease in the western population and expanding disease in the world. Pathological changes in fatty liver are like alcohol liver damage, which can lead to end-stage liver disease. The prevalence of NAFLD in obese or overweight people is higher than general population, and it seems that people with high Body Mass Index (BMI) or abnormality in some laboratory tests are more susceptible for severe fatty liver and high grade of NAFLD in ultrasonography (U.S). Objectives: This study aimed to evaluate the correlation of BMI and laboratory tests with NAFLD in ultrasonography. Materials and Methods: During a multi-step process, we selected two-hundred and thirteen cases from four hundred and eighteen patients with NAFLD. Laboratory tests performed included: ALT, AST, FBS, Triglyceride and cholesterol levels, hepatitis B surface antigen, hepatitis C antibody, ceruloplasmin, serum iron, TIBC, transferrin saturation, ferritin, AMA, ANA, ANTI LKM1, serum protein electrophoresis, TSH, anti TTG (IgA). BMI and ultrasonography for 213 patients were performed, and then data was analyzed. These parameters and grades of ultrasonography were compared with the values obtained using one way ANOVA. An ordinal logistic regression model was used to estimate the probability of ultrasonography grade. The Statistical Package for the Social Science program (SPSS, version 16.0) was used for data analysis. Results: Two-hundred and thirteen cases including 140 male and 73 female, were studied. In general, 72.3% of patients were overweight and obese. Post-hoc tests showed that only BMI (P < 0.001) and TG (P < 0.011) among variables had statistically significant associations with ultrasonography grade (USG), and ordinal logistic regression model showed that BMI and AST were the best predictors. Discussion: Our results suggest that in patients with NAFLD, BMI and TG are most effective factors in severity of fatty liver disease and ultrasonography grade (USG). On the other hand, BMI as a predictor can be helpful. But, AST has not been a reliable finding, because it changes in many conditions. PMID:24719704

Correlation of Body Mass Index and Serum Parameters With Ultrasonographic Grade of Fatty Change in Non-alcoholic Fatty Liver Disease.

PubMed

Abangah, Ghobad; Yousefi, Atefeh; Asadollahi, Rouhangiz; Veisani, Yousef; Rahimifar, Paria; Alizadeh, Sajjad

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease in the western population and expanding disease in the world. Pathological changes in fatty liver are like alcohol liver damage, which can lead to end-stage liver disease. The prevalence of NAFLD in obese or overweight people is higher than general population, and it seems that people with high Body Mass Index (BMI) or abnormality in some laboratory tests are more susceptible for severe fatty liver and high grade of NAFLD in ultrasonography (U.S). This study aimed to evaluate the correlation of BMI and laboratory tests with NAFLD in ultrasonography. During a multi-step process, we selected two-hundred and thirteen cases from four hundred and eighteen patients with NAFLD. Laboratory tests performed included: ALT, AST, FBS, Triglyceride and cholesterol levels, hepatitis B surface antigen, hepatitis C antibody, ceruloplasmin, serum iron, TIBC, transferrin saturation, ferritin, AMA, ANA, ANTI LKM1, serum protein electrophoresis, TSH, anti TTG (IgA). BMI and ultrasonography for 213 patients were performed, and then data was analyzed. These parameters and grades of ultrasonography were compared with the values obtained using one way ANOVA. An ordinal logistic regression model was used to estimate the probability of ultrasonography grade. The Statistical Package for the Social Science program (SPSS, version 16.0) was used for data analysis. Two-hundred and thirteen cases including 140 male and 73 female, were studied. In general, 72.3% of patients were overweight and obese. Post-hoc tests showed that only BMI (P < 0.001) and TG (P < 0.011) among variables had statistically significant associations with ultrasonography grade (USG), and ordinal logistic regression model showed that BMI and AST were the best predictors. Our results suggest that in patients with NAFLD, BMI and TG are most effective factors in severity of fatty liver disease and ultrasonography grade (USG). On the other hand, BMI as a predictor can be helpful. But, AST has not been a reliable finding, because it changes in many conditions.

New ways of looking at very small holes - using optical nanoscopy to visualize liver sinusoidal endothelial cell fenestrations

NASA Astrophysics Data System (ADS)

Øie, Cristina I.; Mönkemöller, Viola; Hübner, Wolfgang; Schüttpelz, Mark; Mao, Hong; Ahluwalia, Balpreet S.; Huser, Thomas R.; McCourt, Peter

2018-02-01

Super-resolution fluorescence microscopy, also known as nanoscopy, has provided us with a glimpse of future impacts on cell biology. Far-field optical nanoscopy allows, for the first time, the study of sub-cellular nanoscale biological structures in living cells, which in the past was limited to electron microscopy (EM) (in fixed/dehydrated) cells or tissues. Nanoscopy has particular utility in the study of "fenestrations" - phospholipid transmembrane nanopores of 50-150 nm in diameter through liver sinusoidal endothelial cells (LSECs) that facilitate the passage of plasma, but (usually) not blood cells, to and from the surrounding hepatocytes. Previously, these fenestrations were only discernible with EM, but now they can be visualized in fixed and living cells using structured illumination microscopy (SIM) and in fixed cells using single molecule localization microscopy (SMLM) techniques such as direct stochastic optical reconstruction microscopy. Importantly, both methods use wet samples, avoiding dehydration artifacts. The use of nanoscopy can be extended to the in vitro study of fenestration dynamics, to address questions such as the following: are they actually dynamic structures, and how do they respond to endogenous and exogenous agents? A logical further extension of these methodologies to liver research (including the liver endothelium) will be their application to liver tissue sections from animal models with different pathological manifestations and ultimately to patient biopsies. This review will cover the current state of the art of the use of nanoscopy in the study of liver endothelium and the liver in general. Potential future applications in cell biology and the clinical implications will be discussed.

Prescriber Compliance With Liver Monitoring Guidelines for Pazopanib in the Postapproval Setting: Results From a Distributed Research Network.

PubMed

Shantakumar, Sumitra; Nordstrom, Beth L; Hall, Susan A; Djousse, Luc; van Herk-Sukel, Myrthe P P; Fraeman, Kathy H; Gagnon, David R; Chagin, Karen; Nelson, Jeanenne J

2017-04-20

Pazopanib received US Food and Drug Administration approval in 2009 for advanced renal cell carcinoma. During clinical development, liver chemistry abnormalities and adverse hepatic events were observed, leading to a boxed warning for hepatotoxicity and detailed label prescriber guidelines for liver monitoring. As part of postapproval regulatory commitments, a cohort study was conducted to assess prescriber compliance with liver monitoring guidelines. Over a 4-year period, a distributed network approach was used across 3 databases: US Veterans Affairs Healthcare System, a US outpatient oncology community practice database, and the Dutch PHARMO Database Network. Measures of prescriber compliance were designed using the original pazopanib label guidelines for liver monitoring. Results from the VA (n = 288) and oncology databases (n = 283) indicate that prescriber liver chemistry monitoring was less than 100%: 73% to 74% compliance with baseline testing and 37% to 39% compliance with testing every 4 weeks. Compliance was highest near drug initiation and decreased over time. Among patients who should have had weekly testing, the compliance was 56% in both databases. The more serious elevations examined, including combinations of liver enzyme elevations meeting the laboratory definition of Hy's law were infrequent but always led to appropriate discontinuation of pazopanib. Only 4 patients were identified for analysis in the Dutch database; none had recorded baseline testing. In this population-based study, prescriber compliance was reasonable near pazopanib initiation but low during subsequent weeks of treatment. This study provides information from real-world community practice settings and offers feedback to regulators on the effectiveness of label monitoring guidelines.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Clinical research on liver reserve function by 13C-phenylalanine breath test in aged patients with chronic liver diseases

PubMed Central

2010-01-01

Background The objective of this study was to investigate whether the 13C-phenylalanine breath test could be useful for the evaluation of hepatic function in elderly volunteers and patients with chronic hepatitis B and liver cirrhosis. Methods L-[1-13C] phenylalanine was administered orally at a dose of 100 mg to 55 elderly patients with liver cirrhosis, 30 patients with chronic hepatitis B and 38 elderly healthy subjects. The breath test was performed at 8 different time points (0, 10, 20, 30, 45, 60, 90, 120 min) to obtain the values of Delta over baseline, percentage 13CO2 exhalation rate and cumulative excretion (Cum). The relationships of the cumulative excretion with the 13C-%dose/h and blood biochemical parameters were investigated. Results The 13C-%dose/h at 20 min and 30 min combined with the cumulative excretion at 60 min and 120 min correlated with hepatic function tests, serum albumin, hemoglobin, platelet and Child-Pugh score. Prothrombin time, total and direct bilirubin were significantly increased, while serum albumin, hemoglobin and platelet, the cumulative excretion at 60 min and 120 min values decreased by degrees of intensity of the disease in Child-Pugh A, B, and C patients (P < 0.01). Conclusions The 13C-phenylalanine breath test can be used as a non-invasive assay to evaluate hepatic function in elderly patients with liver cirrhosis. The 13C-%dose/h at 20 min, at 30 min and cumulative excretion at 60 min may be the key value for determination at a single time-point. 13C-phenylalanine breath test is safe and helpful in distinguishing different stages of hepatic dysfunction for elderly cirrhosis patients. PMID:20459849

Technique Development for a Polytrauma Model to Study Partial Resuscitative Endovascular Balloon Occlusion of the Aorta (P-REBOA) in Swine (Sus scrofa)

DTIC Science & Technology

2016-06-01

widely in literature, limiting comparisons. Methods: Yorkshire-cross swine were anesthetized, instrumented, and splenectomized. A simple liver...applicable injury in swine . Use of the tourniquet allowed for consistent liver injury and precise control over hemorrhage.

Influence of G-forces and hypodynamia on the portal system of the liver

NASA Technical Reports Server (NTRS)

Drozdova, A. V.

1975-01-01

Longitudinally and transversely applied g-forces as intolerable levels cause damage to the interlobular veins of the liver, with maximum damage caused by dorso-ventral g-force application. The portal vein system is more resilient with respect to g-forces at the limit of tolerance.

Acoustic radiation force impulse elastography: comparison and combination with other noninvasive tests for the diagnosis of compensated liver cirrhosis.

PubMed

Pfeifer, Lukas; Adler, Werner; Zopf, Steffen; Siebler, Jürgen; Wildner, Dane; Goertz, Ruediger S; Schellhaas, Barbara; Neurath, Markus F; Strobel, Deike

2017-05-01

The aim of this study was to compare acoustic radiation force impulse (ARFI) elastography with other noninvasive tests and to develop a new score for the assessment of liver fibrosis/cirrhosis. B-mode ultrasound (including high-frequency liver surface evaluation), routine blood tests, ARFI quantification, and mini-laparoscopic liver evaluation were obtained in compensated patients scheduled for mini-laparoscopic biopsy. Our new cirrhosis score (CS) for the assessment of liver cirrhosis, based on a linear combination of ARFI, platelet (PLT), liver surface, and prothrombin index (PI), was calculated by linear discriminant analysis. Its performance was compared with ARFI-elastography, APRI, FIB-4, alanine aminotransferase (ALT)/aspartate aminotransferase (AST)-ratio, PLT, and PI. For the diagnosis of cirrhosis, a combined gold standard (cirrhosis at histology and/or at macroscopic liver evaluation) was used. In total, 171 patients, of whom 38 had compensated cirrhosis, were included. The CS was significantly better for the diagnosis of cirrhosis compared with ARFI (P=0.028), APRI (P=0.012), PLTs (P=0.013), PI (P=0.025), and ALT/AST ratio (P=0.001), but not the FIB-4 score (P=0.207), with an area under the receiver operating characteristic curve of 0.92 [95% confidence interval (CI): 0.87-0.97], 0.86 (95% CI:0.79-0.93), 0.80 (95% CI: 0.72-0.87), 0.79 (95% CI: 0.7-0.87), 0.81 (95% CI: 0.73-0.89), 0.72 (95% CI:0.64-0.81), and 0.86 (95% CI: 0.8-0.93), respectively. Sensitivity, specificity, positive predictive value, and negative predictive value for CS were 87%, 86%, 63%, and 96%, respectively. The FIB-4 score was significantly superior to the APRI score (P=0.041) and the ALT/AST ratio (P=0.011), with no significant difference from ARFI elastography (P=0.88) for the diagnosis of cirrhosis. Combining ARFI elastography with other noninvasive tests that are used routinely in the workup of patients with suspected liver disease can improve diagnostic accuracy for compensated liver cirrhosis as compared with ARFI elastography alone. The FIB-4 score showed an overall comparable diagnostic accuracy to ARFI-elastography for compensated cirrhosis.

The therapeutic effects of bone marrow-derived mesenchymal stem cells and simvastatin in a rat model of liver fibrosis.

PubMed

Motawi, Tarek M K; Atta, Hazem M; Sadik, Nermin A H; Azzam, May

2014-01-01

Liver fibrosis is the excessive accumulation of extracellular matrix (ECM) proteins including collagen that occurs in most types of chronic liver diseases. Studies concerning the capacity of mesenchymal stem cells (MSCs) and simvasatain (SIMV) to repair fibrotic tissues through reducing inflammation, collagen deposition, are still controversial. This study aimed to investigate the therapeutic efficacy of bone marrow (BM)-derived MSCs and SIMV on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Rats were divided into: normal, CCl4, CCl4/MSCs, CCl4/SIMV, CCl4/MSCs/SIMV, and SIMV groups. BM-derived MSCs were detected by RT-PCR of CD29 and were then infused into the tail vein of female rats that received CCl4 injection to induce liver fibrosis. Sex-determining region Y (SRY) gene on Y-chromosome gene was assessed by PCR to confirm homing of the male stem cells in liver tissue of the female recipients. Serum liver function tests, liver procollagens I and III, tissue inhibitors of metalloproteinase-1 (TIMP-1), endoglin, matrix metalloproteinase-1 (MMP-1) gene expressions, transforming growth factor-beta (TGF-β1) immunostaining, and histopathologicl examination were performed. MSCs and SIMV decreased liver procollagens I and III, TIMP-1 and endoglin gene expressions, TGF-β1 immunostaining, and serum liver function tests compared with the CCl4 group. MMP-1 expression was increased in the CCl4/MSCs group. Histopathological examination as well as fibrosis score supports the biochemical and molecular findings. It can be concluded that MSCs and SIMV were effective in the treatment of hepatic CCl4-induced fibrosis-rat model. Treatment with MSCs was superior to SIMV. This antifibrotic effect can be attributed to their effect on the MMPs/TIMPs balance which is central in fibrogenesis.

Real-time tracking of liver motion and deformation using a flexible needle

PubMed Central

Lei, Peng; Moeslein, Fred; Wood, Bradford J.

2012-01-01

Purpose A real-time 3D image guidance system is needed to facilitate treatment of liver masses using radiofrequency ablation, for example. This study investigates the feasibility and accuracy of using an electromagnetically tracked flexible needle inserted into the liver to track liver motion and deformation. Methods This proof-of-principle study was conducted both ex vivo and in vivo with a CT scanner taking the place of an electromagnetic tracking system as the spatial tracker. Deformations of excised livers were artificially created by altering the shape of the stage on which the excised livers rested. Free breathing or controlled ventilation created deformations of live swine livers. The positions of the needle and test targets were determined through CT scans. The shape of the needle was reconstructed using data simulating multiple embedded electromagnetic sensors. Displacement of liver tissues in the vicinity of the needle was derived from the change in the reconstructed shape of the needle. Results The needle shape was successfully reconstructed with tracking information of two on-needle points. Within 30 mm of the needle, the registration error of implanted test targets was 2.4 ± 1.0 mm ex vivo and 2.8 ± 1.5 mm in vivo. Conclusion A practical approach was developed to measure the motion and deformation of the liver in real time within a region of interest. The approach relies on redesigning the often-used seeker needle to include embedded electromagnetic tracking sensors. With the nonrigid motion and deformation information of the tracked needle, a single- or multimodality 3D image of the intraprocedural liver, now clinically obtained with some delay, can be updated continuously to monitor intraprocedural changes in hepatic anatomy. This capability may be useful in radiofrequency ablation and other percutaneous ablative procedures. PMID:20700662

Opportunities and challenges in the wider adoption of liver and interconnected microphysiological systems

PubMed Central

Kostrzewski, Tomasz; Sceats, Emma L

2017-01-01

Liver disease represents a growing global health burden. The development of in vitro liver models which allow the study of disease and the prediction of metabolism and drug-induced liver injury in humans remains a challenge. The maintenance of functional primary hepatocytes cultures, the parenchymal cell of the liver, has historically been difficult with dedifferentiation and the consequent loss of hepatic function limiting utility. The desire for longer term functional liver cultures sparked the development of numerous systems, including collagen sandwiches, spheroids, micropatterned co-cultures and liver microphysiological systems. This review will focus on liver microphysiological systems, often referred to as liver-on-a-chip, and broaden to include platforms with interconnected microphysiological systems or multi-organ-chips. The interconnection of microphysiological systems presents the opportunity to explore system level effects, investigate organ cross talk, and address questions which were previously the preserve of animal experimentation. As a field, microphysiological systems have reached a level of maturity suitable for commercialization and consequent evaluation by a wider community of users, in academia and the pharmaceutical industry. Here scientific, operational, and organizational considerations relevant to the wider adoption of microphysiological systems will be discussed. Applications in which microphysiological systems might offer unique scientific insights or enable studies currently feasible only with animal models are described, and challenges which might be addressed to enable wider adoption of the technologies are highlighted. A path forward which envisions the development of microphysiological systems in partnerships between academia, vendors and industry, is proposed. Impact statement Microphysiological systems are in vitro models of human tissues and organs. These systems have advanced rapidly in recent years and are now being commercialized. To achieve wide adoption in the biological and pharmaceutical research communities, microphysiological systems must provide unique insights which translate to humans. This will be achieved by identifying key applications and making microphysiological systems intuitive to use. PMID:28504617

Opportunities and challenges in the wider adoption of liver and interconnected microphysiological systems.

PubMed

Hughes, David J; Kostrzewski, Tomasz; Sceats, Emma L

2017-10-01

Liver disease represents a growing global health burden. The development of in vitro liver models which allow the study of disease and the prediction of metabolism and drug-induced liver injury in humans remains a challenge. The maintenance of functional primary hepatocytes cultures, the parenchymal cell of the liver, has historically been difficult with dedifferentiation and the consequent loss of hepatic function limiting utility. The desire for longer term functional liver cultures sparked the development of numerous systems, including collagen sandwiches, spheroids, micropatterned co-cultures and liver microphysiological systems. This review will focus on liver microphysiological systems, often referred to as liver-on-a-chip, and broaden to include platforms with interconnected microphysiological systems or multi-organ-chips. The interconnection of microphysiological systems presents the opportunity to explore system level effects, investigate organ cross talk, and address questions which were previously the preserve of animal experimentation. As a field, microphysiological systems have reached a level of maturity suitable for commercialization and consequent evaluation by a wider community of users, in academia and the pharmaceutical industry. Here scientific, operational, and organizational considerations relevant to the wider adoption of microphysiological systems will be discussed. Applications in which microphysiological systems might offer unique scientific insights or enable studies currently feasible only with animal models are described, and challenges which might be addressed to enable wider adoption of the technologies are highlighted. A path forward which envisions the development of microphysiological systems in partnerships between academia, vendors and industry, is proposed. Impact statement Microphysiological systems are in vitro models of human tissues and organs. These systems have advanced rapidly in recent years and are now being commercialized. To achieve wide adoption in the biological and pharmaceutical research communities, microphysiological systems must provide unique insights which translate to humans. This will be achieved by identifying key applications and making microphysiological systems intuitive to use.

Testing an aflatoxin B1 gene signature in rat archival tissues.

PubMed

Merrick, B Alex; Auerbach, Scott S; Stockton, Patricia S; Foley, Julie F; Malarkey, David E; Sills, Robert C; Irwin, Richard D; Tice, Raymond R

2012-05-21

Archival tissues from laboratory studies represent a unique opportunity to explore the relationship between genomic changes and agent-induced disease. In this study, we evaluated the applicability of qPCR for detecting genomic changes in formalin-fixed, paraffin-embedded (FFPE) tissues by determining if a subset of 14 genes from a 90-gene signature derived from microarray data and associated with eventual tumor development could be detected in archival liver, kidney, and lung of rats exposed to aflatoxin B1 (AFB1) for 90 days in feed at 1 ppm. These tissues originated from the same rats used in the microarray study. The 14 genes evaluated were Adam8, Cdh13, Ddit4l, Mybl2, Akr7a3, Akr7a2, Fhit, Wwox, Abcb1b, Abcc3, Cxcl1, Gsta5, Grin2c, and the C8orf46 homologue. The qPCR FFPE liver results were compared to the original liver microarray data and to qPCR results using RNA from fresh frozen liver. Archival liver paraffin blocks yielded 30 to 50 μg of degraded RNA that ranged in size from 0.1 to 4 kB. qPCR results from FFPE and fresh frozen liver samples were positively correlated (p ≤ 0.05) by regression analysis and showed good agreement in direction and proportion of change with microarray data for 11 of 14 genes. All 14 transcripts could be amplified from FFPE kidney RNA except the glutamate receptor gene Grin2c; however, only Abcb1b was significantly upregulated from control. Abundant constitutive transcripts, S18 and β-actin, could be amplified from lung FFPE samples, but the narrow RNA size range (25-500 bp length) prevented consistent detection of target transcripts. Overall, a discrete gene signature derived from prior transcript profiling and representing cell cycle progression, DNA damage response, and xenosensor and detoxication pathways was successfully applied to archival liver and kidney by qPCR and indicated that gene expression changes in response to subchronic AFB1 exposure occurred predominantly in the liver, the primary target for AFB1-induced tumors. We conclude that an evaluation of gene signatures in archival tissues can be an important toxicological tool for evaluating critical molecular events associated with chemical exposures.

[Value of non-invasive models of liver fibrosis in judgment of treatment timing in chronic hepatitis B patients with ALT < 2×upper limit of normal].

PubMed

Zhou, Q Q; Hu, Y B; Zhou, K; Zhang, W W; Li, M H; Dong, P; Di, J G; Hong, L; Du, Q W; Xie, Y; Sun, Q F

2016-09-20

Objective: To investigate the value of non-invasive liver fibrosis models, FIB-4, S index, aspartate aminotransferase to platelet ratio index(APRI), globulin-platelet(GP)model, aspartate aminotransferase/platelet/gamma-glutamyl transpeptidase/alpha-fetoprotein(APGA), and platelet/age/phosphatase/alpha-fetoprotein/aspartate aminotransferase(PAPAS), in the diagnosis of marked liver fibrosis in chronic hepatitis B(CHB)patients with ALT < 2×upper limit of normal(ULN), as well as treatment timing for this population. Methods: A total of 389 CHB patients with ALT < 2×ULN who were admitted to Beijing Ditan Hospital and whose treatment timing was difficult to judge were enrolled. Transdermal liver biopsy was performed to obtain pathological results, and routine serological tests were performed, including routine blood test, serum biochemical parameters, hepatitis B virus(HBV)markers, and HBV DNA. According to liver pathology, the patients were divided into non-marked liver fibrosis group(S < 2)with 324 patients and marked liver fibrosis group(S≥2)with 65 patients. The non-invasive models for predicting liver fibrosis was established with reference to original articles. SPSS 19.0 software was used for statistical analysis, and the receiver operating characteristic(ROC)curve was used to compare the value of different non-invasive models in predicting marked liver fibrosis in this population. Results: All the non-invasive models had a certain diagnostic value for liver fibrosis degree in these patients, and the areas under the ROC curve for APRI, FIB-4, APGA, S index, PAPAS, and GP model were 0.718, 0.691, 0.758, 0.729, 0.673, and 0.691, respectively. APGA had the largest area under the ROC curve(0.758, 95% CI 0.673-0.844), and gamma-glutamyl transpeptidase was significantly positively correlated with liver fibrosis degree. Conclusion: The non-invasive models of liver fibrosis can identify marked liver fibrosis in CHB patients with ALT < 2×ULN in whom it is difficult to judge treatment timing and help to determine treatment timing for them. APGA model has the highest value and can reduce the need for liver biopsy to the certain degree.