A common polymorphism in the ABCB11 gene is associated with advanced fibrosis in hepatitis C but not in non-alcoholic fatty liver disease

2010 ◽  
Vol 120 (7) ◽  
pp. 287-296 ◽  
Author(s):  
Rika Iwata ◽  
Katharina Baur ◽  
Bruno Stieger ◽  
Joachim C. Mertens ◽  
Ann K. Daly ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Hepatitis C ◽  
Fatty Liver ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Chronic Hcv ◽  
Alcoholic Fatty Liver Disease

Chronic HCV (hepatitis C virus)-associated cirrhosis represents a major indication for liver transplantation. Bile acids contribute to hepatic stellate cell activation as a key event in fibrogenesis. The aim of the present study was to investigate the role of bile acids and polymorphisms in bile acid level-regulating genes on fibrosis progression. A total of 206 subjects with chronic HCV infection were included for ABCB11 (ATP-binding cassette, subfamily B, member II) 1331T>C and NR1H4 (nuclear receptor) −1G>T genotyping, 178 of which were analysed for fibrosis stage. Exclusion criteria were HBV (hepatitis B virus) or HIV coinfection, alcohol >40 g/day and morbid obesity. A total of 358 patients with NAFLD (non-alcoholic fatty liver disease) were genotyped for comparison with a non-viral liver disease. Caucasian individuals (n = 110), undergoing liver resection for focal hepatic metastasis, served as controls. The ABCB11 1331C allele was significantly overrepresented in HCV patients compared with controls {allelic frequency 62.9%; OR (odds ratio), 1.41 [95% CI (confidence interval), 1.012–1.965]}. Median plasma bile acid levels were not significantly increased in the CC compared with TT genotype [7.2 (1–110) μmol/l compared with 3.5 (1–61) μmol/l; values are medians (range). A significant association between the presence of cirrhosis and ABCB11 genotype (CC compared with CT or TT, P=0.047) was observed in the χ2 test and independent of other risk factors of age, gender, body mass index and disease duration in multivariate analysis (P = 0.010). No such association could be observed in fatty liver patients with regard to advanced fibrosis (F≥2). The common ABCB11 1331CC genotype, which is present in 40% of HCV patients and renders the carrier susceptible to increased bile acid levels, is associated with cirrhosis.

scholarly journals Aryl Hydrocarbon Receptor (AhR) Activation by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) Dose-Dependently Shifts the Gut Microbiome Consistent with the Progression of Non-Alcoholic Fatty Liver Disease

2021 ◽  
Vol 22 (22) ◽  
pp. 12431
Author(s):  
Russell R. Fling ◽  
Timothy R. Zacharewski
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Fatty Liver ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Acid Metabolism ◽  
Bile Acid Metabolism ◽  
Alcoholic Fatty Liver ◽  
Dose Dependent ◽  
Alcoholic Fatty Liver Disease

Gut dysbiosis with disrupted enterohepatic bile acid metabolism is commonly associated with non-alcoholic fatty liver disease (NAFLD) and recapitulated in a NAFLD-phenotype elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice. TCDD induces hepatic fat accumulation and increases levels of secondary bile acids, including taurolithocholic acid and deoxycholic acid (microbial modified bile acids involved in host bile acid regulation signaling pathways). To investigate the effects of TCDD on the gut microbiota, the cecum contents of male C57BL/6 mice orally gavaged with sesame oil vehicle or 0.3, 3, or 30 µg/kg TCDD were examined using shotgun metagenomic sequencing. Taxonomic analysis identified dose-dependent increases in Lactobacillus species (i.e., Lactobacillus reuteri). Increased species were also associated with dose-dependent increases in bile salt hydrolase sequences, responsible for deconjugation reactions in secondary bile acid metabolism. Increased L. reuteri levels were further associated with mevalonate-dependent isopentenyl diphosphate (IPP) biosynthesis and o-succinylbenzoate synthase, a menaquinone biosynthesis associated gene. Analysis of the gut microbiomes from cirrhosis patients identified an increased abundance of genes from the mevalonate-dependent IPP biosynthesis as well as several other menaquinone biosynthesis genes, including o-succinylbenzoate synthase. These results extend the association of lactobacilli with the AhR/intestinal axis in NAFLD progression and highlight the similarities between TCDD-elicited phenotypes in mice to human NAFLD.

scholarly journals FibroTest for Evaluating Fibrosis in Non-Alcoholic Fatty Liver Disease Patients: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (11) ◽  
pp. 2415
Author(s):  
Yasaman Vali ◽  
Jenny Lee ◽  
Jérôme Boursier ◽  
René Spijker ◽  
Joanne Verheij ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Meta Analysis ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Multiple Thresholds ◽  
Meta Analyses ◽  
Alcoholic Fatty Liver Disease

(1) Background: FibroTest™ is a multi-marker panel, suggested by guidelines as one of the surrogate markers with acceptable performance for detecting fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). A number of studies evaluating this test have been published after publication of the guidelines. This study aims to produce summary estimates of FibroTest™ diagnostic accuracy. (2) Methods: Five databases were searched for studies that evaluated FibroTest™ against liver biopsy as the reference standard in NAFLD patients. Two authors independently screened the references, extracted data, and assessed the quality of included studies. Meta-analyses of the accuracy in detecting different levels of fibrosis were performed using the bivariate random-effects model and the linear mixed-effects multiple thresholds model. (3) Results: From ten included studies, seven were eligible for inclusion in our meta-analysis. Five studies were included in the meta-analysis of FibroTest™ in detecting advanced fibrosis and five in significant fibrosis, resulting in an AUC of 0.77 for both target conditions. The meta-analysis of three studies resulted in an AUC of 0.69 in detecting any fibrosis, while analysis of three other studies showed higher accuracy in cirrhosis (AUC: 0.92). (4) Conclusions: Our meta-analysis showed acceptable performance (AUC > 0.80) of FibroTest™ only in detecting cirrhosis. We observed more limited performance of the test in detecting significant and advanced fibrosis in NAFLD patients. Further primary studies with high methodological quality are required to validate the reliability of the test for detecting different fibrosis levels and to compare the performance of the test in different settings.

scholarly journals 343 Obstructive Sleep Apnea and Hypoxia are Associated With More Advanced Fibrosis in Pediatric Non-Alcoholic Fatty Liver Disease

2012 ◽  
Vol 142 (5) ◽  
pp. S-80 ◽  
Author(s):  
Shikha S. Sundaram ◽  
Jillian S. Sullivan ◽  
Ronald J. Sokol ◽  
Kristen N. Robbins ◽  
Kelley Capocelli ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Liver Disease ◽  
Sleep Apnea ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Obstructive Sleep ◽  
Alcoholic Fatty Liver Disease

scholarly journals Simple non-invasive biomarkers of advanced fibrosis in the evaluation of non-alcoholic fatty liver disease

2014 ◽  
Vol 2 (4) ◽  
pp. 276-280 ◽  
Author(s):  
E. B. Tapper ◽  
K. Krajewski ◽  
M. Lai ◽  
T. Challies ◽  
R. Kane ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Alcoholic Fatty Liver Disease

scholarly journals Portal lymphadenopathy predicts non-alcoholic steatohepatitis and advanced fibrosis in non-alcoholic fatty liver disease

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0207479 ◽  
Author(s):  
Saleh Daher ◽  
Namma Lev Cohen ◽  
Muhammad Massarwa ◽  
Mahmud Mahamid ◽  
Mira Nasser ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Alcoholic Fatty Liver Disease

Liver disease

2019 ◽  
pp. 367-384
Author(s):  
Nina Vodošek Hojs ◽  
Aftab Ala ◽  
Debasish Banerjee
Keyword(s):  
Cardiovascular Disease ◽  
Liver Disease ◽  
Hepatitis C ◽  
Fatty Liver ◽  
Viral Hepatitis ◽  
Liver Dysfunction ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Cardiovascular disease in patients with liver disease, previously uncommon, is rising because of an increasing incidence of non-alcoholic fatty liver disease and better survival of patients with viral hepatitis, particularly hepatitis C. Liver dysfunction alters the pharmacokinetics and pharmacodynamics of many drugs, and hence careful use and dose adjustments are necessary. This chapter describes common cardiovascular conditions and the pharmacotherapy in patients with different liver diseases.

scholarly journals Bile Acid and Fibroblast Growth Factor 19 Regulation in Obese Diabetics, and Non-Alcoholic Fatty Liver Disease after Sleeve Gastrectomy

2019 ◽  
Vol 8 (6) ◽  
pp. 815 ◽  
Author(s):  
Hsien-Hao Huang ◽  
Wei-Jei Lee ◽  
Shu-Chun Chen ◽  
Tung-Fang Chen ◽  
Shou-Dong Lee ◽  
...  
Keyword(s):  
Bile Acid ◽  
Fatty Liver ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Total Bile Acid ◽  
Alcoholic Fatty Liver ◽  
Liver Index ◽  
Fatty Liver Index ◽  
Total Bile Acids ◽  
Alcoholic Fatty Liver Disease

Background: Sleeve gastrectomy (SG) is an effective treatment for obesity and type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD); however, the mechanism is not completely understood. Bile acids and fibroblast growth factors (FGFs) are involved in the regulation of energy metabolism. Methods: We investigated the roles of total bile acid and FGF 19 in T2DM remission and NAFLD improvement in obese subjects undergoing SG. A total of 18 patients with obesity and T2DM undergoing laparoscopic SG were enrolled in this study. Serial plasma total bile acid and FGF 19 levels were measured, while the fatty liver index was calculated before and after surgery. Results: The FGF 19 level significantly increased, and the total bile acid level and fatty liver index decreased 1 year after surgery. The complete T2DM remission rate was 66.7% one year after surgery; the complete remitters had significantly lower FGF 19 levels and higher insulin levels than the non-complete remitters. The complete remitters also had significantly decreased total bile acid levels and increased FGF 19 levels 1 year after surgery compared with those before surgery. The fatty improvers had significantly decreased total bile acid levels and increased FGF 19 levels 1 year after surgery compared with those before surgery. Conclusion: The total bile acids level and fatty liver index decreased, and the FGF 19 levels increased 1 year after SG. Both T2DM complete remitters and NAFLD improvers showed significantly decreased total bile acid levels and increased FGF 19 levels 1 year after SG. Plasma total bile acids and FGF 19 might have roles in T2DM remission and NAFLD improvement. Low preoperative FGF 19 levels might be a predictor for NAFLD improvement after SG.

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