Association of Obesity, Diabetes, and Alcohol Use With Liver Fibrosis Among US Adults With Hepatitis C Virus Infection.
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ABSTRACT:
SUBMITTER: Migdal AL
PROVIDER: S-EPMC8933742 | biostudies-literature | 2022 Mar
REPOSITORIES: biostudies-literature
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Association of Obesity, Diabetes, and Alcohol Use With Liver Fibrosis Among US Adults With Hepatitis C Virus Infection.
Migdal Alexandra L AL Jagannathan Ram R Qayed Emad E Cusi Kenneth K McCoy Rozalina G RG Pasquel Francisco J FJ Miller Lesley S LS
JAMA network open 20220301 3
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Project description:ImportanceKnowing the rate of liver fibrosis progression in hepatitis C virus (HCV)-infected persons can help inform patients and providers (clinicians, medical institutions or organizations, and third-party payers) in making treatment decisions.ObjectiveTo determine the rate and factors associated with liver fibrosis progression and hepatic decompensation in persons after acquiring HCV infection.Design, setting, and participantsSecondary data analysis of persons in the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a national Veterans Affairs (VA) database, between 2002 and 2012. Among 610 514 persons in ERCHIVES (half were HCV positive), we identified those with an initial negative and subsequent positive test result for HCV antibody and positive HCV RNA test result (HCV+). Controls had 2 negative HCV antibody test results (HCV-) in a comparable time frame and were matched 1:1 on age (in 5-year blocks), race, and sex. We excluded persons with human immunodeficiency virus, hepatitis B, less than 24 months of follow-up, hepatocellular carcinoma, and cirrhosis at baseline.Main outcomes and measuresProgression of liver fibrosis as estimated by the Fibrosis-4 (FIB-4) index; development of cirrhosis, defined by a FIB-4 score greater than 3.5; and development of hepatic decompensation.ResultsThe evaluable data set consisted of 1840 persons who were HCV+ and 1840 HCV- controls. The HCV+ persons were younger and had a lower mean (SD) body mass index (27.39 [5.51] vs 29.49 [6.16]; P < .001), a higher prevalence of alcohol and drug abuse and dependence diagnoses, and higher serum aminotransferase levels, but had a lower prevalence of diabetes and hypertension. Fibrosis progression started early after infection among HCV+ persons and tapered off after 5 years. A total of 452 cirrhosis and 85 hepatic decompensation events were recorded. After 10 years of follow-up, HCV+ persons were more likely to have a diagnosis of cirrhosis compared with HCV- controls (18.4% vs 6.1%). Nine years after diagnosis of cirrhosis, hepatic decompensation events were uncommon but had a higher rate in the HCV+ group (1.79% vs 0.33%).Conclusions and relevancePersons who seroconverted for HCV have a more rapid progression of liver fibrosis and accelerated time to development of cirrhosis after seroconversion compared with HCV- controls. Fibrosis progression occurs early after infection; however, hepatic decompensation is uncommon after diagnosis of cirrhosis.
| S-EPMC5017246 | biostudies-literature
Project description:BACKGROUND: Chronic infection with hepatitis C virus (HCV) is a risk factor for liver diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. HCV genetic heterogeneity was hypothesized to be associated with severity of liver disease. However, no reliable viral markers predicting disease severity have been identified. Here, we report the utility of sequences from 3 HCV 1b genomic regions, Core, NS3 and NS5b, to identify viral genetic markers associated with fast and slow rate of fibrosis progression (RFP) among patients with and without liver transplantation (n = 42). METHODS: A correlation-based feature selection (CFS) method was used to detect and identify RFP-relevant viral markers. Machine-learning techniques, linear projection (LP) and Bayesian Networks (BN), were used to assess and identify associations between the HCV sequences and RFP. RESULTS: Both clustering of HCV sequences in LP graphs using physicochemical properties of nucleotides and BN analysis using polymorphic sites showed similarities among HCV variants sampled from patients with a similar RFP, while distinct HCV genetic properties were found associated with fast or slow RFP. Several RFP-relevant HCV sites were identified. Computational models parameterized using the identified sites accurately associated HCV strains with RFP in 70/30 split cross-validation (90-95% accuracy) and in validation tests (85-90% accuracy). Validation tests of the models constructed for patients with or without liver transplantation suggest that the RFP-relevant genetic markers identified in the HCV Core, NS3 and NS5b genomic regions may be useful for the prediction of RFP regardless of transplant status of patients. CONCLUSIONS: The apparent strong genetic association to RFP suggests that HCV genetic heterogeneity has a quantifiable effect on severity of liver disease, thus presenting opportunity for developing genetic assays for measuring virulence of HCV strains in clinical and public health settings.
| S-EPMC4120150 | biostudies-literature
Project description:BackgroundChronic hepatitis C is a major cause of liver fibrosis and cirrhosis. It is generally accepted that inflammation that occurs in response to hepatocyte infection by the hepatitis C virus (HCV) is the main mechanism that triggers myofibroblast differentiation and stimulation in chronic hepatitis C. The aim of this study was to determine if HCV might infect human liver myofibroblasts (HLMF) and directly stimulate their fibrogenic activities.MethodsWe evaluated the expression of the viral entry receptors, levels of HCV-RNA and HCV-protein and the expression of fibrosis markers in HLMF by using quantitative PCR, western blot and immunofluorescence analyses. Pseudoparticles (HCVpp) and cell culture-derived HCV (HCVcc) were used to study the ability of HLMF to support viral entry, replication and fibrosis induction.ResultsWe showed that HLMF expressed all known molecules of the HCV receptor complex, i.e. CD81, LDL-R, scavenger receptor-BI, claudin-1 and occludin. These cells were also permissive to HCVpp entry. Inoculation with HCVcc caused short-term infection of these cells, as shown by their content in positive- and negative-strand HCV RNA, in core and NS3 viral proteins, and by their release of core protein levels in the culture supernatants. HCV infection stimulated myofibroblastic differentiation, proliferation and collagen production in these cells. In addition, evidence of in vivo infection was provided by the detection of positive- and negative-strand HCV RNA in preparations of HLMF obtained from HCV-infected patients.ConclusionThese findings indicate that HCV infection of HLMF can occur and trigger extracellular matrix overproduction, thereby contributing to the development of HCV-related liver fibrosis.
| S-EPMC4516308 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and the second most common cause of cancer deaths worldwide. The top three causes of HCC are hepatitis B virus (HBV), hepatitis C virus (HCV), and alcoholic liver disease. Owing to recent advances in direct-acting antiviral agents, HCV can now be eradicated in almost all patients. HBV infection and alcoholic liver disease are expected, therefore, to become the leading causes of HCC in the future. However, the association between alcohol consumption and chronic hepatitis B in the progression of liver disease is less well understood than with chronic hepatitis C. The mechanisms underlying the complex interaction between HBV and alcohol are not fully understood, and enhanced viral replication, increased oxidative stress and a weakened immune response could each play an important role in the development of HCC. It remains controversial whether HBV and alcohol synergistically increase the incidence of HCC. Herein, we review the currently available literature regarding the interaction of HBV infection and alcohol consumption on disease progression.
| S-EPMC5403744 | biostudies-literature
Project description:AimTo analyze the association of the CD36 polymorphism (rs1761667) with dietary intake and liver fibrosis (LF) in chronic hepatitis C (CHC) patients.MethodsIn this study, 73 patients with CHC were recruited. The CD36 genotype (G > A) was determined by a TaqMan real-time PCR system. Dietary assessment was carried out using a three-day food record to register the daily intake of macronutrients. Serum lipids and liver enzymes were measured by a dry chemistry assay. LF evaluated by transient elastography (Fibroscan(®)) and APRI score was classified as mild LF (F1-F2) and advanced LF (F3-F4).ResultsOverall, the CD36 genotypic frequencies were AA (30.1%), AG (54.8%), and GG (15.1%), whereas the allelic A and G frequencies were 57.5% and 42.5%, respectively. CHC patients who were carriers of the CD36 AA genotype had a higher intake of calories attributable to total fat and saturated fatty acids than those with the non-AA genotypes. Additionally, aspartate aminotransferase (AST) serum values were higher in AA genotype carriers compared to non-AA carriers (91.7 IU/L vs 69.8 IU/L, P = 0.02). Moreover, the AA genotype was associated with an increase of 30.23 IU/L of AST (β = 30.23, 95%CI: 9.0-51.46, P = 0.006). Likewise, the AA genotype was associated with advanced LF compared to the AG (OR = 3.60, 95%CI: 1.16-11.15, P = 0.02) or AG + GG genotypes (OR = 3.52, 95%CI: 1.18-10.45, P = 0.02).ConclusionThis study suggests that the CD36 (rs1761667) AA genotype is associated with higher fat intake and more instances of advanced LF in CHC patients.
| S-EPMC5026998 | biostudies-literature
Project description:Liver cirrhosis and other chronic liver diseases are usually compartmentalized into separate categories based on etiology (e.g., due to alcohol, virus infection, etc.), but it is important to study the intersection of, and possible interactions between, risk factors. The aim of this study is to summarize evidence on the association between alcohol use disorders (AUDs) and decompensated liver cirrhosis and other complications in patients with chronic Hepatitis C virus (HCV) infection. A systematic search of epidemiological studies was conducted using Ovid Medline databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Relative Risk estimates were combined using random-effects meta-analyses. The proportion of cases with liver disease progression that could be avoided if no person with a chronic HCV infection had an AUD was estimated using an attributable fraction methodology. A total of 11 studies fulfilled the inclusion criteria, providing data from 286,641 people with chronic HCV infections, of whom 63,931 (22.3%) qualified as having an AUD. Using decompensated liver cirrhosis as the outcome for the main meta-analysis (n = 7 unique studies), an AUD diagnosis was associated with a 3.3-fold risk for progression of liver disease among people with a chronic HCV infection (95% Confidence Interval (CI): 1.8-4.8). In terms of population-attributable fractions, slightly less than 4 out of 10 decompensated liver cirrhosis cases were attributable to an AUD: 35.2% (95% CI: 16.2-47.1%). For a secondary analyses, all outcomes related to liver disease progression were pooled (i.e., liver deaths or cirrhosis in addition to decompensated liver cirrhosis), which yielded a similar overall effect (n = 13 estimates; OR = 3.7; 95% CI: 2.2-5.3) and a similar attributable fraction (39.3%; 95% CI: 21.9-50.4%). In conclusion, AUDs were frequent in people with chronic HCV infections and contributed to worsening the course of liver disease. Alcohol use and AUDs should be assessed in patients who have liver disease of any etiology, and interventions should be implemented to achieve abstinence or to reduce consumption to the greatest possible extent.
| S-EPMC7325038 | biostudies-literature
Project description:Background & aimsRecurrent hepatitis C with ensuing fibrosis is the leading cause of liver allograft loss. We investigated whether histologic features in early posttransplant liver biopsies could predict the rate of fibrosis progression in this population.MethodsFrom 1999 to 2007 there were 476 liver transplants performed for hepatitis C at our center. We reviewed all available posttransplant biopsies for these patients; patients were categorized as rapid, intermediate, or slow fibrosers based on their METAVIR fibrosis score at 24 months. Stage F0 biopsies for rapid and slow fibrosers were analyzed histologically and immunohistochemically.ResultsWe identified 52 rapid fibrosers and 61 slow fibrosers in our cohort. There was a significant increase in the fibrosis progression rate in the group transplanted between 2003 and 2007 compared with between 1999 and 2002. The course of fibrosis progression was determined early in the posttransplant period and the rate was constant. Rapid fibrosers had more hepatocyte apoptosis than slow fibrosers (P = .001), but no difference in hepatitis activity on stage F0 biopsies. Rapid fibrosers also experienced more episodes of acute rejection after transplantation (P < .001). Cytokeratin 19 (CK19) and vimentin expression on F0 stage biopsies could distinguish rapid from slow fibrosers (CK19: area under the curve, 0.71; P = .0034; vimentin: P = .0219).ConclusionsCK19, vimentin, and hepatocellular apoptosis are promising early markers of rapid fibrosis progression in patients transplanted for hepatitis C. The rate of fibrosis progression is established early in the posttransplant period; this initial rate dictates long-term outcome.
| S-EPMC2834881 | biostudies-literature
Project description:Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection is associated with progressive liver disease. However, the rate of progression is variable and the ability to differentiate patients with stable versus progressive HCV disease is limited. The objective of this study was to assess the incidence of and risk factors for fibrosis progression in a prospective cohort of coinfected patients. Overall, 435 liver biopsy pairs from 282 patients without cirrhosis were analyzed. Biopsies were scored according to the METAVIR system by a single pathologist blind to biopsy sequence. Fibrosis progression was defined as an increase of at least one METAVIR fibrosis stage between paired biopsies. The majority of patients were African American (84.8%), male (67.7%), and infected with HCV genotype 1 (93.4%). On initial biopsy, no or minimal fibrosis was identified in 243 patients (86%). The median interval between biopsies was 2.5 years. Fibrosis progression was observed in 97 of 282 (34%) patients and 149 of 435 (34%) biopsy pairs. After adjustment, greater body mass index (adjusted odds ratio [aOR]: 1.04 per 1 unit increase), diabetes (aOR: 1.56), and hepatic steatosis (aOR: 1.78) at the time of initial biopsy were marginally associated with subsequent fibrosis progression. Between biopsies, elevated serum aspartate and alanine aminotransferase (AST, ALT) (aOR AST: 3.34, ALT: 2.18 for >25% values >100 U/L versus <25% values >100 U/L) were strongly associated with fibrosis progression.Fibrosis progression is common among HIV/HCV coinfected patients; these data suggest that progression can be rapid. Persistent elevations in serum transaminase levels may serve as important noninvasive markers to identify subsets of patients who are more likely to progress and thus warrant closer monitoring and consideration of HCV treatment.
| S-EPMC3943751 | biostudies-literature
Project description:Background & aimsLiver fibrosis is a significant concern for patients with hepatitis C virus/human immunodeficiency virus co-infection. Fibrosis staging by biopsy is accurate, but costly and invasive. Several fibrosis prediction models using noninvasive biomarkers have been developed but are suboptimal in co-infected patients. We compared results from different staging models and ordinal regression with biopsy data.MethodsData from the Adult Acquired Immune Deficiency Syndrome Clinical Trials Group protocol A5178 were used to evaluate 5 models of fibrosis staging; areas under receiver-operator characteristic curves (AUROC) were assessed. Individual covariates were assessed with univariable regression and then entered into an ordinal logistic regression model from which a stage-wise index was developed.ResultsData from 173 patients were evaluated; 85% were on antiretroviral therapy, 31.2% had severe fibrosis (F3/F4), and 14% had cirrhosis (F4). Differences in CD4+ cell and platelets counts and international normalized ratio values were observed between those with and without F3/F4. Among existing models, the FIB-4 index ([age x AST])/[platelet count x (ALT)(1/2)]) performed best, with 88% specificity for F4 and greater than 86% negative predictive values for F3/F4, although AUROC values were low (0.56 +/- 0.03 for F3/F4). By using patients' demographic, clinical, and laboratory data, the ordinal regression model outperformed others, with an AUROC of 0.85 (standard error, 0.03) for predicting stage F3/F4 and 0.89 (standard error, 0.05) for stage 3 alone.ConclusionsCurrent noninvasive methods of fibrosis assessment have poor discriminatory capacity in hepatitis C virus/human immunodeficiency virus co-infected patients. Ordinal regression analysis outperformed other noninvasive fibrosis prediction models. Longitudinal studies with paired biopsies will assist in refining the Ordinal Regression Index.
| S-EPMC3159915 | biostudies-literature
Project description:BackgroundThis study aimed to compare the diagnostic accuracy of transient elastography (TE) and biopsy for the detection of liver fibrosis in children with chronic hepatitis B (CHB).MethodsThis single-center prospective study included 157 CHB children aged 0-6 years. All patients underwent liver stiffness measurement (LSM) by TE and liver biopsy, separated by an interval of less than 1 week.ResultsThe LSM, aspartate aminotransferase-platelet ratio index (APRI), and fibrosis-4 index (FIB-4) were positively correlated with activity grade and fibrosis stage in CHB children. The areas under the receiver operating characteristic curves (AUCs) of LSM for identifying significant (F ≥ 2) and advanced (F ≥ 3) fibrosis were 0.732 and 0.941, respectively. The cut-off values, specificity, and sensitivity for significant fibrosis were 5.6 kPa, 75.7%, and 67.4%, respectively; the corresponding values for advanced fibrosis were 6.9 kPa, 91.5%, and 81.3%, respectively. Compared to LSM, the overall diagnostic performances of APRI and FIB-4 for significant and advanced fibrosis were suboptimal, with low AUCs and sensitivity. Since LSM, platelet, and Log10 (hepatitis B surface antigen) were independent factors associated with the fibrosis stage (F < 2 and F ≥ 2), they were used to formulate the "LPS" index for the prediction of F ≥ 2. The AUC of LPS (for F ≥ 2) was higher than that of LSM (0.792 vs. 0.732, p < 0.05), and had an improved sensitivity (76.6% vs. 67.4%).ConclusionsTE is a promising technology for the diagnosis of advanced fibrosis in CHB children aged 0-6 years.
| S-EPMC8286936 | biostudies-literature