Dataset Information

Virus Genotype-Dependent Transcriptional Alterations in Lipid Metabolism and Inflammation Pathways in the Hepatitis C Virus-infected Liver.

ABSTRACT: Despite advances in antiviral therapy, molecular drivers of Hepatitis C Virus (HCV)-related liver disease remain poorly characterised. Chronic infection with HCV genotypes (1 and 3) differ in presentation of liver steatosis and virological response to therapies, both to interferon and direct acting antivirals. To understand what drives these clinically important differences, liver expression profiles of patients with HCV Genotype 1 or 3 infection (n?=?26 and 33), alcoholic liver disease (n?=?8), and no liver disease (n?=?10) were analysed using transcriptome-wide microarrays. In progressive liver disease, HCV genotype was the major contributor to altered liver gene expression with 2151 genes differentially expressed >1.5-fold between HCV Genotype 1 and 3. In contrast, only 6 genes were altered between the HCV genotypes in advanced liver disease. Induction of lipogenic, lipolytic, and interferon stimulated gene pathways were enriched in Genotype 1 injury whilst a broad range of immune-associated pathways were associated with Genotype 3 injury. The results are consistent with greater lipid turnover in HCV Genotype 1 patients. Moreover, the lower activity in inflammatory pathways associated with HCV genotype 1 is consistent with relative resistance to interferon-based therapy. This data provides a molecular framework to explain the clinical manifestations of HCV-associated liver disease.

SUBMITTER: d'Avigdor WMH

PROVIDER: S-EPMC6646375 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Virus Genotype-Dependent Transcriptional Alterations in Lipid Metabolism and Inflammation Pathways in the Hepatitis C Virus-infected Liver.

d'Avigdor W M H WMH Budzinska M A MA Lee M M Lam R R Kench J J Stapelberg M M McLennan S V SV Farrell G G George J J McCaughan G W GW Tu T T Shackel N A NA

Scientific reports 20190722 1

Despite advances in antiviral therapy, molecular drivers of Hepatitis C Virus (HCV)-related liver disease remain poorly characterised. Chronic infection with HCV genotypes (1 and 3) differ in presentation of liver steatosis and virological response to therapies, both to interferon and direct acting antivirals. To understand what drives these clinically important differences, liver expression profiles of patients with HCV Genotype 1 or 3 infection (n = 26 and 33), alcoholic liver disease (n = 8), ...[more]

PMID: 31332246

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Project description:The impact of sex on metabolic alterations in individuals with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection remains elusive.A community-based study was performed to assess sex, age, body mass index, the lipid profile, blood pressure, glucose, alanine aminotransferase, HBV surface antigen (HBsAg), and HCV antibody levels, smoking and alcohol drinking habits, and cardiometabolic diseases, including diabetes, hypertension, cardiovascular events, and renal diseases. The HCV-RNA level and genotype were further assessed in HCV antibody-positive subjects, and the hepatitis B e antigen and HBV-DNA levels were further examined in HBsAg-positive subjects.Among the 10,959 adults enrolled, 1949 (17.8%) and 1536 (14.0%) were HBV and HCV-infected, respectively. Univariate and multivariate analyses showed that the lipid profile and hypertension were independently associated with HCV infection (95% confidence intervals of odds ratios [OR 95% CI]: total cholesterol [TC]?=?0.508-0.677; triglycerides?=?0.496-0.728; hypertension?=?0.669-0.937), but not with HBV infection. Consistently, HCV, but not HBV infection, was negatively associated with the TC and triglyceride levels (OR 95% CI for TC: 0.450-0.601; triglycerides: 0.443-0.671). Generalized linear models revealed that HCV infection, sex, and age interactively affected the lipid profile (OR 95% CI TC?=?1.189-1.385; triglycerides?=?1.172-5.289). Age-stratification analysis showed that the lipid levels were lower in both the HCV-positive females aged ?49 years (TC, P?<?0.001; triglycerides, P?=?0.001) and males of all ages (TC, P?<?0.001; triglycerides, P?<?0.001) compared with their sex and age-matched HCV-negative counterparts. HCV infection was associated with a higher body mass index (?49 years, ??=?0.405, P?=?0.002) and increased rates of cardiovascular events (<49 years, OR 95% CI 1.23-9.566), diabetes (?49 years, OR 95% CI 1.114-1.932), and renal diseases (?49 years, OR 95% CI 1.23-9.55), and with a lower rate of hypertension (?49 years, OR 95% CI 0.616-0.964) in the females, but not in the males, as determined by multivariate analyses.Only HCV infection was associated with metabolic alterations in this HBV/HCV-hyperendemic area. Females aged ?49 years and males of all ages exhibited HCV-associated hypolipidemia. HCV-associated cardiometabolic diseases were evident only in the females. Sex dimorphism in HCV-associated metabolic complications warrants personalized follow-up of HCV-positive patients.

Dataset Information

Virus Genotype-Dependent Transcriptional Alterations in Lipid Metabolism and Inflammation Pathways in the Hepatitis C Virus-infected Liver.

Publications

Virus Genotype-Dependent Transcriptional Alterations in Lipid Metabolism and Inflammation Pathways in the Hepatitis C Virus-infected Liver.

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