Characterization of Hepatitis B Virus (HBV) and Host Cytokine Patterns in a Multiethnic Cohort of Patients with Non-alcoholic Fatty Liver Disease (NAFLD) and Chronic Hepatitis B (CHB)
Date
2020-01-06
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Abstract
Studies have reported conflicting data on the relationship between non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis B (CHB). We aimed to identify how metabolic factors associated with NAFLD (diabetes, hypertension, central obesity and dyslipidemia) affects the hepatitis B virus (HBV) in patients with CHB. Patients with CHB and NAFLD were prospectively enrolled from 3 Canadian liver clinics. Patients underwent standardized liver tests (liver stiffness measurement [LSM] by transient elastography, controlled attenuation parameter [CAP]) and HBV clinical tests (quantitative [q] HBV surface antigen [HBsAg], HBeAg). Plasma levels of HBV DNA and RNA were measured by quantitative (q)PCR. Viral genotype was identified by population and next generation sequencing of the precore (C)/C and presurface (S)/S genes and analyzed using MEGA 7. Peripheral blood mononuclear cells (PBMCs) were stimulated ex vivo for 72h by HBV core antigen (HBcAg) or HBsAg peptides. PBMC supernatant and serum were analyzed for cytokine/chemokine markers using a 13-plex immunoassay. Kruskal-Wallis, multiple linear regression, Chi-square, and Fischer’s exact tests were performed using R commander. Of 48 subjects enrolled (median age 44.5 [IQR 16.8]), most were male (n=31), of Asian descent (n=29), and HBeAg negative (n=45). In HBeAg negative patients, the mean CAP was 30652 dB/m, ALT was 4026 IU/mL, and LSM was 5.82.0 kPa, indicating high steatosis without fibrosis. In all patients, the HBV genotypes were 13% A, 16% B, 46% C, 17% D, 6% E. Mutations associated with severe liver disease, anti-viral drug resistance, immune escape, and HBeAg negativity were identified in all subjects. Obese patients had increased qHBsAg levels, while diabetic patients had increased S gene diversity. Hepatic steatosis severity did not relate to viral factors analyzed. Ex vivo PBMC responses to HBcAg or HBsAg stimulation were not different to unstimulated controls. In this study, a multi-ethnic cohort of CHB and NAFLD patients were prospectively evaluated with novel virologic and host immunological markers. We found that metabolic factors associated with NAFLD correlated to inflammatory cytokine levels, viral genetic characteristics, and HBV replication markers. These viral and host factors can influence the risk of liver disease progression in patients with both NAFLD and CHB, warranting further study.
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Keywords
Hepatitis B, Virus, NAFLD, Fatty liver
Citation
Lucko, A. M. (2020). Characterization of Hepatitis B Virus (HBV) and Host Cytokine Patterns in a Multiethnic Cohort of Patients with Non-alcoholic Fatty Liver Disease (NAFLD) and Chronic Hepatitis B (CHB) (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.