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)

Lucko, Aaron Michael

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)

dc.contributor.advisor	Coffin, Carla S.
dc.contributor.author	Lucko, Aaron Michael
dc.contributor.committeemember	Chadee, Kris C.
dc.contributor.committeemember	Raman, Maitreyi
dc.date	2020-06
dc.date.accessioned	2020-01-17T17:06:25Z
dc.date.available	2020-01-17T17:06:25Z
dc.date.issued	2020-01-06
dc.description.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 30652 dB/m, ALT was 4026 IU/mL, and LSM was 5.82.0 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.	en_US
dc.identifier.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.	en_US
dc.identifier.doi	http://dx.doi.org/10.11575/PRISM/37470
dc.identifier.uri	http://hdl.handle.net/1880/111513
dc.language.iso	eng	en_US
dc.publisher.faculty	Cumming School of Medicine	en_US
dc.publisher.institution	University of Calgary	en
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.	en_US
dc.subject	Hepatitis B	en_US
dc.subject	Virus	en_US
dc.subject	NAFLD	en_US
dc.subject	Fatty liver	en_US
dc.subject.classification	Virology	en_US
dc.title	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)	en_US
dc.type	master thesis	en_US
thesis.degree.discipline	Medicine – Microbiology & Infectious Diseases	en_US
thesis.degree.grantor	University of Calgary	en_US
thesis.degree.name	Master of Science (MSc)	en_US
ucalgary.item.requestcopy	false	en_US