Characterization of hepatitis B viral genotypes and their biomarkers among patients attending Moi Teaching and Referral Hospital Liver Clinic

Abstract

Background; Hepatitis B Virus (HBV) belongs to the genus orthohepadnavirus and is the smallest human deoxyribonucleic acid (DNA) virus with a genome of 3200bp in a partially double stranded circular DNA. Globally, about 2 billion people are infected with HBV. Of these, over 65 million who reside in Africa are chronically infected and are therefore at increased risks of HBV related complications including hepatocellular carcinoma (HCC). At least 10 hepatitis B virus genotypes (A to J) have been reported with distinct geographic distributions and are predictive of liver disease progression. Problem statement: Kenya has one of the leading prevalence rates of HBV infection in the WHO African Region, thus there is an urgent need to conduct local studies on HBV genotyping to better understand its potential usefulness in clinical practice. Objectives: To establish the prevalence and characteristics of the various HBV genotypes and their biomarkers among hepatitis B patients chronically infected with HBV attending Moi Teaching and Referral Hospital (MTRH) liver/ gastrointestinal (GI) clinic Methods: A cross-sectional descriptive study with laboratory investigation was conducted. Purposive sampling was used to identify records of all chronic HBV positive adult patients (n=83) attending MTRH liver/ GI clinic during the study period who were then reviewed for potential inclusion into the study. A census was conducted to enroll all consenting adult patients with a history of >6 month of positive HBV status post-diagnosis (confirmed: HbsAg and Anti-HBc positive). Participants’ demographic data (age/gender) was collected using the laboratory form and tabulated. Plasma samples were obtained for HBV genotyping and DNA viral load using Rotor gene Q PCR machine. Serum biochemical (alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT)) - marker levels were estimated using Hitachi c311 equipment whereas virological (surface antigen -HbsAg, envelop antigen - HbeAg and core antibody - Anti-HBc) markers were assayed on Cobas e411 platform. Results: Out of the 83 HBV positive patients at the clinic, 43 (52%) met the full eligibility criteria. Males were 29 (67.4%) while females were 14 (32.6%) with no disparity in mean ages: (males = 35.1±10.8, females = 34.3±9.3). Characterization of HBV genotypes were A: n=34(79.1%), B: n=5(11.6%) and others uncharacterized (E-J): n= 9(20.9%). All cases of genotype B detection were associated with co-infection with genotype A. Genotypes C and D were not detected. ALT levels were normal in 31 (72.1%), abnormal 12 (27.8 %) while GGT levels were normal in 33 (76.7%) and abnormal in 10 (23.3%) cases with varied genotypes. Biochemical markers showed no statistical significance across the genotypes (p>0.05). A majority had HBeAg negative status and HBV DNA >10 IU/ml (81.4 % and 86.0 % respectively) with distribution among all the genotypes. HBeAg percentage negativity rate was 75.9, 80 and 88.9 for genotypes A, A/B and E-J respectively. Across genotypes, viral load mean percentage comparisons were: A vs. A/B = 2600 (p=0.09), A vs. E-J = 5260 (p=0.09) and A/B vs. E-J = 200 (p=0.28). Conclusion: Genotype A was the most predominant with a higher proportion among the participants and with normalized biochemical markers and elevated viral loads. The study population in MTRH has mixed genotype (A and B). A sizable proportion had other genotypes (E-J) not characteristic of the African region needs characterization. Recommendations: Adoption of HBV genotyping and the demonstrated markers to help improve on patient’s outcome at MTRH to reduce the risk of HCC is recommended. Further characterization of the other genotypes (E – J) should be conducted in this population as the study has demonstrated its possible contribution to the current genotypes with further understanding of the new population with the co-infection in MTRH.