Stage of disease in hepatitis B virus infection in Zambian adults is associated with large cell change but not well defined using classic biomarkers

Background: Hepatocellular malignancy in young adults is a prominent feature of hepatitis B virus (HBV) infection in southern Africa. Here we report a cross-sectional study of liver pathology correlated with biomarkers in adults with HBV infection in Zambia. Methods: We analysed liver biopsies from Zambian patients with persistent HBV infection. Results: We analysed 104 patients with HBV infection and evidence of liver disease. We obtained liver biopsies from 53 adults; of these, 12 (23%) were hepatitis B e antigen seropositive. The genotype was evenly distributed between A and E. One biopsy showed malignancy. Stage was 3 or more in 11 of 52 (21%) biopsies free of malignancy and lobular inflammation was found in 50 (94%). Neither alanine aminotransferase (ALT) nor the gamma-glutamyl transferase: platelet ratio (GPR) were correlated with the stage of disease but were correlated with total Ishak score (rho=0.47, p=0.0004 and rho=0.33, p=0.02, respectively). Large cell change was observed in 10 of 11 biopsies with fibrosis stage 3 or more and 16 of 41 with early disease (p=0.005). Serum alpha-fetoprotein was elevated, although still within the normal range, in patients with large cell change (median 3.6 [interquartile range {IQR} 1.6-5.1]) compared with those without (1.7 [IQR 1.0-2.8]; p=0.03). Neither ALT nor GPR predicted large cell change. Conclusions: Large cell change was common in young HBV-infected adults in Zambia. Only serum a-fetoprotein was identified as a biomarker of this phenotype.