Relationship Between Level of Hepatitis B Virus DNA and Liver Disease: A Population-based Study of Hepatitis B e Antigen–Negative Persons With Hepatitis B

Background & Aims There is little information on the proportion of persons with chronic hepatitis B virus (HBV) infection with active hepatitis. We aimed to determine the proportion of persons with hepatitis B e antigen–negative chronic HBV infection who develop immune-active HBV infection over time and the relationship between demographic and viral factors on severity of disease on liver biopsy. Methods We performed a longitudinal population-based cohort study of 754 Alaska Native patients with chronic HBV infection. Levels of alanine aminotransferase (ALT) were measured every 6 months, and levels of HBV DNA were measured at study entry and whenever ALT levels exceeded the upper limit of normal (ULN). Immune-active chronic HBV infection was defined as levels of ALT ≥30 U/L in men and >20 U/L in women and levels of HBV DNA >2000 IU/mL at 1 or more time points from 2001–2008. Liver biopsies were scored by using the modified histology activity index score of Knodell and the Ishak fibrosis score. Results Of the study participants, 186 (25%) met the criteria for immune-active HBV, 56% of these initially and 44% later during follow up. Of the 38 patients with liver biopsy results, only 1 of 16 with ALT levels consistently below twice the ULN and 1 of 19 with HBV DNA between 2000 and 20,000 IU/mL, vs 12 of 22 (55%) with ALT > twice ULN ( P = .002) and 11 of 18 (61%) with 1 or more measurements of HBV DNA >20,000 IU/mL ( P < .001), had moderate or severe hepatitis or fibrosis. Conclusions In a cohort of Alaska Natives with chronic HBV infection, 25% met criteria for immune-active HBV. There is a low probability of advanced fibrosis if levels of HBV DNA never exceed 20,000 IU/mL.