Liver Histology and HBV DNA Levels in Chronically HBV Infected Patients with Persistently Normal Alanine Aminotransferase

Background: Data on histological activity and HBV DNA levels in patients with chronic HBV infection and persistently normal alanine aminotransferase levels are sparse. We aimed to investigate the histological activity and HBV DNA levels in these patients. Methods: There were 132 patients with HBeAg negative chronic HBV infection and persistently normal alanine aminotransferase levels that were included prospectively. Data were dichotomized according to the median levels. Associations of histology with HBV DNA and other variables were assessed. Results: A total of 80 patients were male. The median age was 36 years. The median baseline HBV DNA was 2.9Log10 IU/ mL. There were 50 cases (38%) with a total score _5, 53 cases (40.2%) had grade _4 and 40 cases (30.3%) had stage _2. A baseline HBV DNA <2000 IU/mL was seen in 24 cases (48 %) of those with total score _5, 28 cases (53%) of those with grade _4 and 9 cases (22.5%) with stage _2. Multivariate analysis of baseline HBV DNA above the median level signi_cantly predicted the total score, grade and stage with an adjusted odds ratio of 5.43, 3.47, and 4.23, respectively when compared to below median values. A second liver biopsy was performed in 61 patients. The median time interval between the two biopsies was 40 months. Total scores of 23 cases (38%) progressed by _2 scores and the HBV DNA of 18 cases (22.5 %) increased by _1 Log10 IU when compared to baseline values. Conclusions: HBeAg negative chronic HBV infection with persistently normal alanine aminotransferase is not a silent disease. Active liver disease may be seen in such patients with viral loads less than 2000 IU/mL.