Longitudinal observation of viral load changes in untreated HBeAg negative chronic hepatitis B

Introduction: An HBV DNA level of 2000 IU/ml has been used to differentiate HBeAg negative chronic hepatitis B from the inactive carrier state. We sought to examine the nature and frequency of fluctuations in viral load and ALT around this threshold. Methods: A retrospective review of St Vincent's Hospital database was performed to identify patients who had been observed, untreated, with HBV DNA and ALT levels over a period of at least 18 months. Results: 27 HBeAg negative patients with HBV DNA < 2000 IU/ ml at baseline (Group 1) and 20 HBeAg negative patients with HBV DNA ≥ 2000 IU/ml (Group 2) were identified. Of group 1 patients, only 8/27 had persistently normal ALT and HBV DNA persistently < 2000 IU/ml over a median followup of 24 months. 11/27 (41%) Group 1 patients showed fluctuations above 2000 IU/ml over a median of 24 months followup, most of which were transient and in the range < 20,000 IU/ml. They were accompanied by persistently normal ALT in 5/11 (45%). 8 of 20 (40%) Group 2 patients had a drop of HBV DNA to < 2000 IU/ml over followup. These had a significantly lower baseline HBV DNA (8610 v/s 208763, p = 0.03) than those that remained persistently > 2000 IU/ml. Conclusions: Minor fluctuations in HBV DNA up to 20,000 IU/ ml, accompanied by persistently normal ALT occur frequently in HBeAg negative chronic hepatitis B.