Evaluation of adefovir & lamivudine in chronic hepatitis B: Correlation with HBV viral kinetic, hepatic-necro inflammation & fibrosis

BACKGROUND & OBJECTIVES: Chronic hepatitis B is an important cause of morbidity and mortality. We conducted a study comparing the efficacy of adefovir and lamivudine with respect to their impact on serum and hepatic viral DNA clearance, and improvement in hepatic necro-inflammatory score, in naive patients of chronic hepatitis B. METHODS: This prospective randomized pilot study was conducted in Lok Nayak Hospital, New Delhi, involving 30 patients of chronic hepatitis B (both e antigen positive and negative); 15 were randomly selected to receive either adefovir or lamivudine for a period of 6 months. Quantification of serum and hepatic HBV DNA levels was done by real time PCR and liver biopsy was done at the beginning and end of 6 months. RESULTS: Serum ALT was elevated to 2 or more times normalized in both the groups. In the adefovir group, two patients became HBeAg negative. In the lamivudine group, one patient became HBeAg negative. After therapy HBV DNA was negative in 26.7 per cent patients from adefovir group and 13.3 per cent patients from lamivudine group. Serum HBV DNA levels were correlated with the hepatic levels before therapy (r=0.843; P<0.001) and after therapy (r=0.713, P<0.001) showing strong correlation. There was a median reduction of 1.92 and 2.06 log copies per ml in serum HBV DNA load after adefovir and lamivudine therapy, respectively. The mean reduction in the histotogy activity index (HAI) score was 2 and 1.53, fibrosis score was 2.33 and 3.06 after adefovir and lamivudine therapy respectively. INTERPRETATION & CONCLUSIONS: Adefovir and lamivudine treatment caused biochemical and serological improvement when administered for about 6 months with significant reduction in HBV DNA, serum and hepatic viral load without completely clearing the virus from either serum or liver. It also helped in reduction of the necro-inflammatory and fibrosis score of patients with chronic hepatitis B. Our study also showed significant correlation between serum and hepatic HBV DNA levels both before and after therapy. There was not enough evidence to show therapeutic advantage of one drug over the other in any of the parameters measured.