Prospective Study of Withdrawal of Antiviral Therapy in Patients with Chronic Hepatitis B after Prolonged Virological Response.

ABSTRACT

Nucleoside analogue (NA) therapy for chronic hepatitis B (CHB) is associated with improved clinical outcomes, but usually requires long-term use. Whether treatment can be safely withdrawn and the factors associated with post-withdrawal outcome are not well defined. To assess long-term outcomes after stopping antiviral therapy, patients with hepatitis B e antigen (HBeAg)-negative CHB who had received antiviral therapy for 4 or more years with hepatitis B virus (HBV) DNA (≤100 IU/mL) were prospectively withdrawn from antiviral therapy and monitored monthly for the initial 6 months and every 3 months thereafter. Those with clinical relapse were retreated according to severity of relapse. Fifteen patients were withdrawn from lamivudine (4), adefovir (5), or a combination of the two (6) after a mean treatment duration of 8.4 years. The mean age was 45 years, 13 were male, and 8 were initially HBeAg-positive before treatment. After a mean follow-up of 6.6 years, outcomes differed by pretreatment HBeAg status. All patients who were HBeAg+ before treatment experienced virological relapse (8 of 8); 6 of 8 experienced clinical relapse; 4 of 8 had ALT flares; 5 of 8 required re-initiation of treatment, one of whom cleared hepatitis B surface antigen (HBsAg); and 3 of 8 remained off treatment, one of whom cleared HBsAg. In contrast, 4 of 7 patients who were HBeAg-negative before treatment experienced virological relapse, 3 of 7 experienced clinical relapse, and 1 of 7 had an alanine aminotransferase (ALT) flare. None restarted treatment, and 4 of 7 cleared HBsAg. Low pre-withdrawal HBsAg level was predictive of HBsAg loss. Conclusion: NA therapy can be safely withdrawn with long-term remission and high rates of HBsAg loss in most HBeAg-negative patients without cirrhosis. Patients who were initially HBeAg+ should not be withdrawn from treatment, because clinical relapse was frequent and often severe.