Long-term clinical outcome of HBeAg-negative chronic hepatitis B patients who discontinued nucleos(t)ide analogues.

Abstract

Discontinuation of nucleos(t)ide analogues (NA) remains a debatable issue in HBeAg-negative chronic hepatitis B (CHB). This study aimed to address the outcome of HBeAg-negative CHB patients who discontinued NA therapy. This prospective study included 57 non-cirrhotic HBeAg-negative Caucasian CHB patients who discontinued NA therapy after median virological remission of 6years. All patients had regular blood tests. Virological relapse was defined as HBV DNA>2000IU/mL or >20000IU/mL and biochemical relapse as ALT>ULN (40IU/mL) or >2xULN. All patients with retreatment predefined criteria restarted entecavir or tenofovir. Of the 57 patients, 29 remained without retreatment after median follow-up of 65months (range: 36-87) following treatment discontinuation. At 3, 6, 12, 24, 36 and 48months, cumulative rates of retreatment were 16%, 20%, 32%, 35%, 46% and 50%, while the proportion of patients with HBV DNA<2000IU/mL and ALT<ULN were 73%, 60%, 52%, 52%, 47% and 37% respectively. All patients had virological and biochemical response after retreatment. No patient developed liver failure, hepatocellular carcinoma or death. Cumulative rates of HBsAg loss were 2%, 4%, 7%, 10% and 20% at 3, 6, 12, 24 and 36months. HBsAg levels<100IU/mL at the end of NA treatment could predict HBsAg loss (P=.001). Our study supports that NA therapy can be safely stopped in non-cirrhotic patients with HBeAg-negative CHB. Over a median follow-up of more than 5years, half of the patients remained without retreatment with a substantial proportion of them achieving functional cure.