Long-Term Clinical Outcome Of Hbeag-Negative Chronic Hepatitis B Patients Who Discontinued Nucleos(T)Ide Analogues

Background & Aims 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.Methods This prospective study included 57 non-cirrhotic HBeAg-negative Caucasian CHB patients who discontinued NA therapy after median virological remission of 6 years. All patients had regular blood tests. Virological relapse was defined as HBV DNA > 2000 IU/mL or >20 000 IU/mL and biochemical relapse as ALT > ULN (40 IU/mL) or >2xULN. All patients with retreatment predefined criteria restarted entecavir or tenofovir.Results Of the 57 patients, 29 remained without retreatment after median follow-up of 65 months (range: 36-87) following treatment discontinuation. At 3, 6, 12, 24, 36 and 48 months, cumulative rates of retreatment were 16%, 20%, 32%, 35%, 46% and 50%, while the proportion of patients with HBV DNA < 2000 IU/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 36 months. HBsAg levels < 100 IU/mL at the end of NA treatment could predict HBsAg loss (P = .001).Conclusions 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 5 years, half of the patients remained without retreatment with a substantial proportion of them achieving functional cure.