Can we stop nucleoside analogues before HBsAg loss?

Abstract

Most of the current guidelines and the existing data suggest that long-term therapy with nucleos(t)ide analogue(s) [NA(s)] may be stopped in carefully selected chronic hepatitis B patients who remain HBsAg positive. In particular, NA(s) may be discontinued in such patients without pre-existing cirrhosis who achieved long-term on-therapy virological remission (>12months of HBeAg seroconversion and HBV DNA undetectability for initially HBeAg-positive cases; ≥3years of HBV DNA undetectability for HBeAg-negative cases) and are expected to remain under close follow-up after NA(s) discontinuation. The majority of patients will develop post-NA(s) virological relapses and a proportion of them will have biochemical relapses and occasionally flares, but prompt retreatment can reintroduce remission. No reliable predictor(s) of post-NA(s) relapses have been identified so far. HBsAg loss develops in a progressively increasing proportion of chronic hepatitis B patients who discontinue NA(s) with HBsAg loss rates being higher in Caucasian patients with HBeAg-negative chronic hepatitis B. Follow-up at least every 3months for the first year seems to be appropriate for all chronic hepatitis B patients who discontinue NA(s), while HBeAg-negative patients need to be followed more closely (monthly) during the first 3months. Predefined criteria for retreatment are quite important, and the best candidates for retreatment are probably the patients with persistent (≥3months) liver disease activity and those with severe flares.