LAUSR

Long-term administration of potent nucleos (t)ide analogs (NAs) is the cornerstone of antiviral therapy for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B, as it reduces liver-related complications by efficiently suppressing viral replication. Although there is agreement that the best and safest stopping rule in this setting is hepatitis B surface antigen (HBsAg) loss, it remains highly debated whether NA discontinuation before HBsAg loss can be recommended, when it should be recommended, and with what aim. In this issue of HEPATOLOGY, two publications address relevant questions concerning the finite NA approach in HBeAg-negative patient populations. The first study, a collaboration between two expert centers in Greece and Taiwan, aimed to better characterize the patterns of relapse after stopping NA therapy and to elucidate whether an early relapse pattern might be predictive for long-term outcome and need for retreatment. The study included 130 HBeAgnegative patients without cirrhosis who had ontreatment undetectable hepatitis B virus (HBV) DNA levels for at least 24 months. Fourteen different relapse patterns were predefined, ranging from very stringent criteria for virologic relapses to more clinically relevant combined virologic and biochemical relapses. The posttreatment cumulative rates at 6, 12, and 24 months were approximately 70%, 80%, and 90% for HBV DNA >200 IU/mL and approximately 55%, 70%, and 70% for HBV DNA >2000 IU/mL, respectively, By using a relapse definition of HBV DNA >2000 IU/ mL in combination with any elevation of alanine aminotransferase (ALT) levels, 35%, 50%, and 55% of patients would have been considered to have a clinically relevant relapse by 6, 12, and 24 months, respectively. No liver decompensation or death occurred. Cumulative retreatment rates, however, did not mirror the relapse rates and were only 15%, 22%, and 40% after 6, 12, and 24 months, respectively, after NA discontinuation. Although no strong and independent predictors of virologic relapse were identified, the probability of relapse defined as HBV DNA >2000 IU/mL and ALT above the upper limit of normal was found to be significantly associated with the use of tenofovir compared with entecavir therapy in multivariate analyses (P 5 0.029). Likewise, the need for retreatment could not be independently predicted by any of the available markers in multivariate analyses. However, HBsAg levels at baseline or at NA cessation, a parameter that has been shown to predict postcessation outcomes in other studies, were not available in this study, limiting the conclusions regarding relapse and retreatment prediction. The second study, by Jeng et al., reviewed the incidence and predictors of HBsAg seroclearance after NA cessation in 691 Taiwanese patients with HBeAgAbbreviations: ALT, alanine aminotransferase; EOT, end-oftreatment; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; NA, nucleos(t)ide analog.