Off-Treatment Hepatitis B Virus (HBV) DNA Levels and the Prediction of Relapse After Discontinuation of Nucleos(t)ide Analogue Therapy in Patients With Chronic Hepatitis B: A Prospective Stop Study.

ABSTRACT

Background: The optimal management remains unknown after nucleos(t)ide analogue (NA) discontinuation in patients with chronic hepatitis B (CHB). This prospective study investigated the role of off-treatment viral kinetics in predicting relapse after discontinuation of NA therapy. Methods: A total of 82 noncirrhotic Asian patients with CHB who discontinued NA therapy according to international guidelines were prospectively followed. Patients with a hepatitis B virus (HBV) DNA level of >2000 IU/mL and an alanine aminotransferase (ALT) level of >2 times the upper limit of normal (clinical relapse) were retreated. Results: Sixty patients were HBV envelope antigen (HBeAg) positive at the start of treatment, and 22 were HBeAg negative. Clinical relapse developed in 28 patients (2-year rates, 31% among HBeAg-positive patients and 53% among HBeAg-negative patients). Age of ≤35 years (hazard ratio [HR], 0.37; P = .026) and end-of-treatment HBsAg level of ≤200 IU/mL (HR, 0.39; P = .078) were independently associated with lower relapse rates. A high risk of biochemical relapse (defined as an ALT level of >2 times the upper limit of normal) was observed if the HBV DNA level was >200000 IU/mL when the level was initially elevated, compared with HBV DNA levels of >2000 to ≤200000 IU/mL (HR, 8.42; P < .001). The risk of biochemical relapse was also high in patients with persistent elevation in the HBV DNA level (confirmed to be >2000 IU/mL within 3 months), compared with the group with transient elevation (HR, 6.87; P < .001). Conclusions: After NA discontinuation, a lower relapse rate was observed in younger patients and in those with low end-of-treatment HBsAg levels. The level and persistence of off-treatment elevated HBV DNA levels were useful in the prediction of a subsequent biochemical relapse and may thus be used to guide off-treatment management.