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 ≥200 000 IU/mL when the level was initially elevated, compared with HBV DNA levels of ≥2000 to <200 000 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-oftreatment 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.

Additional Metadata
Keywords antiviral agents, hepatitis B, off-treatment management, Treatment cessation
Persistent URL dx.doi.org/10.1093/infdis/jix025, hdl.handle.net/1765/99088
Journal The Journal of Infectious Diseases
Citation
Cao, J, Chi, H, Yu, T, Li, Z, Hansen, B.E, Zhang, X, … Peng, J. (2017). 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. The Journal of Infectious Diseases, 215(4), 581–589. doi:10.1093/infdis/jix025