The Role of Hepatitis B Surface Antigen in Nucleos(t)ide Analogues Cessation among Asian Chronic Hepatitis B Patients: A Systematic Review

Abstract

In actual clinical practice, infinite nucleos(t)ide analogues (NAs) treatment for chronic hepatitis B virus (HBV) infection is unrealistic. The most commonly used endpoint is suppression of HBV DNA to undetectable levels with normalization of alanine aminotransferase (ALT). However, this criterion for cessation of treatment is associated with various incidences of virological and clinical relapse. Recent studies suggest that decreasing hepatitis B surface antigen (HBsAg) level at the end of treatment (EOT) to an appropriate cutoff value appears to be a practicable and attainable cessation criterion. We performed a systematic review to explore the optimal cutoff value of HBsAg at EOT for the cessation of NAs treatment. Eleven studies with 1716 patients were included in this review. When the HBsAg levels at EOT were < 100 IU/mL and > 100 IU/mL, the respective off‐therapy virological relapse rates were 9.1%–19.6% (range) and 31.4%–86.8% (range) at ≥ 12 months off‐therapy regardless of HBeAg status, the respective off‐therapy clinical relapse rates were 15.4%–29.4% (range) and 48.1%–63.6% (range) at ≥ 12 months off‐therapy regardless of HBeAg status, and the respective off‐therapy HBsAg loss rates were 21.1%–58.8% (range) and 3.3%–7.4% (range) for HBeAg‐negative patients at ≥ 39 months off‐therapy. Conclusion: Cessation of long‐term NAs therapy prior to HBsAg seroclearance in patients with chronic hepatitis B is a feasible alternative to indefinite treatment. A HBsAg level < 100 IU/mL at EOT seems to be a useful marker for deciding when to discontinue NAs therapy. However, regular monitoring is required after the cessation of NAs treatment, and long‐term outcomes must be further evaluated.

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