Jiaye Liu1,2, Tao Li3, Li Zhang1,2, Aiqiang Xu1,2. 1. Academy of Preventive Medicine, Shandong University, Jinan, China. 2. Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Provincial Center for Disease Control and Prevention, Jinan, China. 3. Department of Infectious Diseases and Hepatology, the Second Hospital of Shandong University, Jinan, China.
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. However, this criterion for cessation of treatment is associated with various incidences of virological and clinical relapse. Recent studies suggest that decreasing the hepatitis B surface antigen (HBsAg) level at the end of treatment (EOT) to an appropriate cut-off value appears to be a practicable and attainable cessation criterion. We performed a systematic review to explore the optimal cut-off value of HBsAg at EOT for the cessation of NAs treatment. Eleven studies with 1,716 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 hepatitis B e antigen (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 before HBsAg seroclearance in patients with chronic hepatitis B is a feasible alternative to indefinite treatment. An 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.
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. However, this criterion for cessation of treatment is associated with various incidences of virological and clinical relapse. Recent studies suggest that decreasing the hepatitis B surface antigen (HBsAg) level at the end of treatment (EOT) to an appropriate cut-off value appears to be a practicable and attainable cessation criterion. We performed a systematic review to explore the optimal cut-off value of HBsAg at EOT for the cessation of NAs treatment. Eleven studies with 1,716 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 hepatitis B e antigen (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 before HBsAg seroclearance in patients with chronic hepatitis B is a feasible alternative to indefinite treatment. An 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.
Authors: Erwin Ho; Stijn Van Hees; Sofie Goethals; Elke Smits; Manon Huizing; Sven Francque; Benedicte De Winter; Peter Michielsen; Thomas Vanwolleghem Journal: Front Med (Lausanne) Date: 2019-08-20