Hepatitis B: modern end points of treatment and the specter of viral resistance.

The goal of antiviral treatment of chronic hepatitis B is to prevent the complications of cirrhosis, hepatic decompensation, HCC, and death. Because these clinical outcomes may take a long period of time to develop, it is important to use intermediate or surrogate end points to evaluate the efficacy and response to antiviral treatment, and to determine whether treatment can be safely stopped, especially given concern for the development of antiviral resistance with NUC therapy. Although normalization of ALT and suppression of HBV DNA viral replication are associated with favorable outcomes, the durability of their response is low, and these end points are insufficient markers for stopping treatment. HBeAg seroconversion is currently used to discontinue NUC treatment in patients with HBeAg-positive chronic hepatitis B, whereas the stopping rule for HBeAg-negative disease relies on HBsAg loss. However, HBsAg loss occurs very infrequently and is not a practical end point for clinical use, although quantitative HBsAg levels may be useful in identifying patients who could achieve a sustained virologic response to treatment.