Predictors of response to antiviral treatment for chronic hepatitis B.

Chronic hepatitis B virus (HBV) infection is prevalent in many Asian countries, notwithstanding three decades of universal hepatitis B vaccination programs. The invention of nucleos(t)ide analogs (NUCs) was a breakthrough in the treatment of chronic hepatitis B (CHB). However, HBV continues to be a challenging disease to completely eradicate using current treatment agents. According to the treatment guidelines recommended by the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver, NUCs with either entecavir or tenofovir is the first-line treatment of choice for CHB. Another treatment option is pegylated interferon (PEG-IFN). For those cases involving hepatitis B e antigen (HBeAg)-positive patients, HBeAg seroconversion is the surrogate end point of treatment; nevertheless, some cases would progress to HBeAg-negative CHB and could experience virological or clinical relapse even after achieving HBeAg seroconversion. In general, the HBeAg seroconversion rate is around 20% by NUCs treatment for 1 year, and an average of 30% after 48 weeks or 52 weeks of PEG-IFN treatment. It is generally understood that stronger host immunity against the virus by presenting a high alanine transaminase (ALT) and lower HBV viral load before the NUCs or PEG-IFN treatment has an elevated chance of achieving HBeAg seroconversion. For HBeAg-negative CHB, another phase of chronic HBV infection requiring antiviral treatment, the treatment end point is hepatitis B surface antigen (HBsAg) loss or HBsAg seroconversion by NUCs treatment. Alternatively, PEG-IFN treatment involves a sustained off-treatment virological response as defined by a serum HBV DNA of <2000 IU/mL at 48 weeks post-treatment as the treatment goal. To achieve HBsAg loss or HBsAg seroconversion, indefinite or long-term NUCs treatment is required. Regarding PEG-IFN treatment, the baseline predictor of virological response is poorly defined for HBeAg-negative CHB. However, a low HBsAg level or a higher chemokine level (CXCL9) at baseline is associated with a higher sustained response by PEG-IFN treatment in patients with HBeAg-negative CHB. Recently, on-treatment HBsAg decline has been proposed as a significant ontreatment predictor of virological response or HBsAg loss for HBeAg-positive and HBeAg-negative CHB undergoing