Further increasing selleck inhibitor the dose of peg-interferon might pose tolerability problems. The question remains: can we extend the duration of peg-interferon therapy to improve the chance

of response? In the study by Chen et al., in this issue of the Journal of Gastroenterology and Hepatology, 38 HBeAg-positive patients who achieved HBsAg seroclearance by combination therapy with interferon-α and a nucleos(t)ide analog (lamivudine, adefovir, or entecavir) were described.15 All these patients received extended combination therapy until 6 months post-HBsAg clearance, which occurred at a median of 25.5 (range: 9–63) months. Although this is not a well-designed or prospective study to investigate the role of extended peg-interferon therapy, it does shed some light on the possible results of extending peg-interferon beyond week 48. In this report, most patients had HBeAg seroconversion either before or together with HBsAg seroconversion, and such HBeAg seroconversion usually occurred in the first 2 years.15 In a few patients who had delayed HBeAg seroconversion in the third year of treatment, HBsAg seroclearance had already developed before year 2. That is,

extending peg-interferon to beyond year 2 does not seem too rewarding if HBeAg seroconversion and/or HBsAg seroclearance do not occur by then. One uncertainty is how long one needs to continue peg-interferon treatment after HBeAg seroconversion has developed. In this report, HBsAg seroclearance developed approximately this website DOK2 6 months after HBeAg seroconversion when treatment was continued, but there was no control arm without HBsAg seroclearance, which is actually the case in the majority of patients in real-life practice. Another point of interest is the serial trend of HBsAg levels among these patients, who cleared HBsAg with extended interferon therapy. Although the serial trend of HBsAg level was not described in detail in this report, it was evident that most patients had some reduction in HBsAg levels during the early phase

of treatment.15 This observation concurs with the findings of previous studies and the concept of response-guided therapy. Thus, extended peg-interferon therapy can be considered among intermediate on-treatment responders, but it is probably not a good idea for the poor on-treatment responders. With serum HBsAg level monitoring, we are now midway of the response-guided therapy algorithm for peg-interferon treatment. Stopping rules for poor on-treatment responders are close to mature. To complete the algorithm, prospective, controlled studies are required to address what is next for the good and intermediate on-treatment responders. For the good responders, a standard 48-week peg-interferon treatment should be acceptable to most patients, but it would be better if a shorter duration of treatment can be offered to some patients with very favorable response.