It should be noted that, in Japanese clinical trials, ≥95% of subjects are aged <50 years, in both HBeAg positive and negative groups, and the efficacy of Peg-IFN therapy has not been adequately assessed in patients aged ≥50 years.[100] A full explanation may be warranted that the HBeAg seroconversion rate and HBV DNA negative conversion rate are not necessarily high, that it is difficult to efficacy in individual cases prior to treatment, and possible adverse Metformin reactions. On the other hand, in cases where Peg-IFN is contraindicated for tolerability, or in cases with cirrhosis, entecavir therapy is administered initially with the aim of maintaining long term

remission. However, lamivudine therapy is recommended in cases of acute exacerbation of hepatitis associated with jaundice, because transaminases can rise in

these patients following entecavir administration. When a prolonged treatment period is likely, a switch should be made to entecavir. Before commencing entecavir therapy, it is necessary to fully explain the need for long term continuous treatment, possible safety problem during pregnancy and the risk of resistant mutations, before obtaining informed consent. In cases where the HBV DNA and see more ALT levels declined and hepatitis became quiescent following treatment with conventional IFN or Peg-IFN treatment, retreatment with Peg-IFN therapy should be considered if hepatitis recurs.

Even in patients where quiescence of hepatitis was not obtained by conventional IFN therapy, retreatment with Peg-IFN D-malate dehydrogenase is an option. However, in cases where tolerability of conventional IFN therapy is poor, and in cases where quiescence of the hepatitis is not obtained by the preceding Peg-IFN therapy, entecavir therapy is administered with the aim of maintaining long term remission. Even in cases of recurrence of hepatitis following cessation of entecavir therapy, retreatment with entecavir should be considered. The criteria for recurrence of hepatitis are HBV DNA levels ≥5.8 log copies/mL, or ALT levels ≥80 U/L.[209] In Japan, there is insufficient evidence for the efficacy and safety of IFN treatment for HBV cirrhosis, and it is not officially approved. The initial treatment for liver cirrhosis is long term continuous entecavir therapy. Recommendations In general, Peg-IFN monotherapy should be considered the first choice treatment for chronic hepatitis, irrespective of HBeAg status or HBV genotype. Retreatment using Peg-IFN should be considered in patients with chronic hepatitis when recurrence of hepatitis occurs following treatment with conventional IFN or Peg-IFN. Entecavir therapy should be administered to IFN non-responders, with no efficacy from earlier IFN therapy.