[92, 93] An Asian study of IFN therapy regimens lasting six to ten months identified therapeutic benefits six months after the end of therapy in 30% of cases, compared to just 7% in the control group. An even longer therapy regimen of 24 months achieved sustained quiescence of hepatitis in 30% of cases and 18% HBsAg elimination after six years. In light of these findings, continued administration of IFN is recommended overseas for patients with HBeAg negative
chronic hepatitis B. IFN therapy has also been shown to selleck compound library suppress carcinogenesis and deliver improved life expectancies in HBeAg negative patients with chronic hepatitis B, as with HBeAg positive patients. Recommendation IFN therapy has been shown to produce significant improvements in HBeAg positive chronic HBV patients with respect to HBeAg negative conversion, HBeAg seroconversion, HBV DNA negative conversion and ALT normalization, compared to an untreated control group. Pegylated IFN is available as Peg-IFNα-2a (40kD branched strand PEG covalently bonded to IFNα-2a)
and Peg-IFNα-2b (12kD single strand PEG urethane bonded to IFNα-2a). In Japan, only Peg-IFNα-2a is approved by medical insurance for the treatment of chronic active hepatitis B. PEG is a neutral, water-soluble molecule with no inherent toxicity. The molecular weight is governed by the number of ethylene oxide subunits. Pegylation of IFN has two objectives: to alter the pharmacokinetics check details in the body, and to prevent IFN from being recognized
and rejected by the host’s immune system. The concentration of Peg-IFNα-2a in the blood remains within the therapeutic range for approximately 168 hours after administration, reaching the peak concentration (Cmax) 72 to 96 hours after administration. A study in Asia comparing the therapeutic effects of Peg-IFNα-2a and conventional IFNα-2a reported a complete response (i.e. elimination of HBeAg, suppression of HBV DNA and normalization of ALT) in 28% of patients treated with Peg-IFNα-2a compared to 12% of patients treated with conventional IFNα-2a, a statistically significant difference (P = 0.036). The HBeAg seroconversion rate was also higher for Peg-IFNα-2a (33% versus 25%), indicating the superiority of the pegylated agent. In an overseas comparative study, 814 HBeAg positive patients were divided into three groups: Clomifene the first was administered Peg-IFNα-2a for 48 weeks, the second Peg-IFNα-2a together with lamivudine for 48 weeks, and the third lamivudine only for 48 weeks. While all three groups returned similar HBeAg seroconversion rates at the end of the treatment period (27%, 24% and 20% respectively), the Peg-IFNα-2a groups showed significantly better HBeAg seroconversion rates 24 weeks after the end of treatment (32%, 27% and 19%). Virological outcomes 24 weeks after treatment were also better in the Peg-IFNα-2a groups, with 32% of patients <5 log copies/mL HBV DNA, 14% < 400 copies/mL, and HBsAg seroconversion in 3%.