Peginterferon Alfa-2a in Patients with Chronic Hepatitis C and Cirrhosis

Heathcote, E. Jenny; Shiffman, Mitchell L.; Cooksley, W. G. E.; Dusheiko, Geoffrey; Lee, S. S.; Balart, Luis A.; Reindollar, Robert; Reddy, Rajender; Wright, Teresa L.; Lin, Amy; Hoffman, Joseph H.; Pamphilis, Jean De

doi:10.1056/nejm200012073432302

Cited by 800 publications

(542 citation statements)

References 17 publications

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“…The development of pegylated IFNs with improved pharmacokinetics has been shown to yield a better efficacy and convenience than the conventional IFNs in the treatment of chronic hepatitis C. [41][42][43][44][45] Regarding the treatment of chronic hepatitis B, recent pilot trials also demonstrated that pegylated IFN was more effective than conventional IFN or other nucleotide/nucleoside analogues in either HBeAg-positive or -negative chronic hepatitis B. 8,10,15,25,45 Whether pegylated IFN-based therapy in combination with other antiviral agents such as ribavirin could enhance the treatment efficacy in patients with chronic hepatitis B awaits further clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Interferon α-2b with and without ribavirin in the treatment of hepatitis B e antigen–positive chronic hepatitis B: A randomized study

et al. 2006

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To study whether interferon (IFN) ␣ and ribavirin combination therapy has a beneficial effect for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, we enrolled 119 such patients in a randomized study. Fifty-nine patients received 5 million units of IFN-␣2b daily for 4 weeks followed by 5 million units three times a week for 28 weeks, plus 1,200 mg ribavirin daily. Sixty patients received the same dosage of IFN plus placebo. They were followed up for 24 weeks posttreatment, and 105 patients (88%) completed the entire course of 56 weeks. By intention-to-treat analysis, the rate of combined response (serum hepatitis B virus [HBV] DNA <2.5 pg/mL and HBeAg seroconversion) was 17% versus 25% between the IFN/ribavirin and IFN/placebo group, respectively, at the end of treatment (P ‫؍‬ .35) and 25% vs. 20% at the end of follow-up (P ‫؍‬ .32). Using quantitative real-time polymerase chain reaction assay, the log(10) reduction of serum HBV DNA was 1.05 ؎ 1.72 (mean ؎ SD) versus 1.29 ؎ 1.91 between the two groups at the end of treatment (P ‫؍‬ .49) and was 2.15 ؎ 2.15 versus 1.21 ؎ 2.48 at the end of follow-up (P ‫؍‬ .04). Prolonged observations in 83 patients suggested that the combined response was 29% (n ‫؍‬ 17) versus 20% (n ‫؍‬ 12) at 48 weeks after the end of treatment, respectively (P ‫؍‬ .17). The safety profile was similar, except that the IFN/ribavirin group had a higher risk of anemia (15% vs. 0%; P ‫؍‬ .002). In conclusion, for the treatment of HBeAg-positive chronic hepatitis B, adding ribavirin does not seem to increase the efficacy of IFN. (HEPATOLOGY 2006;43:742-749.)

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Section: Discussionmentioning

confidence: 99%

Interferon α-2b with and without ribavirin in the treatment of hepatitis B e antigen–positive chronic hepatitis B: A randomized study

et al. 2006

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“…We analyzed data on individual patients from three RCTs of peginterferon alfa-2a. 11,12,14 These studies are the only three RCTs that compare peginterferon alfa-2a with conventional IFN and include previously untreated patients with pretreatment and post-treatment liver biopsies. Written consent was obtained from the principal investigator at each trial center.…”

Section: Methodsmentioning

confidence: 99%

“…Nonetheless, the results of published studies on the effects of this new drug on liver histology remain inconsistent, and the overall effect of treatment is difficult to evaluate. [11][12][13][14] To overcome some of the limitations associated with the use of histologic findings, to increase the relevance of statistical analysis, and to improve estimates of effect magnitudes, we performed a meta-analysis of individual patient data (MIPD). The aims of the current MIPD were 1) to assess the differences between peginterferon alfa-2a and conventional IFN with respect to changes in liver histology; 2) to identify predictors of histologic improvement; and 3) to evaluate the optimal treatment schedule for bringing about histologic improvement.…”

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confidence: 99%

Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: A meta-analysis of individual patient data

et al. 2004

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Multicenter randomized trials have shown that once-weekly pegylated interferon (peginterferon) alfa-2a is more efficacious than conventional interferon alfa-2a (IFN) in patients with chronic hepatitis C. We performed a meta-analysis of 1,013 previously untreated patients (from 3 randomized trials) with pretreatment and post-treatment liver biopsies to assess the differences between peginterferon alfa-2a and IFN in terms of their effects on liver histology. Reported values were standardized mean differences (SMD) between patients receiving peginterferon alfa-2a and those receiving IFN (post-treatment value minus baseline value for each group). We used a random-effects model to quantify the average effect of peginterferon alfa-2a on liver histology. Peginterferon alfa-2a significantly reduced fibrosis compared with IFN (SMD, ؊0.14; 95% CI: ؊0.27, ؊0.01; P ‫؍‬ .04). A reduction in fibrosis was observed among sustained virologic responders (SMD, ؊0.59; 95% CI: ؊0.89, ؊0.30; P < .0001) and patients with recurrent disease (SMD, ؊0.34; 95% CI: ؊0.54, ؊0.14; P ‫؍‬ .0007), whereas no significant reduction was observed among nonresponders (SMD, ؊0.

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“…Consequently, HCV infection is the foremost reason for performing liver transplants. 2 Antiviral therapy consisting of peginterferon alfa-2a/ribavirin leads to a sustained response in only half of all patients infected with HCV genotypes 1 and 4, 3,4 resulting in the need to develop new antiviral therapies. In addition, the emergence of drug resistance in RNA virus infections emphasizes the requirement for multiple drug targets to limit viral escape.…”

Section: Introductionmentioning

confidence: 99%

Baculovirus-mediated interferon alleviates dimethylnitrosamine-induced liver cirrhosis symptoms in a murine model

et al. 2008

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The wild-type baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects a range of mammalian cell types in vitro but does not replicate in these cells. The current study investigated the in vivo effect of AcMNPV in the mouse model of liver cirrhosis induced by the mutagen dimethylnitrosamine. Intraperitoneal injection of AcMNPV induced an immune response. The baculovirus was taken up by the liver and spleen where it suppressed liver injury and fibrosis through the induction of interferons. This study presents the first evidence of the feasibility of using baculovirus to treat liver cirrhosis. Gene Therapy (2008) 15, 990-997;

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Peginterferon Alfa-2a in Patients with Chronic Hepatitis C and Cirrhosis

Abstract: In patients with chronic hepatitis C and cirrhosis or bridging fibrosis, 180 microg of peginterferon alfa-2a administered once weekly is significantly more effective than 3 million units of standard interferon alfa-2a administered three times weekly.

Cited by 800 publications

References 17 publications

Interferon α-2b with and without ribavirin in the treatment of hepatitis B e antigen–positive chronic hepatitis B: A randomized study

Interferon α-2b with and without ribavirin in the treatment of hepatitis B e antigen–positive chronic hepatitis B: A randomized study

Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: A meta-analysis of individual patient data

Baculovirus-mediated interferon alleviates dimethylnitrosamine-induced liver cirrhosis symptoms in a murine model

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