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Evidence summaries

Interferon for Chronic Hepatitis C

Interferon treatment is effective in achieving viral clearance and improving liver biochemistry and histology in chronic hepatitis C. About 17% of the patients have sustained virologial response to interferon alpha. Interferon monotherapy retreatment cannot be recommended for patient with severe cirrhosis. Level of evidence: "A"

A Cochrane review 5 (abstract , review [Abstract]) included 54 trials with a total of interferon naive 6545 subjects. Compared with no treatment, interferon 3 MU thrice weekly for 12 months increased the probability of a virologic sustained response (SR) (Peto odds ratio (OR) 4.60; 95% confidence interval (CI) 1.53 to 13.85). The rate of virologic SR was 17% (95% CI 10 to 28%) in interferon-treated patients versus 3% (95% CI 1 to 10%) in controls. A dose of 6 MU was more effective than 3 MU thrice weekly (OR for 12 months treatment, 2.21; 95% CI 1.10 to 4.45), as were durations of 12 months or greater versus six months (OR 1.87; 95% CI 1.30 to 2.67). Compared with no therapy, interferon increased the probability of histologic improvement (OR 9.22; 95% CI 5.69 to 14.94). The response to interferon in cirrhotic patients (virologic SR, 17%; 95% CI 11 to 26%) was similar to that in non-cirrhotic patients.

A Cochrane review 6[Abstract] included seven trials. Two of them were at low risk of bias and included 1676 patients. Both of these trials addressed the role of long-term low-dose pegylated interferon therapy in patients with severe fibrosis and were designed to assess the clinical outcomes. The remaining five trials included 300 patients and were at high risk of bias.

Based on all trials reporting the outcomes, no significant difference was observed in either all-cause mortality (78/843 (9.3%) versus 62/867 (7.2%); RR 1.30, 95% CI 0.95 to 1.79; 3 trials) or hepatic mortality (41/532 (7.7%) versus 40/552 (7.2%); RR 1.07, 95% CI 0.70 to 1.63; 2 trials); however, when only the two trials at low risk of bias were combined, all-cause mortality was significantly higher in the recipients of the pegylated interferon (78/828 (9.4%) versus 57/848 (6.7%); RR 1.41, 95% CI 1.02 to 1.96). There was less variceal bleeding in the recipients of the interferon (4/843 (0.5%) versus 18/867 (2.1%); RR 0.24, 95% CI 0.09 to 0.67; 3 trials). No significant differences were seen with regard to the development of ascites, encephalopathy, hepatocellular carcinoma, or the need for liver transplantation. One trial reported quality of life data; the pain score was significantly worse in the recipients of the pegylated interferon. Adverse effects tended to be more common in the interferon recipients; the ones that were significantly more common included hematologic complications, infections, flu-like symptoms, and rash. The recipients of interferon had significantly more sustained viral responses (20/557 (3.6%) versus 1/579 (0.2%); RR 15.38, 95% CI 2.93 to 80.71; 4 trials). The METAVIR activity score also improved (36/55 (65%) versus 20/46 (43.5%); RR 1.49, 95% CI 1.02 to 2.18; 2 trials). No significant differences were seen with regard to histologic fibrosis assessments.

Retreatment with interferon did not appear to provide significant clinical benefit and, when only the trials at low risk of bias were considered, retreatment for several years may even have increased all-cause mortality. Such treatment also produced adverse events. The treatment did result in improvement in some surrogate outcomes, namely sustained viral responses and histologic evidence of inflammation. No clinical data are available for patients with less severe fibrosis.

    References

    • Myers RP, Regimbeau C, Thevenot T, Leroy V, Mathurin P, Opolon P, Zarski JP, Poynard T. Interferon for interferon naive patients with chronic hepatitis C. Cochrane Database Syst Rev 2002;(2):CD000370. [PubMed]
    • Koretz RL, Pleguezuelo M, Arvaniti V et al. Interferon for interferon nonresponding and relapsing patients with chronic hepatitis C. Cochrane Database Syst Rev 2013;(1):CD003617. [PubMed]

Primary/Secondary Keywords