Interferon-alpha for patients with chronic hepatitis delta: a systematic review of randomized clinical trials

Abstract

BACKGROUND: Hepatitis delta virus (HDV) infection therapy is unclear. This systematic analysis aimed to clarify the evidence on the efficacy of interferon (IFN)-alpha-based therapy in HDV. METHODS: We performed a systematic search on electronic databases including MEDLINE (1970 to January 2011), Web of Science, The Cochrane Library and ClinicalTrials.gov. Randomized clinical trials (RCTs) comparing IFN-alpha-based therapy with either another drug, placebo or no intervention were included. We excluded paediatric studies. We calculated relative risks (RRs) for comparison of treatment options on the primary outcome measure, which was defined as undetectable levels of HDV RNA and normal alanine aminotransferase at end of treatment (EOT; 1 year). RESULTS: Nine RCTs were included. Seven trials evaluated the treatment with IFN-alpha (n=132). The remaining two trials evaluated treatment with pegylated (PEG)-IFN-alpha (n=45). We found that 1-year treatment with high-dose IFN-alpha achieved better primary outcome rates than with PEG-IFN-alpha (RR=4.14, 95% CI 1.00, 17.14). Data for 1-year treatment with low-dose IFN-alpha compared with PEG-IFN-alpha were similar (RR=2.83, 95% CI 0.65, 12.40), as were low-dose IFN-alpha versus high-dose IFN-alpha (RR=0.68, 95% CI 0.31, 1.50). High-dose IFN-alpha and PEG-IFN-alpha reached similar HDV RNA suppression 24 weeks after EOT (RR=1.00, 95% CI 0.51, 1.97). None of the 55 patients assigned to no intervention obtained undetectable levels of HDV RNA and only one patient achieved normalization of alanine aminotransferase level. CONCLUSIONS: Based on available RCTs, 1-year high-dose IFN-alpha monotherapy appears to be more effective than PEG-IFN-alpha for treatment of HDV patients, with efficacy rates of approximately 30%. There is a lack of head-to-head comparisons. Combination therapies and longer treatment duration need to be investigated.