Interferon-α for patients with chronic hepatitis delta: a systematic review of randomized clinical trials.
BACKGROUND
Hepatitis delta virus (HDV) infection therapy is unclear. This systematic analysis aimed to clarify the evidence on the efficacy of interferon (IFN)-α-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-α-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-α (n=132). The remaining two trials evaluated treatment with pegylated (PEG)-IFN-α (n=45). We found that 1-year treatment with high-dose IFN-α achieved better primary outcome rates than with PEG-IFN-α (RR=4.14, 95% CI 1.00, 17.14). Data for 1-year treatment with low-dose IFN-α compared with PEG-IFN-α were similar (RR=2.83, 95% CI 0.65, 12.40), as were low-dose IFN-α versus high-dose IFN-α (RR=0.68, 95% CI 0.31, 1.50). High-dose IFN-α and PEG-IFN-α 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-α monotherapy appears to be more effective than PEG-IFN-α 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.
Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. m.lamers@mdl.umcn.nl
Mieke H
MH
Lamers
Özlem Özentürk
ÖÖ
Kirgiz
Benjamin
B
Heidrich
Heiner
H
Wedemeyer
Joost P H
JP
Drenth
D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000379:methods; D019701:Hepatitis D, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D003698:Hepatitis Delta Virus / Q000472:pathogenicity; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D012367:RNA, Viral / Q000032:analysis* / Q000235:genetics; D016032:Randomized Controlled Trials as Topic; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D012307:Risk Factors; D016896:Treatment Outcome
D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D019259:Lamivudine; D012254:Ribavirin; D000410:Alanine Transaminase