Copyright ©The Author(s) 2015.
World J Hepatol. Nov 18, 2015; 7(26): 2681-2687
Published online Nov 18, 2015. doi: 10.4254/wjh.v7.i26.2681
Table 1 Factors associated with the efficacy of interferon treatment
FactorsMain findingsRef.
Classically identified viral and host factors
Age, HCV genotype, Viral load, Liver fibrosisOlder age, HCV genotype 1, high viral load, and advanced liver fibrosis were associated with poor treatment results[3,4]
Viral factors
ISDRMutations of the ISDR (NS5A 2209-2234) were positively related to the HCV eradication with IFN-α monotherapy[14]
Amino acid mutations of the core region (Nos. 70 and 91)Mutations of amino acids were associated with a poor response to IFN-α plus RBV treatment[15]
IRRDRMutations of the IRRDR (NS5A 2334-2379) were associated with a favorable response to the IFN-α plus RBV treatment[16,17]
Drug resistant mutation1[27,28]
Host factors
IL28B SNPsThe hero/minor allele of IL28B SNPs was related to a poor response to Peg-IFN-α plus RBV treatment[18-20]
Table 2 Possible involvement of anti-IFN-α neutralizing antibodies in the response to interferon-α treatment for chronic hepatitis C
TreatmentCohortMain resultsRef.
IFN-α monotherapy47Fifteen of 47 patients (31.9%) developed detectable levels of NAbs within two to eight months after starting treatment. Patients who developed anti-IFN NAbs showed poor responses to IFN (4/15: 26.6%) compared to antibody-negative patients (26/32: 81.3%) (P = 0.0009)[29]
IFN-α monotherapy63Fifteen of 63 patients were positive for neutralizing anti-IFN-α NAbs. The responsive rate of all patients was 60.3% (38/63), while that of patients with anti-IFN NAbs was 13.3% (2/15), showing that NAbs development could significantly affect the therapeutic efficacy of IFN (P < 0.01)[30]
IFN-α monotherapy28Among 28 patients treated with recombinant IFN-α-2a, anti-IFN-α NAbs were detected in 75% (6/8) of the patients who did not respond to IFN therapy. During IFN treatment, the mean ALT level of anti-IFN negative patients was decreased and continuously suppressed during treatment with the 3 MU of IFN-α-2a, while that of anti-IFN positive patients was reelevated without a dose-reduction of IFN[31]
IFN-α monotherapy84In 84 patients with initial responses to IFN-α treatment, anti-IFN-α NAbs developed in 38.5% (5/13) of patients with breakthrough, as compared to 2.8% (2/71) of complete-responder patients (P < 0.0005) The emergence of anti-IFN-α NAbs three months after the initiation of therapy was the only factor to be predictive of breakthrough (RR = 9.5, 95%CI: 1.6-64.7, P = 0.007)[32]
Peg-IFN-α plus RBV42A total of 42 non-response patients to previous conventional IFN treatment were re-treated with Peg-IFN-α-2a plus RBV. A decrease in HCV-RNA greater than 2 log10 copies/mL at week 12 relative to baseline values was not associated with the presence of anti-IFN-α NAbs (7/19, 36.8% in responders vs 6/23, 26.1% in non-responders at week 12; P = 0.73)[35]
Peg-IFN-α plus RBV129A total of 129 patients who received Peg-IFN-α plus RBV were studied. Of the 47 patients who did not achieve an end of treatment response, seven patients (14.9%) were positive for anti-IFN-α NAbs, while no anti-IFN-α NAbs were detected in the 82 end of treatment responders (P = 0.0001). Anti-IFN-α NAbs were associated with a non-response to Peg-IFN-α plus RBV treatment, regardless of the patient IL28B-type and other treatment response-related characteristics[36]