Factors associated with the response to interferon-based antiviral therapies for chronic hepatitis C

Table 2 Possible involvement of anti-IFN-α neutralizing antibodies in the response to interferon-α treatment for chronic hepatitis C

Treatment	Cohort	Main results	Ref.
IFN-α monotherapy	47	Fifteen 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 monotherapy	63	Fifteen 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 monotherapy	28	Among 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 monotherapy	84	In 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 RBV	42	A 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 RBV	129	A 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]

IFN: Interferon; Peg-IFN-α: Pegylated-interferon-α; RBV: Ribavirin; NAbs: Neutralizing antibodies; ALT: Alanine aminotransferase; RR: Relative risk; HCV: Hepatitis C virus; IL28B: Interleukin 28B.