Efficacy and Safety of Combination Therapy of Natural Human Interferon Beta and Ribavirin in Chronic Hepatitis C patients

Abstract

Objective The aim of this study was to evaluate the efficacy and safety of combination therapy of natural human interferon-beta and ribavirin for patients for whom prior interferon therapy was discontinued due to depression induced by interferon-alpha. Methods Inclusion criteria were as follows; 1) HCV-genotype 1b, 2) serum HCV RNA level of !100 KIU/mL, 3) stopping the prior interferon-alpha monotherapy or combination therapy of interferon-alpha and ribavirin due to the appearance of depression. A total of 14 were enrolled in this prospective cohort study. The treatment period of combination therapy was 48 weeks. Depression states, reflected by Beck depression inventories and Hamilton depression rating scale, were assessed during combination therapy. Nonparametric procedures were employed for the analysis of background features of the patients with sustained virological response (SVR) and without SVR. A p value of <0.05 was considered to indicate a significant difference. Results Five of 14 patients (37.5%) had SVR by the intention to treat analysis. The SVR rate in patients who showed negative HCV RNA at 12 and 24 weeks after the initiation of combination therapy was 100% (4/4) and 83.3% (5/6), respectively. All of the patients continued the combination therapy owing to disappearance of severely adverse events contained the exacerbation of depression. Combination therapy did not yield a statistical difference in Beck depression inventories and Hamilton depression rating scale. Conclusion The combination therapy of IFN-beta and ribavirin is a possible therapy selection for the patients for whom interferon therapy was discontinued due to depression induced by interferon-alpha.

Guidelines for the Management of Hepatitis C Virus Infection

“…A retrospective study of natural human IFN‐β + ribavirin combination therapy in the treatment of 40 cases with genotype 1b HCV infections reported fewer discontinuations due to adverse reactions, and only mild decreases in platelet counts . Even patients with a history of discontinuing IFN‐α therapy due to depression tolerated IFN‐β + ribavirin combination therapy well in terms of depressive symptoms and other adverse reactions . IFN therapy with natural human IFN‐β is therefore recommended in patients in whom IFN‐α therapy is not tolerated, for example, those with a history of depression.…”

“…If the previous treatment was IFN or Peg‐IFN monotherapy, as a general rule, retreatment should be with Peg‐IFN + ribavirin combination therapy. When Peg‐IFN‐α is contraindicated due to depression or depressive symptoms, IFN‐β can be used instead of Peg‐IFN . When the previous therapy included ribavirin, telaprevir + Peg‐IFN + ribavirin combination therapy should be used.…”

“…SVR rates ≥50% have been reported . When Peg‐IFN‐α is contraindicated due to depression or depressive symptoms, IFN‐β can be used instead of Peg‐IFN …”

Treatment of Chronic Hepatitis C with Viral-Suppression linked to Restoration of Innate-Immune Responses with Induction-Therapy with n-IFN-beta followed by Simeprevir

“…IFN-beta was previously shown to have different signaling and biological activities from those of IFN-alpha, and achieved a higher rate of viral clearance than IFN-alpha [18][19][20][21][22][23]. The incidence of AEs such as depression, alopecia, general fatigue, and hematological changes were lower during therapies with n-IFN-beta than those with IFN-alpha [24][25][26]. In constrict to the actions of IFN-alpha, IFN-beta and IFN-lambda signaling in the liver did not become refractory during stimulation of the IFN signaling transduction pathway.…”

Natural interferon-beta treatment for patients with chronic hepatitis C in Japan

“…We also observed a patient infected with HCV genotype 1 who failed to respond to interferon with or without ribavirin seven times but then achieved a SVR using natural interferon-beta plus ribavirin for 48 wk [25] . Arase et al [42] observed that re-treatment with natural interferon-beta plus ribavirin for 48 wk led to an SVR in 38% (5/14) of previously treated-patients infected with HCV genotype 1b and a high viral load; moreover, the SVR rates were 100% (4/4) and 83% (5/6) in patients who were negative for HCV RNA at 12 wk and 24 wk, respectively (Table 1). It has recently been reported that anti-interferonalpha neutralizing antibody is associated with a non-SVR to peginterferon-alpha plus ribavirin in chronic hepatitis C patients [43] .…”