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

Abstract

Complications associated with hepatitis C virus (HCV) infection may be prevented by viral eradication. Response rates with direct-acting antivirals regimens are generally lower in chronic hepatitis C (CHC) patients who have failed to respond to previous interferon (IFN) treatments. HCV persistence in the host results from in efficient innate and adaptive immune responses. The resolution of a HCV infection may restore impairments in innate and adaptive immunities. Our previous study suggested that induction treatment with natural (n)-IFN-beta followed by maintenance treatment with n-IFN-alpha restored innate immune responses, as indicated by the significant increase of IL-12, and IL-15 and significant decrease of CXCL-8. Persistent virologic clearance and the restoration of innate immune responses with Simeprevir plus Pegylated (Peg) -IFN-alpha/ribavirin (RBV) were more likely to result in a sustained virologic response (SVR). On the basis of these findings, we conducted to treat a CHC patient with genotype 1b, a high viral load, a prior null response to IFN treatments and chronic active hepatitis with advanced fibrosis using induction therapy with n-IFN-beta followed by Simeprevir plus Peg-IFN-alpha-2b/RBV. This is the first case of difficult-to-treat CHC with genotype 1b, a high viral load, null response to previous IFN treatment and advanced hepatic fibrosis that was successfully treated with induction therapy using n-IFN-beta, which induced the viral clearance of serum HCV RNA, followed by Simeprevir plus Peg-IFN-alpha-2b/RBV. Persistent viral clearance linked to restoration of innate immune responses and SVR were achieved 12 weeks after cessation of the treatment without virologic breakthrough or relapse and sustained biochemical response. Anemia and thrombocytopenia were managed without discontinuation of the treatment. Induction therapy with n-IFN-beta followed by Simeprevir plus Peg-IFN-alpha-2b/RBV was tolerated well and only mild adverse effects were noted. It also effectively eradicated HCV infection in a difficult-to-treat CHC patient with advanced fibrosis.

A Protease Inhibitor with Induction Therapy with Natural Interferon-β in Patients with HCV Genotype 1b Infection

“…The benefits of IT with CPIT in enhancing RVR and EVR rates may be relevant in treatment strategies involving the combination of IT with CPIT with nIFN-β followed by PR with DAAs in difficult-to treat CHC patients. In our previous study [ 23 ], we demonstrated that a difficult-to-cure patient with HCV genotype 1b, who was a prior null responder to IFN treatments and had chronic active hepatitis with advanced fibrosis was successfully treated by IT with CPIT with nIFN-β followed by PI (simeprevir) with PR, and that these treatments were tolerated well with only mild AEs being noted. The present study showed that the virologic responses rates of IT with CPIT with nIFN-β followed by PI with PR were significantly higher than those of IT with CPIT with nIFN-β followed by PR alone in patients infected with HCV genotype 1b and high viral loads.…”

“…In addition to the restoration of innate immune responses due to viral supression with CPIT during the initial early course of therapy, persistent virologic clearance with triple therapy consisting of protease inhibitor (PI) (simeprevir or vaniprevir) with PR is more likely to result in higher RVR, EVR, ETVR, and SVR. We previously reported that a difficult-to-cure CHC patient with genotype 1b, a high viral load, null response to previous IFN treatments, and advanced hepatic fibrosis was treated by IT with n-IFN-β followed by triple therapy with simeprevir with PR, which resulted in SVR and a sustained biochemical response (SBR) [ 23 ]. On the basis of these findings, we herein compare the efficacies and safeties of CPIT with n-IFN-β as induction therapy followed by triple therapy with PI with PR and CPIT with n-IFN-β followed by PR alone in CHC patients with genotype 1b and high viral loads.…”

Induction Therapy with Natural Interferon-Beta and a Protease Inhibitor Restores Innate-Immune Responses and Suppresses Chronic Hepatitis C Infection

“…The efficacy and safety of IT with n-IFN-beta followed by Peg-IFN-alpha and RBV (PR) alone were compared with those of IT plus protease inhibitor (PI) plus PR (NCT with a PI) in patients with CHC with GT 1b and high viral load. IT plus PI and PR is beneficial for treating patients with intractable CHC [12]. CPIT with n-IFN-beta as IT, followed by triple therapy with PI and PR is more effective than IT with n-IFN-beta followed by PR alone in the treatment of patients with intractable CHC with GT 1b and high viral load.…”

“…Thus, more effective, tolerable, and/or tailored therapies are required for patients with a prior null response to PR therapy [18]. In addition to the restoration of innate immune responses due to viral suppression with CPIT during the initial early course of therapy, persistent virologic clearance with CPIT followed by triple therapy consisting of PI (Simeprevir or Vaniprevir) with PR is more likely to result in higher RVR, EVR, ETVR, and SVR than those with NCT alone [12]. On the basis of these findings, I treated a patient with CHC with GT 1b, a high viral load, a prior null response to IFN treatments and chronic active hepatitis with advanced fibrosis by using IT with n-IFN-beta followed by triple therapy with Simeprevir (Sovriad ® , Janssen, Titusville, NJ, USA, 100 mg/day per os, daily), Peg-IFN-alpha and RBV, which resulted in SVR and SBR.…”

“…Levels of serum alanine amino transferase (ALT) decreased within 3 weeks after the initiation of CPIT and were only slightly elevated during the CPIT. After the initiation of triple therapy, levels of serum ALT decreased to a normal range and subsequently remained normal (SBR) (Figure 4) [12].…”