scholarly journals Two-Year Follow-Up Analysis of Telaprevir-Based Antiviral Triple Therapy for HCV Recurrence in Genotype 1 Infected Liver Graft Recipients as a First Step towards Modern HCV Therapy

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Fritz Klein ◽  
Ruth Neuhaus ◽  
Dennis Eurich ◽  
Jörg Hofmann ◽  
Sandra Bayraktar ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Triple Therapy ◽  
Antiviral Treatment ◽  
Treatment Options ◽  
Dual Therapy ◽  
Liver Graft ◽  
Genotype 1 ◽  
Long Term Treatment ◽  
Hepatitis C Reinfection

Objective. The introduction of protease inhibitors telaprevir and boceprevir in 2011 had extended the antiviral treatment options especially in genotype 1 infected hepatitis C relapsers and nonresponders to interferon/ribavirin therapy. The aim of this study was to analyze the long-term treatment efficiency of telaprevir-based triple therapy for patients with hepatitis C reinfection after orthotopic liver transplantation. Patients and Methods. We included 12 patients with histologically confirmed graft fibrosis due to hepatitis C reinfection. The treatment duration was scheduled as 12 weeks of telaprevir-based antiviral triple therapy followed by 36 weeks of dual therapy with pegylated interferon/ribavirin. The patients were followed up for two years after the end of triple therapy. Results. Of the 12 patients, 6 (50%) completed the full 48 weeks of antiviral treatment. An end of treatment response and a sustained virological response 52 weeks after the end of the antiviral treatment course were achieved in 8/12 (67%) and 7/12 (58%) patients, respectively. Conclusion. Telaprevir-based triple therapy was shown to be a long-term effective but complex treatment option for individual patients with hepatitis C graft. With the recent improvements in hepatitis C therapy options telaprevir may not be recommended as a standard therapy for this indication anymore.

scholarly journals Economic Evaluation of Boceprevir for the Treatment of Patients with Genotype 1 Chronic Hepatitis C Virus Infection in Hungary

10.36469/9854 ◽  
2013 ◽  
Vol 1 (1) ◽  
pp. 62-82
Author(s):  
Raymond Odhiambo ◽  
Jagpreet Chhatwal ◽  
Shannon Allen Ferrante ◽  
Antoine El Khoury ◽  
Elamin Elbasha
Keyword(s):  
Liver Transplantation ◽  
Hepatitis C Virus ◽  
Cost Effectiveness ◽  
Hepatitis C ◽  
Triple Therapy ◽  
Dual Therapy ◽  
Hcv Infection ◽  
Genotype 1 ◽  
Life Years ◽  
Treatment Naïve

Background: Recent international, randomized, placebo-controlled clinical trials (SPRINT-2; RESPOND-2) demonstrated that the triple combination of peginterferon (PEG), ribavirin (RBV) and boceprevir (BOC) was more efficacious than the standard dual therapy of PEG and RBV in treatment of patients chronically infected with genotype 1 hepatitis C virus (HCV) infection. The objective of this study was to evaluate the cost-effectiveness of triple therapy in both treatment-naive and treatment-experienced patients in Hungary. Methods: A Markov model was developed to evaluate the long-term clinical benefits and the costeffectiveness of the triple therapy from the Hungarian payer perspective. Model states were fibrosis (F0–F4, defined using METAVIR fibrosis scores), decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), liver transplantation (LT), and liver-related deaths (LD). Efficacy was estimated from SPRINT-2 and RESPOND-2 studies. Disease progression rates and health state utilities used in the model were obtained from published studies. Estimates of probability of liver transplantation and cost were based on an analysis of the Hungarian Sick Fund database. All cost and benefits were discounted at 5% per year. Results: Compared to dual therapy, triple therapy was projected to increase the life expectancy by 0.98 and 2.42 life years and increase the quality-adjusted life years (QALY) by 0.59 and 1.13 in treatment-naive and treatment-experienced patients, respectively. The corresponding incremental cost-effectiveness ratios were HUF7,747,962 (€26,717) and HUF5,888,240 (€20,304) per QALY. The lifetime incidence of severe liver disease events (DC, HCC, LT, LD) were projected to decrease by 45% and 61% in treatment-naïve and treatment-experienced patients treated with triple therapy groups in comparison with PEG-RBV treatment. Conclusion: The addition of boceprevir to standard therapy for the treatment of patients with genotype 1 chronic HCV infection in Hungary is projected to be cost-effective using a commonly used willingness to pay threshold of HUF 8.46 million (3 times gross domestic product per capita).

What is expected from the novel triple combination antiviral treatment of patients infected with hepatitis C virus genotype 1?

2013 ◽  
Vol 154 (7) ◽  
pp. 257-261
Author(s):  
Anna Tusnádi ◽  
Anna Szabó
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Antiviral Treatment ◽  
Dual Therapy ◽  
Virologic Response ◽  
Triple Combination ◽  
Genotype 1 ◽  
Virus Genotype ◽  
Response Method

Introduction: Since May 2011, protease inhibitor/ribavirin/peginterferon combination has become the standard treatment for both treatment-naive and treatment-experienced patients infected with hepatitis C virus genotype 1. In Hungary, due to limited resources, the therapy of treatment-experienced patients might only be financed in the near future. Aim: The aim of this retrospective study was to find out characteristics of the patient group waiting for new triple combination in a single hepatology centre in Hungary, and to estimate the possible rate of their sustained virologic response. Method: Between January 2004 and September 2012, 269 patients with chronic hepatitis C virus infection were treated with peginterferon/ribavirin therapy. 142 patients failed to achieve sustained virologic response, but out of them, 93 individuals are the possible candidates for the triple antiviral treatment. In the latter group, the previous virologic response to dual therapy was determined. To register fibrosis scores, findings of liver biopsy and/or fibroelastography were also collected. Interleukin28B genotypes of 49 patients were determined. Results: Among the 93 treatment-experienced patients, 25 relapsed, 26 responded partially , 6 broke through, and 36 null-responders were found. 29% of patients had mild or moderate fibrosis and 71% of those already had severe fibrosis. Of the 49 patients with known interleukin28B genotype only 8 patients had the CC genotype. Conclusions: About half of the patients (mostly relapsers, and some partial responders as well) have a good chance of achieving sustained virologic response, which may be influenced by the fibrosis score. Orv. Hetil., 2013, 154, 257–261.

scholarly journals Adapted J6/JFH1-Based Hepatitis C Virus Recombinants with Genotype-Specific NS4A Show Similar Efficacies against Lead Protease Inhibitors, Alpha Interferon, and a Putative NS4A Inhibitor

2013 ◽  
Vol 57 (12) ◽  
pp. 6034-6049 ◽  
Author(s):  
Judith M. Gottwein ◽  
Sanne B. Jensen ◽  
Stéphanie B. N. Serre ◽  
Lubna Ghanem ◽  
Troels K. H. Scheel ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Alpha Interferon ◽  
Genotype 1 ◽  
Culture Systems ◽  
Genotype 1A ◽  
Long Term Treatment ◽  
Ns3 Protease

ABSTRACTTo facilitate studies of hepatitis C virus (HCV) NS4A, we aimed at developing J6/JFH1-based recombinants with genotype 1- to 7-specific NS4A proteins. We developed efficient culture systems expressing NS4A proteins of genotypes (isolates) 1a (H77 and TN), 1b (J4), 2a (J6), 4a (ED43), 5a (SA13), 6a (HK6a), and 7a (QC69), with peak infectivity titers of ∼3.5 to 4.5 log10focus-forming units per ml. Except for genotype 2a (J6), growth depended on adaptive mutations identified in long-term culture. Genotype 1a, 1b, and 4a recombinants were adapted by amino acid substitutions F772S (p7) and V1663A (NS4A), while 5a, 6a, and 7a recombinants required additional substitutions in the NS3 protease and/or NS4A. We demonstrated applicability of the developed recombinants for study of antivirals. Genotype 1 to 7 NS4A recombinants showed similar responses to the protease inhibitors telaprevir (VX-950), boceprevir (Sch503034), simeprevir (TMC435350), danoprevir (ITMN-191), and vaniprevir (MK-7009), to alpha interferon 2b, and to the putative NS4A inhibitor ACH-806. The efficacy of ACH-806 was lower than that of protease inhibitors and was not influenced by changes at amino acids 1042 and 1065 (in the NS3 protease), which have been suggested to mediate resistance to ACH-806 in replicons. Genotype 1a, 1b, and 2a recombinants showed viral spread under long-term treatment with ACH-806, without acquisition of resistance mutations in the NS3-NS4A region. Relatively high concentrations of ACH-806 inhibited viral assembly, but not replication, in a single-cycle production assay. The developed HCV culture systems will facilitate studies benefitting from expression of genotype-specific NS4A in a constant backbone in the context of the complete viral replication cycle, including functional studies and evaluations of the efficacy of antivirals.

Successful treatment of hepatitis C reinfection with interferon-alpha2b and ribavirin after liver transplantation. A long-term follow-up.

2005 ◽  
Vol 25 (4) ◽  
pp. 717-722 ◽  
Author(s):  
Suleyman Yedibela ◽  
Detlef Schuppan ◽  
Volker Muller ◽  
Vera Schellerer ◽  
Andrea Tannapfel ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Hepatitis C ◽  
Successful Treatment ◽  
Long Term Follow Up ◽  
Hepatitis C Reinfection

scholarly journals Hepatitis C virus-associated cryoglobulinemic vasculitis: A 20-year experience with treatment

2017 ◽  
Vol 89 (5) ◽  
pp. 46-52 ◽  
Author(s):  
T M Ignatova ◽  
L V Kozlovskaya ◽  
N B Gordovskaya ◽  
O A Chernova ◽  
S Yu Milovanova ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Combined Therapy ◽  
Multivariate Logistic Regression Analysis ◽  
Virologic Response ◽  
Term Treatment ◽  
Cryoglobulinemic Vasculitis ◽  
Multidisciplinary Therapy ◽  
Long Term Treatment

Aim. To summarize the experience of a multidisciplinary therapy hospital in treating patients with hepatitis C virus (HCV)-associated cryoglobulinemic vasculitis (CV). Subjects and methods. Seventy-two patients (mean age, 49.4±10.3 years) with HCV-associated CV were examined and followed up for an average period of 2.8±3.6 years. The efficiency of traditional (corticosteroids ± cyclophosphamide) and selective (rituximab) immunosuppressive therapy (IST) was estimated in 31 and 15 observations, respectively, and that of antiviral therapy (AVT) in 25. Vasculitis activity was assessed using the Birmingham vasculitis activity score (BVAS). The patients’ survival was studied; multivariate logistic regression analysis was carried out. Results. 24 (33.4%) of the 72 patients had a stage of liver cirrhosis (LC). The pretreatment mean BVAS was 11.9±7.2 (range 2 to 36). Severe CV (BVAS ≥15) was present in 30.6% of the patients. AVT was accompanied by achievement of sustained virologic response in 48% of the patients, clinical remission in 68% and had an advantage over IST in relation to long-term treatment results. Rituximab was significantly more effective than traditional immunosuppressants (remission rates of 73 and 13%, respectively). Combined therapy (rituximab and AVT) was most effective in patients with severe forms of vasculitis. Sixteen patients died from complications of vasculitis (37.5%), infection (37.5%), and LC (25%). The factors adversely affecting prognosis were age >55 years (odds ratio (OR), 4.49), the presence of LC (OR, 3.68), renal failure (OR, 4.66) and the use of glucocorticosteroids (OR, 3.91). Conclusion. HCV-associated CV can determine the prognosis of chronic HСV infection. AVT is the treatment of choice in all patients with HСV-associated CV. AVT must be combined with rituximab therapy in patients with severe forms of vasculitis.

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