Comparative Effectiveness of Antiviral Treatment for Hepatitis C Virus Infection in Adults: A Systematic Review
ABSTRACT Multiple treatments are available for chronic hepatitis C virus (HCV) infection.
To compare benefits and harms of antiviral regimens for chronic HCV infection in treatment-naive adults.
English-language literature from MEDLINE (1947 to August 2012), the Cochrane Library Database, Embase, Scopus, PsychINFO, and clinical trial registries.
Randomized trials of antiviral treatments and cohort studies examining associations between sustained virologic response (SVR) after therapy and clinical outcomes.
Several investigators abstracted study details and quality by using predefined criteria.
No trial evaluated effectiveness of treatment on long-term clinical outcomes. Dual therapy with pegylated interferon alfa-2b plus ribavirin was associated with a lower likelihood of SVR than was pegylated interferon alfa-2a plus ribavirin (absolute difference, 8 percentage points [95% CI, 3 to 14 percentage points]) on the basis of 7 poor- to fair-quality trials. For genotype 2 or 3 infection, dual therapy for 12 to 16 weeks was associated with a lower likelihood of SVR than was therapy for 24 weeks, and lower doses of pegylated interferon alfa-2b were less effective than standard doses (2 to 4 fair-quality trials). For genotype 1 infection, fair-quality trials found that triple therapy with pegylated interferon, ribavirin, and either boceprevir (2 trials) or telaprevir (4 trials) was associated with a higher likelihood of SVR than was dual therapy (absolute difference, 22 to 31 percentage points). Compared with dual therapy, boceprevir triple therapy increased risk for hematologic adverse events and telaprevir triple therapy increased risk for anemia and rash. A large well-designed cohort study and 18 smaller cohort studies found that an SVR after antiviral therapy was associated with lower risk for all-cause mortality than was no SVR.
Trials involved highly selected populations. Observational studies did not always adequately control for confounders.
SVR rates for genotype 1 infection are higher with triple therapy that includes a protease inhibitor than with standard dual therapy. An SVR after antiviral therapy appears associated with improved clinical outcomes.
Agency for Healthcare Research and Quality.
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ABSTRACT: The first interferon-free regimens have been approved for the treatment of patients with chronic hepatitis C virus (HCV). In the liver transplant (LT) setting, these regimens are expected to have an important effect, because graft loss due to HCV recurrence is a serious problem after LT. The response to the hitherto conventional treatment with pegylated interferon and ribavirin is poor. The significantly better response rates achieved with boceprevir-based and telaprevir-based triple therapy have led to better graft and patient survival rates, but severe drug interactions with immunosuppressants limit the feasibility of this therapy for LT patients. With the approval of sofosbuvir in January 2014, of simeprevir in May 2014, and of daclatasvir in August 2014, three antiviral agents are now available and promise to be applicable without relevant adverse effects or negative interactions with immunosuppressants. Thus, 2014 marks the beginning of a new era of treatment options for HCV recurrence after LT. Although safety and efficacy studies of several interferon-free regimens for patients with HCV recurrence after LT have achieved good preliminary results, reports of clinical experiences with LT patients are scarce. The lack of randomized studies, the small number of enrolled and carefully selected patients, and the heterogeneity of these studies make the results questionable. Real-life experiences are eagerly awaited so that clinicians can estimate the usefulness and the pitfalls of these new regimens. Additionally, the high costs of these agents may limit their accessibility for many patients. The aim of this review is to summarize the current experience with and the expectations of the new direct-acting antiviral agents for LT patients.03/2015; 7(3):532-8. DOI:10.4254/wjh.v7.i3.532
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ABSTRACT: Hepatitis C virus (HCV) is a leading cause of chronic hepatitis and infects approximately three to four million people per year, about 170 million infected people in total, making it one of the major global health problems. In a minority of cases HCV is cleared spontaneously, but in most of the infected individuals infection progresses to a chronic state associated with high risk to develop liver cirrhosis, hepatocellular cancer, or liver failure. The treatment of HCV infection has evolved over the years. Interferon (IFN)-α in combination with ribavirin has been used for decades as standard therapy. More recently, a new standard-of-care treatment has been approved based on a triple combination with either HCV protease inhibitor telaprevir or boceprevir. In addition, various options for all-oral, IFN-free regimens are currently being evaluated. Despite substantial improvement of sustained virological response rates, some intrinsic limitations of these new direct-acting antivirals, including serious side effects, the risk of resistance development and high cost, urge the development of alternative or additional therapeutic strategies. Gene therapy represents a feasible alternative treatment. Small RNA technology, including RNA interference (RNAi) techniques and antisense approaches, is one of the potentially promising ways to investigate viral and host cell factors that are involved in HCV infection and replication. With this, newly developed gene therapy regimens will be provided to treat HCV. In this chapter, a comprehensive overview guides you through the current developments and applications of RNAi and microRNA-based gene therapy strategies in HCV treatment.Advances in Experimental Medicine and Biology 01/2015; 848:1-29. DOI:10.1007/978-1-4939-2432-5_1 · 2.01 Impact Factor
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ABSTRACT: Hepatitis C virus (HCV) infection still exists as a health concern among the transplant patients. Because of the severity of the disease, different responses to treatment, and side effects resulting from long therapeutic period, determination of genotypes and viral loads can help choose the best treatment protocols. This study aimed to determine the HCV genotypes and its distribution patterns among liver, kidney, and bone marrow recipient candidates across Iran, referred to Namazi Hospital, southern Iran. A total of 101 individuals, including 44 (43.6%) liver, 55 (54.5%) kidney, and 2 (2%) bone marrow recipient candidates, with ages ranging between 5 and 74 years (Mean ±SD: 46.53 ± 13.73 y) participated in this study. From those, whole blood sample were collected and anti-HCV antibodies, RNA detection, and genotyping were performed on plasma using commercial chromatographic immunoassay, TaqMan one-step real-time polymerase chain reaction (RT-PCR), and genotyping RT-PCR kits, respectively. The frequencies of anti-HCV antibodies, RNA, various genotypes, and the viral load were compared with respect to gender, age, and transplant recipient groups. Of 101 individuals, 47 (46.5%) were positive for anti-HCV antibodies and 34 (33.7%) for RNA with a significant difference (P < 0.05). RNA copy number ranged from 4.6 × 103 to 3.11 × 107 copies/mL, median: 2.92 × 106 copies/mL, with no statistical differences in all groups. Analyses revealed no significant differences between the frequencies of anti-HCV antibodies or RNA in different groups. The frequencies of the genotypes 1 (50%) and 3 (35.3%) were higher than those of the genotypes 2 (2.9%), 4 (2.9%), and undetermined one (8.8%). Genotype 1 was significantly more prevalent in liver transplant recipients, those older than 40 years, and male cases (P < 0.05). Considering the high frequency of genotypes 1 and 3 among the studied groups, it is suggested that before and after transplantation programs be improved to manage and treat the disease efficiently, based on the standard protocols for such genotypes in the region. Accordingly, the occurrence of post-transplant complications due to immunosuppression among all the recipients as well as reinfection in HCV infected liver transplant patients can be diminished.Jundishapur Journal of Microbiology 02/2015; 8(2). DOI:10.5812/jjm.16722 · 0.78 Impact Factor