Comparative Effectiveness of Antiviral Treatment for Hepatitis C Virus Infection in Adults: A Systematic Review

Oregon Health & Science University, Portland, USA.
Annals of internal medicine (Impact Factor: 17.81). 01/2013; 158(2):114-23. DOI: 10.7326/0003-4819-158-2-201301150-00576
Source: PubMed


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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Available from: Ngoc Wasson, Jun 22, 2015
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    • "Most relapses following historical treatment protocols as well as current protocols occur within 1–4 weeks after the end of treatment (EOT) time point. Yet, a minority of relapses occur months to years later [6] [7] [8]. Although the origin of these late relapses is uncertain, an increasing amount of data suggests that they may represent activation of an occult hepatitis C virus infection (OCI) [9] [10] [11] [12] [13]. "
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    ABSTRACT: Background. The prevalence of occult hepatitis C infection (OCI) in the population of HCV-RNA negative but anti-HCV positive individuals is presently unknown. OCI may be responsible for clinically overt recurrent disease following an apparent sustained viral response (SVR) weeks to years later. Purpose. To review the available current literature regarding OCI, prevalence, pathogenic mechanisms, clinical characteristics, and future directions. Data Sources. Searching MEDLINE, article references, and national and international meeting abstracts for the diagnosis of OCI (1990-2014). Data Synthesis. The long-term followup of individuals with an OCI suggests that the infection can be transient with the loss of detectable HCV-RNA in PPBMCs after 12-18 months or alternatively exist intermittently and potentially long term. The ultimate outcome of HCV infection is decided by interplay between host immune responses, antiviral therapies, and the various well-identified viral evasion mechanisms as well as the presence of HCV infection within extrahepatic tissues. Conclusion. The currently widely held assumption of a HCV-cure in individuals having had "SVR" after 8-12 weeks of a course of DAA therapy as recently defined may not be entirely valid. Careful longitudinal followup utilizing highly sensitive assays and unique approaches to viral isolation are needed.
    Gastroenterology Research and Practice 07/2015; 2015:579147. DOI:10.1155/2015/579147 · 1.75 Impact Factor
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    • "There has been one comprehensive review on the comparative effectiveness research for HCV by Chou et al published in 2013 . 13 Our study identified the most recent publication on the effectiveness of HCV therapies beyond this study , and also provided a careful review of the study . "
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    ABSTRACT: Background: With increasing treatment options for hepatitis C, evidence of comparative effectiveness of these treatment options is required to improve treatment outcomes. The purpose of this study was to evaluate the most recent comparative effectiveness research and suggest future directions for hepatitis C research. Methods: We identified and evaluated the literature on comparative effectiveness research and conducted a literature search for additional studies since the most current review. A review of ongoing clinical trials in hepatitis C was performed to assess how forthcoming research is addressing the research gaps and limitations. Results: Since a comprehensive comparative effectiveness research review by Chou et al new studies have been published, which were mostly consistent with the consensus in the literature. A few of them added to comparative effectiveness research knowledge by addressing issues of the likelihood of sustained virologic response in an older cohort, the effect of genomics and individualizing treatment duration, or the effect of delayed treatment. Research gaps and limitations of the existing comparative effectiveness research and future study needs were well identified in the second study from Chou et al. Some of the gaps and limitations were filled by additional research over the past year, though many of them still remained unanswered. Conclusion: To have complete information on the effectiveness of alternative treatments for hepatitis C virus, further research is needed on results in the general population, the effectiveness of treatment methods such as noninvasive treatment and individualized treatment, and the long-term effects of triple therapies. Additionally, evidence from a real-world setting is lacking. Methodologically thorough and independently funded retrospective research will help to generalize the effectiveness of current therapies for hepatitis C virus. Keywords: PEG-interferon, ribavirin, telaprevir, boceprevir
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    • "These data are in agreement with what we could observe in a larger population of HCV patients with or without MC during and after treatment with the standard of care dual therapy (Peg-IFN plus RBV; paper in preparation). In spite of the small size of the study population, suggesting that further prospective and controlled studies are needed, these findings are strengthened by the homogeneity of our patients in terms of the main variables affecting viral response, including HCV and IL28B genotypes , Caucasian ethnicity, type of therapy [22] as well as severity of liver disease (F3/F4), even if the patients with MC seemed to be older and 4 of the 5 MCS patients had cirrhosis (F4). The reasons for a lower propensity to eradicate HCV are at present unknown. "
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    ABSTRACT: Background Mixed cryoglobulinaemia is strongly related to hepatitis C virus infection. Treatment with peg-interferon and ribavirin has been indicated as first-line therapy for mild/moderate hepatitis C virus-related mixed cryoglobulinaemia. Aim To evaluate the safety and efficacy of triple boceprevir-based antiviral therapy in patients with or without mixed cryoglobulinaemia previously treated with peg-interferon and ribavirin, and with advanced liver disease. Methods Thirty-five hepatitis C virus-positive patients (17 with asymptomatic mixed cryoglobulinaemia, 5 with symptomatic mixed cryoglobulinaemia, and 11 without mixed cryoglobulinaemia) were treated with triple boceprevir-based antiviral therapy. Results In 19/22 cryoglobulinaemic subjects (86%), the addition of boceprevir induced cryocrit disappearance. Cryocrit behaviour was related to virological response, with improvement of symptoms upon undetectable viraemia and reappearance after virological breakthrough. The rate of sustained virological response was lower in cryoglobulinaemic patients than in patients without mixed cryoglobulinaemia (23.8% vs 70% respectively, p = 0.01). Conclusion Boceprevir-based therapy was safe and effective in cryoglobulinaemic patients. The correlation between direct inhibition of hepatitis C virus replication and clinical improvement in mixed cryoglobulinaemic patients is definitive proof of the key pathogenetic role played by viral replication. Further studies are needed to confirm and clarify the reduced virological response in patients with mixed cryoglobulinaemia.
    Digestive and Liver Disease 05/2014; 46(9). DOI:10.1016/j.dld.2014.05.017 · 2.96 Impact Factor
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