Roger Chou, MD; Daniel Hartung, PharmD, MPH; Basmah Rahman, MPH; Ngoc Wasson, MPH; Erika Barth Cottrell, PhD, MPP; Rongwei Fu, PhD
Disclaimer: The findings and conclusions in this document are those of the authors, who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.
Acknowledgment: The authors thank Robin Paynter, MLIS; Rose Campbell, MLIS; AHRQ Task Order Officer Christine Chang, MD, MPH; and USPSTF Medical Officer Iris Mabry-Hernandez, MD, MPH. They also thank Tracy Dana, MLS; Christina Bougatsos, MPH; and Ian Blazina, MPH, from Oregon Health & Science University, who assisted in data extraction and quality checking.
Grant Support: By AHRQ (contract 290-2007-10057-I, task order 8), Rockville, Maryland.
Potential Conflicts of Interest: Disclosures can be found at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-1658.
Requests for Single Reprints: Roger Chou, MD, 3181 SW Sam Jackson Park Road, Mail Code BICC, Portland, OR 97239; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Chou, Hartung, Rahman, Wasson, Cottrell, and Fu: 3181 SW Sam Jackson Park Road, Mail Code BICC, Portland, OR 97239.
Author Contributions: Conception and design: R. Chou, D. Hartung.
Analysis and interpretation of the data: R. Chou, D. Hartung, N. Wasson, E.B. Cottrell, R. Fu.
Drafting of the article: R. Chou, D. Hartung.
Critical revision of the article for important intellectual content: R. Chou, D. Hartung, N. Wasson, R. Fu.
Final approval of the article: R. Chou, D. Hartung, R. Fu.
Statistical expertise: R. Chou, D. Hartung, R. Fu.
Obtaining of funding: R. Chou.
Administrative, technical, or logistic support: B. Rahman, N. Wasson.
Collection and assembly of data: R. Chou, D. Hartung, B. Rahman, N. Wasson.
Chou R, Hartung D, Rahman B, Wasson N, Cottrell EB, Fu R. Comparative Effectiveness of Antiviral Treatment for Hepatitis C Virus Infection in Adults: A Systematic Review. Ann Intern Med. 2013;158:114-123. doi: 10.7326/0003-4819-158-2-201301150-00576
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Published: Ann Intern Med. 2013;158(2):114-123.
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.
Analytic framework for treatment of HCV in adults.
This analytic framework outlines the population, interventions, and outcomes considered in the review. It is a modified version of a larger framework depicting the effect of both screening for and treatment of hepatitis C in adults. This figure focuses on the treatment portion of the framework. The population includes adults with chronic HCV infection. The interventions include pegylated interferon alfa-2a with ribavirin or pegylated interferon alfa-2b with ribavirin, with or without the protease inhibitors telaprevir or boceprevir. Intermediate outcomes include liver function, sustained virologic remission, and histologic changes. Final outcomes include morbidity and mortality from HCV (including hepatic cirrhosis, hepatocellular carcinoma, liver transplantation rates, and quality of life) and harms of antiviral therapies (including influenza-like symptoms, hematologic effects, and psychiatric effects). HCV = hepatitis C virus; KQ = key question.
* Including but not limited to HCV genotype, age, race, sex, stage of disease, or genetic markers.
Summary of evidence search and selection.
For key questions, see Appendix Figure 1. Reproduced from reference 11.
* Some studies applied to more than 1 key question. Studies of induction versus fixed-dose regimens and outcomes related to quality of life and histologic changes are not reported here but can be found in the full report (11).
Appendix Table 1.
Summary of Evidence on Comparative Effectiveness of Treatment for Hepatitis C
Appendix Table 2.
Trials Comparing Dual-Therapy Regimens
Sustained virologic response, comparisons of dual-therapy regimens.
Relative risks >1 favor dual therapy with pegylated interferon alfa-2b over dual therapy with pegylated interferon alfa-2a, 24 wk over 12 to 16 wk, and lower-dose versus higher-dose pegylated interferon alfa-2b.
Appendix Table 3.
Trials of Triple Therapy With Boceprevir or Telaprevir, Pegylated Interferon, and Ribavirin
Sustained virologic response, triple therapy with a protease inhibitor versus dual therapy.
The boceprevir regimen consisted of 4 wk of dual-therapy lead-in with pegylated interferon alfa-2b plus ribavirin, followed by the addition of boceprevir for 44 more wk. The telaprevir regimen consisted of 12 wk of telaprevir, pegylated interferon alfa-2a or -2b, and ribavirin, followed by 12 wk of dual therapy (pegylated interferon plus ribavirin without telaprevir). Relative risks >1 favor triple therapy.
Appendix Table 4.
Harms of Triple Therapy With Boceprevir or Telaprevir With Pegylated Interferon, and Ribavirin Versus Dual Therapy With Pegylated Interferon α-2b Plus Ribavirin
Appendix Table 5.
Sustained Virologic Response and Clinical Outcomes Summary Results
Clinician Research Summary.
This article, "Comparative Effectiveness of Anitviral Treatment for Hepatitis C Virus Infection in Adults: A Systematic Review," is derived from a systematic review from the Agency for Healthcare Research and Quality (AHRQ) titled Treatment for Hepatitis C Virus Infection in Adults, CER No. 76. To facilitate use of this evidence in clinical decision making, AHRQ has created additional materials for clinicians and patients.
This Clinician Research Summary provides the graded findings of the review within the context of clinical practice to assist clinicians in shared decision making with their patients. It includes evidence of benefits and harms for treatment options, a discussion of current gaps in knowledge, and suggested topics for conversations with patients or caregivers. The summary is a brief synopsis of the evidence findings from the review and is not intended to serve as recommendations or guidelines.
This summary was developed by the John M. Eisenberg Center for Clinical Decisions and Communications Science at Baylor College of Medicine, Houston, TX, which is under a contract (#HHSA290200810015C) with the Agency for Healthcare Research and Quality.
Consumer Review of the Research.
This Consumer Review of the Research is written in plain language to educate patients or caregivers about the research. The summary includes evidence of benefits and side effects for treatment options to enable discussion and shared decision making with a clinician. It also includes information on patient risk factors, available treatments, and suggestions of questions to ask a clinician during an office visit
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