Rebecca L. Morgan, MPH; Brittney Baack, MPH; Bryce D. Smith, PhD; Anthony Yartel, MPH; Marc Pitasi, BS; Yngve Falck-Ytter, MD
Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Acknowledgment: The authors thank Rebecca K. Satterthwaite, MS, for help with search strategies and reference management.
Financial Support: By the Division of Viral Hepatitis at the Centers for Disease Control and Prevention.
Potential Conflicts of Interest: None disclosed. Forms can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-2021.
Requests for Single Reprints: Rebecca L. Morgan, MPH, Centers for Disease Control and Prevention, 1600 Clifton Road, MS G-37, Atlanta, GA 30333; e-mail, firstname.lastname@example.org.
Current Author Addresses: Ms. Morgan, Ms. Baack, Dr. Smith, and Mr. Yartel: Centers for Disease Control and Prevention, 1600 Clifton Road, MS G-37, Atlanta, GA 30333.
Mr. Pitasi: Emory University, 1518 Clifton Road, Atlanta, GA 30322.
Dr. Falck-Ytter: Louis Stokes Cleveland Veterans Affairs Medical Center, 10701 East Boulevard, Cleveland, OH 44106.
Author Contributions: Conception and design: R.L. Morgan, B. Baack, Y. Falck-Ytter.
Analysis and interpretation of the data: R.L. Morgan, B. Baack, A. Yartel, Y. Falck-Ytter.
Drafting of the article: R.L. Morgan, B. Baack, B.D. Smith, A. Yartel, Y. Falck-Ytter.
Critical revision of the article for important intellectual content: B.D. Smith, A. Yartel, Y. Falck-Ytter.
Final approval of the article: R.L. Morgan, B. Baack, B.D. Smith, A. Yartel, M. Pitasi, Y. Falck-Ytter.
Provision of study materials or patients: R.L. Morgan, B. Baack.
Statistical expertise: R.L. Morgan, A. Yartel, Y. Falck-Ytter.
Administrative, technical, or logistic support: R.L. Morgan, M. Pitasi.
Collection and assembly of data: R.L. Morgan, B. Baack, M. Pitasi, Y. Falck-Ytter.
Morgan RL, Baack B, Smith BD, Yartel A, Pitasi M, Falck-Ytter Y. Eradication of Hepatitis C Virus Infection and the Development of Hepatocellular Carcinoma: A Meta-analysis of Observational Studies. Ann Intern Med. 2013;158:329-337. doi: 10.7326/0003-4819-158-5-201303050-00005
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Published: Ann Intern Med. 2013;158(5_Part_1):329-337.
Hepatitis C virus (HCV) is a leading cause of hepatocellular carcinoma (HCC). In the United States, this form of cancer occurs in approximately 15 000 persons annually. A systematic review of the evidence is needed to assess the benefits of treatment of HCV-infected persons on development of HCC.
To systematically review observational studies to determine the association between response to HCV therapy and development of HCC among persons at any stage of fibrosis and those with advanced liver disease.
MEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science, and the Database of Abstracts of Reviews and Effectiveness from inception through February 2012.
English-language observational studies that compared therapy-derived sustained virologic response (SVR) with no response to therapy among HCV-infected persons, targeted an adult population, and had an average follow-up of at least 2 years.
Two investigators independently extracted data into uniform relative risk measures. The Grading of Recommendations Assessment, Development and Evaluation framework was used to determine the quality of the evidence.
Thirty studies fulfilled the inclusion criteria, and 18 provided adjusted effect estimates that were used to calculate pooled relative risks. Among HCV-infected persons, SVR was associated with reduced risk for HCC (relative risk for all persons, 0.24 [95% CI, 0.18 to 0.31], moderate-quality evidence; advanced liver disease hazard ratio, 0.23 [CI, 0.16 to 0.35], moderate-quality evidence).
In the meta-analyses, some variables could not be controlled for because of the observational design of the included studies.
Sustained virologic response after treatment among HCV-infected persons at any stage of fibrosis is associated with reduced HCC. The evidence was determined to be of moderate quality.
Centers for Disease Control and Prevention.
Summary of evidence search and selection.
DARE = Database of Abstracts of Reviews and Effectiveness; NR = nonresponse; SVR = sustained virologic response.
Appendix Table 1. Search Strategy
Table 1. Characteristics of Included Studies
Appendix Table 2. Risk of Bias of Included Studies
Table 2. GRADE Evidence Profile for Association of SVR Versus Nonresponse to Treatment With the Development of HCC Among HCV-Infected Persons
Forest plot of adjusted hazard effects in persons at all stages of fibrosis.
IV = inverse variance; NR = nonresponse; SVR = sustained virologic response.
Forest plot of adjusted hazard effects in persons with advanced liver disease.
Funnel plots of studies reporting adjusted (top) and unadjusted (bottom) analyses (all stages of fibrosis and advanced fibrosis).
OR = odds ratio.
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