Diagnosis and evaluation of chronic hepatitis C virus infection
- Norah A Terrault, MD, MPH
Norah A Terrault, MD, MPH
- Professor of Medicine
- University of California San Francisco
- Sanjiv Chopra, MD, MACP
Sanjiv Chopra, MD, MACP
- Editor-in-Chief — Gastroenterology/Hepatology
- Section Editor — General Hepatology; Gallbladder and Biliary Tract Disease
- Professor of Medicine
- Harvard Medical School
- Senior Consultant in Hepatology
- James Tullis Firm Chief
- Beth Israel Deaconess Medical Center
Diagnostic tests for hepatitis C virus (HCV) can be divided into two broad categories:
●Serologic assays that detect antibodies to hepatitis C
●Molecular assays that detect or quantify HCV RNA
Other investigations such as genotype testing, serum fibrosis panels and liver biopsy may help to predict the response to treatment and prognosis.
This topic will review the approach to diagnostic testing and evaluation of chronic HCV infection.
- Recommendations for Testing, Managing, and Treating Hepatitis C. Joint panel from the American Association of the Study of Liver Diseases and the Infectious Diseases Society of America. http://www.hcvguidelines.org/ (Accessed on August 01, 2016).
- Centers for Disease Control and Prevention (CDC). Testing for HCV infection: an update of guidance for clinicians and laboratorians. MMWR Morb Mortal Wkly Rep 2013; 62:362.
- Pereira BJ, Levey AS. Hepatitis C virus infection in dialysis and renal transplantation. Kidney Int 1997; 51:981.
- Lau JY, Davis GL, Brunson ME, et al. Hepatitis C virus infection in kidney transplant recipients. Hepatology 1993; 18:1027.
- Barrera JM, Bruguera M, Ercilla MG, et al. Persistent hepatitis C viremia after acute self-limiting posttransfusion hepatitis C. Hepatology 1995; 21:639.
- Seeff LB. Natural history of chronic hepatitis C. Hepatology 2002; 36:S35.
- Page K, Osburn W, Evans J, et al. Frequent longitudinal sampling of hepatitis C virus infection in injection drug users reveals intermittently detectable viremia and reinfection. Clin Infect Dis 2013; 56:405.
- Houghton M, Weiner A, Han J, et al. Molecular biology of the hepatitis C viruses: implications for diagnosis, development and control of viral disease. Hepatology 1991; 14:381.
- Gretch DR. Diagnostic tests for hepatitis C. Hepatology 1997; 26:43S.
- Kao JH, Lai MY, Hwang YT, et al. Chronic hepatitis C without anti-hepatitis C antibodies by second-generation assay. A clinicopathologic study and demonstration of the usefulness of a third-generation assay. Dig Dis Sci 1996; 41:161.
- Colin C, Lanoir D, Touzet S, et al. Sensitivity and specificity of third-generation hepatitis C virus antibody detection assays: an analysis of the literature. J Viral Hepat 2001; 8:87.
- Busch MP, Tobler LH, Tegtmeier G, et al. Use of third-generation hepatitis C virus (HCV) enzyme immunoassay (EIA) to resolve second-generation HCV EIA-reactive and second-generation recombinant immunoblot assay-indeterminate blood samples: data to support current Food and Drug Administration guidance on HCV lookback. Transfusion 2000; 40:10.
- Uyttendaele S, Claeys H, Mertens W, et al. Evaluation of third-generation screening and confirmatory assays for HCV antibodies. Vox Sang 1994; 66:122.
- Maheshwari A, Thuluvath PJ. Management of acute hepatitis C. Clin Liver Dis 2010; 14:169.
- Farci P, Alter HJ, Wong D, et al. A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. N Engl J Med 1991; 325:98.
- Kamili S, Drobeniuc J, Araujo AC, Hayden TM. Laboratory diagnostics for hepatitis C virus infection. Clin Infect Dis 2012; 55 Suppl 1:S43.
- Morris SJ, Shifrin HD, Feinberg A, Rogers AI. Duodenal leiomyoma as a cause of gastrointestinal hemorrhage. South Med J 1978; 71:470.
- Mullis CE, Laeyendecker O, Reynolds SJ, et al. High frequency of false-positive hepatitis C virus enzyme-linked immunosorbent assay in Rakai, Uganda. Clin Infect Dis 2013; 57:1747.
- Kim S, Kim JH, Yoon S, et al. Clinical performance evaluation of four automated chemiluminescence immunoassays for hepatitis C virus antibody detection. J Clin Microbiol 2008; 46:3919.
- Dufour DR, Talastas M, Fernandez MD, Harris B. Chemiluminescence assay improves specificity of hepatitis C antibody detection. Clin Chem 2003; 49:940.
- Gretch D, Lee W, Corey L. Use of aminotransferase, hepatitis C antibody, and hepatitis C polymerase chain reaction RNA assays to establish the diagnosis of hepatitis C virus infection in a diagnostic virology laboratory. J Clin Microbiol 1992; 30:2145.
- Gorrin G, Friesenhahn M, Lin P, et al. Performance evaluation of the VERSANT HCV RNA qualitative assay by using transcription-mediated amplification. J Clin Microbiol 2003; 41:310.
- Lok AS, Chien D, Choo QL, et al. Antibody response to core, envelope and nonstructural hepatitis C virus antigens: comparison of immunocompetent and immunosuppressed patients. Hepatology 1993; 18:497.
- Pereira BJ, Milford EL, Kirkman RL, et al. Prevalence of hepatitis C virus RNA in organ donors positive for hepatitis C antibody and in the recipients of their organs. N Engl J Med 1992; 327:910.
- Stockman LJ, Guilfoye SM, Benoit AL, et al. Rapid hepatitis C testing among persons at increased risk for infection--Wisconsin, 2012-2013. MMWR Morb Mortal Wkly Rep 2014; 63:309.
- Lee SR, Yearwood GD, Guillon GB, et al. Evaluation of a rapid, point-of-care test device for the diagnosis of hepatitis C infection. J Clin Virol 2010; 48:15.
- Lee SR, Kardos KW, Schiff E, et al. Evaluation of a new, rapid test for detecting HCV infection, suitable for use with blood or oral fluid. J Virol Methods 2011; 172:27.
- Shivkumar S, Peeling R, Jafari Y, et al. Accuracy of rapid and point-of-care screening tests for hepatitis C: a systematic review and meta-analysis. Ann Intern Med 2012; 157:558.
- Smith BD, Drobeniuc J, Jewett A, et al. Evaluation of three rapid screening assays for detection of antibodies to hepatitis C virus. J Infect Dis 2011; 204:825.
- Chevaliez S, Bouvier-Alias M, Brillet R, Pawlotsky JM. Overestimation and underestimation of hepatitis C virus RNA levels in a widely used real-time polymerase chain reaction-based method. Hepatology 2007; 46:22.
- Vermehren J, Kau A, Gärtner BC, et al. Differences between two real-time PCR-based hepatitis C virus (HCV) assays (RealTime HCV and Cobas AmpliPrep/Cobas TaqMan) and one signal amplification assay (Versant HCV RNA 3.0) for RNA detection and quantification. J Clin Microbiol 2008; 46:3880.
- Martinot-Peignoux M, Marcellin P, Gournay J, et al. Detection and quantitation of serum HCV-RNA by branched DNA amplification in anti-HCV positive blood donors. J Hepatol 1994; 20:676.
- Vermehren J, Maasoumy B, Maan R, et al. Applicability of Hepatitis C Virus RNA Viral Load Thresholds for 8-Week Treatments in Patients With Chronic Hepatitis C Virus Genotype 1 Infection. Clin Infect Dis 2016; 62:1228.
- Lontok E, Mani N, Harrington PR, Miller V. Closing in on the target: sustained virologic response in hepatitis C virus genotype 1 infection response-guided therapy. Clin Infect Dis 2013; 56:1466.
- Freiman JM, Tran TM, Schumacher SG, et al. Hepatitis C Core Antigen Testing for Diagnosis of Hepatitis C Virus Infection: A Systematic Review and Meta-analysis. Ann Intern Med 2016; 165:345.
- WHOM TO TEST
- DIAGNOSIS AND TESTING APPROACH
- Testing algorithm
- Nonreactive anti-HCV antibody
- - Severely immunocompromised and hemodialysis patients
- - Patients with acute hepatitis or recent exposure
- Reactive antibody and positive RNA test
- Reactive antibody and negative RNA test
- DIAGNOSTIC TESTS
- Antibody testing
- - Standard immunoassay testing
- - Rapid immunoassay tests
- - Self-collected tests
- - Recombinant immunoblot assay
- HCV RNA assays
- - Methods of RNA detection
- - Quantitative tests
- - Qualitative tests
- HCV core antigen test
- ADDITIONAL EVALUATION
- History and physical exam
- Basic laboratory testing
- HCV genotype testing
- Assessment of fibrosis stage
- Testing for HIV, hepatitis B, and hepatitis A
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS