This statement summarizes the U.S. Preventive Services Task Force (USPSTF) recommendations on screening for hepatitis C virus (HCV) infection based on the USPSTF's examination of evidence specific to asymptomatic persons for HCV testing and treatment.

• Established risk factors for HCV infection include current or past intravenous drug use, transfusion before 1990, dialysis, and being a child of an HCV-infected mother. Surrogate markers, such as high-risk sexual behavior (particularly sex with someone infected with HCV) and the use of illegal drugs, such as cocaine or marijuana, have also been associated with increased risk for HCV infection. The proportion of people who received blood or blood product transfusions before 1990 will continue to decline, and HCV infection will be associated mainly with intravenous drug use and, to some extent, unsafe sexual behaviors.
• Initial testing for HCV infection is typically done by enzyme immunoassay (EIA). In a population with a low prevalence of HCV infection (e.g., 2 percent), approximately 59 percent of all positive tests using the third-generation EIA test with 97 percent specificity would be false positive. As a result, confirmatory testing is recommended with the strip recombinant immunoblot assay (third-generation RIBA).
• Important predictors of progressive HCV infection include older age at acquisition; longer duration of infection; and presence of comorbid conditions, such as alcohol misuse, HIV infection, or other chronic liver disease. Asymptomatic individuals with HCV infection identified through screening may benefit from interventions designed to reduce liver injury from other causes, such as counseling to avoid alcohol misuse and immunization against hepatitis A and hepatitis B. However, there is limited evidence of the effectiveness of these interventions.

HCV infection is the most common bloodborne pathogen in the United States.³ Eight thousand to 10,000 deaths are associated with HCV infection annually.^3-5 The yearly incidence of HCV infection during the 1980s was estimated to be 230,000 cases per year and has declined to 25,000 cases in 2001 with the advent of measures to screen blood products for HCV infection.¹ HCV infection related end-stage liver disease accounts for more than 30 percent of adult liver transplantation. HCV infection is acquired primarily by large or repeated percutaneous exposure to blood. The natural course of chronic HCV infection varies widely. A proportion of patients with chronic HCV infection may have only mild liver disease even after decades of infection or may never develop histologic evidence of liver disease.⁶ The National Health and Nutrition Epidemiologic Survey-III (NHANES-III), conducted from 1988 through 1994, found a prevalence of 2.3 percent of anti-HCV antibody in adults older than 20 in the U.S. population.⁷ The National Hepatitis Screening Survey found that intravenous drug use was the strongest risk factor for HCV infection (adjusted odds ratio [OR], 23), followed by hemodialysis, sex with an intravenous drug user, a history of blood transfusion, and male gender.⁸ In cross-sectional studies of intravenous drug users, 65 percent of those who reported injecting drugs for 1 year or less and 50 percent to 90 percent of all intravenous drug users are infected with HCV.^9-14

The USPSTF conducted a systematic review of the evidence on the effectiveness of screening tests and interventions aimed at improving intermediate and long-term health outcomes for HCV-infected adults. The review evaluated the magnitude of benefit of screening adults at average risk and those at high risk for HCV infection. Enzyme immunoassay (EIA) is the initial screening test for anti-HCV antibodies. Polymerase Chain Reaction (PCR) is considered the gold standard in HCV-infection testing, as it is the only blood test for active infection. In 4 studies reviewed, third-generation EIA had a sensitivity ranging from 94 percent to 100 percent when compared with PCR or RIBA. One good quality study found EIA specificity to be 97 percent using PCR as the reference standard.¹⁵ In populations with a low prevalence of HCV infection (2 percent), approximately 59 percent of all positive tests using the third-generation EIA test with 97 percent specificity would be false-positive tests.¹⁶ Since the prevalence of HCV infection in high-risk groups is 50 percent to 90 percent, the yield of screening in individuals at increased risk would be substantially higher. The RIBA has 100 percent sensitivity when compared with EIA, but is a more expensive test. In two other studies, RIBA was found to have a sensitivity of 80 percent and 100 percent, respectively, compared with PCR.¹

Because screening detects the presence of anti-HCV antibodies but does not discriminate between persistent and resolved infection, medical evaluation to determine the need for treatment of HCV infection includes PCR for viremia along with transaminase levels and liver biopsy. Pretreatment liver biopsy is currently recommended by the National Institutes of Health (NIH).^17-19

To determine the magnitude of benefit of screening average- and high-risk adults for HCV infection, the USPSTF evaluated the evidence for the prevalence of HCV infection in these populations, the effectiveness of screening tests, the rate of disease progression, and the effectiveness of interventions in preventing disease progression. The prevalence estimates of HCV infection in average-risk groups and high-risk groups, such as intravenous drug users, vary significantly: 2.3 percent for those at average risk and 50 percent to 90 percent for those at high risk. No studies have evaluated the rate of disease progression in asymptomatic patients.

Potential harms from screening include effects of both false-positive and true-positive tests, which may lead to anxiety, effects on partner relationships, unnecessary liver biopsies, and treatment regimens that have a high incidence of adverse effects. Although false-positive tests do occur, they are uncommon if proper confirmatory tests are performed.¹⁶ The harmful effects of true-positive results include anxiety and interventions in patients who would not have progressed to chronic liver disease.² The majority of patients receiving interferon-based therapies alone or in conjunction with ribavirin experience adverse effects. Patient withdrawal due to adverse effects from interferon monotherapy averaged 5 percent, and patient withdrawal from combination therapy ranged from 10 percent to 20 percent.² The most common adverse event was flu-like syndrome, including myalgia, fatigue, headache, and fever.

Based on several cohort studies, cirrhosis develops in 10 percent to 20 percent of persons with chronic hepatitis C over a period of 20 to 30 years. Among those who are referred for treatment of HCV infection, only 30 to 40 percent were eligible for therapy and received treatment. Results from 3 well-conducted randomized controlled trials (RCTs) show that combination anti-viral therapy with pegylated interferon and ribavirin is effective in achieving a sustained virologic response, which is an intermediate health outcome, in 54 percent to 60 percent of patients 6 to 12 months after treatment.² Systematic reviews indicate lower efficacy (33%-41%) of non-pegylated interferon with ribavirin.² Because treatment of HCV infection is a relatively recent development, there is limited evidence of the long-term effectiveness of anti-viral therapy, especially combination therapy, on outcomes such as morbidity or mortality from chronic liver disease. Results from some studies, mostly international, suggest that patients treated with interferon have lower rates of hepatocellular cancer and lower mortality than untreated patients, but this association could reflect other differences between treated and untreated patients.² The extent to which these results are generalizable to the U.S. population is uncertain. There are limited data to determine the benefit of other interventions in infected patients, including immunization against hepatitis A and B and counseling to reduce damage from alcoholism and to decrease the probability of transmission.²

Currently, there is little evidence to determine which patients are likely to benefit from screening and current treatment regimens. Because the prevalence of HCV infection and rate of disease progression is low in adults at average risk, the harms of HCV-infection screening outweigh the benefits in this population. Those at high risk for HCV infection are also at increased risk for progression to cirrhosis and would be more likely to benefit from HCV-infection therapy. Although there is good evidence that anti-viral therapy improves intermediate outcomes, there is, as yet, no evidence that newer treatment regimens for HCV infection (pegylated interferon plus ribavirin) improve long-term health outcomes. As a result, the magnitude of the net benefit of screening high-risk adults for HCV infection is unknown.

Important gaps remain in the information needed to determine the benefits of hepatitis C screening. Because of the variability in the progression of HCV infection, it would be useful to define more precisely the rate of progression to clinically important liver disease among patients detected by screening and to identify those who would most likely benefit from therapy. Studies are also needed to evaluate the effect of diagnosis and treatment on the quality of life. Studies are needed on the benefit of other interventions, such as counseling to prevent alcohol misuse and vaccinations for hepatitis A and hepatitis B, in HCV-infected individuals. Studies of risk factor assessment are needed to guide selective screening strategies. Since liver biopsy is part of the current workup for HCV infection and is a potentially harmful invasive procedure, studies to evaluate outcomes of patients who do not undergo biopsy would help to determine whether all or only selected patients should undergo this procedure.

Recommendations for HCV-infection screening from other major entities can be obtained from the NIH Consensus Panel (2002)¹⁷ and from the Centers for Disease Control and Prevention (CDC).¹⁶ Both recommend screening for groups at high risk for HCV infection, although the way they define high-risk groups differs slightly. Both recommend screening for users of injection drugs, hemodialysis patients, and recipients of transfusions or organs (CDC recommendations cover the years before 1992, and NIH recommendations cover the years before 1990). In addition, the NIH panel recommends screening for individuals with multiple sexual partners, spouses or household contacts of HCV-infected patients, and those who share instruments for intranasal cocaine use. The CDC recommends screening for children born to mothers infected with HCV, those who received clotting factor concentrates before 1987, those with occupational exposure to HCV-positive blood, and patients with persistently abnormal alanine aminotransferase levels. Other groups identified by the CDC for whom routine screening is uncertain include recipients of transplanted tissue, those who use intranasal cocaine and other noninjecting illegal drugs, persons with a history of tattooing or body piercing, those with a history of multiple sex partners or sexually transmitted diseases, and long-term steady partners of HCV-positive persons. The CDC guidelines for reporting HCV test results can be accessed at http://www.cdc.gov/mmwr/PDF/rr/rr5203.pdf.

1. Chou R. Screening for Hepatitis C Virus Infection: Systematic Evidence Review No. 24. (Prepared by the Oregon Evidence-based Practice Center, Oregon Health & Science University under Contract No. 290-97-0018). Rockville, MD. Agency for Healthcare Research and Quality. March 2004. (Available at: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=es24.)
2. Chou R, Clark EC, Helfand MH. Screening for hepatitis C Virus Infection: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2004;140(6):465-79.
3. Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47:(RR-19):1-39.
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13. Bell J, Batey RG, Farrell GC, et al. Hepatitis C virus in intravenous drug users. Med J Aust 1990;153:(5):274-6.
14. Alter MJ, Hadler SC, Judson FN, et al. Risk factors for acute non-A, non-B hepatitis in the United States and association with hepatitis C virus infection. JAMA 1990;264:(17):2231-5.
15. Huber KR, Sebesta C, Bauer K. Detection of common hepatitis C virus subtypes with a third-generation enzyme immunoassay. Hepatology 1996;24:(3):471-3.
16. Alter MJ, Kuhnert WL, Finelli L. Guidelines for laboratory testing and result reporting of antibody to hepatitis C virus. Centers for Disease Control and Prevention. MMWR 2003;52:(RR-3):1-16.
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19. Perrillo RP. The role of liver biopsy in hepatitis C. Hepatology 1997;26:(Suppl 1):57S-61S.

Members of the U.S. Preventive Services Task Force* are Alfred O. Berg, M.D., M.P.H., Chair, USPSTF (Professor and Chair, Department of Family Medicine, University of Washington, Seattle, WA); Janet D. Allan, Ph.D., R.N., C.S., Vice-chair, USPSTF (Dean, School of Nursing, University of Maryland Baltimore, Baltimore, MD); Ned Calonge, M.D., M.P.H. (Acting Chief Medical Officer, Colorado Department of Public Health and Environment, Denver, CO); Paul Frame, M.D. (Tri-County Family Medicine, Cohocton, NY, and Clinical Professor of Family Medicine, University of Rochester, Rochester, NY); Joxel Garcia, M.D., M.B.A. (Deputy Director, Pan American Health Organization, Washington, DC); Russell Harris, M.D., M.P.H. (Associate Professor of Medicine, Sheps Center for Health Services Research, University of North Carolina School of Medicine, Chapel Hill, NC); Mark S. Johnson, M.D., M.P.H. (Professor of Family Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ); Jonathan D. Klein, M.D., M.P.H. (Associate Professor, Department of Pediatrics, University of Rochester School of Medicine, Rochester, NY); Carol Loveland-Cherry, Ph.D., R.N. (Executive Associate Dean, School of Nursing, University of Michigan, Ann Arbor, MI); Virginia A. Moyer, M.D., M.P.H. (Professor, Department of Pediatrics, University of Texas at Houston, Houston, TX); C. Tracy Orleans, Ph.D. (Senior Scientist, The Robert Wood Johnson Foundation, Princeton, NJ); Albert L. Siu, M.D., M.S.P.H. (Professor of Medicine, Chief of Division of General Internal Medicine, Mount Sinai School of Medicine, New York, NY); Steven M. Teutsch, M.D., M.P.H. (Senior Director, Outcomes Research and Management, Merck & Company, Inc., West Point, PA); Carolyn Westhoff, M.D., M.Sc. (Professor of Obstetrics and Gynecology and Professor of Public Health, Columbia University, New York, NY); and Steven H. Woolf, M.D., M.P.H. (Professor, Department of Family Practice and Department of Preventive and Community Medicine and Director of Research, Department of Family Practice, Virginia Commonwealth University, Fairfax, VA).

* Member of the USPSTF at the time this recommendation was finalized. For a list of current Task Force members, go to https://www.uspreventiveservicestaskforce.org/Page/Name/about-us.

This document is in the public domain within the United States. Requests for linking or to incorporate content in electronic resources should be sent via the USPSTF contact form.