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Screening for Hepatitis C in Adults

Recommendation Statement


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.


Summary of Recommendations

  • The USPSTF recommends against routine screening for hepatitis C virus (HCV) infection in asymptomatic adults who are not at increased risk (general population) for infection.

    Rating: D Recommendation.

    Rationale: The USPSTF found good evidence that screening with available tests can detect HCV infection in the general population. The prevalence of HCV infection in the general population is low, and most who are infected do not develop cirrhosis or other major negative health outcomes. There is no evidence that screening for HCV infection leads to improved long-term health outcomes, such as decreased cirrhosis, hepatocellular cancer, or mortality. Although there is good evidence that anti-viral therapy improves intermediate outcomes, such as viremia, there is limited evidence that such treatment improves long-term health outcomes. The current treatment regimen is long and costly and is associated with a high patient dropout rate due to adverse effects. Potential harms of screening include unnecessary biopsies and labeling, although there is limited evidence to determine the magnitude of these harms. As a result, the USPSTF concluded that the potential harms of screening for HCV infection in adults who are not at increased risk for HCV infection are likely to exceed potential benefits.

  • The USPSTF found insufficient evidence to recommend for or against routine screening for HCV infection in adults at high risk for infection.

    Rating: I Recommendation.

    Rationale: The USPSTF found no evidence that screening for HCV infection in adults at high risk (go to Clinical Considerations) leads to improved long-term health outcomes, although the yield of screening would be substantially higher in a high-risk population than in an average-risk population and there is good evidence that anti-viral therapy improves intermediate outcomes, such as viremia. There is, as yet, no evidence that newer treatment regimens for HCV infection, such as pegylated interferon plus ribavirin, improve long-term health outcomes. There is limited evidence from non-U.S. studies that older therapies have some long-term health benefits for patients referred for treatment, but the generalizability of these results to the U.S. population is unknown. Of those infected with HCV, the proportion who progress to liver disease is uncertain. There is limited evidence that 10% to 20% of patients with chronic HCV infection develop cirrhosis within 20 to 30 years after infection. There is also limited evidence that available treatments are effective in preventing cirrhosis in patients with asymptomatic HCV infection. Potential harms of screening and treatment include labeling, adverse treatment effects, and unnecessary biopsies, although there is limited evidence to determine the magnitude of these harms. As a result, the USPSTF could not determine the balance of benefits and harms of screening for HCV infection in adults at increased risk for infection.


Contents

Clinical Considerations
Discussion
Recommendations of Others
References
Members of the Task Force
Contact the Task Force
Available Products
Copyright and Source Information

Task Force Ratings
Strength of Recommendations and Quality of Evidence

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Clinical Considerations

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Discussion

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.

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Recommendations of Others

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 (PDF Help).

References

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.

4. Busch MP. Insights into the epidemiology, natural history and pathogenesis of hepatitis C virus infection from studies of infected donors and blood product recipients. Transfus Clin Biol 2001;8:(3):200-6.

5. Kim WR. The burden of hepatitis C in the United States. Hepatology 2002;36:S30-4.

6. Schreiber GB, Busch MP, Kleinman SH, Korelitz JJ. The risk of transfusion-transmitted viral infections. The Retrovirus Epidemiology Donor Study. N Engl J Med 1996;334(26):1685-90.

7. Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med 1999;341:(8):556-62.

8. Kaur S, Rybicki L, Bacon BR, et al. Performance characteristics and results of a large-scale screening program for viral hepatitis and risk factors associated with exposure to viral hepatitis B and C: results of the National Hepatitis Screening Survey. National Hepatitis Surveillance Group. Hepatology 1996;24:(5):979-86.

9. Garfein RS, Vlahov D, Galai N, et al. Viral infection in short-term injection drug users: the prevalence of the hepatitis C, hepatitis B, human immunodeficiency, and human t-lymphotropic viruses. Am J Public Health 1996;86:655-61.

10. Alter MJ. Epidemiology of hepatitis C. Hepatology 1997;26:(3 Suppl 1):62S-5S.

11. Patrick DM, Tyndall MW, Cornelisse PG, et al. Incidence of hepatitis C virus infection among injection drug users during an outbreak of HIV infection. Can Med Assoc J 2001;165:(7):889-95.

12. Villano SA, Vlahov D, Nelson KE, et al. Incidence and risk factors for hepatitis C among injection drug users in Baltimore, Maryland. J Clin Microbiol 1997;35:(12):3274-7.

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.

17. Management of hepatitis C: 2002. NIH Consens Statement 2002. 2003;19(3):1-46.

18. Dienstag JL. The role of liver biopsy in chronic hepatitis C. Hepatology 2002;36:S152-60.

19. Perrillo RP. The role of liver biopsy in hepatitis C. Hepatology 1997;26:(Suppl 1):57S-61S.

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Members of the Task Force

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 http://www.uspreventiveservicestaskforce.org/about.htm.

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Contact the Task Force

Address correspondence to: Ned Calonge, M.D., M.P.H., Chair, U.S. Preventive Services Task Force; c/o Project Director, USPSTF; 540 Gaither Road; Rockville, MD 20850.

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Available Products

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.

Source: U.S. Preventive Services Task Force. Screening for Hepatitis C: Recommendation Statement. Ann Intern Med 2004;140(6):462-4.

Recommendations made by the USPSTF are independent of the U.S. Government. They should not be construed as an official position of AHRQ or the U.S. Department of Health and Human Services.

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Copyright and Source Information

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.

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Current as of March 2004


Internet Citation:

U.S. Preventive Services Task Force. Screening for Hepatitis C: Recommendation Statement. March 2004. http://www.uspreventiveservicestaskforce.org/3rduspstf/hepcscr/hepcrs.htm


 


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