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Hepatitis C virus (HCV) infection is a major cause of chronic liver disease in the United States and worldwide.  At least 85% of persons with HCV infection become chronically infected, and chronic liver disease with persistently elevated liver enzymes develops in approximately 70% of all HCV-infected persons. ¹    Persons with chronic hepatitis C are at risk for cirrhosis and primary hepatocellular carcinoma. Most HCV transmission is associated with direct percutaneous exposure to blood.  Health-care workers (HCWs) are at occupational risk for acquiring this viral infection.  However, no vaccine is available to prevent hepatitis C, and immune globulin is not recommended for postexposure prophylaxis.

In the absence of 1) pre-exposure or postexposure prophylaxis, 2) recommendations that are unique for HCV to prevent HCV transmission to others, and 3) effective therapy for most persons with chronic hepatitis C, the overall public health benefit associated with the identification of HCV infections in HCWs will be limited. However, to address individual workers’ concerns about risk and outcome, CDC, in collaboration with the Hospital Infection Control Practices Advisory Committee, recommends that individual health-care institutions consider implementing policies and procedures for follow-up for HCV infection after percutaneous or permucosal exposures to blood.²   At a minimum, such policies should include

• for the source, baseline testing for antibody to HCV (anti-HCV);

• for the person exposed to an anti-HCV–positive source, baseline and follow-up (e.g., 6-month) testing for anti-HCV and alanine aminotransferase activity;

• confirmation by supplemental anti-HCV testing of all anti-HCV results reported as repeatedly reactive by enzyme immunoassay (EIA);

• recommending against postexposure prophylaxis with immune globulin or anti-viral agents (e.g., interferon); and

• education of HCWs about the risk for and prevention of bloodborne infections, including hepatitis C, in occupational settings, with the information routinely updated to ensure accuracy.

Follow-up studies of HCWs who sustained a percutaneous exposure to blood from an anti-HCV–positive patient have reported an average incidence of anti-HCV seroconversion after unintentional needlesticks or sharps exposures of 1.8% (range: 0–7%). ^{1, 2, 3, 4, 5}   A seroconversion rate of 6% was documented in the United States⁴ ; in Japan, the incidence was 10% based on detection of HCV RNA by PCR. ⁵ Although these follow-up studies have not documented transmission associated with mucous membrane or nonintact skin exposures, the transmission of HCV from a blood splash to the conjunctiva was described in one case report. ⁶

In February 1994, the Advisory Committee on Immunization Practices reviewed data about the prevention of HCV infection with immune globulin and concluded that there was no basis for supporting the use of immune globulin for postexposure prophylaxis of hepatitis C. There have been no assessments of the prevention of HCV infection with antiviral agents (e.g., alpha interferon), and the mechanisms of the effect of interferon in treating patients with hepatitis C are poorly understood; an established infection may need to be present for interferon to be an effective treatment. ⁷    Interferon must be administered by injection and may cause severe side effects. Based on these considerations, postexposure prophylaxis regimens with antiviral agents for HCV infection are not recommended.

Several studies suggest that interferon treatment begun early in the course of HCV infection is associated with a higher rate of resolved infection.   Among HCWs in the postexposure period, onset of HCV infection could be detected earlier by measuring HCV RNA using polymerase chain reaction (PCR) rather than by measuring anti-HCV using EIA.   However, PCR is not a licensed assay, and the accuracy of the results are highly variable.   In addition, there are no data indicating that treatment begun early during the course of chronic HCV infection is less effective than treatment begun during the acute phase of infection. Furthermore, alpha interferon is approved for the treatment only of chronic hepatitis C.   Determination of whether treatment of HCV infection is more beneficial in the acute phase than in the early chronic phase will require evaluation with well-designed research protocols.

In the absence of postexposure prophylaxis, at least six issues need to be considered in defining a protocol for the follow-up of HCWs occupationally exposed to HCV:

1. Limited data about the occupational risk for transmission.
   Although needlestick exposure to infectious blood is a risk factor for hepatitis C and this risk is intermediate between that of hepatitis B virus and human immunodeficiency virus, data are limited or nonexistent about the risk for transmission associated with other types of occupational exposures. Thus, meaningful estimates of the risk for HCV infection cannot be provided to HCWs who sustain such exposures.
2. Limitations of available serologic testing for detecting infection and determining infectivity.
   Testing methods readily available in the clinical setting are subject to some limitations. For the commercially available EIAs that detect anti-HCV, the average interval between exposure and seroconversion is 8–10 weeks. In many populations, including HCWs, the rate of false positivity for anti-HCV is at least 50%, and supplemental assays always should be used to assess the validity of repeatedly reactive EIA results.  Approximately 5% of infections will not be detected unless PCR is used to detect HCV RNA.  Although such assays are available from several commercial laboratories for research use, they are not standardized, and each test costs approximately $200. Both false-positive and false-negative results can occur as a consequence of improper handling and storage or contamination of test samples. In addition, the detection of HCV RNA may be intermittent, and a single negative PCR test result is not conclusive.
3. Poorly defined risk for transmission by sexual and other exposures.
   All anti-HCV– positive persons should be considered potentially infectious; however, neither the presence of antibody nor the presence of HCV RNA is a direct measure of infectivity in settings where inapparent parenteral or mucosal exposures occur. Although epidemiologic studies have implicated exposure to infected sexual and household contacts as well as to multiple sex partners in the transmission of HCV, the efficiency of transmission from these exposures is low ( 1 ). Studies of infants born to anti-HCV–positive mothers have documented an average rate of perinatal transmission of 5%, increasing to 9% among infants born to mothers who were HCV RNA-positive at the infant’s birth ( 8 ). Acquisition of HCV infection from breast milk has not been documented, and in studies of breastfeeding among infants born to HCV-infected women, the average rate of infection was 4% in both breastfed and bottle-fed infants. ⁸  
4. Limited benefit of therapy for chronic disease.
   One benefit from a follow-up protocol is the opportunity for eligible HCWs to seek evaluation for chronic liver disease and treatment. Although alpha interferon therapy is safe and effective for the treatment of chronic hepatitis C ⁹, sustained response rates generally are low (10%– 20% in the United States); the occurrence of mild to moderate side effects in most patients has required discontinuation of therapy in up to 15% of patients. No clinical, demographic, serum biochemical, serologic, or histologic features have been identified that reliably predict which patients will respond to treatment and sustain a long-term remission.
5. Cost of follow-up.
   The estimated annual cost of providing postexposure follow-up testing nationally is $2–$4 million; the estimated cost for each person for a 6-month course of therapy is $200,000 (CDC, unpublished data, 1995).
6. Medical and legal implications.
   A postexposure follow-up protocol will address individual workers’ concerns about their risk for HCV infection and possible disease outcomes, and identify those HCWs who become infected with HCV; this information provides HCWs with the opportunity to be counseled about their risk for transmitting HCV to others and to be evaluated for development of chronic disease, and, if eligible, for therapy for chronic hepatitis C.

Counseling recommendations to prevent transmission of HCV to others¹⁰ are that 1) persons who are anti-HCV–positive should refrain from donating blood, organs, tissues, or semen, and 2) household contacts should not share toothbrushes and razors. However, there are neither recommendations against pregnancy or breastfeeding nor recommendations for changes in sexual practices among HCV-infected persons with a steady partner. Although HCV sometimes can be transmitted from persons with chronic disease to their steady sex partners, the risk for transmission is low despite long-term, ongoing sexual activity. Infected persons should be informed of the potential risk for sexual transmission to assist in decision-making about precautions. Persons with multiple sex partners should adopt safer sex practices, including reducing the number of sex partners and using barriers (e.g., latex condoms) to prevent contact with body fluids.

Reported by: Hepatitis Br, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

References

1. Alter MJ. Epidemiology of hepatitis C in the West. Semin Liver Dis 1995;15:5–14.

2. CDC. Risk of acquiring hepatitis C for health care workers and recommendations for prophylaxis and follow-up after occupational exposure. Hepatitis surveillance report no. 56. Atlanta, Georgia: US Department of Health and Human Services, Public Health Service, 1995:3– 6.

3. Puro V, Petrosillo N, Ippolito G, Italian Study Group on Occupational Risk of HIV and Other Bloodborne Infections. Risk of hepatitis C seroconversion after occupational exposures in health care workers. Am J Infect Control 1995;23:273–7.

4. Lanphear BP, Linnemann CC Jr, Cannon CG, DeRonde MM, Pendy L, Kerley LM. Hepatitis C virus infection in health care workers: risk of exposure and infection. Infect Control Hosp Epidemiol 1994;15:745–50.

5. Mitsui T, Iwano K, Masuko K, et al. Hepatitis C virus infection in medical personnel after needle-stick accident. Hepatology 1992;16:1109–14.

6. Sartori M, La Terra G, Aglietta M, Manzin A, Navino C, Verzetti G. Transmission of hepatitis C via blood splash into conjunctiva. Scand J Infect Dis 1993;25:270–1.

7. Peters M, Davis GL, Dooley JS, Hoofnagle JH. The interferon system in acute and chronic viral hepatitis. Prog Liver Dis 1986;8:453–67.

8. Mast EE, Alter MJ. Hepatitis C. Semin Ped Infect Dis 1997;8:17–22.

9. Hoofnagle JH, Di Bisceglie AM. Drug therapy: the treatment of chronic viral hepatitis. N Engl J Med 1997;336:347–56.

10. CDC. Public Health Service inter-agency guidelines for screening donors of blood, plasma, organs, tissues, and semen for evidence of hepatitis B and hepatitis C. MMWR 1991;40(no. RR-4):1–17. 

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