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Case 4: Discussion

The Risk of Acquiring HCV after Occupational Exposure

The risk of transmission from a source patient with known hepatitis C virus (HCV) infection to a health care worker is estimated to be 1.5%, with studies showing a range from 0 to 22%[1,2,3,4,5]. The major factors that best determine the actual risk are the infectivity of the source patient's body fluid and the type of exposure that occurs. The infectivity of the body fluid depends on both the concentration of HCV in the body fluid and the inoculum involved in the exposure. Hollow-bore needle exposures typically involve a larger inoculum than solid-bore needle exposures and thus, a greater risk of transmission[6]. Hepatitis C virus can be found in body fluids other than blood, including saliva, semen, menstrual fluid, spinal fluid, ascites fluid, and urine[2]. The occupational risk with these fluids remains unknown, but presumably the risk is markedly lower than with blood. The infectivity of the source patient's HCV can also depend on how long the fluid has been outside of the body, since the level of HCV significantly declines within hours. The risk related to the type of exposure correlates with the tissue involved in the exposure. No cases of occupational HCV have been documented with exposure to intact skin. Two cases have documented transmission from mucous membrane exposure, both of which involved large splashes of blood into the eyes[7,8]. The vast majority of cases of occupational HCV transmission have involved percutaneous exposures. As with HIV, deep penetration of the needle into the skin appears to increase the risk of transmission.

Recommendations for HCV Postexposure Prophylaxis

In the case presented, the health care worker suffered exposure to both HIV and HCV. Immediately following this needlestick injury, the health care worker should have thoroughly washed the wound. In addition to the specific measures required to reduce the likelihood of HIV transmission, the health care worker should undergo baseline testing for HCV antibody and liver enzymes. Unfortunately, there is currently no HCV vaccine that could be used for preventive or postexposure purposes. In addition, the CDC does not recommended using immune globulin for postexposure prophylaxis in persons exposed to HCV[1]. A prior small study in chimpanzees showed that immune globulin containing anti-HCV antibodies failed to prevent transmission of HCV when given within 1 hour of an exposure[9]. Moreover, currently available immune globulin does not contain HCV antibodies. Although interferon with or without ribavirin could theoretically have a preventive effect if given in the postexposure setting, there are no clinical data regarding the safety or efficacy of interferon in this setting, and some experts believe these medications would only have activity in individuals with established infection. There is no evidence that HIV antiretroviral medications have any activity against HCV. In summary, other than washing the wound, there is no postexposure prophylactic measure recommended that would decrease the risk of HCV transmission following an occupational exposure.

Follow-Up of the Health Care Worker

Most persons who acquire HCV, including those with occupational acquisition, do not have an obvious clinical illness associated with seroconversion. Thus, the lack of an obvious clinical illness makes follow-up laboratory testing extremely important in the setting of an occupational exposure. Currently, the CDC recommends follow-up alanine aminotransferase (ALT) levels and HCV serologic testing 4-6 months after the exposure. Antibodies against HCV develop at a mean of 50-70 days after exposure. All persons with a positive HCV enzyme immunoassay test should undergo supplemental testing with an HCV RNA test. Available data suggest that current virologic assays can detect HCV RNA within 10 days after an exposure. The CDC recommends that HCV RNA testing be considered at 4-6 weeks if an earlier diagnosis of HCV is desired[1]. Some institutions have taken an aggressive approach to diagnosing acute HCV and have monitored HCV RNA levels every 2 weeks after the exposure[2]. During the first several months following acute infection, HCV levels can fluctuate dramatically, thus a single negative HCV RNA test would not rule out HCV infection[3]. No changes in sexual practices are recommended after exposure to HCV. In the case presented, however, the health care worker should exercise safe sex practices for at least 6 months based on the exposure to HIV. The CDC does not routinely recommend work-related restrictions for a health care worker based solely on exposure to HCV-contaminated blood[1]. Several reports have documented iatrogenic health care worker-to-patient transmission of HCV[2]. To date, however, no clear-cut guidelines exist that outline restrictions of professional activities for HCV-infected health care workers.

Treatment of HCV-Infected Health Care Workers

If the health care worker acquires HCV, treatment of HCV in this early phase may be considered. The efficacy of therapy early in acute HCV has been controversial, mainly because the studies have involved different timing, types, and duration of therapy. In general, treatment responses have been more favorable in the acute setting than with chronically infected patients[2]. One recent study showed excellent responses in persons with acute HCV treated with interferon-alpha[10]. In this study, 44 persons with acute HCV infection received subcutaneous interferon-alpha (5 million IU daily x 3 weeks, then 3 times per week for 20 weeks); 98% had a sustained virological response (Figure 1). Limitations of this study include the lack of a control group, and the relative insensitivity of the HCV RNA assay (less than 600 IU/ml) used to define sustained response. Furthermore, most of these patients were symptomatic (68% had jaundice), a finding previously shown to predict a higher likelihood of spontaneous clearance of HCV. Thus, it remains unclear whether initiating therapy in the first 6 months is the optimal strategy. Other studies have not shown such promising results, and at least 20% of persons with acute HCV will spontaneously clear the infection without therapy. Most experts would only consider therapy for acute HCV in the setting of a repeatedly positive HCV RNA test, and many would limit treatment to those with elevated ALT (biochemical evidence of hepatitis). In those with established HCV infection, use of pegylated interferon has generally shown superior results compared with conventional interferon (Pegasys or PEG-Intron), and addition of ribavirin to interferon has further enhanced the response. In patients with acute HCV infection, however, insufficient data exist regarding the use of pegylated interferon or the use of combination therapy that includes ribavirin.

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    Figure 1. Cumulative Incidence of Undectable Serum HCV RNA in Patients

    Forty-four patients with acute HCV infection received 5 million U interferon alpha-2b given subcutaneously daily for 4 weeks, followed by 3 times per week for 20 weeks. The graph shows the cumulative incidence of undetectable (lower limit 600 copies/ml) serum HCV levels during treatment and in follow-up. Hepatitis C virus levels were measured by reverse transcriptase polymerase chain reaction (RT-PCR).The mean baseline HCV RNA level was 420,000 copies/ml. Sixty-one percent of the patients had genotype 1A. The mean time from infection to the start of therapy was 89 days. Adapted from Jaeckel E, Cornberg M, Wedemeyer H, et al. Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med. 2001;345:1452-7. Reproduced with permission from the Massachusetts Medical Society. Copyright © 2001 Massachusetts Medical Society. All rights reserved.

    Figure 1