The Risk of Acquiring HCV after Occupational Exposure
The estimated risk of transmission from a source patient with known hepatitis C virus (HCV) infection to a health care worker is approximately 1.5%, with studies showing a range from 0 to 22%.[,,,,,] The major factors that best determine the actual risk of transmission 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 of fluid involved in the exposure. Hollow-bore needle exposures typically involve a larger inoculum of fluid than solid-bore (suture) needle exposures and thus pose a greater risk of transmission.[,] For needlestick injuries, the risk of transmission is higher when the needle that had been placed in the source patient's vein or artery, and when the source patient has a high serum HCV RNA level. Hepatitis C virus can be found in body fluids other than blood, including saliva, semen, menstrual fluid, spinal fluid, ascites fluid, and urine. The risk of occupational acquisition of HCV with these fluids remains poorly defined, but presumably the risk is substantially lower than with blood. The infectivity can also depend on how long the fluid has been outside of the body, since the level of HCV significantly declines within hours when outside of the body. No cases of occupational HCV have been documented with exposure to intact skin. Several cases have documented transmission from mucous membrane exposure, all of which involved splashes of blood into the eyes.[,,] 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
Immediately following a needlestick injury, the health care worker should thoroughly wash the wound. In addition to the specific measures required to address the exposure to HIV in a patient with HCV-HIV coinfection, the health care worker should undergo baseline testing for HCV antibody and liver enzymes. If the source patient has HIV or hepatitis B virus infection, then the health care worker should have this addressed in addition to addressing HCV. In contrast to prevention of hepatitis B virus infection, there is 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. 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. Use of peginterferon and ribavirin for HCV postexposure prophylaxis is not recommended due to lack of data, cost, and very high rates of significant side effects. There are several new well-tolerated, safe, direct-acting antiviral agents (DAAs) used to treat chronic HCV infection and these agents could theoretically provide benefit in the postexposure prophylaxis setting. There are, however, multiple reasons why the new DAAs are not recommended for postexposure prophylaxis. First, there are no data validating that DAAs would be effective in preventing HCV transmission in the postexposure prophylaxis setting. Second, the hepatitis C guidance from the American Association for the Study of Liver Disease-Infectious Diseases Society of American, and International Antiviral Society USA (AASLD/IDSA/IAS-USA) recommends against using HCV postexposure prophylaxis with antiviral therapy. Third, if DAAs were used, the treatment duration is unknown—choosing duration of prophylaxis would be extremely important considering that most DAA-based regimens cost at least $1,000 per day. Fourth, considering the relatively low risk of acquiring HCV via an occupational exposure (approximately 1.5%) treatment of all exposures with DAAs would be prohibitively expensive and hard to justify when patients with known chronic HCV are currently having difficulty obtaining access to treatment with DAAs due to the extremely high cost of a treatment course. Fifth, approximately 25% of persons who acquire HCV have spontaneous viral clearance and thus are naturally cured of their infection. Last, considering that DAAs cure HCV in greater than 90 to 95% of patients with chronic HCV, any health care worker who developed occupational HCV could receive treatment with DAAs and have an extremely high likelihood of achieving cure with treatment using DAAs.[,]
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 to 6 months after the exposure. Antibodies against HCV develop at a mean of 50 to 70 days after exposure. All persons with occupational exposure to HCV and a new 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 to 15 days after an exposure if transmission of HCV has occurred. The CDC recommends considering HCV RNA testing at 4 to 6 weeks if an earlier diagnosis of HCV is desired. In addition, some institutions have taken an aggressive approach to diagnosing acute HCV and have monitored HCV RNA levels at a minimum of every 8 weeks (out to 6 months after the exposure). During the first several months following acute HCV infection, HCV levels can fluctuate dramatically; thus, a single negative HCV RNA test does not rule out HCV infection. 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.
Treatment of HCV-Infected Health Care Workers
For newly infected health care workers, we advise obtaining expert consultation with (or referral to) a hepatitis C expert to help counsel and guide the management in this early period of HCV infection. For persons with newly acquired HCV, the AASLD/IDSA/IAS-USA guidance advises close monitoring with HCV RNA levels every 4 to 8 weeks for 6 to 12 months to determine if they spontaneously clear the HCV infection. Patients with symptomatic acute HCV and those with IL-28B CC genotype have a higher likelihood of spontaneous clearance of HCV.[,,] If spontaneous clearance of HCV occurs, it usually takes place by 6 months in approximately 75 to 85% of persons and by 12 months in 88 to 95%. Prior the availability of the highly effective DAA agents, some experts had substantial enthusiasm for treating patients with acute HCV, given that treatment studies of patients with acute HCV showed much higher sustained virologic response (SVR) rates than with chronic HCV; these studies utilized interferon, peginterferon, or either drug in combination with ribavirin.[,,] For example, in one 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) and 98% achieved an SVR (Figure 1). Considering that current DAA-based therapies generate SVR rates of greater than 90% with chronic HCV, the advantage of treating acute HCV infection is markedly diminished. Nevertheless, some experts may recommend treating in this early period and the AASLD/IDSA/IAS-USA guidance provides general recommendations if treatment is considered (Figure 2). Several reports have documented iatrogenic health care worker-to-patient transmission of HCV. To date, however, no clear-cut guidelines exist that outline restrictions of professional activities for HCV-infected health care workers.