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What is the risk of acquiring hepatitis C for health care workers and what are the recommendations for prophylaxis and follow-up after occupational exposure to hepatitis C virus? http://www.hivdent.org/ Hepatitis C virus (HCV) is most efficiently transmitted by large or repeated percutaneous exposures to blood, such as through the transfusion of blood or blood products from infectious donors and sharing of contaminated needles among injection drug users. Other bloodborne viruses, such as the hepatitis B virus (HBV), are transmitted not only by overt percutaneous exposures, but by mucous membrane and in apparent parenteral exposures. Although these types of exposures are prevalent among health-care workers, the risk factors for HCV transmission in this occupational setting are not well-defined. Occupational Transmission A case-control study of patients with acute non-A, non-B hepatitis, conducted prior to the discovery of HCV, found a significant association between acquiring disease and health-care employment, specifically patient care or laboratory work (1). Seroprevalence studies have reported antibody to HCV (anti-HCV) rates of 1% among hospital-based health-care workers in western countries (2). In the one study that assessed risk factors for infection, a history of accidental needle sticks was independently associated with anti-HCV positivity (3). Case reports have documented the transmission of HCV infection from anti-HCV positive patients to health-care workers as a result of accidental needle sticks or cuts with sharp instruments (2), and one reported the transmission of HCV from a blood splash to the conjunctiva (4). In follow-up studies of health-care workers who sustained percutaneous exposures to blood from anti-HCV positive patients, the incidence of anti-HCV seroconversion (based on second-generation testing) averaged 3.5% (range, 0%-7%) (5-9); in the one study that used polymerase chain reaction(PCR) to measure HCV infection by detecting HCV RNA, the incidence was 10% (5). Nosocomial Transmission Nosocomial transmission of HCV is also possible if breaks in technique occur or disinfection procedures are inadequate and contaminated equipment is shared between patients. Hospitalized patients may serve as a reservoir for transmission; the prevalence of anti-HCV among such patients has been reported to range from 2% to 18% (10-12). Case control studies have not found an association between standard medical care procedures and transmission of HCV in the United States (1,13). However, in one report from Greece, 6 patients with acute non-A, non-B hepatitis (5 of whom were anti-HCV positive) all had onset of their disease within a 9 day period, and all had been hospitalized 2 to 3 months previously at the same hospital; none had received transfusions or undergone surgery (14). In Australia, four patients who underwent outpatient surgery on the same day became infected with HCV of the same genotype as a chronically infected patient who underwent surgery just prior to the cases (15). The factors responsible for transmission could not be identified, and none of the surgical personnel were anti-HCV positive. In a report from Spain, however, five open heart surgery patients with documented acute HCV infection appeared to have acquired their infection from a cardiovascular surgeon with chronic hepatitis C (16). By sequence analysis, a high degree of homology was demonstrated between the virus of the surgeon and those of the patients. The factors responsible for transmission were not identified. Postexposure Prophylaxis Unfortunately, postexposure prophylaxis with immune globulin does not appear to be effective in preventing hepatitis C. Historically, several studies have attempted to assess the value of prophylaxis with immune globulin for the prevention of posttransfusion NANB hepatitis, but the results are difficult to compare and interpret because of lack of uniformity in diagnostic criteria, mixed sources of donors (volunteer and commercial), and different study designs (some lack blinding and placebo controls). In some of these studies, immune globulins seemed to reduce the rate of clinical disease although not overall infection rates; in one, patients receiving immune globulin were less likely to develop chronic hepatitis. None of these data have been reanalyzed since anti-HCV testing became available, and in only one study was the first dose of immune globulin given after, rather than before, the exposure, making it difficult to assess its value for postexposure prophylaxis. At least 85% of persons with HCV infection become chronically infected, and chronic liver disease with persistently elevated liver enzymes develops in an average of 67% (2). These extraordinarily high rates of chronic disease and persistent viremia in humans, as well as animal transmission experiments demonstrating the failure of antibody elicited by infection with one genotype to cross-neutralize either heterologous genotypes or closely related but heterogeneous species within the same genotype indicate the absence of an effective neutralizing immune response (17,18). Furthermore, immune globulin is now manufactured from plasma that has been screened for anti-HCV. A recently conducted experimental study in chimpanzees found that immune globulin manufactured from screened plasma administered 1 hour after exposure to HCV did not prevent infection or disease (19). In February 1994, the Immunization Practices Advisory Committee reviewed the available data and concluded that there was no support for the use of immune globulin for postexposure prophylaxis of hepatitis C (CDC, unpublished data). There is no information regarding the use of anti-viral agents, such as alpha interferon, in the postexposure setting, and such treatment is not recommended. ♥   ♥ Issues Regarding Follow-Up After Exposure In the absence of postexposure prophylaxis, multiple issues need to be considered in deciding if there should be a defined protocol for the follow-up of health-care workers for HCV infection after occupational exposures. These areas include the limited data on the risk of transmission, the limitations of available serologic testing for detecting infection and determining infectivity, the poorly defined risk of transmission by sexual, household, and perinatal exposures, the limited benefit of therapy for chronic disease, the cost of follow-up, and the medical-legal implications. Although it seems clear that needle-stick exposure to infectious blood is a risk factor for hepatitis C, and that this risk appears to be intermediate between that of HBV and human immunodeficiency virus, the data are limited or nonexistent on the risk of transmission associated with other types of occupational exposure. This makes it difficult to provide health-care workers who sustain such exposures with a meaningful estimate of their chances of developing HCV infection. Testing methods readily available in the clinical setting also have limitations. With the commercially manufactured enzyme immunoassays (EIAs) that detect anti-HCV, there may be a prolonged interval between exposure and seroconversion, although the average time period is 8-10 weeks. In many populations, including health-care workers, the rate of false positivity for anti-HCV is high, and supplemental assays should always be used to judge the validity of repeatedly reactive EIA results. About 5% to 10% of infections will not be detected unless PCR is used to detect HCV RNA. Although such assays for HCV RNA are available from several commercial laboratories on a research-use basis, they are not standardized and the cost is high, about $200 per test. Both false-positive and false-negative results can occur from improper handling and storage or contamination of the test samples. In addition, the detection of HCV RNA may be intermittent, and the meaning of a single negative PCR test result is not conclusive. 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 in apparent parenteral or mucosal exposures occur. Epidemiologic studies have implicated exposure to infected sexual and household contacts as well as to multiple sexual partners in the transmission of HCV (1,13). Serologic studies of the long-term sexual and household contacts of patients with chronic hepatitis C have found evidence of HCV infection in an average of 5% of sexual partners and in an average of 3% of children (2). Studies of infants born to anti-HCV-positive mothers have reported rates of perinatal transmission ranging from 0% to 13% (average 6%); in two small studies, only mothers with "high" titers of HCV RNA transmitted HCV to their infants (20,21). The inconsistent results of these as well as studies that looked for HCV RNA in body fluids other than serum and plasma may reflect different concentrations of virus in the infected persons sampled. The risk that an HCV-infected individual will transmit the virus may be related to the type and size of the inoculum and the route of transmission, as well as the titer of virus, but data on the threshold concentration of virus needed to transmit infection are insufficient. In the absence of such data and standardized tests to measure infectivity, it is difficult to counsel anti-HCV-positive persons about their risk of transmission to others (22). Because the risk of HCV transmission between long-term steady sexual partners appears to be low, there are no recommendations for changes in sexual practices for persons with a steady sexual partner, although infected persons should be informed of the possible risk so they can decide if they wish to take precautions. Household articles such as toothbrushes and razors should not be shared. There are no data to support discouraging either pregnancy or subsequent breast feeding (see reference 22 for further details on counseling) The most obvious benefit from a follow-up protocol would appear to be the opportunity for the health-care worker to seek evaluation for chronic liver disease and treatment, if eligible. Studies have shown that alpha interferon therapy may have a beneficial effect among some patients (23). In these studies, however, the patients were highly selected and therapy resulted in sustained improvement in 20% or fewer of those treated; 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. The nationwide cost of providing postexposure follow-up testing is estimated at $2 to $4 million; the cost for each person who benefits from therapy is estimated at $200,000 (CDC, unpublished data). Even in the absence of both available postexposure prophylaxis and limited specific measures for disease prevention, individual institutions should consider implementing policies and procedures for follow-up after percutaneous or per mucosal exposure to anti-HCV positive blood to address individual workers' concerns about their risk and outcome. Above all, institutions should ensure education of health-care providers regarding the risk and prevention of blood borne infections in the occupational setting (24), including hepatitis C, and such information should be routinely updated to ensure accuracy. ♥   ♥ Summary Recommendations No postexposure prophylaxis is available for hepatitis C; immune globulin is not recommended. Institutions should provide to health-care workers accurate and up-to-date information on the risk and prevention of all blood borne pathogens, including hepatitis C. Institutions should consider implementing policies and procedures for follow-up of health-care workers after percutaneous or per mucosal exposure to anti-HCV positive blood. Such policies might include baseline testing of the source for anti-HCV and baseline and 6 month follow-up testing of the person exposed for anti-HCV and ALT activity. All anti-HCV results reported as repeatedly reactive by EIA should be confirmed by supplemental anti-HCV testing. There are currently no recommendations regarding restriction of health-care workers with hepatitis C. The risk of transmission from an infected worker to a patient appears to be very low. Furthermore, there are no serologic assays that can determine infectivity nor are there data to determine the threshold concentration of virus required for transmission. As recommended for all health-care workers, those who are anti-HCV positive should follow strict aseptic technique and standard (universal) precautions, including appropriate use of hand washing, protective barriers, and care in the use and disposal of needles and other sharp instruments. Selected References Alter MJ, Gerety RJ, Smallwood L, et al. Sporadic non-A, non-B hepatitis: frequency and epidemiology in an urban United States population. J Infect Dis 1982;145:886-893. Alter MJ. Epidemiology of hepatitis C in the West. Semin Liver Dis 1995;15:5-14. Polish LB, Tong MJ, Co RL, et al. Risk factors for hepatitis C virus infection among health care personnel in a community hospital. Am J Infect Control 1993;21:196-200. Sartori M, La Terra G, Aglietta M, et al. Transmission of hepatitis C via blood splash into conjunctiva. Scand J Infect Dis 1993;25:270-271. Mitsui T, Iwano K, Masuko K, et al. Hepatitis C virus infection in medical personnel after needlestick accident. Hepatology 1992;16:1109-1114. Hernandez ME, Bruguera M, Puyuelo T, Barrera JM, Sanchez Tapias JM, Rodes J. Risk of needle-stick injuries in the transmission of hepatitis C virus in hospital personnel. J Hepatol 1992;16:56-58. Zuckerman J, Clewley G, Griffiths P, Cockcroft A. Prevalence of hepatitis C antibodies in clinical health-care workers. Lancet 1994;343:1618-1620. Petrosilla N, Puro V, Ippolito G, and Italian Study Group on Blood-borne Occupational Risk in Dialysis. Prevalence of hepatitis C antibodies in health-care workers. Lancet 1994;344:339-340. Lanphear BP, Linnemann CC, Cannon CG, et al. Hepatitis C virus infection in health care workers: risk of exposure and infection. Infect Control Hosp Epidemiol 1994;15:745-750. Louie M, Low DE, Feinman SV, et al. Prevalence of bloodborne infective agents among people admitted to a Canadian hospital. Can Med Assoc J 1992;146:1331-1334. Kelen GD, Green GB, Purcell RH, et al. Hepatitis B and hepatitis C in emergency department patients. N Engl J Med 1992;326:1399-1404. Bile K, Aden C, Norder H, et al. Important role of hepatitis C virus infection as a cause of chronic liver disease in Somalia. Scand J Infect Dis 1993;25:559-564. Alter MJ, Coleman PJ, Alexander WJ, et al. Importance of heterosexual activity in the transmission of hepatitis B and non-A, non-B hepatitis. JAMA 1989;262:1201-1205. Tassopoulos NC, Hatzakis A, Vassilopoulou-Kada H, et al. Hepatitis C virus is associated with hospital epidemic of acute non-a, non-B hepatitis [abstract]. Program and Abstracts of the 1990 International Symposium on Viral Hepatitis and Liver Disease, Houston, 1990, p.155. NSW Health Department. Investigation of possible patient-to-patient transmission of hepatitis C in a hospital. NSW Public Health Bulletin 1994;5:47-51. Esteban JI, Gomez J, Martell M, et al. Repeated transmission of HCV from surgeon to patients during cardiac surgery [abstract]. Hepatology 1995;22:347A. Bukh J, Miller RH, Purcell RH. Genetic heterogeneity of hepatitis C virus: quasispecies and genotypes. Sem Liv Dis 1995;15:41-63. Farci P, Alter HJ, Wong DC, et al. Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated in vitro neutralization. Proc Natl Acad Sci 1994;91:7792-7796. Krawczynski K, Alter MJ, Tankersley DL, et al. Effect of immune globulin on the prevention of experimental hepatitis C virus infection. J Infect Dis 1996, in press. Ohto H, Terazawa S, Sasaki N, et al. Transmission of hepatitis C virus from mothers to infants. N Engl J Med 1994;330:744-750. Lin HH, Kao JH, Hsu HY, et al. Possible role of high-titer maternal viremia in perinatal transmission of hepatitis C virus. J Infect Dis 1994;169:638-641. Centers for Disease Control. Public Health Service interagency guidelines for screening donors of blood, plasma, organs, tissues, andsemen for evidence of hepatitis B and hepatitis C. MMWR 1991:40(RR4):13-14. Fried MW, Hoofnagle, JH. Therapy of hepatitis C. Semin Liver Dis 1995;15:82-91. Centers for Disease Control. Update: universal precautions for prevention of transmission of human immunodeficiency virus, hepatitis B virus, and other bloodborne pathogens in health-care settings. MMWR 1988;37:377-382,387-388. Is the recent increase in the reported cases of hepatitis C / NANB a real increase? Introduction The numbers of hepatitis C and non-A, non-B (NANB) hepatitis cases reported in the United States have fluctuated dramatically in the last 5 years, particularly since tests for antibody to hepatitis C virus (anti-HCV) were introduced in 1990. In addition, the reported incidence of this disease has varied considerably between different surveillance systems (Table 1). The incidence of hepatitis C reported to the National Electronic Telecommunications System for Surveillance (NETSS) declined moderately from 1985 to 1990, but then increased by almost 130% from 1990 to 1992. The incidence rate in 1994 was still 73% higher than its 1990 level. In contrast, the incidence of hepatitis C in the Sentinel Counties Study of Acute Viral Hepatitis (1), which was initially 4-fold higher than the NETSS reported incidence, declined by 80% from 1989 through 1984. A similar decline was also observed in cases reported to the Viral Hepatitis Surveillance Program (VHSP). Possible reasons for these discrepancies include the widespread use of new diagnostic tests in laboratory-based reporting. The increase in cases reported to NETSS may have been the result of laboratory reports of chronically infected patients, or anti-HCV positive patients identified through screening programs. To better determine the reasons for these changes in nationwide reporting, during July-August of 1995 the Hepatitis Branch conducted a survey of a sample of county health departments to determine their practices and policies with regard to the reporting of hepatitis C and NANB hepatitis cases. Table 1. Reported Cases of Hepatitis C/non-A, non-B Hepatitis per 100,000 Population in Two Surveillance Systems, 1985-94 Year NETSS* Sentinel Counties† 1985 1.81 8.29   1986 1.55 8.65   1987 1.23 6.83   1988 1.07 7.64   1989 1.02 9.06   1990 1.03 5.51   1991 1.42 3.41   1992 2.36 2.35   1993 1.86 1.83   1994 1.78 1.70   * National Electronic Telecommunications System for Surveillance † Sentinel Counties Study of Acute Viral Hepatitis   Methods Counties were selected as a stratified random sample of those counties that had reported at least one case of hepatitis C/NANB in 1993. The selection list consisted of 790 such counties, and a 20% sample of 161 counties was selected. Stratification of the sample by population size ensured that large counties would have a high probability of selection. Each county health department was asked to complete a questionnaire that covered seven categories: reporting sources of data, case definitions, laboratory reporting, follow-up for incomplete case reports, resources for surveillance, uses to which data were put, and information on respondents. Results The data presented here are based on a preliminary analysis of the first 90 questionnaires that were returned. This represented an early response rate of 56%. In a preliminary analysis comparing county health departments that had or had not responded, no differences were found in population size or geographic location. Respondents included public healthnurses and epidemiologists. About half of the respondents had worked at the health department for more than 10 years. Respondents cited hospitals (34%) as the most common source of case reports prior to 1991; laboratories were next (20%). From 1991 to the present, they cited laboratories as the most common source of case reports (53%); hospitals were second (30%). Physicians were cited as the third most common reporting source in each period. Blood banks and other sources were cited with similar rankings in each period. Nearly half of the health departments surveyed did not apply published case definition criteria when reporting acute hepatitis C/NANB cases. Fifty-six percent of respondents said that a case would be reported as hepatitis C/NANB on the basis of a physician’s diagnosis alone. Forty-nine percent said that they accepted cases on the basis of laboratory reports alone. Discrete dates of onset of symptoms were required by only 36% of respondents, and exclusion of hepatitis A and B was required by 40% of respondents. A large percentage of respondents said they followed up on incomplete case reports; however, 39% of these respondents also stated that they would accept and report a case on the basis of a laboratory report alone. When asked how they obtained the information required to provide an accurate diagnosis, 96% of respondents said they contacted the physician who made the report. Sixty-eight percent did follow-up that included contacting the patient. Only 39% determined if supplemental testing was done on specimens that were reported positive for anti-HCV. Among the 23% of respondents who did not do follow-up on incomplete case reports, 52% said other public health problems took priority, while 50% cited lack of personnel. Thirty-six percent cited the lack of any effective intervention for hepatitis C/NANB patients as a reason. Eighty-five percent of respondents reported increases in the number of cases reported during the past 5 years, mostly owing to laboratory reporting of anti-HCV positivity without evidence of acute disease. Only 12% cited a true increase in the disease incidence in their county or jurisdiction. When asked to cite actions taken by the county health department in response to reported cases of hepatitis C/NANB, 77% of respondents said they provided counseling to patients. Thirty percent said they published newsletters containing data on hepatitis C/NANB. We asked respondents to suggest ways that CDC could improve reporting of hepatitis C/NANB. Most pronounced was an expression of confusion regarding what should be done with case reports of persons with chronic hepatitis C/NANB. Many respondents felt that CDC should publish a clearer, updated case definition. Many also wanted guidelines from CDC for follow-up of incomplete case reports. Respondents suggested that CDC create educational programs targeting health-care workers in an effort to increase the reporting of diseases to the county health departments. Summary Since testing for anti-HCV became widely available, county health departments have increasingly relied on laboratories as sources of case reports for hepatitis C/NANB. This has resulted in an artifactual increase in the reported incidence of hepatitis C because of the reporting of anti-HCV-positive persons with no clinical or epidemiologic evidence of acute disease. Physician-reported cases continue to be a small proportion of all reported hepatitis C/NANB cases. In addition, many county health departments confirmed that they pass these laboratory test positive results on to the state health departments without sufficient confirmation of acute disease. Primarily because of lack of personnel and other diseases being seen as higher priority, county health departments do not attempt to obtain additional information necessary to confirm acute disease. Further analysis of the survey results is being conducted. Issues to be examined include the purpose of surveillance of viral hepatitis; the importance of focusing on acute, symptomatic disease to determine true incidence; and the need for separate surveillance systems to monitor patients with chronic infections and chronic liver disease. Such surveillance efforts in the future will depend on strict adherence to case definitions, and onadequate resources to support them. References 1. Alter MJ, Mast, EE. The epidemiology of viral hepatitis in the United States. Gastroenterology Clinics of North America 1994;23:437-455.