Transmission of Hepatitis Viruses

Hepatitis A virus (HAV) is shed in the feces, and peak titers occur during the 2 weeks before and 1 week after onset of illness [1]. Virus is also present in serum and saliva during this period, although in concentrations several orders of magnitude less [2]. Consequently, the most common mode of transmission is fecal-oral, with the virus being transmitted from person to person or by contaminated food or water [3]. On the basis of cases of hepatitis A reported in 1992 to the Centers for Disease Control and Prevention (CDC), the most frequently reported risk factor was household or sexual contact with a person with hepatitis (24%), followed by day-care attendance or employment (15%), recent international travel (6%), and association with a suspected food- or water-borne outbreak (5%). Many persons with hepatitis A do not identify risk factors; their source of infection may be other infected persons who are asymptomatic.

Because of the viremic phase during HAV infection, transfusion-related hepatitis A occurs occasionally. The source of infection is usually a blood donor who is incubating the virus at the time of donation. Predonation interviews regarding hepatitis symptoms as well as screening of blood donations for alanine aminotransferase elevations are important safeguards for preventing blood-borne HAV transmission. Blood-borne HAV transmission to neonates or other patients has resulted in nosocomial hepatitis A outbreaks among hospital personnel.

The investigation of HAV transmission to hemophiliacs receiving contaminated factor VIII units, described in this issue of the Annals [4], along with other such outbreaks in Europe, represents further examples of blood-borne HAV transmission. Contamination presumably occurred from plasma donors who were incubating HAV at the time of donation and was substantial enough that the virus was purified along with factor VIII during the preparation process; the solvent-detergent step used in factor VIII preparation to inactivate lipid-containing viruses is ineffective against HAV. Less likely is the possibility that contamination occurred sometime during processing. Transmission of HAV by factor VIII preparations has not been reported in the United States.

Hepatitis B virus (HBV) is present in high titers in blood and exudates (for example, from skin lesions) of acutely and chronically infected persons [5]. Moderate viral titers are found in semen, vaginal secretions, and saliva. Other body fluids that do not contain blood or serous fluid, such as feces or urine, are not a source of HBV. Therefore, the three principal modes of HBV transmission are percutaneous (injection drug use, blood or body-fluid exposures among health care workers, and blood transfusions), sexual (heterosexual or male homosexual), and mother-to-infant (through blood exposure at the time of birth) [6]. Transmission between siblings and other household contacts readily occurs, through transmission from skin lesions such as eczema or impetigo, sharing of potentially blood-contaminated objects such as toothbrushes and razor blades, and occasionally through bites [7]. Nosocomial outbreaks, although rare, have occurred due to improper use or disinfection of medical devices (for example, fingerstick devices, acupuncture needles) or due to transmission from infected health care workers to patients during invasive procedures [8, 9].

The number of reported cases of hepatitis B has decreased in recent years among drug users and homosexual men because of behavioral changes in response to the acquired immunodeficiency syndrome (AIDS) epidemic; however, heterosexual transmission now accounts for more cases than any other factor. The most frequent risk factor among patients with cases reported from 1990 to 1992 in the Sentinel Counties Study, a surveillance system operated by CDC in four U.S. counties, was heterosexual exposure to a contact with hepatitis or to multiple partners (36%), followed by injection drug use (13%), homosexual activity (11%), household contact (3%), and health care employment (2%). Transmission from blood transfusions is rare because of donor deferral and screening for hepatitis B surface antigen and antibody to hepatitis B core antigen (anti-HBc). Perinatal transmission and transmission to young children in households, although not reflected in surveillance data because acute infection at these ages is largely asymptomatic, account for a substantial proportion of chronic disease caused by HBV infection [10].

Hepatitis delta virus (HDV) is a defective virus, dependent on HBV for replication. Hepatitis delta virus is only transmitted as a co-infection with HBV or as a superinfection to a person who is already infected with HBV. An estimated 4% of acute HBV infections are co-infections with HDV [11]. Seroepidemiologic studies indicate that in the United States, transmission is mostly through injection drug use and less commonly through sexual transmission. The seroprevalence of antibody to HDV among HBV-infected injection drug users ranges from 20% to 53%.

Hepatitis C virus (HCV), discovered in the late 1980s, is the agent that most often causes non-A, non-B hepatitis in the United States. Hepatitis C virus circulates in low titers in the blood of infected persons and is detected inconsistently in other body fluids [12, 13]. The most efficient mode of HCV transmission is direct percutaneous blood exposure, such as through blood or blood products or through needle sharing among drug users or through transfusion of blood or blood products. The risk for HCV transmission after a needlestick exposure to blood from a source positive for antibody to HCV (anti-HCV) is 3% to 10% [14]. In the Sentinel Counties Study, cases among injection drug users account for nearly 40% of acute hepatitis C cases. Donor deferral and screening for surrogate markers (anti-HBc and alanine aminotransferase) and for anti-HCV have made post-transfusion hepatitis C relatively rare. Follow-up studies of blood transfusion recipients indicate that the risk for acquiring HCV infection from a blood transfusion is less than 0.5% [15].

Studies examining the risk for sexual and perinatal HCV transmission have been limited by small sample size and variable types of serologic testing and, in some cases, have produced conflicting results. Some studies among sexual contacts and spouses of anti-HCV-positive persons have found HCV infection rates, determined by anti-HCV or detection of HCV by the polymerase chain reaction, as high as 32% [16, 17], whereas other studies among similar contacts and among homosexual men have found little or no HCV infection [18, 19]. Studies of infants born to HCV-infected women negative for the human immunodeficiency virus have found the risk for transmission, determined by persistent anti-HCV positivity, to be from 0% to 13% [20-22]. In the Sentinel Counties Study, 14% of patients with acute hepatitis C had exposure to a household or sexual contact with hepatitis or to multiple sexual partners. An additional 42% did not report a source of infection; these persons may have denied risk factors or may have had unrecognized exposures (for example, sexual contact with a person who is asymptomatically infected). Although it appears that sexual, perinatal, and possibly household HCV transmission can occur, further studies are needed to quantify the risk.

In recent years, hepatitis E virus (HEV), the causative agent of enterically transmitted non-A, non-B hepatitis, has been isolated, and serologic assays have been developed to detect HEV infection [23]. Hepatitis E occurs in large outbreaks in areas with extremely poor sanitary conditions, such as refugee camps in developing countries. The virus is excreted in feces, and fecally contaminated drinking water has been the most frequently documented vehicle of transmission; person-to-person transmission has not been felt to play a substantial role. Sporadic endemic transmission also occurs in many developing countries, but few studies have addressed how such transmission occurs. Hepatitis E has only occasionally been reported in the United States; all cases have occurred in recent travelers to HEV endemic areas, and no secondary transmission has been observed [24].

How should persons who are infected with one of the hepatitis viruses be counseled regarding transmission to others? A common misconception among some patients and providers is that persons with hepatitis should refrain from casual contact (including hugging and kissing) and from sharing silverware, glassware, or other eating utensils and that they should use separate bathrooms and wash clothes separately. These are not recognized routes of transmission for any of the hepatitis viruses, and therefore such precautions are not necessary. Household articles with the potential for blood contamination, such as razor blades or toothbrushes, should not be shared. None of the hepatitis viruses are readily transmitted between children in school settings or between employees in the workplace; therefore, persons who are infected with any of these viruses can generally return to school or work activities without any restrictions as soon as their medical condition allows. The exceptions are retail food-handlers who have hepatitis A, for whom most local health departments recommend work restrictions for 1 week after onset of illness, and HBV-infected health care workers who are hepatitis B e antigen positive and who do invasive procedures, whose activities should be reviewed by an expert panel to determine which procedures, if any, they can perform [9].

On the basis of the limited available data, the U.S. Public Health Service does not recommend a change in current sexual practices for persons with HCV infection who have a steady sexual partner [25]. For HCV-infected persons with multiple sexual partners, safe sex practices should be followed to prevent transmission of HCV and other sexually transmitted diseases. No special treatments or precautions for HCV-infected pregnant women or their offspring are recommended.

Immunoprophylaxis is available to protect contacts of persons with hepatitis A and B. Household and sexual contacts of persons with hepatitis A should receive immune globulin within 2 weeks of last exposure [26]. Children with hepatitis A in day care can return to their centers after all other children and employees receive immune globulin [26]. Sexual contacts of persons with acute HBV infection and others with direct percutaneous (needlestick, laceration, or bite) or permucosal (ocular or mucous-membrane) exposure to blood of HBV-infected persons should receive hepatitis B immune globulin and hepatitis B vaccine. Household and sexual contacts of persons who are identified with chronic HBV infection should receive hepatitis B vaccine [27]. Available data indicate that immune globulin does not offer protection against HEV infection; to prevent transmitting HEV to others, careful attention should be paid to hand washing and personal hygiene.

To prevent and control transmission within populations, effective vaccines exist for two of the hepatitis viruses. The challenge is to develop effective strategies for vaccine delivery. Hepatitis B vaccine has been available in the United States since the early 1980s. The failure of vaccination strategies targeting adult high-risk groups to have a substantial effect on disease rates has led to recent recommendations for routine childhood hepatitis B immunization [27]. An inactivated hepatitis A vaccine has been commercially available in Europe and Asia for several years and should be available soon in the United States. Although international travelers are a relatively accessible group for vaccination, how to use the vaccine in other groups to prevent hepatitis A remains to be determined. Vaccines against HCV and HEV, and against HDV to protect HBV carriers, are distant possibilities. Ultimately, the prevention and control of transmission of hepatitis viruses will best be achieved through a combination of modification of risk behavior, availability of vaccines, and development of successful strategies for vaccine delivery.

• Copyright ©2004 by the American College of Physicians