– Eliminate transmission of viral hepatitis in the United States
– Effective and widespread use of vaccines (for hepatitis A and hepatitis B)
– Reduce high-risk behaviors and activities that facilitate transmission
– Use appropriate and cost effective screening strategies to identify persons at highest risk
– Maintain adequate infection control procedures
– Develop safe and more effective therapies
Viral hepatitis refers to a primary infection of the liver caused by at least five unrelated viruses, and acute and chronic liver disease due to viral hepatitis accounts for substantial morbidity and mortality. Two of these viruses, hepatitis A virus (HAV) and hepatitis E virus (HEV), are primarily transmitted by the fecal-oral route and cause acute self-limited disease. The other three viruses, hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV), are transmitted by percutaneous or permucosal exposures to blood or body fluids that contain blood. All three can result in chronic infection that places the individual at risk for chronic liver disease or primary hepatocellular carcinoma.
Accomplishments during the past 50 years that have contributed to the prevention and control of viral hepatitis include identification of the viral agents, development of sensitive and specific serologic and nucleic acid tests for detection, implementation of donor screening, effective inactivation procedures for plasma-derived products; widespread use of universal precautions; development and use of safe and effective vaccines against hepatitis A and hepatitis B; and development and implementation of nationwide prevention programs based on well-described epidemiology of these diseases.
Challenges to be faced in the next 50 years include effective and widespread use of vaccines; reducing high-risk behaviors and activities; implementing appropriate and cost-effective screening strategies; maintaining adequate infection control procedures; and developing safe and more effective therapies for persons with chronic disease.
The three major types of viral hepatitis in the United States are hepatitis A, hepatitis B, and hepatitis C. The serologic exclusion of the known hepatitis viruses continues to leave cases of hepatitis that clinically appear to be viral in origin. The majority of these cases of “non-ABCDE” hepatitis appear to be parenterally transmitted. Several new viruses have been recently identified and proposed as the putative agents of non-ABCDE hepatitis, but to date, studies of these viruses have failed to show an association with either acute or chronic liver disease
Hepatitis A virus is an RNA virus classified in the Picornavirus family. The severity of clinical disease associated with HAV infection increases with increasing age; icteric disease occurs among <10% of children younger than 6 years of age, 40%-50% of older children, and 70% – 80% of adults. In the United States, the overall reported case-fatality rate is low (<1 per 1000), but high case-fatality rates have been reported among children <5 years of age (1.5 per 1000) and among persons >50 years of age (27 per 1000). Chronic HAV infection does not occur. Most transmission is by the fecal-oral route leading to spread between close contacts. Hepatitis A is vaccine preventable.
In the United States, hepatitis A incidence varies by age, race/ethnicity, and geographic region. Almost 30% of cases occur among children <15 years of age, with the highest rates among children 5-14 years of age. Since many children have unrecognized asymptomatic infection, they likely represent a major reservoir for HAV transmission. Among racial/ethnic groups, rates among American Indians and Alaska Natives are highest, and more than 10 times that in order racial/ethnic groups. Rates among Hispanics are approximately three times higher than among non-Hispanics. Disease rates are substantially higher in the western and southwestern United States compared with other regions.
Data from disease surveillance systems indicate that the most commonly reported source for infection is household or sexual contact with a person who has hepatitis A (15% – 30% of reported cases). An additional 10% – 15% of reported cases occur among children and employees of child care centers and members of their households. International travel (5% to 7%) and suspected food or waterborne outbreaks (2% – 5%) each account for a small proportion of cases, and vary little by year. In contrast, the proportions of cases associated with men who have sex with men or injection drug use vary widely (5% – 30% of cases) as a result of periodic outbreaks occurring in these subgroups in some communities.
Nearly 50% of patients with hepatitis A do not have a recognized source for infection. Many of these patients may have acquired their infection from household contact with persons, especially children, with asymptomatic or unrecognized infection. In one study of adults without an identified source of infections, 52% of their households included a child <6 years old, and the presence of a young child was associated with HAV transmission within the household. In studies where serologic testing of the household contacts of adults without an identified source of infection was performed, 25% – 40% of their contacts <6 years old had serologic evidence of acute HAV infection (IgM anti-HAV).
The Advisory Committee on Immunization Practices recommends pre-exposure hepatitis A vaccination for persons at increased risk, which includes travelers to countries with moderate or high HAV endemic rates; men who have sex with men; illegal drug users (injecting and non-injecting); recipients of clotting factor concentrates; and persons with chronic liver disease. Postexposure administration of immune globulin is recommended for household and sex contacts and for persons exposed to a common source (e.g., infected food handler or infected child in day care) if IG can be given within 14 days of the exposure.
Vaccination of persons at increased risk for hepatitis A will have little effect on national disease rates, because most cases do not occur among persons in these groups. To achieve a sustained reduction in national incidence of hepatitis A, widespread routine vaccination is needed. In the United States, routine vaccination of children beginning at or after 2 years of age is recommended in communities with persistently elevated rates of hepatitis A (approximately twice the national average) and should be considered in communities with rates greater than (but less than twice) the national average. Vaccination of successive cohorts of young children should significantly lower the incidence of hepatitis A over time and eventually provide the opportunity to eliminate HAV transmission. To achieve this goal, children throughout the United States will need to be vaccinated against hepatitis A. This effort would be facilitated by the availability of a vaccine for use in infants or children in the second year of life and combination vaccines that include hepatitis A vaccine.
Hepatitis B virus is a DNA virus classified in the Hepadnavirus family. It causes both acute disease and asymptomatic infection. The risk of developing acute icteric disease increases with age, but the risk of developing chronic HBV infection varies inversely with the age at infection. Only 10% of children and 30% – 50% of adults with acute HBV infection will have icteric disease. However, chronic infection occurs in 90% of infants infected at birth, 25% – 50% of children infected at 1-5 years of age, and about 2% – 6% of persons infected as older children or adults. HBV is both a bloodborne and sexually transmitted infection and is vaccine preventable.
After a period of relative stability ending in 1987, incidence of hepatitis B declined by >70% in the United States. However, an estimated 185,000 new HBV infections occurred in 1997, with the highest incidence of disease among young adults (20-29 years old), and higher rates among blacks and Hispanics compared with whites.
The highest rate of decline was observed in persons aged 10 – 19 years and is most likely related to the cumulative effect of recent hepatitis B immunization recommendations. Routine hepatitis B immunization of infants began in 1992 in the United States, and not enough time has elapsed for universal infant immunization to have directly influenced disease incidence. However, earlier recommendations issued in the 1980s to vaccinate infants and older children at increased risk for HBV infection probably contributed to some of the decrease in incidence in older children.
The decline in overall disease incidence reflects a decrease in the number of cases among adults in groups known to be at increased risk for HBV infection. The decrease in cases among health care workers and men who have sex with men began in the 1980’s, and in the 1990’s was followed by a decrease in the number of cases among injection drug users and heterosexual men and women engaging in high-risk sexual activity. Factors thought to have contributed to the overall and risk group-specific declines in disease incidence include hepatitis B immunization and changes in high-risk activities. Nevertheless, among adults, sexual exposure to an infected partner or to multiple partners and injecting drug use account for the majority of HBV infections.
Approximately one half of persons with acute hepatitis B report a lifetime history of having been treated for an STD or of imprisonment. Had hepatitis B vaccine been routinely administered in STD clinics or prisons, as is recommended, up to one half of all cases of acute hepatitis B could potentially have been prevented. With such a strategy, even persons who did not report a risk factor for their infection would have been vaccinated. This is compelling evidence for the need for routine hepatitis B vaccination programs in STD clinics and prisons, as well as family planning clinics, drug treatment centers, needle exchange programs, and juvenile detention centers. In addition, not vaccinating sexual and household contacts of persons with HBV infection represents another missed opportunity to administer hepatitis B vaccine. Surveillance data indicate that one-half to two-thirds of cases whose source for infection was a sexual or household contact knew their contact was infected, and appropriate prophylaxis could have prevented infection in the majority of these cases.
A substantial number of children become infected with HBV in well-defined settings and the epidemiology of these infections is quite different from that of infections acquired by adults. Since over 90% of childhood HBV infections are asymptomatic, the true incidence of childhood disease is not accurately represented by national surveillance data, which reflect reported cases of clinically apparent disease. Thus, only 1% – 3% of all acute HBV infections occurring in the United States are reported among children <5 years of age, but infections in this age group account for 20% – 30% of all chronic HBV infections.
The strategy for elimination of HBV transmission in the United States includes routine infant and adolescent vaccination, screening of pregnant women for HBsAg and administration of postexposure prophylaxis (HBIG and vaccine) to infants born to infected women, and vaccination of children, adolescents, and adults at increased risk for hepatitis B. Routine infant immunization ensures the prevention of HBV infections in subpopulations that have high rates of early childhood infection (i.e., Eskimos, Asian/Pacific Islanders, infants of immigrant women from high endemicity areas), assures high immunization coverage rates because of the proven vaccine delivery system, and should prevent infections in adolescents and young adults because of the proven long-term efficacy of hepatitis B immunization. However, because most clinical disease occurs in adults, the addition of routine adolescent vaccination will achieve a more rapid reduction in HBV transmission. Until the cohorts of vaccinated children reach adolescence and adulthood, efforts must be strengthened to vaccinate older adolescents and adults with high-risk behaviors or occupations.
Hepatitis C virus is an RNA virus classified in the Flavivirus family. Like HBV infection, infection with HCV can cause a broad spectrum of disease. Persons with acute HCV infection typically are either asymptomatic or have a mild clinical illness; <20% may have jaundice. The course of acute hepatitis C is variable, although elevations in serum alanine aminotransferase (ALT) levels, often in a fluctuating pattern, are its most characteristic feature. Normalization of ALT levels might occur and suggests full recovery, but this is frequently followed by ALT elevations that indicate progression to chronic disease. Fulminant hepatic failure following acute hepatitis C is rare. Transmission of HCV is usually by direct percutaneous exposure to infectious blood and less commonly by perinatal or sexual exposures. There is no vaccine for hepatitis C.
In the United States, the estimated annual incidence of acute HCV infection was low (18 per 100,000) before 1965, increased steadily through 1980, and remained high (130 per 100,000) through 1989, corresponding to an average of 240,000 infections per year in the 1980s. Since 1989, the incidence of HCV infection has declined by more than 80%, primarily as a result of a decrease in cases among injecting drug users. HCV infection occurs among persons of all ages, but the highest incidence of acute hepatitis C is found among persons 20-29 years old, and males predominate slightly. Non-Hispanic blacks and whites have similar incidence of acute disease; persons of Hispanic ethnicity have higher rates.
In the United States, the relative importance of the two most common exposures associated with the transmission of HCV, blood transfusion and injecting drug use, has changed over time. Blood transfusion, which accounted for 20% – 40% of HCV infections acquired >15 years ago, accounts for <5% of infections acquired during the past 15 years. In contrast, injecting drug use consistently has accounted for a substantial proportion of HCV infections and currently accounts for 60% of HCV transmission in the United States. An average of 20% of persons with HCV infection report sexual exposures (i.e., exposure to an infected sexual partner or to multiple partners) in the absence of percutaneous risk factors. Other known exposures (occupational, hemodialysis, household, perinatal) together account for about 10% of infections. Thus, a potential risk factor can be identified for approximately 90% of persons with HCV infection. In the remaining 10%, no recognized source of infection can be identified, although more than two-thirds of persons in this category are associated with low socioeconomic level.
Case-control and population-based studies have found no association between HCV infection and exposures resulting from medical, surgical, or dental procedures, tattooning, acupuncture, ear piercing, military service, or foreign travel. If transmission from such exposures does occur, the frequency may be too low to detect. Although any percutaneous or mucosal exposure has the potential for transferring infectious blood and potentially transmitting bloodborne pathogens, there are no data showing that persons with a history of exposures such as intranasal cocaine use, tattooning, or body piercing are at increased risk for HCV infection based on these exposures alone. Further studies are needed to determine if these types of exposures and the settings in which they occur (e.g., correctional institutions, unregulated commercial establishments), are risk factors for HCV infection.
To prevent new infections, public health programs should focus on ensuring a safe blood supply, implementing appropriate infection control practices, and preventing initiation of high-risk drug and sexual behaviors. Risks for chronic disease might be reduced by identifying HCV-infected persons through diagnostic testing and by providing appropriate medical management and antiviral therapy. Identification of persons at risk for HCV infection also provides infected persons the opportunity to obtain information about how they can prevent further harm to their liver and prevent transmitting the infection to others. In addition, more effective therapies for treatment of persons with chronic hepatitis C need to be developed, and approaches designed for treating current or former injecting drug users.
Miriam J. Alter, PhD
Bell BP, Shapiro CN, Alter Mj, et. Al. The diverse patterns of hepatitis A epidemiology in the United States – implications for vaccination strategies. J Infect Dis 1998;178:1579-84.
Centers for Disease Control and Prevention. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1999;48(No.RR-12):1-37.
Alter Mj, Margolis HS. The emergence of hepatitis B as a sexually transmitted disease. Med Clin No Amer 1990;74:1529 41.
Alter Mj, Hadler SC, Margolis HS, et al. The changing epidemiology of hepatitis B in the United States: need for alternative vaccination strategies. JAMA 1990;263:1218-22.
Margolis HS, Alter Mj, Hadler SC. Hepatitis B: Evolving epidemiology and implications for control. Semin Liver Dis 1991;11:84-92.
Coleman Pj, McQuillan GM, Moyer LA, et al. Incidence of hepatitis B virus infection in the United States, 1976 – 1994: Estimates from the National Health and Nutrition Examination Surveys. J Infect Dis 1998;178:954-959.
McQuillan GM, Coleman Pj, Kruszon-Moran D, et al. Prevalence of hepatitis B virus infection in the United States: the National Health and Nutrition Examination Surveys 1976 through 1994. Am J Public Health 1999;89:14-18.
Centers for Disease Control: Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991;40 (No. RR-13):1-25.
Armstrong GL, Alter Mj, McQuillan GM, et al. The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the United States. Hepatology 2000;31:777-782.
Alter Mj, Hadler SC, Judson FN, et al. Risk factors for acute non-A, non-B hepatitis in the United States and association with hepatitis C virus infection. JAMA 1990;264:2231-2235.
Alter Mj, Margolis HS, Krawczynski K, et al. The natural history of community-acquired hepatitis C in the United States N Engl J Med 1992;327:1899-1905.
Wasley A, Alter Mj. Epidemiology of hepatitis C: geographic differences and temporal trends. Semin Liver Dis 2000;20:111-126.
Alter Mj, Kruszon-Moran D, Nainan OV, et al. Prevalence of hepatitis C virus infection in the United States. N Engl J Med 1999;341:556-62.
Centers for Disease Control and Prevention.
Recommendations for the prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47(No.RR-19);1-39.