Hepatitis A, B, C, D, and E: Focus on Adult Infections

Epidemiology

According to the World Health Organization (WHO), hepatitis A caused approximately 7134 deaths in 2016, which accounted for 0.5% of mortality due to viral hepatitis. Transmission being primarily fecal-oral, risk factors are lack of safe water and poor sanitation and hygiene (such as dirty hands). Worldwide, the endemicity of HAV infection differs markedly among and within countries depending on the age groups in which the majority of transmission occurs. In areas with a high endemic pattern of infection, represented by low-income countries in parts of Africa, Asia, and Central and South America, most persons are infected as young children, and essentially the entire population becomes infected and immune before reaching adolescence. At the other end of the spectrum are the higher-income countries in most areas of North America and Western Europe, in which the endemicity of HAV infection is low. Relatively fewer children are infected, and disease often occurs in the context of communitywide outbreaks, as well as in defined risk groups such as men who have sex with men (MSM), injection drug users (IDUs), and travelers returning from areas with a high or intermediate endemicity of infection ( Fig. 68.1 ).

HAV replicates in the liver, is excreted in bile, and is shed in stool. Peak infectivity occurs during the 2-week period before onset of jaundice or elevation of liver enzymes, when concentration of the virus in stool is highest. The concentration of the virus in stool declines after jaundice appears. Children can shed HAV for longer periods than adults, with shedding lasting up to 10 weeks after onset of clinical illness; infants infected as neonates in one nosocomial outbreak shed HAV for up to 6 months, but lifelong shedding of the virus does not occur.

In the United States, person-to-person transmission through the fecal-oral route is the primary means of HAV transmission. Transmission occurs most frequently among close contacts, especially in households, extended family settings, daycare facilities, correctional facilities, and unsheltered populations. Common-source outbreaks and sporadic cases can occur from exposure to food or water contaminated at the source or by infected food handlers. Outbreaks in the context of floods or other natural disasters (e.g., hurricanes) have not been reported in the United States. On rare occasions, HAV infection has been transmitted by transfusion of blood or blood products collected from donors during the viremic phase of their infection. In the United States and other countries where the hepatitis A vaccine has been incorporated into standard childhood immunization programs, the burden of HAV infections has shifted to older unimmunized age groups who are more likely to be symptomatic (see Chapter 14 ).

Clinical Illness

HAV, a 27-nm ribonucleic acid (RNA) agent classified as a picornavirus, can produce either asymptomatic or symptomatic infection in humans after an average incubation period of 28 days (range 15 to 50 days). Illness caused by HAV infection typically has an abrupt onset that can include fever, malaise, anorexia, nausea, abdominal discomfort, dark urine, and jaundice. The likelihood of having symptoms with HAV infection is related to age. In children younger than 6 years, 70% of infections are asymptomatic; if illness does occur, it is typically not accompanied by jaundice. Among older children and adults, infection is typically symptomatic, with jaundice occurring in more than 70% of patients. Signs and symptoms typically last less than 2 months, although 10% to 15% of symptomatic persons have prolonged or relapsing disease lasting up to 6 months ( Fig. 68.2 ). However, persistent infections with HAV are not well documented and may never occur. The overall case-fatality ratio among reported cases in the United States is approximately 0.3% to 0.6% but reaches 1.8% among adults older than 50 years; persons with preexisting chronic liver disease are at increased risk of acute liver failure from HAV infection.

Diagnosis

HAV cannot be differentiated from other types of viral hepatitis on the basis of clinical or epidemiologic features alone. Two serologic tests are licensed for the detection of antibodies to HAV: (1) immunoglobulin M antibody to HAV (IgM anti-HAV) and (2) total anti-HAV (i.e., IgM and IgG anti-HAV). Serologic testing to detect IgM anti-HAV is required to confirm a diagnosis of acute HAV. In the majority of persons, serum IgM anti-HAV becomes detectable 5 to 10 days before onset of symptoms and declines to undetectable levels less than 6 months after infection. IgG anti-HAV, which appears early in the course of infection, remains detectable for the person’s lifetime and provides lifelong protection against the disease.

Treatment

HAV does not cause persistent infection and rarely causes hepatic failure. Supportive care is the mainstay of treatment for HAV infections. Individuals with acute HAV with altered mental status or severe dehydration from nausea and vomiting require hospitalization. Laboratory results revealing increased international normalized ratio (INR) and/or reduced albumin may indicate systemic dysfunction that requires consultation with a hepatologist. If hepatic encephalopathy develops, liver transplantation may be indicated. Patients with minimal symptoms can be managed on an outpatient basis.

Prevention

Depending on conditions, HAV can be stable in the environment for months. Heating foods at temperatures greater than 185°F (85°C) for 1 minute or disinfecting surfaces with a 1:100 dilution of sodium hypochlorite (i.e., household bleach) in tap water is necessary to inactivate HAV. HAV can be prevented by (1) general measures of good personal hygiene, particularly hand washing, provision of safe drinking water, and proper disposal of sanitary waste; (2) preexposure or postexposure immunization with HAV vaccine; and (3) preexposure or postexposure immunization with immunoglobulin (see Chapter 14 ). In the United States, preexposure administration of HAV vaccine is recommended for all children 1 year of age and older, international travelers, MSM, injection and noninjection illicit drug users, and individuals with chronic liver disease. Inactivated HAV vaccines are safe, highly immunogenic, and well tolerated. Table 68.2 lists the HAV vaccines and schedules approved by the US Food and Drug Administration (FDA). Other HAV vaccine products, including attenuated live vaccines, may be available in other countries.

Epidemiology

Approximately one-third of the global population has been infected with HBV. Around 5% of this population are chronic carriers and a quarter of these carriers develop serious liver diseases such as chronic hepatitis, cirrhosis, and hepatic carcinoma. Globally, hepatitis B prevalence is highest in the WHO Western Pacific Region and the WHO African Region, where 6.2% and 6.1% of the adult population is infected, respectively. In the general US population, the overall age-adjusted prevalence of HBV infection (including persons with chronic infection and those with previous infection) is 4.9%. The estimated prevalence of chronic HBV infection is 0.5%, corrected for the disproportionate contribution of foreign-born persons (particularly Asian/Pacific Islanders) who have emigrated from countries in which HBV is highly endemic. It is estimated that there were 862,000 persons with chronic HBV infection in 2016, and 22,000 new infections in 2017 nationwide.

HBV is a blood-borne and sexually transmitted virus. Transmission from infected mothers to their newborns at the time of birth is the most common source for HBV infection among infants. For adults, the primary sources are sexual (male to female and male to male) and percutaneous (e.g., injection drug use) exposures to blood. For all age groups, unsafe therapeutic injections, unscreened blood transfusions, and long-term nonsexual household contact with chronically infected persons are risks for acquiring HBV infection.

Chronic infection (serum positivity for hepatitis B surface antigen [HBsAg]) is more likely to develop in infants infected at birth (90%) or young children infected at ages 1 to 5 years (25% to 50%), most of whom do not have symptoms. Rates of symptomatic acute disease are higher among older children and adults, who are less likely to develop chronic infection. Prevalence of chronic infection with HBV is high in countries or regions where HBV infections were historically acquired primarily by infants and young children, including countries in South America, Africa, the Middle East, Asia, Southeast Asia, Greenland, the First Nation populations of northern Canada, and Alaskan Native Americans ( Fig. 68.3 ). In those countries or regions where universal childhood hepatitis B immunization programs have been implemented, early-age infections have been virtually eliminated and adults account for the remaining chronic infections (see Chapter 15 ).

Clinical Presentation

HBV is a 42-nm DNA virus classified in the family Hepadnaviridae. HBV infection can produce either asymptomatic or symptomatic infection. The average incubation period is 90 days (range 60 to 150 days) from exposure to onset of jaundice, 60 days (range 40 to 90 days) from exposure to onset of abnormal serum alanine aminotransferase (ALT) levels, and 30 days (range 6 to 60 days) from exposure to detection of HBsAg. The onset of acute disease is usually insidious. Infants, young children, and immunosuppressed adults with newly acquired HBV infection are typically asymptomatic. When present, clinical symptoms and signs might include anorexia, malaise, nausea, vomiting, abdominal pain, and jaundice (see Fig. 68.2 ). Extrahepatic manifestations of disease include skin rashes, arthralgias, and arthritis. The case-fatality rate for acute HBV is 0.5% to 1%.

Most (≥95%) primary infections in adults with normal immune status are self-limited, with elimination of the virus from the blood and development of lasting immunity to reinfection. In contrast, primary infection develops into chronic infection in 30% of children younger than age 5 and in 80% to 90% of infants, with continuing viral replication in the liver and persistent viremia.

Although the consequences of acute HBV can be severe, most of the serious sequelae associated with the disease occur in chronically infected persons, who are at increased risk for developing cirrhosis, decompensated liver disease, and primary HCC. Persons who should be tested for chronic HBV infection include those born in geographic regions with HBsAg prevalence ≥2% (see Fig. 68.3 ), persons with unexplained elevations in liver enzymes, persons infected with HIV, and persons undergoing immunosuppressive therapy.

Host and viral risk factors associated with disease progression include older age (longer duration of infection), high levels of HBV deoxyribonucleic acid (DNA), habitual alcohol consumption, and concurrent infection with HCV, HDV, or HIV. Persons with chronic infection also serve as the reservoir for continued HBV transmission. Extrahepatic manifestations related to chronic HBV infection include immune complex–mediated diseases such as membranoproliferative glomerulonephritis.