Hepatitis A Virus : Clinical Features, Laboratory Diagnosis, and Medical Management
Hepatitis A is caused by infection with HAV, a nonenveloped RNA virus that is classified as a picornavirus. It was first isolated in 1979. Humans are the only natural host, although several nonhuman primates have been infected in laboratory conditions. Depending on conditions, HAV can be stable in the environment for months. The virus is relatively stable at low pH levels and moderate temperatures but can be inactivated by high temperature (185°F [85°C] or higher), formalin, and chlorine.
Pathogenesis
HAV is acquired by mouth (through fecal-oral transmission) and replicates in the liver. After 10–12 days, virus is present in blood and is excreted via the biliary system into the feces. Peak titers occur during the 2 weeks before onset of illness. Although virus is present in serum, its concentration is several orders of magnitude less than in feces. Virus excretion begins to decline at the onset of clinical illness, and has decreased significantly by 7–10 days after onset of symptoms. Most infected persons no longer excrete virus in the feces by the third week of illness. Children may excrete virus longer than adults.
Clinical Features
The incubation period of hepatitis A is approximately 28 days (range 15–50 days). The clinical course of acute hepatitis A is indistinguishable from that of other types of acute viral hepatitis. The illness typically has an abrupt onset of fever, malaise, anorexia, nausea, abdominal discomfort, dark urine and jaundice. Clinical illness usually does not last longer than 2 months, although 10%–15% of persons have prolonged or relapsing signs and symptoms for up to 6 months. Virus may be excreted during a relapse.
The likelihood of symptomatic illness from HAV infection is directly related to age. In children younger than 6 years of age, most (70%) infections are asymptomatic. In older children and adults, infection is usually symptomatic, with jaundice occurring in more than 70% of patients.
Complications
Severe clinical manifestations of hepatitis A infection are rare, however atypical complications may occur, including immunologic, neurologic, hematologic, pancreatic, and renal extrahepatic manifestations. Relapsing hepatitis, cholestatic hepatitis A, hepatitis A triggering autoimmune hepatitis, subfulminant hepatitis, and fulminant hepatitis have also been reported. Fulminant hepatitis is the most severe rare complication, with mortality estimates up to 80%. In the prevaccine era, fulminant hepatitis A caused about 100 deaths per year in the United States.
The hepatitis A case-fatality rate among persons of all ages with reported cases was approximately 0.3% but may have been higher among older persons (approximately 2% among persons 40 years of age and older) More recent case-fatality estimates range from 0.3%–0.6% for all ages and up to 1.8% among adults aged >50 years. Vaccination of high risk groups and public health measures have significantly reduced the number of overall hepatitis A cases and fulminant HAV cases. Nonetheless, hepatitis A results in substantial morbidity, with associated costs caused by medical care and work loss.
Laboratory Diagnosis
Hepatitis A cannot be distinguished from other types of viral hepatitis on the basis of clinical or epidemiologic features alone. Serologic testing is required to confirm the diagnosis. Virtually all patients with acute hepatitis A have detectable IgM anti-HAV. Acute HAV infection is confirmed during the acute or early convalescent phase of infection by the presence of IgM anti-HAV in serum. IgM generally becomes detectable 5–10 days before the onset of symptoms and can persist for up to 6 months.
IgG anti-HAV appears in the convalescent phase of infection, remains present in serum for the lifetime of the person, and confers enduring protection against disease. The antibody test for total anti-HAV measures both IgG anti-HAV and IgM anti-HAV. Persons who are total anti-HAV positive and IgM anti-HAV negative have serologic markers indicating immunity consistent with either past infection or vaccination.
Molecular virology methods such as polymerase chain reaction (PCR)-based assays can be used to amplify and sequence viral genomes. These assays are helpful to investigate common-source outbreaks of hepatitis A. Providers with questions about molecular virology methods should consult with their state health department or the CDC Division of Viral Hepatitis.
Medical Management
There is no specific treatment for hepatitis A virus infection. Treatment and management of HAV infection are supportive.
Epidemiology
Occurrence
Hepatitis A occurs throughout the world. It is highly endemic in some areas, particularly Central and South America, Africa, the Middle East, Asia, and the Western Pacific.
Reservoir
Humans are the only natural reservoir of the virus. There are no insect or animal vectors. A chronic HAV state has not been reported.
Transmission
HAV infection is acquired primarily by the fecal-oral route by either person-to-person contact or ingestion of contaminated food or water. Since the virus is present in blood during the illness prodrome, HAV has been transmitted on rare occasions by transfusion. Although HAV may be present in saliva, transmission by saliva has not been demonstrated. Waterborne outbreaks are infrequent and are usually associated with sewage-contaminated or inadequately treated water.
Temporal Pattern
There is no appreciable seasonal variation in hepatitis A incidence. In the prevaccine era, cyclic increases in reported acute cases were observed every 5- 10 years, and were characterized by large community outbreaks of disease. Since introduction of vaccination in the United States, these increases no longer occur.
Communicability
Viral shedding persists for 1 to 3 weeks. Infected persons are most likely to transmit HAV 1 to 2 weeks before the onset of illness, when HAV concentration in stool is highest. The risk then decreases and is minimal the week after the onset of jaundice.
Risk Factors
Groups at increased risk for hepatitis A or its complications include international travelers (particularly high-risk itineraries like travel to rural areas in high-risk countries), contacts of recent international adoptees from HAV endemic countries, men who have sex with men, and users of illegal drugs. Outbreaks of hepatitis A have also been reported among persons working with hepatitis A–infected primates. This is the only occupational group known to be at increased risk for hepatitis A.
Persons with chronic liver disease are not at increased risk of infection but are at increased risk of acquiring fulminant hepatitis A. Persons with clotting factor disorders may be at increased risk of HAV because of administration of solvent/ detergent-treated factor VIII and IX concentrates.
Foodhandlers are not at increased risk for hepatitis A because of their occupation, but are noteworthy because of their critical role in common-source foodborne HAV transmission. Health-care personnel do not have an increased prevalence of HAV infections, and nosocomial HAV transmission is rare. Nonetheless, outbreaks have been observed in neonatal intensive care units and in association with adult fecal incontinence. Institutions for persons with developmental disabilities previously were sites of high HAV endemicity. However, as fewer children have been institutionalized, conditions within these institutions have improved, and more children have been vaccinated.
HAV incidence and prevalence have decreased, but sporadic outbreaks can occur. Schools are not common sites for HAV transmission. Multiple cases among children at a school require investigation of a common source and efforts to improve vaccination coverage. No worker related HAV infection have been reported in the United States. Consistently, serologic studies in the US have shown no or mildly increased risk of HAV infection in wastewater workers.
Children play an important role in HAV transmission. Children generally have asymptomatic or unrecognized illnesses, so they may serve as a source of infection, particularly for household or other close contacts.
In 2010, 75% of hepatitis A cases (who responded to any question about risk behaviors and exposures) indicated no risk factors for their infection. Of cases indicating at least one risk factor 2-6 weeks prior to the onset of illness, the most frequently reported source of infection was personal contact (sexual or household) with an infected person (7.3%). Employment or attendance at a nursery, day-care center, or preschool involved 3.1% of cases; 4% involved contact with a child or employee in child care; 14.1% occurred among persons reporting recent international travel; and 10.4% occurred in the context of a recognized foodborne or waterborne outbreak. Injection-drug use was a reported risk factor in 2% of cases; men who have sex with men represented 4.9% of cases.
Of the 1,398 case reports of acute hepatitis A received by CDC during 2011, a total of 571 (41%) cases did not include a response (i.e. a “yes” or “no” response to any of the questions about risk behaviors and exposures) to enable assessment of risk behaviors or exposures. Of the 827 case reports that had a response, 646 (78%) indicated no risk behaviors/exposures for acute hepatitis A, and 181 (22%) indicated at least one risk behavior/exposure for acute hepatitis A during the 2-6 weeks prior to onset of illness.
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