Hepatitis A Virus (HAV)

Subjects: virology, microbiology · Systems: virology, microbiology · Tags: virology, microbiology

Hepatitis A Virus (HAV)

Hepatitis A virus belongs to the Picornaviridae family, specifically the genus Hepatovirus. Like all picornaviruses, it is a small, non-enveloped virus with an icosahedral capsid about 27–32 nm in diameter. Its genome is a positive-sense, single-stranded RNA molecule of roughly 7.5 kb, covalently linked at the 5′ end to VPg and ending with a poly(A) tail. Translation is initiated by an internal ribosome entry site (IRES) rather than a cap, and the viral genome is translated as a single polyprotein that is cleaved into structural and nonstructural proteins. HAV differs from many enteroviruses in that it replicates relatively slowly in culture and is non-cytopathic in its natural host; its pathogenesis stems not from direct viral destruction of hepatocytes but from the host immune response to infected cells.

Transmission is fecal–oral. The virus is acid stable, bile resistant, and environmentally hardy, making it well suited for spread via contaminated food and water. It can survive in shellfish, fresh produce, or inadequately treated water, and it resists many household disinfectants, though chlorine and high temperatures are effective. Epidemiologically, HAV infections were once nearly universal in childhood in areas with poor sanitation, leading to widespread immunity. As sanitation improves, infection shifts to adolescents and adults, in whom disease is more severe. Today, outbreaks are most common in travelers to endemic regions, people who use illicit drugs, homeless populations, and men who have sex with men. Unlike hepatitis B or C, HAV does not establish chronic infection, but the acute illness can be debilitating and, rarely, fulminant.

After ingestion, HAV replicates initially in the oropharynx and intestine, then spreads via the bloodstream to the liver. Hepatocytes and Kupffer cells support viral replication. The virus is released into bile and shed in stool in massive quantities, particularly in the late incubation period and early prodrome—patients are therefore most infectious before jaundice. Histopathologically, infected hepatocytes often appear intact, while periportal inflammation and lymphocytic infiltration reflect immune-mediated injury. Cytotoxic T cells and cytokines clear infection but also produce hepatocellular necrosis, giving rise to clinical hepatitis.

The incubation period averages four weeks (range two to six). Disease typically begins with a prodrome of fatigue, malaise, anorexia, nausea, vomiting, low-grade fever, and right upper quadrant discomfort. Within several days, dark urine and pale stools may appear, followed by jaundice and pruritus. Adults are symptomatic in the majority of cases, whereas many children have subclinical or anicteric infections, contributing to silent spread. The illness usually resolves in several weeks, but prolonged cholestatic hepatitis or relapsing courses with recurrent jaundice can occur. Fulminant hepatic failure is rare but can be life-threatening, particularly in older adults or those with underlying liver disease.

Diagnosis relies on serology. The presence of anti-HAV IgM in serum is diagnostic of acute infection. Anti-HAV IgG appears later and confers lifelong immunity, whether from natural infection or vaccination. Liver function tests show elevated aminotransferases, often in the thousands, along with hyperbilirubinemia and elevated alkaline phosphatase. PCR for HAV RNA is used mainly in research or outbreak investigations rather than routine clinical care.

Treatment is supportive, as no specific antivirals exist. Management emphasizes hydration, avoidance of hepatotoxic drugs or substances (especially alcohol and acetaminophen), and monitoring for signs of acute liver failure. Most patients recover fully without sequelae. In rare fulminant cases, liver transplantation may be necessary.

Prevention is the cornerstone of control. Hygiene measures such as proper handwashing, safe food handling, and adequate sanitation are essential but insufficient in endemic or outbreak settings. Inactivated HAV vaccines, given intramuscularly in two doses, elicit robust anti-HAV IgG responses and long-term protection. These vaccines are recommended universally for children in many countries and for at-risk adults. Immune globulin can provide post-exposure prophylaxis, particularly for unvaccinated contacts, with the choice between vaccine and immunoglobulin depending on age, comorbidities, and timing. Importantly, because HAV is shed before symptom onset, vaccination strategies focus on population immunity rather than ring containment.

In summary, hepatitis A is a classic enterically transmitted picornavirus infection that produces acute but not chronic hepatitis. Its clinical course reflects host immune clearance rather than direct viral cytopathology. Diagnosis is straightforward with serology, treatment is supportive, and prevention through vaccination and sanitation has dramatically reduced its burden. For the clinician and student alike, HAV exemplifies the intersection of virology, immunopathology, and public health.

Disclaimer: For education only. Not medical advice; always follow your institution's guidance.