What are the clinical manifestations of Hepatitis A Virus (HAV) infection?

Clinical Manifestations of Hepatitis A Virus (HAV) Infection

The clinical presentation of HAV infection is highly age-dependent: children under 6 years are asymptomatic in >90% of cases, while adults typically develop symptomatic illness with jaundice in >70% of cases. 1

Age-Dependent Symptom Patterns

Children

• Children younger than 6 years experience asymptomatic infection in more than 90% of cases, and when symptoms do occur, they typically present without jaundice 1
• The likelihood of jaundice increases with age: fewer than 10% of children aged 0-4 years develop jaundice, rising to 30-40% in children aged 5-9 years, and 60-80% in youths aged 10-17 years 2
• Children can shed virus for longer periods than adults, up to 10 weeks after illness onset, with neonatal infections potentially shedding for up to 6 months 1

Adults

• Among adults aged ≥18 years, 80-90% develop symptomatic illness with jaundice 2
• Older adults face higher mortality risk, with case-fatality rates reaching 1.8% in those >50 years compared to 0.6% in younger adults 2

Timeline and Clinical Course

Incubation Period

• The average incubation period is 28 days (range: 15-50 days) from exposure to symptom onset 2, 1

Prodromal Phase

• A 1-7 day prodromal illness precedes jaundice, characterized by vague symptoms including anorexia, malaise, fever, and nausea 1
• Fatigue and loss of appetite typically precede jaundice by 1-2 weeks 2

Acute Symptomatic Phase

• Dark urine is often the first noticeable symptom prompting medical attention 1
• Within days of bilirubinuria onset, feces become clay-colored and jaundice appears in the sclera, skin, and mucous membranes 1
• The illness typically includes fever, malaise, anorexia, nausea, abdominal discomfort, dark urine, and jaundice 2

Physical Examination Findings

• Jaundice is the predominant clinical sign in symptomatic cases 2
• Hepatomegaly and splenomegaly may be present 2
• Mild to moderate liver tenderness is usually detected 3

Infectivity Period

Peak infectivity occurs during the 2-week period before onset of jaundice or elevation of liver enzymes, when viral concentration in stool is highest 2, 1. This represents a critical public health concern as patients are most contagious before they know they are ill.

Disease Duration and Complications

Typical Course

• When signs and symptoms occur, they typically last <2 months 2
• The period of jaundice persists for <2 weeks in approximately 85% of cases 3

Prolonged or Relapsing Disease

• Approximately 10-20% of patients experience prolonged or relapsing disease lasting up to 6 months 2, 1, 4
• About 20% of patients with relapsing disease have multiple relapses 1

Fulminant Hepatitis

• Fulminant hepatitis A occurs in <1% of cases but carries significant mortality risk 1, 4
• The overall case-fatality ratio is approximately 0.3-0.6%, but reaches 1.8% in adults >50 years 1
• Patients with chronic liver disease face increased risk for acute liver failure 2

Extrahepatic Manifestations

• Although rare, extrahepatic manifestations have been described in approximately 14% of cases 5
• These can include skin rash, arthralgias, arthritis, cardiomyopathy, and aplastic anemia 5
• Such manifestations are more common in older patients with high bilirubin levels 5

Diagnostic Considerations

Hepatitis A cannot be differentiated from other types of viral hepatitis based on clinical features alone 1. Serologic testing to detect IgM antibody to HAV (IgM anti-HAV) is required to confirm acute infection 1. Serum IgM anti-HAV becomes detectable 5-10 days before symptom onset in most persons 1.

Important Clinical Pitfalls

• The asymptomatic nature of infection in young children makes them efficient silent transmitters, particularly in household and daycare settings 1
• Peak infectivity precedes symptoms, making isolation after symptom onset less effective for outbreak control 2, 1
• Complete clinical recovery is the rule, with restoration of normal liver function by 6 months in nearly all adult patients; chronic hepatitis does not occur with HAV 3