Lecture Notes: Hepatitis A Virus Infection in Adults

Hepatitis A Virus Infection in Adults 

• Introduction
• Synonym
• Transmission of Hepatitis A Virus 
• Pathogenesis of Hepatic Injury
• Clinical Features
• Laboratory findings
• Diagnosis 
• Treatment 
• Prognosis 
• Prevention  
  

Introduction

Hepatitis A has infected human by causing an acute hepatitis associated with significant morbidity and occasional mortality.

Two distinct forms of hepatitis were recognized in 1947 and were designated hepatitis A and hepatitis B; the hepatitis A virus (HAV) was identified in 1973. In recent years, extensive research has culminated in the development of vaccines that can prevent acute hepatitis A.
In addition, although most patients recover spontaneously, liver transplantation has revolutionized the treatment of fulminant hepatic failure resulting from infection.

Synonym

• Epidemic jaundice,
• Acute catarrhal jaundice, and
• Campaign jaundice.

Transmission of Hepatitis A Virus

• Person to person contact.
• Homosexual contact.
• Contact with contaminated food or water.
• Raw or undercooked shellfish (oysters, clams, mussels).
• Foods contaminated by infected food handlers.
• Persons in daycare centers.
• Persons in institutions.
• Military personnel.
• Transmission through blood transfusions.
• Transmission via intravenous drug use.
• No identifiable risk factor.

Pathogenesis of Hepatic Injury

Injury to the liver is secondary to the host's immune response. Replication of HAV occurs exclusively within the cytoplasm of the hepatocyte, where the virus causes a non cytopathic infection. Hepatocellular damage and destruction of infected hepatocytes is mediated by HLA-restricted, HAV-specific CD8+ T lymphocytes and natural killer cells. Interferon gamma appears to have a central role in promoting clearance of infected hepatocytes. An excessive host response (observable clinically by a marked degree of reduction of HAV RNA during acute infection) is associated with severe hepatitis.

Clinical Features

HAV infection usually results in an acute, self-limited illness and only rarely leads to fulminant hepatic failure. Fulminant hepatic failure occurs more commonly in patients with underlying liver disease, particularly chronic hepatitis C virus infection.

The manifestations also vary with age. HAV infection is usually silent or subclinical in children. In contrast, infection in adults can vary in severity from a mild flu-like illness to fulminant hepatitis.

The incubation period averages 30 days (range 15 to 49 days), after which the illness begins in symptomatic patients with the abrupt onset of prodromal symptoms including, fatigue, malaise, nausea, vomiting, anorexia, fever, and right upper quadrant pain. Within a few days to one week, these patients note dark urine, acholic stool (light-colored stools lacking bilirubin pigment), jaundice, and pruritus. The prodromal symptoms usually diminish when jaundice appears; jaundice typically peaks within two weeks. HAV is rarely associated with a relapsing or cholestatic clinical illness, and may serve as a trigger for autoimmune hepatitis in genetically susceptible individuals.

The two most common physical examination findings are jaundice and hepatomegaly. Less common findings include splenomegaly, cervical lymphadenopathy, evanescent rash, arthritis, and, rarely, a leukocytoclastic vasculitis.

A variety of extrahepatic manifestations have been associated with acute HAV infection including vasculitis, arthritis, optic neuritis, transverse myelitis, thrombocytopenia, aplastic anemia, and red cell aplasia. These conditions are more likely in patients who have protracted illness.

Laboratory findings

Laboratory findings in symptomatic patients are notable for marked elevations of serum aminotransferases (usually >1000 IU/dL), serum total and direct bilirubin, and alkaline phosphatase. The serum alanine aminotransferase (ALT) is commonly higher than the serum aspartate aminotransferase (AST). The serum aminotransferase elevations precede the bilirubin elevation, with the peak bilirubin concentration occurring after the peak aminotransferase elevations. Serum bilirubin levels above 10 mg/dL are common. Other laboratory abnormalities include nonspecific elevations of acute phase reactants, elevated erythrocyte sedimentation rate, and increased immunoglobulins.

Diagnosis

The diagnosis of acute HAV infection is made by the detection of anti-HAV antibodies in a patient with the typical clinical presentation. Serum IgM anti-HAV is the gold standard for the detection of acute illness. The presence of serum IgM anti-HAV antibodies in adults without clinical features of viral hepatitis does not necessarily indicate acute infection. Such patients may have previous HAV infection with prolonged presence of IgM anti-HAV, a false-positive result, or asymptomatic infection (which is much more common in children less than six compared with older children and adults).

Anti-HAV is positive at the onset of symptoms, peaks during the acute or early convalescent phase of the disease, and remains positive for approximately four to six months. The serologic detection of antibodies is simpler, easier, and less expensive than other techniques, such as HAV detection in stool and body fluids by electron microscopy and HAV RNA detection in stool, body fluids, serum, and liver tissue. IgG anti-HAV appears early in the convalescent phase of the disease, and remains detectable for decades.

Treatment

Because the disease is usually self-limited, the treatment is supportive. Patients who develop fulminant infection require aggressive supportive therapy, and should be transferred to a center capable of performing liver transplantation.

Prognosis

Fatalities due to hepatitis A are more common with advancing age and in patients with chronic hepatitis C.

Prevention

Hepatitis A is transmitted predominantly by the fecal-oral route. The incubation period is 2 to 6 weeks; infected individuals are contagious during the incubation period and remain so for about a week after jaundice appears.

Prevention can be aided by adherence to sanitary practices such as:

• handwashing,
• heating foods appropriately,
• avoidance of water and foods from endemic areas,
• chlorination and certain disinfecting solutions (household bleach 1:100 dilution).