Hepatitis A virus (HAV) infection can cause typical complications, such as prolonged cholestasis and relapsing hepatitis. However, other complications are rarely reported but need attention, such as acute liver failure, acute renal failure, interstitial nephritis, erythrocyte aplasia, bone marrow aplasia, Guillain-Barré syndrome.

Hepatitis A virus is transmitted via the fecal-oral route. Humans are known to be the only reservoir for HAV. The prognosis of hepatitis A cases is generally good, in which most patients do not experience sequelae, recurrence, or progression to chronic disease. However, some patients may experience complications, ranging from self-limiting to more fatal ones.

Typical Complications of Hepatitis A

Acute HAV infection will cause necroinflammation in the liver, which usually resolves spontaneously without chronic sequelae (> 99% of cases). Common symptoms include fever, malaise, fatigue, loss of appetite, diarrhea, anorexia, myalgia, arthralgia, headache, dark urine, and jaundice.

Complications typical of HAV infection are cholestatic hepatitis (about 5%), relapsing hepatitis (3–20%), and autoimmune hepatitis. Cholestatic hepatitis is characterized by:
  • a long period of jaundice (can be> 3 months), 
  • Elevated serum bilirubin (often> 10 mg / dL), alkaline phosphatase, aminotransferase, and serum cholesterol. In general, cholestatic hepatitis will resolve spontaneously without sequelae.
Approximately 3–20% of hepatitis A patients also experience hepatitis A relapse within six months of infection onset. The duration of clinical relapse is generally <3 weeks, but the liver biochemical relapse duration may be longer. The clinical manifestations are milder than the initial episodes of disease and generally also resolve spontaneously without sequelae. Autoimmune hepatitis is also possible, where this complication is thought to be caused by molecular mimicry processes and genetic susceptibility.

Rare Complications of Hepatitis A

Many atypical complications can result from HAV infection. These complications can arise in the organs:
  • kidneys: interstitial nephritis or acute renal failure, 
  • liver: acute liver failure, 
  • heart: myocarditis or cardiomyopathy, 
  • nervous system: Guillain-Barré syndrome, transverse myelitis, or optic neuritis. 

There are other atypical complications, such as red cell aplasia, bone marrow aplasia, and acute arthritis.

Although rare, fulminant hepatitis with acute liver failure can cause death, especially if a liver transplant cannot be performed. Hepatitis A mortality due to acute liver failure can be as high as 90% in adults who have not had a liver transplant and 74% in children who have not had liver transplants.

The pathogenetic mechanisms behind these atypical complications are not well understood. Some hypotheses suggest that the complex immune response in susceptible individuals may play a role. However, this hypothesis has yet to be proven.

Management of Atypical Complications of Hepatitis A

The treatment of complications that are not common in hepatitis A is generally the same as that of ordinary hepatitis A, namely in supportive therapy and additional special therapy according to each patient's condition. For example, aspirin can be given in myocarditis cases, while hemodialysis can be recommended for acute renal failure patients.

Immunosuppressive therapy (e.g., corticosteroids) or intravenous immunoglobulin can be given in red cell aplasia, Guillain-Barré syndrome, transverse myelitis, and optic neuritis. Other special therapies, such as bone marrow transplant, can be used in severe aplastic anemia, and liver transplantation can be done in acute liver failure cases.

Factors Affecting the Clinical Outcome of Hepatitis A and its Complications

The clinical outcome of hepatitis A virus infection appears to be age-related. Most of the asymptomatic cases occurred in children aged <6 years, whereas symptomatic cases generally occurred in older children, adults, and geriatrics. Disease severity and fatal outcome were more frequently reported in the older age group.

The estimated case-fatality ratio for hepatitis A is reported to vary depending on age, namely 0.1% in the <15 years age group, at 0.3% in the 15–39 year age group, and increasing to 1.8–5.4% over 50 years old.

According to Argentina's epidemiological data, since the introduction of universal hepatitis A immunization, the percentage of fulminant hepatitis due to HAV has decreased from 54.6% in 1993–2005 to 27.7% in 2005–2008. These data demonstrate the benefits of hepatitis A immunization in reducing the incidence of fulminant hepatitis.

The epidemiological data from Argentina are also supported by the results of a study by Vizzotti et al., which showed that implementing a single-dose hepatitis A vaccination strategy effectively controlled hepatitis A infection.

Hepatitis A cases generally have a good prognosis, in which most patients experience recovery without chronic sequelae. However, a minority of patients can experience complications. Typical complications of hepatitis A are cholestatic hepatitis, relapsed hepatitis, and autoimmune hepatitis. Atypical complications that are not common but need to be aware of are acute liver failure, acute renal failure, interstitial nephritis, red cell aplasia, bone marrow aplasia, Guillain-Barré syndrome.

Age and history of hepatitis A vaccination appear to play a role in determining the clinical outcome of hepatitis A cases and its complications. This needs clinicians and health policymakers' attention to reduce morbidity and mortality due to HAV infection in the future.