Hepatitis A

Essentials of Diagnosis

• Prodrome of anorexia, nausea, vomiting, malaise, aversion to smoking

• Fever, enlarged and tender liver, jaundice

• Normal to low white blood cell count; markedly elevated aminotransferases

General Considerations

• Transmission of hepatitis A virus (HAV) is by the fecal-oral route by either person-to-person contact or ingestion of contaminated food or water

• The incubation period averages 30 days

• HAV is excreted in feces for up to 2 weeks before the clinical illness and rarely persists in feces after the first week of illness

• There is no chronic carrier state

Demographics

• Globally, 15 million people are infected with HAV annually

• HAV spread is favored by crowding and poor sanitation

• HAV infection is hyperendemic in developing countries

• Common source outbreaks result from contaminated water or food

• In 2017, an outbreak in California and four other states affected a large number of homeless persons and resulted in many deaths

• HAV has been described as a reemerging food-borne public health threat in Europe

• Outbreaks have been reported among injection drug users

• Since introduction of HAV vaccine in the United States in 1995, the incidence rate of HAV infection has declined from 14 to 0.4 per 100,000 population

Symptoms and Signs

• Onset may be abrupt or insidious

• Malaise, myalgia, arthralgia, easy fatigability, upper respiratory symptoms, and anorexia

• A distaste for smoking, paralleling anorexia, may occur early

• Nausea and vomiting are frequent, and diarrhea or constipation may occur

• Defervescence and a fall in pulse rate often coincide with the onset of jaundice

• Abdominal pain

  • Usually mild and constant in the right upper quadrant or epigastrium

  • Often aggravated by jarring or exertion

  • Rarely severe enough to simulate cholecystitis

• Jaundice

  • Never develops in many patients

  • Occurs after 5–10 days but may appear at the same time as the initial symptoms

  • With its onset, prodromal symptoms often worsen, followed by progressive clinical improvement

  • Stools may be acholic

• Hepatomegaly—rarely marked—is present in over 50% of cases; liver tenderness is usually present

• Splenomegaly occurs in 15% of patients

• Soft, enlarged lymph nodes—especially in the cervical or epitrochlear areas—may occur

• The acute illness usually subsides over 2–3 weeks

• Complete clinical and laboratory recovery by 9 weeks

• Clinical, biochemical, and serologic recovery may be followed by one or two relapses, but recovery is the rule

• A protracted course has been reported to be associated with HLA DRB1*1301

Differential Diagnosis

• Other viruses that cause hepatitis, particularly hepatitis B and C viruses, as well as Epstein-Barr (infectious mononucleosis) virus, cytomegalovirus, herpes simplex virus, Middle East respiratory syndrome virus, yellow fever virus, influenza virus, Ebola virus, and others

• Spirochetal diseases, such as leptospirosis and secondary syphilis

• Brucellosis

• Rickettsial diseases, such as Q fever

• Autoimmune hepatitis

• Drug-induced liver disease

• Ischemic hepatitis (shock liver)

• Rarely, metastatic cancer, lymphoma, or leukemia

• The prodromal phase of viral hepatitis must be distinguished from other infectious disease such as influenza, upper respiratory infections, and the prodromal stages of exanthematous diseases

Laboratory Tests

• Antibody to hepatitis A (anti-HAV) appears early in the course of the illness

• Both IgM and IgG anti-HAV are detectable in serum soon after the onset

• Peak titers of IgM anti-HAV occur during the first week of clinical disease and usually disappear within 3–6 months

• Detection of IgM anti-HAV is an excellent test for diagnosing acute hepatitis A (but is not recommended for evaluation of asymptomatic patients with persistent serum aminotransferase elevations)

• Titers of IgG anti-HAV peak after 1 month of the disease and may persist for years

• IgG anti-HAV indicates previous exposure to HAV, noninfectivity, and immunity. In the United States, about 30% of the population have serologic evidence of previous infection

• The white blood cell count is normal to low, especially in the preicteric phase. Large atypical lymphocytes may occasionally be seen

• Mild proteinuria is common, and bilirubinuria often precedes the appearance of jaundice

• Strikingly elevated serum alanine or aspartate aminotransferases occur early, followed by elevations of bilirubin and alkaline phosphatase; in a small number of patients, the latter persist after aminotransferase levels have normalized

• Cholestasis is occasionally marked

Medications

• If nausea and vomiting are pronounced or if oral intake is substantially decreased, intravenous 10% glucose is indicated

• Small doses of oxazepam are safe, since its metabolism is not hepatic; morphine sulfate should be avoided

• Corticosteroids have no benefit in patients with viral hepatitis, including those with acute liver failure

Therapeutic Procedures

• Bed rest is recommended only for marked symptoms

• Dietary management consists of palatable meals as tolerated, without overfeeding; breakfast is usually best tolerated

• Strenuous physical exertion, alcohol, and hepatotoxic agents should be avoided

Complications

• Acute liver failure due to hepatitis A is uncommon; the frequency is increased when hepatitis A occurs in a patient with chronic hepatitis C

• Other occasional extrahepatic complications include

  • Acute kidney injury

  • Arthritis

  • Vasculitis

  • Acute pancreatitis

  • Aplastic anemia

  • Variety of neurologic manifestations

Prognosis

• Generally, clinical recovery is complete in 9 weeks

• Hepatitis A does not cause chronic liver disease, though it may persist for up to 1 year, and clinical and biochemical relapses may occur before full recovery

• The mortality rate is < 1%, with a higher rate in older adults than in younger persons

Prevention

• Strict isolation is not necessary, but hand washing after bowel movements is required

• Thorough hand washing by anyone who may contact contaminated utensils, bedding, or clothing is essential

Immune globulin

• Give to all close (eg, household) personal contacts and consider giving it to persons who consume food prepared by an infected food handler

• The recommended dose, 0.02 mL/kg intramuscularly, is protective if administered during incubation

Vaccination

• Two effective inactivated hepatitis A vaccines are recommended for

  • Persons living in or traveling to endemic areas (including military personnel)

  • Patients with chronic liver disease on diagnosis

  • Persons with clotting-factor disorders who are treated with factor concentrates

  • Men who have sex with men

  • Animal handlers

  • Illicit drug users

  • Sewage workers

  • Food handlers

  • Close personal contacts of international adoptees

  • Children and caregivers in day care centers and institutions

• HAV vaccine is effective in the prevention of secondary spread to household contacts of primary cases

• The recommended dose for adults

  • 1 mL (1440 ELISA units) of Havrix (GlaxoSmithKline) or 1 mL (50 units) of Vaqta (Merck) intramuscularly

  • Follow with a booster dose at 6–18 months

• A combined hepatitis A and B vaccine (Twinrix, GlaxoSmithKline) is available

When to Admit

• Encephalopathy is present

• INR > 1.6

• The patient is unable to maintain hydration