• Incubation period: 30–180 days, typically about 3 months
• Most infections are asymptomatic.
• More likely to be severe in patients co-infected with hepatitis C or D
• Constitutional symptoms may precede the onset of jaundice by 1–2 weeks (prodromal symptoms).
  • Anorexia
  • Nausea
  • Vomiting
  • Fatigue
  • Malaise
  • Arthralgias
  • Myalgias
  • Headache
  • Photophobia
  • Pharyngitis
  • Cough
  • Coryza
  • Low-grade fever
• Symptoms and signs related to liver dysfunction
  • Jaundice
  • Dark urine
  • Clay-colored stools
  • Tender hepatomegaly
  • Right upper-quadrant pain
• Uncommon symptoms and signs
  • Splenomegaly (10–20% of patients with acute hepatitis)
  • Cervical adenopathy (10–20% of patients with acute hepatitis)
  • Spider angiomata
• Extrahepatic manifestations
  • Signs of extensive acute immune reactivity: arthritis, urticaria, angioedema
  • Hematuria
  • Proteinuria
• Rare presentation in childhood
  • Papular acrodermatitis of childhood or Gianotti–Crosti syndrome
    • Anicteric hepatitis
    • Non-pruritic papular rash of the face, buttocks, and limbs
    • Lymphadenopathy

Differential Diagnosis

• Other hepatitis viruses
• Other viral illnesses that frequently involve the liver
  • Infectious mononucleosis
  • Cytomegalovirus
  • Herpes simplex
  • Coxsackieviruses
• Toxoplasmosis
• Rare causes of liver injury confused with viral hepatitis
  • Leptospira species
  • Candida species
  • Brucella species
  • Mycobacteria species
  • Pneumocystis species
• Many drugs and certain anesthetic agents
• Alcoholic hepatitis
• Acute cholecystitis
• Common duct stone
• Ascending cholangitis
• Carcinoma of the pancreas
• Other clinical constellations that may mimic acute hepatitis
  • Right ventricular failure with passive hepatic congestion
  • Hypoperfusion syndromes
    • Shock
    • Severe hypotension
    • Severe left ventricular failure
  • Any disorder that interferes with venous return to the heart
    • Right-atrial myxoma
    • Constrictive pericarditis
    • Hepatic vein occlusion (Budd–Chiari syndrome)
    • Veno-occlusive disease
• Disorders in pregnancy that may be confused with viral hepatitis
  • Acute fatty liver of pregnancy
  • Cholestasis of pregnancy
  • Eclampsia
  • HELLP syndrome (hemolysis, elevated liver enzyme levels, and low platelet count)
• Genetic or metabolic liver disorders
  • Wilson disease
  • α₁–Antitrypsin deficiency
  • Hemochromatosis
• Nonalcoholic fatty liver disease
• Cancers that metastasize to the liver (rarely present similarly to acute viral hepatitis)

Diagnostic Approach

• All patients with acute hepatitis should undergo 4 serologic tests.
  • HBsAg
  • IgM anti-HBc
  • IgM anti–hepatitis A virus (HAV)
  • Anti–hepatitis C virus (HCV)
• The presence of HBsAg, with or without IgM anti-HBc, confirms HBV infection.
• If IgM anti-HBc is present, HBV infection is considered acute.

Laboratory Tests

Diagnostic tests for acute HBV infection

• Serum HBsAg
  • Indicative of acute or chronic HBV infection
  • Infrequently, levels of HBsAg are too low to be detected during acute HBV infection.
• Serum IgM anti-HBc
  • Indicative of acute HBV infection
• Serum IgG anti-HBc
  • Indicative of chronic HBV infection
• HBeAg
  • Presence of HBeAg is associated with high infectivity.
  • Because HBeAg is invariably present during early acute hepatitis B, HBeAg testing is indicated primarily during follow-up of acute infection as it progresses to a chronic state.
• Serum anti-HBs
  • Immunization with HBsAg (after vaccination)
  • Hepatitis B in the remote past
  • False-positive result
• Quantitative HBV DNA [3]
  • Typically < 0.5 pg/mL in acute infection
  • Levels > 0.5 pg mL associated with chronic infection
  • Useful in chronic disease to assess viral activity
  • Serum
  • Liver

Diagnostic tests for acute hepatitis due to other viruses

• IgM anti-HAV
  • Indicative of acute hepatitis A virus infection
  • False positive: rheumatoid factor
• Anti-HCV
  • Indicative of acute or chronic hepatitis C virus infection

Laboratory abnormalities in acute viral hepatitis

• Serum alanine aminotransferase and aspartate aminotransferase levels
  • Variable increase during the prodromal phase of acute viral hepatitis
    • Precedes the increase in bilirubin level
  • Acute levels of these enzymes do not correlate well with the degree of liver-cell damage.
  • Peak levels vary from 400–4000 IU.
• Serum bilirubin
  • Jaundice is usually visible in the sclera or skin when the serum bilirubin value exceeds 43 μmol/L (2.5 mg/dL).
  • In most instances, the total bilirubin is equally divided between the conjugated and unconjugated fractions.
  • Bilirubin levels > 340 μmol/L (20 mg/dL) that increase and persist late into the course of viral hepatitis are more likely to be associated with severe disease.
    • In patients with underlying hemolytic anemia, such as glucose-6-phosphate dehydrogenase deficiency and sickle-cell anemia, a high serum bilirubin level is common (due to superimposed hemolysis).
    • Bilirubin levels > 513 μmol/L (30 mg/dL) have been observed and are not necessarily associated with a poor prognosis.
• Prothrombin time
  • Prolonged value may:
    • Reflect a severe hepatic synthetic defect
    • Signify extensive hepatocellular necrosis
    • Indicate a worse prognosis
• Serum alkaline phosphatase level
  • May be normal or only mildly elevated
• Albumin level
  • Decrease is uncommon in uncomplicated cases.

Imaging

• There are no specific imaging tests for the diagnosis of hepatitis B.
• In patients with significant cholestasis, imaging of the biliary tree may be necessary to rule out obstruction from stone or neoplasm.

Diagnostic Procedures

• Liver biopsy is rarely necessary or indicated in acute viral hepatitis.
  • Exceptions
    • Question about the diagnosis
    • Clinical evidence suggesting a diagnosis of chronic hepatitis