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Causes of Hepatitis

By Anna E. Rutherford, MD, MPH

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Hepatitis is an inflammation of the liver characterized by diffuse or patchy necrosis.

Hepatitis may be acute or chronic (usually defined as lasting > 6 mo). Most cases of acute viral hepatitis resolve spontaneously, but some progress to chronic hepatitis.

Common Causes

Common causes of hepatitis include

At least 5 specific viruses appear to be responsible (see Table: Characteristics of Hepatitis Viruses). Other unidentified viruses probably also cause acute viral hepatitis.

Less Common Causes

Less common causes of hepatitis include other viral infections (eg, infectious mononucleosis, yellow fever, cytomegalovirus infection) and leptospirosis.

Parasitic infections (eg, schistosomiasis, malaria, amebiasis), pyogenic infections, and abscesses that affect the liver are not considered hepatitis. Liver involvement with TB and other granulomatous infiltrations is sometimes called granulomatous hepatitis, but the clinical, biochemical, and histologic features differ from those of diffuse hepatitis.

Various systemic infections and other illnesses may produce small focal areas of hepatic inflammation or necrosis. This nonspecific reactive hepatitis can cause minor liver function abnormalities but is usually asymptomatic.

Some types of infectious and noninfectious liver inflammation are summarized in Selected Diseases or Organisms Associated With Liver Inflammation.

Selected Diseases or Organisms Associated With Liver Inflammation

Disease or Organism

Manifestations

Viruses

In neonates: Hepatomegaly, jaundice, congenital defects

In adults: Mononucleosis-like illness with hepatitis; may occur posttransfusion

Epstein-Barr

Clinical hepatitis with jaundice in 5–10%; subclinical liver involvement in 90–95%

Acute hepatitis sometimes severe in young adults

Jaundice, systemic toxicity, bleeding

Liver necrosis with little inflammatory reaction

Other

Hepatic infection occasionally due to echovirus or coxsackievirus infections, varicella, herpes simplex, rubella, or rubeola

Bacteria

Granulomatous reaction of liver with progressive necrotizing abscesses

Pyogenic abscess*

Serious infection acquired via portal pyemia, cholangitis, or hematogenous or direct spread; due to various organisms, especially gram-negative and anaerobic

Illness and toxicity, yet only mild liver dysfunction

Hepatic involvement (common; usually subclinical) with granulomatous infiltration; jaundice (rare)

Disproportionately increased alkaline phosphatase

Other

Minor focal hepatitis in numerous systemic infections (common; usually subclinical)

Fungi

Granulomas in liver and spleen (usually subclinical) that heal with calcification

Other

Granulomatous infiltration sometimes occurring in cryptococcosis, coccidioidomycosis, blastomycosis, or other infections

Protozoa

Important disease, often without obvious dysentery

Usually a large single abscess with liquefaction

Systemic illness, tender hepatomegaly, surprisingly mild liver dysfunction

A common cause of hepatosplenomegaly in endemic areas

Jaundice absent or mild unless active hemolysis is present

Transplacental infection

In neonates: Jaundice, CNS and other systemic manifestations

Infiltration of reticuloendothelial system by parasite, hepatosplenomegaly

Helminths

Biliary obstruction by adult worms, parenchymal granulomas caused by larvae

Biliary tract infestation, cholangitis, stones, cholangiocarcinoma

One or more hydatid cysts, which usually have a calcified rim and may be large but which often are asymptomatic and do not disrupt liver function

Can rupture into the peritoneum or biliary tract

Acute: Tender hepatomegaly, fever, eosinophilia

Chronic: Biliary fibrosis, cholangitis

Periportal granulomatous reaction to ova with progressive hepatosplenomegaly, pipestem fibrosis, portal hypertension, and varices

Hepatocellular function preserved; not true cirrhosis

Visceral larva migrans syndrome

Hepatomegaly with granulomas, eosinophilia

Spirochetes

Acute fever, prostration, jaundice, bleeding, renal injury

Liver necrosis (often mild despite severe jaundice)

Congenital: Neonatal hepatosplenomegaly, fibrosis

Acquired: Variable hepatitis in secondary stage, gummas with irregular scarring in tertiary stage

Borrelia infection

Systemic symptoms, hepatomegaly, sometimes jaundice

Unknown

Active chronic granulomatous inflammation not resulting from known causes (sarcoid variant?)

May cause mainly systemic symptoms (eg, fever, malaise) and can occur when certain drugs are used

Granulomatous infiltration (common, usually subclinical), jaundice (rare)

Occasionally, progressive inflammation with scarring and portal hypertension

Spectrum of hepatic disease, especially in ulcerative colitis; includes periportal inflammation (pericholangitis), sclerosing cholangitis, cholangiocarcinoma, and autoimmune hepatitis

Poor correlation between hepatic function and activity of bowel disorder

*Differentiate from amebiasis with serologic tests for amebas and direct percutaneous abscess aspiration.

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