Viruses

Cytomegalovirus

In neonates: Hepatomegaly, jaundice, congenital defects

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

Epstein-Barr virus infections

Infectious mononucleosis

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

Acute hepatitis sometimes severe in young adults

SARS-CoV-2 infection (COVID-19) (1)

Mild aminotransferase elevation

Direct infection of virus contributes to hepatic impairment

Correlates with disease severity but can occur in asymptomatic infection as well

Herpes simplex virus

Anicteric hepatitis, usually in immunocompromised patients (but can also occur in immunocompetent patients)

Fever in the majority; rash in 50%

Acute hepatitis, often severe

Yellow fever

Jaundice, systemic toxicity, bleeding

Liver necrosis with little inflammatory reaction

Other

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

Bacteria

Actinomycosis

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

Tuberculosis

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

Histoplasmosis

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

Other

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

Protozoa

Amebiasis*

Important disease, often without obvious dysentery

Usually a large single abscess with liquefaction

Systemic illness, tender hepatomegaly, surprisingly mild liver dysfunction

Malaria

A common cause of hepatosplenomegaly in endemic areas

Jaundice absent or mild unless active hemolysis is present

Toxoplasmosis

Transplacental infection

In neonates: Jaundice, central nervous system (CNS) and other systemic manifestations

Visceral leishmaniasis

Infiltration of reticuloendothelial system by parasite, hepatosplenomegaly

Helminths

Ascariasis

Biliary obstruction by adult worms, parenchymal granulomas caused by larvae

Clonorchiasis

Biliary tract infestation, cholangitis, stones, cholangiocarcinoma

Echinococcosis

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

Fascioliasis

Acute: Tender hepatomegaly, fever, eosinophilia

Chronic: Biliary fibrosis, cholangitis

Schistosomiasis

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

Hepatocellular function preserved; not true cirrhosis

Toxocariasis

Visceral larva migrans syndrome

Hepatomegaly with granulomas, eosinophilia

Spirochetes

Leptospirosis

Acute fever, prostration, jaundice, bleeding, renal injury

Liver necrosis (often mild despite severe jaundice)

Syphilis

Congenital: Neonatal hepatosplenomegaly, fibrosis

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

Relapsing fever

Borrelia infection

Systemic symptoms, hepatomegaly, sometimes jaundice