Amebic liver abscess is caused by the same organism, Entamoeba histolytica, that causes amebiasis, an intestinal infection. The organism is carried through the blood to the liver where the abscess is formed. Patients may or may not have symptoms of intestinal infection concurrently with liver abscess.

The infection is present worldwide, but is most common in tropical areas where crowded living conditions and poor sanitation exist. Africa, Latin America, Southeast Asia, and India have significant health problems associated with this disease. Transmission occurs through ingestion of cysts in fecally contaminated food or water, use of human excrement as fertilizer, and person-to-person contact.

Risk factors for amebic liver abscess include malnutrition, old age, pregnancy, steroid use, malignancy, immunosuppression and alcoholism. Recent travel to a tropical region is a risk factor. In the U.S., institutionalized people and male homosexuals are known high risk groups.