Amebic liver abscesses are caused by Entamoeba histolytica, a protozoan parasite that is acquired via ingestion of food or water contaminated by human feces. Most infections with E. histolytica are asymptomatic. Among symptomatic infections, amebic dysentery is the most common presentation. More rarely, it can cause extraintestinal disease, when the trophozoite invades the intestinal mucosa and disseminates hematogenously. Liver abscesses are the most common extraintestinal presentation; the trophozoites reach the liver via the portal venous circulation.[2-4] Figure 1 shows the life cycle of E. histolytica.
right upper quadrant
E. histolytica affects about 500 million people worldwide, although the exact prevalence is difficult to discern due to the high prevalence of colonization with the morphologically identical commensal Entamoeba dispar. The highest rates of infection with E. histolytica are seen in India, Africa, Mexico, Central America, and South America. In developed countries, patients who present with amebic liver abscess have usually traveled to one of these endemic regions. Colonic amebic disease affects all gender groups equally, but amebic liver abscess rates are 3-20 times higher in adult men than other groups.[5-9] The reason for this adult male predisposition is unclear. Amebic liver abscesses are also increased in patients with altered cell-mediated immunity; HIV infection, for example, increases the likelihood of E. histolytica infection causing liver disease.
Patients with amebic liver abscesses typically present with right upper quadrant (RUQ) pain and fever. The onset of symptoms is usually subacute. Less than one-third of patients have associated diarrhea, although some will report a history of dysentery in the prior months. Less than 10% present with jaundice.
When returning from an endemic area, patients usually present within 8-20 weeks (median of 12 weeks), although there are reports of years lapsing between presentation and prior travel.
On physical examination, patients typically have tenderness to palpation over the RUQ. On laboratory evaluation, there is usually a leukocytosis without eosinophilia and an elevated alkaline phosphatase out of proportion to any elevation in aminotransferases.
The diagnosis of an amebic liver abscess is made through a combination of characteristic findings on imaging and serologic testing. On imaging, there is a cystic intrahepatic cavity that is usually indistinguishable from other causes of liver abscesses. The majority of amebic liver abscesses are solitary lesions, although there can occasionally be multiple lesions, and they are more often found in the right lobe than the left.[13, 14] On ultrasound, the lesion is a round, well-defined hypoechoic mass (Fig. 2). After healing, the periphery of the abscess may calcify and form a round, thin rim.
The characteristic radiographic findings are not specific enough to make a diagnosis and must be interpreted in conjunction with either serological or serum antigenic confirmation. A total of 99% of patients with amebic liver abscesses will develop detectable antibodies to E. histolytica, although the test may be negative in the first seven days of illness.[13, 16] Antibodies are detectable at presentation in 92%-97% of patients with amebic liver abscesses.[13, 16, 17] In endemic areas, up to 35% of presently uninfected individuals will have a positive serology due to prior infection, so a positive serology may not indicate active infection and should be interpreted with caution.[18, 19] Patients lose seroreactivity to the antigen faster than antibody testing.
Aspiration of amebic liver abscesses is not necessary for establishing the diagnosis. When aspirated, they contain acellular debris that forms a brown, thick fluid (called “anchovy paste”). Trophozoites are seen in a minority of aspirates (<20%) and typically only seen when the wall of the cyst is sampled.
Of note, when patients present with amebic liver abscesses, their stool microscopy is often negative for E. histolytica, so stool microscopy cannot be relied upon for making the diagnosis, although a positive test is helpful.
It may be reasonable to initiate treatment for patients who present with RUQ pain, fever, and have a lesion that is consistent with amebic liver abscess on imaging, if they have the right epidemiological exposures, before serology testing is completed. Treatment consists of a tissue agent and a luminal agent. The tissue agent of choice is metronidazole, the cure rate for which is >90%. There is no known resistance to metronidazole. Alternatives include tinidazole, ornidazole, and nitazoxanide.[22-24] The luminal agent is used to remove any intraluminal cysts, even if the stool microscopy is negative. Paromycin is typically used. Alternatives include diiodohydroxyquin or diloxanide furoate. See Table 1 for detailed treatment recommendations. No clinical benefit has been demonstrated with drainage of amebic liver abscesses, and thus is not recommended as part of routine treatment. Drainage should only be considered when risk of rupture is high (particularly with large left-sided abscesses at risk for rupturing into the pericardium) and when there is a slow clinical response to metronidazole (after four days of treatment) because this may indicate bacterial superinfection of the amebic abscess. Short-term follow-up imaging should be interpreted cautiously, because the lesion may transiently worsen radiographically after treatment.
|Tissue Agent||Metronidazolea||500-750 mg IV/PO every 8 hours||7-10 days|
|Tinidazole||2 g PO daily||3-5 days|
|Ornidazole||0.5-1 g IV ×1, followed by 0.5 g IV every 12 hours||3-6 days|
|Nitazoxanide||500 mg PO every 12 hours||3 days|
|Luminal Agent||Paromycina||25-30 mg/kg PO per day in 3 divided doses||7 days|
|Diiodohydroxyquin||650 mg PO TID after meals||20 days|
|Diloxanide furoate||500 mg every 8 hours||10 days|
|Salvage||Drainage of abscess and/or prolonged course of metronidazole|
The most important complication is abscess rupture. Depending on the location of the abscess within the liver, the abscess may rupture into the peritoneum, the pleural space, or the pericardial space. Approximately 7% of amebic liver abscesses rupture into the peritoneum, causing subphrenic abscesses and/or peritonitis. Between 7% and 20% will rupture into the pleural space causing empyema. Rupture into the pericardium can be rapidly fatal due to purulent pericarditis with cardiac tamponade; this is more common among left-sided abscesses.
Other complications include bacterial superinfection of the amebic liver abscess and thrombosis of the hepatic vein or inferior vena cava.
The mortality rate for amebic liver abscesses is <1%. One study of patients in India that included 135 patients, and had an overall mortality of 17%, found that independent risk factors for mortality included a bilirubin >3.5 mg/dL, albumin <2 g/dL, large volume abscess, multiple abscess cavities, and encephalopathy.