Amebic Liver Abscess

Etiology

E histolytica is a parasitic protozoan responsible for approximately 40 million infections and up to 100,000 deaths annually.[7] In contrast, Entamoeba despar and Entamoeba moshkovskii, which also infect humans via the fecal-oral route, are nonpathogenic; individuals may remain asymptomatic carriers.[7] Among the Entamoeba species infecting humans, only E histolytica causes clinical amebiasis. Humans and non-human primates are the only known natural hosts.[8] 

Epidemiology

Amebic liver abscesses are uncommon in children and occur 10 times more frequently in men than in women, most commonly affecting individuals between the ages of 18 and 50. The reason for this disparity remains unclear but may relate to hormonal influences and alcohol consumption. Most cases in the United States occur in immigrants from endemic regions and individuals living along the US-Mexico border. E histolytica is widely distributed globally, with the highest infection rates in India, Africa, Mexico, and Central and South America.

Risk is most significant in areas with poor sanitation and unsafe municipal water supplies.[7] Transmission typically occurs through ingestion of contaminated food or water. Other routes include oral and anal sexual contact, particularly among men who have sexual intercourse with men.[9] Approximately 2% to 5% of patients with intestinal amebiasis progress to liver abscess formation.[2]

Pathophysiology

Clifford Dobell first described the life cycle of E histolytica in 1928. The organism has 2 stages: the infective cystic stage and the invasive trophozoite stage.[2] Infection begins with the ingestion of quadrinucleate cysts through contaminated food or water.  Excystation occurs in the small intestine, releasing motile trophozoites. In most cases, these remain in the intestinal mucosa and form new cysts. Sometimes, trophozoites adhere to and lyse the colonic epithelium, leading to tissue invasion.

This invasion triggers a neutrophilic response, causing further cellular damage at the invasion site. Trophozoites can then disseminate via the portal circulation to extraintestinal sites, most commonly the liver, where they can cause inflammation and necrosis, leading to abscess formation.[10][11] Hepatocyte death, through apoptosis or necrosis, contributes to abscess development.[12]

Toxicokinetics

E histolytica adheres to colonic epithelial cells via a galactose/N-acetylgalactosamine-specific lectin. The organism exhibits cytolytic activity and can induce apoptosis in mammalian cells. Upon reaching the liver, trophozoites form abscesses characterized by well-circumscribed areas of liquified cellular debris and necrotic hepatocytes. These lesions are surrounded by a rim of connective tissue containing inflammatory cells and amebic trophozoites. The relatively low number of organisms within large abscesses suggests that E histolytica can mediate hepatocyte destruction without direct cell contact.

History and Physical

Patients can present with an amebic liver abscess months to years after travel to an endemic region, making a detailed travel history and awareness of epidemiologic risk factors imperative. In the United States, typical cases occur in Hispanic immigrant men aged 20 to 40. About 80% of patients develop symptoms within 2 to 4 weeks of exposure, including fever, dull right upper quadrant or epigastric pain, and cough. Subacute presentations may involve weight loss with less frequent fever or abdominal pain. Gastrointestinal symptoms occur in 10% to 35% of cases, including nausea, vomiting, abdominal cramps, diarrhea, constipation, or distention.

Risk factors include:

• Recent travel to tropical regions
• Malnutrition
• Immunosuppression
• Alcohol abuse

On physical examination, hepatomegaly with point tenderness in the right upper quadrant or right intercostal spaces is typical of a liver abscess. A minority of patients may present with severe distress or shock, including septic or anaphylactic shock in rare cases, such as hydatid cyst rupture. 

Evaluation

On laboratory evaluation, patients with amebic liver abscesses typically exhibit leukocytosis, elevated serum transaminases, and increased alkaline phosphatase levels. Most abscesses are located in the right hepatic lobe and measure 2 to 6 cm in diameter. Radiographic findings are sensitive but not specific for amebic liver abscess. Common imaging modalities include ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), with typical findings as follows:

• Ultrasound:
  • Round or oval, internally homogeneous, hypoechoic masses
• CT:
  • Low-density lesion with a peripheral enhancing rim (see Image. Hepatic Abscess, Computed Tomography [CT])
  • May show septations or fluid-solid levels
• MRI: 
  • Low signal intensity on T1-weighted image
  • High signal intensity on the T2-weighted image

A history of travel to an endemic area, combined with typical clinical features and characteristic imaging findings, should raise suspicion for amebic liver abscess. Serologic testing via indirect hemagglutination has over 95% sensitivity, though sensitivity is 70% to 80% in acute disease and exceeds 90% in the convalescent phase. False-negative results may occur during the first week of illness. Stool microscopy is limited, with a sensitivity of only 10% to 40%.[13] Aspiration is generally not indicated, but if performed, the abscess yields a thick, odorless, chocolate-brown fluid classically described as "anchovy paste".[12][14]

Treatment / Management

Treatment involves a nitroimidazole, preferably metronidazole 500 to 750 mg orally 3 times daily for 7 to 10 days. Alternatively, tinidazole 2 g can be administered once daily for 3 days. Because intestinal colonization persists in 40% to 60% of cases, nitroimidazole therapy must always be followed by a luminal agent, such as paromomycin 500 mg 3 times daily for 7 days or iodoquinol 650 mg 3 times daily for 20 days [11]. Metronidazole and paromomycin should not be administered simultaneously, as paromomycin-induced diarrhea may complicate assessment of treatment response. Clinical improvement typically occurs within 72 to 96 hours.[15]

Approximately 15% of patients do not respond to medical treatment and may require abscess aspiration or surgical intervention. Therapeutic percutaneous aspiration can be performed via needle aspiration or catheter drainage. These procedures are indicated in patients who fail to improve within 5 to 7 days of antibiotic therapy, have a high risk of rupture (eg, abscess >5 cm or left lobe involvement), or present with bacterial coinfection of the amebic liver abscess.[16] 

Among the 2 techniques, percutaneous catheter drainage has shown superior outcomes, with higher success rates and faster symptom resolution than needle aspiration.[17] Surgical intervention is reserved for the following indications: (A1)

• Multiple loculated abscesses or those in inaccessible locations for percutaneous drainage
• Failure of percutaneous drainage to eradicate the abscess(es)
• Bacterial superinfection of the abscess(es)
• Rupture of the abscess into the peritoneum or pericardium poses a significant risk for amebic peritonitis, cardiac complications, and death; these are considered a surgical emergency.[18] 
(B3)

When feasible, laparoscopic drainage is preferred over open surgery as it offers reduced postoperative pain, shorter hospital stays, and faster recovery while maintaining effective abscess resolution.

Differential Diagnosis

The diagnosis of amebic liver abscess requires careful distinction from other causes of hepatic lesions. A broad differential is essential to avoid misdiagnosis and ensure appropriate management. The differential includes:

• Pyogenic liver abscesses
  • These often arise from cholangitis, intra-abdominal infection, or hematogenous spread. Common pathogens include Staphylococcus, Streptococcus, and intestinal gram-negative organisms, such as Escherichia coli and Klebsiella spp.
• Cholangitis, a frequent source of hepatic infection
• Echinococcal liver abscesses
• Melioidosis, caused by disseminated Burkholderia pseudomallei bacterial infection
• Hydatid cysts due to Echinococcus granulosus 
  • These may rupture or become secondarily infected. 
• Fungal abscesses, especially Candida spp
  • These typically occur in immunocompromised individuals. 
• Hepatic trauma
• Secondary spread from intra-abdominal infections, such as diverticulitis, appendicitis, or bowel perforation
• Hepatocellular carcinoma or other malignancies involving the liver

Prognosis

For uncomplicated amebic liver abscesses, the prognosis is excellent with appropriate medical therapy. Most patients respond well to treatment without requiring invasive intervention. However, when an abscess ruptures into the peritoneum, the mortality rate after surgical management ranges from 20% to 50%. In such cases, percutaneous catheter drainage is the preferred approach.[19] Cardiac involvement, though rare, carries a high mortality rate, often due to cardiac tamponade.[20] Prompt recognition and emergency intervention are critical in these cases.

Complications

An amebic liver abscess may rupture into the lungs, pleural cavity, pericardium, or abdomen. Abdominal rupture can lead to peritonitis, increasing the risk of shock and death. Cardiac involvement, usually due to rupture into the pericardium, may result in acute pericarditis, pericardial abscess, tamponade, constrictive pericarditis, myocarditis, or congestive heart failure.[20] Rare complications include thrombosis of the inferior vena cava or hepatic vein and hematogenous spread to distant organs, such as the brain.