Amebic Hepatic Abscesses

Background: Amebic liver abscess is the most frequent extraintestinal manifestation of Entamoeba histolytica infection. This infection is caused by the protozoa E histolytica, which ascends the portal venous system. Amebic liver abscess is an important cause of space-occupying lesions of the liver, mainly in developing countries. Prompt recognition and appropriate treatment of amebic liver abscess lead to improved morbidity and mortality rates.

Pathophysiology: E histolytica exists in 2 forms. The cyst stage is the infective form, and the trophozoite stage causes invasive disease. People who chronically carry E histolytica shed cysts in their feces; these cysts are transmitted primarily by food and water contamination. Rare cases of transmission via oral and anal sex or direct colonic inoculation through colonic irrigation devices have occurred. Cysts are resistant to gastric acid, but the wall is broken down by trypsin as it passes through the small intestine. Trophozoites are released and colonize the cecum. To initiate symptomatic infection, E histolytica trophozoites present in the lumen must adhere to the underlying mucosa and penetrate the mucosal layer.

Liver involvement occurs following invasion of E histolytica into mesenteric venules. Amebae then enter the portal circulation and travel to the liver where they typically form large abscesses. The abscess contains acellular proteinaceous debris, which is thought to be a consequence of induced apoptosis and is surrounded by a rim of amebic trophozoites invading the tissue.

The right lobe of the liver is more commonly affected than the left lobe. This has been attributed to the fact that the right lobe is supplied predominantly by the superior mesenteric vein, whereas the left lobe is supplied by the splenic vein.

Frequency:

• In the US: Amebic liver abscess is rare and currently is seen almost exclusively in immigrants or travelers. In 1994, 2,983 cases of amebiasis were reported to the Centers for Disease Control (CDC). The disease was removed from the National Notifiable Diseases Surveillance System in 1995. The overall prevalence of amebic infection can be as high is 4%. An estimated 4% of patients with amebic colitis develop an amebic liver abscess.

  An estimated 10% of the population is infected with Entamoeba dispar. Previously thought to be a nonpathogenic strain of E histolytica, this type of amoeba does not produce clinical symptoms even in the immunocompromised host.

• Internationally: Worldwide, approximately 40-50 million people are infected annually, with the majority of infections occurring in developing countries. The prevalence of infection may be as high as 50% in less-developed areas. The highest prevalence is found in developing countries in the tropics, particularly in Mexico, India, Central and South America, and tropical areas of Asia and Africa.

Mortality/Morbidity: Infection with E histolytica ranks second worldwide among parasitic causes of death, following malaria.

• Annually, 40,000-100,000 deaths are caused by infection with E histolytica.

• Per year, a 10% risk of developing symptomatic invasive amebiasis exists after the acquisition of a pathogenic strain.

Race: All races can be affected by amebic liver abscess. Risk factors for infection include travel or residence in endemic areas.

Sex: Amebic liver abscess is marked by a 7-12 times higher incidence in males than in females despite an equal sex distribution of noninvasive colonic amebic disease among adults. However, no sexual preponderance exists among children.

Age: Peak incidence of amebic liver abscess occurs in people in their third, fourth, and fifth decades, although it can occur in any age group.

Treatment
Medical Care: Most uncomplicated amebic liver abscesses can be treated successfully with amebicidal drug therapy alone. Use tissue amebicides to eradicate the invasive trophozoite forms in the liver. After completion of treatment with tissue amebicides, administer luminal amebicides for eradication of the asymptomatic colonization state. Failure to use luminal agents can lead to relapse of infection in approximately 10% of patients. In general, metronidazole, tinidazole, emetine, and dehydroemetine are active in invaded tissues; chloroquine is active only in the liver; tetracycline acts on the bowel wall; and diloxanide furoate, paromomycin, and iodoquinol are luminal agents only. The details on tissue and luminal amebicidal agents are discussed.

• Metronidazole remains the drug of choice for amebic liver abscess. Metronidazole enters the protozoa by passive diffusion and is converted to reactive cytotoxic nitroradicals by reduced ferredoxin or flavodoxin. Tinidazole, another nitroimidazole closely related to metronidazole, was recently approved for the treatment of amebic liver abscess and invasive amebiasis. Tinidazole is well tolerated by patients. Tinidazole may be administered once daily and appears to be at least as effective as metronidazole, with a clinical cure rate of more than 90%.

• Metronidazole, 750 mg 3 times a day orally for 10 days, was reported to be curative in 90% of patients with amebic liver abscess. The drug also is available for intravenous administration for those patients who are unable to take medication by the oral route.

• Resolution of symptoms is fairly rapid and is observed within 3 days in most of the patients in the United States. In endemic areas outside the United States, it takes relatively longer to resolve symptoms because the abscesses are quite large or multiple by the time patients seek medical attention.
• Surprisingly, in vivo resistance to metronidazole by E histolytica has not been reported, although metronidazole is a frequently used drug. Nevertheless, in vitro studies have shown an association between metronidazole resistance and decreased expression of ferredoxin 1 and flavodoxin and increased expression of iron-containing superoxide dismutase and peroxiredoxin in E histolytica.
• Usual adverse effects of metronidazole include nausea, headache, and metallic taste. Abdominal cramps, vomiting, diarrhea, and dizziness also may occur. Dark urine may occur from a metabolite of the drug.

• Anecdotal evidence suggests that the addition of dehydroemetine for the first few days of therapy hastens the recovery in severe cases, with less cardiotoxicity, compared to a full 10-day course of dehydroemetine. However, no randomized controlled trials exist that demonstrate the benefits of combination therapy over monotherapy.
• Outside the United States, other closely related amebicidal agents, such as secnidazole or ornidazole, can be substituted in appropriate dosages. These drugs are not available in the United States.
• Chloroquine phosphate may be substituted or added in the event of failure of resolution of clinical symptoms with metronidazole or another nitroimidazole within 5 days or intolerance to metronidazole or a nitroimidazole. Chloroquine has the disadvantage of being associated with higher relapse rates than nitroimidazoles. Adverse effects include gastrointestinal upset, headache, dizziness, and blurred vision. Retinopathy does not occur at the dose used for amebic liver abscess.
• Emetine or dehydroemetine has a direct lethal action on the trophozoites of E histolytica. These agents are very toxic and, therefore, should be used only as a second-line therapy. Their toxicity includes cardiac arrhythmias, precordial pain, muscle weakness, vomiting, and diarrhea. Dehydroemetine is less toxic than emetine.
• Administer a luminal amebicidal agent to eradicate the intestinal carriage after the amebic liver abscess has been treated with one of the above tissue amebicides. Failure to use luminal agents can lead to relapse of infection in approximately 10% of patients. Luminal agents with proven efficacy include diloxanide furoate, iodoquinol, and paromomycin.

• Diloxanide furoate is free of major adverse effects. The most common adverse effect is flatulence and occasional gastrointestinal upset.
• Iodoquinol (diiodohydroxyquin) rarely causes abdominal pain, diarrhea, or rash. A structurally related diiodohydroxyquin caused subacute myelopticoneuropathy and is obsolete now.

• Although paromomycin may occasionally cause nausea, abdominal cramps, or diarrhea, it is the preferred luminal amebicidal.

• The details on the luminal amebicides are discussed.

Surgical Care:

• Consider therapeutic aspiration of amebic liver abscess in the following situations: (1) high risk of abscess rupture, as defined by cavity size greater than 5 cm; (2) left lobe liver abscess, which is associated with higher mortality and frequency of peritoneal leak or rupture into the pericardium; (3) failure to observe a clinical medical response to therapy within 5-7 days; and (4) cannot differentiate from a pyogenic liver abscess.

• Imaging-guided needle aspiration or catheter drainage is the procedure of choice. Simple needle aspiration is less invasive, less expensive, and has the advantage of being able to drain multiple abscesses in the same session. Simple needle aspiration avoids problems related to catheter care

• Rajak et al compared the efficacy of sonographically guided percutaneous needle aspiration and percutaneous catheter drainage in the treatment of patients with liver abscesses, two thirds of which were amebic abscesses.

• Although percutaneous needle aspiration was successful in only 60% of cases after 1 or 2 aspirations, catheter drainage was curative in all patients.

• The average time for clinical improvement and mean hospital stay were similar among the patients who were successfully treated in the 2 treatment groups.

• The average time taken for total resolution of the abscesses was the same in both groups.

• Generally, surgical drainage is not necessary and should be avoided; however, consider open surgical drainage when the abscess is inaccessible to needle drainage or a response to therapy has not occurred in 4-5 days.

Consultations:

• Interventional radiologist for imaging-guided aspiration of the abscess

• General surgeon for open surgical drainage of the abscess under rare circumstances
  

Diet: No specific diet change or modification is required. However, discuss food hygiene with patients because amebiasis is associated with suboptimal personal or food hygiene.

Activity:

• No restriction of activity is needed, except during the first few days of acute illness with pain.

If emetine or dehydroemetine is used, the patient should remain sedentary for approximately 4 weeks after completing therapy because of their toxicity.