AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

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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

United States

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.

International

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.

CLINICAL

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History

The signs and symptoms of amebic liver abscess often are nonspecific, resembling those of pyogenic liver abscess or other febrile diseases.

• Time of onset
• • Patients with amebic liver abscess usually present acutely (duration of symptoms <14 d), with the most frequent complaints being fever and abdominal pain. This presentation is characteristic of younger patients.
  • The subacute presentation mostly is characterized by weight loss, and, in less than half the cases, abdominal pain and fever are present.
• Abdominal pain
• • Abdominal pain is the most common element in the history and is present in 90-93% of patients.
  • The pain most frequently is located in the right upper quadrant (54-67%) and may radiate to the right shoulder or scapular area.
  • Pain increases with coughing, walking, and deep breathing, and it increases when patients rest on their right side.
  • The pain usually is constant, dull, and aching.
• Constitutional symptoms
• • Fever is present in 87-100% of cases.
  • Rigors are present in 36-69% of cases.
  • Nausea and vomiting are present in 32-85% of cases.
  • Weight loss is present in 33-64% of cases.
• Diarrhea
  • Diarrhea is present in less than one third of patients at the time of diagnosis.
  • Some patients describe a history of having had dysentery within the previous few months.
  • Bloody diarrhea is present in 7% of cases.
• Pulmonary symptoms
• • Pulmonary symptoms are present in 18-26% of cases.
  • The most frequent symptoms are cough and chest pain, which may represent a sign of secondary pulmonary involvement by abscess rupture in the pleural cavity.
  • When coughing produces an odorless brown substance similar to anchovy paste, a bronchopleural fistula has developed.
• Recent travel to endemic areas
• • Onset of symptoms usually occurs within 8-12 weeks from the date of travel.
  • In 95% of cases, onset occurs within 5 months of returning from travel to an endemic area.
  • A remote travel history of as many as 12 years has been reported.

Physical

• Fever is the most common sign and is found in as many as 99% of cases.
• Hepatomegaly is present in some cases.
• • The frequency varies widely in different series published, reporting as high as 63% in one series and as low as 18% in another.
  • Hepatomegaly with pain upon palpation is one of the most important signs of amebic liver abscess.
  • Point tenderness over the liver, below the ribs, or in the intercostal spaces is a typical finding.
• Abdominal tenderness
• • In 55-75% of cases, abdominal tenderness is located in the right upper abdominal quadrant.
  • When the abscess is located in the left lobe (28% of cases), epigastric tenderness is noted.
• Pulmonary abnormalities
• • These are present in 20-45% of cases and consist of dullness and rales at the right lung base and nonproductive cough.
  • Breath sounds over the right lung base may be diminished.
  • Pleural rub may be audible.
• Jaundice ( <10% of cases) mostly occurs in complicated cases with multiple abscesses or a large abscess compressing the biliary tract.
• Signs of complications
• • Signs of peritoneal irritation, such as rebound tenderness, guarding, and absence of bowel sounds, are present when the abscess ruptures in the peritoneal cavity. Peritonitis occurs in 2-7% of cases.
  • Pericardial friction rub can be audible when the abscess extends into the pericardium. This sign is associated with very high mortality.
  • Signs of pleural effusion are present when the abscess ruptures in the pleural cavity.

Causes

The following are the risk factors associated with amebic liver abscess:

• People who immigrate from endemic areas
• Populations that are institutionalized, especially people with mental retardation
• Persons living communally
• Promiscuous male homosexuals (secondary to sexually acquired amebic colitis)
• Presence of immunosuppression (eg, HIV infection, malnutrition with hypoalbuminemia, alcohol abuse, chronic infections, posttraumatic splenectomy, steroid use)

DIFFERENTIALS

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Other Problems to be Considered

Febrile illnesses (eg, malaria, typhoid fever)
Hepatitis
Metastatic liver carcinoma
Peritonitis
Pneumonia
Pulmonary disease

WORKUP

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Lab Studies

• Hematology
• • Approximately three fourths of patients with an amebic liver abscess have leukocytosis. This most likely will appear if symptoms are acute or complications have developed.
  • Eosinophilia is rare.
  • Anemia may be present, but the cause usually is multifactorial.
• Chemistry
• • Hyperbilirubinemia is present in only a small proportion of cases.
  • In acute liver abscess, the alkaline phosphatase level tends to be within normal limits and the aspartate aminotransferase (AST) level tends to be elevated.
  • In chronic liver abscess, the alkaline phosphatase level tends to be elevated and the AST level tends to be within normal limits. Overall, the alkaline phosphatase level is elevated in about 70% of cases of amebic liver abscess.
  • Similar complete blood count and liver test abnormalities are found in patients with pyogenic liver abscesses and are not specific.
• Stool examination
• • The role of microscopic stool examination is controversial. Less than 30-40% of patients with amebic liver abscess have concomitant intestinal amebiasis, and 10% of the population is infected with the nonpathogenic strain of E dispar. Hence, the microscopic examination of stool for the identification of cysts is of little value. If positive, it may confirm the diagnosis. Fecal findings suggestive of amebic colitis include a positive test for heme, a paucity of neutrophils, and the presence of Charcot-Leyden crystal protein. The stool examination is still of great value if the serologic and antigen identification tests are not available.
  • Examination of the stool for hematophagous trophozoites of E histolytica must be made on at least 3 fresh specimens because the trophozoites are very sensitive to water, drying, or barium and may be excreted intermittently. Examination is made with a combination of wet mount, iodine-stained concentrates, and trichrome-stained preparations, with which cysts or trophozoites can be seen.
  • Upon examination of the stool, trophozoites may be easily confused with neutrophils. Cysts must be differentiated morphologically from Entamoeba hartmanni, Entamoeba coli, and Endolimax nana, which do not cause clinical disease and do not require treatment. Nonpathogenic E dispar cannot be differentiated morphologically and require fecal antigen detection.
• Stool antigen detection: Stool antigen detection facilitates early diagnosis before an antibody response occurs ( <7 d) and differentiates pathogenic from nonpathogenic Entamoeba infection. This assay uses monoclonal antibodies that detect the galactose-inhibitable adherence protein (adhesin, galactose lectin) of the pathogenic E histolytica. The primary drawback is the requirement for fresh, unpreserved stool specimens. The test is 96-100% sensitive and 94-100% specific for detecting amebiasis when compared with culture/zymodeme analysis, but no more than 40% of patients with amebic liver abscess have intestinal amebiasis at the time of the diagnosis. Currently, the real-time polymerase chain reaction (PCR) stool antigen test shows the highest sensitivity for detecting E histolytica and for distinguishing nonpathogenic amoebas; however, this test is still quite expensive and not widely available.
• Stool culture: Stool culture for amoeba is sensitive but has limited availability.
• Serologic testing
• • Serologic testing is a more useful diagnostic tool than stool microscopy. It can be used for (1) diagnosis of symptomatic patients, (2) assessment of the risk of invasive disease in people who are asymptomatic and are passing cysts in nonendemic areas (nonpathogenic strains do not cause seroconversion), and (3) testing patients with inflammatory bowel disease before starting corticosteroid therapy to prevent complications from unsuspected amebiasis.
• • Indirect hemagglutination (IHA) test is positive in 90-100% of patients with amebic liver abscess. It has fallen out of favor because of newer techniques. Because antibodies persist for month to years after the eradication of infection, a positive titer can represent a previous infection rather than current illness.
  • Enzyme immunoassay (EIA) has now largely replaced IHA testing. EIA is relatively simpler, easy to perform, rapid, stable, and inexpensive.
  • • In addition, the EIA serologic assays that detect antibodies to E histolytica of either the immunoglobulin G (IgG) class or total immunoglobulin are more sensitive and specific than other diagnostic tests.
    • The EIA test detects antibody specific for E histolytica in approximately 95% of patients with extraintestinal amebiasis, 70% of patients with active intestinal infection, and 10% of persons who are asymptomatic and passing cysts of E histolytica.
    • The results of these tests revert to negative in 6-12 months following eradication of infection. Even in highly endemic areas, fewer than 10% of patients who are asymptomatic have positive amebic serology findings.
    • Initial negative test results may appear in as many as 10% of patients with amebic liver abscess. Under these circumstances, order repeat serology testing in 1 week. This test result will usually be positive.
• Serum antigen detection: E histolytica galactose lectin antigen is detectable by ELISA in at least 75% of serum samples obtained from patients with amebic liver abscess. Haque et al reported an antigen seropositivity of 96% with a reversal rate of 82% after 1 week of treatment with metronidazole. This test may be useful for patients who present acutely, before an antibody response occurs. The sample needs to be obtained before starting the treatment. It is also useful in highly endemic areas because of the high prevalence of serum antiamebic antibodies; the treatment leads to a reversal from an antigen-positive state to an antigen-negative state. Rapid antigen and antibody tests are currently under development.

Imaging Studies

• Ultrasonography is the preferable initial diagnostic test. It is rapid, has a low cost, and is only slightly less sensitive than CT scan (75-80% sensitivity vs 88-95% for CT scan).
• • Ultrasonography simultaneously evaluates the gallbladder and avoids radiation exposure.
  • As opposed to scanning with technetium-99m, sonography often can distinguish an abscess from a tumor or other solid focal lesion.
  • A space-occupying lesion is observed in 75-95% of patients with liver abscesses. The lesions tend to be round or oval with well-defined margins and lack prominent peripheral echoes. The lesions are primarily hypoechoic.
• CT scan is sensitive (88-95%), but the findings are not specific.
• • The abscess may be of low density with smooth margins and a contrast-enhancing peripheral rim.
  • The use of injected contrast may differentiate hepatic abscesses from vascular tumors.
• MRI is sensitive, but the findings are not specific. This test provides information comparable with less-expensive imaging procedures.
• Technetium-99m liver scanning is useful for differentiating an amebic liver abscess from a pyogenic abscess.
• • Because amebic liver abscesses do not contain leukocytes, they appear as cold lesions on hepatic nuclear scanning, with a typical hot halo or rim of radioactivity surrounding the abscess.
  • In contrast, pyogenic liver abscesses contain leukocytes and, therefore, typically appear as hot lesions on nuclear scanning.
• Gallium scanning is helpful in differentiating pyogenic abscess (similar to technetium-99m nuclear hepatic scanning) but requires delayed images, which makes the test less helpful.
• Hepatic angiography shows the mass effect, with stretching or displacement of blood vessels and an avascular area surrounded by a blush of contrast observed during the capillary-venous phase of the angiogram. This test is only useful to differentiate liver abscesses from vascular lesions.
• Plain chest or abdominal films may show elevation and limitation of motion of the right diaphragm, basilar atelectasis, and right pleural effusion or gas within the abscess cavity.
• None of the imaging tests can definitely differentiate a pyogenic liver abscess, an amebic abscess, or malignant disease. Clinical, epidemiological, and serological correlation is needed for diagnosis.

Procedures

• Aspiration of the abscess content is indicated only if rupture of the abscess is thought to be imminent or if differentiation between amebic abscess and pyogenic abscess is critical.
• • Aspiration also may be indicated if no response to antibiotic therapy has occurred after 3-5 days (see Surgical Care).
  • Aspiration may be performed under CT scan or sonographic guidance.
  • Send the collected specimen for Gram stain and cultures.
  • Amebas rarely are recovered from the aspirate (15%), and often they are present only in the peripheral parts of the abscess, invading and destroying adjacent tissue.
  • Amebic liver abscesses only rarely yield positive bacterial cultures following secondary bacterial infection of the abscess cavity.
  • Detecting E histolytica antigen in the aspirate is possible and is accomplished as previously described for stool specimens. It is highly specific. The sensitivity was only 20% using ELISA, but newer PCR-based assays have a sensitivity of 83% and a specificity of 100%. However, currently, PCR-based detection is not widely available.
• Many possible complications are associated with aspiration of the abscess.
• • The most common are infection and bleeding.
  • Other complications include amebic peritonitis or inadvertent puncture of an echinococcal cyst.

Histologic Findings

The liver involvement in amebiasis consists of necrotic abscesses and periportal inflammation. The abscess contains acellular proteinaceous debris and is surrounded by a rim of amebic trophozoites invading tissue. The abscess contains a chocolate-colored fluid that resembles anchovy paste and consists predominantly of necrotic hepatocytes. Triangular areas of hepatic necrosis, possibly due to ischemia from amebic obstruction of portal vessels, have been observed. E histolytica can also induce hepatocyte and neutrophilic apoptosis. Some authors postulate that amebic liver abscess probably results from the coalescence of small microabscesses. Periportal fibrosis may be present, but whether this represents prior trophozoite invasion or a host reaction to amebic antigens or toxins is not known.

TREATMENT

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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 in Medication.

• 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 (see Medication) 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 in Medication.

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 (see Procedures).
• 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 (see Surgical Care)

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. See Deterrence/Prevention.

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.

MEDICATION

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The goals of pharmacotherapy are to eradicate the infection, reduce morbidity, and prevent complications.

Drug Category: Amebicides

Used to eliminate the trophozoites of E histolytica in the liver and bowel wall.

Drug Name	Tinidazole (Tindamax, Fasigyn)
Description	Nitroimidazole derivative used for susceptible protozoal infections. Eradicates amebic tissue infections, including liver abscess, but it is only partially effective against luminal forms. Luminal amebicide must also be used to eradicate bowel luminal infection. Only effective against trophozoites and not cyst forms.
Adult Dose	600 mg PO bid or 800 mg PO tid for 5 d; alternatively, 2 g PO qd for 3-5 d with food
Pediatric Dose	<3 years: Not established >3 years: 50 mg/kg/d PO for 3-5 d with food; not to exceed 2 g/dose, limited data exist for pediatric patients treated > 3 d (monitor closely)
Contraindications	Documented hypersensitivity; first trimester of pregnancy
Interactions	Limited data exist; interaction information based on experience with other nitroimidazole derivatives (ie, metronidazole); may prolong PT when coadministered with warfarin; avoid alcoholic beverages and preparations containing ethanol or propylene glycol during and 3 d after administration (may cause disulfiramlike reaction); may increase serum levels of lithium, phenytoin, cyclosporine, tacrolimus, and fluorouracil; CYP450 inducers (eg, phenobarbital, rifampin, phenytoin) may increase elimination; CYP450 inhibitors (eg, cimetidine, ketoconazole) may decrease elimination; concurrent administration with cholestyramine may decrease oral bioavailability; oxytetracycline may antagonize effect
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Carcinogenicity has been observed in mice and rats receiving long-term treatment with metronidazole (another nitroimidazole); although not observed with tinidazole, use cautiously; seizures and peripheral neuropathy have been reported; caution with history of blood dyscrasia; may cause metallic/bitter taste, nausea, anorexia, vomiting, weakness, fatigue, dizziness, or headache; if administered on day of hemodialysis, administer additional dose equivalent to half of recommended dose following dialysis

Drug Name	Dehydroemetine (Dametine)
Description	Preferred agent because it is less toxic than emetine. Eradicates amebic tissue infections, including liver abscess, but does not act on luminal forms. Luminal amebicide also must be used to eradicate the bowel luminal infection. Only effective against the trophozoite forms and not the cyst form. Available in US only from the Parasitic Disease Drug Service, Centers for Disease Control and Prevention (Atlanta, GA 30333; telephone: 404-639-3356).
Adult Dose	1-1.5 mg/kg/d SC/IM qd for 8-10 d; not to exceed 90 mg/kg/d
Pediatric Dose	1-1.5 mg/kg/d SC/IM divided bid for 8-10 d; not to exceed 90 mg/kg/d
Contraindications	Documented hypersensitivity; cardiac disease, renal disease, recent history of polyneuritis
Interactions	None reported
Pregnancy	X - Contraindicated in pregnancy
Precautions	Caution in women who are pregnant and small children; hospitalize when administered because of the potential of serious cardiotoxicity and neuromuscular toxicity; monitor pulse and blood pressure at least tid; perform ECG prior to first injection, on day 5, day 10, and then weekly for 2 wk after last injection; discontinue if resting pulse >110/min, marked hypotension, precordial pain, marked neuromuscular symptoms, T-wave depression, arrhythmias, or proteinuria occur

Drug Name	Emetine (Ipecac)
Description	Eradicates amebic tissue infections, including liver abscess, but does not act on luminal forms. Luminal amebicide also must be used to eradicate the bowel luminal infection. Only effective against the trophozoite forms. Not available in US.
Adult Dose	1 mg/kg/d IM, single daily dose for 8-10 d; not to exceed 65 mg
Pediatric Dose	Administer as in adults, but divide dose bid
Contraindications	Documented hypersensitivity; cardiac disease, renal disease, recent history of polyneuritis
Interactions	None reported
Pregnancy	X - Contraindicated in pregnancy
Precautions	Caution in women who are pregnant and small children; hospitalize when administered because of the potential of serious cardiotoxicity and neuromuscular toxicity; monitor pulse and blood pressure at least tid; perform ECG prior to first injection, on day 5, day 10, and then weekly for 2 wk after last injection; discontinue if resting pulse >110/min, marked hypotension, precordial pain, marked neuromuscular symptoms, T-wave depression, arrhythmias, or proteinuria occur

Drug Name	Iodoquinol (Yodoxin)
Description	Diiodohydroxyquin. Amebicidal against E histolytica and is considered effective against trophozoite and cyst forms. Used to eradicate concurrent intestinal amebiasis in order to prevent recurrence of hepatic amebiasis.
Adult Dose	650 mg PO tid for 20 d
Pediatric Dose	30-40 mg/kg/d PO tid for 20 d; not to exceed 650 mg/dose
Contraindications	Documented hypersensitivity; hepatic dysfunction
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in thyroid disease; protein-bound serum iodine levels may be increased during treatment, interfering with certain thyroid function tests for as long as 6 mo by increasing serum levels of protein-bound iodine; caution in preexisting optic neuropathy and renal or hepatic disease (other then amebiasis); infants and young children are more susceptible to ocular toxicity (perform ophthalmological examination before and during therapy)

Drug Name	Diloxanide (Entamide, Furamide)
Description	Dichloroacetamide derivative. Amebicidal against trophozoite and cyst forms of E histolytica. Available in US only from the Parasitic Disease Drug Service, Centers for Disease Control and Prevention (Atlanta, GA 30333; telephone: 404-639-3356).
Adult Dose	500 mg PO tid with meals for 10 d; second course of treatment may be repeated after several wk prn
Pediatric Dose	<2 years: Not recommended >2 years: 20 mg/kg/d PO divided tid for 10 d; second course of treatment may be repeated after several wk prn
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Has not been studied in pregnant women, but showed no birth defects or other problems in animal studies; adverse GI effects (eg, flatulence, abdominal cramps, nausea, emesis, diarrhea) may occur; esophagitis rarely occurs but should be kept in mind if patient develops retrosternal pain, odynophagia, or dysphagia; not studied in pregnant women (no birth defects or other problems reported in animal studies)

Drug Name	Paromomycin (Humatin)
Description	Amebicidal and antibacterial aminoglycoside active in intestinal amebiasis. Not significantly absorbed from GI tract. Amebicidal against luminal forms.
Adult Dose	30 mg/kg/d PO divided tid for 7 d
Pediatric Dose	25 mg/kg/d PO divided tid for 7 d; not to exceed 2 g/d
Contraindications	Documented hypersensitivity; intestinal obstruction
Interactions	Nephrotoxic potential may increase with concurrent administration of other aminoglycosides, penicillins, cephalosporins, amphotericin B, and loop diuretics
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Due to narrow therapeutic index and toxic hazards associated with extended administration, not for long-term therapy; caution in renal failure, hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission; adjust dose in renal impairment; caution in ulcerative bowel lesions (inadvertent absorption may occur, resulting in nephrotoxicity)

Drug Name	Chloroquine (Aralen)
Description	Inhibits growth by concentrating within acid vesicles of parasite, which increases internal pH of organism. Also inhibits hemoglobin utilization and metabolism of parasite. In vitro studies with trophozoites of E histolytica demonstrate that chloroquine possesses amebicidal activity comparable to that of emetine. Highly effective in treatment of amebic liver abscess when administered with emetine or dehydroemetine. Like emetine and dehydroemetine, it is not effective against luminal forms. Irreversible retinal damage does not occur with dose and duration used for treatment of hepatic amebiasis.
Adult Dose	500 mg salt (300-mg base) PO bid for 2 d, followed by 250 mg salt (150-mg base) bid for 2-3 wk
Pediatric Dose	10-mg base/kg/d PO divided bid for 2-3 wk
Contraindications	Documented hypersensitivity; retinal and visual field changes attributable to 4-aminoquinolones; porphyria is considered a contraindication by some authors because drug may exacerbate condition
Interactions	Cimetidine may increase serum levels (possibly other 4-aminoquinolones); magnesium trisilicate may decrease absorption of 4-aminoquinolones
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hepatic disease, G-6-PD deficiency, psoriasis, and porphyria; perform periodic ophthalmologic examinations; if any abnormality in visual acuity, visual field, or retinal macular areas (eg, pigmentary changes, loss of foveal reflex) or any visual symptoms (eg, light flashes, streaks) occur, discontinue immediately and closely observe for possible progression; test for muscle weakness; fatalities have been reported following accidental ingestion, sometimes in relatively small doses (0.75-1 g chloroquine phosphate in 3-y-old child); warn to keep this drug out of the reach of children because they are especially sensitive to 4-aminoquinoline compounds If any severe blood disorder appears that is not attributable to the disease under treatment, discontinue agent unless benefit clearly outweighs risk; potential for serious adverse reactions in breastfeeding infants if chloroquine is administered to breastfeeding women

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Outpatient Care

• Follow-up ultrasonography or CT scan is unnecessary after resolution of symptoms and signs because the radiological resolution may take several months to years. See Prognosis.
• Luminal amebicides fail to eradicate the luminal forms of E histolytica in approximately 10-15% of patients treated with these agents; therefore, a follow-up stool examination is recommended after completion of therapy. A second course of a luminal amebicide is required in a few weeks if the first course fails to eradicate the intestinal carriage.

Deterrence/Prevention

• Control of amebiasis can be achieved by exercising proper sanitary measures and avoiding fecally contaminated food and water.
• • Regular examination of food handlers and thorough investigation of diarrheal episodes may identify the source of infection in some communities.
  • Vegetables must be cleaned with a strong detergent soap and soaked in acetic acid or vinegar for approximately 15 minutes to eradicate the cyst forms.
  • Boiling is the only effective means of eradicating the cysts in water.
• Change in sexual practices to avoid fecal-oral contamination is of importance in the male homosexual population.
• Travelers to areas with suboptimal sanitation and hygiene should eat only cooked foods or fruits peeled by themselves and should avoid drinking local water, including ice cubes frequently used for cocktails.
• Notably, many types of bottled water in developing countries are not properly disinfected.
• No prophylactic drug or vaccine currently is available for amebiasis.
• • Recombinant versions of 3 amebic antigens have protective efficacy in animal studies.
  • A serine-rich E histolytica protein (SREHP) has been expressed in avirulent vaccine strains of Salmonella. Based on these findings, development of an oral vaccine and a combined typhoid fever/amebiasis vaccine is in progress.
  • E histolytica galactose/N-acetyl-D-galactosamine (Gal/GalNAc) has been extensively studied as an attractive candidate for vaccine development.

Complications

• Pleuropulmonary infection is the most common complication. Mechanisms of infection include development of a sympathetic serous effusion; rupture of a liver abscess into the chest cavity, leading to empyema; or hematogenous spread, resulting in parenchymal infection.
• Bronchopleural fistula may occur in rare instances when patients expectorate a substance that resembles anchovy paste. Trophozoites may be demonstrated in the fluid. Occasionally, this complication may be followed by a spontaneous cure of the amebic liver abscess.
• Cardiac involvement results following the rupture of an abscess involving the left lobe of the liver. It usually is associated with very high mortality.
• Intraperitoneal rupture occurs in 2-7% of patients. Left lobe abscesses are more likely to progress to rupture because of their later clinical presentation.
• Bacterial superinfection can occur.
• Rupture into peritoneal organs (eg, stomach) and mediastinum can occur.
• Cases of hepatic artery pseudoaneurysm have been reported.

Prognosis

• In most cases, rapid clinical improvement is observed in less than 1 week with antiamebic drug therapy alone. Radiological resolution lags behind the resolution of clinical symptoms. The average time to radiological resolution is approximately 12 months, with a range of 3 months to 11 years.
• Death occurs in approximately 5% of persons having extraintestinal infection, including liver abscess. Rupture into the peritoneal cavity and the pericardium are responsible for most deaths.
• The following are the independent risk factors predicting a higher mortality:
• • Bilirubin level greater than 3.5 mg/dL
  • Encephalopathy
  • Volume of abscess cavity greater than 500 mL at presentation
  • Serum albumin less than 2 g/dL
  • Hemoglobin less than 8 g/dL
  • Multiple abscesses

Patient Education

• Direct patient and public education at sanitary measures; personal hygiene, including hand washing; and food hygiene.
• Educate travelers to endemic areas about the precautions needed. The details are discussed in Deterrence/Prevention.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Persistence of cavity alone after therapy, without associated signs and symptoms, does not indicate the need for repeating antibiotic therapy. See Prognosis.
• The cavitary lesions of amebic liver abscess and hepatocellular carcinoma can be confused, particularly in areas of the world where the frequency of both conditions is high.
• Absence of rapid response to medical therapy warrants further diagnostic evaluation to rule out pyogenic abscess or hepatoma.
• Failure to use luminal agents after tissue amebicides can lead to relapse of infection in approximately 10% of patients.

Special Concerns

• Treat women who develop hepatic amebiasis during pregnancy with metronidazole, although some theoretical risks are involved. No adverse outcomes have been reported in a long-term follow-up study of pregnant women given metronidazole for trichomoniasis.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  CT scan of the abdomen with IV and oral contrast is shown. Note the thick-walled cavity with low attenuation center and contrast-enhanced periphery. CT scan cannot differentiate amebic liver abscess from pyogenic liver abscess.
	View Full Size Image
Media type:  CT

Media file 2:  CT scan of the abdomen of the same patient in Image 1 is shown without contrast. A thick-walled cavity with low attenuation center is located in the right lobe of the liver.
	View Full Size Image
Media type:  CT

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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Article Last Updated: Dec 8, 2006