Amebic liver abscess

Amebic liver abscess :

is the most frequent extraintestinal manifestation ofEntamoeba histolytica infection. This infection is caused by the protozoa E histolytica, which enter the portal venous system from the colon. 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.

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 in 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 Gal/GalNAc lectin is an adhesion protein complex that sustains tissue invasion.^[1] The abscess contains acellular proteinaceous debris, which is thought to be a consequence of induced apoptosis^[2] 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 portal laminar blood flow is supplied predominantly by the superior mesenteric vein, whereas the left lobe portal blood flow is supplied by the splenic vein.

Epidemiology

Frequency

United States

Amebic liver abscess is rare and is currently 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. 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.

Race-, sex-, and age-related demographics

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

Amebic liver abscess is marked by a 7-12–fold higher incidence in males than in females despite an equal sex distribution of noninvasive colonic amebic disease among adults.^[3] However, no sexual preponderance exists among children.

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

International

Worldwide, approximately 40-50 million people are infected annually, with the majority of infections occurring in developing countries. The prevalence of infection is higher than 5-10% in endemic areas^[4] and sometimes as high as 55%.^[5] 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.^[6]

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.

History

The signs and symptoms of amebic liver abscess often are nonspecific, resembling those of pyogenic liver abscess or other febrile diseases.^{[7, 8, 9, 10]}

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 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 is usually constant, dull, and aching, and it is most frequently located in the right upper quadrant (54-67%) and may radiate to the right shoulder or scapular area.

The pain increases with coughing, walking, and deep breathing, as well as when patients rest on their right side.

Constitutional symptoms

Fever is present in 87-100% of cases, and rigors are present in 36-69% of cases.

Nausea and vomiting are present in 32-85% of cases, and 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.^[11]

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.

Right upper abdominal quadrant tenderness is present in 55-75% of cases. When the abscess is located in the left lobe (28% of cases), epigastric tenderness is noted.

Pulmonary abnormalities are present in 20-45% of cases, and they 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) most often occurs in complicated cases with multiple abscesses or a large abscess compressing the biliary tract.

Signs of complications include the following:

• Signs of peritoneal irritation, such as rebound tenderness, guarding, and absence of bowel sounds, are present when the abscess ruptures into 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 a very high mortality.
• Signs of pleural effusion are present when the abscess ruptures into the pleural cavity.

Causes

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

• Immigrants from endemic areas
• Institutionalized persons, especially people with mental retardation
• Crowding and poor hygiene
• Men who have sex with men (secondary to sexually acquired amebic colitis)
• Presence of immunosuppression (eg, HIV infection, malnutrition with hypoalbuminemia, alcohol abuse, chronic infections, posttraumatic splenectomy, steroid use) 

• 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

  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 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 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.

  In vivo resistance to metronidazole by E histolytica has not been reported. 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.

  Other items to consider

  Other considerations include the following:

  • 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 ofE 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. Note the following:

  • 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.

  Consultations

  Consult with an interventional radiologist for imaging-guided aspiration of the abscess.

  Consult with a general surgeon for open surgical drainage of the abscess under rare circumstances (see Surgical Care).

  Diet and activity

  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).

  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.

  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.

  The following are predictive of the need for aspiration: (1) age older than 55 years, (2) abscess greater than 5 cm in diameter, and (3) failure of medical therapy after 7 days.^[25] In endemic areas, because of the late presentation and the existence of multiple abscesses, as many as 50% of patients may require aspiration.^[26]However, routine needle aspiration offers only minimal benefit over medical care alone for uncomplicated amebic liver abscess and, unless one of the above indications exists, should be avoided.^[27] Prompt medical care decreases the need for aspiration.^[28]

  Imaging-guided needle aspiration and catheter drainage are the procedures of choice. 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 5-7 days.

  Simple needle aspiration is less invasive, is 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).

  Although catheter drainage may be more effective than needle aspiration, in a study by Rajak et al,^[29] the average time for clinical improvement, mean hospital stay, and time to resolution were similar among the patients who were successfully treated in the 2 treatment groups.