Thursday, April 10, 2008

AMEBIC LIVER ABSCESS (Part One)

AMEBIC LIVER ABSCESS

  • Although knowledge of pyogenic hepatic abscess has existed since the time of Hippocrates, it was not realized that amebic liver abscess was a separate entity until the nineteenth century.
  • Even before 1887, when Lösch discovered that E. histolytica was the causal agent of amebic dysentery, several European investigators had suggested a relationship between dysentery and liver abscess.
  • Not until 1890, however, did Osler first report the presence of amebae in a liver abscess as well as in the stool of the same patient.
  • Until that time, open surgical drainage had been the treatment recommended for both pyogenic and amebic liver abscesses.
  • In 1935, Ochsler and DeBakey confirmed earlier reports demonstrating a great reduction in mortality when aspiration and emetine were used instead of surgical drainage for amebic liver abscesses.
  • Serologic tests, noninvasive radiologic and radionucleotide techniques, and the use of newer amebicidal agents have led to earlier diagnosis and the ability to avoid aspiration in many of these patients.

Incidence

  • Amebiasis has a worldwide distribution, and the highest incidence is found in subtropical and tropical climates and in areas with poor sanitation.
  • The ease of world travel, increased United States military presence in tropical climates, and more visitors and immigrants from tropical countries continue to contribute to a significant incidence of amebiasis in the United States.
  • Fortunately, hepatic liver abscess occurs in only 3 to 7% of all patients with amebiasis in US.
  • Although significant numbers of patients with amebic liver abscesses are being reported from the south central and southwestern portions of the United States, the largest series continue to come from such countries as Korea, India, Malaysia, and South Africa.

Age, Sex, and Race

  • In the 1930s, Ochsner and DeBakey collected large series of both amebic and pyogenic liver abscesses and found that the mean age was in the 30s for both types of abscesses.
  • Since then, however, the age of the average patient who develops a pyogenic abscess has increased significantly, whereas the mean age of patients with amebic liver abscesses remains in the 30s.
  • Although amebic liver abscess has been reported in the very young and the very old, its occurrence at the extremes of age is unusual.
  • Among 401 patients collected from 6 published series, only 24 were younger than 20 years or older than 70 years.
  • The age distribution among patients reported from the United States and from other countries is similar.
  • In the 1930s, Ochsner and DeBakey reported a male-to-female ratio of 2:1 among patients with pyogenic liver abscesses and 6.5:1 among their patients with amebic abscesses.
  • Although the reason for this male predisposition remains obscure, almost all series reported from this country and many others confirm that 85 to 95% of patients with amebic liver abscesses are men.

As with pyogenic liver abscess, no racial predisposition has been established for amebic liver abscess.

Etiology and Pathogenesis

  • E. histolytica in the cystic form gains access to the body by oral ingestion of infected material, usually contaminated water.
  • Hygienic standards therefore play an important role in the control and spread of the disease.
  • The mature cysts of E. histolytica, which measure only 10 to 20 µm in diameter, are resistant to acid pH and to drying.
  • After ingestion of contaminated water or food, these cysts pass unchanged through the stomach into the intestine.
  • The resistant cyst wall is then digested by trypsin, and four invasive trophozoites are released.
  • Trophozoites live and multiply in the lumen of the large intestine, especially the cecum.
  • Trophozoites exist in two forms:
  • a small form 10 to 20 µm in diameter and
  • a large 20- to 60-µm form.
  • The large trophozoites are present in invasive amebiasis and generally contain ingested erythrocytes within vacuoles in their cytoplasm.
  • Trophozoites that pass into the distal colon may change into round or oval cysts and may pass in the feces as a resistant cyst.
  • Human carriers who pass cysts of E. histolytica in their stools are the primary source of infection.

E. histolytica may live within the lumen of the colon in the small form without tissue invasion.

  • When tissue invasion occurs, trophozoites ingest erythrocytes and become large forms.
  • Demonstration of these hematophagous trophozoites in the stool is excellent evidence that the parasite has become invasive.
  • Examination of the cecum in invasive amebiasis reveals minute superficial ulcerations where trophozoites have entered the mucosa.
  • Further invasion may result in hemorrhage, perforation, and enterocolic or cutaneous fistulas, amebic appendicitis, or an ameboma.
  • Amebic trophozoites also may enter the mesenteric venules or lymphatics and may be carried to the liver, lungs, or other organs.
  • The most frequent site of extraintestinal colonization, however, is the liver.
  • The three possible routes by which amebae may gain access to the liver are
  • (1) through the portal vein,
  • (2) through lymphatic vessels, and
  • (3) by direct extension through the colonic wall into the peritoneum and then through the liver's capsule.
  • Most experts agree, however, that amebae usually reach the liver through the portal vein.

If sufficient numbers of amebic trophozoites enter the liver and become lodged in smaller venules, thrombosis and infarction of small areas of hepatic parenchyma occur.

  • Further destruction of the liver results from the cytolytic activity of the amebae.
  • This early stage has been called amebic hepatitis, but the pathologic features of this stage have not been studied adequately because patients are seen rarely at this point in their illness.
  • The state of the host's nutrition and the host's immune status may be factors that determine whether the initial hepatic infestation will heal or progress to macroabscess.
  • Development of an amebic liver abscess presumably results from coalition of small areas of necrosis and amebic cytolytic destruction of hepatic parenchyma.

The fluid contained within an amebic liver abscess is usually dark reddish-brown and has been described most often as "anchovy sauce" or "anchovy paste."

  • This material, which is typically sterile and consists of a mixture of blood and destroyed liver cells, has also been described as resembling "chocolate sauce," "crushed strawberries," or "wine dregs."
  • Amebic trophozoites are rarely found within the "pus" of a liquefied amebic abscess, but they are found characteristically in the zone of necrotic tissue adjacent to the outer abscess wall.
  • Demonstration of trophozoites is more frequent during the earlier stages of an abscess and is less likely in an older abscess with a thick fibrotic capsule.
  • Histologic examination during the early stages reveals cytolysed and degenerated liver cells, erythrocytes, a few leukocytes, and occasionally an ameba.
  • As the lesion progresses, a well-defined wall of connective tissue appears and surrounds the cavity that contains necrotic liver tissue.
  • In an amebic abscess, however, leukocytic infiltration and an inflammatory reaction are characteristically absent.
  • Abscess cavities vary in size from 1 to 25 cm, and if the condition is untreated, these cavities will rupture into adjacent organs or into the peritoneum, pleural cavity, lung, or pericardium.

Location and Number of Abscesses

Amebic hepatic abscesses are more likely to be solitary and to be located in the right hepatic lobe than are pyogenic liver abscesses.

  • In a collected series of 722 amebic abscesses published from 1970 to 1980, 613 patients (85%) had a solitary abscess.
  • In comparison, only 53% of 330 cases of pyogenic hepatic abscesses collected over the same time period were solitary.

The preponderance of amebic liver abscesses in the right lobe may be explained by streaming of blood in the portal vein.

  • Amebiasis most frequently affects the right side of the colon.
  • Flow from the superior mesenteric vein, which drains the right side of the colon, goes to the right hepatic lobe, whereas flow from the inferior mesenteric and splenic veins goes to the left lobe.



Symptoms and Physical Findings

  • As with pyogenic hepatic abscesses, amebic abscess of the liver may present either as an acute inflammatory process or as a chronic indolent disease suggestive of a malignant process.
  • In analyzing 400 consecutive admissions for amebic liver abscess at the University of Natal, Durban, South Africa, Adams and MacLeod found that 59% of their patients had symptoms lasting less than 2 weeks.
  • An additional 20% of their patients had symptoms lasting 2 to 4 weeks.
  • Only 5% of their patients gave a history of symptoms that lasted more than 12 weeks.
  • Most patients, however, do not have symptoms of dysentery at the time of presentation with an amebic liver abscess.

The major complaint of patients with an amebic liver abscess is pain, which is usually localized in the right upper quadrant.

  • However, pain may also be localized to the epigastrium, or it may be generalized, pleuritic, or radiating to the right shoulder.
  • In comparing patients with amebic and pyogenic abscesses, Conter and associates found that, in addition to abdominal pain, patients with amebic abscesses were more likely to present with diarrhea, abdominal tenderness, and hepatomegaly.
  • In comparison, patients with pyogenic abscesses were more likely to have pruritus, jaundice, septic shock, or a palpable mass at the time of presentation.
  • In summary, patients with an amebic liver abscess are more likely than those with a pyogenic abscess to present with pain and diarrhea and to have hepatomegaly and a tender liver on physical examination.
  • Fever is present in most patients with either type of liver abscess, but high, spiking fevers associated with chills are seen most frequently with pyogenic hepatic abscesses.

Diagnosis

  • Differentiation of an amebic liver abscess from a pyogenic hepatic abscess on clinical grounds may be impossible.
  • Likewise, both entities may be confused with various intrahepatic neoplastic processes.
  • Several of the newer noninvasive radiologic diagnostic modalities aid in these differentiations.
  • In addition, several serologic tests are available to aid in the diagnosis of amebic hepatic abscesses.
  • However, demonstration of E. histolytica in the stool is still the only definitive proof of intestinal amebiasis.

Stool Examination

  • The reported incidence of finding amebic cysts or trophozoites in the stool of patients with an amebic liver abscess varies considerably.
  • These variations may be explained by the finding that identification of E. histolytica trophozoites or cysts requires careful handling of specimens, an experienced technician, and avoidance of interfering substances.

Microscopic examination of a fresh stool specimen or of material obtained by scraping or biopsy of the rectal mucosa during sigmoidoscopy provides the best chance of identifying the motile amebic trophozoites.

  • If an experienced technician is not readily available, the specimen may be preserved in formalin or polyvinyl alcohol.
  • Examination of several stools may be necessary because excretion of cysts may be intermittent.
  • The use of several stains (e.g., buffered methylene blue, trichrome, and iodine) also may assist in identification of amebae.
  • Krogstad and associates pointed out that numerous substances, including antibiotics, antiparasitic drugs, laxatives, antacids, radiologic contrast media, enemas, and antidiarrheal drugs, may interfere with stool examination for parasites.
  • These reasons explain why amebae are not found in the stools of most patients with an amebic liver abscess.

Serologic Tests

  • Because stools from many patients with amebic liver abscess are negative for amebae, serologic tests are particularly useful in evaluating these patients.
  • Numerous serologic tests for amebiasis have been developed.
  • These tests include indirect hemagglutination (IHA), gel diffusion precipitin (GDP), complement fixation, latex agglutination, cellulose acetate precipitin, enzyme-linked immunosorbent assay, and identification of a recombinant protein.
  • For tests that provide titers, little correlation exists between the degree of seropositivity and the severity of infection.
  • If results are positive, however, these tests indicate current or previous amebic infection. Therefore, these tests have the greatest use in non-endemic areas.

The IHA and GDP have been the most frequently used serologic tests.

  • Several investigators have reported that the IHA frequently remains positive for many years after invasive amebiasis, whereas in two thirds of their patients, the GDP was negative in 6 months.
  • The GDP test has the additional advantages that it is inexpensive and simple to perform, and it can provide information in 24 to 48 hours.
  • The cellulose acetate diffusion and countercurrent immunoelectrophoresis tests yield results within a few hours, but, to date, experience with these tests has not been compared with that of either IHA or GDP in a large population of patients with amebic abscesses.
  • The most recently developed test measures a 29-kD peripheral membrane protein of pathogenic E. histolytica.
  • This test can differentiate patients with pathogenic and nonpathogenic strains and is highly specific and reasonably sensitive.

Laboratory Data

  • Results of hematologic and liver function tests are similar in patients with amebic and pyogenic liver abscesses.
  • Approximately 70% of patients with amebic abscess will present with leukocytosis, and leukocyte counts greater than 20,000/mm3 are not uncommon.
  • Eosinophilia, however, is a rare finding.
  • Almost half of 592 patients were anemic at the time of presentation.
  • Likewise, approximately 50% of patients with an amebic liver abscess will have an elevated alkaline phosphatase level.
  • Mild elevations of serum glutamic-oxaloacetic or serum glutamic-pyruvic transaminases are seen in 35 to 45% of patients with amebic hepatic abscesses.
  • Large increases in transaminase levels are uncommon, however, because of the localized nature and lack of inflammatory reaction observed with most amebic abscesses.
  • Mild elevations in serum bilirubin levels were present in 30% of 592 collected cases of amebic liver abscess.
  • The incidence of jaundice varied considerably, however, from as low as 6% to as high as 53% in individual studies.
  • The presence of jaundice in patients with amebic abscesses has been associated with both a higher incidence of complications and a higher mortality rate.



Roentgenographic Findings

  • Approximately two thirds of patients with an amebic liver abscess will have an abnormal chest radiograph.
  • The most common radiologic finding in these patients is elevation of the right hemidiaphragm.
  • Fluoroscopy of the diaphragm also reveals decreased motion in many of these patients.
  • Other plain roentgenographic findings, seen less frequently, include right pleural effusion, right lower lobe infiltrate, and hepatomegaly.
  • Barium studies may show displacement of the stomach or colon by an enlarged liver. Cohen and Reynolds also reported nonvissualization on oral cholecystography or intravenous cholangiography in 11 of 13 patients studied.
  • None of these patients was vomiting, had diarrhea or acute pancreatitis, or was jaundiced.
  • After treatment of the amebic abscess, however, 6 of 7 patients restudied had a normal cholangiogram.

Liver Scanning

Hepatic scanning demonstrates amebic liver abscesses larger than 2 cm in diameter.

  • A review of 105 collected cases of amebic abscess in patients in whom a diagnostic liver scan was obtained revealed correct identification of the abscess in 91 patients (87%).
  • In a 1986 analysis of 57 patients with amebic abscesses, Thompson and Glasser found that 99mTc liver scans were 100% accurate in establishing the diagnosis.
  • Another important advantage of liver scanning is that the exact number and location of abscesses can be determined; as a result, therapy can be individualized.
  • Liver scanning is also an excellent noninvasive method of following the progress of amebic abscesses that are being treated nonoperatively.
  • At present, 99mTc and 67Ga are the most widely used scans.
  • Several investigators have reported the use of gallium scanning to differentiate amebic abscesses from pyogenic abscesses.
  • With gallium scanning, an amebic abscess demonstrates peripheral uptake around a central cold area, whereas a pyogenic abscess has increased uptake of gallium throughout the abscess.
  • Liver scanning was the first radiographic method used in the diagnosis, localization, and follow-up of amebic abscesses, but now ultrasound and, to a lesser extent, CT are being used more frequently in the management of these patients.

Ultrasound

  • Several reports suggest that sonography is accurate in the diagnosis of amebic liver abscess.
  • Thompson and Glaser reported ultrasound identification of amebic liver abscesses in 94% of their patients in Los Angeles, and Maltz and Knauer reported a 92% accuracy for ultrasound in 39 patients from San Jose.
  • Several sonographic features of amebic liver abscesses make this diagnosis possible.
  • The wall is smooth in two thirds of patients,
  • internal echoes are less dense than the surrounding normal liver in 85%,
  • and a decrease in echoes of two thirds or more was present in 90 to 95%.
  • Ultrasound is the accurate and in most cases can differentiate amebic abscesses from other hepatic lesions.
  • Sonography can determine the number, size, and location of abscesses and can be used as a guide for percutaneous aspiration.
  • Because ultrasound is non-invasive, rapid, relatively inexpensive, and reproducible, it is also ideal for follow-up of patients with amebic abscesses, most of whom are managed nonoperatively.


Computed Tomography

Although large numbers of patients with amebic liver abscesses have been studied with ultrasound, relatively few have undergone CT or hepatic arteriography.

  • The great advantage of CT over ultrasound is that smaller lesions can be detected.
  • This advantage is important in patients with multiple small (<2 cm) pyogenic abscesses.
  • However, most amebic abscesses are solitary and are of sufficient size (>2 cm) to be easily detected by ultrasound.
  • However, because of the additional expense with CT, this diagnostic modality should be reserved for patients suspected of having an amebic abscess in whom ultrasound is not diagnostic.

Magnetic Resonance Imaging

Reports by both Elizondo and associates and Ralls and colleagues suggest that MRI is a sensitive way to detect and follow amebic liver abscesses.
  • Pretreatment T1-weighted images show a sharply circumscribed heterogeneous mass of low signal intensity, whereas T2-weighted images demonstrate a hyperintense region.
  • On MRI, amebic abscesses also often have multiple rims of variable signal intensity.
  • After treatment, the abscess cavity demonstrates concentric rings corresponding to an inner area of inflamed tissue, a band of collagen, and an outer margin of inflamed liver tissue.
  • Unfortunately, bacterial abscesses, intrahepatic hematomas, and necrotic tumors may have MRI characteristics similar to those observed with amebic liver abscesses.
  • Thus, for reasons of cost and availability, ultrasound remains the procedure of choice for screening and for following patients at risk of amebic hepatic abscesses.

Aspiration

The main reasons to aspirate a liver abscess are

  • (1) to establish a diagnosis and
  • (2) to reduce the likelihood of rupture of a large abscess.
  • Even before the advent of ultrasound- or CT-guided aspiration, most experts found that diagnostic needle aspiration was a safe procedure.
  • Using only clinical means for localization, Adams and MacLeod reported that successful aspiration was possible in two thirds of patients with amebic liver abscesses.
  • However, as reliable serologic tests, which can yield results in less than 24 to 48 hours, have become available, the need for diagnostic aspiration has been questioned by several investigators.
  • When the diagnosis remains uncertain despite serologic tests and stool examination, or when bacterial superinfection of an amebic abscess is suspected, diagnostic aspiration is indicated.

The reported incidence of recovery of amebae from amebic abscess cavities varies considerably. Explanations for this wide variation include

  • (1) differences in handling of specimens,
  • (2) the availability of expert technicians to analyze the fluid, and
  • (3) a higher yield in some series when scrapings of the abscess wall obtained during surgical drainage were included.

Because amebae cannot always be demonstrated, careful analysis of the fluid is important.

  • Fluid from a true amebic abscess should be sterile when it is cultured aerobically and anaerobically, and no organisms should be seen on Gram staining.
  • Other characteristics of the aspirated fluid also may be helpful.
  • Although fluid from an amebic abscess has been characterized classically as reddish-brown "anchovy paste," both the color and the consistency of aspirated fluid vary.
  • Perhaps a more reliable characteristic than color is the odor of the fluid.
  • Amebic abscesses, unless they are superinfected, have no odor.
  • Pyogenic abscesses, and particularly those involving anaerobic bacteria, have a foul odor.

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