Liver Abscess

NATALIE J. ToÈ RoÈ K AND GREGORY J. GORES

Mayo Clinic and Foundation

hematogenous spread Dissemination via the circulation.

hydatid cyst Vesicular structure formed as a consequence of

Echinococcus infection.

pyogenic Pus forming.

scoleces Anterior parts of the Echinococcus; they are formed

within the hydatid cyst.

trophozoite Vegetative form of a parasite.

Liver abscesses do not represent a speci®c liver disease,

but rather a ®nal common pathway of many pathologic

processes. In the preantibiotic era, liver abscesses were

typically sequelae of intraabdominal infectious processes

(e.g., appendicitis) or of tuberculosis. Currently, most

liver abscesses are secondary to biliary tract diseases or

amebiasis. Many advances, including the development of

antibiotics, recognition of the role of the anaerobic bac-

teria, the advent of noninvasive imaging, and the use of

nonsurgical drainage for pyogenic abscesses, have im-

proved outcome.

EPIDEMIOLOGY

The incidence of liver abscess shows a wide range ofvariation, depending on the etiology. The incidence ofpyogenic liver abscess ranges from 8 to 20 cases permillion people. With the availability of effective antimi-crobials, pyogenic liver abscess has become a disease ofmiddle-aged persons, probably because of the preva-lence of biliary disease as a major cause is higher inthis population. No signi®cant sex, ethnic, or geo-graphic differences seem to exist in disease prevalence,in contrast to the epidemiology of amebic liver abscess.Amebic liver abscess is marked by a signi®cant malepreponderance and is a disease seen most commonlyin patients who reside in or have emigrated from anendemic area, or who have travel history to an endemicarea. Countries with the highest Entamoeba histolyticaendemic activity include Mexico, India, East and SouthAfrica, and Central and South America. As estimated bythe World Health Organization (WHO) in 1995, ap-proximately 40 million to 50 million people worldwideare symptomatic with amebic colitis or liver abscess,resulting in 40,000ÿ100,000 deaths each year. In the

United States, immunosuppression seems to be animportant risk factor. Patients with HIV infection,malnourishment, and alcoholism are at risk of devel-oping amebiasis.Echinococcosis may result in hydatidliver cyst formation; the most common pathogen isEchinococcus granulosus. The resulting cystic hydatiddisease has worldwide distribution. In tuberculosis,the liver is commonly involved, with a granulomatousreaction, but the formation of tuberculous liver abscessis rare worldwide and usually is not considered in thedifferential diagnosis of liver abscesses. Worldwide,only 43 cases have been reported.

PATHOGENESIS

Pyogenic liver abscesses are classi®ed by the presumedroute of hepatic invasion: (1) biliary tree, (2) portal vein,(3) hepatic artery, (4) direct extension from contiguousfocus of infection, and (5) penetrating trauma.Cholangitis is now the major cause of pyogenic liverabscess. Patients with Caroli's disease and primary scle-rosing cholangitis (PSC) have a particularly high rate ofpyogenic abscess formation. In Third World countries,infection of the biliary tree by Cryptococcus neoformansor direct invasion by Ascaris lumbricoides may occur.Mechanical manipulation of the biliary tree, such asafter endoscopic retrograde cholecystopancreatography(ERCP), or percutaneous biliary tube placement can becomplicated by abscess formation. The portal venoussystem drains almost all of the abdominal viscera.Pylephlebitis from diverticulitis, in¯ammatory boweldisease, pancreatitis, and prostatitis can result in pyo-genic abscess formation (Table I). Historically, un-treated appendicitis was a major cause of liverabscess in the past, but its occurrence has greatly dimin-ished with the use of antibiotics. Systemic bacteremiamay also result in microabscess formation in the liverbecause bacteria are disseminated via the hepatic artery.Direct extension from a contiguous source of infectioncan occur with cholecystitis and subphrenic abscesses.

In terms of pathogens, Escherichia coli and Klebsiellaspecies are by the far the most common isolates.

Encyclopedia of Gastroenterology 507 Copyright 2004, Elsevier (USA). All rights reserved.

Klebsiella abscesses are frequently associated with gasformation. Enterococci and the viridans streptococci arealso common, especially in polymicrobial abscesses,whereas Staphylococcus aureus is more commonlyassociated with monomicrobial abscesses. In hemo-chromatosis, abscesses are often caused by Yersiniaenterocolitica.

Amebiasis is caused by ingestion of infectiveE. histolytica cysts through a fecalÿoral route of expo-sure. The cysts are resistant to degradation in the stom-ach and pass to the small intestine, where excystationand liberation of the trophozoite form of the parasiteoccur. The trophozoites then pass to the colon, wherethey cause mucosal invasion and subsequent spread tothe liver. The pathology in amebic abscess involvesthree consecutive stages: acute in¯ammation, granu-loma formation, and progressively advancing necrosiswith abscess formation and periportal ®brosis. The ab-scess contains necrotic tissue surrounded by a rim ofamebic trophozoites.

Echinococcosis causes human disease when humansbecome hosts for a cystic intermediate stage of caninetapeworms. Echinococcus granulosus most ofteninfects humans in contact with sheep-herding dogs.The hydatid liver cysts are ¯uid-®lled structures linedby a parasite-derived membrane. The cysts caused byEchinococcus multilocularis are less de®ned; they tend toinvade the liver parenchyma and also seed the adjacentorgans.

CLINICAL PRESENTATION

Only 10% of patients with pyogenic liver abscess presentwith the classic triad of fever, jaundice, and right upperquadrant pain. Fever and constitutional symptoms in-cluding malaise, fatigue, and anorexia are common. Inthe presence of cholangitis, pruritus and jaundice mayalso be additional features. There seems to be an asso-ciation between the cause of the abscess and the dura-tion of the symptoms: hematogenous liver abscessespresent most acutely (3 days), whereas those secondaryto pylephlebitis (42 days) have the longest duration ofsymptoms.

In the case of amebic liver abscesses, 80% of patientspresent with symptoms that develop over 2ÿ4 weeks.The symptoms are similar to those in patients with pyo-genic abscesses; gastrointestinal symptoms also occur in10ÿ35% of patients and may include nausea, vomiting,diarrhea, abdominal cramping, diarrhea, or constipation.

Echinococcal liver cysts are often asymptomatic andpresent as a hepatic mass with a typical appearance oncomputer tomography (CT) or magnetic resonanceimaging (MRI).

DIAGNOSIS

Laboratory tests in cases of pyogenic liver abscessesreveal leukocytosis in many cases. Liver biochemistriesare also abnormal in most of the patients; however,normal results do not exclude the diagnosis. Serumalkaline phosphatase level is elevated in two-thirds ofpatients and tends to be more markedly elevated thantransaminase levels. Blood cultures are positive in abouthalf of the patients. Multiple samples should be ob-tained, because this may be the only clue to the path-ogenic agent prior to starting antimicrobial therapy.

Leukocytosis is moderate in cases of amebic liverabscesses, and eosinophilia is rare. Anemia is a typical®nding. Overall, the incidence of liver test abnormalitiesis the same in patients with amebic liver abscess or withpyogenic liver abscess. Most patients (470%) withamebic abscess do not have detectable parasites inthe stool, therefore serologic testing for antibodies toE. histolytica is the most useful diagnostic test. The mostcommonly used serologic test currently is the enzymeimmunoassay (EIA), because it is rapid, stable, andmore speci®c and sensitive than other diagnostic tests.

In hydatid liver disease, the Echinococcus cysts arerarely found in the stool. Eosinophilia is usually present.Enzyme-linked immunosorbent assay (ELISA) is thetest of choice and is positive in about 90% of caseswith the disease.

Radiographic imaging studies are essential in mak-ing the diagnosis. Ultrasonography (US) and CT haveproved particularly useful for abscess visualization andsubsequent drainage (see Fig. 1). US is the study ofchoice in patients with suspected biliary disease. Intra-venous contrast-enhanced CT offers improved sensitiv-ity and is superior for guiding complex drainingprocedures. MRI studies are now also recognized tobe useful alternatives to CT imaging, especially if theabscesses arise as a result of cholangitis, allowing betterde®nition of disease extent. Magnetic resonance chol-angiography may further add to the sensitivity, espe-cially if there is a suspicion of a cholangiocarcinoma.Chest radiographs are abnormal about half of the time,

TABLE I Occult Causes of Pyogenic Liver Abscesses

Diverticulitis

In¯ammatory bowel disease

Prostatitis

Pelvic in¯ammatory disease

Pancreatitis

Appendicitis

508 LIVER ABSCESS

but are of no real value in making the diagnosis. A 99 mTcnuclear hepatic scan is useful in differentiating an ame-bic abscess from a pyogenic abscess. Because amebicliver abscesses do not contain leukocytes, they appearas `̀ cold'' lesions on a nuclear scan, with a typical `̀ hot''halo of radioactivity surrounding the abscess due toincreased focal activity of leukocytes.

TREATMENT

The treatment of pyogenic abscesses consists of antibi-otic administration and drainage of the abscesses.Radiographically guided percutaneous drainage isnow pursued in most patients. Over the past 20 years,several studies have shown that percutaneous catheterdrainage with antibiotic therapy has a success ratebetween 70 and 90%. Observations by Giorgio andco-workers suggest that repeated needle aspiration inselected patients with low viscous material within theabscess cavity may be a reasonable alternative.

Antibiotics should be started as soon as the diagnosisis suspected, after blood cultures are obtained. Pyogenicabscesses that arise in patients with biliary disease ofteninclude enterococci and enteric gram-negative bacilli.Biliary drainage is also essential if the abscess is second-ary to an obstructed bile duct. If the source of the in-fection is the colon or pelvic organs, antibiotic coveragefor coliforms and anaerobes is needed. The usual courseof treatment is 2ÿ3 weeks of parenteral antibiotic ther-apy with adequate abscess cavity drainage. The clinicalresponse is followed by serial interval studies.

Treatment options for uncomplicated amebic liverabscess include amebicidal drugs and, if indicated, per-cutaneous or open aspiration of the abscesses. Thera-peutic aspiration of the amebic liver abscess should beconsidered in patients with (1) high risk of abscess rup-ture as de®ned by a cavity size of 5 cm or greater, (2) leftlobe abscess (because of the associated higher mortalityrate), and (3) failure to respond to drug therapy.Metronidazole remains the drug of choice for treatingamebic liver disease. Metronidazole, 750 mg orallythree times a day for 10 days, has been reported to becurative in more than 90% of patients with amebic liverabscess. If a patient fails to respond to metronidazole in5 days, then chloroquine (base) may be substituted oradded to the therapy.

Albendazole has become the current standard formedical therapy of hydatid disease. It is generally ad-ministered two to three times daily at doses rangingbetween 10 and 50 mg/kg/day, for 12 weeks. Frequentmonitoring for leukopenia and elevation of aminotrans-ferase levels is required. The standard and ®nal therapyis surgery, with the careful aspiration the of cyst ¯uid toavoid spillage of viable scoleces or anaphylaxis. Lapa-roscopic drainage and ultrasound-guided drainage havealso been reported.

See Also the Following Articles

Amebiasis � Computed Tomography (CT) � Liver Cysts �Magnetic Resonance Imaging (MRI) �Percutaneous Drainage

� Ultrasonography

Further Reading

Akgun, Y., Tacyildiz, I. H., et al. (1999). Amebic liver abscess:

Changing trends over 20 years. World J. Surg. 23(1), 102ÿ106.

Babba, H., Messedi, A., et al. (1994). Diagnosis of human

hydatidosis: Comparison between imagery and six serologic

techniques. Am. J. Trop. Med. Hyg. 50(1), 64ÿ68.

Balci, N. C., Semelka, R. C., et al. (1999). Pyogenic hepatic

abscesses: MRI ®ndings on T1- and T2-weighted and serial

gadolinium-enhanced gradient-echo images. J. Magn. Reson.

Imaging 9(2), 285ÿ290.

Chou, F. F., Sheen-Chen, S. M., et al. (1997). Single and multiple

pyogenic liver abscesses: Clinical course, etiology, and results

of treatment. World J. Surg. 21(4), 384ÿ388; discussion,

388ÿ389.

Giorgio, A., Tarantino, L., et al. (1995). Pyogenic liver abscesses: 13

years of experience in percutaneous needle aspiration with US

guidance. Radiology 195(1), 122ÿ124.

Gottstein, B. (1992). Molecular and immunological diagnosis of

echinococcosis. Clin. Microbiol. Rev. 5(3), 248ÿ261.

Hansen, P. S., and Schonheyder, H. C. (1998). Pyogenic hepatic

abscess. A 10-year population-based retrospective study. Apmis

106(3), 396ÿ402.

FIGURE 1 CT image of a pyogenic liver abscess (arrow); note

the peripheral enhancement.

LIVER ABSCESS 509