4/14/2018 Liver Abscess: Background, Pathophysiology, Etiology

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Liver Abscess
Updated: Jun 08, 2017
Author: Ruben Peralta, MD, FACS; Chief Editor: John Geibel, MD, DSc, MSc, AGAF more...

OVERVIEW

Background
Bacterial abscess of the liver is relatively rare; however, it has been described since the time of
Hippocrates (400 BCE), with the first published review by Bright appearing in 1936. In 1938,
Ochsner's classic review heralded surgical drainage as the definitive therapy; however, despite the
more aggressive approach to treatment, the mortality remained at 60-80%. [1]

The development of new radiologic techniques, the improvement in microbiologic identification,

and the advancement of drainage techniques, as well as improved supportive care, have reduced
mortality to 5-30%; yet, the prevalence of liver abscess has remained relatively unchanged.
Untreated, this infection remains uniformly fatal.

The three major forms of liver abscess, classified by etiology, are as follows:

Pyogenic abscess, which is most often polymicrobial, accounts for 80% of hepatic abscess
cases in the United States
Amebic abscess due to Entamoeba histolytica accounts for 10% of cases [2]
Fungal abscess, most often due to Candida species, accounts for fewer than 10% of cases

For patient education resources, see the Infections Center and the Digestive Disorders Center, as
well as Skin Abscess and Antibiotics.

Pathophysiology
The liver receives blood from both systemic and portal circulations. Increased susceptibility to
infections would be expected given the increased exposure to bacteria. However, Kupffer cells
lining the hepatic sinusoids clear bacteria so efficiently that infection rarely occurs. Multiple
processes have been associated with the development of hepatic abscesses (see the image
below).

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4/14/2018 Liver Abscess: Background, Pathophysiology, Etiology

Table 4: Underlying etiology of 1086 cases of liver abscess compiled from the literature.

Appendicitis was traditionally the major cause of liver abscess. As diagnosis and treatment of this
condition has advanced, its frequency as a cause for liver abscess has decreased to 10%.

Biliary tract disease is now the most common source of pyogenic liver abscess (PLA). Obstruction
of bile flow allows for bacterial proliferation. Biliary stone disease, obstructive malignancy affecting
the biliary tree, stricture, and congenital diseases are common inciting conditions. With a biliary
source, abscesses usually are multiple, unless they are associated with surgical interventions or
indwelling biliary stents. In these instances, solitary lesions can be seen.

Infections in organs in the portal bed can result in a localized septic thrombophlebitis, which can
lead to liver abscess. Septic emboli are released into the portal circulation, trapped by the hepatic
sinusoids, and become the nidus for microabscess formation. These microabscesses initially are
multiple but usually coalesce into a solitary lesion.

Microabscess formation can also be due to hematogenous dissemination of organisms in

association with systemic bacteremia, such as endocarditis and pyelonephritis. Cases also are
reported in children with underlying defects in immunity, such as chronic granulomatous disease
and leukemia.

Approximately 4% of liver abscesses result from fistula formation between local intra-abdominal
infections.

Despite advances in diagnostic imaging, cryptogenic causes account for a significant proportion of
cases; surgical exploration has impacted this minimally. These lesions usually are solitary in
nature.

Penetrating hepatic trauma can inoculate organisms directly into the liver parenchyma, resulting in
pyogenic liver abscess. Nonpenetrating trauma can also be the precursor to pyogenic liver
abscess by causing localized hepatic necrosis, intrahepatic hemorrhage, and bile leakage. The
resulting tissue environment permits bacterial growth, which may lead to pyogenic liver abscess.
These lesions are typically solitary.

PLA has been reported as a secondary infection of amebic abscess, hydatid cystic cavities, and
metastatic and primary hepatic tumors. It is also a known complication of liver transplantation,
hepatic artery embolization in the treatment of hepatocellular carcinoma, and the ingestion of
foreign bodies, which penetrate the liver parenchyma. Trauma and secondarily infected liver
pathology account for a small percentage of liver abscess cases.

The right hepatic lobe is affected more often than the left hepatic lobe by a factor of 2:1. Bilateral
involvement is seen in 5% of cases. The predilection for the right hepatic lobe can be attributed to
anatomic considerations. The right hepatic lobe receives blood from both the superior mesenteric
and portal veins, whereas the left hepatic lobe receives inferior mesenteric and splenic drainage. It
also contains a denser network of biliary canaliculi and, overall, accounts for more hepatic mass.
Studies have suggested that a streaming effect in the portal circulation is causative.

Etiology
Polymicrobial involvement is common, with Escherichia coli and Klebsiella pneumoniae being
the two most frequently isolated pathogens (see the image below). Reports suggest that K
pneumoniae is an increasingly prominent cause. [3]

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4/14/2018 Liver Abscess: Background, Pathophysiology, Etiology

Table 2: Microbiologic results from 312 cases of liver abscess compiled from the literature.

Enterobacteriaceae are especially prominent when the infection is of biliary origin. Abscesses
involving K pneumoniae have been associated with multiple cases of endophthalmitis.

The pathogenic role of anaerobes was underappreciated until the isolation of anaerobes from 45%
of cases of pyogenic liver abscess was reported in 1974. Since that time, increasing rates of
anaerobic involvement have been reported, likely because of increased awareness and improved
culturing techniques. The most frequently encountered anaerobes are Bacteroides species,
Fusobacterium species, and microaerophilic and anaerobic streptococci. A colonic source is
usually the initial source of infection.

Staphylococcus aureus abscesses usually result from hematogenous spread of organisms

involved with distant infections, such as endocarditis. S milleri is neither anaerobic nor
microaerophilic. It has been associated with both monomicrobial and polymicrobial abscesses in
patients with Crohn disease, as well as with other patients with pyogenic liver abscess.

Amebic liver abscess is most often due to E histolytica. Liver abscess is the most common
extraintestinal manifestation of this infection.

Fungal abscesses primarily are due to Candida albicans and occur in individuals with prolonged
exposure to antimicrobials, hematologic malignancies, solid-organ transplants, and congenital and
acquired immunodeficiency. Cases involving Aspergillus species have been reported.

Other organisms reported in the literature include Actinomyces species, Eikenella corrodens,
Yersinia enterocolitica, Salmonella typhi, and Brucella melitensis.

A small case series in Taiwan investigated pyogenic liver abscess as the initial manifestation of
underlying hepatocellular carcinoma. In regions with a high prevalence of both pyogenic liver
abscess and hepatocellular carcinoma, clinicians should be aware of the possibility of underlying
hepatocellular carcinoma in patients with risk factors for the disease. [4]

Epidemiology
United States statistics
The incidence of pyogenic liver abscess has essentially remained unchanged by both hospital and
autopsy data. Liver abscess was diagnosed in 0.7%, 0.45%, and 0.57% of autopsies during the
periods of 1896-1933, 1934-1958, and 1959-1968, respectively. The frequency in hospitalized

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patients is in the range of 8-16 cases per 100,000 persons. Studies suggest a small, but
significant, increase in the frequency of liver abscess.

Age-related demographics
Prior to the antibiotic era, liver abscess was most common in the fourth and fifth decades of life,
primarily due to complications of appendicitis. With the development of better diagnostic
techniques, early antibiotic administration, and the improved survival of the general population, the
demographic has shifted toward the sixth and seventh decades of life. Frequency curves display a
small peak in the neonatal period followed by a gradual rise beginning at the sixth decade of life.

Cases of liver abscesses in infants have been associated with umbilical vein catheterization and
sepsis.

When abscesses are seen in children and adolescents, underlying immune deficiency, severe
malnutrition, or trauma frequently exists.

Sex-related demographics

While abscesses once showed a predilection for males in earlier decades, no sexual predilection
currently exists. Males have a poorer prognosis from hepatic abscess than females.

Prognosis
Untreated, pyogenic liver abscess remains uniformly fatal. With timely administration of antibiotics
and drainage procedures, mortality currently occurs in 5-30% of cases. The most common causes
of death include sepsis, multiorgan failure, and hepatic failure. [5]

Indicators of a poor prognosis have been described since 1938 and include multiplicity of
abscesses, underlying malignancy, severity of underlying medical conditions, presence of
complications, and delay in diagnosis. [5]

Indicators of a poor prognosis in amebic abscess include a bilirubin level of greater than 3.5 mg/dL,
encephalopathy, hypoalbuminemia (ie, serum albumin level of <2 g/dL), and multiple abscesses; all
are independent factors that predict poor outcome.

An underlying malignant etiology and an Acute Physiology and Chronic Health Evaluation
(APACHE II) score greater than 9 increases the relative mortality by 6.3-fold and 6.8-fold,
respectively.

Chen et al examined prognostic factors for elderly patients with pyogenic liver abscess. [6] Results
from the study, which included 118 patients aged 65 years or older and 221 patients below age 65
years, indicated that age and an APACHE II score of 15 or greater at hospital admission were risk
factors for mortality. The evidence ultimately suggested that outcomes for older patients with
pyogenic liver abscess are on a par with those for younger patients. The investigators also found
that in the younger patient group, there was greater frequency of males suffering from alcoholism,
a cryptogenic abscess, and K pneumoniae infection.

Clinical Presentation

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