Pyogenic liver abscesses are encountered infrequently in healthy children and generally have been reported more commonly in the compromised pediatric host. The rarity of liver abscesses may be explained partly by the rich blood supply, unique architecture, and extensive reticuloendothelial system of the liver, all of which present an effective barrier against bacterial invasion.
The precise incidence of pyogenic liver abscesses in children is unknown. Adult patients with hepatic abscesses constitute approximately 8 to 20 per 100,000 admissions; a 0.29% to 0.57% incidence of liver abscesses has been found in autopsies of adult patients. In an early large series of liver abscesses in children, Dehner and Kissane reported a 0.38% incidence at autopsy in patients younger than 15 years; 11 of 27 (41%) patients were younger than 2 years, and 18 of 27 (67%) patients were younger than 6 years. In a review of admissions to Milwaukee Children’s Hospital, Chusid found 5 children (four of whom were <6 months old) with at least one hepatic abscess and estimated an incidence of three cases per 100,000 admissions. Pineiro-Carrero and Andres estimated an incidence of approximately 25 cases per 100,000 admissions in their pediatric population (11 patients >14 years old). Pyogenic liver abscess in children is encountered more frequently in developing countries than in developed countries. In Taiwan the overall incidence of pyogenic liver abscesses increased from 11.2 per 100,000 population in 1996 to 17.6 per 100,000 in 2004.
Pathogenesis
Bacteria can establish an inflammatory focus in the liver by four major routes. Direct extension from contiguous structures is the most common mode in adults, accounting for up to 60% of hepatic abscesses in adults. Biliary tract infection (cholangitis, cholecystitis), pancreatitis, and penetrating gastric or duodenal ulcer are examples of diseases associated with liver abscesses caused by extension from a contiguous focus of infection. In a review of this problem at St. Louis Children’s Hospital, three of 27 children (11%) were considered to have a liver abscess secondary to inflammation of contiguous organs. Although biliary tract disease occurs infrequently in children, ascending cholangitis is a particularly frequent complication of the hepatic portoenterostomy procedure for congenital biliary atresia and may lead to infections of the liver in such patients. Liver abscesses also may develop as a complication of liver transplantation, especially if technical problems related to vascular supply or biliary drainage develop.
The portal system is the second most common route by which bacteria may reach the liver in adults; 6% to 27% of liver abscesses in adults derive from this source. In newborns, solitary liver abscesses, especially abscesses caused by gram-negative organisms, have complicated the use of umbilical vein catheterization or have been secondary to omphalitis. Prematurity and necrotizing enterocolitis also are important predisposing conditions.
Portal vein inflammation and bacteremia can be associated with infections within the abdominal cavity. Appendicitis, diverticulitis, perirectal abscesses, regional enteritis, ulcerative colitis, and omphalitis are possible sources of portal vein sepsis. In a large study conducted in Taiwan, patients with inflammatory bowel disease (IBD) had an increased risk of developing a pyogenic liver abscess compared with controls without IBD. A pyogenic liver abscess may be an unusual complication of an ingested foreign body, with subsequent development of portal venous bacteremia. Since antibiotics have been available, portal vein inflammation and pyelophlebitis have become less common sources of hepatic infection in children.
Systemic bacteremia with hematogenous spread of bacteria to the liver through the hepatic artery seems to be the most common source of liver abscess in children, but it is implicated in less than 20% of adult patients. In the St. Louis series, the systemic hematogenous route was responsible for 21 of 27 (78%) cases of liver abscesses. Of 13 patients encountered after 1940, seven had bacteremia associated with leukemia. Anaerobic bacteremia associated with retropharyngeal or peritonsillar abscesses presumably has preceded development of anaerobic liver abscesses in several children. Likewise liver abscesses in neonates may be preceded by a systemic bacteremia without evidence of portal or biliary tract involvement.
Liver abscesses occur more frequently in compromised pediatric hosts, especially those with chronic granulomatous disease, than in healthy children. In a registry of 368 patients with chronic granulomatous disease from the United States, a liver abscess occurred in 27% of patients. Over the course of 10 years, 15 children were diagnosed with pyogenic liver abscess in a large referral center for pediatric liver disease in the United Kingdom. Three children (20%) had chronic granulomatous disease. In addition to functional disorders of phagocytes, chronic neutropenia predisposes to the development of liver abscesses. Wintch and colleagues noted that five of 10 children with hepatic abscesses in their institution had an underlying defect in host defense. Primary hemochromatosis predisposes to multiple liver abscesses caused by Yersinia enterocolitica in particular. Pyogenic liver abscesses also are associated with Papillon-Lefèvre syndrome, a rare autosomal recessive disease characterized by palmoplantar keratoderma and periodontitis.
Penetrating and nonpenetrating trauma to the liver may lead to liver abscesses, presumably caused by bacterial proliferation within small collections of blood and bile that result from the trauma. Hepatic abscess may be a rare complication of ventriculoperitoneal shunts after penetration of a peritoneal catheter into the liver. Liver abscess also is a complication of percutaneous liver biopsy.
Unexplained or cryptogenic hepatic abscesses are encountered in most series and accounted for 40% to 50% of cases in many series. Lee and Block have proposed that these cryptogenic liver abscesses “originate from anaerobic bacterial invasion of hepatic infarcts.” This theory is supported by reports that describe pyogenic liver abscesses as a complication of hepatic infarction in patients with sickle-cell anemia. Normal gastrointestinal bacterial flora were isolated from nine of 11 patients with liver abscesses at the Mayo Clinic. This finding suggested to Lazarchick and associates that unrecognized intraabdominal collections of pus were responsible. Although the reasons are unclear, diabetes mellitus also predisposes to the development of liver abscesses. In a study from Taiwan, three of 15 children with pyogenic liver abscesses seen over a 15-year period had diabetes mellitus as an underlying condition. Nematode infection with larvae migrating through the liver is thought to be another predisposing factor for the development of pyogenic abscesses in children. The larvae induce liver granulomata that trap bacteria, leading to formation of an abscess. In one study from Brazil, positive serology for Toxocara canis was significantly more frequent for patients with pyogenic liver abscess (10 of 16) than for the 32 age-matched controls (four of 32).
Biliary tract disease generally predisposes to the development of multiple liver abscesses. In contrast, blunt trauma to the liver or portal system inflammation most commonly predisposes to a single abscess. In neonates, liver abscesses may be solitary or multiple because of systemic bacteria. Solitary abscesses are the most common findings in the right lobe of the liver.
Hepatic and splenic abscesses caused by Candida spp. are well described in patients with cancer. Multiple abscesses are typical findings. These organs presumably are infected hematogenously, usually when the host is neutropenic.
Microbiology
Gram-negative organisms have been the predominant isolates from liver abscesses in adults. Escherichia coli and Klebsiella, Aerobacter, Pseudomonas, and Proteus spp. have been implicated most frequently. Klebsiella spp. are the most common organism isolated from children with pyogenic liver abscess in Taiwan. Klebsiella spp. also predominated in Taiwan overall and in adult Asian patients in a report from New York. Anaerobic organisms also are important; anaerobic organisms were recovered from 45% of patients with liver abscesses in the University of California–Los Angeles series.
In contrast to the adult experience, Dehner and Kissane reported that 33% of liver abscesses in children were caused by Staphylococcus aureus, whereas gram-negative organisms were found in only 32%. Two or more organisms were recovered from liver abscesses in 52% of children. In a review of 96 children (no neonates) with pyogenic liver abscesses, S. aureus, gram-negative enteric organisms, and anaerobes were the organisms isolated most commonly, in that order. S. aureus is the most common isolate that causes pyogenic liver abscess in patients with chronic granulomatous disease. In neonates, gram-negative enteric organisms are isolated most commonly. Anaerobes, particularly Fusobacterium necrophorum, have been isolated from liver abscesses in children without underlying disease. Fungi, particularly Candida albicans, have been associated with liver abscesses in children with leukemia and neutropenia who have received parenteral hyperalimentation. Liver or splenic abscesses also may be an unusual complication of brucellosis. Human rotavirus–like particles were identified in the material aspirated from a liver abscess, but they were considered a secondary phenomenon and not the primary etiology of the liver abscess.
Clinical Manifestations
The clinical manifestations of pyogenic liver abscesses are nonspecific. A high index of suspicion and an awareness of this illness are necessary to establish the diagnosis. A history of preceding abdominal surgery or trauma is helpful when present, as is the knowledge that the host’s response to infection is compromised.
Fever, nausea, vomiting, anorexia, weakness, and malaise are prominent symptoms that may last several weeks. Abdominal or pleuritic pain, weight loss, and diarrhea are less common manifestations. A history of abdominal pain and fever of unknown origin in an otherwise healthy child suggests the diagnosis of pyogenic liver abscess. In contrast, fever often is not observed in neonates. Patients with a macroscopic or single abscess frequently experience a subacute to chronic course. In contrast, patients with multiple abscesses generally experience a more acute febrile illness.
Hepatomegaly occurs in 40% to 80% of patients; abdominal tenderness occurs less frequently. Right upper quadrant tenderness or even a mass may be subtle and not appreciated unless the physician specifically and carefully examines this region. Other physical findings include jaundice (generally associated with biliary tract disease and not liver abscesses), abdominal distention, and evidence of pleuropulmonary involvement (i.e., elevated or fixed hemidiaphragm, rales, and pleural effusion).
Diagnosis
Routine laboratory studies are of little help in establishing a diagnosis. Anemia, leukocytosis, and an elevation in C-reactive protein are common findings. Liver function tests generally reflect underlying disease of the liver itself and usually are not caused by the abscess. When abscesses occur secondary to biliary tract obstruction, alkaline phosphatase and bilirubin concentrations generally are elevated. Transaminase concentrations usually are normal to mildly elevated in most cases. A rapidly enlarging, tender liver in a patient with normal transaminase concentrations should alert the clinician to the possibility of liver abscess. Lazarchick and colleagues found that the serum albumin concentration was the most important test with regard to prognosis in adults; 14 of 16 patients with a serum albumin level of less than 2 g/dL died.
Blood cultures are positive more commonly in patients with multiple abscesses than in patients with solitary abscesses. Overall, however, blood cultures usually are sterile in children with pyogenic liver abscess.
More than 50% of adult patients have abnormalities on chest radiography. Atelectasis, pulmonary infiltrates, pleural effusion, and elevated or fixed right hemidiaphragm are the most common findings.
Computed tomography (CT) currently provides the most accurate information concerning the size, location, and number of abscesses within the liver parenchyma ( Fig. 49.1 ). Lesions measuring 1 cm in diameter can be detected by CT. Multiple small abscesses may appear in clusters in a pattern suggesting early coalescence of the abscesses. Liver abscesses appear as areas of low attenuation. The target lesions of hepatic candidiasis are not visualized by CT when the patient is neutropenic, and scans may need to be repeated before these characteristic lesions are observed. Structures contiguous with the liver also are shown by CT; this information is important when a surgical approach to drainage is being planned.
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