LIVER ABSCESS ( Part One)

Liver Abscess
The two major types of liver abscesses are pyogenic, defined as those caused by bacteria, and amebic, defined as those caused by Entamoeba histolytica.

• Pyogenic hepatic abscesses have predominated in reports from medical centers in the more temperate climates.
• In comparison, amebic abscesses have been reported with moderate frequency from centers in the southern United States as well as in semitropical and tropical climates.
• In 1938, Ochsner and associates reported that amebic liver abscesses were almost three times as common as pyogenic hepatic abscesses among patients treated at the Charity Hospital in New Orleans.
• More recently, reports from centers in the southern portions of the United States have documented either an equal distribution or a slight preponderance of pyogenic hepatic abscesses.
• This trend is most likely the result of improvements in sanitation, which have essentially eliminated amebiasis in persons native to the United States.

However, workers in medical centers in the United States that treat larger populations of patients who have recently immigrated from countries where amebiasis is endemic have noted an increased incidence of amebic hepatic abscess.

Within the last decade, however, fungal and tuberculous abscesses have been observed more commonly in immunocompromised patients with cancer or acquired immunodeficiency syndrome (AIDS).
PYOGENIC LIVER ABSCESS

• Although ancient Greek physicians were aware of pyogenic hepatic abscess, the first description in modern times has been credited to Bright in 1835.
• One hundred-two years later, Ochsner and co-workers published their classic review documenting appendicitis as the etiologic entity in more than one third of these cases.
• Since the introduction of antibiotics, pyogenic hepatic abscess secondary to appendicitis-induced pylephlebitis has become rare.
• Patients with pyogenic liver abscess are now more likely to be older, to be female, and to have a biliary cause and an underlying malignant disease.
  

Incidence
A more recent publication from that same institution comparing a pair of 21-year time periods suggests that the incidence of pyogenic hepatic abscesses has increased significantly to 20 per 100,000 admissions.

Age, Sex, and Race

• Several series documented a preponderance of pyogenic abscess among elderly patients.
• The trend toward the development of pyogenic hepatic abscess in older patients most likely reflects both an older general population and a significant shift in etiologic factors.
• A male-to-female ratio of 1.8:1 among previously reported patients was calculated in 1972 by Barbour and Juniper.
• This tabulation included a 2.1:1 ratio among 877 cases collected in 1938 by Ochsner and co-workers.
• However, the striking male preponderance seen in earlier series was not present in more recent studies.
• One possible explanation for the increase in the percentage of women with pyogenic abscesses may be a shift in etiologic factors.

Etiology and Pathogenesis

• Most pyogenic liver abscesses are caused by infection in the biliary or intestinal tracts.
• As a result, the causes of liver abscesses have been divided into six categories, based on the route of extension of infection:
• (1) biliary, from ascending cholangitis;
• (2) portal vein, as in pylephlebitis resulting from appendicitis or diverticulitis;
• (3) hepatic artery, from septicemia;
• (4) direct extension, from a contiguous disease process;
• (5) traumatic, from blunt or penetrating injuries; and
• (6) cryptogenic, when no primary source of infection is found even after abdominal exploration of autopsy.

Most authors have adhered to this classification, which excludes patients in whom multiple hepatic and splenic abscesses are the result of massive sepsis, usually secondary to bacterial endocarditis.

Changing Trends

• Before the introduction of antibiotics, appendicitis and other intra-abdominal infections resulting in pylephlebitis were the leading causes of pyogenic hepatic abscess.
• In a collected series of 622 patients published by Ochsner and associates in 1938, the route of infection was through the portal vein in 43% and through the biliary tree in only 14% of their patients.
• Appendicitis was the leading cause and accounted for 34% of all pyogenic liver abscesses. This figure is in marked contrast to the 0 to 2% incidence of appendicitis as an etiologic factor in more recent large series.
• This change may be caused, at least in part, by the introduction of antibiotics.
• In the 1975 report by Pitt and Zuidema from the Johns Hopkins Hospital, 51% of the patients had a hepatobiliary or pancreatic neoplasm (23%) or a benign biliary tract condition (28%). When this series was updated by Huang et al. in 1996, 60% of patients had an associated hepatobiliary or pancreatic disease.
• However, in the more recent series from Johns Hopkins, the underlying problem was a malignant disease in 42% of the patients (P < .05). Similar trends have been reported by Branum and associates at Duke University in North Carolina.

Analysis of abscesses with a portal cause reveals that several other intra-abdominal disease processes have replaced appendicitis as the leading cause in this category.

• At present, the frequent sources of portal vein sepsis resulting in liver abscess include diverticulitis, perforated ulcers, and perforated carcinomas.

The relative incidence of pyogenic hepatic abscesses resulting from systemic bacteremia, direct extension, and trauma have remained relatively constant since 1950.

In more recent years, the incidence of liver abscesses after hepatic artery embolization has increased.
Although a wide variation exists in individual reports, the incidence of cryptogenic abscesses in large collected series has remained relatively constant, at approximately 15 to 20%.

• The pathogenesis of cryptogenic abscesses is still uncertain, although several theories have been proposed. In 1972, Lee and Block noted an increased incidence of anaerobic infections in their patients.
• They suggested that cryptogenic abscesses may develop from small areas of intrahepatic thromboembolism or infarction that become infected secondarily by anaerobic organisms present in portal blood.
• Pitt and Zuidema also noted anaerobic or sterile cultures in 9 of 16 patients with cryptogenic abscesses.
• Most likely, the pathogenesis of cryptogenic abscesses is multifactorial.

Predisposing Factors

• Pyogenic hepatic abscess is an unusual occurrence in infants and children.
• In 1978, Chusid emphasized that children with abnormalities of host defense mechanisms are most likely to develop a pyogenic liver abscess.
• The most common clinical setting is one of sepsis, usually with a gram-positive organism, in a child with acute leukemia or a chronic granulomatous disease.

Pyogenic hepatic abscesses are distinctly uncommon in older children and young adults.

• In this age group, liver abscesses are seen most often after liver trauma.

In middle-aged and elderly adults, factors predisposing to diminished resistance to bacterial infection are important.

• Several reports published since 1975 noted that many patients with pyogenic hepatic abscesses have an associated malignant disease.
• In 1975, Pitt and Zuidema noted associated malignant diseases in 28% of their patients. Malignant extrahepatic biliary obstruction was found in 22% of the patients.
• Jaundice resulting from benign extrahepatic obstruction has been shown to alter immune response, and, therefore, it may be a contributing factor in some patients.
• Underlying diabetes mellitus and cirrhosis, pancreatitis, or prior ulcer surgery were noted as predisposing factors by Pitt and Zuidema.
• These authors additionally reported that 6% of their patients were receiving steroids, and 5% had pyelonephritis.
• Despite frequent steroid dependence and a high incidence of intra-abdominal infection, patients with inflammatory bowel disease do not seem to be particularly likely to develop liver abscesses.
• More aggressive treatment of hepatobiliary malignant diseases has led to more liver abscesses.
• Patients with long-term indwelling stents for management of cholangiocarcinoma are at particularly high risk.
• In addition, patients undergoing hepatic artery chemoembolization for hepatocellular carcinoma are also likely to form abscesses as the tumor and surrounding liver become ischemic.
• Patients with hematologic malignant neoplasms who undergo aggressive chemotherapeutic regimens are also at high risk for developing liver abscesses.
• Another group of patients at increased risk comprises those with benign bile duct strictures secondary to chronic pancreatitis.
• In these patients, long-standing alcoholism may contribute to poor nutrition and decreased host resistance.
• Similarly, patients with AIDS are prone to liver abscesses as well as other rare infections.
  

Location and Number of Abscesses

• In most reviews, more than 60% of pyogenic hepatic abscesses are in the right lobe, whereas 20 to 25% are bilateral, and fewer than 15% are confined to the left lobe.
• This propensity for hepatic abscesses to develop in the right lobe has been attributed to a streaming effect of mesenteric blood flow within the portal vein.
• This explanation does not apply, however, to abscesses of biliary origin, which are multiple and involve both lobes in 90% of cases.
• Likewise, abscesses resulting from septicemia tend to be multiple and to involve the entire liver.

The mortality correlates closely with the number of abscesses.

• In three reports published since 1980, mortality was 36% for patients with multiple abscesses and 17% for those with a solitary abscess.
• Nevertheless, mortality remains high and may be explained, at least in part, by the relative increase in the number of abscesses of biliary origin, 90% of which are multiple.

Bacteriology
In the preantibiotic era, gram-positive aerobes were the organisms most often isolated from pyogenic liver abscesses.

• In the last 4 decades, however, gram-negative aerobes have been cultured most frequently.
• Only since the 1970s have reports documented an increased incidence of anaerobic hepatic abscesses.
• Possible explanations for these trends include the introduction of antibiotics in the 1940s and the change in etiologic factors that has occurred since 1950.
• In a report from the Johns Hopkins Hospital, the incidence of streptococci, Pseudomonas, and fungal species increased, whereas Escherichia coli decreased .
• These changes probably result from the increased use of broad-spectrum antibiotics and endoscopic cholangiography.
• Several authors noted that pyogenic liver abscesses from which anaerobic bacteria are isolated are more likely to be solitary.
• Anaerobic abscesses, therefore, have been associated with a lower mortality.
• Furthermore, an association between anaerobes and liver metastases was made by Trump and associates.
• These authors suggested that liver metastases, with their reduced oxidation-reduction potential, provide an excellent setting for anaerobic bacteria.
• They also conjectured that colonization by anaerobic organisms may explain the fever present in patients with hepatic metastases.

Symptoms and Physical Findings

• Most patients with pyogenic hepatic abscesses present with symptoms of less than 2 weeks' duration.
• The most common presenting symptom is fever, which is noted in approximately 90% of patients.
• Pain is the next most common symptom.
• Chills and weight loss occur in approximately one half of the patients.
• On physical examination, a tender liver and jaundice are noted in about one half of the patients.

• The most common physical sign is an enlarged tender liver, which is found in 55% of patients with pyogenic hepatic abscess.
• Jaundice is also found on physical examination in approximately one half of the patients.
• Chest symptoms and physical findings are found in approximately one fourth of the patients.
• Abdominal examination reveals a palpable mass or ascites in about 25% of patients, whereas splenomegaly is detected in only 10%.

Diagnosis
The persistently high mortality associated with pyogenic hepatic abscesses attests to the difficulty in establishing a diagnosis on clinical grounds alone.

To establish a diagnosis of pyogenic hepatic abscess, the physician must have a high index of suspicion and must rely frequently on newer diagnostic modalities.

Laboratory Data

• Most patients with this condition have some liver function test abnormalities.
• Patients with a solitary abscess and those with indwelling biliary stents may be more likely to have normal laboratory data.
• Most patients also have leukocytosis, anemia, and hypoalbuminemia, but these abnormalities are not specific for liver abscesses.

Roentgenographic Findings

• Before the development of ultrasound and CT in the mid 1970s, chest and plain abdominal radiographs were obtained in the majority of patients.
• The most common findings are elevation of the right hemidiaphragm, right lower lobe atelectasis or infiltrate, and right pleural effusion.
• Abnormalities on plain abdominal radiographs, such as gas within the abscess (20%) or hepatomegaly (25 to 30%), are noted in slightly less than one half of the patients.
• Contrast studies of the stomach, colon, or urinary tract occasionally demonstrate displacement of organs adjacent to the liver or give a clue to the source of infection.

Cholangiography

• With the increased incidence of biliary causes of pyogenic liver abscess, cholangiography has become more important in the diagnosis of many of these patients.
• Either ERC or PTC were helpful in defining biliary anatomy as well as in outlining the abscess cavities in approximately two thirds of the studies.
• Both ERC and PTC increase intrabiliary pressure and therefore may exacerbate the septic process.
• However, placement of an endoscopic endoprosthesis or of a transhepatic biliary drainage tube decompresses the biliary tree after the procedure.
• In selected patients with biliary communication of the abscess, decompression of the biliary tree in combination with systemic antibiotics may be adequate treatment without additional abscess drainage.

Liver Scanning (Nuclear Medicine)
One of the first steps toward eliminating delay in diagnosis of patients with pyogenic hepatic abscess was the clinical introduction of hepatic scanning techniques in the 1960s.

• The decreased accuracy of liver scanning in patients with multiple abscesses is explained by the finding that abscesses smaller than 2 cm are not detected by this technique.
• Differentiation between abscess and tumor, however, is frequently not possible with either technetium sulfur colloid (99mTc) or gallium citrate (67Ga) scans.
• Furthermore, the role of liver scanning in patients with hepatic abscesses changed with the introduction of ultrasound and CT.

Ultrasound

• With improvements in ultrasound technology, delineation of liver lesions as small as 1 to 2 cm is possible.
• Reports by Balasegaram and by Verlenden and Frey found that ultrasound examination provided a correct diagnosis of pyogenic hepatic abscess in 37 of 38 patients studied.
• The one false-positive result in these two series was in a patient with a cavitated hepatocellular carcinoma that mimicked an abscess.
• Barreda and Ros considered ultrasound to be the modality of choice in studying the internal nature of hepatic abscesses.
• However, these authors pointed out potential drawbacks of ultrasound.
• First, ultrasound cannot always visualize the liver dome and may miss lesions in this area.
• Second, multiple microscopic abscesses, such as those generally found with ascending cholangitis, may not be appreciated by ultrasound.
• Third, fatty infiltration may produce a markedly echogenic liver, with resulting failure to detect a small abscess.
• Nevertheless, ultrasound is safe and may be helpful in differentiating tumors from abscesses.
• In addition, ultrasound can be used for guidance when diagnostic aspiration is indicated.

Computed Tomography

• CT has an advantage over both liver scanning and ultrasound in its ability to detect intrahepatic lesions as small as 0.5 cm.
• The entire liver is easily visualized with CT, and fatty infiltration does not represent a problem.
• Hepatic abscesses are demonstrated by CT as well-demarcated lesions with a low density compared with that of normal liver parenchyma.
• These authors found that 3 of 46 cases suspected of being neoplasms were, in fact, abscesses.
• In addition, of 10 suspected abscesses, 1 was found to be a cyst and another was an empyema.
• Despite some difficulty in differentiation of the exact type of liver lesion, CT currently provides the best resolution for detection of small and multiple abscesses.
• This advantage probably outweighs the additional cost of this procedure and currently makes CT the diagnostic procedure of choice in patients suspected of having multiple small liver abscesses.

Magnetic Resonance Imaging
MRI has emerged as an important tool for hepatic imaging.

• Hepatic imaging with MRI has improved greatly.
• The combination of findings on T1- and T2-weighted images as well as well as gadolinium-enhanced gradientecho images may be diagnostic for pyogenic hepatic abscesses.
• In addition, results of an animal study by Stark and colleagues suggested that microabscesses as small as 3 mm can be visualized by MRI.
• However, the lack of easy acess for drainage limits the usefulness of MRI in managing patients with liver abscesses.

Angiography
Various forms of angiography, including selective hepatic arteriography, splenography, inferior venacavography, and transumbilical hepatography, have been used in the diagnosis of liver abscesses. These techniques were used generally before the introduction of ultrasound, CT, and MRI, when liver scans were unable to differentiate hepatic abscesses from neoplasms.

Complications
In the preantibiotic era, Ochsner and associates reported complications in 31% of 453 collected cases.

• The most commonly reported categories of complication after pyogenic hepatic abscesses include pulmonary and pleural complications, septicemia, and subphrenic abscesses.
• Pleuropulmonary complications, including pneumonitis, pleural effusions, empyema, lung abscess, and bronchopleural fistula, were the most common complications reported in 1938 by Ochsner and co-workers.
• Pitt and Zuidema, however, noted bacteremia to be the most common complication.
• These later authors noted a significantly higher mortality (86%) among their patients who had bacteremia, and all 14 of their patients with polymicrobial bacteremia died.
• In this analysis, pleuropulmonary complications, which occurred in 31% of patients, were not associated with an increase in mortality.
• Balasegaram noted that subphrenic or subhepatic abscesses were the most common complication, occurring in 11% of his patients.
• Rupture of an intrahepatic pyogenic abscess into the peritoneal cavity or into the pericardium occurs rarely, but it is usually fatal. Multiple organ failure with involvement of the liver, kidneys, heart, lungs, and gastric mucosa frequently occurs before death in these patients, all of whom have an underlying septic process within the liver.