1. What is liver abscess?
2. What is pathophysiology?
3. What are the causes of liver abscess?
4. What are complications of liver abscess?

Liver Abscess.
Bacterial abscess of the liver is relatively rare. It has been described since the time of Hippocrates (400 BC), with the first published review by Bright appearing in 1936. In 1938, Ochsner’s classical review heralded surgical drainage as the definitive therapy; however, despite the more aggressive approach to treatment, the rate of mortality has remained at 60-80%.

The development of new radiologic techniques, the improvement in microbiologic identification, and the advancement of drainage techniques have decreased mortality rates to 5-30%; yet, the incidence has remained relatively unchanged. Untreated, this infection remains uniformly fatal.

Pathophysiology.
The liver receives blood from both the 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.

Biliary tract disease remains the most common source of pyogenic liver abscess (PLA) and accounts for 60% of cases. Obstruction of bile flow allows for bacterial proliferation. Through pressurization and distention of canaliculi, portal tributaries and lymphatics are invaded, with subsequent pylephlebitic abscess formation. Cholecystitis, stricture (benign or malignant), malignancy, 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.

The portal venous system can be a source of abscess resulting from infections involving any organ drained by this system. Appendicitis was the leading source of PLA in the preantibiotic era, but it essentially has been eliminated in recent times. The association through which this is thought to occur is pylephlebitis (septic thrombophlebitis) of any tributary of the portal venous system. Infections in organs in the portal bed can result in a localized septic thrombophlebitis. Septic emboli are released into the portal circulation, trapped by the hepatic sinusoids, and become the nidus for microabscess formation. Thus, abscesses initially are multiple but usually coalesce into a solitary lesion. Of liver abscesses, 24% can be attributed to this cause.

Microabscess formation due to hematogenous dissemination of organisms can be seen in association with illness that involves 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. This etiology accounts for 15% of cases.

Contiguous spread from localized infection of the gallbladder and the perihepatic space can result in PLA. Abscesses can result from fistula formation between local intraabdominal infections. Of abscesses, 4% develop in this manner.

Despite advances in diagnostic imaging, cryptogenic causes account for approximately 20% of cases; surgical exploration has impacted this minimally. These lesions usually are solitary in nature.

Penetrating hepatic trauma can inoculate organisms directly into liver parenchyma, resulting in PLA. Nonpenetrating trauma results in localized hepatic necrosis, intrahepatic hemorrhage, and bile leakage due to disruption of canaliculi. The resulting tissue environment permits bacterial growth with resultant PLA. Lesions of this etiology typically are solitary in nature.

PLA has been reported as a secondary infection of amebic abscess, hydatid cystic cavities, and metastatic and primary hepatic tumors. It also has been a 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 less than 5% of liver abscess cases.

The right hepatic lobe is affected more often than the left by a factor of 2:1. Bilateral involvement is seen in 5% of cases. The predilection for the right lobe can be attributed to anatomic considerations. The right hepatic lobe receives blood from both the superior mesenteric and portal veins, whereas the left 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.

Mortality/Morbidity
Untreated, PLA remains uniformly fatal. With timely administration of antibiotics and drainage procedures, mortality currently occurs in 5-30% of cases.

Sex
While abscesses once showed a predilection for males in earlier decades, no sexual predilection currently exists.

Age

• Prior to the antibiotic era, persons in the fourth and fifth decades of life were most commonly afflicted, 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.
• 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 and trauma frequently exist, respectively.

History

• The most frequent symptoms of hepatic abscess include the following:
  • Fever (either continuous or spiking)
  • Chills
  • Malaise
  • Anorexia
  • Weight loss
• Cough or hiccoughs due to diaphragmatic irritation may be reported.
• Referred pain to the right shoulder may be present.
• Individuals with solitary lesions usually have a more insidious course with weight loss and anemia of chronic disease. With such symptoms, malignancy often is the initial consideration.
• Fever of unknown origin (FUO) frequently can be an initial diagnosis in indolent cases. Multiple abscesses usually result in more acute presentations, with symptoms and signs of systemic toxicity.

Physical

• Physical sequelae most commonly seen include fever and tender hepatomegaly, with point tenderness being highly specific.
• A palpable mass need not be present.
• Mid epigastric tenderness, with or without a palpable mass, is suggestive of left lobe involvement.
• Decreased breath sounds in the right basilar lung zones, with signs of atelectasis and effusion on examination or radiologically, may be present.
• A pleural or hepatic friction rub can be associated with diaphragmatic irritation or inflammation of Glisson capsule.
• Jaundice may be present in as many as 25% of cases and usually is associated with biliary tract disease or the presence of multiple abscesses

Causes.
Polymicrobial involvement with aerobes and anaerobes usually is the rule. The most commonly isolated organisms are enteric gram-negative bacilli, Streptococcus milleri, and Bacteroides species.

• Enterobacteriaceae are especially prominent when the infection is of biliary origin. Abscesses involving Klebsiella pneumonia 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 PLA 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 or microaerophilic. It has been associated with both monomicrobial and polymicrobial abscesses in patients with Crohn disease, as well as with other patients with PLA.
• 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.

Lab Studies

• Complete blood count
  • Anemia of chronic disease
  • Neutrophilic leukocytosis
• Liver function studies
  • Hypoalbuminemia and elevation of alkaline phophatase (most common abnormalities)
  • Elevations of transaminase and bilirubin levels (variable)
• Blood cultures are positive in roughly 50% of cases.
• Culture of abscess fluid should be the goal in establishing microbiologic diagnosis.

Imaging Studies

• The advancement in radiologic techniques has been credited with the improvement in mortality rates.
• CT evaluation with contrast and ultrasonography remain the radiologic modalities of choice as both screening procedures also can be used as techniques for guiding percutaneous aspiration and drainage.
• CT scan (sensitivity 95-100%)
  • Lessons on CT evaluation are well-demarcated areas hypodense to the surrounding hepatic parenchyma. Peripheral enhancement is seen when IV contrast is administered.
  • Gas can be seen in as many as 20% of lesions.
  • CT scan is superior in its ability to detect lesions less than 1 cm.
  • This technique also enables the evaluation for an underlying concurrent pathology throughout the abdomen and pelvis. Indium-labeled WBC scans are somewhat more sensitive in this regard.
• Ultrasound (sensitivity 80-90%)
  • Ultrasound evaluation reveals hypoechoic masses with irregularly shaped borders. Internal septations or cavity debris may be detected.
  • Ultrasound allows for close evaluation of the biliary tree and simultaneous aspiration of the cavity.
  • The major benefits of this technique are its portability and diagnostic utility in patients who are too critical to undergo prolonged radiologic evaluation or to be moved out of monitored setting.
  • Operator dependence affects its overall sensitivity.
• Gallium and technetium radionuclide scanning (sensitivity 50-90%)
  • The initial studies are used in diagnosis.
  • These techniques utilize the fact that the radiopharmaceuticals share the same uptake, transport, and excretion pathways as bilirubin and, thus, are effective agents in evaluating liver disease.
  • Sensitivity varies with the radiopharmaceutical utilized, technetium (80%), gallium (50-80%), and indium (90%).
  • Limitations include a delay in diagnosis and the need for confirmatory procedures; thus they offer no benefit over other imaging modalities.
• Chest x-ray findings of basilar atelectasis, right hemidiaphragm elevation, and right pleural effusion are present in approximately 50% of cases; before advancements in radiologic technique, these served as diagnostic clues. Pneumonias or pleural diseases often are initially considered because of the radiographic findings.

Procedures

• Percutaneous needle aspiration
  • Under CT scan or ultrasound guidance, needle aspiration of cavity material can be performed.
  • Enables rapid recovery of material for microbiologic and pathologic evaluation
  • Can be performed with the initial diagnostic procedure
• Percutaneous catheter drainage
  • This was introduced in the 1970s as an alternative to surgery.
  • Overall success rate is reported as being equal or superior to surgical drainage.
  • Advantages include reduced costs, recovery time, and postprocedure recovery rate; it eliminates the need for general anesthesia.
  • Catheter is placed under ultrasound or CT guidance using the Seldinger or trocar techniques.
  • Catheter is flushed daily until output is less than 10 cc/d or cavity collapse is documented by serial CT scanning.
  • Multiple abscesses have been drained successfully by this method.
  • Failure to respond to catheter drainage is the main reported complication, and an indication for surgical intervention.
  • Other complications reported (rarely) are bleeding at catheter site and peritonitis from intraperitoneal spillage of cavity fluid.
  • Contraindications include coagulopathy; a difficult access path to the cavity; and/or a complicated, multiloculated, thick-walled abscess with viscous pus.

Medical Care

• An untreated hepatic abscess is nearly uniformly fatal due to complications that include sepsis, empyema, or peritonitis from rupture into the pleural or peritoneal spaces, and retroperitoneal extension.
• Antibiotic therapy as a sole treatment modality is not routinely advocated, though it has been successful in a few reported cases.
  • It may be the only alternative in patients too ill to undergo invasive procedures or in those with multiple abscesses not amenable to either drainage technique.
  • In these instances, patients are likely to require many months of antimicrobial therapy with serial imaging and close monitoring for associated complications.
• Percutaneous aspiration with antimicrobial therapy
• Percutaneous catheter drainage with antimicrobial therapy

Surgical Care
Surgical drainage was the standard of care until the introduction of percutaneous drainage techniques in the mid-1970s.

• Current indications for surgical treatment of PLA include signs of peritonitis; existence of a known abdominal surgical pathology (such as diverticular abscess); failure of previous drainage attempts; and the presence of a complicated, multiloculated, thick-walled abscess with viscid pus.
• Shock with multi-system organ failure (major), respiratory-renal failure, septic shock, weight loss greater than 10 kg, and an albumin level less than 3 g/dL have been considered major and moderate contraindications to surgery as the initial intervention.
• Surgery can be performed by 2 approaches.
  • A transperitoneal approach allows for abscess drainage and abdominal exploration to identify previously undetected abscesses and the location of an etiologic source.
  • For high posterior lesions, a posterior transpleural approach can be utilized. Although this allows easier access to the abscess, the identification of multiple lesions or a concurrent intraabdominal pathology is lost. Postoperative complications occur in approximately 20-40% of cases and include recurrent PLA, intraabdominal abscess, hepatic or renal failure, and wound infection.

Consultations

• Diagnostic interventional radiology: Obtain a consultation as soon as the diagnosis is considered to allow rapid collection of cavity fluid and the potential for early therapeutic drainage of abscess.
• General surgery
  • Immediately seek a consultation with a general surgeon if a known, underlying, abdominal pathology is the source of the abscess or if complications are present on presentation.
  • In cases undergoing percutaneous drainage, seek the involvement of a general surgery consultation if drainage of the abscess cavity is unsuccessful.
• Gastroenterology involvement may be useful after successful drainage to evaluate for underlying gastrointestinal disease using colonoscopy or endoscopic retrograde cholangiopancreatography (ERCP).
• Infectious disease consultation should be considered in complicated cases and when the involved pathogens are unusual or difficult to treat, such as in fungal abscesses.

Further Inpatient Care

• Aggressively seek an underlying source of the abdominal pathology.
• Perform weekly serial CT scans or ultrasound examinations to document adequate drainage of abscess cavity.
• Maintain drains until the output is less than 10 cc/d.
• Monitor fever curves. Persistent fever after 2 weeks of therapy may indicate the need for more aggressive drainage.

Further Outpatient Care

• Patients may require prolonged parenteral antimicrobial therapy after discharge. Monitoring of medication levels, renal function, and blood counts may be needed.
• Drain care may be required.
• Continue radiologic evaluation to document progress of therapy after discharge.

Complications.

• Sepsis
• Empyema resulting from contiguous spread or intrapleural rupture of abscess
• Rupture of abscess with resulting peritonitis
• Endophthalmitis when an abscess is associated with Klebsiella pneumonia bacteremia

Prognosis

• If a liver abscess is left untreated, the prognosis is uniformly fatal.
• Indicators of a poor prognosis have been described since 1938 and include multiplicity of lesions, severity of underlying medical conditions, presence of complications, and the delay in diagnosis.
• More recently, laboratory indicators of a poor prognosis have been described and include hemoglobin less than 11 mg/dL (RR = 5.6), bilirubin greater than 1.5 mg/dL (RR = 5.6), WBC greater than 15 (RR = 3.4), albumin less than 2.5 g/dL, and an elevated partial thromboplastin time.
• 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.
• The clinical finding of jaundice has been cited as a marker for a complicated treatment course and is likely to be a marker of multiple abscesses, hyperbilirubinemia, and a serious underlying pathology.

Medical/Legal Pitfalls

• Although specific medicolegal issues may not exist, morbidity or mortality related to undiagnosed or misdiagnosed infection possibly could result in legal action.