Pyogenic Liver Abscess

A pyogenic liver abscess is a polymicrobial infection arising from contiguous or hematogenous spread. Pyogenic liver abscess is the most common type of visceral abscess. Patients may present with a triad of fever, malaise, and RUQ pain. Laboratory analysis can be informative with elevated WBC and abnormal liver function tests, and imaging may reveal solitary or multiple lesions on ultrasound or CT scan. On contrast imaging, the lesions generally appear well defined with rim enhancement. Diagnosis requires aspiration with Gram stain and culture and, in some cases, a drainage catheter may be placed. A combination of drainage and IV antibiotic therapy is the primary method of treatment. Surgical drainage or resection is utilized in specific cases.

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Epidemiology and Etiology

Epidemiology

  • Most common type of visceral abscess
    • 48% of all visceral abscesses
    • 13% of intra-abdominal abscesses
  • Most commonly presents in the 5th decade of life 
  • Incidence: 2 cases per 100,000 people 
  • Incidence of men to women is 3:1

Etiology

Types of liver abscesses:

  • Pyogenic (bacterial):
    • Polymicrobial
    • Most commonly due to mixed enteric facultative and anaerobic organisms
  • Causative organisms:
    • Escherichia coli (E. coli): most common
    • Klebsiella pneumonia (K. pneumonia):
      • Common in Asia
      • Strongly associated with underlying colorectal carcinoma
    • Streptococci: United States
    • Others: Enterococci, Staphylococcus aureus (S. aureus), Proteus vulgaris (P. vulgaris), anaerobes 
  • Parasitic: Echinococcal cyst, Entamoeba histolytica (E. histolytica) (amebic)
  • Fungal: Candida

Risk factors:

  • Immunocompromised state (e.g., CKD, HIV)
  • Hepatobiliary or pancreatic disorder (e.g., cholelithiasis, hepatic tumors)
  • Colorectal carcinoma
  • Crohn’s disease
  • Diabetes mellitus 
  • Liver transplant
  • Regular use of proton pump inhibitor
  • Chronic granulomatous disease (CGD)

Pathophysiology

The right lobe is the most common site of infection because of its larger size and blood supply. Multiple pathways exist to infect the liver with bacteria:

  • Biliary tract disease (most common source):
    • Gallstones
    • Malignant obstruction
    • Strictures
  • Via portal circulation from:
    • Bowel perforation
    • Peritonitis
    • Crohn’s disease
  • Hematogenous seeding from bacteremia: Suspect infectious endocarditis in cases of monomicrobial infection with Streptococci or Staphylococcal species.
  • Direct spread via:
    • Subphrenic abscess
    • Perinephric abscess
    • Pancreatic abscess
  • Trauma:
    • Surgical wounds
    • Penetrating wounds
  • Secondary infection of:
    • Hepatic tumors
    • Amebic liver abscess 
    • Hydatid cyst

Portal circulation is the primary route: seeding of the liver with bacteria, causing a pyogenic liver abscess.

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Clinical Presentation

  • Triad of pyogenic liver abscess:
    • Fever
    • Malaise
    • RUQ pain (50%–75%)
  • Symptoms:
    • Fever (90%), chills 
    • Malaise
    • Anorexia
    • Weight loss
    • Nausea
    • RUQ pain
  • Exam findings:
    • RUQ tenderness
    • Hepatomegaly
    • Jaundice

Diagnosis

Laboratory findings

  • Leukocytosis +/- anemia of chronic disease
  • Liver function:
    • Alkaline phosphatase (ALP)
    • ↑ AST and ALT
    • ↑ Bilirubin
  • Inflammatory markers: ↑ erythrocyte sedimentation rate (ESR) and CRP 
  • Blood cultures positive in 50%:
    • Streptococcal or staphylococcal growth → look for hematogenous source (e.g., infectious endocarditis)
    • Negative growth: Consider atypical organisms.
  • E. histolytica serology or stool testing if no predisposing factors to pyogenic abscess or presence of risk factors for amebic infection

Imaging

  • Abdominal ultrasound:
    • 1st-line modality
    • Solitary or multiple hypoechoic lesions within the liver 
    • Increased blood flow and edematous background due to inflammation
  • Abdominal CT scan with IV contrast:
    • Confirms the findings of abdominal ultrasound
    • Used if high suspicion for a pyogenic liver abscess with a negative ultrasound
    • Well-defined, round/rim-enhanced lesion with central hypoattenuation
  • Percutaneous aspiration or drainage is done under ultrasound or CT guidance for nearly all pyogenic abscesses: 
    • Diagnostic and therapeutic
    • Aspirate sent for:
      • Gram stain and culture (aerobic and anaerobic)
      • Cytology and molecular testing for E. histolytica
  • Findings suggestive of a pyogenic abscess on chest imaging:
    • Elevated right hemidiaphragm
    • Right pleural effusion
    • Right basilar infiltrate

Management

Medical management

 Initial broad-spectrum IV antibiotics

  • Regimen options (include metronidazole until E. histolytica is definitively ruled out):
    • Ceftriaxone and metronidazole
    • Piperacillin-tazobactam and metronidazole
    • Ampicillin, gentamicin, and metronidazole
    • Fluoroquinolone and metronidazole
    • Carbapenem and metronidazole
  • Add vancomycin in cases of septic shock or suspected Staphylococcus infection.

Drainage strategies

  • Drainage:
    • Therapeutic and diagnostic
    • Either percutaneous or surgical 
  • Options for drainage include:
    • Ultrasound-guided aspiration +/- drainage catheter placement
    • CT-guided aspiration +/- drainage catheter placement
    • Drainage with endoscopic retrograde cholangiopancreatography (ERCP):
      • Relatively new technique for drainage
      • Particularly useful for abscesses in proximity to the biliary system
      • Utilizes internal drainage (no external catheter placement)
  • Surgical (open or laparoscopic) drainage:
    • Inadequate response to initial drainage
    • Abscess with viscous contents causing blockage of the drainage catheter
    • Multiple abscesses (consider accessibility for percutaneous drainage)
    • Deep-seated abscess not accessible for percutaneous access

Drainage of unilocular pyogenic abscess:
With abscess ≤ 5 cm, percutaneous drainage is recommended (needle aspiration or catheter placement). Repeated needle aspiration attempts may be necessary. Drainage catheters remain in place until there is minimal drainage. For an abscess > 5 cm, percutaneous aspiration with catheter placement is recommended. Surgical drainage is done when repeated percutaneous drainage fails.

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Complications and Prognosis

Complications

  • Rupture
    • Rare complication leading to:
      • Peritonitis
      • Pleural effusion or empyema
      • Retroperitoneal abscess or intraperitoneal abscess
    • Risk factors for rupture:
      • Abscess > 6 cm
      • Cirrhosis
  • Sepsis
  • Pneumonia due to direct spread to the right lower lobe of the lung

Prognosis

  • Overall mortality ranges from 2%–12% 
  • Uniformly fatal if untreated
  • Risk factors for mortality:
    • Abscess requiring open surgical drainage
    • Underlying malignancy
    • Anaerobic infection
    • Delay in diagnosis

Comparison of Liver Masses

Table: Types of infectious liver abscesses
Amebic liver abscessPyogenic liver abscessEchinococcal cyst
Number Single Single/multiple Single/multiple
Associated symptoms Diarrhea RUQ pain Perianal pruritus
Fever +/- +
Imaging (CT) Solitary lesion in the right lobe of the liver Peripheral rim enhancement is seen with IV contrast administration Peripheral enhancement even without IV contrast administration (due to eggshell calcification) along with internal septations
CBC ↑ Lymphocytes ↑ Neutrophils ↑ Eosinophils
Diagnosis Amebic serology Imaging + aspiration Imaging + serology
Management
  • Metronidazole
  • Drain only in presence of pressure symptoms
IV antibiotics and surgical/percutaneous drainage of the abscess Dependent on classification (surgical resection, albendazole, percutaneous treatment)
Table: Benign liver tumors mimicing liver abscesses
Hepatic hemangiomaFocal nodular hyperplasiaHepatocellular adenoma
Biopsy Cavernous vascular spaces lined by flat endothelial cells Localized hepatocyte nodules with large malformed arterial branches and centralized fibrous tissue Enlarged hepatocytes with small and regular nuclei (no anaplasia); normal hepatic lobular architecture is absent
CT scan findings Well-demarcated, hypodense mass with peripheral enhancement on arterial phase and centripetal filling on delayed phases Central stellate scar  Well-demarcated mass with heterogeneous enhancement on arterial phase and isodense on venous phase (without washout of contrast) 
Table: Liver cysts may mimic liver abscesses
Simple cystPolycystic liver diseaseCholedochal cystCystadenoma/cystadenocarcinoma
DescriptionMost common hepatic cyst, contains clear fluid, lacks communication with the intrahepatic biliary treeSeveral cysts replace large portion of the liverCongenital malformations of the pancreaticobiliary tree, multiple types based on location in biliary system
  • Cystadenoma: rare cystic tumors in the liver parenchyma or the extrahepatic bile ducts
  • Cystadenocarcinoma: an invasive carcinoma
Clinical PresentationUsually asymptomatic
  • Progressive pain
  • 50% associated with polycystic kidney disease
  • Recurrent abdominal pain
  • Intermittent jaundice
  • RUQ mass
  • Cholangitis
  • Pancreatitis
  • Upper abdominal mass
  • Abdominal pain
  • Anorexia
Diagnosis
  • Ultrasound: for diagnosis and follow-up
  • CT: a well-demarcated lesion not enhanced with contrast
Ultrasound: replacement of the liver parenchyma by cysts of varying sizesUltrasound, CT, transhepatic cholangiography, liver function test
  • CT: complex cysts with internal septae, papillary projections, and irregular lining
  • Histology for definite diagnosis
ManagementTreat with excision (only if symptomatic)Partial liver resection or, in rare cases, transplantation (only if symptomatic)
  • Complete excision of cysts
  • Liver transplant if cyst involves intrahepatic bile ducts (Caroli disease)
All complex, multiloculated cysts (except chinococcal) should be excised because of the risk of malignancy.

Differential Diagnosis

  • Hepatocellular carcinoma (HCC): the most common primary liver cancer. Hepatocellular carcinoma typically arises in a chronically diseased or cirrhotic liver. Lesions are often found incidentally on imaging. Constitutional symptoms are rare and RUQ pain does not occur often. Imaging features of pyogenic liver abscesses (peripheral enhancement) help to differentiate it from HCC, which demonstrates arterial enhancement and enhancing capsule/border on delayed phase. An increase in size in < 6 months is also noted. The mainstay of treatment is liver resection.
  • Liver metastasis: Multiple primary cancers can have metastatic spread to the liver, which is most often identified during staging. On contrast CT imaging, lesions present as multiple ring-enhanced lesions of the liver. A history of extrahepatic malignancy makes metastasis a more likely cause of liver lesions. The presence of fever and RUQ tenderness favors the diagnosis of pyogenic liver abscess. Biopsy is necessary to confirm diagnosis and treatment involves management of the primary malignancy.

References

  1. Davis, J., and McDonald, M. (2020). Pyogenic liver abscess. UpToDate. Retrieved March 17, 2021, from, https://www.uptodate.com/contents/pyogenic-liver-abscess
  2. Peralta, R. (2020). Liver abscess. In Geibel, J. (Ed.), Medscape. Retrieved March 17, 2021, from https://emedicine.medscape.com/article/188802-overview#a2
  3. Regey, A. and Reddy, R. (2020). Diagnosis and management of cystic lesions of the liver. UpToDate. Retrieved March 18, 2021, from https://www.uptodate.com/contents/diagnosis-and-management-of-cystic-lesions-of-the-liver
  4. Chopra, S. (2019). Focal nodular hyperplasia. UpToDate. Retrieved March 18, 2021, from https://www.uptodate.com/contents/focal-nodular-hyperplasia
  5. Curry, M. P. and Chopra, S. (2019). Hepatic hemangioma. UpToDate. Retrieved March 18, 2021, https://www.uptodate.com/contents/hepatic-hemangioma
  6. Curry, M. P. and Afdhal, N. H. (2020). Hepatocellular adenoma. UpToDate. Retrieved March 18, 2021, from https://www.uptodate.com/contents/hepatocellular-adenoma
  7. Schwartz, J, M., Carithers Jr, R. L., and Sirlin, C. B. (2019). Clinical features and diagnosis of hepatocellular carcinoma. UpToDate. Retrieved March 18, 2021, from https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-hepatocellular-carcinoma

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