Hepatic Abscess

Christopher F. Carpenter, M.D., Nick Gilpin, D.O.

PATHOGENS

CLINICAL

  • Risk factors for development of hepatic abscess include:
    • Diabetes
    • Liver cirrhosis
    • Immunocompromised state
    • Male sex
    • Advanced age
    • Proton-pump inhibitor use
  • Signs and symptoms: include fever +/- RUQ pain, tenderness w/ hepatomegaly.
    • Some may only have nonspecific symptoms such as fever (60%) associated with chills and malaise.
    • Presentation may be subacute or chronic including weight loss, anorexia.
    • Occasionally, patients may be acutely ill with mental status changes.
    • Rarely, patients may present with sepsis and peritoneal signs from intraperitoneal rupture of the abscess.
  • Approximately 50% of patients have a solitary hepatic abscess.
    • Majority of abscesses involve in the right hepatic lobe (~75%), less commonly left (20%) or caudate (5%) lobes.
    • Diaphragmatic irritation from abscess might refer pain to the right shoulder or result in cough or pleural rub.
  • Classified by presumed origin:
    • Bacterial:
      • Up to 50% develop from biliary tract (cholangitis).
      • Remainder are from hepatic artery (bacteremia), portal vein (abdominal source, e.g. diverticulitis), contiguous focus (local abscess or cholecystitis) or penetrating trauma.
      • Many are of cryptogenic origin.
    • Parasitic:
      • Entamoeba histolytica: abscess occurs via the portal system during amebic colitis.
        • Typically manifests as a right lobe solitary lesion.
        • Rare in most locales in U.S., occurring almost exclusively in immigrants (especially South and Central America) and travelers so more common in such regions such as southern California, Texas, etc.
        • Men, especially MSM, at higher risk for invasive disease.
      • Echinococcal (hydatid) cysts: most commonly caused by Echinococcus granulosus and usually acquired from canines (sheep dogs).
        • Rarely seen in the U.S.; generally infections diagnosed in immigrants with late presentation or by incidental identification.
        • Usually asymptomatic; when symptoms develop they are due to the size of enlarging cyst or leakage/rupture.
  • Underlying disease typically is the primary determinant of outcome of hepatic abscess.
    • Increased mortality reported in polymicrobial and fungal infections, and in immunocompromised patients.

DIAGNOSIS

  • Labs:
    • For pyogenic liver abscess(es), positive blood cultures seen in up to 50%; alkaline phosphatase and WBC counts frequently elevated.
      • Hyperbilirubinemia with or without jaundice occurs in < 50% of patients.
  • Imaging:
    • Plain abdominal radiography: dx may be suggested on plain films (e.g., gas within the abscess)
    • Preferred: CT, US and MRI are the imaging modalities of choice in suspected liver abscess or FUO.
    • CT or US-guided percutaneous drainage or surgical drainage should be considered in all cases of hepatic abscess for diagnostic confirmation and culture.
      • Multiple, small abscesses may not be amendable to aspiration.
  • Serology:
    • Positive amebic or echinococcal serology helps differentiate parasitic liver abscess from pyogenic, especially in nonendemic areas. Serology cannot distinguish between active and prior infection.
    • Uncomplicated, small abscesses due to Entamoeba histolytica in endemic areas may not require aspiration; consider empirical rx.

TREATMENT

Drainage and General Management

  • Abscess drainage is the optimal therapy for pyogenic liver abscesses.
    • Aspirate should be sent for Gram stain and aerobic/anaerobic culture.
    • Evaluation for fungal and mycobacterial pathogens. E. histolytica should be considered based on epidemiologic factors.
  • CT- or US-guided percutaneous needle aspiration +/- catheter drainage initial method of choice:
    • Success in up to 90% of cases.
    • If drainage inadequate, surgical drainage may be required.
    • Percutaneous aspiration without catheter placement: recently found to have similar success rates as catheter placement.
      • Repeat aspiration required in approximately 50%.
      • Catheter placement should be considered in larger abscesses (>5 cm diameter).
    • Complications of percutaneous drainage include: perforation of adjacent abdominal organs, pneumothorax, hemorrhage and leakage of abscess contents in peritoneum.
  • General recommendations are for at least one week of drainage with CT follow-up.
  • Surgical drainage: may consider as primary treatment in certain settings.
    • Complex or ruptured abscess
    • Multiple abscesses
    • Percutaneously unreachable abscess
    • Larger abscesses (> 5 cm)
    • If associated surgical problem also present (e.g., peritonitis)
    • Drainage may be done laparoscopically
  • Hepatotomy: generally successful approach, but improvements in percutaneous techniques make it secondary management in most cases.
  • Medical management: consider in patients at high risk for drainage procedures or with small/multiple abscesses (< 3-5 cm in diameter) not amenable to drainage.

Antibiotic treatment

  • Empiric coverage should include Enterobacteriaceae, enterococci, anaerobes, and in certain situations staphylococci and streptococci.
    • In a stable patient antibiotics may be deferred until post-aspiration/drainage to increase culture yield.
    • Consider empiric antifungal treatment in immunosuppressed patients at risk for chronic disseminated candidiasis (CDC, a.k.a. hepatosplenic candidiasis, also see C. albicans module).
    • Culture results may help narrow coverage, but for pyogenic abscess do not discontinue anaerobic coverage given difficulty culturing these organisms.
  • Empiric regimens: may narrow based on culture results.
  • Alternatives:
  • Duration: if adequate drainage achieved with resolution of fever and leukocytosis.
    • Often 14-42 days total.
    • Longer courses (up to several months) may be required in the patient who is inadequately drained or treated without drainage.
    • Follow-up imaging studies: consider in patients with suboptimal clinical response.
      • Use CT or ultrasound.
      • Note: imaging findings may lag behind other markers of clinical response.

Amebic hepatic abscess

  • See Entamoeba histolytica module for additional details.
  • Preferred:
    • Metronidazole 750mg PO three times a day x 7-10 days as a tissue agent, followed by a luminal agent to eliminate residual colonic colonization, usually paromomycin 500mg three times a day PO x 7d.
  • Alternatives:
    • Tissue agent: tinidazole 800mg three times a day or 2g +daily x 3-5d.
  • Percutaneous aspiration has no clear role in therapy, but consider for diagnosis if uncertain (serology inconclusive or not available) or no response to appropriate antibacterial therapy.
    • Predictors of need for aspiration: include age> 55 years, abscesses > 5 cms, involvement of both lobes of liver and failure of medical therapy after 7 days.

Hydatid (Echinococcal) cyst

  • Most commonly E. granulosus, see module for additional details.
  • Serology helpful in most cases in non-endemic areas.
  • In patients with rupture of the cyst into the biliary tree, transient but markedly elevated levels of alkaline phosphatase and bilirubin may occur.
    • Hyperamylasemia and eosinophilia occur in up to 60%.
  • Surgical resection standard intervention:
    • Uncomplicated cysts: PAIR (Percutaneous puncture with CT or US guidance, followed by Aspiration, Injection of a protoscolicidal agent such as hypertonic saline or ethanol, and finally Re-aspiration 15 minutes later) is becoming more accepted treatment of choice at some centers due to high success rates with low morbidity.
    • Open or percutaneous (PAIR) procedures should be combined with albendazole treatment.

Selected Drug Comments

Drug

Recommendation

Ampicillin/sulbactam

Good coverage of Gram-positive, Gram-negative, and anaerobic pathogens; lacks Pseudomonas aeruginosa coverage but good Enterococcus species coverage. Rising rates of resistance in E. coli mean that this is no longer a favored empiric choice, but may be quite acceptable once culture results have returned.

Cefepime

Excellent coverage of Gram-negative w/ some Gram-positive pathogens; use in combination with anaerobic agent for empiric therapy.

Imipenem/cilastatin

Excellent broad-spectrum (Gram-positive, Gram-negative, and anaerobe) coverage; would reserve for seriously ill patients. Has better coverage for E. faecalis than meropenem or doripenem; none of the carbapenems cover E. faecium.

Meropenem

Excellent broad spectrum (Gram-positive, Gram-negative, and anaerobe) coverage; would reserve for seriously ill patients. Will cover E. faecalis; none of the carbapenems cover E. faecium.

Ertapenem

Once-daily carbapenem with excellent broad-spectrum coverage except P. aeruginosa, Acinetobacter spp., and enterococci.

Doripenem

Newer carbapenem approved recently for complicated IAIs. Excellent Gram-positive (except E. faecium), Gram-negative and anaerobic coverage.

Moxifloxacin

Excellent broad-spectrum coverage includes some anaerobic activity, many would still use with metronidazole with liver abscess condition due to resistance among B. fragilis.

Piperacillin/tazobactam

Excellent broad spectrum coverage including Gram-positive and Gram-negative coverage (including Pseudomonas aeruginosa and β-lactamase producing pathogens) and anaerobic coverage.

Ticarcillin/clavulanic Acid

Broad spectrum coverage including Gram-positive coverage, Gram-negative coverage (including Pseudomonas aeruginosa [but less active than piperacillin/tazobactam] and B-lactamase producing pathogens) and anaerobic coverage. No longer available in the U.S. marketplace.

Metronidazole

Remains premier anti-anaerobic drug, and preferred for pyogenic abscesses in combination therapy, also treats amebic liver infection.

Tigecycline

Broad spectrum agent related to minocycline, with excellent gram-positive (including MRSA and VRE), Gram-negative (except Pseudomonas aeruginosa and Proteus mirabilis) and anaerobic activity, approved for complicated intraabdominal infections.

FOLLOW-UP

  • If untreated, mortality rate associated with pyogenic hepatic abscess approaches 100%.
  • With treatment, in some series, mortality is below 15%; the latter mortality is dependent upon underlying disease.
  • Recurrence is more frequent after simple percutaneous aspiration without placement of a temporary drain, or in patients in whom drains are removed too early.

OTHER INFORMATION

  • Hepatic abscesses are frequently polymicrobial.
  • Single/multiple lesions occur in approximately a 1:1 ratio, with the majority in the right lobe (especially when solitary); cryptogenic abscesses are generally solitary.
  • Abscesses are frequently associated with chronic medical conditions (e.g., diabetes), hematologic disease (e.g., leukemia), and chronic granulomatous disease (Staphylococcus aureus).
  • Chronic disseminated candidiasis (CDC, a.k.a. hepatosplenic candidiasis) occurs in immunosuppressed patients, e.g. bone marrow transplant recipients.

Pathogen Specific Therapy

Pathogen

First-Line Agent

Second-Line Agent

Anaerobes

Metronidazole

Piperacillin/tazobactam, ticarcillin/clavulanic acid, ampicillin/sulbactam, imipenem/cilistatin, meropenem, doripenem, ertapenem, tigecycline, clindamycin

Enterococci

Penicillin or ampicillin +/- gentamicin

Vancomycin +/- gentamicin, linezolid, daptomycin, tigecycline

Staphylococcus aureus

MSSA:

Nafcillin or oxacillin, cefazolin

MRSA:

Vancomycin

Vancomycin, linezolid, daptomycin, tigecycline

Coagulase negative staphylococci

Vancomycin

Daptomycin, linezolid, tigecycline

Streptococci

Penicillin or ampicillin

First-, second-, or third-generation cephalosporins

Pseudomonas aeruginosa

Piperacillin, cefepime, ceftazidime,

Imipenem, meropenem, doripenem, ciprofloxacin, Piperacillin/tazobactam

Entamoeba histolytica (amebic liver abscess)

Metronidazole followed by paromomycin

Tinidazole (in place of metronidazole) followed by iodoquinol, or diloxanide furoate in place of paromomycin;

Candida albicans or other Candida species

Amphotericin B
Fluconazole

Lipid formulations of amphotericin B, voriconazole, caspofungin, anidulafungin, micafungin

Echinococcus species

Surgical resection or PAIR procedure

Albendazole

Basis for recommendation

  1. Author opinion

    Comment: Recommendations in this module are based on literature given lack of robust RCT data and guideline statements.

References

  1. Mavilia MG, Molina M, Wu GY. The Evolving Nature of Hepatic Abscess: A Review. J Clin Transl Hepatol. 2016;4(2):158-68.  [PMID:27350946]

    Comment: Authors divide hepatic abscesses into three categories: infectious, iatrogenic and those associated with malignancy.

  2. Cai YL, Xiong XZ, Lu J, et al. Percutaneous needle aspiration versus catheter drainage in the management of liver abscess: a systematic review and meta-analysis. HPB (Oxford). 2015;17(3):195-201.  [PMID:25209740]

    Comment: Review of five RCTs suggests catheter drainage preferred over simple aspiration as it is correlated with higher success rates, faster resolution of cavity size.

  3. Siu LK, Yeh KM, Lin JC, et al. Klebsiella pneumoniae liver abscess: a new invasive syndrome. Lancet Infect Dis. 2012;12(11):881-7.  [PMID:23099082]

    Comment:
    Provides an overview of clinical features and management of hepatic abscesses caused by Klebsiella.

  4. Nasseri-Moghaddam S, Abrishami A, Taefi A, et al. Percutaneous needle aspiration, injection, and re-aspiration with or without benzimidazole coverage for uncomplicated hepatic hydatid cysts. Cochrane Database Syst Rev. 2011.  [PMID:21249654]

    Comment: No RCTs identified to support or refute role of PAIR procedure with or without benzimidazole for hydatid cysts.

  5. Reid-Lombardo KM, Khan S, Sclabas G. Hepatic cysts and liver abscess. Surg Clin North Am. 2010;90(4):679-97.  [PMID:20637941]

    Comment: Contains a review of pyogenic (including a breakdown of pyogenic causes and microbiology) and parasitic (including hydatid cyst and amoebic) liver abscesses.

  6. Benedetti NJ, Desser TS, Jeffrey RB. Imaging of hepatic infections. Ultrasound Q. 2008;24(4):267-78.  [PMID:19060716]

    Comment: Review of imaging of hepatic abscesses and other hepatic infections.

  7. Khan R, Hamid S, Abid S, et al. Predictive factors for early aspiration in liver abscess. World J Gastroenterol. 2008;14(13):2089-93.  [PMID:18395912]

    Comment: Predictive factors for early aspiration in liver abscess

  8. Kurland JE, Brann OS. Pyogenic and amebic liver abscesses. Curr Gastroenterol Rep. 2004;6(4):273-9.  [PMID:15245694]

    Comment: Review of the most common infectious causes of abscess disease in the liver.
    Rating: Important

  9. Yu SC, Ho SS, Lau WY, et al. Treatment of pyogenic liver abscess: prospective randomized comparison of catheter drainage and needle aspiration. Hepatology. 2004;39(4):932-8.  [PMID:15057896]

    Comment: Compares catheter drainage versus needle aspiration.

  10. Solomkin JS, Mazuski JE, Baron EJ, et al. Guidelines for the selection of anti-infective agents for complicated intra-abdominal infections. Clin Infect Dis. 2003;37(8):997-1005.  [PMID:14523762]

    Comment: Consensus, evidence-based general guidelines from IDSA, SIS, ASM, and SIDP.

  11. Lambertucci JR, Rayes AA, Serufo JC, et al. Pyogenic abscesses and parasitic diseases. Rev Inst Med Trop Sao Paulo. 2001;43(2):67-74.  [PMID:11340478]

    Comment: Association of underlying parasitic disease and superinfection with bacteria.

  12. Ghosh JK, Goyal SK, Behera MK, et al. Efficacy of aspiration in amebic liver abscess. Trop Gastroenterol. 2015;36(4):251-5.  [PMID:27509703]

    Comment: Study suggests aspiration for large abscesses (>5-10 cm) plus MTZ hastens resolution and appears to be safe to perform.

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Last updated: October 4, 2017