Hepatic Abscess

Scott M. Smith, M.D., Christopher F. Carpenter, M.D.

PATHOGENS

CLINICAL

  • Risk factors for the development of hepatic abscess include:
    • Diabetes
    • Liver cirrhosis
    • Immunocompromised state, including neutropenia
    • 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 weight loss, chills and malaise.
    • The presentation may be subacute or chronic, including weight loss and 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.
      • Subdiaphramatic presentations may misdirect to initial concern for a pulmonary process.
        • Diaphragmatic irritation from an abscess might refer to pain in the right shoulder or result in a cough or pleural rub.
  • Approximately 50% of patients have a solitary hepatic abscess.
    • The majority of abscesses involve the right hepatic lobe (~75%), less commonly left (20%) or caudate (5%) lobes.
  • Classified by presumed etiology:
    • Bacterial:
      • Up to 50% develop from the biliary tract (cholangitis).
      • The remainder is from the 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 the U.S., occurring almost exclusively among immigrants (especially from South and Central America) and travelers.
          • Identified more often in regions such as southern California, Texas, etc.
        • Men, especially MSM, are at higher risk for invasive disease from this parasite.
      • Echinococcal (hydatid) cysts: most commonly caused by Echinococcus granulosus and usually acquired from canines (sheepdogs).
        • Cystic echinococcosis can be seen worldwide, with the highest prevalence found in people with a history of shepherding sheep.
        • Rarely seen in the U.S.
          • Generally, infections are 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.
  • The underlying disease typically is the primary determinant of the outcome of hepatic abscess.
    • Increased mortality was reported in polymicrobial and fungal infections and immunocompromised patients.

DIAGNOSIS

  • Suspect in people with RUQ pain, fever, weight loss and other systemic symptoms.
  • Differential diagnosis:
    • Before imaging: cholecystitis, cholangitis, biliary colic, viral hepatitis, gastritis, bacterial pneumonia, parapneumonic effusion, empyema, lung abscess, pyelonephritis.
    • After imaging: malignancy (including hepatocellular carcinoma), benign cysts
  • Labs:
    • For pyogenic liver abscess(es), positive blood cultures are seen in up to 50%.
      • Alkaline phosphatase and WBC counts are frequently elevated.
      • Hyperbilirubinemia with or without overt 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 a 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 or therapeutic reponse:
    • Positive amebic or echinococcal serology helps differentiate parasitic liver abscess from pyogenic, especially in nonendemic areas; serology cannot distinguish between active and prior infection.
      • Response to metronidzole-containing regimens doesn’t help distinguish amebic from bacterial explanations.
    • Uncomplicated or small abscesses may be due to Entamoeba histolytica in people living in endemic areas or hailing from them.
      • They may not require aspiration; consider empirical treatment.
      • Often responds dramatically within 72h of instituting metronidazole therapy which should alert to the potential diagnosis[15].

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 is inadequate, surgical drainage may be required.
    • Percutaneous aspiration without catheter placement: recently found to have similar success rates as catheter placement
      • Repeat aspiration is 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 there are associated surgical problems also present (e.g., peritonitis)
    • Drainage may be done laparoscopically.
  • Hepatectomy: generally successful approach, but improvements in percutaneous techniques make it secondary management in most cases.
  • Medical management: consider 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 Enterobacterales, 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 abscesses, do not discontinue anaerobic coverage, given the difficulty of culturing these organisms.
  • Empiric regimens: may narrow based on culture results
  • Duration: if adequate drainage achieved with a resolution of fever and leukocytosis
    • Usually 14-42 days total
      • Duration not well determined.
    • 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 the Entamoeba histolytica module for additional details.
  • Requires treatment for both tissue infection and luminal clearance
  • Preferred Regimen:
    • 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.
  • Tissue agents:
  • Luminal agents:
  • Combined Tissue and Luminal Agents:
  • Percutaneous aspiration has no apparent role in therapy but consider for diagnosis if uncertain (serology inconclusive or not available) or no response to appropriate antibacterial treatment.
    • Predictors of need for aspiration if initially targeting only amebic liver abscess include: age> 55 years, abscesses > 5 cm, involvement of both lobes of the liver, and failure of medical therapy after 7 days.

Hydatid (Echinococcal) cyst

  • Most commonly, E. granulosus; see module for additional details.
  • Serology is helpful in most cases in non-endemic areas; sensitivity for liver cysts is 85-98%, and specificity is limited.
  • In patients with a 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 the 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.
  • Preferred Antiparasitic Therapy:
    • Albendazole is 10-15mg/kg/day in two doses with a fat-rich meal
  • Alternative Antiparasitic Therapy:
    • Mebendazole 40-50mg/kg/day in three divided doses with a fat-rich meal
    • Praziquantel 40mg/kg once weekly used in combination with albendazole
  • Duration of Antiparasitic Therapy
    • Limited evidence for the duration of therapy
    • typically 1-3 months, occasionally up to 6 months in duration
  • Follow up:
    • Repeat the US examination every 3-6 months initially, then yearly after stability.
    • Serologic markers are difficult to interpret after treatment and may rise even in the setting of successful 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 favored as an 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 an anaerobic agent for empiric therapy.

Imipenem/cilastatin

Excellent broad-spectrum (Gram-positive, Gram-negative, and anaerobe) coverage; would reserve for seriously ill patients. It 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 for organisms such as MRSA, P. aeruginosa, Acinetobacter spp., and enterococci.

Doripenem

Most recently approved carbapenem 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 metronidazole with liver abscess condition due to resistance amongB. 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

It remains the premier anti-anaerobic drug and is preferred for pyogenic abscesses in combination therapy, it also treats amebic liver infections.

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, the mortality rate associated with pyogenic hepatic abscess approaches 100%.
  • With treatment, in some series, mortality is below 15%; the latter mortality depends on the underlying disease/comorbidities.
  • Recurrence is more frequent after simple percutaneous aspiration without placement of a temporary drain or in patients whose 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

Basis for recommendation

  1. Author opinion

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

References

  1. Sharma S, Ahuja V. Liver Abscess: Complications and Treatment. Clin Liver Dis (Hoboken). 2021;18(3):122-126.  [PMID:34691398]

    Comment: The dosing regimen for nitazoxanide is used as an alternative in some parasitic infections.

  2. Roediger R, Lisker-Melman M. Pyogenic and Amebic Infections of the Liver. Gastroenterol Clin North Am. 2020;49(2):361-377.  [PMID:32389368]

    Comment: The authors give a sound review of the two most common liver abscess presentations in North America. Amebic abscesses respond well to MTZ, and only ~ 15% require percutaneous drainage.

  3. Jun JB. Klebsiella pneumoniae Liver Abscess. Infect Chemother. 2018;50(3):210-218.  [PMID:30270580]

    Comment: First well described in S Korea and Taiwan in the 1980s, there have been noted increasing infection rates with this troublesome organism with hypermucoid properties. It also has a propensity for extra-hepatic manifestations of infection.

  4. Stojković M, Weber TF, Junghanss T. Clinical management of cystic echinococcosis: state of the art and perspectives. Curr Opin Infect Dis. 2018;31(5):383-392.  [PMID:30124496]

    Comment: Complicated entity for clinicians, radiologists and surgeons at centers that rarely encounter this parasite; this helpful review focuses on the confusing staging and mostly expert recommendations that guide selecting a management approach.

  5. 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.

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

  7. 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. They may evolve to include metastatic foci from bacteremias such as as meningitis, endophthalmitis, and necrotizing fasciitis.

  8. Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010;11(1):79-109.  [PMID:20163262]

    Comment: This guideline is slated for an update (as of Nov 2022). Consensus, evidence-based general guidelines from IDSA & SIS. Though hepatic abscesses don’t have an in-depth discussion, the principles of drainage and targeting pathogens from the GI tract are appropriate for pyogenic liver abscesses.

  9. 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.

  10. 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 are described as advanced age, abscess size > 5 cm, both lobes of the liver involvement and duration of symptoms > 7 d.

  11. 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.

  12. 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.

  13. 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: The study suggests aspiration for large abscesses (>5-10 cm), plus MTZ hastens resolution and appears safe to perform.

  14. Thompson JE, Forlenza S, Verma R. Amebic liver abscess: a therapeutic approach. Rev Infect Dis. 1985;7(2):171-9.  [PMID:4001714]

    Comment: An older series highlights that amebic liver abscesses respond well to metronidazole (85% in this report of 48 patients); however, the lack of including this parasite in the differential diagnosis led to unnecessary surgery in some. Response to MTZ can be significant and happen quickly within 72h.

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Last updated: November 9, 2022