Hepatic Abscess
PATHOGENS
- Gram-positive cocci: Streptococcus species (especially S. intermedius group), enterococci, and Staphylococcus aureus.
- Anaerobes: Bacteroides species, Fusobacterium sp, Actinomyces sp, Clostridium sp, etc.
- Enterobacteriaceae (E. coli, Klebsiella spp., etc) and other Gram-negative bacilli.
- Yersinia enterocolitica: rare cause of liver abscess; if identified, consider underlying hemochromatosis.
- Candida species
- Entamoeba histolytica: amebic liver abscesses may complicate up to 10% of the cases of amebic colitis.
- Echinococcus granulosus: most common cause of hydatid cysts.
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.
- Entamoeba histolytica: abscess occurs via the portal system during amebic colitis.
- Bacterial:
- 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.
- For pyogenic liver abscess(es), positive blood cultures seen in up to 50%; alkaline phosphatase and WBC counts frequently elevated.
- 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.
- Traditional: ampicillin 2.0g IV q6h plus gentamicin 1.7mg/kg IV q8h plus metronidazole 0.5g IV q8h
- First line:
- Cefotaxime 2.0g IV q8h or ceftriaxone 2.0g IV q24h plus metronidazole 0.5g IV q8h
- Piperacillin/tazobactam 3.375g IV q 6h
- Consider adding metronidazole if amebic liver abscess a possibility.
- Alternatives:
- Carbapenems: appropriate for monotherapy, especially if the patient is at high risk for resistant GNRs or has a documented multidrug-resistant organism.
- Fluoroquinolones: often used as an oral regimen for prolonged therapy after completion of initial parenteral therapy course.
- 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.
- Luminal agents:
- Iodoquinol 650mg three times a day x 20d
- Diloxanide furoate 500mg three times a day x 10d
- 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 |
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. | |
Excellent coverage of Gram-negative w/ some Gram-positive pathogens; use in combination with anaerobic agent for empiric therapy. | |
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. | |
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. | |
Once-daily carbapenem with excellent broad-spectrum coverage except P. aeruginosa, Acinetobacter spp., and enterococci. | |
Newer carbapenem approved recently for complicated IAIs. Excellent Gram-positive (except E. faecium), Gram-negative and anaerobic coverage. | |
Excellent broad-spectrum coverage includes some anaerobic activity, many would still use with metronidazole with liver abscess condition due to resistance among B. fragilis. | |
Excellent broad spectrum coverage including Gram-positive and Gram-negative coverage (including Pseudomonas aeruginosa and β-lactamase producing pathogens) and anaerobic coverage. | |
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. | |
Remains premier anti-anaerobic drug, and preferred for pyogenic abscesses in combination therapy, also treats amebic liver infection. | |
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 | Piperacillin/tazobactam, ticarcillin/clavulanic acid, ampicillin/sulbactam, imipenem/cilistatin, meropenem, doripenem, ertapenem, tigecycline, clindamycin | |
Penicillin or ampicillin +/- gentamicin | Vancomycin +/- gentamicin, linezolid, daptomycin, tigecycline | |
MSSA: Nafcillin or oxacillin, cefazolin MRSA: Vancomycin | ||
First-, second-, or third-generation cephalosporins | ||
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 | Lipid formulations of amphotericin B, voriconazole, caspofungin, anidulafungin, micafungin | |
Surgical resection or PAIR procedure |
Basis for recommendation
- Author opinion
Comment: Recommendations in this module are based on literature given lack of robust RCT data and guideline statements.
References
- Mavilia, Marianna G., et al. "The Evolving Nature of Hepatic Abscess: a Review." Journal of Clinical and Translational Hepatology, vol. 4, no. 2, 2016, pp. 158-68. [PMID:27350946]
Comment: Authors divide hepatic abscesses into three categories: infectious, iatrogenic and those associated with malignancy.
- Cai, Yu-Long, et al. "Percutaneous Needle Aspiration Versus Catheter Drainage in the Management of Liver Abscess: a Systematic Review and Meta-analysis." HPB : the Official Journal of the International Hepato Pancreato Biliary Association, vol. 17, no. 3, 2015, pp. 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.
- Chang, Feng-Yee, et al. "Klebsiella Pneumoniae Liver Abscess: a New Invasive Syndrome." The Lancet Infectious Diseases, vol. 12, no. 11, 2012, pp. 881-7. [PMID:23099082]
Comment:
Provides an overview of clinical features and management of hepatic abscesses caused by Klebsiella. - Abrishami, Amir, et al. "Percutaneous Needle Aspiration, Injection, and Re-aspiration With or Without Benzimidazole Coverage for Uncomplicated Hepatic Hydatid Cysts." Cochrane Database of Systematic Reviews (Online), 2011, p. CD003623. [PMID:21249654]
Comment: No RCTs identified to support or refute role of PAIR procedure with or without benzimidazole for hydatid cysts.
- Khan, Saboor, et al. "Hepatic Cysts and Liver Abscess." The Surgical Clinics of North America, vol. 90, no. 4, 2010, pp. 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.
- Benedetti, Nancy J., et al. "Imaging of Hepatic Infections." Ultrasound Quarterly, vol. 24, no. 4, 2008, pp. 267-78. [PMID:19060716]
Comment: Review of imaging of hepatic abscesses and other hepatic infections.
- Abbas, Zaigham, et al. "Predictive Factors for Early Aspiration in Liver Abscess." World Journal of Gastroenterology : WJG, vol. 14, no. 13, 2008, pp. 2089-93. [PMID:18395912]
Comment: Predictive factors for early aspiration in liver abscess
- Brann, Oscar S., and Jayde E. Kurland. "Pyogenic and Amebic Liver Abscesses." Current Gastroenterology Reports, vol. 6, no. 4, 2004, pp. 273-9. [PMID:15245694]
Comment: Review of the most common infectious causes of abscess disease in the liver.
Rating: Important - Ho, Simon S M., et al. "Treatment of Pyogenic Liver Abscess: Prospective Randomized Comparison of Catheter Drainage and Needle Aspiration." Hepatology (Baltimore, Md.), vol. 39, no. 4, 2004, pp. 932-8. [PMID:15057896]
Comment: Compares catheter drainage versus needle aspiration.
- Infectious Diseases Society of America, et al. "Guidelines for the Selection of Anti-infective Agents for Complicated Intra-abdominal Infections." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 37, no. 8, 2003, pp. 997-1005. [PMID:14523762]
Comment: Consensus, evidence-based general guidelines from IDSA, SIS, ASM, and SIDP.
- Lambertucci, J R., et al. "Pyogenic Abscesses and Parasitic Diseases." Revista Do Instituto De Medicina Tropical De São Paulo, vol. 43, no. 2, 2001 Mar-Apr, pp. 67-74. [PMID:11340478]
Comment: Association of underlying parasitic disease and superinfection with bacteria.
- Behera, Manas Kumar, et al. "Efficacy of Aspiration in Amebic Liver Abscess." Tropical Gastroenterology : Official Journal of the Digestive Diseases Foundation, vol. 36, no. 4, 2015 Oct-Dec, pp. 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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