Liver abscess

Three types of abscess, differentiated by causative organism:

Pyogenic
Amoebic
Fungal

Pyogenic abscesses

Risk factors
- Diabetes
- Underlying hepatobiliary disease (cirrhosis)
- CKD
- History of malignancy
- Liver transplant
  - Specifically risks are:
    - Hepatic infarction from vascular thrombosis or anastomotic stenosis
    - Ischaemic cholangiopathy
    - Biliary anastomotic stricture
  - Treatment is similar to non-transplant setting
Aetiology
- Cryptogenic process (43%)
  - ?undiagnosed abdominal disease, resolved infectious process, host factors making infection more likely
  - ERCP is only indicated in patients with some sort of finding suggesting a malignancy
  - Need a thorough workup for cause
- Biliary ductal system (ascending cholangitis) - 38% - mostly underlying malignancy, in non-transplant setting
  - Risks - biliary-enteric anastomosis, Caroli disease, biliary ascariasis, any biliary tract surgery
- Seeded through portal blood flow (5%)
  - Diverticulitis, appendicitis, pancreatitis, IBD, PID, perforated viscus, omphalitis, CRC
- Haematogenous spread - hepatic artery (3%)
  - Endocarditis, pneumonia, osteomyelitis
  - More common in immunosuppressed patients
- Injury from trauma or liver-directed therapy (2%)
- Direct extension from adjacent disease (1%)
  - Cholecystitis, subphrenic abscess, perinephric abscess, perforation of bowel directly into liver

Pathophysiology
- Abscess occurs when an inoculum of bacteria exceeds the liver's ability to clear it, resulting in tissue invasion, neutrophil infiltration, and formation of an organised abscess
- Sources described above
  - Biliary - usually occurs as biliary obstruction causing stasis, colonisation, infection, and ascension (ascending suppurative cholangitis). Mostly intra-hepatic stones in Asia and malignancy in Western countries.
  - Ascending PV infection - has become much less frequent after antibiotics
  - Systemic - micro-abscess formation is quite common at autopsy in patients dying of sepsis
  - Trauma - intra-hepatic haematoma or necrosis can become an abscess, can present several weeks post-injury
- 75% of cases involve the right hemi-liver (unknown reason), caudate 5%, left hemi-liver 20%. Bilobar involvement is uncommon.
- Typically 1mm-4cm
- Most commonly gram-negative aerobes, and anaerobes
  - Abscesses from pyelophlebitis or cholangitis are usually poly-microbial, while systemic infections are usually mono-microbial
  - Sterile in 10-20%

Presentation
- Classic presentation is fever, jaundice and RUQ pain (seen in only 10%)
- Malaise, anorexia, nausea
- Jaundice is often due to underlying biliary disease
- Diaphragmatic symptoms - cough, dyspnoea
- ALP mildly elevated in 80%, bilirubin elevated in 20-50%, transaminases mildly elevated in 60%
- Endogenous endophthalmitis - specific to Klebsiella, most common in diabetics

Complications
- Rupture - peritonitis
Imaging
- CXR
  - Elevated right hemidiaphragm
  - Right pleural effusion
  - RLL atelectasis
  - Abnormal extraluminal gas in RUQ
  - PV gas if pylephlebitis is source (GIT -> PV)
- USS
  - Sensitivity 80-95%
  - Not as good for lesions high up in the dome of the liver
- CT
  - Sensitivity 95-100%
  - Gas, rim enhancement
- MRI/MRCP
  - Equally sensitive to CT
Differential diagnosis
- Sub-phrenic or other intra-peritoneal abscess
- Amoebic abscess
  - Sometimes not possible to differentiate - need to aspirate or trial anti-amoebic antibiotics
- Echinococcal cyst/hydatid disease (differentiate on imaging)
Management
- Principles
  - Treat abscess and its primary source
  - Test for amoebic serology if indicated
  - Abx and drainage
- Medical
  - BCs then Abx
  - Base Abx on presumed source
    - Colonic - cef/met
    - Biliary - taz
    - Consider meropenem if recurrent cholangitis
    - Liver transplant - cover fungi
    - Skin or endocarditis - vanc for MRSA
  - Extended duration Abx - up to 6/52, but duration is not well-defined
- Drainage (almost always required)
  - Percutaneous (successful in 66-90% of cases)
    - Send pus for culture, including mycobacterium and fungi if immunosuppressed
    - Success rate seems to be higher with drainage catheter rather than one-off aspiration (100% vs 60%)
    - Contraindications: multiple large abscesses >5cm (however generally still worth trying), intra-abdominal source requiring surgery, ascites, requirement for transpleural drainage, coagulopathy, proximity to vital structures.
  - Surgical
    - Indications: percutaneous contra-indicated, failed non-op therapy, surgery required for something else, abscesses >5cm
    - Remember to send histo looking for entamoeba and cancer
    - Very rarely, partial hepatectomy is required
      - Infected hepatic malignant neoplasm
      - Hepatolithiasis
      - Intra-hepatic biliary stricture
      - Severe destruction from infection
Prognosis
- Mortality now <10%

Amoebic liver abscess (extraintestinal manifestation of Entamoeba histolytica infection)

Epidemiology

55% of those in endemic areas are infected, but <50% of those are symptomatic
Mexico, India, Africa, parts of central and south America

Risk factors

Most common in adult men (20-40), despite more even gender balance for colonic amoebic disease
Migrants from India, Africa, Mexico, Central/South America
- Generally uncommon in short-term travellers
HIV or other immunosuppression

Pathophysiology

Entamoeba histolytica infection - protozoan, existing as a trophozoite or cyst
All other species in the genus Entamoeba are non-pathogenic, and not all strains of histolytica are virulent
Faecal-oral transmission - ingestion of mature cyst, excystation occurs in small bowel which releases trophozoites which migrate to large bowel. These produce cysts, which are passed in faeces.
Asymptomatic carriers - cysts confined to intestinal lumen
Symptomatic - cysts invade through intestinal mucosa
Liver is most common extraintestinal manifestation
- Also brain and lungs
Liver abscesses occur in 1% of patients with amoebiasis (ascends via portal system)
Mostly causes a single focus in right lobe
- Liquefactive necrosis
- Fluid described as 'anchovy sauce' and is odourless unless secondary bacterial infection has occurred
- Progressive hepatic necrosis continues until the Glisson capsule is reached, which is resistant to hydrolysis by the amoebae; therefore the cavity tends to abut the liver capsule when found
- Chronic abscesses can develop a fibrous capsule and even calcify
Patients rapidly develop anti-amoebic antibodies, but this does not appear to halt progression of disease

Presentation

Between months to several years after return from endemic area
Usually 1-2 weeks RUQ pain, high fever.
- Cough, sweating, malaise, weight loss, anorexia, hiccough
Hepatomegaly, point tenderness over liver
Be aware of rupture risk - peritonitis, but can also extend into chest
Can also cause hepatic vein/IVC thrombosis
Leukocytosis without eosinophilia
Elevated ALP +/- other LFTs, hyperbilirubinaemia is unusual
10-20% have diarrhoea

Diagnosis

Definitive diagnosis is with identification of E. histolytica trophozoites in pus or serum antibodies
Aspiration is diagnostic only 10-20% of the time
Abnormalities will be seen on USS or CT or MRI
- CXR - abnormal in 50% - elevated hemidiaphragm, atelectasis, pleural effusion
- USS - round, well-defined hypoechoic mass
- CT - low-density mass with peripheral enhancing rim
- MRI - low T1, high T2
- Will be seen as 'cold' on a liver radionucleotide scan as opposed to a 'hot' pyogenic abscess
- Can take up to 2 years for complete radiologic resolution
- Most commonly posterior right lobe, mostly solitary subcapsular lesions
- If in left lobe, concern for pericardial extension
Commonly also see raised right hemidiaphragm on CXR
Confirm with serological or antigenic testing - can take 7 days to become positive but 99% sensitivity after that
- Currently difficult to differentiate between active acute infection and past infection
Maybe stool microscopy

Differential diagnosis

See pyogenic abscess section for differentiating features
Echinococcal disease - differentiate based on imaging/serology
Malignancy - usually no symptoms from mass

Management

Principles
- Drainage is only necessary if:
  - No clinical response after 5-7 days of Abx
  - Abscess at high risk for rupture (5cm in diameter, or in the left liver)
  - Deterioration - diagnosis confirmation needed
- Drainage is actually rarely required
- If no response to medication, could have bacterial coinfection - usually responds in 3 days
Don't commonly see trophozoites in aspirate but you can do other antigen/PCR testing
Treat with tissue agent (to eliminate liver organisms) + luminal agent (to eliminate intraluminal cysts, even if not seen in the stool)
- Tissue agent - metronidazole 400mg PO TDS 7-10 days
  - Tinidazole also an option
- Luminal - eg paramomycin 25-30 mg/kg per day, in 3 divided doses, for 7 days
- If no improvement, consider aspiration/drainage or extended course
Peritoneal rupture (size of abscess is most important risk factor)
- Percutaneous drainage of collections
- Laparotomy if doubtful diagnosis, hollow viscus perforation, fistulisation resulting in haemorrhage or sepsis, failure of conservative therapy
Pleural rupture
- Thoracentesis
Look for other extraintestinal manifestations
- Pleuropulmonary infection
- Cardiac infection
- Brain abscess
- Cutaneous infection

Follow-up

Should do follow-up imaging to ensure resolution
May take up to 9 months to resolve

Fungal abscesses

Risk factors
- Almost always immunosuppressed patients, typically from chemotherapy
- Solid organ or bone marrow transplant
- Indwelling stents/drains
Causative agents
- Typically Candida (80%)
- Aspergillus
- Cryptococcus
Treatment
- Antimicrobials
  - Step down to oral fluconazole
  - Beware of combined fungal/bacterial abscesses
- Drainage
  - Aspiration
  - Drainage
  - Surgical drainage