Hepatic Candidiasis

Hepatic candidiasis (hepatosplenic candidiasis) is invasive Candida infection that forms multiple small abscesses in the liver and spleen. It occurs mainly in patients with acute leukaemia after neutropenia, and presents as fever that persists after neutrophil recovery.

It occurs in 3% to 7% of patients treated for acute leukaemia, and in stem cell transplant recipients. Candida albicans and Candida tropicalis are the commonest species. Mortality is under 20% with prompt therapy, but is higher with delay.

Pathophysiology.

Candida crosses the damaged gut mucosa during chemotherapy related neutropenia, reaches the liver and spleen by the portal vein, and forms microabscesses. Inflammatory reaction (including immune reconstitution) becomes apparent when neutrophils recover.

Chronic course extends over months.

Persistent fever after neutrophil recovery, right upper quadrant pain, nausea, hepatomegaly, splenomegaly and raised alkaline phosphatase. Blood cultures are often negative.

Red flags.

• Septic shock.
• Progressive liver dysfunction.
• Rupture or bleeding from splenic lesions.

Contrast CT, magnetic resonance imaging or ultrasound shows multiple small (under 2 cm) hypodense or hypoechoic lesions, with target or wheel-within-wheel patterns. Liver biopsy with histology, fungal culture and PCR confirms the diagnosis. Serum beta-D-glucan and galactomannan help, but blood cultures are often negative. Exclude bacterial abscess, other fungi and tuberculosis.

Differential diagnosis.

• Pyogenic liver abscesses.
• Hepatic tuberculosis.
• Aspergillosis and other invasive fungal infection.
• Lymphomatous or leukaemic infiltration.
• Metastases.
• Cat scratch disease and other microabscesses.

Start with an echinocandin or liposomal amphotericin B, then step down to fluconazole for a long course until lesions resolve or calcify (months). Continue antifungal treatment through further chemotherapy or transplant. Corticosteroids are added for refractory fever from inflammatory reaction.

• Liposomal amphotericin B: 3 mg/kg IV once daily for 1 to 2 weeks; maximum 5 mg/kg daily; monitor creatinine, potassium, magnesium and infusion reactions; adjust the dose for renal impairment by extending the interval, and replace potassium and magnesium.
• Caspofungin: 70 mg IV loading dose, then 50 mg IV once daily for 1 to 2 weeks; maximum 70 mg daily (100 mg with weight over 80 kg); monitor liver tests; reduce to 35 mg daily in moderate hepatic impairment (Child-Pugh B).
• Micafungin (alternative echinocandin): 100 mg IV once daily for 1 to 2 weeks; maximum 150 mg daily; monitor liver tests; no adjustment in renal impairment.
• Fluconazole (step down): 400 mg (6 mg/kg) orally or IV once daily until lesions resolve or calcify, usually for 3 to 6 months or longer; maximum 800 mg daily; monitor liver tests, QT interval and interactions; halve the dose when creatinine clearance is under 50 mL/min.
• Prednisolone (inflammatory reaction): 20 to 40 mg orally once daily for 1 to 2 weeks then taper; maximum 1 mg/kg daily; monitor glucose and infection; reduce in older adults.

Monitoring. Fever curve, liver tests and C-reactive protein weekly; repeat imaging at 4 to 8 weeks, then every 2 to 3 months.

Referral and escalation. Haematology and infectious disease.