Fungal liver infections in children are uncommon but carry high morbidity, especially in immunocompromised hosts. Prompt recognition, appropriate imaging, and targeted antifungal therapy guided by IDSA and AASLD recommendations are essential for optimal outcomes.
Description & Epidemiology
Deep‐seated Candida infection forming microabscesses in liver and spleen.
Predominantly affects children with prolonged neutropenia during chemotherapy for acute leukemia or after hematopoietic stem cell transplant (HSCT).
Risk Factors
Prolonged neutropenia (absolute neutrophil count <500/µL for >7–10 days)
Intensive chemotherapy (especially for AML)
Broad‐spectrum antibiotics
Corticosteroids or other immunosuppressants
Pathogenesis
Translocation of Candida from damaged gastrointestinal mucosa into the bloodstream → seeding of hepatic and splenic microvasculature → microabscess formation
Clinical Presentation
Persistent or recurrent fever unresponsive to broad‐spectrum antimicrobials
RUQ or epigastric pain; may have tender hepatomegaly and splenomegaly
Weight loss and fatigue
Laboratory Findings
Neutropenia (ANC <500)
Elevated inflammatory markers (C‐reactive protein, ESR)
Mild–moderate increases in ALP, GGT, AST, ALT
Blood cultures positive in <30%
Fungal biomarkers: β-D-glucan assay; Candida mannan antigen and anti-mannan antibodies
Imaging
Ultrasound: multiple small (1–3 cm) hypoechoic “bull’s eye” lesions
Contrast CT/MRI: numerous low‐attenuation lesions with peripheral rim enhancement
Diagnosis
Clinical syndrome in at‐risk child + compatible imaging
Confirm with blood culture or nonculture markers
Liver biopsy (rare): granulomatous inflammation with budding yeasts on PAS or GMS stain
Treatment (2020 IDSA Guidelines)
Initial Therapy
Echinocandin (micafungin 1–2 mg/kg/day or caspofungin 70 mg/m² loading dose then 50 mg/m²/day)
Or liposomal amphotericin B (3–5 mg/kg/day) for severe disease
Step‐down Therapy
Transition to fluconazole (6–12 mg/kg/day) once patient is stable and isolate is susceptible
Duration
Continue until neutrophil recovery and resolution of lesions on imaging (typically 6–8 weeks total)
Monitoring
Weekly liver enzymes, renal function
Repeat imaging at 4–6 weeks
Description & Epidemiology
Dimorphic fungus (Coccidioides immitis/posadasii) endemic to southwestern U.S. desert regions.
Hepatic involvement occurs as part of disseminated disease, especially in infants and immunocompromised children.
Risk Factors
Residence or travel in San Joaquin Valley, AZ, NM, West TX
Immunosuppression (HIV, HSCT, steroids)
Very young age (<2 years)
Pathogenesis
Inhalation of arthroconidia → pulmonary infection → hematogenous dissemination to liver, skin, bones, CNS
Clinical Presentation
Fever, cough, chest pain, malaise
RUQ discomfort; hepatomegaly may be present
Cutaneous lesions or osteoarticular pain in disseminated cases
Laboratory Findings
Peripheral eosinophilia
Mild–moderate ↑ AST/ALT
Imaging
Ultrasound/CT: hepatomegaly; possible focal granulomatous nodules
Diagnosis
Serology: IgM and IgG by EIA; complement‐fixation titers correlate with disease severity
Culture of spherules (biosafety risk)
Histopathology: spherules containing endospores
Treatment (IDSA 2016 Guidelines)
Mild Disseminated Disease: oral fluconazole 6–12 mg/kg/day (max 400 mg/day) or itraconazole 5–10 mg/kg/day (max 400 mg/day) for 6–12 months
Severe/Progressive Disease: liposomal amphotericin B 3–5 mg/kg/day until clinical improvement, then azole consolidation
Description & Epidemiology
Dimorphic fungus Histoplasma capsulatum, endemic in Ohio, Mississippi, and Missouri River valleys, and in areas with bird/bat droppings.
Progressive disseminated histoplasmosis with hepatic involvement primarily affects immunocompromised children and infants.
Risk Factors
Immunosuppression: HIV, HSCT, organ transplant, corticosteroids
Infants (<1 year)
High‐dose exposure (spelunking, demolition of old buildings)
Pathogenesis
Inhalation of microconidia → transformation to yeasts in lungs → uptake by macrophages → lymphohematogenous spread to liver, spleen, bone marrow
Clinical Presentation
Fever, weight loss, malaise
Hepatomegaly (>70% of progressive cases), splenomegaly
Lymphadenopathy, respiratory symptoms
Laboratory Findings
Pancytopenia (bone marrow involvement)
↑ ALP, GGT, AST, ALT
Hyperferritinemia, elevated LDH
Imaging
Ultrasound: hepatosplenomegaly; may show hypoechoic nodules
CT: diffuse or focal hepatic lesions in severe cases
Diagnosis
Antigen detection: Histoplasma polysaccharide antigen in urine and serum (high sensitivity)
Serology: complement‐fixation and immunodiffusion
Culture: blood, bone marrow (slow growth)
Histopathology: small intracellular yeasts on GMS stain
Treatment (IDSA 2020 Guidelines)
Moderate–Severe Disseminated Disease
Liposomal amphotericin B 3–5 mg/kg/day for 1–2 weeks or until clinical improvement
Follow with itraconazole 5–10 mg/kg/day (max 400 mg/day) for at least 12 months
Mild–Moderate Disease
Itraconazole 5–10 mg/kg/day for 6–12 months
Monitoring
Histoplasma antigen levels monthly for first 3 months, then every 3 months
Liver function tests, complete blood counts
Key Points
In immunocompromised children, persistent fever with hepatosplenic lesions warrants early imaging and fungal diagnostics.
IDSA guidelines favor echinocandins for invasive candidiasis and amphotericin B followed by azoles for severe dimorphic mycoses.
Duration of therapy is prolonged (months) to ensure eradication and prevent relapse.
Coordination among pediatric infectious diseases, hepatology, and interventional radiology is critical for drainage decisions and management of complications.