Liver disease in Shwachman-Diamond syndrome: A comprehensive characterization across the age spectrum

Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure disorder, and its hepatic phenotype is poorly defined. Our objective was to systematically characterize the prevalence, features, and outcomes of liver injury in a multicenter SDS cohort.

Retrospective registry study of 171 patients with biallelic Shwachman-Bodian-Diamond syndrome (SBDS) mutations and evaluable hepatic data. Clinical, laboratory, imaging, elastography, and biopsy findings were extracted from medical records.

Chronic hepatitis (CH) was observed in 94 of 171 patients (55%), with a median age at onset of 1.0 year (range 0.04-37.9). At presentation, 71% had alanine aminotransferase (ALT) ≥ 2× upper limit of normal (ULN) (interquartile range [IQR] 81-228.5 U/mL). In contrast, adult-onset CH (n = 5) was characterized by only mild (1-2× ULN) transaminase elevations. CH persisted for a median of 6 years, with resolution in 36% of cases. Hematopoietic stem cell transplantation (HSCT) exposure and liver-related mortality did not differ between patients with and without CH. Ultrasound (226 studies) was the principal imaging modality; 55% of scans in the CH cohort displayed increased echogenicity with preserved size, mirroring no-CH findings. Elastography (n = 41) showed comparable liver stiffness, though controlled attenuation parameter (CAP)-defined steatosis was more common without CH (40% vs. 18%). Biopsies (n = 30) revealed hepatitis (69%) and fibrosis (65%) in pediatric CH, whereas adults showed universal steatosis, often with fibrosis or cirrhosis.

Liver disease is common in individuals with SDS. Longitudinal prospective surveillance and mechanistic studies are needed to inform targeted prevention and therapy.