Although Shwachman Diamond syndrome (SDS) is rare, up to one-third of patients undergo HSCT, offering a unique lens on transplant-related liver risk. The liver is central to conditioning tolerance and post-HSCT outcomes, yet injury may remain silent until stress-tested by transplantation. What was once considered transient liver disease now appears persistent and clinically significant, raising broad implications for evaluation of hepatic risk in transplant populations. We systematically characterized prevalence, features, and outcomes of liver injury in SDS, defining chronic hepatitis (CH) as persistent AST/ALT elevation above the upper limit of normal on ≥3 blood draws ≥1 month apart. To isolate SDS-associated disease, aminotransferase values within 6 months of chemotherapy or HSCT were excluded. Of 246 patients with biallelic SBDS mutations in the North American SDS Registry, 171 were evaluable; 94 (55%) developed CH. CH occurred almost exclusively in childhood and was linked to younger age at SDS diagnosis (median 1.1 vs. 7.0 years, p1000 U/L (Figure 2B). Imaging underestimated pathology: 92% had normal imaging prior to biopsy, yet histology revealed fibrosis (58%), inflammation (58%), steatosis (33%), bile duct changes (25%), and iron deposition in a minority (Figure 3A–B). In SDS, chronic hepatitis is common, often unresolved at HSCT, and poorly detected by imaging. Despite reassuring imaging, most biopsies demonstrated significant pathology, underscoring occult hepatic vulnerability at transplant. Nonetheless, patients with CH generally tolerated conditioning without major added toxicity. These findings support routine biochemical surveillance, suggest that normal imaging does not exclude risk, and highlight the need for larger studies to define how liver pathology modifies transplant outcomes.
Koo et al. (Sun,) studied this question.