Severe hepatic steatosis contributes to liver dysfunction in non-obese patients with insulin-resistant diabetes mellitus after hematopoietic stem cell transplantation.

BACKGROUND

Non-obese survivors of childhood hematopoietic stem cell transplantation (HSCT) often exhibit severe insulin resistance and mild hepatic dysfunction. Although the exact pathophysiology remains unclear, one possible explanation is the increasingly recognized condition known as HSCT-associated partial lipodystrophy. In lipodystrophy, hepatic dysfunction is characterized by fibrosis and severe steatosis, resembling nonalcoholic steatohepatitis. Accordingly, detailed hepatic assessment would improve our overall understanding of the condition. This study aimed to evaluate hepatic dysfunction using a non-invasive method (FibroScan) in patients who developed glucose intolerance post-HSCT.

METHODS

Fourteen non-obese childhood HSCT survivors from two institutions underwent FibroScan. They were classified according to the presence or absence of diabetes mellitus (DM) with insulin resistance (HOMA-IR >2.5 or insulin therapy >1.5 U/kg/day). FibroScan provided controlled attenuation parameter (CAP) for hepatic steatosis and liver stiffness measurements (LSM) for fibrosis. Serum hepatic fibrosis markers (collagen type IV and hyaluronic acid) were also measured.

RESULTS

Seven patients developed insulin-resistant DM while seven had normal glucose/lipid metabolism. All DM patients showed "Dunnigan"-type subcutaneous fat distribution. CAP values were higher in the DM group [307 (261.0-343.5) vs. 237 (216.5-271.0), p = 0.041], as were LSM scores [6.7 (5.9-9.9) vs. 4.1 (3.5-4.7), p = 0.007], indicating more severe steatosis and increased liver stiffness. However, serum hepatic fibrosis markers did not differ significantly.

CONSLUSIONS: Non-obese HSCT survivors with insulin-resistant DM exhibited severe hepatic fat accumulation and progression of liver fibrosis attributable to lipodystrophy. FibroScan may have potential utility for monitoring liver health in this population.