Efficacy of ibrutinib and diagnostic liver biopsy for idiopathic refractory ascites after allogeneic stem cell transplantation

Idiopathic portal hypertension-related refractory ascites (IRA) is a rare but potentially life-threatening complication following allogeneic hematopoietic cell transplantation (allo-HCT). Its pathogenesis remains unclear, and optimal diagnostic and therapeutic strategies have yet to be established. Here, we report a case of a 58-year-old man who developed progressive ascites after allo-HCT. Although the clinical findings met diagnostic criteria for hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), liver histology revealed no hallmark features of VOD/SOS, such as sinusoidal dilatation or central venous fibrosis. Instead, portal venopathy with lymphocytic infiltration and fibrosis suggested a subclinical chronic graft-versus-host disease (GVHD)-like pathology, supporting a diagnosis of IRA by exclusion. Treatment with belumosudil, one of the available treatment options for chronic GVHD, was ineffective. Subsequent treatment with ibrutinib, a Bruton’s tyrosine kinase inhibitor, led to resolution of ascites within three days. This is the second reported case of successful treatment of IRA with ibrutinib, and highlights the importance of considering ibrutinib-responsive immune-mediated mechanisms in the differential diagnosis of post-transplant ascites. Given the fundamental differences in treatment strategies between IRA and VOD/SOS, our findings underscore the need for accurate diagnosis, including histopathological evaluation, to guide effective therapy and improve patient outcomes in this challenging clinical scenario.