S5688 Non-Cirrhotic Portal Hypertension Secondary to Hepatoportal Sclerosis in a Hematopoietic Stem Cell Transplant Patient

Introduction: Non-cirrhotic portal hypertension (NCPH) is an uncommon but important complication following hematopoietic stem cell transplantation (HSCT). We present a HSCT patient who developed features of portal hypertension. Liver biopsy revealed sinusoidal fibrosis consistent with hepatoportal sclerosis. Case Description/Methods: A 57-year-old man with history of obesity, diabetes, and high-grade myelodysplastic syndrome (RAEB-1) underwent allogeneic HSCT following conditioning with busulfan and fludarabine. He received methotrexate and tacrolimus after transplant. He followed with gastroenterology for esophageal strictures from gastrointestinal graft-versus-host-disease (GVHD), requiring frequent dilation. Approximately 2 years after his transplant, he was noted to have new findings of portal hypertension with grade 1 esophageal varices, portal hypertensive gastropathy, and new high serum ascites albumin gradient ascites. Subsequent work-up for ascites involved an unremarkable echocardiogram that showed no evidence of sinusoidal obstruction syndrome (SOS) or liver nodularity suggesting cirrhosis. Elastography was also not consistent with cirrhosis, but liver ultrasound was read calling cirrhosis. Given discrepancy in findings, a liver biopsy was ultimately performed and revealed fatty liver, iron deposition, sinusoidal fibrosis, and features consistent with hepatoportal sclerosis, but no evidence of cirrhosis. Etiology of his NCPH was attributed to cumulative endothelial injury from chemotherapy and immunosuppression. Discussion: The most common cause of NCPH worldwide is schistosomiasis infection, and in western countries, common causes include portal vein thrombosis, hepatic vein thrombosis and alcoholic hepatitis. NCPH less commonly occurs as a result of hepatoportal sclerosis, a condition marked by obliterative portal venopathy and sinusoidal fibrosis. Hepatoportal sclerosis can result from chemotherapy, immunosuppressants, and chronic GVHD in post-transplant patients. Liver biopsy is often essential for diagnosis, and early recognition allows for tailored care, endoscopic monitoring and may inform decisions for future hepatotoxic therapies. While SOS is a well-recognized complication of busulfan-based regimens, differentiating hepatopulmonary syndrome (HPS) from SOS is critical, as clinical courses and management differ. This case highlights the importance of considering HPS in patients with portal hypertension after HSCT, especially in the absence of cirrhosis.