S5474 Chronic Hepatic Graft Versus Host Disease Leading to Cirrhosis and Portal Hypertension

Introduction: Graft-versus-host disease (GVHD) is an immune-mediated complication occurring in up to 70% of hematopoietic stem cell transplant (HCT) recipients. Hepatic involvement is common (38%-52%) but typically mild. Progression to cirrhosis is rare, with a cumulative incidence of about 0.6% at 10 years post-transplant. Case Description/Methods: A 46-year-old man with acute myeloid leukemia (AML) diagnosed in 2014 underwent allogeneic HCT in 2016. Post-transplant, he developed cutaneous GVHD. He had failed tacrolimus therapy and was being treated with Ruxolitinib with intermittent steroids for acute flares. He had persistent cholestatic-pattern elevation of elevated liver enzymes (alkaline phosphatase 494 U/L, aspartate aminotransferase 93 U/L, alanine aminotransferase 112 U/L, total bilirubin 1.0 mg/dL), and was believed to be associated with mild GVHD. In March 2025, the patient underwent abdominal CT for new onset abdominal pain, which incidentally revealed a portal vein thrombosis (PVT). He was started on apixaban given no history of prior PVT. Seven days later, he presented to our center with massive hematemesis. Upper endoscopy showed large esophageal varices, which were banded. Computed tomography imaging was reevaluated in our center and revealed significant cavernous transformation, suggesting chronic PVT. Magnetic resonance cholangiopancreatography revealed no biliary obstruction. Workup for other liver diseases—including viral hepatitis, autoimmune, genetic, and metabolic etiologies—was unremarkable. Liver biopsy revealed periportal and pericellular bridging fibrosis (stage 3/4), mild lobular inflammation, and some portal tracts lacking bile ducts—findings consistent with chronic hepatic GVHD with ductopenia. The patient was started on ursodeoxycholic acid (UDCA) and carvedilol. Discussion: This case illustrates a rare progression of chronic GVHD to cirrhosis with portal hypertension. While hepatic GVHD often presents with cholestatic enzyme abnormalities, with ductopenia in later phase, cirrhosis is an uncommon outcome. Histologic confirmation is critical, as chronic hepatic GVHD can mimic other cholangiopathies. UDCA may improve biochemical profiles and symptoms such as pruritus. Post HCT GVHD prophylaxis with calcineurin inhibitors and steroids is crucial. JAK-2 inhibitors are newer therapies that have been used for GVHD prevention. Early recognition, monitoring of liver function, and perhaps early intervention in HCT recipients with GVHD are essential to prevent irreversible liver damage.