First report of liver transplantation in Blau syndrome: The challenges faced in this rare granulomatous liver disease.

Abstract Blau syndrome is a rare autoinflammatory granulomatous disease caused by mutations in the NOD2 gene, classically presenting in childhood. Hepatic manifestations are recognized including cholestasis and granulomatous liver disease. We describe a novel NOD2 gene variant c.1471A > C, p.(Met491Leu) in an adult who developed cirrhotic complications despite selective immunotherapy, including recurrent esophageal bleeding and spontaneous bacterial peritonitis which resulted in liver transplantation. He required a second liver transplant as his first graft failed due to ischemic cholangiopathy. Disease recurrence has been observed (hitherto unreported). Of 84 patients with Blau syndrome treated with antibody therapy, 5 hepatic cases responded to anti-TNF therapy, with promising results if instigated before decompensation occurs. We report the first case of liver transplantation for Blau syndrome in an adult with a novel NOD2 variant. Anti-TNF therapy appears promising if instigated before decompensation occurs. Blau related liver disease can occur post transplantation and is an important consideration for any future graft. Lay summary Blau syndrome is a rare immune disease which presents in childhood. We describe the first liver transplant for this condition following development of progressive liver disease in adulthood. The patient had a newly described variant in the Blau gene (NOD2). We discuss the effectiveness of antibody therapy currently being used to control the disease, and the role of liver transplantation in Blau syndrome.