Liver Transplantation and Development of Diabetes in an Adolescent Male With HNF1B Disease

**Background:** Mutations in the hepatocyte nuclear factor-1-beta (HNF1B) gene cause a spectrum of diseases affecting the liver, kidneys, pancreas, and urogenital tract. HNF1B disease can present with neonatal cholestasis, maturity-onset diabetes of the young type 5, renal cysts, and pancreatic atrophy. Liver transplantation for HNF1B-related liver disease has rarely been reported. This case describes a male patient who presented with cholestatic liver disease in infancy, progressed to end-stage liver disease by age 14, underwent liver transplantation at age 15, and subsequently developed diabetes requiring insulin.

**Methods:** This is a single case report from a tertiary care center. The patient's clinical course was followed from infancy through 12 months post-liver transplant. Genetic testing confirmed a c.884G>A (p.R295H) mutation in the HNF1B gene. Immunosuppression post-transplant included prednisone, tacrolimus (goal level 8–10 ng/mL), and mycophenolate mofetil. Blood glucose, HbA1c, insulin levels, and diabetes autoantibodies were monitored.

**Key Results:** The patient presented with jaundice at 4 weeks of age. Liver biopsy at 6 weeks showed paucity of interlobular bile ducts and zone 3 canalicular cholestasis. He had bilateral simple renal cysts and multiple long bone fractures from metabolic bone disease. At age 12, genetic testing revealed the HNF1B mutation. At age 14, he developed decompensated cirrhosis with jaundice, coagulopathy, peripheral edema, hepatic encephalopathy, and refractory hypovitaminosis D. Imaging showed an atrophic pancreas but normal HbA1c and glucose. He underwent deceased donor whole organ liver transplant at age 15. Explant histology showed chronic biliary-type disease with loss of intrahepatic bile ducts in approximately 90% of portal tracts. Two weeks post-transplant, serum glucose was 658 mg/dL, HbA1c 4.1%, random insulin 29.9 mcIU/mL (reference 2.6–24.9), bicarbonate 15 mmol/L (reference 21–29), and beta-hydroxybutyrate 0.1 mmol/L. He was on prednisone 15 mg daily (86 mg/m²/day), mycophenolate mofetil 750 mg every 12 h, and tacrolimus 7.5 mg every 12 h. Tacrolimus level was slightly above goal. He was started on insulin aspart and glargine, with total insulin dose 0.88 units/kg/day at discharge. Type 1 diabetes autoantibodies (IA-2, GAD65, insulin antibodies, ZnT8) were negative. Steroids were discontinued by 4 months, mycophenolate by 6 months; tacrolimus continued. At 12 months post-transplant, he remained insulin-dependent but requirements decreased to 0.3 units/kg/day. Insulin was stopped for 2 weeks but resumed due to rising glucose after tacrolimus dose increase. The transplanted liver functioned well.

**Clinical Implications:** This case highlights that HNF1B disease can progress to decompensated cirrhosis requiring liver transplantation in adolescence. Post-transplant diabetes developed despite negative autoantibodies and persisted after corticosteroid withdrawal, implicating tacrolimus as a likely contributor. Clinicians should monitor for diabetes in HNF1B patients undergoing liver transplantation, especially with calcineurin inhibitor use. This is the first reported case of liver transplantation for cirrhosis due to HNF1B disease.