Living Donor Liver Transplantation for an Infant with Osteogenesis Imperfecta and Intrahepatic Cholestasis: Report of a Case
A one-month-old male infant was transferred to the Seoul National University Children's Hospital because of neonatal cholestasis and bone fragility on December 29, 2011.\nFibular fracture and bilateral bowing of the femora were noticed just after birth. And right femur shaft fracture, left humerus fracture and left femur fracture occurred at 1, 2, and 3 months of age respectively (). He showed blue sclerae with a triangular face and his father showed the OI type IB. In mutation analysis for COL1A1 and COL1A2 encoding alpha 1 and 2 chains of type I collagen (MIM 120150 and 120160), a novel heterozygous mutation c.1036-2A > C, (of IVS19) in COL1A2 was identified in both the patient and his father.\nAt one month after birth, he developed white stool and abdominal distension. Liver function tests were abnormal; total bilirubin 7.3 mg/dL, AST 128 IU/L, ALT 82 IU/L, alkaline phosphatase 386 IU/L, albumin 4.0 g/dL, prothrombin time (PT, INR) 1.04, platelet 853 × 103/µL. The screening tests for metabolic diseases were normal. Viral markers for hepatitis A, B, C, and TORCH were all negative. Ultrasonography was incompatible with biliary atresia. Liver biopsy showed cholestasis with periportal fibrosis and damaged bile ducts without definite cause. At the seven month follow-up, his liver function had deteriorated (total bilirubin 19.3 mg/dL, direct bilirubin 12.9 mg/dL, AST 211 IU/L, ALT 165 IU/L, albumin 3.0 g/dL, PT INR 1.09, Platelet 254×103/µL). His CTP score was 9 and pediatric end stage liver disease (PELD) score was 13. Preoperative dynamic liver CT revealed hepatomegaly with surface nodularity and splenomegaly. Because his cholestasis had begun in infancy and had progressed to cirrhosis within seven months, progressive familial intrahepatic cholestasis (PFIC) was suspected. But abnormality was not detected in PFIC type III gene. Body weight was 7.9 kg (10th percentile) and height was 69.6 cm (20th percentile) at the time of LT.\nBefore surgery, the patient was treated with pamidronate infusion therapy (1.5 mg/kg per each cycle) for 4 cycles with vitamin D and calcium medications. His dual energy X-ray absorptiometry (DEXA) bone density showed 0.254 g/cm2 in spine L1-4, 0.301 g/cm2 in femur neck, and 0.393 g/cm2 in femur total after 3rd cycle of pamidronate therapy before LT. These values were comparable to reference values (-).\nLT was performed at the age of 8 months using the left lateral section from his mother under intravenous anesthesia because of the risk of malignant hyperthermia. An endotracheal tube was inserted smoothly under laryngoscopy without a difficult airway related with neck extension. There was no intractable metabolic acidosis during and after LT. Hyperthermia did not develop during the operation.\nThe graft weight was 215 gm and a graft versus recipient weight ratio was 2.72%. The retractors were not used because of high risk for rib fracture. Instead of that, skin was fixed to upper lateral portion in the chest wall with sutures to form the operation field (). The operation lasted for 420 min; cold ischemic time - 78 min, warm ischemic time - 24 min. Hepatic vein was anastomosed via piggyback method with strengthened fencing venoplasty. The recipient's main portal vein was anastomosed to the graft portal vein. The hepatic artery was anastomosed under a surgical microscope (×10). And hepatico-jejunostomy was done. The estimated blood loss was 530 mL. One unit of leukocyte depleted packed red blood cell was transfused during operation.\nHyperthermia developed up to 40℃ on postoperative day (POD) one, and went down within normal range at POD 2 without any cause. A newly developed fracture line of his right humerus shaft was detected at POD 2 (), but it healed under conservative treatment. He was transferred to the general ward from intensive care unit at POD 10 and discharged at POD 15. The pathologic report of the explant liver was secondary biliary cirrhosis, damaged interlobular bile duct, bile duct proliferation with cholestasis and septal fibrosis. He remains well on follow-up 9 months later at the outpatient clinic.