Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families.

BACKGROUND & AIMS: Patients with severe bile salt export pump (BSEP) deficiency present as infants with progressive cholestatic liver disease. We characterized mutations of ABCB11 (encoding BSEP) in such patients and correlated genotypes with residual protein detection and risk of malignancy. METHODS: Patients with intrahepatic cholestasis suggestive of BSEP deficiency were investigated by single-strand conformation polymorphism analysis and sequencing of ABCB11. Genotypes sorted by likely phenotypic severity were correlated with data on BSEP immunohistochemistry and clinical outcome. RESULTS: Eighty-two different mutations (52 novel) were identified in 109 families (9 nonsense mutations, 10 small insertions and deletions, 15 splice-site changes, 3 whole-gene deletions, 45 missense changes). In 7 families, only a single heterozygous mutation was identified despite complete sequence analysis. Thirty-two percent of mutations occurred in >1 family, with E297G and/or D482G present in 58% of European families (52/89). On immunohistochemical analysis (88 patients), 93% had abnormal or absent BSEP staining. Expression varied most for E297G and D482G, with some BSEP detected in 45% of patients (19/42) with these mutations. Hepatocellular carcinoma or cholangiocarcinoma developed in 15% of patients (19/128). Two protein-truncating mutations conferred particular risk; 38% (8/21) of such patients developed malignancy versus 10% (11/107) with potentially less severe genotypes (relative risk, 3.7 [confidence limits, 1.7-8.1; P = .003]). CONCLUSIONS: With this study, >100 ABCB11 mutations are now identified. Immunohistochemically detectable BSEP is typically absent, or much reduced, in severe disease. BSEP deficiency confers risk of hepatobiliary malignancy. Close surveillance of BSEP-deficient patients retaining their native liver, particularly those carrying 2 null mutations, is essential.

One hundred and thirty-seven living donor pediatric liver transplants at Riyadh Military Hospital. Results and outlook for future.

OBJECTIVE: To review the results of 137 living donor pediatric liver transplants performed at Riyadh Military Hospital (RMH). METHODS: Retrospective analysis of the in- and out-patient case notes was carried out. Data were collected regarding age, gender, nationality, diagnosis, type of procedure, complications and survival of the grafts and the recipients. RESULTS: The first 137 living donor pediatric liver transplants were performed in 113 months. The age range was 4.5 months to 14 years. Eighty-four recipients (61%) were male. One hundred and twelve children were Saudi. Left lateral segment was used as allograft in 135 cases. One child each received full left lobe and full right lobe. Six auxiliary partial orthotopic liver transplants were carried out. Familial metabolic liver disorders made the largest group of children needing transplant. The most common indications were progressive familial intrahepatic cholestasis and biliary atresia (45 cases each). The numbers of major complications are: hepatic artery thrombosis (n=8); portal vein thrombosis (n=3); portal vein stenosis (n=3); hepatic vein stenosis (n=3) and biliary strictures (n=4). Fifteen patients died. Three further allografts have been lost. Thus, the overall patient survival rate is 89% and graft survival rate is 86.8%. CONCLUSION: Living donor liver transplantation is a viable option for children with end-stage liver disease. Metabolic liver disease is the most common indication in Saudi Arabia. The cadaveric donor supply is in shortage and living donation is a practical alternative. The incidence of complications and recipient and graft survival rates of the program at RMH are acceptable.

Pediatric living-related liver transplantation in Saudi Arabia.

OBJECTIVE: The purpose of this paper is to report our experience of the first 29 consecutive living-related liver transplants in pediatric recipients and to demonstrate the feasibility of living-related liver transplantation in the Arab World. The first living-related liver transplantation in the Kingdom of Saudi Arabia was performed in November 1998 by Bassas et al following an appropriate period of multi-disciplinary preparation. METHODS: This study was carried out at the Armed Forces Hospital, Riyadh, Kingdom of Saudi Arabia, during the period November 1998 through to October 2001. A review of the data of the transplanted children and adult donors was carried out. The data recorded for recipients included age, sex, patient's weight, preoperative diagnosis, intraoperative surgical complications, graft size and weight, medical and surgical postoperative complications, immunosuppression, rejection and overall survival rate. Data recorded for the donors included age, sex and any postoperative complications. RESULTS: The most frequent indication for living-related liver transplantation in our series was metabolic liver disease. Post-operative complications included biliary leaks in 10% (N=3), vascular occlusion in 13% (N=4), acute cellular rejection in 38% (N=11), positive cytomegalovirus PP65 antigen in 38% (N=11), wound infection in 3.4% (N=one), and systemic infections in 14% (N=4). One urgent retransplantation was necessary due to thrombosis of the hepatic artery. Patient and graft survival rates are 96% and 93%. One patient, treated for acute liver failure, died 2 months post-transplant. CONCLUSION: Our experience has shown pediatric living-related liver transplantation to be a success whilst alleviating the need for sending Saudi patients overseas for treatment and providing a solution to organ shortages for pediatric patients. In general, this endeavor has broadened the spectrum of our experience in surgery, anesthetics, intensive care and pediatrics.