Clinical and laboratory features of biliary atresia and patterns of management practices: Saudi national study (2000-2018).

BACKGROUND: We utilized the data from the Saudi national biliary atresia (BA) study (2000-2018) to describe the clinical, biochemical, imaging, and histopathological features of BA and the perioperative clinical practices among local pediatric gastroenterologists. METHODS: This is a retrospective, multicenter, nationwide study that included 10 tertiary care governmental hospitals including the four liver transplant (LT) centers in different regions across Saudi Arabia. RESULTS: BA was diagnosed in 204 infants (106 females; 10% preterm). The median age at referral was 65 days. Congenital anomalies were present in 68 patients (33%); 22 were splenic malformation (10.8%). The medians of laboratory investigations were total bilirubin (189 µmol/l), direct bilirubin (139 µmol/l), ALT (164 u/l), and GGT (472 u/l). The level of serum GGT was normal in 26 cases (12.7%). The ultrasound findings included hypoplastic or atrophic gall bladder (GB) (65%), normal GB (30%), and cord sign (5%). A HIDA scan was performed in 99 cases (48.52%). Magnetic resonance cholangiopancreatography (MRCP) was performed in 27 cases (13%). A total of 179 liver biopsies (88%) were obtained. The most common histopathologic findings were bile duct proliferation (92%), canalicular cholestasis (96%), bile plugs (84%), and portal fibrosis (95%). Cholangiography was performed in 139 cases (68%): operative in 122 (60%) and percutaneous in 17 (8%). A total of 143 children (70%) underwent Kasai portoenterostomy (KPE) at a median age of 70 days. After KPE, steroid was used in 37% of the cases and 100 cases (70%) were prescribed prophylactic antibiotics for variable duration (ranging between 3 and 12 months). CONCLUSION: Our data show marked variation in the diagnostic evaluation and perioperative management of BA cases among the different tertiary centers. There is a need to establish a national BA registry in Saudi Arabia aiming to standardize pre- and postoperative clinical practices. Additionally, normal serum GGT level, normal GB size on ultrasound, and being a premature baby should not preclude the diagnostic workup for BA.

Predictors of biliary atresia outcome: Saudi National Study (2000 - 2018).

Background: Outcomes in biliary atresia (BA) have been well-documented in large national cohorts from Europe, North America, and East Asia. Understanding the challenges that preclude success of the Kasai portoenterostomy (KPE) is the key to improve the overall outcomes of BA and implementing intervention strategies. Here, we analyzed the data from the Saudi national BA study (204 BA cases diagnosed between 2000 and 2018) to identify the prognostic factors of BA outcomes. Methods: One hundred and forty-three cases underwent KPE. Several prognostic factors (center case load, congenital anomalies, serum gamma-glutamyl transferase, use of steroids, ascending cholangitis post-operatively, and degree of portal fibrosis at time of KPE) were investigated and correlated with the primary outcomes of interest: 1) success of KPE (clearance of jaundice and total serum bilirubin <20 mmol/l after KPE), 2) survival with native liver (SNL), and 3) overall survival. Results: Use of steroids after KPE was associated with clearance of jaundice, 68% vs. 36.8% in the BA cases that did not receive steroids (P = 0.013; odds ratio 2.5) and a significantly better SNL rate at 2 - and 10-year of 62.22% and 57.77% vs. 39.47% and 31.57%, respectively (P = 0.01). A better 10-year SNL was observed in centers with caseload <1/year (group 1) as compared to centers that performed ≥1/year (group 2) [45.34% vs. 26.66%, respectively; P = 0.047]. On comparison of the 2 groups, cases in group 1 had KPE at significantly earlier age (median 59.5 vs. 75 days, P = 0.006) and received steroids after KPE more frequently than group 2 (69% vs. 31%, P < 0.001). None of the remaining prognostic variables were identified as being significantly related to BA outcome. Conclusion: Steroids use post-KPE predicted clearance of jaundice and better short- and long-term SNL. There is a need to establish a national BA registry in Saudi Arabia aiming to standardize the pre- and post-operative clinical practices and facilitate clinical and basic research to evaluate factors that influence BA outcome.

The Epidemiology and Outcome of Biliary Atresia: Saudi Arabian National Study (2000-2018).

Background: The epidemiology and outcomes of biliary atresia (BA) have been well-documented in national cohorts from two main ethnicities, namely, the Asian Orientals and Caucasians, with incidence ranging from 1 in 5,000 to 1 in 9,000 live births in East Asia and 1 in 15,000 to 19,000 live births in Europe and North America. Objective: We report the first nationwide BA study outside North America, Europe, and East Asia to describe the epidemiology and outcomes of BA in Saudi Arabia. Methods: A national database of BA cases diagnosed between 2000 and 2018 was analyzed. We assessed clearance of jaundice (bilirubin <20 µmol/L) in all cases that underwent Kasai portoenterostomy (KPE). We then estimated survival using the Kaplan-Meier method with endpoints of liver transplantation (LT), death, or survival with native liver (SNL). Results: BA was diagnosed in 204 infants (106 females; 10% pre-term). The incidence of BA was 1 in 44,365, or 2.254 in 100,000 live births (range, 0.5-4 in 100,000). Polysplenia was diagnosed in 22 cases (11%). The median age at referral was 65 days. A total of 146 children (71.5%) underwent KPE at a median age of 70 days. Clearance of jaundice was achieved in 66 of the 146 (45%) infants. The 10-year SNL after KPE was 25.5%, and the overall 10-year estimated survival was 72.5%. The Kaplan-Meier survival curves for patients undergoing KPE at the age of <60, 61-90, and >90 days showed a SNL rate at 51.6, 33, and 12.5%, respectively, at 5 years (P < 0.001). The 2-, 5-, and 10-year post-LT survival rates were 92.5, 90.6, and 90%, respectively. Undergoing an initial KPE did not impact negatively on the overall LT survival rate when compared to BA cases that underwent primary LT (P = 0.88). Conclusion: The incidence rate of BA in Saudi Arabia is lower than the incidence reported elsewhere. Late referral of BA cases remains a problem in Saudi Arabia; as a result, the SNL rate was lower than reported by other national registries. Hence, national policies devoted to timely referral and earlier age at KPE are needed.

Deleterious Variants in ABCC12 are Detected in Idiopathic Chronic Cholestasis and Cause Intrahepatic Bile Duct Loss in Model Organisms.

BACKGROUND & AIMS: The etiology of cholestasis remains unknown in many children. We surveyed the genome of children with chronic cholestasis for variants in genes not previously associated with liver disease and validated their biological relevance in zebrafish and murine models. METHOD: Whole-exome (n = 4) and candidate gene sequencing (n = 89) was completed on 93 children with cholestasis and normal serum γ-glutamyl transferase (GGT) levels without pathogenic variants in genes known to cause low GGT cholestasis such as ABCB11 or ATP8B1. CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 genome editing was used to induce frameshift pathogenic variants in the candidate gene in zebrafish and mice. RESULTS: In a 1-year-old female patient with normal GGT cholestasis and bile duct paucity, we identified a homozygous truncating pathogenic variant (c.198delA, p.Gly67Alafs∗6) in the ABCC12 gene (NM_033226). Five additional rare ABCC12 variants, including a pathogenic one, were detected in our cohort. ABCC12 encodes multidrug resistance-associated protein 9 (MRP9) that belongs to the adenosine 5'-triphosphate-binding cassette transporter C family with unknown function and no previous implication in liver disease. Immunohistochemistry and Western blotting revealed conserved MRP9 protein expression in the bile ducts in human, mouse, and zebrafish. Zebrafish abcc12-null mutants were prone to cholangiocyte apoptosis, which caused progressive bile duct loss during the juvenile stage. MRP9-deficient mice had fewer well-formed interlobular bile ducts and higher serum alkaline phosphatase levels compared with wild-type mice. They exhibited aggravated cholangiocyte apoptosis, hyperbilirubinemia, and liver fibrosis upon cholic acid challenge. CONCLUSIONS: Our work connects MRP9 with bile duct homeostasis and cholestatic liver disease for the first time. It identifies a potential therapeutic target to attenuate bile acid-induced cholangiocyte injury.

Percutaneous endoscopic gastrostomy in children: A single center experience in Saudi Arabia.

OBJECTIVES: To evaluate the demographic data and complications in children who had undergone percutaneous endoscopic gastrostomy (PEG) over 9 years period. METHODS: The demographic data, complications, length of hospital admission related to PEG insertion and follow-up findings of 39 patients who had undergone percutaneous endoscopic gastrostomy using the standard pull-through technique between 2011 and 2020 were examined. The study took place at the Gastroenterology Division, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia RESULTS: The most common indications of feeding with a gastrostomy tube include neurological diseases (n=30, 76.9%), followed by metabolic disorders (n=3, 7.69%), chronic diarrhea (n=2, 5.1%), chronic kidney diseases (n=2, 5.1%), cystic fibrosis (n=1, 2.56%), feeding aversion fibrosis (n=1, 2.56%). Out of the 39 patients, 20 (51%) did not have any complications. However, minor complication are expected. Most common complications included local infection (n=14, 35.89%) followed by granulation tissue (n=6, 15.38%), "buried bumper syndrome" developed in one. CONCLUSION: Percutaneous endoscopic gastrostomy tube is the desirable method for patients who are unable to feed orally, feeding is not adequate for demands, has special feeding requirements, or swallowing dysfunction. The technique has become more widespread because of its simplicity, safety, and low cost. Major complications are rare. The procedure is safe and effective and could be carried out by pediatric gastroenterologists after training.

New paradigms of USP53 disease: normal GGT cholestasis, BRIC, cholangiopathy, and responsiveness to rifampicin.

Biallelic variants in the USP53 gene have recently been reported to segregate with normal gamma glutamyltransferase (GGT) cholestasis. Using whole-exome sequencing (WES), we detected two USP53 homozygous variants (c.951delT; p. Phe317fs and c.1744C>T; p. Arg582*) in five additional cases, including an unpublished cousin of a previously described family with intractable itching and normal GGT cholestasis. Three patients, a child and two adults, presented with recurrent episodes of normal GGT cholestasis, consistent with a diagnosis of benign recurrent intrahepatic cholestasis (BRIC). Cholangiopathic changes, possibly autoimmune in origin, were recognized in some patients. Additional phenotypic details in one patient included an enlarged left kidney, and speech/developmental delay. Notably, two patients exhibited a complete response to rifampicin, and one responded to ursodeoxycholic acid (UDCA). Two adult patients were suspected to have autoimmune liver disease and treated with steroids. This report describes new cases of USP53 disease presenting with normal GGT cholestasis or BRIC in three children and two adults. We also describe the novel finding of a dramatic response to rifampicin. The association of cholangiopathy with normal GGT cholestasis provides a diagnostic challenge and remains poorly understood.

Analysis of transcript-deleterious variants in Mendelian disorders: implications for RNA-based diagnostics.

BACKGROUND: At least 50% of patients with suspected Mendelian disorders remain undiagnosed after whole-exome sequencing (WES), and the extent to which non-coding variants that are not captured by WES contribute to this fraction is unclear. Whole transcriptome sequencing is a promising supplement to WES, although empirical data on the contribution of RNA analysis to the diagnosis of Mendelian diseases on a large scale are scarce. RESULTS: Here, we describe our experience with transcript-deleterious variants (TDVs) based on a cohort of 5647 families with suspected Mendelian diseases. We first interrogate all families for which the respective Mendelian phenotype could be mapped to a single locus to obtain an unbiased estimate of the contribution of TDVs at 18.9%. We examine the entire cohort and find that TDVs account for 15% of all "solved" cases. We compare the results of RT-PCR to in silico prediction. Definitive results from RT-PCR are obtained from blood-derived RNA for the overwhelming majority of variants (84.1%), and only a small minority (2.6%) fail analysis on all available RNA sources (blood-, skin fibroblast-, and urine renal epithelial cells-derived), which has important implications for the clinical application of RNA-seq. We also show that RNA analysis can establish the diagnosis in 13.5% of 155 patients who had received "negative" clinical WES reports. Finally, our data suggest a role for TDVs in modulating penetrance even in otherwise highly penetrant Mendelian disorders. CONCLUSIONS: Our results provide much needed empirical data for the impending implementation of diagnostic RNA-seq in conjunction with genome sequencing.

Identification of novel loci for pediatric cholestatic liver disease defined by KIF12, PPM1F, USP53, LSR, and WDR83OS pathogenic variants.

PURPOSE: Genetic testing in pediatric cholestasis can be very informative but genetic causes have not been fully characterized. METHODS: Exome sequencing and positional mapping in seven families with cholestatic liver disease and negative clinical testing for known disease genes. RESULTS: KIF12, which encodes a microtubule motor protein with a tentative role in cell polarity, was found to harbor three homozygous likely deleterious variants in three families with sclerosing cholangitis. KIF12 expression is dependent on HNF-1ß, deficiency which is known to cause bile duct dysmorphogenesis associated with loss of KIF12 expression. In another extended family, we mapped an apparently novel syndrome of sclerosing cholangitis, short stature, hypothyroidism, and abnormal tongue pigmentation in two cousins to a homozygous variant in PPM1F (POPX2), a regulator of kinesin-mediated ciliary transport. In the fifth family, a syndrome of normal gamma glutamyltransferase (GGT) cholestasis and hearing loss was found to segregate with a homozygous truncating variant in USP53, which encodes an interactor with TJP2. In the sixth family, we mapped a novel syndrome of transient neonatal cholestasis, intellectual disability, and short stature to a homozygous variant in LSR, an important regulator of liver development. In the last family of three affected siblings, a novel syndrome of intractable itching, hypercholanemia, short stature, and intellectual disability was mapped to a single locus that contains a homozygous truncating variant in WDR83OS (C19orf56), known to interact with ATP13A2 and BSEP. CONCLUSION: Our results expand the genetic heterogeneity of pediatric cholestatic liver disease and highlight the vulnerability of bile homeostasis to a wide range of molecular perturbations.

Outcomes of surgical management of familial intrahepatic cholestasis 1 and bile salt export protein deficiencies.

Progressive familial intrahepatic cholestasis (PFIC) with normal circulating gamma-glutamyl transpeptidase levels can result from mutations in the ATP8B1 gene (encoding familial intrahepatic cholestasis 1 [FIC1] deficiency) or the ABCB11 gene (bile salt export protein [BSEP] deficiency). We investigated the outcomes of partial external biliary diversion, ileal exclusion, and liver transplantation in these two conditions. We conducted a retrospective multicenter study of 42 patients with FIC1 deficiency (FIC1 patients) and 60 patients with BSEP deficiency (BSEP patients) who had undergone one or more surgical procedures (57 diversions, 6 exclusions, and 57 transplants). For surgeries performed prior to transplantation, BSEP patients were divided into two groups, BSEP-common (bearing common missense mutations D482G or E297G, with likely residual function) and BSEP-other. We evaluated clinical and biochemical outcomes in these patients. Overall, diversion improved biochemical parameters, pruritus, and growth, with substantial variation in individual response. BSEP-common or FIC1 patients survived longer after diversion without developing cirrhosis, being listed for or undergoing liver transplantation, or dying, compared to BSEP-other patients. Transplantation resolved cholestasis in all groups. However, FIC1 patients commonly developed hepatic steatosis, diarrhea, and/or pancreatic disease after transplant accompanied by biochemical abnormalities and often had continued poor growth. In BSEP patients with impaired growth, this generally improved after transplantation. Conclusion: Diversion can improve clinical and biochemical status in FIC1 and BSEP deficiencies, but outcomes differ depending on genetic etiology. For many patients, particularly BSEP-other, diversion is not a permanent solution and transplantation is required. Although transplantation resolves cholestasis in patients with FIC1 and BSEP deficiencies, the overall outcome remains unsatisfactory in many FIC1 patients; this is mainly due to extrahepatic manifestations. (Hepatology Communications 2018;2:515-528).

Incidence of pediatric inflammatory bowel disease in Saudi Arabia: a multicenter national study.

BACKGROUND: Pediatric inflammatory bowel disease (IBD) is increasingly recognized in developing countries; however, the incidence and trend over time have not been reported. METHODS: This retrospective study included children diagnosed with IBD in gastroenterology centers in the Kingdom of Saudi Arabia between 2003 and 2012. The date of birth, date and age at diagnosis, gender, and final diagnosis were collected on special forms. Clinical, laboratory, imaging, endoscopy, and histopathology results were reviewed to confirm the final diagnosis. Descriptive statistics were used to compare ulcerative colitis and Crohn's disease in different age groups, and significance was assessed by the chi-square test. Incidence rates and trend over time were analyzed with the assumption of Poisson distribution. The incidence rate over time was compared in 2 periods (2003-2007 and 2008-2012). A P value of <0.05 and 95% confidence intervals were used to assess the significance and precision of the estimates. RESULTS: A total of 340 Saudi Arabian children aged 0 to 14 years were diagnosed. The mean incidence rate per 100,000 individuals was 0.2, 0.27, and 0.47 for ulcerative colitis, Crohn's disease, and IBD, respectively. Except for the 0- to 4-year age group, there was a significant increase in incidence over time. CONCLUSIONS: Although the incidence of pediatric IBD in Saudi Arabian children is lower than suggested in the Western literature, there is a significantly increasing trend over time. However, decreased trend in the younger age group over time is identified. Prospective studies will be important to identify the risk factors for IBD in different age groups.

In search of triallelism in Bardet-Biedl syndrome.

Bardet-Biedl syndrome (BBS) is a model disease for ciliopathy in humans. The remarkable genetic heterogeneity that characterizes this disease is consistent with accumulating data on the interaction between the proteins encoded by the 14 BBS genes identified to date. Previous reports suggested that such interaction may also extend to instances of oligogenic inheritance in the form of triallelism which defies the long held view of BBS as an autosomal recessive disease. In order to investigate the magnitude of triallelism in BBS, we conducted a comprehensive analysis of all 14 BBS genes as well as the CCDC28B-modifier gene in a cohort of 29 BBS families, most of which are multiplex. Two in trans mutations in a BBS gene were identified in each of these families for a total of 20 mutations including 12 that are novel. In no instance did we observe two mutations in unaffected members of a given family, or observe the presence of a third allele that convincingly acted as a modifier of penetrance and supported the triallelic model of BBS. In addition to presenting a comprehensive genotype/phenotype overview of a large set of BBS mutations, including the occurrence of nonsyndromic retinitis pigmentosa in a family with a novel BBS9 mutation, our study argues in favor of straightforward autosomal recessive BBS in most cases.

Differences in presentation and progression between severe FIC1 and BSEP deficiencies.

BACKGROUND & AIMS: Progressive familial intrahepatic cholestasis (PFIC) with normal serum levels of gamma-glutamyltranspeptidase can result from mutations in ATP8B1 (encoding familial intrahepatic cholestasis 1 [FIC1]) or ABCB11 (encoding bile salt export pump [BSEP]). We evaluated clinical and laboratory features of disease in patients diagnosed with PFIC, who carried mutations in ATP8B1 (FIC1 deficiency) or ABCB11 (BSEP deficiency). Our goal was to identify features that distinguish presentation and course of these two disorders, thus facilitating diagnosis and elucidating the differing consequences of ATP8B1 and ABCB11 mutations. METHODS: A retrospective multi-center study was conducted, using questionnaires and chart review. Available clinical and biochemical data from 145 PFIC patients with mutations in either ATP8B1 (61 "FIC1 patients") or ABCB11 (84 "BSEP patients") were evaluated. RESULTS: At presentation, serum aminotransferase and bile salt levels were higher in BSEP patients; serum alkaline phosphatase values were higher, and serum albumin values were lower, in FIC1 patients. Elevated white blood cell counts, and giant or multinucleate cells at liver biopsy, were more common in BSEP patients. BSEP patients more often had gallstones and portal hypertension. Diarrhea, pancreatic disease, rickets, pneumonia, abnormal sweat tests, hearing impairment, and poor growth were more common in FIC1 patients. Among BSEP patients, the course of disease was less rapidly progressive in patients bearing the D482G mutation. CONCLUSIONS: Severe forms of FIC1 and BSEP deficiency differed. BSEP patients manifested more severe hepatobiliary disease, while FIC1 patients showed greater evidence of extrahepatic disease.

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.

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.

Donor experience and outcome of pediatric living-related liver transplantation in Saudi Arabia.

BACKGROUND/PURPOSE: The purpose of this article is to present the first series of living donation of liver grafts in Saudi Arabia, as well as in the Arab World, and to report the morbidity and mortality of the living donors after such procedures. METHODS: A retrospective review of the medical charts of 37 living donors who were involved in the procedure of living-related liver transplantation (LRLT), that took place in Riyadh Armed Forces Hospital in the period between November 1998 and July 2002, is conducted. RESULTS: The age of living donors ranged between 21 and 41 years, and there were 22 women and 15 men. All donors are first-degree relatives, apart from 2 donors who were the cousins of the recipients. There was no mortality among the donors. The morbidity was minimal, including 3 cases of biliary leakage and 1 of incisional hernia. Of 39 pediatric liver transplantations that have been done over the above period, only 2 cases had cadaveric liver transplantation and these were excluded from this study. All donors had left lateral segment donation, apart from one who had right lobe, segments V-VIII donation to a 14-year-old recipient. CONCLUSION: Living donation of hepatic graft is a safe procedure for the donors with an excellent outcome. Living-related liver transplantation is the optimal treatment for end-stage liver disease and the solution for the scarcity of cadaveric liver grafts. The level of acceptance of living donation of hepatic grafts among the Saudi people is favorable.

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.

Living-related liver transplantation for Crigler-Najjar syndrome in Saudi Arabia.

OBJECTIVE: To analyse the outcome of six children with Crigler-Najjar syndrome type I (CNS-I) and report the first three living-related liver transplants for this syndrome in Saudi Arabia and the Middle East. SETTINGS: To review the medical records of six children suffering from CNS-I, three of whom underwent living-related liver transplantation (LRLT) between 22 November 1998 and January 2001. MAIN RESULTS: Living-related liver transplantation was performed in three children with a pre-transplant unconjugated bilirubin level of 362, 381 and 502 micromol/L, respectively, despite daily phototherapy of >or= 12 h. Two of the transplanted children developed acute hepatocellular rejection, which was successfully treated with methylprednisolone pulse therapy. One tested cytomegalovirus positive (using the PP65 method), but showed no signs of clinical infection and was treated with ganciclovir. One patient had a biliary leak at the cut surface of the graft which was surgically repaired. Post-operative bilirubin levels returned to normal in all three transplanted children and no further phototherapy was required. One patient, who was not transplanted but received phototherapy, developed severe neurological damage prior to the start of our living-related liver transplant programme with a bilirubin level of 450 micromol/L, her sister is still awaiting transplantation. A 14-yr-old child with a bilirubin level of 420 micromol/L is presently undergoing phototherapy whilst awaiting orthotopic liver transplantation because of the lack of a suitable living-related donor. Six siblings of the six children in our series were reported dead by the families. CONCLUSION: Crigler-Najjar syndrome type I is a relatively common disease in Saudi Arabia for which LRLT is a curative treatment when performed at an early age before the development of kernicterus and neurological deficiency. In countries where there is a severe shortage of cadaveric organs, as is the case in Saudi Arabia, LRLT is the optimum treatment modality for this syndrome.