Mohamed Rela

Living donor liver transplantation for biliary atresia – An Indian experience

LT has played a significant role in improving the outcome of children with BA. We review our five‐yr experience of LDLT for children with BA. Records of all children who underwent LDLT in our institution over a five‐yr period (August 2010–June 2015) were reviewed and those with a primary diagnosis of BA were selected for our study. Data were extracted from a prospectively maintained database. Additional data were collected by review of case notes and imaging studies. Analysis was carried out using standard statistical means. One hundred and thirty‐two children underwent LDLT at our center over the study period, of which 58 children (31 females) had a primary diagnosis of BA. Thirty‐three (56.9%) children had undergone a prior KPE and 25 (43.1%) had a primary LT. Thirty‐four children had at least one post‐op complication, of which 13 had minor complications (Clavien grades I and II) and 21 had major complications (Clavien grade >II). Thirty‐day survival was 96.6% and one‐yr survival was 91.4%. Univariate analysis of variables comparing children who did and did not have a KPE prior to LT showed that age at LT, weight at LT, PELD, and GRWR were significantly different. LDLT provides excellent outcomes in children with BA. Primary LDLT and LT after KPE provide equivalent results, although the former is technically more challenging as the child is younger.

Recent trends in the diagnosis and management of biliary atresia in developing countries

Need and purpose of reviewBiliary atresia is a progressive obstructive cholangiopathy and is fatal if left untreated within 2 years of life. Delay in referral is because of difficulties in differentiating it from physiologic jaundice and identifying an abnormal stool color. This paper presents an overview on the diagnosis and discusses the current strategies in the management of this disease in developing countries.MethodsArticles were retrieved from the PubMed database using the terms ‘biliary atresia’, ‘Kasai portoenterostomy’ and ‘pediatric liver transplantation’. Contents of the article are also based on personal experience of the authors.ConclusionA national screening program using stool color cards as part of standard care in the neonatal period will greatly improve early detection of biliary atresia. Outcomes will improve if it is diagnosed at the earliest after birth, the child is referred to an experienced pediatric hepatobiliary unit for evaluation, and undergoes an early Kasai procedure. If an early Kasai portoenterostomy is performed, nearly half of all children survive into adolescence, and about one-third are likely to have a long-term, symptom-free life with normal liver biochemistry. Sequential treatment combining Kasai as first line and liver transplantation as second line results in 90% survival for children with biliary atresia.

Liver pathology in severe multidrug resistant 3 protein deficiency: a series of 10 pediatric cases ☆

Multidrug resistance protein 3 (MDR3) is a hepatocyte canalicular membrane protein encoded by the ABCB4/MDR3 gene located on chromosome 7. Several liver diseases are known to be associated with MDR3 deficiency. The basic defect is reduced secretion of biliary phospholipid causing disturbance in the primary bile composition, leading to injury to biliary epithelium inducing cell death and inflammation. Severe MDR3 deficiency typically presents during the first year of life or early childhood, often progressing to chronic liver disease with cirrhosis and portal hypertension, requiring liver transplantation. Negative MDR3 immunostaining is suggestive of MDR3 deficiency. Herein, we report the clinical and histopathologic features of 10 cases (6 male/4 female) in infants and children with severe MDR3 deficiency (age range of 8 months to 7 years) diagnosed with negative MDR3 immunostaining in hepatic canaliculi. Three cases underwent liver transplantation. The cases showed periportal bridging fibrosis to micronodular cirrhosis, ductular proliferation with bile plugs, and lobular canalicular bile stasis with rosetting. All 3 explant livers demonstrated cystically dilated large ducts with crystallization of cholesterol. One case showed well-differentiated hepatocellular carcinoma. We conclude that MDR3 immunostaining on formalin-fixed and paraffin-embedded sections is a useful tool to diagnose severe MDR3 deficiency in pediatric liver cholestatic disease cases where genetic testing is not available.

Pediatric hepatocellular carcinoma in a developing country: Is the etiology changing?

HCC is the second most common malignant liver tumor of childhood. It typically affects children with a median age of 10–14 yr on background hepatitis B‐related liver disease and is often metastatic or locally advanced at diagnosis. Children below the age of five yr typically constitute <10% of all children with HCC. In these children, it occurs on a background of congenital or metabolic liver disease. The records of all children with HCC who presented to our department over a six‐yr study period were reviewed. Twelve patients with a median age of 5.9 yr (range 1.6–15.4) were diagnosed to have HCC. All patients underwent liver transplantation, and none were resected. Eleven patients had background congenital or metabolic liver disease. All five of those with hereditary tyrosinemia type 1 who presented to us were found to have HCC. No patient had hepatitis B‐related liver (HBV) disease. Eight (66.7%) patients had incidentally discovered HCC on examination of the explant. Incidentally discovered HCC were smaller, well differentiated, and did not show microvascular invasion compared to those diagnosed preoperatively. There was no recurrence with a median follow‐up of five months. The patient demographic for pediatric HCC is changing probably as a consequence of successful immunization against HBV. Younger patients with congenital and metabolic liver disease in whom liver transplantation is the ideal treatment are likely to constitute an ever‐increasing proportion of patients with pediatric HCC as HBV disease is controlled or eradicated.

Hepatocarcinogenesis in multidrug‐resistant P‐glycoprotein 3 deficiency

MDR3 is a hepatocyte canalicular membrane protein encoded by the ABCB4 gene located on chromosome 7. MDR3 mediates the translocation of phosphatidylcholine into bile. Severe MDR 3 deficiency typically presents during early childhood with chronic cholestasis evolving to cirrhosis and portal hypertension, requiring liver transplantation. Herein, we report a case of severe MDR3 deficiency in a male child diagnosed with negative MDR3 immunostaining in hepatic canaliculi who underwent LDLT at our centre. We also describe single incidentally detected early well‐differentiated HCC in the explant liver. The patient is on regular follow‐up and is doing well. Our report shows that MDR3 deficiency may be a risk factor for the development of HCC.

Surgical management of hepatic arterioportal fistula in a neonate

Congenital arterioportal fistulae in the liver are rare malformations which can lead to portal hypertension. We report a hepatic arterioportal fistula in a neonate who presented with intestinal hypoperfusion. Computerised tomography angiography showed a fistulous communication between the left hepatic artery and portal vein with hypoperfusion of small and large bowel. A formal left hepatectomy was done followed by clinical improvement and reduction in portal venous pressures. The case and the literature pertaining to it are discussed.

Caroli’s Syndrome with Incidental Fibrolamellar Carcinoma on Liver Explant

To the Editor: Caroli’s syndrome (CS) is a manifestation of cystic dilatation of the entire intrahepatic biliary tree with congenital hepatic fibrosis (CHF). It does carry a risk of hepatobiliary malignancy especially cholangiocarcinoma but hepatocellular carcinoma (HCC) is exceedingly rare [1]. We report a unique presentation of incidental fibrolamellar hepatocellular carcinoma (FLHCC) in a pediatric patient with a background of CS. A 9-y-old boy was referred for management of CHF with autosomal recessive polycystic kidney disease. Laboratory investigations showed pancytopenia with normal liver and kidney function. He had growth failure with history of recurrent cholangitis and variceal bleeding. Hence liver transplantation was planned and performed. His post op period was uneventful and he is under regular follow-up. On gross examination, an irregular grayish white nodule 0.6 cm in maximum diameter was identified in the right lobe of the liver. The sections from the nodule showed an infiltrative tumor demonstrating large, round to polygonal, malignant hepatocytes with dense, eosinophilic, granular cytoplasm, discrete cell borders, vesicular nuclei, and prominent eosinophilic nucleoli. The intervening stroma consisted of thick, hyalinized bundles of collagen. The final impression was that of incidental fibro lamellar variant of HCC on a background of Caroli’s syndrome (Fig. 1). Primary hepatic malignancies account for less than 2% of hepatic neoplasms in children, with hepatoblastoma being the most common. Hepatocellular carcinoma (HCC) is usually seen after 10 y of age and its presence with CHF is extremely uncommon with only four cases reported in literature and all these have been reported in an older age group [2, 3]. FLHCC, a distinctive subtype of HCC, observed in this patient has a median age of diagnosis of 33 y compared to 66 y for the typical variant [4]. Despite its younger age of onset, the most common form in children and young adults is still typical variant. Also, FLHCC patients usually present with jaundice and hepatomegaly or an abdominal mass, and have no history of chronic liver disease and cirrhosis. FLHCC has never been reported in the background of liver disease. We feel that the FLHCC that occurred in this patient was from the background hepatocytes, which were unremarkable. To conclude, FLHCC can occur in the background of liver disease. * Mohamed Safwan msafwan89@yahoo.co.in

Well-Differentiated Neuroendocrine Tumour of the Extrahepatic Bile Duct: a Case Report with Review of Literature.

Neuroendocrine tumours (NETs) are defined as epithelial neoplasms with predominant neuroendocrine differentiation. They arise from the neuroendocrine cell system that consists of organoid cell aggregations disseminated across various organs of the body. They are found in greatest amounts in the small intestine, with decreasing frequency in the appendix, rectum, lung and pancreas and rarely in the ovaries, testes, liver and bile ducts. About 60 % of NETs arise within the gastrointestinal system [1]. NETs of the biliary system are rare, accounting for only 0.2–2 % of all gastrointestinal NETs [2], and are difficult to distinguish from cholangiocarcinoma preoperatively. Preoperative brush cytology is known to have low sensitivity in detecting tumours of the biliary tract [3] and is inconclusive in most cases of NETs considering the sub-mucosal nature of the lesion. We report a case of a nonfunctioning well-differentiated NET of the extrahepatic bile duct diagnosed by endoscopic ultrasonography (EUS)-guided fine-needle aspiration cytology (FNAC) and treated with surgical resection.

Genotypic detection of Epstein-Barr Virus in pediatric transplant recipients from India

ObjectiveTo determine the rate of occurrence and genotypes of Epstein-Barr Virus (EBV) among pediatric renal and liver transplants recipients.DesignObservational study.SettingVision Research Foundation referral center and Institute of Liver Disease and Transplantation, Chennai, India.Participants70 pediatric solid organ transplant recipients and 60 voluntary healthy donors.MethodsPolymerase chain reaction (PCR) for detection and genotyping of EBV were carried out using genes targeting Viral capsid antigen, Nuclear antigen 1, 2 and 3, followed by real time PCR for viral load determination and further confirmed by phylogenetic analysis.ResultsEBV was detected in 35 (51.4%) samples (32 liver and 4 renal transplants) with high viral load. Type A was detected in 33 samples, Type B in 2 liver transplant patients, and co-infection in one liver transplant patient who developed Post-transplant Lymphoproliferative Disorder (PTLD). Real time PCR results correlated with conventional PCR. The mean viral load for patients who did not develop PTLD was 50,424 copies/mL. Overall EBV load in patient with PTLD ranged from 1,40,392 copies/mL prior to PTLD diagnosis to 62,124 copies /mL post treatment.ConclusionEBV infection is the high risk factor for PTLD after liver transplantation. PCR targeting of EBV can be applied to diagnose EBV infections and monitor treatment for EBV in pediatric solid organ transplant recipients.