Hasan Ali Yuksekkaya

Liver transplantation for progressive familial intrahepatic cholestasis: Clinical and histopathological findings, outcome and impact on growth

Abstract:  In this study, we analyze the demographic features, clinical and histopathological findings in patients who underwent liver transplantation for progressive familial intrahepatic cholestasis. We also analyze outcome and impact of liver transplantation on growth and bone mineral content. Most of the patients were presented with jaundice mainly beginning within the first six months. At the time of initial admission; eight patients had short stature (height SD score <2), and four patients had weight SD score <2. Liver transplantation were performed at the age of 43.2 ± 27 months (range 9 to 96 mfonths), 6.5 ± 3.5 months later after the first admission. Infection, surgical complications and osmotic diarrhea associated with severe metabolic acidosis were noted in 41.4%, 16.6% and 33.3%, respectively. One patient developed posttransplant lymphoproliferative disorder. Overall; 1 year graft and patient survival was 69.2% and 75%, respectively. At the end of the 1st year only 2 patients had height SD score <2. Linear regression of height gain against increase in total body BMD measured at the time of transplantation and 1 year after liver transplantation gave a coefficient r = 0.588 (p = 0.074). No correlation was found between the height gain and age and PELD score at time of transplantation, and no difference was noted between the sexes and donor type. Liver transplantation is effective treatment modality with good outcome and little morbidity, and increases the growth acceleration in patients with PFIC associated with cirrhosis.

Helicobacter pylori infection in children with celiac disease

Objective. To analyze the prevalence of Helicobacter pylori (H. pylori) infection in children with celiac disease (CD) and to examine the role of H. pylori infection in clinical, laboratory and histopathological presentations of CD. Material and methods. Data on 96 children with CD and 235 children who underwent endoscopy were compared for the prevalence and gastric histology pattern of H. pylori. Clinical presentation, laboratory and histological findings of CD children with and without H. pylori infection were compared. Results. Twenty-one subjects (21.8%) in the CD group and 56 subjects (23.8%) in the control group had H. pylori gastritis. Gastric metaplasia is higher in CD patients with H. pylori gastritis (19%) than in patients without H. pylori gastritis (1.3%) and in the control group (3.5%) (p<0.05 for all groups). Abdominal distension is more common at initial admission in CD patients with H. pylori gastritis (57.1% versus 14.6%, p<0.05). No significant difference was found between H. pylori (+) and (−) CD patients in terms of prevalence of anemia, iron deficiency and iron-deficiency anemia. Only mild duodenal histological findings were more common in H. pylori patients (57.1% versus 26.7%, p<0.05). Conclusions. CD may be associated with H. pylori gastritis, but it does not affect the clinical presentation of the disease, except for abdominal distension; CD is associated with mild duodenal lesions. A gluten-free diet improves the symptoms in all patients independently of the presence of H. pylori gastritis. Gastric metaplasia increases in the presence of H. pylori gastritis. Further prospective studies are needed to examine the clinical and histopathological outcomes of gastric metaplasia associated with H. pylori gastritis in CD patients.

Childhood cirrhosis, hepatopulmonary syndrome and liver transplantation

Abstract:  Objectives:  The hepatopulmonary syndrome (HPS) is characterized as a triad: liver disease, intrapulmonary vascular dilatatiton, and arterial hypoxemia. The aim of this study is to analyze outcome of children with HPS in liver transplant era.

Impact of liver transplantation on rate‐corrected QT interval and myocardial function in children with chronic liver disease*

Abstract:  Prolonged QTc interval (>440 ms) is a common abnormality in adult patients with CLD and has been reported to predict patient survival. In this study, 88 children who underwent evaluation for LT, including a 12‐lead electrocardiogram and echocardiogram included to determine the frequency of QTc prolongation and related factors in children with CLD and the effect of LT on these factors. Sixty‐nine healthy, age‐ and sex‐matched children served as controls. QTc interval was prolonged in 40 CLD patients (45.4%). It was found to be related to PELD score and presence of portal hypertension. Mean QTc was higher in patients who died prior to LT than in the survivors without LT. Mortality risk was increased 3.66‐fold in patients with prolonged QTc (p = 0.001, 95% CI: 2–7.2). Cox regression analysis showed that only PELD score was an independent predictor of survival (p = 0.001, β = −0.41, 95% CI: 5.58–1.82). Five of 48 transplanted children died within three months post‐transplant; QTc was not related to post‐transplant survival (p = 0.27). QTc normalized in 63.8% patients after LT. After LT, LAD, LVEF, and LVPWT decreased. In conclusion, QTc prolongation is common in children with CLD and associated with high mortality. It may be useful for assessment of the severity of CLD and for the timing for transplantation.

Chylous ascites after living related liver transplantation treated with somatostatin analog and parenteral nutrition.

Chylous ascites are the accumulation of chylomicron-rich lymphatic fluid within the peritoneal cavity, resulting from obstruction or disruption of abdominal lymphatic channels. This rare condition may be associated with neoplastic or infectious infiltration of lymphatics, with pancreatitis, and with abdominal surgery. It may occur spontaneously in 0.5% of patients with cirrhosis; but only among a few liver transplantation cases. The management of chylous ascites is controversial; the variety of described treatments include repeated paracentesis, dietary control, peritoneovenous shunting, and surgical ligation of the disrupted lymphatic channels. In this article, we report 2 cases of rapid resolution of chylous ascites after liver transplantation following 5 days of treatment using a somatostatin analog and total parenteral nutrition (TPN). A 3.5-year-old girl and a 5-year-old girl underwent living related liver transplantation for biliary atresia and hepatoblastoma, respectively. Chylous ascites, diagnosed by ascitic fluid examination, developed within the 2 weeks after transplantation in the 2 cases. Treatment by fasting, TPN, and somatostatin analog resulted in rapid resolution of the ascites within 1 week. The prevalence of chylous ascites was noted in 1.6% of children (2/119) after liver transplantation. These cases highlight the use of somatostatin analog and parenteral nutrition in chylous ascites after liver transplantation.

Successful treatment of a child having generalized Kaposi's sarcoma after living donor liver transplantation with conversion to sirolimus.

Abstract:  SRL is a new and potent immunosuppressive agent that has been successfully introduced in organ transplantation. In contrast to other immunosuppressive agents, SRL has a potent antitumor activity both in vitro and in vivo. Herein, we report a child with Kaposi’s sarcoma that was diagnosed 30 months after LDLT and treated successfully with only conversion to SRL monotherapy. KS regressed completely at the end of the first month and remained in remission during 28 months follow‐up.

Liver involvement in children with Familial Mediterranean fever

AIM Familial Mediterranean fever is characterised by recurrent, febrile, inflammatory attacks of the serosal membranes. Prolonged inflammatory response is triggered secondary to cytokine stimulation due to reduced activity of pyrin. Inflammatory cytokines play major role in the pathogenesis of acute liver injury; and chronic, recurrent cytokine production may cause chronic hepatitis/cirrhosis. We aimed to analyse liver involvement in children with Familial Mediterranean fever. PATIENTS The study included 58 patients with Familial Mediterranean fever. Patients with liver involvement were examined in detail. RESULTS Liver involvement was seen in 11 of 58 patients (18.9%). Two patients (3.4%) had abnormal liver enzymes during the diagnostic evaluation, whilst 9 patients (15.5%) were admitted with the features of liver diseases, and had final diagnosis of Familial Mediterranean fever (2 had Budd-Chiari syndrome, 5 had chronic hepatitis/cirrhosis, 2 had acute hepatitis). None of the demographic factors or laboratory findings was different between the patients with or without liver involvement M694V allele was more common in patients with liver involvement but did not reach significant difference (50% vs. 33.6%, p=0.21). All the patients showed clinical and laboratory improvement after colchicine. CONCLUSION Paediatric hepatologists must keep Familial Mediterranean fever in mind in the patients with cryptogenic hepatitis/cirrhosis especially in regions where hereditary inflammatory diseases are common.

Liver transplantation for acute liver failure due to toxic agent ingestion in children

Abstract:  ALF is characterized by sudden onset, impaired liver function, jaundice and encephalopathy, without previous liver disease. We analyzed the patients who underwent LT due to toxic agent induced ALF to raise community awareness about preventing the toxic agent induced ALF. Five children (three boys, two girls) underwent LT due to toxic agent ingestion. Toxic agents were mushroom poisoning (n = 2), Datura stramonium (n = 1), yellow phosphorous (n = 1) and INH (n = 1). On admission, one patient had stage IV, two had stage III and two had stage II hepatic encephalopathy but worsened during the follow‐up. One patient had renal failure, and three patients required mechanical ventilation. Three patients underwent LRLT and others from a DD. Post‐operative complications were managed by supportive managements successfully, and overall all the patients are alive (100% survival) without any organ sequelae. Although outcome of these patients are excellent, ALF may be prevented in these cases by educating the public about consuming mushrooms and toxic effects of wild plants, prohibiting fireworks and serial liver enzyme measurements after initiating INH.

Inflammatory bowel disease in Turkish children

BackgroundThis study was undertaken to evaluate demographics, clinical manifestations, laboratory findings and outcomes of children with inflammatory bowel disease (IBD) in Turkey.MethodsWe analyzed the medical records of 127 children diagnosed with IBD (under 18 years old) between January 2004 and January 2012 in 8 pediatric gastroenterology centers.ResultsOf the 127 patients, 90 (70.9%) suffered from ulcerative colitis (UC), 29 (22.8%) from Crohn’s disease (CD), and 8 (6.3%) from IBD unclassified. The mean age of the 127 patients was 11.6±4.1 years, and 11.8% of the patients were below 5 years old. Of the patients, 49.6% were male, and males were more predominant in patients with CD than in those with UC (72.4% vs. 42.2%, P=0.008; a male/female ratio of 2.62 in CD, P=0.0016). Approximately one fifth of the patients had extra-intestinal manifestations and 13.3% of the patients had associated diseases. Extraintestinal manifestations and associated diseases were more common in early onset disease [P=0.017, odds ratio (OR)=4.02; P=0.03, OR=4.1]. Of the patients, 15% had normal laboratory parameters including anemia, high platelet count, hypoalbuminemia, hypoferritinemia, and high sedimentation rate. Area under receiver operation characteristics was used to predict pancolitis in patients with UC. The values of C-reactive protein, sedimentation rate and pediatric ulcerative colitis activity were 0.61 (P=0.06), 0.66 (P=0.01) and 0.76 (P=0.0001), respectively. Four (4.4%) patients with UC underwent colectomy, and finally two (1.5%, 95% confidence interval: 0-3.7%) patients died from primary disease or complications.ConclusionsIBD is an increasing clinical entity in Turkey. Features of IBD are similar to those in other populations, but prospective multicenter studies are needed to analyze the true incidence of IBD in Turkish children.

An autoimmune disease refractory to immunosuppressive regimens: Celiac disease diagnosed long after liver transplantation

CD is defined as T‐lymphocyte‐mediated gluten sensitivity. Although CD is known to affect the small intestine, it is nonetheless a multisystem disorder. Liver involvement in CD may vary from isolated hypertransaminasemia to cirrhosis. Because CD is an inappropriate immune response to gluten proteins, strict gluten‐free diet is the principal therapy, along with management of liver dysfunction. In patients who fail to respond to a gluten‐free diet, immunosuppressive drugs may improve intestinal inflammatory activity in untreated CD. The present case report is of a 25‐yr‐old woman with diarrhea lasting several weeks. The patient had received a liver transplant 13 yr earlier, and presented with cryptogenic cirrhosis diagnosed as CD. This appears to be the first case of its kind in which a pediatric long‐term liver transplant patient presents with diarrhea eventually diagnosed as CD whose diet included gluten, and who was treated by an immunosuppressive drug regimen. Because of the normalization of CD‐related antibodies in the post‐transplantation period without gluten restriction, CD should be part of a list of diagnostic possibilities in liver transplant patients presenting with diarrhea of unknown etiology.