- Email: [email protected]
433 SERUM ADIPOKINES CONCENTRATION IN CHILDREN WITH NON-ALCOHOLIC FATTY LIVER DISEASE
07: PEDIATRIC HEPATOLOGY − INHERITED DISEASES OF THE LIVER 432 CA19.9 AS A DIAGNOSTIC MARKER FOR HEPATIC CYST INFECTION IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE Z. Hassoun1 , E. Goffin2 , Y. Pirson2 , O. Devuyst2 , N. Kanaan2 . 1 Division of Gastroenterology, 2 Division of Nephrology, Cliniques Universitaires Saint-Luc (Universit´e Catholique de Louvain), Brussels, Belgium E-mail: [email protected] Background and Aims: Hepatic cyst infection is a serious complication in autosomal dominant polycystic kidney disease (ADPKD) patients, with a potentially unfavourable outcome if diagnosis and treatment are delayed. The diagnosis of hepatic cyst infection in ADPKD is difficult because symptoms and imaging techniques can be non-specific. Furthermore, there is no specific blood marker for this infection. We hypothesized that Carbohydrate antigen 19.9 (CA19.9), secreted by the biliary epithelium lining the cysts, is overproduced in case of cyst infection. Methods: CA19.9 was measured in the serum of three kidney transplant ADPKD patients who presented with hepatic cyst infection, and in the cystic fluid of 2 of them. CA19.9 was also measured in the serum of 19 consecutive ADPKD and 22 non-ADPKD renal transplant recipients. CA19.9 immunostaining was done in 5 polycystic livers of ADPKD patients and compared with control normal livers. Results: Three ADPKD patients were diagnosed with hepatic cyst infection based on clinical grounds, biological inflammation, and positron emission tomography scan. All had at that time markedly elevated serum CA19.9 levels (963, 2975, and 601 U/ml respectively; N < 35 U/ml). Two patients required cystic fluid drainage. CA19.9 level was extremely elevated in the cystic fluid (728,200 and 124,200 U/ml respectively). With clinical improvement, a striking decrease in serum CA19.9 level was observed in all patients. Serum CA19.9 from 19 consecutive asymptomatic ADPKD patients with liver cysts was significantly higher than in controls (median: 29.55 vs. 10.3 U/ml, p < 0.001). Bilirubin level was normal in all patients of both groups. Immunostaining for CA19.9 revealed strong staining in biliary tree epithelia and cysts of human polycystic livers, significantly more intense than in normal livers. Conclusions: CA19.9 is synthesized by the biliary cystic epithelium and can be elevated in ADPKD patients with liver cysts. A marked increase in serum CA19.9 level is observed with liver cyst infection. Our data strongly suggest that the serum level of CA19.9 can be a diagnostic tool for hepatic cyst infection, contributing to early diagnosis and appropriate management. Measurement of baseline serum CA19.9 level in ADPKD patients could serve as a reference value. 433 SERUM ADIPOKINES CONCENTRATION IN CHILDREN WITH NON-ALCOHOLIC FATTY LIVER DISEASE D. Lebensztejn1 , E. Skiba1 , D. Kowalczuk2 , E. Tarasow3 , A. Romanowska1 , I. Werpachowska1 , M. Kaczmarski1 . 1 Department of Pediatrics, Gastroenterology and Allergology, Medical University of Bialystok, 2 Department of Radiology, Children Teaching Hospital, 3 Department of Radiology, Medical University of Bialystok, Bialystok, Poland E-mail: [email protected] Background and Aims: Non-invasive markers that predict both fatty liver in obese children and the degree of liver steatosis and thus could replace liver biopsy are lacking. Adipokines which are involved in pathogenesis of non-alcoholic fatty liver disease (NAFLD) seem to be promising. Therefore the aim of the study was to evaluate serum adipokines levels in obese children with NAFLD. Methods: Forty-five obese (BMI > 97pc) children, age range 7−17, mean 12 years, were admitted to our Department with suspected liver disease (hepatomegaly, and/or ultrasonographic liver brightness and/or increased ALT activity). Viral hepatitis (HBV, HCV), autoimmune and metabolic liver diseases (Wilson’s disease, alpha 1 antitrypsin deficiency) were excluded. Fasting serum levels of TNFa, sTNFR1, sTNFR2, IL-6, sILR and adiponectin were determined (ELISA, R&D Systems Inc., USA). The
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degree of liver steatosis in ultrasound (USG) was graded according to Saverymuttu et al. Advanced liver steatosis was defined as a score >1. 1 HMR spectroscopy was performed with 1.5 T scanner and with PRESS sequency; total lipid concentration was assessed in relative units in comparison to unsupressed water signal. ROC analysis was used to calculate the power of the assays to detect fatty liver or advanced steatosis (AccuROC, Canada). Results: NAFLD was confirmed in 32 children by USG and in 33 patients by 1 HMRS. The ability of serum TNFa (cut-off 1.89pg/ml, Se=82%, Sp = 58%) and adiponectin (cut-off 8.3 mg/ml, Se=88%, Sp = 50%) to differentiate obese children with fatty liver from those without steatosis was significant (AUC=0.7071, p = 0.036; AUC=0.7083; p = 0.034 respectively). Adiponectin > 6.5 mg/ml had a sensitivity of 92% and a specificity of 53%; AUC=0.7368, p = 0.025 and IL-6 >1.21 pg/ml had a sensitivity of 92% and a specificity of 53%; AUC=0.7308, p = 0.029 in predicting advanced liver steatosis. All other markers did not allow a useful prediction. Conclusion: Adiponectin seems to be the most suitable non-invasive biomarker in predicting both advanced liver steatosis in children with NAFLD and fatty liver in obese children. 434 CHARACTERIZATION OF ATP8B1 GENE MUTATIONS AND A HOT LINKED MUTATION FOUND IN CHINESE CHILDREN WITH PROGRESSIVE INTRAHEPATIC CHOLESTASIS AND LOW GGT L.Y. Liu, X.H. Wang, J.-S. Wang. Children’s Hospital of Fudan University, Shanghai, China E-mail: [email protected] Aims: To elucidate the role and characteristics of ATP8B1 gene mutations in Mainland Chinese with progressive intrahepatic cholestasis and low GGT. Methods: ABCB11 gene was first sequenced in 24 children who presented with progressive intrahepatic cholestasis and low GGT and admitted in a tertiary pediatric hospital in eastern China to exclude BSEP deficiency. Afterwards, all the encoding exons and their flanking areas of ATP8B1 gene were sequenced in the remaining 19 patients in whom only one or no mutations of ABCB11 were found. Results: 10 mutations of ATP8B1 gene were found in 9 patients. All of them were novel except for mutation I694N and mutation R952X. Linked P209T and IVS6+5T>G mutation was found in 4 of 9 patients, including 2 homozygotes and 2 heterozygotes. Liver biopsy had been performed in 6 patients with ATP8B1 mutations and 5 with ABCB11 mutations. Variety portal fibrosis was showed in 2 patients with ATP8B1 mutations and 4 patients with ABCB11 mutations. Giant cell transformation was demonstrated in one patient with ATP8B1 mutations and in 4 patients with ABCB11 mutations. Conclusion: ATP8B1 gene mutations play an important role in Chinese progressive intrahepatic cholestasis patients with low GGT. The linked mutation P209T and IVS6+5T>G is a hot mutation. Histological examination may be helpful in differentiating FIC1- from BSEP-related disease. 435 PORTAL HYPERTENSION AND HEPATIC VENOUSVENOUS COMMUNICATIONS IN PATIENTS WITH BILIARY ATRESIA R. Miraglia1 , A. Luca1 , S. Riva1 , M. Spada1 , L. Maruzzelli1 , B. Gridelli1 , J. Bosch2 . 1 Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IsMeTT), Palermo, Italy; 2 Hepatic Hemodynamic Laboratory, Liver Unit Hospital Clinic, IDIBAPS and Ciberehd, Barcelona, Spain E-mail: [email protected] Aim: Approaches to the management of portal hypertension in children are anedoctical and pediatricians have difficulty in the management of this clinical problem. Aim of this study is to review our preliminary experience with Hepatic Vein Portal Pressure Gradient (HVPG) measurement in pediatric patients with end stage liver disease (ESLD). Materials and Methods: Data of 11 pediatric patients with ESLD undergoing hepatic vein catheterization and HVPG measurement were
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degree of liver steatosis in ultrasound (USG) was graded according to Saverymuttu et al. Advanced liver steatosis was defined as a score >1. 1 HMR spectroscopy was performed with 1.5 T scanner and with PRESS sequency; total lipid concentration was assessed in relative units in comparison to unsupressed water signal. ROC analysis was used to calculate the power of the assays to detect fatty liver or advanced steatosis (AccuROC, Canada). Results: NAFLD was confirmed in 32 children by USG and in 33 patients by 1 HMRS. The ability of serum TNFa (cut-off 1.89pg/ml, Se=82%, Sp = 58%) and adiponectin (cut-off 8.3 mg/ml, Se=88%, Sp = 50%) to differentiate obese children with fatty liver from those without steatosis was significant (AUC=0.7071, p = 0.036; AUC=0.7083; p = 0.034 respectively). Adiponectin > 6.5 mg/ml had a sensitivity of 92% and a specificity of 53%; AUC=0.7368, p = 0.025 and IL-6 >1.21 pg/ml had a sensitivity of 92% and a specificity of 53%; AUC=0.7308, p = 0.029 in predicting advanced liver steatosis. All other markers did not allow a useful prediction. Conclusion: Adiponectin seems to be the most suitable non-invasive biomarker in predicting both advanced liver steatosis in children with NAFLD and fatty liver in obese children. 434 CHARACTERIZATION OF ATP8B1 GENE MUTATIONS AND A HOT LINKED MUTATION FOUND IN CHINESE CHILDREN WITH PROGRESSIVE INTRAHEPATIC CHOLESTASIS AND LOW GGT L.Y. Liu, X.H. Wang, J.-S. Wang. Children’s Hospital of Fudan University, Shanghai, China E-mail: [email protected] Aims: To elucidate the role and characteristics of ATP8B1 gene mutations in Mainland Chinese with progressive intrahepatic cholestasis and low GGT. Methods: ABCB11 gene was first sequenced in 24 children who presented with progressive intrahepatic cholestasis and low GGT and admitted in a tertiary pediatric hospital in eastern China to exclude BSEP deficiency. Afterwards, all the encoding exons and their flanking areas of ATP8B1 gene were sequenced in the remaining 19 patients in whom only one or no mutations of ABCB11 were found. Results: 10 mutations of ATP8B1 gene were found in 9 patients. All of them were novel except for mutation I694N and mutation R952X. Linked P209T and IVS6+5T>G mutation was found in 4 of 9 patients, including 2 homozygotes and 2 heterozygotes. Liver biopsy had been performed in 6 patients with ATP8B1 mutations and 5 with ABCB11 mutations. Variety portal fibrosis was showed in 2 patients with ATP8B1 mutations and 4 patients with ABCB11 mutations. Giant cell transformation was demonstrated in one patient with ATP8B1 mutations and in 4 patients with ABCB11 mutations. Conclusion: ATP8B1 gene mutations play an important role in Chinese progressive intrahepatic cholestasis patients with low GGT. The linked mutation P209T and IVS6+5T>G is a hot mutation. Histological examination may be helpful in differentiating FIC1- from BSEP-related disease. 435 PORTAL HYPERTENSION AND HEPATIC VENOUSVENOUS COMMUNICATIONS IN PATIENTS WITH BILIARY ATRESIA R. Miraglia1 , A. Luca1 , S. Riva1 , M. Spada1 , L. Maruzzelli1 , B. Gridelli1 , J. Bosch2 . 1 Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IsMeTT), Palermo, Italy; 2 Hepatic Hemodynamic Laboratory, Liver Unit Hospital Clinic, IDIBAPS and Ciberehd, Barcelona, Spain E-mail: [email protected] Aim: Approaches to the management of portal hypertension in children are anedoctical and pediatricians have difficulty in the management of this clinical problem. Aim of this study is to review our preliminary experience with Hepatic Vein Portal Pressure Gradient (HVPG) measurement in pediatric patients with end stage liver disease (ESLD). Materials and Methods: Data of 11 pediatric patients with ESLD undergoing hepatic vein catheterization and HVPG measurement were