F. Cirillo

Serum transaminases in children with Wilson's disease.

Objectives: The response of serum transaminase levels to penicillamine and zinc treatment in Wilson’s disease is poorly understood. The aim of this multicenter retrospective study was to evaluate transaminase levels after penicillamine and zinc treatment in children with Wilson’s disease. Patients and Methods: One hundred and nine patients with Wilson’s disease (median age at diagnosis, 7.2 years; range, 1 to 18 years), treated for at least 12 months and observed in the last 20 years at 11 Paediatric Departments were studied. Clinical, laboratory and histologic features at diagnosis and initial treatment were recorded. Efficacy parameters were normalization of serum transaminase level and improved clinical and/or laboratory signs. One hundred and two patients had clinical or laboratory signs of liver disease. Results: Fifty-six of 87 patients (64%) given penicillamine normalized serum alanine aminotransferase (ALT) levels within a median of 17 months (range, 2 to 96 months). Of the 29 patients with persistent hyper-ALT, 17 (59%) switched to zinc; only four of these normalized ALT on zinc within a median period of 38 months (range, 7 to 48 months). Eleven (50%) of the 22 patients given zinc alone normalized ALT within a median period of 6 months (range, 1 to 36 months). Of the 11 patients with persistent hyper-ALT, five switched to penicillamine. Three of the five normalized ALT within a median period of 6 months (range, 6 to 9 months). Overall, in penicillamine-treated and zinc-treated patients with persistent hypertransaminasemia, ALT decreased from a basal median of 236 IU/L (range, 54 to 640 IU/L) to a median of 78 (range, 46 to 960 IU/L) at the end of follow-up (P = 0.0245). Poor compliance was suspected in only 10% of cases. No predictive factor of persistent hypertransaminasemia was identified. Liver disease did not worsen in any patient during the study. Conclusions: Although the efficacy of penicillamine and zinc is well documented, it is notable that a subset of children with Wilson’s disease-related liver disease (36%) had hypertransaminasemia despite appropriate treatment with penicillamine or zinc.

Hypertransaminasemia in childhood as a marker of genetic liver disorders

BackgroundThe widespread use of routine biochemical assays has led to increased incidental findings of hypertransaminasemia. We aimed to evaluate the prevalence of different causes of raised aminotransferase levels in children referred to a university department of pediatrics.MethodsWe investigated 425 consecutive children (age range, 1–18 years) with isolated hypertransaminasemia. All patients had raised aminotransferase levels on at least two occasions in the last month before observation. Cases due to major hepatotropic viruses were excluded.ResultsDuring the first 6 months of observation, 259 children showed normalized liver enzymes. Among the remaining 166 patients with hypertransaminasemia lasting for more than 6 months, 75 had obesity-related liver disease; 51, genetic disorders; 7, autoimmune hepatitis; 5, cholelithiasis; 3, choledochal cyst; and 3, celiac disease. Among the 51 children with genetic disorders, 18 had Wilson disease; 14, muscular dystrophy; 4, alpha-1-antitrypsin deficiency; 4, Alagille syndrome; 4, hereditary fructose intolerance; 3, glycogen storage disease (glycogenosis IX); 2, ornithine transcarbamylase deficiency; and 2, Shwachman’s syndrome. In 22 children, the hypertransaminasemia persisted for more than 6 months in the absence of a known cause.ConclusionsGenetic disease accounted for 12% of cases of isolated hypertransaminasemia observed in a tertiary pediatric department. A high level of suspicion is desirable for an early diagnosis of these disorders, which may present with isolated hypertransaminasemia and absence of typical clinical signs.

Fulminant autoimmune hepatitis in a girl with 22q13 deletion syndrome: a previously unreported association.

We report a 7-year-old girl with 22q13 deletion syndrome, 46,XX,Ish del(22)(q13.3)(ARSA-; D22S1726), who developed a fulminant autoimmune hepatitis requiring orthotopic liver transplantation. Recently, it has been suggested that the Shank3 gene product, whose deficiency is responsible for the features observed in this syndrome, could play a role in immunological response. Despite an increased incidence of respiratory infections, autoimmune diseases have thus far not been reported in patients with this syndrome. This is the first case of fulminant autoimmune hepatitis associated with the 22q13 deletion syndrome. The possible relationships between immune system dysfunctions peculiar of this syndrome and autoimmune hepatitis are discussed.

Pediatric Chronic Intestinal Failure in Italy: Report from the 2016 Survey on Behalf of Italian Society for Gastroenterology, Hepatology and Nutrition (SIGENP)

Background: Intestinal failure (IF) is the reduction in functioning gut mass below the minimal level necessary for adequate digestion and absorption of nutrients and fluids for weight maintenance in adults or for growth in children. There is a paucity of epidemiologic data on pediatric IF. The purpose of this study was to determine the prevalence, incidence, regional distribution and underlying diagnosis of pediatric chronic IF (CIF) requiring home parenteral nutrition (HPN) in Italy. Methods: Local investigators were selected in 19 Italian centers either of reference for pediatric HPN or having pediatric gastroenterologists or surgeons on staff and already collaborating with the Italian Society for Pediatric Gastroenterology, Hepatology and Nutrition with regard to IF. Data requested in this survey for children at home on Parenteral Nutrition (PN) on 1 December 2016 included patient initials, year of birth, gender, family’s place of residence and underlying diagnosis determining IF. Results: We recorded 145 CIF patients on HPN aged ≤19 years. The overall prevalence was 14.12/million inhabitants (95% CI: 9.20–18.93); the overall incidence was 1.41/million inhabitant years (95% CI: 0.53–2.20). Conclusion: Our survey provides new epidemiological data on pediatric CIF in Italy; these data may be quantitatively useful in developing IF care strategy plans in all developed countries.

Successful Use of Ursodeoxycholic Acid in Nodular Regenerative Hyperplasia of the Liver

Objective: To report, to our knowledge, the first case of a patient with nodular regenerative hyperplasia of the liver (NRHL) associated with portal hypertension in whom ursodeoxycholic acid (UOCA) therapy had a therapeutic effect on liver enzymes and was associated with nonprogression of portal hypertension. Case Summary: A symptom-free 13-year-old boy was hospitalized for splenomegaly and thrombocytopenia identified during a routine check-up. Infectious, autoimmune, and neoplastic causes were ruled out. Two years later, laboratory findings revealed high levels of aminotransferases and γ-glutamyltransferase (GGT), thrombocytopenia, and neutropenia. Ultrasound scanning of the abdomen confirmed portal hypertension. Results of liver pathology studies showed diagnostic features of NRHL Given the biochemical evidence of cholestasis, UDCA was administered, with an initial dosage of 10 mg/kg/day that was progressively increased to 20 mg/kg/day (1800 mg/day). After 5 months of treatment, GGT and then aminotransferase levels normalized and remained within normal limits in the following months. With arbitrary withdrawal of UDCA after 30 months of therapy, a rapid increase in transaminase levels was observed. Prompt reinstitution of UOCA was followed by sustained normalization of liver enzymes. Laboratory and sonographic signs of portal hypertension remained stable and tended to improve during UDCA therapy, as demonstrated by regularization of the mean portal vein flow velocity, reduction of the congestion index, progressive increase of the platelet count, and improvement of the esophagogastroscopy pattern. Discussion: NRHL is a rare disease that is characterized by multiple regenerative nodules in the hepatic parenchyma that may lead to noncirrhotic portal hypertension. No specific treatment is available, and management of patients with a primary form of NRHL consists mainly of treating the complications of portal hypertension. In our patient, UDCA therapy was followed by a prompt reduction and sustained normalization of liver enzyme levels and no progression of portal hypertension throughout the follow-up period. Conclusions: Since in this patient with primary NRHL, ongoing UDCA administration resulted in improved biochemical and portal hypertension markers, this therapy can be considered in cases of NRHL associated with abnormalities of liver enzymes.

Hepatic steatosis is uncommon in children with chronic hepatitis B.

BACKGROUND Differently from chronic hepatitis C, factors associated with hepatic steatosis in children with chronic hepatitis B are not clearly elucidated. OBJECTIVE Aim of this study was to investigate prevalence of steatosis at liver biopsy in HBV-infected children. STUDY DESIGN A retrospective study including 56 children with chronic hepatitis B undergoing liver biopsy at median age of 8.1 years. In all patients demographic, anthropometric, clinical and laboratory data were evaluated at the time of liver biopsy. RESULTS Steatosis was present in 2 (4%) children. BMI was significantly higher in 2 patients with steatosis compared with those without steatosis. Demographic, biochemical and virological parameters did not differ between children with and those without steatosis. CONCLUSIONS Liver steatosis in HBV-infected children seems to be related to obesity and metabolic factors rather than to viral factors. Detection of steatosis in non-obese children with HBV infection requires a careful investigation to rule out other causes of fatty liver.

Children with chronic hepatitis C: what future?

cise capacity does not necessarily require “strict monitoring ensured by a cardiologist”. In our study, we performed maximal symptomlimited treadmill testing in 37 individuals with NAFLD without adverse events, despite the fact that most patients manifested several comorbidities. Obviously, appropriate management of comorbidities will clearly reduce the risk of an adverse event during physical activity participation of submaximal exertion. Requiring cardiologist supervision for physical activity participation adds another potentially significant barrier (and expense) for these patients to adopt and maintain a regular exercise program. We certainly agree that our lack of appropriate control groups (nonobese, albeit with abdominal obesity, one with both insulin resistance [IR] and NAFLD and the other with only IR) is a limitation of this study. However, the intent of this initial study was to determine whether objective measures of health-related fitness and physical activity differ with severity of NAFLD. Furthermore, in practice, it would be quite difficult to include such control groups of meaningful size for the following reasons: (1) nonobese patients with IR and NAFLD are relatively uncommon and (2) patients with IR without NAFLD frequently lack histological confirmation.4,5 Indeed, reduced lean mass, small cross-sectional muscle fiber area, and increased triglyceride deposition in skeletal muscle in conjunction with dysfunctional/reduced lipolysis can result in reduced cardiorespiratory fitness. However, it is unknown whether these adaptations take place as a result of reduced physical activity, NAFLD, or both. We agree entirely that for exercise to be successfully implemented as a therapeutic strategy there is a strong need for individualized exercise prescription. As such, we have recently submitted a manuscript for publication that reviews the evidence for exercise training as a therapy for NAFLD and also presents the principles for prescribing exercise as a therapeutic intervention. Future studies will endeavor to better determine the relative contributions of IR, adiposity, and NAFLD to reduced fitness. JOANNE B. KRASNOFF, PH.D.1 NATHAN M. BASS, M.D., PH.D.2 PATRICIA L. PAINTER, PH.D.3 RAPHAEL B. MERRIMAN, M.B.4 1University of California San Francisco, Clinical and Translational Science Institute Clinical Research Center, Exercise Physiology & Body Composition Laboratory, San Francisco, CA 2University of California San Francisco, Division of Gastroenterology, San Francisco, CA 3University of Minnesota, Division of Renal Diseases and Hypertension, Minneapolis, MN 4California Pacific Medical Center and Research Institute, Division of Gastroenterology, San Francisco, CA

CO20 RAPAMYCINE AS IMMUNOSUPPRESSIVE TREATMENT IN PEDIATRIC LIVER TRANSPLANT RECIPIENTS WITH POLYMORPHIC, POLYCLONAL, EBV-RELATED POST-TRANSPLANT LYMPHOPROLIFERATIVE DISEASE (PTLD)

for diagnosis of SC in children through a retrospective case-control study. Patients and Methods: ERCs and MRCs of 7 children and adolescents (median age 9, range 7−20 years) with SC and 17 controls (median age 6, range 2 months to 29 years) with liver disease without macroscopic biliary abnormalities, were reviewed in a blinded, random and independent way. Only patients who underwent both examinations within a 6-months slot were included. One radiologist evaluated both ERCs and MRCs and one interventional endoscopist independently reviewed only ERCs. A common and previously validated classification system was used to score all records. Reviewers did not receive any demographic or clinical or laboratory information. Diagnosis of SC was established on the basis of history, laboratory data, radiologic examinations and clinical course and was used as gold standard to compare ERC and MRC diagnostic accuracy. Readers independently recorded: image quality, delineation of the first-, second-, third-, and fourth-order intrahepatic bile ducts, the extrahepatic bile duct, and the gallbladder (non depiction, fair for delineation of less than 90%, good for delineation of at least 90%, excellent for complete delineation); presence or absence of SC and their level of certainty for their diagnosis, recorded with the use of a 5-point rating system (definitely absent, probably absent, equivocal, probably present, definitely present); and they scored the bile duct images by using a classification system validated for PSC patients. Results: Overall image quality was graded as very good in 57% of MRC cases and in 71% of ERC cases; difference was not statistically significant (p = 0.24) although the probability for MRC to be diagnostic increased with age of patient. Depiction of first, second and fourth order intrahepatic bile ducts was better in ERC (p = 0.004, 0.02 and 0.023 respectively), while depiction of extrahepatic bile ducts was comparable (p = 0.052) and depiction of gallbladder was even better in MRCs. Diagnostic accuracy of MRC and ERC resulted very high, without statistically significant difference (p = 0.61). Agreement between MRC and ERC defined as Kendall’s tau-b value was considered good (0.65) even both interobserver readers of ERCs (0.61). Conclusion: Despite an overall better depiction of biliary tree in ERC, especially in younger age, ERC and MRC are comparable for the diagnosis of SC in children. These data support MRC as the first imaging approach in children with suspected SC.