Search

Neonatal and infantile cholestasis (NIC) can represent the onset of a surgically correctable disease and of a genetic or metabolic disorder worthy of medical treatment. Timely recognition of NIC and identification of the underlying etiology are paramount to improve outcomes. Upon invitation by the Italian National Institute of Health (ISS), an expert working grouped was formed to formulate evidence-based positions on current knowledge about the diagnosis of NIC. A systematic literature search was conducted to collect evidence about epidemiology, etiology, clinical aspects and accuracy of available diagnostic tests in NIC. Evidence was scored using the GRADE system. All recommendations were approved by a panel of experts upon agreement of at least 75% of the members. The final document was approved by all the panel components. This position document summarizes the collected statements and defines the best-evidence diagnostic approach to cholestasis in the first year of life.

Background Cyclosporine (CSA) is an alternative treatment for autoimmune hepatitis (AIH), however, its unknown long-term safety and efficacy have limited its use. Aims Examine the long-term outcome of children and young adults with AIH treated with CSA for at least 4 years. Methods Twenty patients were included in this retrospective study: 15 with classical AIH and 5 with autoimmune hepatitis/autoimmune sclerosing cholangitis overlap syndrome (ASC). CSA was administered as first (12 patients) or second-line (8 patients) treatment, alone or in combination with azathioprine or mycophenolate mofetil and/or prednisone. Results CSA determined initial clinical and biochemical remission in all patients. At the end of follow-up (median 8.6; range 4–20.4 years), all patients are alive with their native liver; 15 in complete remission (75%), 2 with incomplete response to treatment and 3 listed for liver transplant. Side effects were mild and transitory after dose tapering or, in 1 case, after CSA withdrawal. Hypertrichosis and moderate gingival hyperplasia were the most frequent. Two patients presented mild transient glomerular filtration rate (GFR) reduction. Median GFR at the beginning and end of treatment was not statistically different for all patients. Conclusions CSA was effective and safe in the long-term treatment of our cohort of patients with AIH, tailoring the treatment remains key-points during CSA administration.

Noonan Syndrome (NS) is characterized by short stature, typical facial dysmorphology and congenital heart defects. The incidence of NS is estimated to be between 1:1000 and 1:2500 live births. The syndrome is transmitted as an autosomal dominant trait. In approximately 50% of cases, the disease is caused by missense mutations in the PTPN11 gene on chromosome 12, resulting in a gain of function of the non-receptor protein tyrosine phosphatase SHP-2 protein. Autoimmune Hepatitis (AIH) is a cryptogenic, chronic and progressive necroinflammatory liver disease. Common features of AIH are hypergammaglobulinemia (IgG), presence of circulating autoantibodies, histological picture of interface hepatitis and response to immunosuppressant drugs. Conventional treatment with Prednisone and Azathioprine is effective in most patients. We describe the case of a 6 years-old girl with Noonan Syndrome and Autoimmune Hepatitis type 1. Molecular analysis of PTPN11 gene showed heterozygous mutation c.923A>G (Asn308Ser) in exon 8. Though association between NS and autoimmune disorders is known, this is the second case of association between Noonan Syndrome and Autoimmune Hepatitis type 1 described in literature. In the management of NS, an accurate clinical evaluation would be recommended. When there is a clinical suspicion of autoimmune phenomena, appropriate laboratory tests should be performed with the aim of clarifying whether the immune system is involved in NS. We think that autoimmunity represents a characteristic of NS, even if the etiopathogenesis is still unknown.

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.

Objective To assess the outcome of giant cell hepatitis combined with autoimmune hemolytic anemia in early childhood. Study design We report on 16 children with this disease evaluated over a 28-year period. Results Children (nine boys; median age, 6 months) presented with jaundice, hepatomegaly, elevated aminotransferases, a positive Coombs test, and diffuse giant-cell transformation of hepatocytes on histology. Treatment with prednisone and azathioprine, plus, in three children, cyclosporine, resulted in complete remission in eight, partial remission in six, and failure in two. Relapses of hepatitis and/or anemia occurred in 11 and 10 children, respectively, requiring prolonged high levels of immunosuppression, and splenectomy or Rituximab, respectively. Treatment was stopped after a mean duration of 6 years, with no relapse, in seven children, with a median follow-up of 14 years. One child is alive 9 years after liver transplantation. Four children died of sepsis or multiple organ failure. Conclusions Giant cell hepatitis combined with autoimmune hemolytic anemia requires rigorous treatment. Immunosuppressive therapy results in remission in most cases. A complete cure can be expected after several years of intensive treatment. Liver transplantation may be associated with prolonged survival.

Objective: To analyze the details of our clinical series of 15 children with eosinophilic esophagitis (EE), focusing the attention on the main clinical manifestations. and endoscopic features in order to better understand the diversity of the disease, thereby improving clinical diagnosis and treatment. Patients and methods: In the last 5 years, EE was diagnosed in 15 patients (11 males, age range 2-18 years, mean age 10.5 years). All patients underwent to an upper endoscopy with multiple biopsy specimens of the esophagus under conscious sedation. EE was defined as greater than 20 eosinophils per high power field after conventional anti-reflux treatment. All patients were tested for food allergies. Results: All studied patients were referred to our Unit after failure of antireflux therapy. The presenting symptoms were dysphagia (63%), vomiting (36%), food bolus impaction (20%), epigastric pain (18%) and chronic anemia (9%). Dysphagia and vomiting were the most common symptom, especially in the younger children, while food bolus impaction for esophageal stenosis occurred in 3 older patients. Endoscopic findings were always aspecific: normal esophagus in 6 cases (40%), low grade hyperemia in 5 (33%); high grade hyperemia in 1 (7%) and esofageal stricture in 3 (20%). The majority of allergic tests resulted negative. All patients were successively treated with swallowed corticosteroids. After 3-4 months, the corticosteroid was substituted by leukotriene receptor antagonists. Corticosteroid therapy was effective in all cases, with a rapid regression of symptoms in all children. However, after the suspension of medications, all children presented a recurrence of the disease, therefore were treated by montelukast as maintenance treatment. A mean follow-up of 2 years was based on periodical clinical evaluations and by repeated endoscopies and biopsies. Conclusions: EE is an emerging clinical entity, probably still underestimated, characterized by age-related symptoms. It has to be always ruled out in case of important clinical manifestations in the absence of a clear GERD condition, in order to avoid major esophageal complications. Montelukast offer benefit as maintenance treatment.

C. Centenari a , M. Fabreb, M. Sciveres c , E. Jacquemind , G. Maggiore a aClinica Pediatrica IIa, Gastroenterologia ed Epatologia, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy; bDepartment of Pathology, University Hospital of Bicetre, AP-HP, University Paris Sud 11, Paris, France; cPediatric Hepatology and Pediatric Liver Transplantation, UPMC Ismett, Palermo, Italy; dPediatric Hepatology University Hospital of Bicetre, AP-HP, University Paris Sud 11, Paris, France

1 d Diagnosis of cholesterol ester storage disease (CESD) as suggested in a 5-year-old girl by a liver biopsy perormed because of a large hepatomegaly of fortuitous nding, and confirmed by the measurement of lysosomal cid lipase activity in cultured skin fibroblasts. The patient eveloped portal hypertension and a new liver biopsy, hen 11-year-old, showed micronodular cirrhosis with iffuse microvesicular steatosis. The child was listed for iver transplantation and received an extended right lobe raft (segments I + IV + VIII) obtained by in situ split liver rocurement from a 13-year-old donor. Histological examination of the native liver showed iffuse cirrhotic transformation, mild mixed inflammaory infiltrate, hydropic degeneration and microvesicular teatosis. A 1.4 cm non-encapsulated nodule of trabecuar hepatocellular carcinoma (HCC) (G1/G2) was identified n segment VII (Figs. 1 and 2). Patient underwent postransplant total body CT scan that excluded extra hepatic ocalizations. Post-operative -fetoprotein was normal. The atient did not received adjuvant chemotherapy and 30 onths after transplantation she is in good clinical condition, ithout evidence of HCC recurrence. CESD is a rare autosomal recessive disorder characterzed by accumulation of cholesterol esters and triglycerides n hepatocytes, adrenal cortical spongiocytes, and in histioytes. Patients with CESD may develop a progressive liver ailure necessitating liver transplantation. HCC has been described in a number of genetic and etabolic disorders in children including progressive familal intrahepatic cholestasis, Alagille syndrome, hereditary yrosinemia type I, glycogen storage diseases, alpha-1ntitrypsin deficiency, liver mitochondrial respiratory chain