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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.

Cytomegalovirus (CMV) infection is the most significant viral infection in hosts with compromised immune systems as solid organ transplant patients. Despite significant progress being made in the prevention of CMV disease in these patients, further therapeutic strategies for CMV disease and for the CMV reactivation prevention are needed. Here, we describe the outcome of the infusion of in vitro expanded CMV-reactive T-cells, taken from a healthy CMV-seropositive donor, in a liver-transplanted recipient with a refractory recurrent CMV. In this particular case, adoptive transfer of allogenic CMV-reactive T-lymphocytes resulted in the clearance of CMV infection and resolution of the pathological manifestations of the patient. In the study we also investigated circulating miRNAs, both cellular and viral, as potential biomarkers during the course of CMV infection. The results indicate that the infusion of allogenic CMV-reactive T-cells can be an effective strategy to treat CMV infection recurrence when the generation of autologous virus specific T cell clones is not possible.

Juvenile autoimmune hepatitis (JAIH) is a rare, chronic, inflammatory disease of the liver characterized by a complex interaction between genetic, immunological, and environmental factors leading to loss of immunotolerance to hepatic antigens. It affects both children and adolescents, most commonly females, and its clinical manifestations are quite variable. JAIH is progressive in nature and if left untreated may lead to cirrhosis and terminal liver failure. Although JAIH was first described almost 50 years ago, there have been few significant advances in the clinical management of these patients, both in terms of available diagnostic tools and therapeutic options. Aminotransferase activity, class G immunoglobulins and autoantibodies are the biomarkers used to diagnose AIH and monitor treatment response alongside clinical and histological findings. Despite their utility and cost-effectiveness, these biomarkers are neither an accurate expression of AIH pathogenic mechanism nor a precise measure of treatment response. Current standard of care is mainly based on the administration of steroids and azathioprine. This combination of drugs has been proven effective in inducing remission of disease in the majority of patients dramatically improving their survival; however, it not only fails to restore tolerance to hepatic autoantigens, but it also does not halt disease progression in some patients, it is often needed life-long and finally, it has deleterious side-effects. The ideal therapy should be enough selective to contrast immune-mediated live damage while preserving or potentiating the ability to develop permanent tolerance vs. pathogenic autoantigens. By reviewing the state of the art literature, this article highlights novel diagnostic and therapeutic strategies for managing pediatric AIH with a special focus on new strategies of immunotherapy. These promising tools could improve the diagnostic algorithm, more accurately predict disease prognosis, and provide targeted, individualized treatment.

Giant cell hepatitis associated with autoimmune hemolytic anemia (GCH-AHA) is a rare and severe disease characterized by autoimmune hemolysis associated with acute liver injury, histologically defined by widespread giant cell transformation. It occurs after the neonatal period, most commonly in the first year of life and uniquely affects pediatric patients. It is still poorly understood and likely underdiagnosed, although in recent years there have been advances in the understanding of its pathogenesis and the liver injury is now hypothesized to be secondary to a humoral immune mechanism. Although no laboratory test specific for the diagnosis currently exists, given its severity, it is fundamental to rule out GCH-AHA when evaluating a patient in the first year of life presenting with AHA and/or with acute liver disease of unknown etiology. While GCH-AHA is progressive in nature as other autoimmune liver disorders, it differs significantly from juvenile autoimmune hepatitis (JAIH) in that a cure can be achieved after several years of intensive treatment in a portion of patients. Conventional first line therapy consist of prednisone/prednisolone combined with azathioprine, however, several immunosuppressive drugs, commonly used in the treatment of JAIH have been tried as second line therapy, including cyclosporine, cyclophosphamide, mycophenolate mofetil, 6-mercaptopurine, calcineurin inhibitors, and sirolimus. Intravenous immunoglobulins have also been used in cases of severe liver dysfunction and/or severe anemia allowing for transitory remission. More recently treatment with B-cell depletion has been attempted in some patients and encouraging results have been reported in refractory cases. Although what constitutes optimal treatment has yet to be determined, the recent progress in the understanding of the pathogenetic mechanisms of GCH-AHA have made positive strides, cautiously pointing toward a hopeful prognosis for some of these patients.

Background Autoimmune hepatitis is a rare inflammatory disease of the liver that most frequently affects children and young adults. It is a multifactorial disease of unknown etiology, characteristically progressive in nature, and if left untreated, may lead to cirrhosis and terminal liver failure. It has been known for several decades now that immunosuppressive treatment convincingly alters the outcome of most patients with autoimmune hepatitis and as such it should be started as soon as diagnosis is made. Primary goals of treatment are: normalization of hepatocellular function, extinction of the hepatic necroinflammatory process, and maintenance of a stable remission, thus preventing progression to cirrhosis and its complications. This article aims to review old and new treatments for this rare chronic disorder, from the oldest and most frequently used treatment consisting of the association of prednisone and azathioprine, to alternative medical treatments, liver transplant and promising medical strategies currently under investigation. Result and conclusion The review will focus on the efficacy and safety profile of each drug, as well as on the published clinical experience with them in pediatric patients with autoimmune hepatitis.

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.

Background A few children with acute or chronic liver disease display histological features compatible with autoimmune hepatitis, but lack specific serological markers. Aim To describe features, management and outcome of childhood seronegative autoimmune hepatitis. Methods From 1988 to 2010, 38 children were included under the following criteria: negative virological studies, no serum autoantibodies, exclusion of other causes of liver diseases, and liver histology compatible with autoimmune hepatitis. Results Four groups were identified: (1) 12 with increased serum gamma globulin concentrations; (2) 10 with normal or low serum gamma globulins and no combined blood disease; (3) 10 with combined aplastic anemia; and (4) 6 with peripheral thrombocytopenia with/without neutropenia. Immunosuppressive treatment was associated with aminotransferases normalization in all but one child who required liver transplantation. Relapses occurred in 10 children. Lymphocytopenia was found at the time of the diagnosis of hepatitis in 13 children, 12 in groups 3 or 4. All 38 children are alive after 4–17 years, 18 still under immunosuppression. Conclusions Childhood seronegative autoimmune hepatitis includes a spectrum of disorders. Early liver histology is recommended and, if compatible with autoimmune hepatitis, immunosuppressive treatment should be started. Initial lymphocytopenia may indicate future hematological complication.

Khan Z, Sciveres M, Salis P, Minervini M, Maggione G, Cintorino D, Riva S, Gridelli B, Emma F, Spada M. Combined split liver and kidney transplantation in a three-year-old child with primary hyperoxaluria type 1 and complete thrombosis of the inferior vena cava. Pediatr Transplantation 2011: 15: E64–E70. © 2009 John Wiley & Sons A/S. Abstract: PH1 is an inborn error of the metabolism in which a functional deficiency of the liver-specific peroxisomal enzyme, AGT, causes hyperoxaluria and hyperglycolic aciduria. Infantile PH1 is the most aggressive form of this disease, leading to early nephrocalcinosis, systemic oxalosis, and end-stage renal failure. Infantile PH1 is rapidly fatal in children unless timely liver-kidney transplantation is performed to correct both the hepatic enzyme defect and the renal end-organ damage. The surgical procedure can be further complicated in infants and young children, who are at higher risk for vascular anomalies, such as IVC thrombosis. Although recently a limited number of children with IVC thrombosis have underwent successful kidney transplantation, successful multi-organ transplantation in a child with complete IVC thrombosis is quite rare. We report here the interesting and technically difficult case of a three-yr-old girl with a complete thrombosis of the IVC, who was the recipient of combined split liver and kidney transplantation for infantile PH1. Although initial delayed renal graft function with mild-to-moderate acute rejection was observed, the patient rapidly regained renal function after steroid boluses, and was soon hemodialysis-independent, with good diuresis. Serum and plasma oxalate levels progressively decreased; although, to date they are still above normal. Hepatic and renal function indices were at, or approaching, normal values when the patient was discharged 15-wk post-transplant, and the patient continues to do well, with close and frequent follow-up. This is the first report of a successful double-organ transplant in a pediatric patient presenting with infantile PH1 complicated by complete IVC thrombosis.

In a review of 382 cases of congenital portosystemic shunt, we found that presentation with neonatal cholestasis strongly predicts spontaneous closure of intrahepatic shunts (OR 8.3, 95% CI 3.4-20.2). Spontaneous closure before the 24th month of age is more likely for distal or multiple shunts, but rare for patent ductus venosus.

Juvenile autoimmune hepatitis (JAIH) is a progressive inflammatory liver disease, affecting mainly young girls, from infancy to late adolescence, characterized by active liver damage, as shown by high serum activity of aminotransferases, by elevated immunoglobulin G levels, high titers of serum non organ-specific and organ-specific autoantibodies, and by interface hepatitis on liver biopsy. It is a multifactorial disease of unknown etiology in which environmental factors act as a trigger in genetically predisposed individuals. Two types of JAIH are identified according to the autoantibody panel detected at diagnosis: AIH-1, characterized by the presence of anti-smooth muscle antibody and/or antinuclear antibody and AIH-2, by anti-liver-kidney microsomal antibody type 1 and/or by the presence of anti-liver cytosol type 1 antibody. Epidemiological distribution, genetic markers, clinical presentation and pattern of serum cytokines differentiate the two types of AIH suggesting possible pathogenetic mechanisms. The most effective therapy for AIH is pharmacological suppression of the immune response. Treatment should be started as soon as the diagnosis is made to avoid severe liver damage and progression of fibrosis. The aim of this review is to outline the most significant and peculiar features of JAIH, based largely on our own personal database and on a review of current literature.

OBJECTIVES Celiac disease (CD) is common in patients with autoimmune liver disease (AILD); however, the long-term response to treatment of patients with AILDs coexistent with CD has not been explored in detail. The aim of the present study was to analyze the features and the long-term response to immunosuppressive treatment in children with autoimmune hepatitis (AIH) associated with CD. METHODS Retrospective and prospective evaluation of patients followed at a single center. RESULTS Among 79 patients with AIH, 15 (19%) had CD (9 type 1, 3 type 2, 3 seronegative). In the group of patients with AIH and CD, female sex was significantly more represented than in the group of patients with AIH alone; also, in the former group, diagnosis was made significantly earlier (P < 0.05). All of the 15 patients on a gluten-free diet achieved sustained remission when treated with prednisone and azathioprine or cyclosporine. The mean period of follow-up was 73 months; discontinuation of therapy was attempted in 9 patients while in remission: 4 patients relapsed, 5 (33%) could definitively stop immunosuppressive treatment with a mean period of treatment-free sustained remission of 89 months (range 26-174). In the same period, treatment discontinuation, attempted in 24 of 64 patients with AIH without CD, was successful in 5 patients (8%; P < 0.05). CONCLUSIONS Patients with AIH coexisting with CD achieve treatment-free sustained remission in a significantly higher proportion, when compared with patients with AIH without CD, suggesting a possible long-term adjuvant effect of a gluten-free diet.

Wilson's disease (WD), an autosomal recessive disorder of copper transport with a broad range of genotypic and phenotypic characteristics, results from mutations in the ATP7B gene. Herein we report the results of mutation analysis of the ATP7B gene in a group of 118 Wilson disease families (236 chromosomes) prevalently of Italian origin. Using DNA sequencing we identified 83 disease-causing mutations. Eleven were novel, while twenty one already described mutations were identified in new populations in this study. In particular, mutation analysis of 13 families of Romanian origin showed a high prevalence of the p.H1069Q mutation (50%). Detection of new mutations in the ATP7B gene in new populations increases our capability of molecular analysis that is essential for early diagnosis and treatment of WD.

Autoimmune diseases of the liver and biliary tract are inflammatory diseases of unknown origin that progress spontaneously, in most cases, to severe fibrosis and cirrhosis (Maggiore et al, 2009). They are characterized by an inflammatory infiltrate in the liver tissue involving the lobule and the portal tract and, most frequently, by the presence of non-organ and liverspecific autoantibody reactivity (Mieli Vergani & Vergani, 2009). There are at least three principal disorders in humans, in which the liver damage is thought to be caused by an autoimmune mechanism: autoimmune hepatitis (AIH), where the target of the autoimmune attack is the hepatocyte, and two other conditions, autoimmune cholangitis (AIC) and primary biliary cirrhosis (PBC), where the target is the cholangiocyte. Between these three disorders exists a range of overlap of liver damage both at diagnosis and/or during the follow-up, recognized as “overlap syndrome” (Alvarez, 2006). Any autoimmune disorder may overlap with the other two. Autoimmune cholangitis may be limited, at diagnosis and during the follow-up, to the smallest intrahepatic (forth order) bile ducts in case of the socalled “small duct sclerosing cholangitis” (Chapman, 2002), or may be diffuse affecting also larger bile duct and giving the typical radiological or MRI imaging of “sclerosing cholangitis”). In children, primary biliary cirrhosis is exceptionally described, particularly before adolescence. Moreover, a rare and peculiar form of autoimmune hepatitis, typical of infancy exists, and is characterized by the unique association of Coombs positive autoimmune hemolytic anemia with the peculiar histopathological finding of diffuse giant cell transformation of the hepatocytes at a very unusual age even for infants (Maggiore et al, 2011). Immunosuppressive treatment is usually efficacious in most cases of AIH, but it is less effective in autoimmune cholangitis, particularly in case of delayed diagnosis at the stage of diffuse sclerosing cholangitis (Maggiore et al, 2009). Immunosuppressive treatment is also the only life-saving treatment recognized in “infantile giant cell hepatitis associated with autoimmune hemolytic anemia” (Maggiore et al, 2011). Liver biopsy is of paramount importance in the diagnostic work-up of autoimmune diseases of the liver and biliary tract as recognized by the major guidelines. Histological examination

The multi-detector computed tomography (MDCT) scan and magnetic resonance (MR) of the abdomen play a key role in the work-up to liver transplantation (LT) by identifying congenital anomalies or cirrhosis-related modifications, conditions that can require changes in surgical technique. Moreover, the MDCT and MR scans allow identification of cirrhotic liver hepatic masses, extrahepatic porto-systemic shunts, eventual thrombosis of portal system and radiological signs of portal hypertension associated with biliary atresia (BA). The aim of this paper is to review MDCT, MR imaging and interventional radiology procedures performed to evaluate morphological changes and degree of portal hypertension in pediatric patients with end-stage liver disease secondary to BA, who are candidates for LT. Advances in the field of MR, MDCT and in percutaneous minimally invasive techniques have increased the importance of radiology in the management of pediatric patients with BA who are candidates for LT.

Background & Aims PFIC2 is caused by mutations in ABCB11 encoding BSEP. In most cases affected children need liver transplantation that is thought to be curative. We report on two patients who developed recurrent normal GGT cholestasis mimicking primary BSEP disease, after liver transplantation. Methods PFIC2 diagnosis was made in infancy in both patients on absence of canalicular BSEP immunodetection and on ABCB11 mutation identification. Liver transplantation was performed at age 9 (patient 1) and 2.8 (patient 2) years without major complications. Cholestasis with normal GGT developed 17 and 4.8years after liver transplantation, in patient 1 and patient 2, respectively, during an immunosuppression reduction period. Results Liver biopsies showed canalicular cholestasis, giant hepatocytes, and slight lobular fibrosis, without evidence of rejection or biliary complications. An increase in immunosuppression resulted in cholestasis resolution in only one patient. Both patients developed atrial fibrillation, and one melanonychia. The newborn of patient 1 developed transient neonatal normal GGT cholestasis. Immunofluorescence staining of normal human liver sections with patient's sera, collected at the time of cholestasis, and using an anti-human IgG antibody to detect serum antibodies, showed reactivity to a canalicular epitope, likely to be BSEP. Indeed, Western blot analysis showed that patient 2 serum recognized rat Bsep. Conclusions Allo-immune mediated BSEP dysfunction may occur after liver transplantation in PFIC2 patients leading to a PFIC2 like phenotype. Extrahepatic features and/or offspring transient neonatal cholestasis of possible immune mediated mechanisms, may be associated. Increasing the immunosuppressive regimen might be an effective therapy.

We report on 6 adopted asymptomatic children in whom chronic HBV infection was identified through the occurrence of an acute hepatitis B in a family member. All of the children had serum HBV-DNA >2000 pg/mL. Acute hepatitis B in a family should alert the physician regarding the possibility of existing chronic HBV infection in other members of the family, especially newly adopted children, leading to a quick evaluation of their HBV status and to an efficacious protection of susceptible family members.

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

Background: Liver involvement, including elevated direct-reacting bilirubin levels, is common in patients with sickle cell disease. Fifty to seventy percent of sickle cell patients have pigmented gallstones due to precipitation of unconjugated bilirubin, and cholelithiasis or choledocholithiasis are common complications. The highest prevalence of these complications occurs in patients with Gilbert’s syndrome because of the combined effect of increased bilirubin production and reduced bilirubin-diphosphate-glucuronosyltransferase enzyme activity. Cholelithiasis is also a common complication in patients with thalassemia. Endoscopic removal of choledochal stones does not always resolve the clinical picture, as in cases of dysfunction of the Vater’s papilla, increased bile density due to persistently impaired bile flow or distortion of the choledocus due to dilatation, or inflammation secondary to gallstone. Case presentation: We report here a case of severe and persistent obstructive jaundice in a child affected with thalassodrepanocytosis and Gilbert’s syndrome, previously, and unsuccessfully, treated with endoscopic removal of choledochal stones. Deep and thorough biliary washing, and stenting with a new removable polytetrafluoroethylene (PTFE)-covered flared-type stent led to complete resolution of the obstructive jaundice. Conclusions: This report shows that an aggressive endoscopic approach in this select category of patients can help resolve the severe complication of hemolytic anemia, thus avoiding surgery. Background Liver involvement is a common finding in patients with sickle cell disease. Three principal clinical pictures have been recognized: acute intrahepatic cholestasis, hepatic crisis, and lithiasis [1-4]. Cholelithiasis and choledocholithiasis are common complications in patients with sickle cell disease or thalassemia. The highest prevalence of these complications occurs in patients with Gilbert’s syndrome. Endoscopic removal of choledochal stones does not always resolve the clinical picture, as in cases of dysfunction of the Vater’s papilla, increased bile density due to persistently impaired bile flow or to distortion of the choledocus due to dilatation, or to inflammation secondary to gallstones. We report here a case of severe and persistent obstructive jaundice in a child affected with thalassodrepanocytosis and Gilbert’s syndrome, previously and unsuccessfully treated with endoscopic removal of choledochal stones. Deep and thorough biliary washing, and stenting with a new removable polytetrafluoroethylene (PTFE)-covered stent led to complete resolution of the obstructive jaundice.