Cholestasis In Infants Research Articles

PO-0592 Distinguishing Congenital Combined Pituitary Hormone Deficiency From Biliary Atresia As A Cause Of Cholestasis In Infants

<h3>Background and aims</h3> Neonatal cholestasis is caused by either biliary atresia or intrahepatic cholestasis. Congenital combined pituitary hormone deficiency (CPHD) is a rare disease and a recognised cause of intrahepatic cholestasis. It is important to differentiate cholestasis due to this entity from cholestasis due to biliary atresia, since both diseases can cause jaundice at about 1 month of age. However, doing so in a timely fashion remains a diagnostic dilemma. This retrospective study was performed to clarify differences between cholestasis due to congenital CPHD and cholestasis due to biliary atresia. <h3>Methods</h3> From 2004 to 2010, 4 infants (2 boys and 2 girls) with cholestasis due to congenital CPHD were admitted to Nagoya City University Hospital. Head magnetic resonance imaging of the 4 infants revealed an invisible pituitary stalk; 3 of these 4 infants had an ectopic posterior pituitary. Liver biopsy was performed in 3 of the 4 infants, and histological findings included giant cell hepatitis. Findings from these 4 infants were then compared with those from55 infants treated in our hospital for cholestasis due to biliary atresia. <h3>Results</h3> The results showed a significant difference in mean gamma-glutamyl transpeptidase levels between the two groups of infants (115.0 IU/l vs. 553.0 IU/l, respectively). <h3>Conclusions</h3> The gamma-glutamyl transpeptidase level was found to be useful for distinguishing congenital CPHD from biliary atresia as the cause of cholestasis. The diagnosis of hypopituitarism should always be considered in infants with unexplained neonatal hepatitis.

Cholestasis and meconium ileus in infants with cystic fibrosis and their clinical outcomes

ObjectiveTo identify the incidence and outcomes of cholestasis and meconium ileus (MI) in infants with cystic fibrosis (CF).DesignRetrospective cohort study.SettingSingle-centre study.PatientsFrom January 1986 to December 2011, 401 infants with CF...

Histopathological features and accuracy for diagnosing biliary atresia by prelaparotomy liver biopsy in Egypt

Background and study aimsBiliary atresia (BA) is the most common cause of chronic cholestasis in infants. The most important objective in such cases is to distinguish obstructive cholestasis from non-obstructive causes. Aim of the studyTo evaluate the hepatic histopathology for the presence of features that correlate best with the diagnosis of BA. Patients and methodsWe retrospectively study the data of 81 infants who presented with neonatal cholestatic syndrome (NCS) (58 diagnosed as BA and 23 as not BA). We evaluated 6 histopathological parameters including ductular proliferation, bile plugs, intracellular bile pigments, giant cells transformation, Portal cellular infiltration and fibrosis. ResultsThe study showed that ductular proliferation, bile plugs and intracellular bile pigments emerged as the best indicators of BA while multinucleate giant cells transformation and portal cellular infiltration were seen in NH. ConclusionIn developing countries, we therefore recommend doing prelaparotomy liver biopsy for all suspected cases of BA to decrease the frequency of negative laparotomy to achieve cost benefit with reduced morbidity.

Thrombocytopenia at birth is a predictor of cholestasis in infants with small for gestational age.

Cholestasis and thrombocytopenia are complications that affect infants born small for gestational age (SGA). In SGA infants, other vital organs develop at the expense of the liver, and the thrombopoietin produced by the liver is low, often resulting in cholestasis. We hypothesized that thrombocytopenia at birth can be used to predict cholestasis in very-low-birth-weight infants (VLBWIs) with SGA. This retrospective cohort study enrolled VLBWIs with SGA admitted to a tertiary neonatal intensive care unit. A platelet cutoff value predictive of cholestasis was determined using receiver operating characteristic analysis. Multivariate logistic regression analysis was performed to evaluate the platelet cutoff value, and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Regarding the onset of cholestasis, survival analysis was performed by calculating the adjusted hazard ratios (HRs) and 95% CIs. A total of 87 infants were evaluated, and the platelet cutoff value was determined as 88×10(3) cells/μl. The adjusted OR for this platelet cutoff value was 10.52 (95% CI 2.26-55.93, p = 0.003), and the adjusted HR was 7.76 (95% CI 2.51-23.50, p = 0.0006). Thrombocytopenia is a useful predictor for cholestasis in VLBWIs with SGA.

Prevalence of Hypoglycemia Among Patients Presenting with Cholestasis of Infancy in a Nigerian Teaching Hospital

This study assesses the prevalence of hypoglycemia among patients presenting at the University of Benin Teaching Hospital, Benin City, Nigeria with cholestasis of infancy. During a period of five years, forty patients aged between 15 days and 12 months who presented with cholestasis of infancy, were admitted and screened for hypoglycemia, using Accutrend glucometer. For patients with low blood glucose values, blood samples were further analyzed, using the standard glucose-oxidase method. Of the 2,835 patients admitted over a five-year period, 40 (1.4%) had cholestasis of infancy, giving an incidence of 14 cases per 1000 admissions, with a sex ratio of 2.1: 1 in favour of males. Nine (22.5%) of the 40 infants with cholestasis had at least one blood glucose concentration less than 2.6 mmol/L (hypoglycemia). Of the nine hypoglycemic infants, three (33.3%) had one blood glucose concentration less than 1.6 mmol/L (severe hypoglycemia). Seven (77.8%) of the nine hypoglycemic infants were diagnosed in the first 36 hours of admission. Lethargy and poor feeding were observed in three infants with severe hypoglycemia and three of them died. Six (66.7%) of the hypoglycemic infants were below 3 months of age. Hypoglycemia was observed among patients with cholestasis of infancy and the prevalence was higher among infants below 3 months of age.

Conjugated Hyperbilirubinemia in Children

A variety of anatomic, infectious, autoimmune, and metabolic diseases can lead to conjugated hyperbilirubinemia, both in the newborn period and later in childhood. The pediatric practitioner is most likely to encounter conjugated hyperbilirubinemia in the neonatal period.It is crucial to maintain a high degree of suspicion for cholestasis in the persistently jaundiced newborn. The goal is recognition of conjugated hyperbilirubinemia between 2 and 4 weeks after birth, allowing for the prompt identification and management of infants who have biliary atresia, which remains the most common cause of neonatal cholestasis.

Neonatal cholestasis in congenital pituitary hormone deficiency and isolated hypocortisolism: characterization of liver dysfunction and follow-up

Neonatal cholestasis due to endocrine diseases is infrequent and poorly recognized. Referral to the pediatric endocrinologist is delayed. We characterized cholestasis in infants with congenital pituitary hormone deficiencies (CPHD), and its resolution after hormone replacement therapy (HRT). Sixteen patients (12 males) were included; eleven with CPHD, and five with isolated central hypocortisolism. Onset of cholestasis occurred at a median age of 18 days of life (range 2-120). Ten and nine patients had elevated transaminases and γGT, respectively. Referral to the endocrinologist occurred at 32 days (range 1 - 72). Remission of cholestasis occurred at a median age of 65 days, whereas liver enzymes occurred at 90 days. In our cohort isolated, hypocortisolism was a transient disorder. Cholestasis due to hormonal deficiencies completely resolved upon introduction of HRT. Isolated hypocortisolism may be a transient cause of cholestasis that needs to be re-evaluated after remission of cholestasis.

Recovery of graft steatosis and protein‐losing enteropathy after biliary diversion in a PFIC 1 liver transplanted child

PFIC 1 is a genetic disorder characterized by hepatic and gastrointestinal disease, often requiring LT during childhood. Extrahepatic symptoms, such as diarrhea and malabsorption, do not improve or may be aggravated after LT, as graft steatosis or steatohepatitis as consequences of the interaction between transplanted liver and native bowel. We describe a patient with PFIC 1 who presented with cholestasis in infancy, who developed intractable pruritus and liver fibrosis. The child underwent living donor LT at 3.6 yr of age, and he early developed severe refractory diarrhea, secondary malabsorption with protein-losing enteropathy, and an early fatty liver disease trough graft steatohepatitis. As the response to cholestyramine was unsatisfactory, we decided to perform an EBD by using the jejunal loop used for the cholangiojejunostomy. Diarrhea resolved rapidly after surgery. He remained well after six months following biliary diversion, with normal stool output and no protein loss. We documented a dramatic improvement of graft steatosis at histology as well as normalization of liver function test. EBD can be considered a valuable treatment option to avoid organ disfunction and loss in PFIC 1 transplanted patients who develop graft steatohepatitis.

Hepatocellular Cholestasis and Pruritus: Beyond Clinical Treatment

Hepatocellular cholestasis in infants can be caused by hepatitis, alfa-1 antitrypsin deficiency, inborn errors of bile acid synthesis, drugs, or total parenteral nutrition. Occasionally, Alagille Syndrome and Progressive Familiar Intrahepatic Cholestasis (PFIC) may result in intrahepatic cholestasis, with an incidence of 1 in 90 000. The affected patients present in infancy or childhood with intermittent painless jaundice. The most apparent and debilitating symptom associated with this disorder is pruritus, which may be out of all proportion to the hyperbilirubinemia and often leads to self-mutilation from scratching. This results in a very poor quality of life, and treatment is very difficult because traditional drugs used to treat itching are typically ineffective [1] [2] [3].

Morphologic Findings in Progressive Familial Intrahepatic Cholestasis 2 (PFIC2)

Progressive familial intrahepatic cholestasis, type 2 (PFIC2), characterized by cholestasis in infancy that may progress to cirrhosis, is caused by mutation in ABCB11, which encodes bile salt export pump (BSEP). We correlated histopathologic, immunohistochemical, and ultrastructural features in PFIC2 with specific mutations and clinical course. Twelve patients with clinical PFIC2 and ABCB11 mutations were identified, and 22 liver biopsy and explant specimens were assessed. All had hepatocellular cholestasis; most had canalicular bile plugs. At least 1 specimen from every patient had centrizonal/sinusoidal fibrosis, often with periportal fibrosis. Neonatal hepatitis-like features (inflammation, giant cells, necrosis) varied. In 2 of the 5 patients with paired specimens obtained >6 months apart, lobular and portal fibrosis worsened. Transmission electron microscopy (EM) in all 9 patients studied showed canalicular dilatation, microvilli loss, abnormal mitochondrial internal structure, and varying intracanalicular accumulation of finely granular bile. Canalicular staining for BSEP was absent in 10 patients and present in 2 patients, 1 of whom had intermittent symptoms. ABCB11 sequencing of all patients identified 6 novel and 10 previously described mutations, with nonsense, missense, and/or noncoding mutations in the 10 patients without immunohistochemically demonstrable BSEP. Missense and/or noncoding mutations were identified in the 2 patients with demonstrable BSEP, whose clinical course was more indolent. Mutations ending ABCB11 transcription appear linked, through hepatocellular necrosis and fibrosis, to worse outcome. In conclusion, light microscopy and electron microscopy findings in clinical PFIC2 can support diagnosis, but are variable and nonspecific. Therefore, no correlation between specific mutations and histopathology is yet possible.

Design and Validation of the Biliary Atresia Research Consortium Histologic Assessment System for Cholestasis in Infancy

Pathologists participating in the National Institutes of Health-sponsored Biliary Atresia Research Consortium (BARC) developed and then evaluated a standardized system for histologic reporting of liver biopsies from infants with cholestasis. A set of 97 anonymous liver biopsy samples was sent to 10 pathologists at BARC centers. A semiquantitative scoring system that had 16 histologic features was developed and then used by the pathologists, who had no knowledge of clinical history, imaging results, or laboratory data. Interobserver agreement was evaluated statistically. Agreement on scoring of each feature and on the pathologists' diagnosis, compared with the final clinical diagnosis, was evaluated by using weighted kappa statistics. There was moderate to substantial interobserver agreement in identification of bile plugs in ducts, giant-cell transformation, extramedullary hematopoiesis, and bile duct proliferation. The pathologists' diagnosis of obstruction in clinically proven cases of biliary atresia (BA) ranged from 79%-98%, with a positive predictive value of 90.7%. Histologic features that best predicted BA, on the basis of logistic regression, included bile duct proliferation, portal fibrosis, and absence of sinusoidal fibrosis (each P<.0001). The BARC histologic assessment system identified features of liver biopsies from cholestatic infants, with good interobserver agreement, that might be used in diagnosis and determination of prognosis. The system diagnosed BA with a high level of sensitivity and identified infants with biliary obstruction with reasonable interobserver agreement. However, distinguishing between BA and disorders such as total parenteral nutrition-associated liver disease and alpha(1)-antitrypsin deficiency is not possible without adequate clinical information.

Erratum.

Rollins MD, Scaife E, Jackson W, Mulroy C, Book L, Meyers R. Elimination of Soybean Lipid Emulsion in Parenteral Nutrition and Supplementation With Enteral Fish Oil Improve Cholestasis in Infants With Short Bowel Syndrome. Nutr Clin Pract. 2010;25:199-204. (Original DOI: 10.1177/0884533610361477 ) In the above article, on page 202, 2 amounts in Table 2 appear incorrectly. Under "20% soybean lipid emulsion," in the "linoleic" line, the amount should be 0.1 g/mL instead of 1.1 g/mL. In the "total fat(kcal/ml)" line, the amount should be 2.0 g/mL instead of 0.2 g/mL.

Elimination of Soybean Lipid Emulsion in Parenteral Nutrition and Supplementation With Enteral Fish Oil Improve Cholestasis in Infants With Short Bowel Syndrome

Parenteral nutrition-associated liver disease (PNALD) is a potentially fatal complication for children with intestinal failure. Fish oil-based lipid emulsions have shown promise for the treatment of PNALD but are not readily available. Six cases are presented in which cholestasis resolved after soybean lipid emulsion (SLE) was removed from parenteral nutrition (PN) and enteral fish oil was given. A retrospective review at a tertiary children's hospital (July 2003 to August 2008) identified 6 infants with intestinal failure requiring PN for >6 months who developed severe hepatic dysfunction that was managed by eliminating SLE and providing enteral fish oil. Twenty-three infants with short bowel syndrome requiring prolonged PN developed cholestasis. SLE was removed in 6 of these patients, and 4 of the 6 received enteral fish oil. Standard PN included 2-3 g/kg/d SLE with total PN calories ranging from 57 to 81 kcal/kg/d at the time of SLE removal. Hyperbilirubinemia resolved after elimination of SLE within 1.8-5.4 months. Total PN calories required to maintain growth generally did not change. Temporary elimination of SLE and supplementation with enteral fish oil improved cholestasis in PN-dependent infants. Further trials are needed to evaluate this management strategy.

Impact of Fish Oil-Based Lipid Emulsion on Serum Triglyceride, Bilirubin, and Albumin Levels in Children With Parenteral Nutrition-Associated Liver Disease

Parenteral nutrition is known to cause liver injury in babies. The aim of this study is to investigate the effects of different lipid emulsions on parenteral nutrition-associated cholestasis in infants. In addition, there may be a relationship between the lipid emulsion and triglyceride levels. Furthermore, triglyceride levels may correlate with direct bilirubin and albumin, as markers of liver impairment and nutritional status. Patients with parenteral nutrition-associated cholestasis who were treated with a fish oil-based lipid emulsion (n = 18) were prospectively followed for triglyceride, direct bilirubin, and albumin levels and compared with patients who were maintained on a soy-based lipid emulsion (n = 59). Triglyceride levels decreased in the fish oil cohort from a mean of 140 mg/dL at wk 0 to 40 mg/dL at wk 20 but remained unchanged at approximately 140 mg/dL in the soybean cohort. Triglyceride levels of patients treated with fish oil declined over time, while those receiving soybean oil did not. Also, changes in triglyceride levels over time were directly correlated with direct bilirubin and inversely related to albumin levels. These findings may indicate an added benefit of reduced triglyceride levels for patients treated with fish oil and this effect coincides with markers for improved liver function and nutritional status.

High Rates of Mortality and Morbidity Occur in Infants With Parenteral Nutrition–Associated Cholestasis

Extremely few data are available about the natural history of parenteral nutrition (PN)-associated cholestasis. The authors evaluated a cohort of infants at a large center to determine the outcome of PN-associated cholestasis in infants with some gastrointestinal function. The authors reviewed the records of all infants admitted to a level 3 neonatal intensive care unit over a 16-month period who had the diagnosis of PN-associated cholestasis. Records were reviewed in these infants for course of cholestasis, laboratory values, outcome, and infection rate. Sixty-six patients were admitted who met the study criteria. There were 10 deaths and 1 referral for liver transplant (Death/TPlant) (17%) in the first year of life. All Death/TPlant infants had at least 1 positive blood culture after the onset of cholestasis. Maximum conjugated bilirubin (MaxCB) in Death/TPlant infants was 15.7 +/- 2.2 (SEM) compared to 8.4 +/- 1.0 mg/dL in babies who recovered. Of 21 infants with a MaxCB > or =10.0, Death/TPlant occurred in 8/21 (38%). Of 40 babies with positive blood cultures, 11 were in the Death/TPlant group vs no deaths among the 25 without positive blood cultures. Average time to resolution from the MaxCB to a CB <2.0 mg/dL was 66 +/- 7 days (n = 49). Infants with PN-associated cholestasis have high rates of mortality despite the presence of some gastrointestinal function. These data support further evaluation and the development of novel forms of therapy for babies with parenteral-associated CB > or =2 mg/dL with emphasis on interventions for infants with a CB >10 mg/dL.

EASL Clinical Practice Guidelines: Management of cholestatic liver diseases

EASL Clinical Practice Guidelines (CPG) on the management of cholestatic liver diseases define the use of diagnostic, therapeutic and preventive modalities, including non-invasive and invasive procedures, in the management of patients with cholestatic liver diseases. They are intended to assist physicians and other healthcare providers as well as patients and interested individuals in the clinical decision-making process by describing a range of generally accepted approaches for the diagnosis, treatment and prevention of specific cholestatic liver diseases. The clinical care for patients with cholestatic liver diseases has advanced considerably during recent decades thanks to growing insight into pathophysiological mechanisms and remarkable methodological and technical developments in diagnostic procedures as well as therapeutic and preventive approaches. Still, various aspects in the care of patients with cholestatic disorders remain incompletely resolved. The EASL CPG on the management of cholestatic liver diseases aim to provide current recommendations on the following issues:

Utility of ERCP in Neonatal and Infant Cholestasis

In neonates and infants with biliary obstruction, the diagnosis is important to establish early. Despite the use of several noninvasive imaging modalities, a definite diagnosis of biliary atresia (BA) or other pancreaticobiliary disorders may be difficult to ascertain. In this paper, we report our experience with endoscopic retrograde cholangiopancreaticography (ERCP) in the clinical situation of neonatal and infant jaundice. Between 1999 and 2006, we performed 23 ERCP procedures in 22 neonates and infants with the provisional diagnosis of biliary obstruction where other imaging was inconclusive. The mean age was 2.4 months and the mean weight was 4.8 kg. A pediatric videoendoscope with an outer diameter of 7.5 mm was used in all patients. ERCP was successful in 20 of 23 patients. BA was suggested in 6 patients, all subsequently verified by surgery. Detailed visualization of biliary structures important for planning of treatment was performed in children with choledochal cysts and spontaneous biliary perforation. Cannulation of the ampulla failed in 3 patients, of whom 1 had BA, 1 a choledochal stone, and 1 bile plug syndrome. Only 1 therapeutic ERCP was performed in a child with a stone completely obstructing the ampulla. The only complications were 1 asymptomatic case of hyperamylasemia and 1 of mild cholangitis successfully treated with antibiotics. ERCP is feasible and safe in the workup of neonatal cholestasis where other imaging modalities are inconclusive. Despite the expanding role of magnetic resonance cholangiography, ERCP may still have a role in the multidisciplinary workup of these patients.

Multidrug resistance protein 3 R652G may reduce susceptibilityto idiopathic infant cholestasis

To evaluate the role of genetic factors in the pathogenesis of idiopathic infant cholestasis. We performed a case-control study, including 78 infants with idiopathic infant cholestasis and 113 healthy infants as controls. Genomic DNA was extracted from peripheral venous blood leukocytes using phenol chloroform methodology. Polymerase chain reaction was used to amplify the multidrug resistance protein 3 (MDR3) R652G fragment, and products were sequenced using the ABI 3100 Sequencer. The R652G single nucleotide polymorphism (SNP) was significantly more frequent in healthy infants (allele frequency 8.0%) than in patients (allele frequency 2.60%) (P < 0.05), odds ratio, 0.29; 95% confidence interval, 0.12-0.84. The conjugated bilirubin in patients with the AG genotype was significantly lower than in those with the AA genotype (44.70 +/- 6.15 micromol/L vs 95.52 +/- 5.93 micromol/L, P < 0.05). MDR3 R652G is negatively correlated with idiopathic infant cholestasis. Children with the R652G SNP in Guangxi of China may have reduced susceptibility to infant intrahepatic cholestasis.

L-Methionine Toxicity in Freshly Isolated Mouse Hepatocytes Is Gender-Dependent and Mediated in Part by Transamination

L-methionine (Met) has been implicated in parenteral nutrition-associated cholestasis in infants and, at high levels, it causes liver toxicity by mechanisms that are not clear. In this study, Met toxicity was characterized in freshly isolated male and female mouse hepatocytes incubated with 5 to 30 mM Met for 0 to 5 h. In male hepatocytes, 20 mM Met was cytotoxic at 4 h as indicated by trypan blue exclusion and lactate dehydrogenase leakage assays. Cytotoxicity was preceded by reduced glutathione (GSH) depletion at 3 h without glutathione disulfide formation. Exposure to 30 mM Met resulted in increased cytotoxicity and GSH depletion. It is interesting to note that female hepatocytes were resistant to Met-induced cytotoxicity at these concentrations and showed increased cellular GSH levels compared with hepatocytes exposed to medium alone. The effects of amino-oxyacetic acid (AOAA), an inhibitor of Met transamination, and 3-deazaadenosine (3-DA), an inhibitor of the Met transmethylation pathway enzyme S-adenosylhomocysteine hydrolase, on Met toxicity in male hepatocytes were then examined. Addition of 0.2 mM AOAA partially blocked Met-induced GSH depletion and cytotoxicity, whereas 0.1 mM 3-DA potentiated Met-induced toxicity. Exposure of male hepatocytes to 0.3 mM 3-methylthiopropionic acid (3-MTP), a known Met transamination metabolite, resulted in cytotoxicity and cellular GSH depletion similar to that observed with 30 mM Met, whereas incubations with D-methionine resulted in no toxicity. Female hepatocytes were less sensitive to 3-MTP toxicity than males, which may partially explain their resistance to Met toxicity. Taken together, these results suggest that Met transamination and not transmethylation plays a major role in Met toxicity in male mouse hepatocytes.

Risks and Efficacy of ERCP in Infants with Obstructive Jaundice

Background: Early differentiation between extrahepatic and intrahepatic causes of cholestasis is essential for the propper management of cholestasis in infancy. Endoscopic retrograde cholangiopancreatography /ERCP/ is the most reliable and useful examination to establish the patency of the bile duct. However, the experience in cholestatic infants is limited and the radiological findings at ERCP vary considerably. Because of its inherent risks we analysed our series in an attepmpt to better define the diagnostic role of ERCP in infants with obstructive jaundice. Methods: All ERCPs performed in our department during a 7 year period in infants were rewiewed retrospectively. All examinations were performed by two endoskopists. An Olympus PJF /PJF 7,5 duodenoscope /Olympus Co. Tokyo/ was used. This 7,5 mm side wieving endoscope has a 2 mm instrumentation channel with cannula elevator. A 4-Fr catheter was used in all patients. Results: We performed ERCP in 69 infants with cholestasis of uncertain etiology, as a diagnostic procedure to establish the patency of extrahepatic bile ducts. The papilla of Vater was identified and cannulated in 66 of 69 patients /95,7%/. A normal gallbladder and bile ducts could be opacified in 18 patients /26,1%/ In 29 patients in whom successful canulation of the papila was possible /42%/ only the pancreatic duct could be visualized /BA type I/ . In 12 patients /17,4%/ only the common bile duct and gallbladder were visualized , without the common hepatic duct /BA type II/.. In 6 patients/8,7%/ choledochal cyst was found, in one case cholelithiasis/1,5%/. In 3 patients was papila not identified/4,3%/ All patients with preoperative diagnosis of BA type I and II underwent laparotomy and the ERCP findings were confirmed at laparotomy\with the exception of 1 infant where ERCP was false positive and surgery found normal findings in hepaticobiliary tree. Three patients where papila of Vater was not identified undervent laparotomy and biliary atresia was found /4,3%/ In three cases a mild asymptomatic elevation of pancreatic enzymes was noted./4,3%/. Conclusion . Our results show, that ERCP can be performed safely in infants with cholestasis of very young age and low weight /lowest weight 1,6 kg/ with unclear diagnosis. We suppose, that is necessary to do ERCP in infants in large endoscopic centers, where skilled endoscopists and pediatric surgeons and peditricians work together closely. A special endoscopic equipment - pediatric side wieving endoscope is for this investigation essential.