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THE CLINIC OF PEDIATRIC GASTROENTEROLOGY AND HEPATOLOGY is a subdivision of The Department of Pediatrics, Medical University in Sofia. Diagnosis and management of the diseases of gastrointestinal tract, liver and pancreas as well as teaching students and research are the basic activities of our clinic. The staff consists of six assistant-professors, every one of us has his / her special fields of interests.
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Dr. Kancho Kanchev, MD - abdominal US
Dr. Radka Kumanova, MD - upper and lower endoscopy
Dr. Penka Yaneva, MD - lower endoscopy
Dr. Emilia Panteleeva, MD - oesophageal pH monitoring and detection of antiendomysium antibodies
Dr. Elena Lazarova,MD - liver biopsy, abdominal US
Dr. Christo Jelev, MD, PhD - metabolic liver diseases
Dr K. Kanchev
Dr. R. Kumanova
Dr. P. Yaneva
Dr. E. Panteleeva 
Dr. Ch. Jelev
Through that home page we would like to present in brief some of our studies and published articles.
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The Endoscopy Center of Pensacola, FL contains lectures by their gastroenterologists, gastro links, patient education links and brochures. They will soon be adding videos of endoscopies and
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LIVER TRANSPLANTATION
We would like to begin with that title although we have not so much experience of our own. We are aware of the rapidly improving survival rate and increasing number of liver transplantations as the only way of management of end-stage liver disease. Liver transplantation has not been performed in Bulgaria yet but the idea of its coming into being is supported by enormous efforts and activities. We are optimistic for its coming true in the near future. More and more parents trust that procedure and accept the new way of living as the only way of saving life and giving good quality of life to their children.
Five Bulgarian children have been transplanted up till now; four of them have been followed up by our clinic. The first child underwent cadaveric liver transplantation in 1993 in Brussels, Belgium because of cryptogenic liver cirrhosis. The second child ( Byler-like syndrome ) was cadaveric liver transplanted, too in The University Surgery Clinic in Hamburg, Germany. The other three children underwent living related transplantation because of biliary atresia. All the children are alive, with good quality of life, two of them passed the 5-year survival period. An infant with Alagille syndrome is on his way to be liver transplanted in Essen, Germany.
To visit of our liver transplanted children please, 
Now you can read some history of liver transplantation:
Thomas E. Starzl 
was the first to perform and report the three attempts at human liver replacement in 1963, Denver, USA. All the patients died and liver transplantation was consigned to a self-imposed 3 - year worldwide moratorium. Meanwhile a lot of work has been done to improve the surgical techniques, to find reliable immunosuppression to prevent organ rejection. It was proved that the introduction of the double drug regimen - prednisone and azathioprine - increased significantly the survival rate of the patients. One-year survival rate has been dramatically changed - 65% - after the discovery and clinical use of Cyclosporine since 1979. Organ preservation was greatly improved by the introduction of UW solution.
In 1983 liver transplantation was proclaimed a treatment ( rather than experimental ) strategy in the USA.
The first attempt to perform a reduced size liver transplantation was made in 1984. That is a way to overcome the difficult operation and complications from implantation of adult-size liver in the abdominal cavity of a child. Liver transplantation of infants was realized. Living related liver transplantation was introduced after 1988.
Here you can find the most frequent ( in % ) indications for liver transplantation in children:
Biliary atresia - 61
Intrahepatic cholestasis - 9
Fulminant liver diseases - 9
Alpha 1 anti-trypsin deficiency - 5
Chronic hepatitis - 5
Biliary cirrhosis - 4
Metabolic liver diseases - 3
Cryptogenic cirrhosis - 2
Congenital hepatic fibrosis - 1
Tumours of the liver and biliary system - 1
Nowadays the 5-year survival rate is reported to be 90% by most of the transplantation centers.
European Transplant Coordinators Organization ( ETCO ) data on the number of liver transplantations in 1998: Spain- 899, Germany- 699, United Kingdom- 690, France- 693, Czech republic- 66, USA- 4450. You can find some more details on Web ETCO page
The cost of liver transplantation is constant - 100000 $.
You can find useful information about transplantation centers clicking here or visiting this site
Also You are Welcome to visit the ABSOLUTE AUTHORITY ON TRANSPLANT PHARMACOLOGY web site at URL:
http://www.absoluteauthority.com/Transplant_Pharmacology/. This is your central hub for exploring the world of Transplant Pharmacology on the Web.
AUGUST 1999
DIAGNOSTIC VALUE OF ANTIENDOMYSIUM ANTIBODIES FOR COELIAC DISEASE IN CHILDREN
E. Panteleeva, Chr. Jelev, R. Kumanova, D. Mondal, P. Yaneva, E. Lazarova, K. Kuncev
To date the antiendomysium antibodies - IgA (EMA) are considered the most reliable serological marker for the diagnosis of Coeliac Disease ( CD ), it is an useful adjunct reducing the number of small intestinal biopsies(SIB). It reflects dietary changes to gluten and correlates best with intestinal histopathology. It is not found in healthy controls. Compared with antigliadin (AGA) and antireticulin ( ARA ) antibodies it is the most predictive test in screening for the disease.
The purpose of the present study was to investigate the diagnostic reliability of EMA in CD in the pediatric age group.
Patients and diagnostic methods: Between 1995 and 1998 we studied the biopsy specimens and sera for AGA ( IgA and IgG ), EMA and ARA of : 118 children divided into 3 groups(CD patients, pathological controls and healthy controls). We screened a total of 260 children with insulin-dependent diabetes mellitus ( IDDM ) and 71 relatives of 40 CD patients using AGA- IgG and IgA as the first screening step. EMA were performed when AGA were found to be elevated.The SIB confirmed the diagnosis of CD.
Results: We determined the normal range and cut-off of AGA - IgA and AGA -IgG in Bulgarian healthy children.The present study found the sensitivity of AGA- IgA - 87%, AGA- IgG - 53,8%, EMA - 97,4%. The specificity of AGA- IgA is 98,2%, of AGA- IgG - 89%, of EMA - 96,8%.
The positive predicive value is as follows: AGA-IgA - 97,1%, AGA- IgG - 72,4%, EMA - 94,8%. The negative predictive value is 91,8% for AGA- IgA, 78,3% for AGA- IgG and 98,4% for EMA.
It has been established that all the three antibodies studied are gluten-dependent. They appear with a gluten-containing diet and decrease and disappear after gluten withdrawal.
The significant correlation between EMA, AGA- IgA and the degree of gut mucosal atrophy as well as their clinical evaluation confirmed the previous studies about the high discriminative value of EMA alone and the combination of EMA + AGA- IgA. EMA appeared to be the most sensitive marker in monitoring the diet changes.
The prevalence of CD in the two high risk groups was found - among IDDM children - 1,92% and among the first degree relatives of CD patients - 1,4 %.
We performed 127 tests of EMA on monkey oesophagus sections and human umbilical cord ( HUC ) sections simultaneously. We found a high level of consistency giving identical results. We recommend the usage of HUC-sections as suitable and highly reliable substrate for testing EMA, bearing in mind it is much more time-consuming, the immunofluorescence reading is more difficult, but the price is significantly lower.
Acknowledgment: This work was supported by a grant from The Bulgarian Ministery of Education and Science. The authors thank Dr. Daniela Baltadgieva, Dr. Iskra Altankova and Tanja Bocheva for their support in testing AGA. The authors thank Maja G. Jordanova for her excellent technical assistance( Immunology Lab of University Hospital "Sveti Ivan Rilski", Sofia).
WILSON DISEASE
Haplotype and mutation analysis in Bulgarian patients with Wilson disease.
Alexey Savov 1, Nina Ignatova 1 ,Christo Jelev 2, Kamen Tzatchev 3, Dinesh Mondal 2, Emilia Panteleeva 2 , Ivo Kremensky1.
1 Laboratory of Molecular Pathology, Medical University, Sofia, Bulgaria
2 Pediatric clinic of Gastoenterology and Hepatology, Medical University, Sofia, Bulgaria
3 Department of clinical laboratory, Medical University, Sofia, Bulgaria
The Wilson disease gene (WND) span at least 80 kb genomic DNA and is comprised of 21 exons. Mutation screening in WD patients has led to identification of more than 70 molecular defects. Given the difficulties of searching for all mutations, haplotype data are important as a guide for mutation detection as for prenatal diagnostics by the linkage principle in this disorder.
In our study we investigate 17 families with Wilson disease for two highly polymorphic dinucleotide repeat polymorphisms showing significant levels of allelic association with the disease. We have determined 12 different haplotypes for D13S314 and D13S316. The most common haplotypes are 141/146, 141/150 (D13S314, D13S316). These markers are fully informative for 80% of families investigated. Including of two additional VNTR markers D13S133 and D13S301 could increase informativeness up to 100%. The haplotype data suggests the presence of many uncommon mutations in the Bulgarian population.
These findings have important implications for mutation detection and molecular diagnostics of the disease. Our findings show that the most common mutation in WND gene - His1070Gln in bulgarian patients is associate with haplotype 141/146, 141/150 (D13S314, D13S316).
See Full Text in: BALKAN JOURNAL OF CLINICAL LABORATORY,
2, 1998, 97
FECAL ALPHA-1 ANTITRYPSIN, ENDOGENOUS MARKER OF PROTEIN-LOSING ENTEROPATHY IN CHILDREN - SOLUTION OF METHODOLOGICAL PROBLEMES.
D.Mondal , A. Radivenska , Ch. Jelev , P. Zacharieva
The aim of the present study to analyze the correlation between the different methods of determination of fecal Alfa-1-Antitrypsin.
ABSTRACT
Diagnosis of excessive enteric loss of serum protein is made by measurement of fecal alpha-1-antitrypsin. Until now different methods of fecal alpha-1-antitrypsin determination were proposed. Unfortunately there is no consensus concerning the choice of the various method for measurement of fecal alpha-1-antitrypsin. To establish the method of determination of fecal alpha-1-antitrypsin, which is reliable and easy for clinical use, we measured fecal alpha-1-antitrypsin concentration and clearance of alpha-1-antitrypsin in lyophilzed and nondried stools in 90 healthy children and in 46 children with various intestinal disorders.
According to our results there is a significant positive correlation between the values of fecal alpha-1-antitrypsin concentration obtained with and without lyophilization of stools (r= 0.81, n= 47, p<0.001). A significant positive correlation was found between the values of alpha-1-antitrypsin clearance in lyophilized and nondried stools (r= 0.91, n= 20, p<0.001). Concentration of fecal alpha-1-antitrypsin correlated well with the clearance of alpha-1-antitrypsin concentration in nondried stools.
We concluded that each of them can be used as a reliable method for diagnosing of PLE and determination of random fecal alpha-1-antitrypsin concentration on nondried stools is a mostly simple, noninvasive and reliable method for measurement of enteric protein loss and is most suitable for clinical implication.
See full text in:
Acknowledgment -We are very thankful to Thrasher Research Fund, Salt Lake City, USA, for financial support. We are also very grateful to Prof.John Udall, Chief, Gastroenterology and Nutrition, School of Medicine, New Orleans, Louisiana State University, Medical center, USA.
Project name - Measurement of Protein Loss Into the Gastrointestinal Tract of Infants and Children.
Thrasher Award ¹ 2902 - 6 (1).
Consultant: John Udall, Professor of Pediatrics, Chief, Gastroenterology and Nutrition, School of Medicine, New Orleans, Lousiana State University, Medical Center.
Principal investigator: Dinesh Mondal, research fellow, University Paediatric Hospital, Clinic of Paediatric Gastroenterology and Hepatology, st. Urvitch ¹ 13, Sofia, Bulgaria.
Coinvestigators: 2. Anna Radivenska, associate professor, Head of the Peadiatric Unit, Fifth City Hospital, Sofia, Bulgaria ( Ex Head of the Clinic of Paediatric Gastroenterology, University Paediatric Hospital, Sofia, Bulgaria ).
Duration of Project: DELAILED SUMMARY OF THE PROJECT
1. Christo Jelev, assistant professor, University Paediatric Hospital, Clinic of Paediatric Gastroenterology and Hepatology, st. Urvitch ¹ 13, Sofia, Bulgaria.
KEYWORDS : faecal alpha-1-antitrypsin, nonlyophilised, children, intestinal disorders, protein-losing enteropathy.
ABBREVIATIONS: CLFAAT- intestinal clearance of alpha-1-antitrypsin, RFAATC- random faecal alpha-1-antitrypsin concentration, AAT- alpha-1-antitrypsin, PLE- protein-losing enteropathy, FAAT- faecal alpha-1-antitrypsin, RID- radial immundodifussion, ITM- immunoturbidimetric method, GM1 - gangliosidosis type1.
ABSTRACT : Random faecal alpha-1-antitrypsin and intestinal clearance of alpha-1-antitrypsin in nonlyophilised and in lyophilised stools were measured in Bulgarian children with various intestinal diseases, systemic disorders and in healthy subjects. Two hundred and twenty three subjects were evaluated : controls (90); chronic non-specific diarrhoea ( 31); active celiac disease (14 ); ulcerative colitis (4); chronic appendicitis (1); cow milk protein intolerance (10); intestinal lymphangiectasia (5); intestinal lambliosis (4); Meckel’s diverticulitis (3); post infectious enteropathy ( 6 ); treated celiac disease (4); cystic fibrosis (11); idiopathic nephrotic syndrome (16); systemic Lupus Erythematosus (4); short stature (5); diabetes mellitus ( 7) , Henoch - Sconlein purpura (4); GM 1 (1); marasmus (2); nephroblastoma (1).
We also compared the radial immunodiffusion plates of Bioagrogen, Sofia, Bulgaria with that of Behring, Marburg, Germany. A trial had done to measure concentration of faecal alpha-1-antitrypsin by autoanalyser.
Mean random faecal alpha-1-antitrypsin concentration (RFFATC) in nonlyophilised stools for controls was 332.9 micrograma / gram stool ( n - 90, SD- 40.41, - 14.80, 97-th percentile - 576 ). We did not find significant difference between the mean value of RFAATC in nonlyophilised stools in different age group (1mo - 12mo, n=30, RFAATC- 332.2; 1yr-3yr, n=30, RFAATC- 327.5; 3yr - 16 yr, n= 30, RFAATC- 339; P>0.05 ). There was no significant difference between the mean values of RFAATC in nonlyophilised stool in infants with different feeding style (breast feeding vs. bottle feeding ; 315 vs. 349.4, p > 0.05). We found a significant negative correlation between RFAATC and stools volume ( r= 0.55, p= 0.01, n= 20), but no correlation was demonstrated with RFAATC and serum value of alpha-1-antitrypsin (AAT) ( r= 0.23, p= 0.3, n= 20 ). Mean RFAATC in lyophilised stools for controls was 1158.25 micrograms / gram ( n= 20, SD- 624.48, - 139.6, 97-th pers.- 2328). We found a significant correlation between the RFAATC in nonlyophilised stool and that in lyophilised stool ( n= 43, r = 0.80, p< 0.0001 ).
Intestinal clearance of alpha-1-antitrypsin ( CLFAAT), measured in nonlyophilised stool for controls ; - mean 4.31 ml / 24 h, SD - 3.43, - 0.44, 97-th per. - 12.95, n= 20 and CLFAAT in lyophilised stool for controls ;- mean 15.09 ml / 24h, SD - 13.36, - 2.9, 97-th per.- 52.9. There was a good correlation between CLFAAT in nonlyophilised stools and that of lyophilised stools
( r= 0.91, p< 0.0001, n= 20 ).
All children with intestinal lymphangiectasia, marasmus, Meckel’s diverticula, post infectious enteritis, 13 of 14 with active celiac disease, 3 of 4 with intestinal lambliosis, 2 of 4 with ulceritive colitis, 2 of 10 with food intolerance, one with chronic appendicitis, 1 of 4 with SLE, 1/4 with Henoch-Schonlein purpura, 1/7 with Dibetes Melitus, 1/5 with short stature, 4/5 steroid resistant nephrotic syndrome, 1/10 steroid sensitive nephrotic syndrome had RFAATC> 576 mcg/g nonlyophilised stool ( value at 97-th percentile for controls).
All children with chronic nonspecific diarrhea, cystic fibrosis, had RFAATC < 576 mcg/g nonlyophilised stool. RFAATC was also less than 576 mcg/g in two children - one with GM1 and another with nehproblastoma. In all with active celiac disease RFAATC turned to normal after 4 weeks gluten free diet. It was also less than upper limit of normal in 4 children with treated celiac disease.
Intestinal clearance of faecal alpha-1-antitrypsin (CLFAAT)in nonlyophilised stools was determined in children with various disorders; 14 with active celiac disease, 5 with intestinal lymhangiectasia, 4 with ulcerative colitis. All children with celiac disease, intestinal lymphangiectasia, ulcerative colitis had CLFAAT > 12.95 ml/24h (97-th percentile for controls ).
RANDOM FAECAL a1-ANTITRYPSIN CONCENTRATION IN CHILDREN WITH IDIOPATHIC NEPHROTIC SYNDROME
D. Mondal, Ch. Jelev, A. Radivenska, A. Anadoliiska
ABSTRACT
We measured random faecal alpha-1-antitrypsin(RFA-1-AT) concentration in children with idiopathic nephrotic syndrome. The mean value of RFA-1-AT in steroid- resistant group was significantly higher than that of steroid-sensitive group (616.8 mcg/g nonlyophilised stool, n= 5 for steroid-resistant group vs. 312 mcg/g nonlyophilised stool, n= 10 for steroid sensitive group). Protein-losing enteropathy, as defined RFA-1-ATconcentration > 576 mcg/g ( value at 97-th percentile for controls) was significantly more common in steroid-resistant group ( 4/5 for steroid resistant group vs. 1/10 for steroid-sensitive group, p =0.02 ).We concluded that enteric loss of serum protein is more common in steroid resistant idiopathic nephrotic syndrome.
DISCUSSION
Enteric loss of serum proteins, as reported by Nussle et al is a frequent finding during the acute phase of the idiopathic nephrotic syndrome in children. Our study showed that protein-losing enteropathy was present in about 25% ( 5/16) of cases with idiopathic nephrotic syndrome in children. We found the mean concentration of FA-1-AT significantly higher in patients, who subsequently did not response to steroid (616.8 vs. 312.8, p= 0.03). Protein-losing enteropathy i.e. faecal concentration of alpha-1-antitrypsin more than 576 mcg/g nondried stool was more frequent in steroid resistant group(4/5 vs.1/10, p= 0.02). Further studies are needed to confirm the significance of FA-1-AT as a prognostic marker of patient's respond to convention treatment of idiopathic nephrotic syndrome in children.
We do not know the exact mechanism of enteric protein loss in these patients yet. Salazar et al. proved that PLE in 2 nephrotic children was due to the association of nephrotic syndrome with primary intestinal lymphangiectasia. Primary intestinal lymphangiectasia is a rare malformation. So it is unlikely to be a common. Unfortunately our patients had not been done intestinal biopsy, so we do not know the nature of intestinal morphology. Secondary Lymphatic dilatation due to oedema of the intestinal mucosa seems to be a tentative hypothesis of PLE in nephrotic children. But we do not find any correlation between severity of oedema and concentration of FA-1-AT. On the other hand , if oedema is the cause of PLE, most of the patients should have had enteric loss of serum proteins, whereas we have found it in 25% only. That hypothesis can not explain the higher frequency of PLE in steroid-resistant patients, too.
CONCLUSION
Random of faecal alpha-1-antitrypsin concentration, as well as the frequency of PLE are higher in steroid-resistant idiopathic nephrotic syndorme in children.
This is a personal communication of Dr. D. Mondal MD, PhD
Acknowledgement: Research was supported by grants from the Thrasher Research Fund, Salt Lake City, Utah, USA. We are also very grateful to Prof. John N. Udall, Jr., M.D., Ph. D. , Chief, Gastroenterology and Nutrition, School of Medicine in New Orleans.
ADDRESS for CORRESPONDENCE:
University Pediatric Hospital
Clinic of Pediatric Gastroenterology and Hepatology
Urvich str.13
1606 Sofia
BULGARIA
Tel. 003592 581 021
Fax 003592 9521 650
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