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BACKGROUND: Recently there are a number of reports on the cardiotoxicity of tacrolimus in post-transplant patients. There is no protocol for cardiovascular evaluation in these patients. This study was performed to evaluate the cardiotoxicity of tacrolimus in liver transplant recipients. METHODS: We evaluated 63 post-liver transplant patients who received tacrolimus. They were evaluated for cardiovascular complications by physical examination, electrocardiographic and echocardiographic examinations within three and six months following liver transplantation. Serum tacrolimus levels were checked by ELISA. For comparison, we selected 50 post-liver transplant patients who received no tacrolimus and evaluated them for cardiovascular function identically. RESULTS: Among 63 patients, 42 were male (66.7%) and 21 were female (33.3%); 70% of the patients were adults, and 19 (30%) were within the pediatric age group. The cardiovascular examinations, electrocardiogram and echocardiography of all patients three months post-transplantation were normal except for two children who developed tacrolimus related cardiac complications. Both had high serum tacrolimus levels. No adults developed cardiovascular complications. In the control group, the results of the cardiovascular evaluations were normal in all cases. CONCLUSION: The cardiovascular toxicity of tacrolimus, such as hypertrophic cardiomyopathy, may be observed in pediatric patients. Therefore, we recommend routine regular cardiovascular evaluation of children after liver transplantation. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to determine the prevalence of celiac disease in children with short stature.Methods: In all children with short stature (height more than 2 SD below the mean for age and sex) and normal physical examination, attending Motahary pediatric clinic in Shiraz, Iran, from 2003 till 2005, work-ups were made to find a cause for their short stature and of course their serum was assayed for IgG anti-tissue transglutaminase (TTG) antibody by ELISA test, as a marker for CD.Results: There were 26 girls and 46 boys with mean age of 9.8 years. Routine work-up showed microcytic hypochromic anemia in four children (5.6%) and giardiasis in five (6.9%). GH stimulation test revealed GH deficiency in five children (6.9%). Elevated IgG anti-TTG antibody level was detected in two children (2.8%). Duodenal biopsies of these children were in favor of celiac disease.Conclusion: Although, the prevalence of CD in this study was not significantly different (P value = 0.14) from the prevalence rate in healthy blood donors in Iran, the findings emphasize the fact that CD must be considered in a child with short stature, especially if the height is more than 3 SD below the mean for sex and age, even in the absence of gastrointestinal symptoms. In conclusion, the measurement of anti-TTG antibody should be included in the diagnostic evaluation of children with short stature. [ABSTRACT FROM AUTHOR]

Hereditary Tyrosinemia Type 1 (HT1) is a genetic disorder characterized by an autosomal recessive inheritance pattern, caused by mutations in the fumarylacetoacetate hydrolase (FAH) gene, which results in a deficiency of fumarylacetoacetase. In our study, we identified a total of 15 mutations, including 12 newly discovered and 3 previously reported pathogenic mutations, in a cohort of 19 Iranian patients with the acute form of HT1. Out of the 12 novel variants identified, 11 were missense variants: p.Asp126His, p.Gln75Glu, p.Leu385Pro, p.Ser92Thr, p.Leu96Arg, p.Val167Glu, p.Ala94Asp, p.Gly353Trp, p.Ser164Pro, p.Glu86His and p.Ala163Pro. Additionally, there was one nonsense variant, p.Try244X, that had not been previously reported. Interestingly, the Arg237X variant was found to be particularly prevalent in this study. Notably, three exons, namely exons 9, 3, and 6, exhibited a higher frequency of mutations. All of the identified variants are presumed to result in loss of function, impacting the clinical signs, disease progression, increasing tyrosine level, and the specific location of the mutation. Our study has provided valuable insights into the mutation spectrum of variants associated with HT1 disease which is reported for the first time from Iran. This information can facilitate the development of targeted mutation screening protocols, focusing on the most prevalent mutations within specific regions or ethnic groups., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: Liver cirrhosis is a major cause of hospital admission and mortality among children. Understanding the factors that influence disease severity is essential for preventing and reducing mortality. This study explored the association between hemoglobin levels and liver disease severity in children with cirrhosis., Methods: This cross-sectional study included 326 children with cirrhosis admitted to Namazi Teaching Hospital between 2015 and 2020. Clinical data, Child-Turcotte-Pugh (CTP) scores, and pediatric end-stage liver disease/model for end-stage liver disease (PELD/MELD) scores were collected to assess disease severity. Anemia was defined based on age, sex, and hemoglobin levels., Results: Among the children with cirrhosis, 275 (84.4%) were anemic, with a mean age of 5.4±4.8 years. The overall mean hemoglobin level was 9.2±2.1 g/dL. A significant inverse correlation was observed between hemoglobin levels and CTP and PELD/MELD scores in children with anemia ( p <0.001). Moreover, lower hemoglobin levels were associated with more higher CTP classes ( p <0.001)., Conclusion: According to the data analysis, a significant correlation was observed between hemoglobin level and the severity of liver disease, and hemoglobin level decreased with increasing severity of liver disease. According to CTP class, the mean hemoglobin level decreased progressively as the disease progressed. A comparison of the mean CTP scores between children with and those without anemia revealed that those with anemia had more severe disease than those without anemia., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2024 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.)

Background: Chronic liver disease (CLD) in children, often leads to cirrhosis and end-stage liver disease (ESLD). CLD poses significant challenges in management and prognosis. Assessing body composition, including sarcopenia, is increasingly recognized as important in understanding outcomes in this population., Methods: We conducted a prospective observational study, involving children aged 2 to 18 years with ESLD awaiting liver transplantation. Socio-demographic, clinical, and laboratory data were collected, and body composition was assessed using Bioelectrical Impedance Analysis (BIA). Sarcopenia was defined using age-specific cut-off points for appendicular skeletal muscle mass (aSMM) and fat-free mass (FFM)., Results: The study included 57 children (42.1% girls, 57.9% boys; median age: 10.9 years) with liver cirrhosis. Of them 11 (19.3%) died during the study. The mean duration of living with end-stage liver disease prior to participation was 5.43 years [IQR: 3.32, 8.39]. The most common etiology was biliary atresia (24.6%), followed by cryptogenic (22.8%). Deceased children exhibited significantly higher sarcopenia prevalence, lower basal metabolic rate and growth scores compared to survivors (P < 0.05), (771.0 vs. 934.0, P = 0.166) (65.0 vs. 80.5, P = 0.005). Total body and limb-specified lean mass were lower in deceased children, although not statistically significant. Similarly, total mineral (90% normal) and bone mineral content were lower in deceased children, with a significant difference observed only in water-to-FFM percentage (72.5 vs. 73.1, P = 0.009)., Conclusion: This study highlights the high prevalence of sarcopenia among children with ESLD and its association with adverse outcomes, including mortality. Bioimpedance analysis emerges as a promising, non-invasive method for assessing body composition in pediatric ESLD, warranting further investigation and integration into clinical practice., (© 2024. The Author(s).)

Background: Spontaneous bacterial peritonitis (SBP) is a fatal complication of ascites fluid infection. The causes of SBP in children differ from those in adults, and these bacteria are frequently resistant to antibiotics. Therefore, this study investigated the clinical findings, bacterial etiology, and antimicrobial resistance in children with SBP., Methods: This study was conducted on all new pediatric ascites patients, who were admitted to the Department of Pediatric Gastroenterology, Namazi Hospital, affiliated with Shiraz University of Medical Sciences (Shiraz, Iran) from 2021 to 2022. Required data such as demographic information, and clinical information such as complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Gram staining, blood culture by Automated Blood Culture System (BACTEC), and antibiogram of ascites fluids by disc diffusion method were all collected. Finally, the data were statistically analyzed using SPSS Software (version 26). Besides, the t test, Fisher's exact, Mann-Whitney, and Chi square tests were used for data analysis. In all tests, P≤0.05 was considered statistically significant., Results: The present study examined 62 children with ascites of which 18 (29%) had SBP. The median (IQR) age was 2.5 (8.1) years. Thirty-four (54.8%) of the participants were girls. Abdominal pain was the most common clinical manifestation in patients (54%), and there was a significant association between abdominal pain and SBP (P=0.02). In 12 positive ascites fluid cultures, coagulase-negative staphylococci had the highest frequency (25%), followed by Escherichia coli (16.7%). Third-generation cephalosporins had a 25% sensitivity in the total positive cultures. This sensitivity was 33.3% for Gram-negative cultures and 16.6% for Gram-positive cultures., Conclusion: Although third-generation cephalosporins are recommended as the primary antibiotic for the empirical treatment of SBP, the present study found high bacterial resistance. Finally, empirical therapy should be tailored to each region's bacterial resistance features., Competing Interests: Mohammad Hadi Imanieh and Gholamreza Pouladfar, as the Editorial Board Members, were not involved in any stage of handling this manuscript. A team of independent experts was formed by the Editorial Board to review the article without their knowledge., (Copyright: © Iranian Journal of Medical Sciences.)

Background: There have been few studies on the effect of Kegel exercises on the treatment of functional constipation in children. Hence, the present study investigated the add-on role of Kegel exercises in children with functional constipation., Methods: This clinical trial was conducted on children with functional constipation, according to Rome IV, who were referred to the pediatric department of Imam Reza Clinic (Shiraz, Iran) in 2022. The sample consisted of 64 children who were randomly assigned to either the intervention or the control groups. In the control group, a pediatrician administered conventional therapy, including diet training, defecation training, and polyethylene glycol (PEG) syrup (0.7 g/Kg daily). In the treatment group, in addition to conventional therapy, a pediatrician taught Kegel exercises to the child both verbally and in writing in the presence of their parents. To investigate the effectiveness of the intervention, frequency of defecation, defecation time, assistance used for defecation, incomplete emptying, unsuccessful defecation, abdominal pain, and painful defecation were selected as the outcomes. Independent sample t test was used for continuous variables. Categorical variables were reported as frequency and percentages. To examine the difference in categorical outcome variables, Wilcoxon (pre and post), Chi square, and Fisher exact tests were used. Data were analyzed using SPSS software version 21. P<0.05 were considered statistically significant., Results: Twenty-seven (88.4%) patients in the Kegel exercise group reported a defecation time of less than 5 min, while only 12 (37.5%) patients in the control group reached this time, and this difference was statistically significant (P=0.001). Moreover, patients in the treatment group showed significant improvements in terms of incomplete emptying of stool, unsuccessful defecation, abdominal pain, and painless defecation (P=0.001, P=0.001, P=0.001, P=0.037, respectively). After intervention, the use of laxatives, digits, or enemas to assist defecation was not significantly different between the groups (P=0.659)., Conclusion: Kegel exercise was an effective adjunctive treatment for pediatric functional constipation. Trial Registration Number: IRCT20230424057984N1., Competing Interests: Mohammad Hadi Imanieh and Naeimehossadat Asmarian, as the Editorial Board Members, were not involved in any stage of handling this manuscript. A team of independent experts was formed by the Editorial Board to review the article without their knowledge., (Copyright: © Iranian Journal of Medical Sciences.)

Biliary atresia (BA) is the primary cause of neonatal jaundice with various pathological mechanisms. Many BA patients may experience progressive liver dysfunction and eventually need a liver transplant. Therefore, identifying potential non-invasive biomarkers for BA is crucial. miR-122, the most abundant microRNA in the liver, plays significant roles in different liver diseases. This study aimed to assess miR-122 levels in BA patients. Eighteen patients with biliary atresia were selected at random from the Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS), along with 18 healthy controls. Blood samples were collected, and biochemical parameters (such as liver function tests) were measured. Quantitative reverse-transcription PCR (RT-PCR) was conducted on serum samples from both the case and control groups to analyze miR-122 levels. The study results indicated that serum miR-122 expression in BA patients was elevated compared to the control group, although it did not reach statistical significance. Additionally, no correlation was found between miR-122 expression and serum levels of liver enzymes or other laboratory findings in BA cases. miR-122 could be a potential target for diagnosing BA; however, further research with a larger population is necessary to determine if miR-122 could serve as a useful biomarker for diagnosing BA., Competing Interests: The authors declare that there is no conflict of interest.

Background: MicroRNAs (miRNAs) are a group of small non-coding RNAs that bind to the target mRNA and regulate gene expression. Recently circulating microRNAs were investigated as markers of diseases and therapeutic targets. Although various studies analyze the miRNA expression in liver disease, these studies on PFIC are few. Progressive familial intrahepatic cholestasis (PFIC) is a rare liver disease with autosomal recessive inheritance. Most children with PFIC progress to cirrhosis and liver failure and consequently need to have a liver transplant. The aim of this study is the investigation of the miR-19b and miR-let7b expression levels in Iranian PFIC children., Methods: 25 PFIC patients, 25 healthy children and 25 Biliary Atresia patients were considered as case and two control groups respectively. Blood samples were obtained and Liver function tests (LFTs) were measured. After RNA extraction and cDNA synthesis, quantitative PCR was performed using specific primers for miR-19b and miR-let7b. The U6 gene is used as an internal control., Results: qPCR on PFIC patients' samples demonstrated that the miR-19b and the miR-let7b expression were significantly decreased in patients compared to the control groups, with a p-value<0.0001 and p-value=0.0006 receptively., Conclusion: In conclusion, circulating micro-RNA like miR-19b and miR-let7b have a potential opportunity to be a non-invasive diagnostic marker or therapeutic target for PFIC in the future., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

Aim: The purpose of this retrospective single-center study was to determine the frequency of sarcopenia and its association with mortality and other morbidities in children with chronic liver disease who had undergone liver transplantation., Background: Sarcopenia, a muscle-wasting syndrome, is common in patients with advanced liver disease and is associated with increased morbidity and mortality. While sarcopenia in adults has been extensively studied, there is little information in this regard about children and adolescents with chronic liver diseases., Methods: The study included 108 children and adolescents who had undergone liver transplantation. Sarcopenia was measured using skeletal muscle index at the third lumbar vertebral level and assessed using abdominal computed tomography imaging., Results: The frequency of sarcopenia in the studied population was found to be 45.7%. Patients with sarcopenia were more likely to be male (P<0.0001), older (P<0.0001), and had lower height-for-age z-scores (P=0.012). Genetic/metabolic diseases were the most common underlying cause of sarcopenia in children. Except for a higher rate of transplant rejection in the sarcopenia group (P=0.035), there was no significant difference in mortality rates (P=0.688) or post-LT complications between the two groups. One year after LT, computed tomography-derived body composition parameters revealed no significant differences between children who survived and those who did not., Conclusion: Our findings indicated a high frequency of sarcopenia in children with chronic liver disease, implying that more research is needed to better understand its impact on clinical outcomes in this population., Competing Interests: The authors report no conflicts of interest in this work., (© 2024, Gastroenterology and Hepatology From Bed to Bench (GHFBB).)

Background: Posttransplant lymphoproliferative disorder is one of the most severe complications after transplantation, caused by uncontrolled proliferation of Epstein-Barr virus-positive B-cells in the setting of chronic immunosuppression. As one of the biggest transplant centers worldwide, we observed a potential increase in the number of patients with posttransplant lymphoproliferative disorder presenting with gastrointestinal symptoms in 1 year, during the coronavirus disease 2019 pandemic. There is limited information about dysregulation of the immune system following coronavirus disease 2019 infection, which may lead to Epstein-Barr virus reactivation in Epstein-Barr virus-positive B-cells and development of posttransplant lymphoproliferative disorder. Furthermore, there is no consensus in literature on a modality that can help in early diagnosis of posttransplant lymphoproliferative disorder with nonspecific gastrointestinal presentations before late and fatal complications occur., Case Presentation: Our case series includes five Iranian (Persian) patients, three female (2, 2.5, and 5 years old) and two male (2 and 2.5 years old), who developed gastrointestinal posttransplant lymphoproliferative disorder after liver transplantation. All of our patients were on a similar immunosuppressant regimen and had similar Epstein-Barr virus serologic status (seronegative at time of transplantation but seropositive at time of posttransplant lymphoproliferative disorder diagnosis). Four patients had either a positive coronavirus disease 2019 polymerase chain reaction test or exposure within the family. Although all of our patients presented with nonspecific gastrointestinal symptoms, four patients developed late posttransplant lymphoproliferative disorder complications such as bowel perforation and obstruction. All five patients with gastrointestinal posttransplant lymphoproliferative disorder received chemotherapy, but only two survived and currently are continuing the therapy. In one of the surviving patients, prompt endoscopic investigation resulted in early diagnosis of posttransplant lymphoproliferative disorder and a better outcome., Conclusion: Since 80% of our patients had exposure to coronavirus, a potential relationship might be suggested between the two. Furthermore, as we witnessed in one case, urgent endoscopic investigation in immunocompromised patients presenting with gastrointestinal symptoms can improve the clinical outcomes and therefore should be considered for early diagnosis of posttransplant lymphoproliferative disorder., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Large-volume paracentesis is the preferred treatment for patients with severe and refractory ascites. Several complications were reported during therapeutical paracentesis. However, there are very few published studies on the change in blood cell count after paracentesis. This study aimed to evaluate any changes in blood cell counts after ascites fluid drainage., Methods: This study was conducted on patients with severe ascites and chronic liver disease who underwent large-volume paracentesis at Namazi Hospital, in Shiraz, Iran, between March 2021 and February 2022. A data gathering form containing the patient's medical history, cause of cirrhosis, ascites fluid volume, as well as routine tests including primarily sodium, potassium, and basal creatinine, was filled out. Before and after the surgery, the total blood cell count was measured. Before the procedure, adjustment was made in the case of coagulopathy and albumin deficiency. The effect of factors such as the volume of drained fluid, splenomegaly, antibiotics, and steroid use was assessed on the changes in the number of blood cells. Using the JAMOVI 2.3.9 software, a paired t test and multiple regression were applied for statistical analysis (P<0.001)., Results: The study included 37 patients. After the paracentesis procedure, the number of blood cells significantly decreased in all groups (P<0.001). The followings are the amounts of each type of blood cells before and after the procedure: Platelet=153837±91862 and 115648±69136, red blood cells=3.53±0.784 and 3.22±0.705, white blood cells=12.3±7.78 and 8.6±5.5. None of the study variables, including drained volume, splenomegaly, antibiotics, and steroid use, were significant predictors of the changes in the blood cell count after paracentesis (P>0.001)., Conclusion: The findings of the present study showed that children with tense ascites who had large-volume paracentesis might experience a sharp drop in blood cell count after the procedure, which was a transient physiological condition., Competing Interests: Dr. Mohammad Hadi Imanieh, as the Editorial Board Member, was not involved in any stage of handling this manuscript. A team of independent experts was formed by the Editorial Board to review the is article without his knowledge., (Copyright: © Iranian Journal of Medical Sciences.)

Background: Large-volume paracentesis has become the first treatment choice for patients with severe and refractory ascites. The studies have reported several complications after therapeutic paracentesis. But there are few published data on the complications with or without Albumin therapy. We aimed to analyze the safety and complications of large-volume paracentesis in children with or without albumin therapy., Methods: This study was conducted on children with severe ascites with chronic liver disease who underwent large-volume paracentesis. They were divided into albumin-infused and albumin non-infused groups. In the case of coagulopathy, no adjustment was made. Albumin was not administered after the procedure. The outcomes were monitored to evaluate the complications. To compare two groups, a t-test was utilized, and the ANOVA test was used to compare several groups. If the requirements for using these tests were not met, Mann-Whitney and Kruskal-Wallis tests were applied., Results: Decreased heart rate was observed in all time intervals and was meaningful six days after paracentesis. MAP also decreased statistically at 48 hours and six days after the procedure ( P < 0.05). Other variables did not show any meaningful change., Conclusion: Children having tense ascites with thrombocytopenia, prolonged PT, Child-Pugh class C, and encephalopathy can undergo large-volume paracentesis without any complication. Albumin administration before the procedure in patients with low levels of Albumin (<2.9) can effectively overcome the problems of tachycardia and increased mean arterial pressure. There will be no need for Albumin administration after paracentesis., Competing Interests: The authors declare that they have no competing interests., (© 2023 Iran University of Medical Sciences.)

Liver diseases in children and adolescents are a significant and arising public health issue and should be surveyed from different dimensions (clinical and para-clinical, psychological, socio-economic) and in diverse populations. Shiraz Liver Transplant Center, Shiraz, Iran is the only center for pediatric liver transplantation and its pre-operative evaluations. This provides a unique and valuable situation for studying this vulnerable population. The Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS) was established to assess cirrhotic children, the course of their disease, and treatment over time. This cohort study aimed to prospectively evaluate the natural course and factors that contributed to complications and death of children with chronic liver disease in the region. SPLCCS was launched in September 2018 after obtaining ethical approval; until August 2022, 370 children with end-stage liver disease were enrolled and followed every six months. Here, the cohort's features, the included population's baseline characteristics, and primary outcomes are reported., (© 2023 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Matrix metalloproteinase 7 (MMP7) has been suggested as a promising biomarker in diagnosing biliary atresia (BA). This study aimed to assess the diagnostic accuracy of serum MMP7 in BA in the Middle Eastern population., Methods and Materials: In this cross-sectional study, neonates and infants with direct hyperbilirubinemia admitted to Namazi referral hospital, Shiraz, Iran, were studied. Baseline demographic and clinical characteristics and blood samples were obtained on admission. MMP7 serum concentration was measured using an enzyme-linked immunosorbent assay (ZellBio GmbH, Ulm, Germany)., Results: 44 infants with a mean age of 65.59 days were studied. Of these patients, 13 cases were diagnosed with BA, and 31 cases' cholestasis related to other etiologies. Serum MMP7 concertation was 2.13 ng/mL in the BA group and 1.85 ng/mL in the non-BA group. MMP7 was significantly higher in those presented with either dark urine or acholic stool. The predictive performance capability of the MMP7 was not significant in the discrimination of BA from the non-BA group based on receiver operating characteristic curve analysis (area under curve: 0.6, 95% confidence interval: 0.45-0.75). In the optimal cut of point 1.9, the sensitivity and specificity were 84.6% and 45.1%, respectively. Further combination of MMP7 with Gamma-glutamyl transferase (GGT), alkaline phosphatase, direct and total bilirubin, and dark urine or acholic stool was not remarkably boosted the diagnostic accuracy of the test. Interestingly, GGT at a cut-off point of 230 U/L was 84.6% sensitive and 90.3% specific for BA., Conclusion: Our results are not consistent with previous studies on this subject. Considering more conventional and available tests like GGT besides conducting future studies with greater samples and different geographical areas is recommended., (© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V.)

Background: Celiac disease (CD) is an autoimmune disease caused by gluten intake. Traditionally CD was believed to be a disease of the gut, although a wide range of extra-intestinal manifestations (EIM) was recognized. The exact prevalence of EIM and the associated risk factors have not been well studied., Aim: We aimed to assess the prevalence of EIM in children with CD and their association with human leukocyte antigen (HLA) typing, and pathological and laboratory indices., Method: We conducted a cross-sectional study on children and adolescents with a definite diagnosis of CD. They were followed in the main Celiac Clinic of Southern Iran., Results: We included 204 children who were visited between 2012 and 2017. Nearly 85% of them were positive for HLA-DQ2 and 40.6% for HLA-DQ8. The most prevalent intestinal complaints reported were abdominal pain (42.6%) and chronic constipation (19.1%). Failure-to-thrive (32.7%), iron deficiency anemia (25%), short stature (20.5%), and eczema (18.6%) were the most common EIMs. However, failure-to-thrive and short stature were presented at significantly younger ages, whereas those patients with concomitant type 1 diabetes mellitus (DM) were significantly older. We also found significant relationships between autoimmune thyroid disease and HLA-DQ5, and the presence of headaches with HLA-DQ7. The prevalence of HLA types of DQ2, DQ8, DQ6, and DQ7 significantly varied among different Marsh groups. Patients who were positive for HLA-DQ8, were significantly older, taller, and weightier. No significant association was found between HLA types and any of the gastrointestinal symptoms, anti-tTG and compliance to gluten free diet. Moreover, there were no statistically significant differences detected between the presence of each individual EIM, the level of IgA anti-tTG, sex, and Marsh typing., Conclusion: This study highlights the presence of EIM in CD and their associated factors. We show the potential role of HLA typing in some EIMs, which may shed light for future studies., (© 2023. The Author(s).)

Background: Cyclic vomiting syndrome (CVS) is a chronic functional gastrointestinal disorder. It is characterized by recurrent episodes of vomiting typically separated by periods of symptom-free or baseline health. The present study aimed at evaluating the effectiveness of propranolol and the relapse rate of clinical symptoms after stopping treatment in children suffering from CVS. Methods: Records of 504 patients below the age of 18 years with CVS who were treated with propranolol from March 2008 to March 2018 were reviewed. The duration of follow-up was 10 years. Results: The average age of CVS affliction was 4.3 years and the average age at the diagnosis was 5.8 years. All subjects were treated with propranolol (for an average of 10 months). 92% of treated subjects were cured, causing a dramatic decrease in the rate of vomiting ( P  < 0.001). Only an average of 10.5% of the studied subjects (53 people) showed a relapse of symptoms after stopping the treatment. The results of a 10-year follow-up period of the patients showed that 24 had abdominal migraine and 6 had migraine headaches, all of whom lacked the symptoms of disease relapse (prognostic evaluation). Conclusion: The findings of this investigation show that the duration of treating CVS with propranolol could be shortened to 10 months with a low percent of symptoms relapse and this shortening may be effective in preventing the undesirable side effects of the drug. The presence of abdominal migraine and migraine headaches in patients after treatment accomplishment and the lack of disease relapse can be prognostic measures for this disease, which require intensive attention., Competing Interests: Competing Interests The authors declare no conflict of interest related to this work., (© 2023 Middle East Journal of Digestive Diseases.)

Ethnopharmacological Relevance: Rosa × damascena Herrm., known as damask rose, is a bushy shrub that is found abundantly in Fars province, Iran. This species has been used in Iranian traditional practices for the treatment of abdominal pain and constipation, as gastrointestinal diseases. Brown sugar (Saccharum officinarum L.) has also shown laxative effects in pediatric patients with functional constipation., Aim of Study: This study aimed to compare the effects of Polyethylene Glycol (PEG) and a syrup made of R. damascena and brown sugar on the treatment of functional constipation in children aged above 12 months., Materials and Methods: This double-blind randomized clinical trial was performed on 100 patients. One group received PEG and the other received an herbal syrup containing the decocted extract of 0.1 g R. damascena petals mixed with 0.85 g brown sugar per 1 mL. The patients were followed up for two and four weeks and their progresses were recorded., Results: The cure rate was 100% in the R. damascena group and 91.7% in the control group. R. damascena and brown sugar syrup had an odds ratio of 1.09 in the treatment of functional constipation compared to PEG, but the difference was not statistically significant. The only adverse effect detected in the R. damascena group after four weeks was the bad taste of the medication that was too sweet. Nonetheless, this could be solved during the pharmaceutical processes., Conclusion: The R. damascena extract and brown sugar syrup can be used as an effective, safe, and inexpensive agent in the treatment of functional constipation., Competing Interests: Declaration of competing interest None declared., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Recently, an unknown hepatitis outbreak among children has concerned many individuals worldwide. These cases are frequently reported, mainly from Europe and other countries. In this study, we present two similar patients, who, to the best of our knowledge, are the first cases reported in the Middle East (Shiraz, Fars Province, Iran). Unlike in similar cases reported up until 30 April 2022, our patients' hepatitis eventually resulted in aplastic anemia., Case Presentation: In this study, we present cases of two Iranian boys aged 13 and 8 years with hepatitis of unknown origin who developed aplastic anemia in the course of hospitalization., Conclusions: Hepatitis-associated aplastic anemia is a well-known immune-mediated form of aplastic anemia that we detected in our patients and treated with immunosuppressive therapy. One patient established a satisfactory response to the treatment, but unfortunately, the other was declared brain dead., (© 2022. The Author(s).)

Objectives: Estimation of liver fat among living donor candidates is necessary before living donor liver transplant. This study aimed to investigate the usefulness of the controlled attenuation parameter compared with liver biopsy for pretransplant estimation of hepatic steatosis in living liver donors., Materials and Methods: In this retrospective study, we included all individuals who underwent transient elastography with controlled attenuation parameter and ultrasonography-guided liver biopsy as a part of donor evaluations before living donor liver transplant. Clinical and laboratory data of living donor candidates were reviewed and collected., Results: Of 49 donor candidates included in this study, 21 (42.9%) had different degrees of hepatic macrosteatosis. Of the 21 donor candidates who had hepatic steatosis in liver biopsy, 13 individuals were diagnosed to have steatosis in transient elastography. Of the 28 donor candidates without hepatic steatosis in liver biopsy, 26 individuals showed no steatosis in transient elastography (odds ratio: 21.12; 95% CI, 3.91- 114.08; P < .001). Controlled attenuation parameter was useful in discriminating presence (P = .001) and grade of hepatic steatosis (P = .009) compared with liver biopsy with good sensitivity and specificity., Conclusions: The controlled attenuation parameter is a noninvasive method for detection of hepatic steatosis in living donor candidates and can be used as an adjunct to liver biopsy for screening of living donor candidates before liver transplant.

Background: The most common infection in children with the hepatic disease with or without cirrhotic ascites is spontaneous bacterial peritonitis (SBP), which occurs in the absence of an evident intra-abdominal source of infection. The present study aims to assess the value of calprotectin in ascitic fluid in the diagnosis of ascitic fluid infection in children with liver cirrhosis., Materials and Methods: In this cross-section study, 80 children with underlying liver disease who attended the Hepatology and Emergency Department in Shiraz University Hospitals were studied. All the patients were evaluated by a thorough history, clinical examination, laboratory investigations, diagnostic paracentesis with PMNLs count, and Calprotectin, which was measured in 1 mL ascitic fluid by ELISA., Results: Thirty-five patients (43.75%) were diagnosed with ascitic fluid infection. Of these children 6 cases had positive ascitic fluid culture (SBP). Calprotectin was high in AFI patients with a statistically significant difference in AFI patients compared to non-AFI patients. The cut-off levels were 91.55 mg /L and the area under the curve was 0.971. So it can serve as a sensitive and specific diagnostic test for detection of AFI in children with underlying liver disease., Conclusion: Elevated ascitic calprotectin levels in cirrhotic patients are a diagnostic and reliable marker for the detection of AFI and are considered a surrogate marker for PMN., (© 2022. The Author(s).)

Purpose: Children with celiac disease (CD) are at an increased risk of low bone mineral density (BMD) owing to malabsorption of fat-soluble vitamins, inflammation, and malnutrition. This study aimed to determine the prevalence and risk factors for low BMD in Iranian children with CD., Methods: This prospective cohort study examined 149 Iranian children with CD between 2011 and 2018 at Zabol University of Medical Sciences. BMD was measured using dual-energy X-ray absorptiometry. Demographic, clinical, and laboratory data were collected from patients ' medical records. Logistic regression analysis was performed to identify the factors associated with low areal BMD (BMD-Z <-2) in the lumbar spine and femoral neck. Descriptive data were analyzed using the mean, standard deviation, and relative frequency. Data were analyzed using the chi-square test, t -test, and analysis of variance., Results: Of the 149 children with CD, 27.5% had osteoporosis. The mean body mass index (BMI) Z score was -1.28±1.2. Lower BMI was associated with a higher likelihood of BMD-Z (odds ratio 2.17; p ≤0.05)., Conclusion: Overall, the findings of this study showed that there was no correlation among Marsh classification, presence of specific human leukocyte antigens, and low BMD in Iranian children with CD. BMI can be a predictor of bone density in children with CD and may be applied clinically in early screenings to evaluate the bone health status in these children., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2022 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.)

Background: Kawasaki Disease (KD) is the most common childhood vasculitis and cause of acquired heart disease for no apparent reason. There is some evidence indicating infectious agents as possible triggers for KD. During the COVID-19 pandemic, vasculitis has been a presentation of COVID-19 in children. We performed this study to assess the association between KD and COVID-19. We evaluated KD hospitalized children during February to September 2020 for COVID-19 (group one) and compared their demographic, clinical, laboratory, and echocardiographic findings with KD patients from the same period time in 2019 (group two). We also compared the same data in COVID-19 positive and COVID-19 negative KD patients in 2020 pandemic period in Shiraz Namazi referral hospital at southwest of Iran., Results: Thirty-two patients in group one compared with 44 patients in group two. Sixty-eight percent of group one KD patients were positive for COVID-19 during the pandemic period. KD Age of onset in the group one was lower than group two (4.38 years VS 5.5 years, P-value = 0.044). There was no difference in the demographic, clinical, laboratory, and echocardiographic features of the patients during and before the COVID-19 pandemic (p-value > 0.05). Moreover, Comparing COVID-19 positive and negative the incidence of rash was higher within COVID-19 positive cases (p < 0.05), and coronary artery abnormalities were more prevalent in COVID-19 negative cases (p < 0.05)., Conclusion: Admission rate of KD was almost similar during the COVID-19 pandemic but 68% of KD admitted patient were COVID-19 positive. Age of onset for KD during the COVID-19 pandemic was lower and skin manifestation was higher than the same period time in last year., (© 2021. The Author(s).)

Aim of the Study: Prognostic scores are highly needed to properly manage children with cirrhosis and improve their clinical outcomes. The relationship between lymphocyte-to-monocyte ratio (LMR) at the time of admission to hospital and outcome of cirrhosis has been studied in adults, but to the best of our knowledge, there is no study regarding its utility as a prognostic marker of poor outcome in children with cirrhosis. Thus, this study aimed to investigate the potential prognostic value of LMR in such patients., Material and Methods: At the time of admission, LMR, Child-Pugh, and Pediatric End-stage Liver Disease/Model for End-stage Liver Disease (PELD/MELD) scores were calculated for 114 children with cirrhosis. LMR and PELD/MELD and Child-Pugh scores were compared between the survivor and non-survivor groups. Receiver operator characteristic (ROC) curve analysis was performed and the cutoff values were calculated using the Youden index., Results: It was found that LMR had a strong negative correlation with PELD/MELD ( r = -0.87, p = 0.36) and a weak negative correlation with Child-Pugh scores ( r = -0.046, p = 0.63). The highest area under the curve (AUC) was found for LMR (0.861). The AUC was also good for PELD/MELD scores (0.804). The AUC values for LMR in patients under and above 6 years old were 0.675 (95% CI: 0.462-0.888) ( p = 0.111) and 0.926 (95% CI: 0.852-1.000) ( p < 0.001), respectively. The PELD/MELD scores were significantly higher in the low LMR group than in the high LMR group ( p = 0.001)., Conclusions: LMR can be used to determine the outcome of cirrhotic children older than 6 years during the hospital stay because it is easy to calculate and its efficacy is comparable to PELD/MELD scores. Meanwhile, further studies are needed to confirm these preliminary results., (Copyright © 2021 Clinical and Experimental Hepatology.)

Aim: The aim of this study was to determine allograft fibrosis by measuring LS using TE in children after liver transplantation at Shiraz Organ Transplant Center., Background: Liver stiffness (LS) assessment using fibro-scanning (transient elastography-TE) is a non-invasive method for evaluating liver fibrosis., Methods: All children undergoing liver transplant from 2012 to 2016 were included in the study. Data on demographics, graft types, immunosuppressive drugs, as well as clinical and paraclinical data were obtained from patients' records. TE was performed to determine LS in all patients. Liver fibrosis was also confirmed based on Metavir score., Results: During this period, more than 400 liver Tx were done in children, but only 54 patients, comprising 20 (37%) girls and 34 (63%) boys who underwent liver transplantation, were available and willing to participate in this study. The mean age of the patients was 12.96 ± 5.32 years. Correlations between FS score (LS) and AST ( p = 0.01), total bilirubin ( p = 0.002), albumin ( p = 0.001), PT ( p = 0.03), and INR ( p = 0.001) were significant. There was no significant relationship between FS score (LS) and type of allograft ( p = 0.79) and underlying disease ( p = 0.36). Positive and significant correlations were observed between Metavir score and AST ( p = 0.01), total bilirubin ( p = 0.01), INR ( p = 0.004), and cholesterol ( p = 0.001). The severity of fibrosis significantly and negatively correlated with albumin ( p = 0.004) and glucose ( p = 0.003). Also, there was no significant relationship between Metavir score and allograft type ( p = 0.7)., Conclusion: The current study demonstrated that 14.9% of LT patients had a METAVIR ≥ F2. The time between LT and TE was significantly correlated with LS and the degree of liver fibrosis based on Metavir score. However, there was no significant relationship between LS with allograft type or underlying liver disease., Competing Interests: The authors declare that they have no conflict of interest., (©2021 RIGLD, Research Institute for Gastroenterology and Liver Diseases.)

Background: Autoimmune hepatitis (AIH) is a progressive inflammatory liver disease with various clinical symptoms, but treatment and prevention of hepatic failure and cirrhosis is possible with early diagnosis. However, no specific test has been approved for the diagnosis of AIH. In 2008, the International Autoimmune Hepatitis Group (IAIHG) developed a simplified diagnostic scoring system that has been widely used in practice. Nevertheless, it cannot distinguish AIH from Primary Sclerosing Cholangitis (PSC) and consensus is lacking with respect to its validity, sensitivity, and applicability for children patients. The newer 2018 version also requires validation. The present study intends to evaluate the validity and efficiency of the IAIHG simplified scoring system and new scoring system in children with AIH., Methods: The present study is a non-interventional case-control study covering 152 patients with hepatic diseases (83 patients with AIH and 69 patients with Wilson disease (WD)). Titers of autoantibodies, IgG levels, hepatic histology, and absence of viral hepatitis were scored and calculated according to IAIHG diagnostic criteria. Statistics software package (SPSS) and draft receiver operating characteristic (ROC) curves was used to analyze data and determine value of diagnostic criteria., Result: In our study, both scoring systems' accuracy was good in AIH diagnosis, although new score displays higher sensitivity and specificity, suggestive of greater accuracy and predictive strength., Conclusion: Our study is the first validation study of the new scoring system in diagnosing AIH, and further studies require verifying this scoring system.

BACKGROUND Celiac disease is a common disorder but there are few studies comparing the clinical features of the disease in adults, adolescents and children. METHODS Demographic and clinical characteristics of all patients with celiac disease referred to the Celiac Clinic were evaluated and compared in different age groups. RESULTS Of 3416 participants, 473 patients were included. 302 (63.8%) were women and 171 (36.2%) were men. Overall, 325 (68.7%) and 411 (86.9%) patients had gastrointestinal (GI) and non-GI manifestations, respectively. The most common symptom in adults was psychiatric problems (66.5%), while abdominal discomfort was the most common symptom in adolescents (45.2%) and children (53.8%). According to age groups, GI manifestations were seen in 79 (66.4%), 119 (59.8%), and 127 (81.9%) children, adolescents, and adults, respectively. Adults had significantly more GI manifestations than the other groups (PR 1.167; 95% CI: 1.094- 1.244; p < 0.001). Non-GI manifestations were seen in 90 (75.6%), 174 (87.4%), and 147 (94.8%) children, adolescents, and adults, respectively. Adults had significantly more non-GI manifestations than the other groups (PR 1.112; 95% CI: 1.060-1.168; p < 0.001). CONCLUSION Our study showed that there were significant differences in the clinical features of celiac disease between the different age groups. Considering these results may help plan for future studies., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest related to this work., (© 2021 The Author(s).)

Glycogen storage diseases (GSDs) are known as complex disorders with overlapping manifestations. These features also preclude a specific clinical diagnosis, requiring more accurate paraclinical tests. To evaluate the patients with particular diagnosis features characterizing GSD, an observational retrospective case study was designed by performing a targeted gene sequencing (TGS) for accurate subtyping. A total of the 15 pediatric patients were admitted to our hospital and referred for molecular genetic testing using TGS. Eight genes namely SLC37A4, AGL, GBE1, PYGL, PHKB, PGAM2, and PRKAG2 were detected to be responsible for the onset of the clinical symptoms. A total number of 15 variants were identified i.e. mostly loss-of-function (LoF) variants, of which 10 variants were novel. Finally, diagnosis of GSD types Ib, III, IV, VI, IXb, IXc, X, and GSD of the heart, lethal congenital was made in 13 out of the 14 patients. Notably, GSD-IX and GSD of the heart-lethal congenital (i.e. PRKAG2 deficiency) patients have been reported in Iran for the first time which shown the development of liver cirrhosis with novel variants. These results showed that TGS, in combination with clinical, biochemical, and pathological hallmarks, could provide accurate and high-throughput results for diagnosing and sub-typing GSD and related diseases.

Purpose: Celiac disease (CD) is a common autoimmune disease with extra-intestinal manifestations, including neurological disorders. There are few reports to assess various factors in increasing the chances of developing neurological disorders in CD, so we designed this study., Methods: All patients with CD at any age who had been referred to the Celiac Clinic were evaluated for neurological problems. CD was defined as IgA anti-transglutaminase antibodies (anti-tTG) of 18 IU/mL or higher in serology and Marsh type I or more severe in histopathological evaluation. Logistic regression analysis was used to evaluate the impact of various independent variables on the neurological manifestations., Results: A total of 540 patients enrolled in this study. A 360 (66.7%) of patients were children. A 64.8% and 35.2% were female and male, respectively. Overall, 34.1% of patients had neurological manifestation, including headache, neuropathy, epilepsy, and ataxia. The odds of developing neurological manifestations in children were significantly lower than in adults (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.45-0.96; p =0.03) and in patients with gastrointestinal (GI) symptoms significantly higher than in the group without GI manifestations (OR, 1.77; 95% CI, 1.18-2.63; p =0.005). Other variables, including Marsh classification (OR, 0.44; 95% CI, 0.18-1.11; p =0.08) and anti-tTG levels (OR, 1.00; 95% CI, 0.999-1.001; p =0.59) did not significantly increase the chances of developing neurological disorders., Conclusion: Our study showed that increasing age and the presence of GI symptoms, but not serological and histological findings, could increase the chances of developing neurological diseases in CD patients., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2021 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.)

Objective: We described our experiences on pediatric liver transplantation (LT) from the largest LT center in the world termed the Shiraz Transplant Center., Background: After the first successful pediatric LT in 1967, pediatric LT has become the routine treatment for children with liver failure worldwide., Methods: Data on a total of 1141 pediatric cases of LT were collected. Specifics on baseline and anthropometric characteristics, clinicopathology, prognosis of recipients of LT, and donor characteristics are reported., Results: Mean age of patients was 7.83 ± 5.55 years old. Most common etiologies for LT were biliary atresia (15.9%), progressive familial intrahepatic cholestasis (13.4%), and Wilson's disease (13.3%), respectively.Whole organs, living donor grafts, and split grafts were used in 47.9%, 41%, and 11.1% of patients, respectively. In-hospital complications were seen among 34.7% of patients and the most common complications were infections (26.8%), bleeding (23.4%), and vascular complications (18%).Median (interquartile range) model for end stage liver disease score was 20 (15, 25). Main causes of death among patients were sepsis (35.2%), followed by post-transplantation lymphoproliferative diseases (10.5%), and primary nonfunction of liver (9%).Patient survival showed improvement over the years (1-year survival of 73.1%, 83.4%, and 84.4%, 2-year survival of 65.2%, 77.1%, and 78.7%, 5-year survival of 58.2%, 72%, and 77.8% for 1997-2007, 2007-2013, and 2013-2019, respectively; P < 0.001)., Conclusions: This is the largest single-center report on pediatric LT in literature which provides valuable experiences in pediatric LT., Competing Interests: The authors have no conflict of interest to report regarding any part of this study., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Celiac disease is a chronic disease that affect small bowel by making its villi become atrophic. Various environmental and genetic factors have been identify as inducing factors for celiac disease. Most of the patients has one of the HLA DQ forms. Although the prevalence of these genes are variable in different areas of the world, we do not have a comprehensive information about this issue in our region. Thus the aim of present study is to investigate the prevalence of HLA DQ typing of patients who visited Emam Reza Gastroenterology clinic of Shiraz(IRAN)., Methods: In this case-control study all under 18 years old children who were diagnosed with celiac disease and have visited Emam Reza gastroenterology clinic were investigated. The diagnosis of celiac disease was made by history, physical exam, serologic test, and histopathology of duodenal biopsy. Blood sample was taken and HLA typing performed using PCR method at Motahari clinic cytology laboratory. Also those people who neither them self nor their first degree relatives were not case of celiac disease and underwent HLA typing for other reason were identified as control group. The statistical analysis was done using SPSS 18 software. The p value < 0.05 was identified as statistically significant., Results: A total of 139 patients with celiac disease and 146 normal children were studied. The mean age of the patient with celiac disease were 9.1 years old with standard deviation of 3.4 years old. 64% of the celiac patients were girls and 36% were boys. While this proportion was 54.4% for boy and 48.6% for girls in control group. The most common HLA in celiac patients group were HLA DQ2 and 8 but the most common ones in control group were HLA DQ 8 and 5. Failure to Thrive were the most common signs of the celiac patients with a prevalence of 60 children. Total IgA titer were normal in 98.6% of the patients and TTG IgA titer were positive in 93.5% of the patients. The most common co existing disease with the celiac disease were diabetes with a prevalence of 30 children (66.7%)., Conclusion: present study reveals that the prevalence of the HLA DQ2 and 8 among patients with celiac disease is 72.6% and 53% in our normal population.

Background. Crigler-Najjar syndrome (CNS) is a rare genetic disorder found in less than 1 per 1.000.000 births. It happens as a result of an error in UGT1A1 enzyme which can cause high unconjugated bilirubin levels., Objective: To describe liver histology changes in patients who have undergone liver transplantation., Methods: This retrospective cross-sectional study was performed to evaluate the liver pathologies of patients with type 1 of Crigler-Najjar syndrome (CNS1). We analyzed medical records and liver histologic specimens of 53 children who were transplanted in Namazi Hospital Organ Transplant Center affiliated with Shiraz University of Medical Sciences between 2009 and 2019. We studied the tissue of the explanted liver, which was replaced by transplants. Most of the patients were less than 2 years old, with an average age of 1.7 years. The collected data were analyzed using SPSS 22 software., Results: The prevalent pathology found in the liver of these patients was periportal fibrosis (96.2%). Cholestasis was the second common finding (94.3%) followed by pericentral fibrosis (86.7%) and ductal reaction (22.6%). A significant correlation was only present between phototherapy time and ductal reaction grade., Conclusion: Our results indicated a high prevalence of fibrosis of different grades among CNS 1 patients which bolds the necessity of histologic examination before considering treatments such as gene therapy or hepatocyte transplantation.

Objectives: Liver transplant has been used as a curative approach for children with end-stage liver diseases. Here, we describe the underlying causes for pediatric liver transplant performed at the Shiraz Organ Transplantation Center, Nemazee Hospital, Shiraz, Iran., Materials and Methods: In this cross-sectional descriptive study, children < 18 years old who were candidates for liver transplant from 2007 to 2010 at the Shiraz Organ Transplantation Center were included. Patients were evaluated for their underlying diseases leading to liver failure. Disease severity was assessed and compared with Pediatric End-Stage Liver Disease model and the Model for End-Stage Liver Disease scores., Results: Of 107 patients, 60.8% were males and 39.2% were females. The mean age was 11.6 ± 4.9 years. Thirteen patients (12.5%) were < 2 years old, 26 (24%) were 2 to 6 years old, 33 (30.8%) were 6 to 12 years old, and 35 (32.7%) were 12 to 18 years old. Underlying liver diseases comprised biliary atresia (27.1%), cryptogenic cirrhosis (21.5%), autoimmune cirrhosis (13.1%), familial intrahepatic cholestasis (11.2%), Wilson disease (9.3%), tyrosinemia (7.4%), neonatal hepatitis (4.7%), congenital hepatic fibrosis (3.7%), and Caroli disease (1.9%). Jaundice (83.2%), ascites (57%), and esophageal varices (43%) were the most common clinical findings. Mean serum direct bilirubin, total bilirubin, international normalized ratio, and serum creatinine values were 3.6 ± 0.8 mg/dL, 9.3 ± 9.1 mg/dL, 2.1 ± 1.1, and 0.6 ± 0.2 mg/dL, respectively. The mean Pediatric End-Stage Liver Disease score in children < 12 years old was 11.4 ± 9.1. The mean Model for EndStage Liver Disease score in children > 12 years old was 13.7 ± 5.9. There were no differences in scores among sex, age groups, or different etiologies., Conclusions: Scores for disease severity were not significantly different with regard to different causes of underlying diseases for liver transplant in Iranian children.

BACKGROUND Functional gastrointestinal system diseases (FGIDs) are a group of childhood disorders, our knowledge of which is relatively limited. More importantly, the different subgroups among such a disease group are closely interrelated, and their natural courses and interrelations have yet to be fully clarified. Functional constipation and gastroesophageal reflux disease (GERD) are most frequently seen among this group. However, evidence as to whether any relationship exists between them is limited. In this study, we tried to examine the existence or absence of this relationship. METHODS First, patients with functional constipation were identified based on ROME III criteria, which included 205 patients. All patients were classified into two groups of 185 and 20 patients based on their ability to respond to the questions. Then age, sex, duration of constipation, treatment, and symptoms associated with reflux were examined based on the GERD questionnaire (in case group 185) and I-GERD (in case group 20). Score > 11 in the GERD questionnaire and score > 15 in the I-GERD questionnaire were considered as reflux disease. The variables that were evaluated using Chi-square and Fisher exact tests using SPSS software version 19 included age, sex, the onset of constipation, constipation duration, duration of treatment of constipation, ROME III criteria, and symptoms associated with reflux. RESULTS In the current study 205 subjects were included (girls = 49.8%, boys = 50.2%). The mean age of the children was 5.51 ± 3.15 years. Among the Rome III criteria, the most frequent were retentive posturing, painful defecation, history of large stool defecation, defecation less than 2 times per week, stool accumulation in the rectum, and fecal incontinency more than once a week, respectively. The lowest symptom among people with chronic constipation was fecal incontinency. Also, 46.8% of all patients in the study had a positive familial history. In general, there were 29 patients (14.1%) with reflux out of the 205 patients with functional constipation. In the present study, no significant relationship was found between Rome III criteria and reflux. CONCLUSION The frequency of GERD among cases with constipation was 14.1%. There was no significant relationship between Rome III criteria and reflux., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest related to this work., (© 2020 The Author(s).)

Purpose: Progressive familial intrahepatic cholestasis (PFIC) is a hereditary disease characterized by cholestasis, which may cause jaundice, severe pruritus, and cirrhosis in the later stages. By the invention of biliary diversion methods, these patients were prevented from undergoing liver transplant. Using biliary diversion techniques, the entero-hepatic cycle was interrupted. This lowers the bile acid pool and resolves the pruritus. Herein, we report 44 cases of PFIC who underwent partial internal biliary diversion (PIBD) and long-term follow-up of these children. This comprises the largest case series of PIBD., Methods: All patients were diagnosed by liver biopsy as PFIC before the operation. All underwent cholecysto colic bypass by jejunal interposition due to severe pruritus unresponsive to medication. Laboratory blood tests, sonography, and physical exam were done before and after the operation once every 3 months. Besides, a questionnaire was designed to ask the patients about the symptoms after the operation, and a pruritus score was measured using the 5D-itch scale., Results: 44 children (25 boys, 19 girls), between 1.75 and 27.5 years (at the time of this study) were followed for a median period of 54 months. Age at operation ranged from 2 months to 18 years, with a median of 29 months. Of these children, 14 were lost to follow up. Results showed a significant decrease in pruritus and sleep disturbance after the surgery (p < 0.001). Also, jaundice decreased from 82.1 before to 7.1% following the surgery. 50% of the patients became medication-free at follow-up., Conclusion: PIBD is a safe procedure which helps non-cirrhotic children preserve their liver function. Therefore, PIBD prevents them from undergoing liver transplant. Effective results were achieved in terms of severe pruritus and jaundice, and children were able to regain their sleep patterns. It also avoided external stoma, which is more convenient from the patient's point of view.

Background: Autoimmune hepatitis (AIH) is an auto-inflammatory liver disease of children and adults, affecting patients of any age, sex, race or ethnicity, with more prevalence in females., Objective: The aim of this study was to evaluate clinical manifestation, laboratory findings, and outcome of children with autoimmune hepatitis., Materials and Methods: We evaluated 86 patients treated and followed with final diagnosis of AIH between years 2010 to 2018. Physical findings (including jaundice, hepatomegaly, splenomegaly and encephalopathy), liver enzymes, liver histology and autoantibodies (including ANA, Anti LKM-1 and ASMA) were extracted from medical files. Then the patients were followed for their final outcome (including response to medical treatment or successful treatment withdrawal, liver transplantation or death)., Results: Among 86 patients with AIH with mean age 9.10±4.36 years old, 66.27% were females. Jaundice (75.6%) and hepatomegaly (46.5%) were the most frequent physical findings, followed by splenomegaly (32.6%) and encephalopathy (17.4%). Aminotransferases including AST and ALT were elevated at least 3 times more than upper limit of normal in most of the patients (61.6% and 55.81%, respectively). Autoantibodies were available in 53 of 86 patients, 24.5% had AIH-1, 3.8% had AIH-II and 67.9% were seronegative. Medical treatment including prednisolone and azathioprine was started for patients, 53 of 86 cases (61.6%) had remission and 11 of 86 (13.7%) tolerated medication withdrawal successfully. Among all cases, 26 (30.2%) patients needed liver transplantation. Mortality rate was 9 among 86 cases (10.5%)., Conclusion: Jaundice and hepatomegaly was the most frequent clinical findings. Mortality rate was 10.5.

Introduction: Renal dysfunction is among the common and considerable complications after liver transplantation and is principally attributable to immunosuppressive medications .The purpose of this study was to define the prevalence of hypertension and renal dysfunction among pediatric liver transplant recipients., Methods: 46 pediatric liver transplant recipients were assessed for hypertension utilizing ambulatory blood pressure monitoring (ABPM), and glomerular, and tubular renal function at the transplant clinic of Shiraz University of Medical Sciences. Results were analyzed using SPSS 19 and P value < .05 was considered statistically significant., Results: The mean age of the patients was 12.2 ± 3.3 years and 24 of them were female. Considering ABPM measurements 20 patients (43.5%) were hypertensive, 37% were systolic and 36.6% were diastolic non-dippers respectively. eGFR was calculated based on different formulations and Cystatin C-based equation estimated lower GFR than Cr-based equation. Micro-albuminuria was noticed in 26.1%. Additional parameters of tubular dysfunction included hyperuricosuria (4.3%), hypercalciuria (6.5%), abnormal fractional excretion of Mg (FeMg) (43.5%), abnormal tubular reabsorption of phosphate (TRP) (4.3%), and abnormal fractional excretion of uric acid (FEUA) in 13% of the patients. We noticed a statistically significant negative correlation between hypercalciuria, microalbuminuria, FeMg (P < .05) and GFR., Conclusion: Renal function impairment and hypertension are frequent complications amongst pediatric liver transplant recipients. Using Cyctatin C instead of Cr based formula for GFR estimation, and blood pressure monitoring by ABPM and regular screening of renal function are essential measures for recognition and treatment of renal dysfunction in these patients.

Objectives: Liver replacement continues to be the only definitive mode of therapy for children with end-stage liver disease. However, it remains challenging because of the rare donor organs, complex surgical demands, and the necessity to prevent long-term complications. Our objectives were to analyze 16 years of experience in the Shiraz University Organ Transplant Center., Materials and Methods: We retrospectively analyzed the records of 752 patients (< 18 years old) who underwent orthotopic liver transplant at our center over a 16-year period. Mean age was 90 months, and male-to-female ratio was 1.25. Of the 752 transplants, 354 were whole organs, 311 were from living related donors, and 87 were in situ split liver allografts. Patient and graft survival rates were determined at 1, 3, and 5 years, and results between groups were compared., Results: Overall mortality was 31.8%. The 1-, 3-, and 5-year patient survival rates were 77%, 69%, and 66%, respectively, whereas the respective graft survival rates were 75%, 68%, and 65%. We observed significant differences in survival according to graft type (log-rank test, P < .001). We also observed significant differences in survival probabilities according to age (log-rank test, P < .001). Cox regression was used to simultaneously analyze effects of age and graft type on survival. Both graft type and age significantly affected survival (P < .001). The 1-, 3, and 5-year survival rates for patients having whole organ transplants were 88%, 81%, and 78%. Patients who received living donor grafts had respective survival rates of 66%, 60%, and 58%, with rates of 65%, 47%, and 47% for patients who received split grafts., Conclusions: Our results were similar to those observed in the literature in terms of indication for transplant and posttransplant survival.

Background: Long-term efficiency of attenuated immunosuppressive therapies is not well characterized in pediatric liver transplantation (LT)., Objective: To assess the efficiency of tacrolimus once daily (TAC-OD) and sirolimus once daily (SLR-OD) immunosuppression in pediatric LT., Methods: We retrospectively evaluated 59 children who underwent LT in our center during 2002 to 2016. Those including children who underwent planned decrease in immunosuppressant dose (stable clinical conditions after 2 years of LT), and those who underwent unplanned decrease in immunosuppressant dose (because of complications such as post-transplant lymphoproliferative disorder [PTLD] and renal failure)., Results: 25 of 59 children underwent planned decrease in immunosuppressant dosage (mean±SD duration of 4.5±1.8, range: 3-11 years); 34 had unplanned decrease (mean±SD of 1.3±0.6, range: 0.5-2.6 years). 19 of 25 children with planned conversion received TAC-OD; 6 received SLR-OD (22 with 1 mg/day dose, and 3 with 1 mg every two days). Of 34 children with unplanned conversion, 27 received TAC-OD, 7 SLR-OD (25 children with 1 mg/day, 7 with 1 mg every two days, 1 with 0.5 mg/day TAC, and 1 with 0.5 mg TAC every two days). We found no adverse events including acute or chronic graft rejection, renal insufficiency, infections, PTLDs, or cardiovascular thrombotic events after initiation of the modified immunosuppression in none of the groups., Conclusion: TAC-OD or SLR-OD monotherapies are safe and effective for long-term management of LT children with either stable clinical conditions or those with LT complications.