[Liver histologic changes in children with type 1 of Crigler-Najjar syndrome]. / Gistologicheskie izmeneniya pecheni u detei s sindromom Kriglera-Nadzhara 1 tipa.

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.

Tacrolimus and Sirolimus Once Daily Monotherapy Regimen as a Safe and Effective Long-Term Maintenance Immunosuppressive Therapy in Pediatric Liver Transplantation.

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.

Diagnostic Value of a Modified Version of Wilson's Diagnostic Score in Pediatrics.

Background: Wilson's disease (WD) is an autosomal-recessive hereditary liver disease affecting copper metabolism. OBJECTIVE: To test the diagnostic value of a questionnaire for the diagnosis of WD in pediatrics age group. METHODS: 70 children with biopsy-proven diagnosis of WD and 70 without WD were included in the study. A modified questionnaire with 4 items was used for the diagnosis of WD. The results were then compared to the definite diagnosis made by pathology (the gold standard test). RESULTS: The median (IQR) modified score in those with WD was 4 (4-5), significantly (p<0.001) higher than that calculated for the comparison group, which was 0 (0-1). The most appropriate cut-off value for the score was 2.5, corresponding to a sensitivity and specificity of 100%, and 98.6%, respectively. Using this cut-off value to classify 20 children with and without WD who underwent liver transplantation resulted in an accuracy of 100%. CONCLUSION: The modified scoring system is a sensitive and specific diagnostic tool for the diagnosis of WD in children. This is especially important in regions with limited access to specific laboratory tests for the diagnosis of WD.

Endocrine Disorders in Pediatric and Adolescent Liver-transplant Recipients.

BACKGROUND: Particular requirements of pediatric and adolescent liver-transplant (LT) recipients necessitate the evaluation of such population from the endocrine viewpoint. OBJECTIVE: To determine the endocrine disorders among LT recipients. METHODS: 129 LT recipients younger than 18 years, and at least 6 months post-LT with no pervious history of endocrine disorders were included in the study. Demographic, anthropometric and biochemical data were collected. RESULTS: 36% of cases had evidence of impaired fasting glucose; the problem, however, was dramatically resolved (decreased to 2.3%) by using of prediabetic diet. Identifying only 1 case of primary hypothyroidism indicated that thyroid dysfunction seems not to be a prevalent finding in the patients. 3 cases of rickets and no case of parathyroid dysfunction were identified. 11% of the study population were hypocalcemic (2 had rickets as well). Pubertal condition in 3 patients and delayed puberty before LT in 6 remained the same; further evaluation revealed they had hypogonadotropic hypogonadism. CONCLUSION: Regular monitoring for development of diabetes and hypocalcemia is indicated. Evaluation of those with delayed puberty for receiving sexual hormones is also recommended.

Acute Hepatic Allograft Rejection in Pediatric Recipients: Effective Factors.

BACKGROUND: Acute cellular rejection (ACR), a reversible process, can affect the graft survival. OBJECTIVE: To evaluate the relation between ACR and clinical factors in recipients of allograft liver transplantation. METHODS: 47 recipients of liver were consecutively enrolled in a retrospective study. Their information were retrieved from their medical records and analyzed. RESULTS: Of the 47 recipients, 38 (81%) experienced acute rejection during 24 months of the transplantation. None of the studied factors for occurring transplant rejection, i.e., blood groups, sex, age, familial history of disease, receiving drugs and blood products, type of donor, Child score, and Child class, was not found to be significant. CONCLUSION: During a limited follow-up period, we did not find any association between ACR and suspected risk factors.

Acute Hepatic Allograft Rejection in Pediatric Recipients: Independent Factors.

BACKGROUND: Acute cellular rejection (ACR) has a reversible effect on graft and its survival. OBJECTIVE: To evaluate the relation between ACR and clinical factors in recipients of liver transplant allografts. METHODS: 47 consecutive liver recipients were retrospectively studied. Their data were extracted from records and analyzed. RESULTS: 38 (81%) of the 47 recipients experienced ACR during a 24-month follow-up. The rate of rejection was associated with none of the studied factors-recipient's blood group, sex, age, familial history of disease, drugs and blood products received, type of donor, and Child score and class. CONCLUSION: During a limited follow-up period, we did not find any association between ACR and suspected risk factors.

Croup as Unusual Presentation of Post-transplantation Lymphoproliferative Disorder after Liver Transplantation in an 18-month-old Child.

Post-transplantation lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation that occurs due to immunosuppression and other risk factors. PTLD may present with involvement of other organs and with unusual presentation. The presentation is often extranodal (e.g., in the gastrointestinal tract, lung, or the central nervous system). Herein, we report on a 1.5-year-old girl who underwent liver transplantation almost 5 months prior to admission. She was on medications such as tacrolimus and prednisolone. Her presentation was started with symptoms of the upper respiratory infection followed by croupy cough and respiratory distress with no response to usual treatments. She had respiratory arrest during broncoscopy. Therefore, emergency tracheostomy was done. Biopsy from the paratracheal mass revealed large B cell non-Hodgkin lymphoma (PTLD, monomorphic and high grade). This case presentation shows that persistent upper airway symptoms, particularly stridor and croupy cough, in children who underwent liver transplant should be further evaluated; the physician needs to have a high degree of clinical suspicion for the diagnosis of PTLD in this situation.

Parents' education level and mortality and morbidity of children after liver transplantation.

BACKGROUND: So far numerous post-transplant outcome predictors have been studied to decrease the loss of resources and grafts after organ transplantation. The role of education, as a predictor, in liver transplantation outcome has so far been studied in several articles. However, in most of the studies it was evaluated as a surrogate for socioeconomic status or other variants. The absolute impact of parents' education has rarely been studied. Adult patients are their own caregivers whereas pediatric liver transplantation recipients are mostly cared by their parents. OBJECTIVE: To evaluate the effect of level of patients' education on the mortality and morbidity of pediatric liver transplant recipients. METHODS: We studied a group of 91 children who had undergone liver transplantation in our center from March 21, 2012 to July 21, 2013. In this retrospective study, patients' medical charts and questionnaire were used to collect the necessary data. Post-transplantation mortality and complications were divided into two categories: Early (<6 months after liver transplantation), and late (≥6 months after the transplantation). Parents' educational level was also categorized into 5 groups. RESULTS: Multivariate analysis of all groups showed that paternal education is an independent predictor of the late post-transplantation complications (p=0.024). Educational level of children's mothers had no significant correlation with the late post-transplantation complications (p=0.45). Neither maternal (p=0.59) nor paternal (p=0.607) education had significant effect on the late post-transplantation mortality. CONCLUSION: Paternal educational level of liver transplanted children is associated with the late post-transplantation complications.

Granulomatous liver involvement in a child with systemic lupus erythematosus: a case report and review of the literature.

Systemic lupus erythematosus (SLE) is uncommon in young children and unusual in infancy. Although a variety of liver pathologies have been reported in SLE, presentation of this disease with granulomatous liver involvement is very rare. In this article, for the first time, we report an infant girl presenting with unexplained hepatosplenomegaly and non-necrotizing granulomatous liver involvement at the age of six months who later developed pancytopenia and proteinuria and was finally diagnosed with SLE at the age of three years. Therefore, we suggest that SLE could be considered as one of the possible differential diagnoses when infants or children present with unexplained granulomatous liver involvement.

Causes of organ donation refusal in southern Iran.

BACKGROUND: Family refusal is an important factor that limits the number of organ donations. Some studies from different centers have reported various reasons for family decisions of organ donation refusal. This study evaluated the reasons for organ donation refusal by family members covered in our organ procurement organization. METHODS: This cross-sectional study was performed among families of potential organ donors who satisfied brain death criteria as identified between March 2009 and March 2010. RESULTS: Among 125 potential donors 73 (58.4%) families refused donation. Their main reasons were as follows: lack of acceptance of brain death n=26 (35.6%), belief in miracle and patient recovery (n=22; 30.1), fear of gossip regarding sale rather than autonomous organ donation (n=11; 15.1%), and fear about deformation of the donor's body (n=9; 12.3%). CONCLUSION: Family members play an important role in the final decision for organ donation. The general public should be encouraged to register their donation preferences in the case of brain death.

Evaluation of cytomegalovirus infection after six months of liver transplantation in children in shiraz, southern iran.

BACKGROUND: Liver transplantation (LT) is a life-saving treatment for end-stage liver diseases (ESLD). Cytomegalovirus (CMV) infection is one of the important causes of morbidity after LT. OBJECTIVE: To evaluate the incidence of late-onset (after 6 months of LT) CMV infection in pediatric recipients. METHODS: A retrospective analysis was conducted to evaluate 50 pediatric patients who underwent LT for 8 years at the LT Unit of Nemazee Hospital affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. We retrospectively investigated episodes of CMV infection after 6 months of LT proven by CMV antigenemia test. RESULTS: Three recipients (6%) developed late-onset CMV infection. These patients finally responded to ganciclovir. CONCLUSION: CMV infection is one of the most common post-LT viral infections that usually occurs in the first six months of LT. Our study shows that the incidence of late-onset CMV infection is relatively low, but it still remains a significant problem. Therefore, monitoring and management is crucial for improving the survival of children.

Liver transplantation and aortic valve replacement.

Surgical procedures involving heart and liver are rare and have been limited to either combined heart and liver transplantation or coronary artery bypass graft surgery (CABG) or aortic valve surgery and orthotopic liver transplantation (OLT). Aortic valve replacement (AVR) and pulmonary valve vegetectomy for bacterial endocarditis after OLT have also been reported. There are only five cases with aortic stenosis and cirrhosis reported to have combined AVR and liver transplantation. In the presence of cirrhosis, AVR has a significant risk for mortality because of bleeding from coagulopathy, renal failure, infection, and poor post-operative wound healing. Herein, we report on a case and management analysis of combined sequential AVR, and OLT in a 40-year-old cirrhotic man with Child and MELD score of C and 29, respectively. Echocardiography detected severe aortic insufficiency (AI) with enlarged left ventricle. Due to severe AI, the cardiologist recommended AVR prior to transplantation. The patient underwent metallic AVR. 4 months later, he received OLT. Both operations were successful and uneventful. Prioritizing AVR before OLT was successful in this patient. However, each patient must be evaluated individually and multiple factors should be assessed in pre-operation evaluation.

Evaluation of Candida infection after six months of transplantation in pediatric liver recipients in iran.

BACKGROUND: Liver transplantation (LT) is the standard treatment of end-stage liver diseases (ESLD). Invasive fungal infection is one of the important causes of morbidity and mortality after transplantation. OBJECTIVE: To determine the incidence of late-onset (after 6 months of LT) Candida infection in recipients. METHODS: A retrospective study was conducted to evaluate 50 pediatric patients after LT for 8 years at the LT Unit of Nemazee Hospital affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. We followed the patients until 6 months post-LT for episodes of Candida infection proven by culture. RESULTS: One recipient (2%) developed late-onset esophageal candidiasis with improvement after intravenous amphotricin therapy but finally expired with a diagnosis of post-transplant lymphoproliferative disorder (PTLD). CONCLUSIONS: The incidence of late-onset Candida infection is not significant in pediatric liver recipient, but it still remains a significant problem. Control of Candida colonization would reduce the risk of invasive fungal infections and possibly more fatal complications.

Prevalence of zinc deficiency in 3-18 years old children in shiraz-iran.

BACKGROUND: Zinc is an essential trace element with a prominent role in human nutrition. Zinc deficiency has been linked to growth retardation, hypogonadism in males, and lack of sexual development in females. It ranges from 50% in sub-Saharan Africa to 5% in high income countries. The aim of this study is to evaluate the prevalence of zinc deficiency in healthy children in Shiraz, southern Iran. METHODS: In this study, 902 children aged 3-18 years old were randomly sampled for serum zinc level. Age, sex, weight, height, BMI, stunting and wasting indices were also recorded. With atomic absorption spectrophotometry method, the serum level of zinc less than 70 µg/dL was considered as deficient. RESULTS: Mean serum level of zinc was 122.3±55 µg/dL. The prevalence of zinc deficiency was 7.9%. There was no relationship among serum zinc level and age, sex, height, weight or BMI, but mild wasting (weight for age) and mild stunting (height for age) were significantly more prevalent among zinc deficient children compared to children with normal or high level of zinc. CONCLUSION: Zinc deficiency in Shiraz is not as prevalent as other areas of Iran. It was significantly more frequent among stunted and wasted (malnourished) children. Difference in soil zinc level, recent wide prescription of zinc supplements by pediatricians and especial pattern of nutrition, considered as possible factors responsible for lower prevalence of zinc deficiency in Shiraz, deserve more investigations.

Congenital hepatic fibrosis and need for liver transplantation.

Herein, we describe two patients who underwent liver transplantation with the clinical diagnosis of hepatic failure and cryptogenic cirrhosis; histopathology of the explanted hepatectomy specimen revealed congenital hepatic fibrosis. To the best of our knowledge, coexistence of hepatic failure and cirrhosis in congenital hepatic fibrosis, have not yet been reported in the English literature.

Pediatric liver transplantation in Iran: a 9-year experience.

BACKGROUND: Liver transplantation (OLT) is accepted as the standard therapy for end-stage liver disease. The current shortage of organ donors has led to the use of split grafts and living related donors to provide timely liver transplants for these children. Herein we have reported our experience with pediatric OLT over a 9-year period. MATERIALS AND METHODS: We retrospectively studied 138 infants and children who underwent OLT from April 1999 to August 2008 including pretransplantation status, medical and surgical complications, and survival. RESULTS: There were 83 (60.1%) boys and 55 (39.9%) girls. The mean patient age was 9.1 +/- 5.6 years (range = 0.5-18) with a mean weight of 28.1 +/- 17.0 kg (range = 7-80). The main indications were Wilson's disease (20.3%); cryptogenic cirrhosis (16.7%); autoimmune cirrhosis (14.5%); biliary atresia (13.8%); tyrosinemia (9.4%); and progressive familial intrahepatic cholestasis (8.7%). We used living related donors in 54 (39.1%) and split livers in 20 (14.5%) cases with 64 (46.4%) patients receiving a whole liver from a deceased donor. The mean follow-up was 25.3 +/- 20.3 months (range = 1-100). The mortality rate was 27.5% with a 26.1% in-hospital mortality. The main causes of mortality were vascular complications (32.6%); primary nonfunction (19.6%); sepsis (17.4%); chronic rejection (17.4%); and biliary complications (6.5%). The mortality rate among patients under 10 kg (58.8%) was higher than that of patients over 10 kg (23.1%). Among those patients who were discharged from the hospital (73.9%), the most common cause of mortality was chronic rejection from noncompliance (n = 4), chronic rejection (n = 3 cases), or posttransplant lymphoproliferative disease (n = 2). CONCLUSION: Our results demonstrated that pediatric OLT is a feasible undertaking in Iran. The organ shortage in our area led to liberal use of living related and split-liver techniques. The overall results of pediatric OLT in Iran were acceptable.

Experience of living donor liver transplantation in Iran: a single-center report.

BACKGROUND: Living donor liver transplantation (LDLT) has been accepted as a valuable treatment for patients with end-stage liver disease seeking to overcome the shortage of organs and the waiting list mortality. The aim of this study was to report our experience with LDLT. METHODS: We retrospectively analyzed 50 LDLTs performed in our organ transplant center from January 1997 to March 2008. We reviewed the demographic data, family history, operative and hospital stay durations as well as postoperation complications among donors and recipients. We also performed a retrospective analysis of recipient chemical and biochemical data. RESULTS: Among 50 patients (30 males and 20 females) of overall mean age of 7.21 +/- 5.35 who underwent LDLT (10 right lobe, 38 left lobe, and 2 left lateral segments), 47 received a liver graft from their parent, two from a brother, and one from an uncle. The most common indications for LDLT were end-stage liver disease due to Wilson's disease (16%), cryptogenic cirrhosis (16%), tyrosinemia (14%), biliary atresia (12%), autoimmune hepatitis (12%), and progressive familial intrahepatic cholestasis (12%). The mean follow-up was 16.91 +/- 23.74 months. There were 13 (26%) recipient mortalities including vascular complications; three to sepsis after bowel perforation, two from liver dysfunction, two from chronic rejection due to noncompliance, and one from diffuse aspergillosis. The morbidity rate was 50%, including 19 reexplorations during the hospital course and five biliary complications. CONCLUSION: This study demonstrated that LDLT can decrease the number of patients awaiting liver transplantation especially in the pediatric group. However, because of relatively high mortality and morbidity, we must improve our treatment outcomes.

Split liver transplantation in Shiraz Transplant Center.

BACKGROUND: Cadaveric organ splitting emerged from an improved understanding of the surgical anatomy of the liver as a possible mechanism to expand the organ pool. In this study, we have reported our first series of split liver transplantations (SLT). MATERIALS AND METHODS: From June 2006 to June 2008, we performed 17 pairs of SLT: 70.6% ex situ and 29.4% in situ. The mean age of the donors (32 males, 2 females) was 23.15 +/- 9 years. All of them had been stable at the time of harvest according to vital signs, liver function tests, electrolytes, and urine output. The decision on splitting was made by the surgical team according to the donor's status and the urgency of the recipient. RESULTS: The main indications were biliary atresia (17.6%) followed by Wilson disease (14.7%) and cryptogenic cirrhosis (14.7%). The left lateral segment and the left lobe were used in 6 and 11 cases, respectively. In-hospital mortalities for the pediatric and adult groups were 68.4% and 26.7%, respectively. Primary graft nonfunction (52.9%), vascular complications (29.4%), sepsis (11.8%), and biliary complications (5.9%) were the main causes of mortality. CONCLUSION: Our experience indicated that SLT showed a high rate of mortality and morbidity.

Liver transplantation for homozygous familial hypercholesterolemia: two case reports.

Homozygous familial hypercholesterolemia (HFHC) is a rare inherited condition with an incidence of one in one million. It is associated with severe premature atherosclerosis and early death from cardiovascular complications. Mutation in the gene that encodes the synthesis of the cellular receptor for low-density lipoprotein (LDL) is responsible for this metabolic disorder. Currently, the only effective treatment for this disease is liver transplantation, which alone or in association with medications, normalizes plasma cholesterol level. The authors report the results of liver transplantation for two cases of HFHC. The first case, a 15-year-old boy received a whole liver from a deceased donor, and the second, an 11-year-old boy, received a left liver lobe transplant from his mother's sister. Their preoperative fasting lipid concentrations were grossly raised. The older boy had severe atherosclerotic heart disease and had undergone coronary artery bypass grafting 5 months before transplantation. Both had preoperative plasma cholesterol levels higher than 750 mg/dL with normal thyroid and liver function tests. After the operation, the patients received methylprednisolone as pulse therapy followed by oral prednisolone, mycophenolate mofetil, and tacrolimus for immunosuppression. Their hospital stays were 24 and 13 days, respectively. The first case needed reexploration because of bleeding on the second day after the operation. The lipid concentrations rapidly returned to the normal range in the first week after the operation, remaining in this range over the first 6 months of follow-up. Liver transplantation offers an highly effective treatment for HFHC. It is better to operate on patients before severe atherosclerotic changes in the coronary arteries. All patients must undergo a complete cardiac evaluation before surgery.

Comparison of Child-Turcotte-Pugh and pediatric end-stage liver disease scoring systems to predict morbidity and mortality of children awaiting liver transplantation.

BACKGROUND: The pediatric end-stage liver disease (PELD) scoring system has been used widely for prioritizing children awaiting orthotopic liver transplantation (OLT). The aim of the present study was to compare the Child-Turcotte-Pugh scoring system with PELD to predict morbidity and mortality of children scheduled for OLT before the organ was available. MATERIALS AND METHODS: From 1999 to 2006, 83 infants and children were evaluated and scheduled for OLT. Child and PELD scores were determined according to the initial assessment at the time of listing. Outcome was examined using records and follow-up data. RESULTS: Among 83 patients, 12% were Child A; 53%, Child B; and 35%, Child C. The mean PELD score at listing was 19.8+/-12.8. Patients with Child scores A, B, and C displayed mean PELD scores of 7.1+/-4.9, 15.7+/-9.3, and 30.5+/-11.7, respectively. Child classification and scoring showed a positive correlation with the PELD score (Spearman's correlation coefficient: 0.666, P=.001). A higher PELD score was associated with greater morbidity and mortality. CONCLUSION: Child classification has several shortcomings; therefore, PELD scores appear to be the best metric to prioritize children listed for OLT.