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Background: Hepatocyte transplantation using isolated human hepatocytes is an alternative source that can be used for the treatment of metabolic diseases and acute liver failure as a time bridge to liver transplantation. These cells can also be used for bioartificial liver systems and in vitro study of drug toxicity. Objective: To determine which cold preservation solution is better maintain the liver function. Methods: We prepared 4 cold preservation solutions made of different combination of antioxidants, chelating, membrane protective, and anti-apoptotic agents as well as inhibitor of cyclophilin D. For hepatocyte isolation, we used livers obtained from unused deceased donor livers and the liver of patients with Crigler-Najjar syndrome who were candidates of partial liver transplantation. After culture and cold preservation, the level of albumin, and urea production were measured as indices of liver functionality. Results: We found that albumin production significantly decreased after cold preservation in solution 1. There was no significant difference in urea production after cold preservation in solution 1 compared with control 24 h. No significant differences in albumin production were found after cold storage in solution 2 and solution 4 compared with control 24 h. Urea production significantly decreased after cold storage in solutions 2 and 4 compared with control 24 h. As a whole albumin and urea production were significantly decreased after cold preservation. Although albumin and urea production were decreased after cold preservation, but the results of albumin production of two solutions were not significantly different from that of the control group (p=0.109 and 0.951). Conclusion: Cold preservation of cultured human hepatocytes in solution 2 and solution 4 could maintain the function of albumin production better than other cold preservation solutions in our experiments; solution 1 was more effective on urea production of cultured human hepatocytes at 4 °C for 24 h. To determine if these hepatocytes are suitable candidates for transplantation, further studies should be performed.

Background: Liver transplantation is the only treatment for end-stage and genetic liver diseases. The main burden of this treatment is the shortage of both living and cadaveric liver donors. An alternative treatment is using liver cell transplantation, which can be obtained from unused livers for transplantation. These hepatocytes should be kept ready in viable and functional situation in a frozen state to be instantly used when they would be needed. In our previous experience, we had isolated hepatocytes from unused livers. Objective: To find a preserving solution for increasing viability and function of the isolated hepatocytes that are stored to be transplanted. Methods: 9 cadaveric donor livers, which were not used for transplantation due to various causes such as severe steatosis, were selected to isolate hepatocytes. Various cold storage solutions were tried to find the best temperature for more viability and functionality for preservation of hepatocytes. University of Wisconsin (UW) solution and Williams E media were used as control media. 2 anti-apoptotic and antioxidative solutions, i.e., α-lipoic acid and ursodeoxycholic acid (UDCA), were used as cold preservatives solutions. The numbers of viable hepatocytes were estimated by trypan blue method; the functionality was assessed by the cells ability to produce urea. Results: The highest number of viable and functional hepatocytes was obtained from freshly isolated cells. However, after preservation, the number of these viable hepatocytes and their functionality were not significantly different in cold storage solutions comparing to the control media used. Functionality of the isolated hepatocytes stored in UW with and without UCDA solution was similar to freshly isolated hepatocytes. Conclusion: Preservatives with anti-apoptotic and antioxidant activity could not increase the number of viable hepatocytes. Functionality of cold storing hepatocytes could be preserved similar to freshly isolated hepatocytes by UW solution with and without UCDA.

Background: Estimation of the amount of blood products required during liver transplantation can help provision of adequate blood supply, minimize transfusion-associated complications, and plan ahead for preventive measures in high risk patients. Objective: To investigate independent predictors of peri-operative blood product transfusion and its impact on short-term survival of liver transplant recipients. Methods: In a cross-sectional study, old charts of patients who underwent liver transplantation between March 2003 and March 2013 at Namazi Hospital, Shiraz, Iran, were reviewed. The mean amount of blood product utilized during surgery and hospital stay and the related factors, including demographic characteristics, pre-transplant laboratory data, pre-transplant clinical data, operation data, and post-transplantation data were recorded. Results: We studied 1198 patients who underwent liver transplantation. The mean±SD amounts of red cells, fresh frozen plasma, and platelet transfusion during surgery and hospital stay were 2.67±3.5, 2.06±3.8, and 1.6±3.8 units, respectively. The mortality rate was significantly higher in patients who received higher amounts of blood products (p

Kidney transplantation is the treatment of choice for patients with end-stage renal disease (ESRD). Prediction of the transplant survival is of paramount importance. The objective of this study was to develop a model for predicting survival in kidney transplant recipients. In a cross-sectional study, 717 patients with ESRD admitted to Nemazee Hospital during 2008-2012 for renal transplantation were studied and the transplant survival was predicted for 5 years. The multilayer perceptron of artificial neural networks (MLP-ANN), logistic regression (LR), Support Vector Machine (SVM), and evaluation tools were used to verify the determinant models of the predictions and determine the independent predictors. The accuracy, area under curve (AUC), sensitivity, and specificity of SVM, MLP-ANN, and LR models were 90.4%, 86.5%, 98.2%, and 49.6%; 85.9%, 76.9%, 97.3%, and 26.1%; and 84.7%, 77.4%, 97.5%, and 17.4%, respectively. Meanwhile, the independent predictors were discharge time creatinine level, recipient age, donor age, donor blood group, cause of ESRD, recipient hypertension after transplantation, and duration of dialysis before transplantation. SVM and MLP-ANN models could efficiently be used for determining survival prediction in kidney transplant recipients.

Background: Metabolic syndrome (MetSx) is common among liver transplant recipients. It contributes to morbidity and mortality. Objective: To determine the prevalence of MetSx in patients undergoing liver transplantation (LTx) in Iran. Methods: 202 liver transplant recipients of both sexes completed this study. Relevant information including age, sex, the underlying disease, systolic and diastolic blood pressure, waist circumference, fasting serum levels of blood sugar (FBS), triglyceride (TG), and HDL-cholesterol were measured. The prevalence of MetSx was evaluated at 1, 3, 6, 9, and 12 months after LTx. Results: The prevalence of MetSx was 36.6% after 1 month that decreased to 28.2% after 12 months of follow-up. The lowest prevalence of MetSx (27.7%) was observed 9 months after LTx. Our data showed a decrease in TG and an increase in HDL-C level and no significant changes in blood pressure, waist circumference and FBS during the study period. Conclusion: The prevalence of MetSx after LTx is high when compared to the normal population. It seems that a change in diet after transplantation may affect the prevalence of MetSx.

Background: Co-stimulatory molecules play a critical role in regulating T-cell function during CMV infection after liver transplantation. Objective: To investigate the relationship between the polymorphisms of the co-stimulatory genes and the susceptibility to CMV infection after liver transplantation. Methods: Single nucleotide polymorphisms (SNPs) in PD-1 gene (PD1.1 A/G, PD1.3 A/G, PD1.9 C/T) ICOS (-693 A/G, 1720 C/T), CTLA-4 gene ( 318 C/T, 1722 T/C, 1661 A/G, 49 A/G) and CD28 (+17 C/T) were analyzed by PCR-RFLP in 70 liver transplant patients. CMV infection was determined in these patients by antigenemia test. Results: CTLA-4 49G showed significant association with CMV infection (p=0.03, OR=3.82, 95% CI: 0–3.5; p=0.01, OR=004, 95% CI: 0–1.3). G and T alleles in CTLA-4 gene ( 318 C/T and 1661 A/G) (p=0.03, OR=0, 95% CI: 0–3.5; p=0.01, OR=0.04, 95% CI: 0–1.3) were significantly higher in CMV-infected rejector group. Conclusion: CTLA-4 have significant role in CMV pathogenesis and rejection among CMV-positive liver transplant patients.

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.

Background: Portal vein thrombosis (PVT) has been mentioned as a potential obstacle to liver transplantation (LTx). Objective: To review the impact of PVT on orthotopic liver transplant (OLT) outcome. Method: Between January 2006 and April 2009, 440 OLT were performed in Shiraz Transplant Unit of whom, 35 (7.9%) cases had old PVT with recanalization. Data were retrospectively collected regarding the demographics, indication for OLT, Child-Turgot-Pugh classification, pre-transplant diagnosis of PVT, perioperative course and managements, relapse of PVT, early post-operative mortality and morbidity. All patients received liver from deceased donors, underwent thrombendvenectomy with end-to-end anastomosis without interposition graft and evaluated daily for 5 days and thereafter, biweekly by duplex sonography during the follow-up period for 2 months. They were treated by therapeutic doses of heparin followed by warfarin to maintain an INR of 2–2.5. Results: The causes of end-stage liver disease were hepatitis B in 11, cryptogenic cirrhosis in 11, primary sclerosing cholangitis in 5 and other causes in 8 recipients. Extension of thrombosis was through confluence of superior mesenteric and splenic vein in 32 and to superior mesenteric vein in 3 patients. The mean±SD operation time was 7.2±1.5 hrs. The mean±SD transfusion requirement was 5.4±2.8 units of packed cells. The mean±SD duration of hospital stay in these patients was 17.7±10.9 days. Eight patients died; 1 developed early in-hospital PVT, 1 had hepatic vein thrombosis, and 1 died of in-hospital ischemic cerebrovascular accident, despite a full anticoagulant therapy. The mean±SD follow-up period for those 28 patients discharged from hospital was 16.6±7.9 months; none of them developed relapse of PVT. The overall mortality and morbidity was 28% and 32%, respectively. There was no relapse of PVT in the other patients. Conclusion: The presence of PVT at the time of OLT is not a contraindication for the operation but those with PVT have a more difficult surgery, develop more postoperative complications, and experience a higher in-hospital mortality.

مقدمه: پیوند کبد به‌ عنوان تنها راه درمان بیماران مبتلا به نارسایی پیشرفته‌ی کبد است. مرکز پیوند شیراز تنها مرکز پیوند کبد ایران است و تعیین بقای بیماران و تعیین الگوهای مؤثر و قابل اصلاح مرتبط به دهنده و گیرنده و فرآیند پیوند که در بقای این بیماران مؤثرند، می‌تواند به برنامه‌ریزی بالینی در جهت افزایش بقای بیماران پس از پیوند کبد منجر شود. روش ها: در این مطالعه‌ی هم‌گروهی، تمامی بیمارانی که در سال‌های 1380 تا 1387 در مرکز پیوند بیمارستان نمازی شیراز، پیوند کبد از جسد برای آنها انجام شده بود، مورد بررسی قرار گرفتند. در این بررسی بقای یک ساله، سه ساله و پنج و شش ساله‌ی بیماران محاسبه گردید. همچنین اثر فاکتورهای مرتبط با گیرنده، دهنده و فرآیند عمل و ارتباط آن با بقای بیماران بررسی شد. یافته ها: در این مطالعه، بقای یک ‌ساله‌ی بیماران 84 درصد و بقای سه ساله و شش ساله 82 درصد بود. در مدل بقای تک متغیره، از بین متغیرهای زمان عمل طولانی، سن دهنده‌ی پیوند، نمره‌ی بالاتر MELD، نیاز به عمل مجدد و وزن کمتر از 60 کیلو گرم بیمار، ارتباط بیشتری با کاهش بقای بیماران داشتند. در مدل Cox تنها سن دهنده‌ی پیوند زیر40 سال و بالای20 سال اثر محافظتی در مدل نشان داد. نتیجه گیری: مقایسه‌ی بقای بیماران پیوند شده در مرکز پیوند بیمارستان نمازی قابل مقایسه با مراکز با سابقه‌ی دنیا است. ضمن این که بقای بیماران در سال‌های آخر بهتر بررسی شده است. واژگان کلیدی: پیوند کبد، بقا، فاکتورهای مرتبط با گیرنده‌ی پیوند، ایران

This study compares outcomes and graft function of right and left grafts of deceased donor. We studied 120 kidney recipients from 60 deceased donors in Shiraz organ transplantation center from 1988 to 2004. We analyzed data regarding age, gender, side of grafts, duration of pre-transplant dialysis, hospital stay, serial creatinine levels, cold ischemic time, complications, graft function, patient survival rates, and post-operative complications. Recipients were divided into two groups: group 1 consisted of 60 recipients who received right renal graft (43 males, 17 females; mean age: 33.6 ± 7.3 years), and group 2 consisted of 60 recipients who received left renal graft (45 males, 15 females; mean age: 29.2 ± 6.4 years). No statistically significant differences were found in duration of pre-transplant dialysis, cold ischemic time, acute rejection rates, post-operative surgical and vascular complications′ rates, hospital stay, renal function, and one year graft survival rates. We conclude that although it is advised to use left kidney from live donors because of longer vessel length, easier surgical technique and organ handling, and shorter ischemic time, we got the same outcome in left and right deceased renal grafts.

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 (

Background: Pathogenesis of neonatal hepatitis relates to various underlying causes including viral infections. Both hepatotropic and non-hepatotropic viruses may induce liver failures in infants before birth, during delivery, or shortly after birth. Objectives: The tissue impact of HCMV, HSV, HBV, HCV, and rotavirus and adenovirus infections was evaluated in studied infants with neonatal hepatitis. Methods: The history of viral infections was analyzed in paraffin-embedded biopsy and autopsy tissues of 22 infants with neonatal hepatitis between years 1996 and 2007, retrospectively. The tissue molecular presentation of HBV, HCV, HCMV, HSV, adenovirus, and rotavirus was evaluated by different qualitative simple and nested PCR and RT-PCR protocols. Immunohistochemistry (IHC) method was used for studying the antigenic prevalence of HSV-1, 2; HBV, HCMV and adenovirus infections. Also the laboratory liver indices of all patients with neonatal hepatitis were analyzed. Results: The HBV and HSV genomes were detected in 3 (14%) of 22 infants. The rotavirus and HCV-RNA and also the HCMV-DNA were detected separately in 1 (4%) of 26 paraffin-embedded autopsy and biopsy tissues. The HBV and HSV-1 specific antigens were separately diagnosed in 1 (4%) of 26 neonatal samples by IHC protocols. Also the HSV-2 antigen was seen in 5 (23%) of 22 liver autopsy and biopsy specimens. Co-infections with HCMV, HSV, HBV, HCV, and rotavirus were detected in these infants with hepatitis. Conclusion: Diagnosis of single and mixed molecular and antigenic traces of HCMV, HSV, HBV, HCV and rotavirus underlines the etiologic role of these viruses in clinical pathogenesis of neonatal hepatitis.

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.

The development of malignancies after solid organ transplants is a well-known complication. Cancer is associated with significant consequences for the organ transplant patient. It is expected that cancer will surpass cardiovascular complications as the leading cause of death in transplant patients within the next few years. We report on a 36-year-old male patient who developed mixed germ-cell testicular tumor seven years after liver transplantation for alcoholic cirrhosis. He was treated with orchiectomy, retroperitoneal lymph node dissection and post-operative chemotherapy.

The aim of this study was to document vascular complications that occurred fol-lowing cadaveric and living donor kidney transplants in order to assess the overall incidence of these complications at our center as well as to identify possible risk factors. In a retrospective cohort study, 1500 consecutive renal transplant recipients who received a living or cadaveric donor kidney between December 1988 and July 2006 were evaluated. The study was performed at the Nemazee Hospital, Shiraz, Iran. The assessment of the anatomy and number of renal arteries as well as the incidence of vascular complications was made by color doppler ultrasonography, angiography, and/or surgical exploration. Clinically apparent vascular complications were seen in 8.86% of all study patients (n = 133) with the most frequent being hemorrhage (n = 91; 6.1%) followed by allo-graft renal artery stenosis (n = 26; 1.7%), renal artery thrombosis (n = 9; 0.6%), and renal vein thrombosis (n = 7; 0.5%). Vascular complications were more frequent in recipients of cadaveric organs than recipients of allografts from living donors (12.5% vs. 7.97%; P= 0.017). The occurrence of vascular complications was significantly more frequent among recipients of renal allografts with multiple arteries when compared with recipients of kidneys with single artery (12.3% vs. 8.2%; P= 0.033). The same was true to venous complications as well (25.4% vs. 8.2%; P< 0.001). Our study shows that vascular complications were more frequent in allografts with multiple renal blood vessels. Also, the complications were much less frequent in recipients of living donor transplants.