Percutaneous Transhepatic Radiologic Intervention of Biliary Complications following Liver Transplantation: A Single-center Experience.

Background: Biliary complications are the leading cause of morbidity and mortality in patients undergo¬ing Liver Transplantation (LT). Post-biliary transplantation strictures (BSs) are a severe problem with a high risk of graft failure. However, management of these BSs has remained controversial, and consid¬erable variability has been reported in Percutaneous Transhepatic Radiological Interventions (PTRIs) related to broad differences in technical procedures. Objective: This study aimed to evaluate the efficacy of percutaneous treatments in managing post-LT BSs in a center in Shiraz. Methods: PTRIs including balloon dilatation, metallic stent, and internal or internal-external hand-made plastic stent insertion were done for 34 transplanted patients with BSs referring to the Interventional Radiology Unit of Shiraz Namazi Hospital. Technical success rate, patency rates, and complications were evaluated. Results: The. In this study, 31 strictures were successfully treated without any significant difference between the anastomotic and non-anastomotic types of stricture (success rate: 91.2%). Based on the results, 12- , 24-, and 36-month primary patency rates were 90.1%, 84.5%, and 76.8%, respectively. The secondary patency rate was 100% at 12 and 24 months and 93.3% at 36 and 60 months. The rate of minor complica¬tions (mild cholangitis and hemobilia) was 6.4%, and no major complications were detected. Conclusion: According to the findings, PTRI is an effective method for treating anastomotic and non-anas- tomotic strictures with a high success rate and low complications.

Effects of Different Cold Preservation Solutions on the Functions of Cultured Isolated Human Hepatocytes.

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.

The Effects of Cold Preservation Solutions Supplemented with UDCA and α-Lipoic Acid on the Viability and Function of Isolated Human Hepatocytes.

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 anti-oxidative 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.

Prevalence of Metabolic Syndrome in Liver Transplant Recipients in Iran.

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.

Graft survival rate following renal transplantation in diabetic patients.

Diabetic nephropathy is the most common cause of kidney failure needing dialysis in most countries of the world. Kidney disease occurs in one-third of diabetic patients, and significantly increases the mortality rates and treatment costs. The aim of the present study was to investigate the survival rate and to determine factors that influence survival among diabetic patients who underwent transplantation at the Shiraz Namazi Hospital Transplant Center during the years 1999 to 2009. This study is a historical cohort study, which examined the graft survival rate among 103 kidney transplant patients with diabetes. The Kaplan-Meier method was used to determine the survival rate and the log-rank test was used to compare survival curves; P-value of less than 0.05 was considered significant. The mean follow-up period of patients was 48.15 ± 31.05 months (range: 3.07-118.03 months), and the estimated nine-year graft survival rate was 84.2% (±0.045). Based on the results of the Cox regression model, age of the donor was a contributing factor to graft survival rate. In summary, the graft survival rate in our cohort is satisfactory and comparable with reports from other larger centers in the world.

En-bloc Transplantation: an Eligible Technique for Unilateral Dual Kidney Transplantation.

BACKGROUND: Kidney transplantation is the best available treatment for patients with end-stage renal disease. OBJECTIVE: To evaluate the en bloc anastomosis technique for unilateral dual kidney transplantation (DKT). METHODS: From May to October 2011, 5 patients (4 women and 1 man) with mean age of 31.8 years underwent unilateral DKT with this technique in which distal end of the aorta and proximal end of inferior vena cava (IVC) were closed with running sutures. Then, proximal end of the aorta and distal end of the IVC were anastomosed to internal (or external) iliac artery and external iliac vein, respectively. RESULTS: Post-operative course was uneventful. No vascular and urologic complications developed; all patient had acceptable serum creatinine at discharge time and up of 2-6 months of post-operation follow up. CONCLUSION: Unilateral DKT is a safe method for performing DKT. The proposed en bloc anastomosis can improve the outcome of the graft by reducing the cold ischemia and the operation time.

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.

Hematologic and biochemical indices and viral hepatitis in liver transplant patients.

BACKGROUND AND PURPOSE OF STUDY: The pathogenic role of important hepatotropic viral agents to induce hepatic dysfunction and failure may lead to the need for liver transplantation. We focused on the use of hematologic and biochemical laboratory diagnostic indexes to follow the clinical impact of hepatitis B virus (HBV); hepatitis C virus (HCV); and hepatitis G virus-related liver complications in transplant patients. MATERIALS AND METHODS: We collected 141 EDTA-treated blood samples pre- and post-liver transplantation for 2 years among 67 transplant patients. We evaluated the statistical relationships between hematologic and biochemical indices with HBV, HCV, and HGV infections among transplant recipient samples using version 15 of SPSS software. RESULTS: HBV polymerase chain reaction (PCR) positivity significantly correlated with partial thromboplastin (P=.011) pretransplant, with creatinine (P=.026) and Na (P=.034) levels at 1-week posttransplant, and also with alkaline phosphatase (P=.027) and mean corpuscular hemoglobin concentration (P=.050) at 2 weeks posttransplantation. Significant correlations were detected between HCV-reverse transcriptase (RT)-PCR-positive results and blood urea nitrogen (P=.008) and Na (P=.021) levels in the first aspartate aminotransferase and with (P=.025) in the second week after liver transplantation. Also, significant relationships were noted between HGV-RT-PCR-positive results and alkaline phosphatase (P=.05) and creatinine (P=.002) levels in the first and second weeks after liver transplant, respectively. CONCLUSION: Detection of significant correlations between HBV, HCV, and HGV infections with laboratory indices suggested that monitoring hematologic and biochemical liver function-related criteria aid the management of clinical complications of viral hepatitis in liver transplant patients.

De novo fatty liver due to vascular complications after liver transplantation.

INTRODUCTION: The incidence, risk factors, and natural history of de novo nonalcoholic fatty liver disease (NAFLD) after liver transplantation have not been well described. In this report we examined the risk factors and demographic characteristics of 3 patients. MATERIALS AND METHODS: During a 16-year period, we performed 900 liver transplantations. We reviewed donor and recipient liver biopsies to identify patients who developed de novo fatty liver following liver transplantation, recording the pretransplantation and posttransplantation blood sugar values and lipid profiles as well as body mass indices (BMI) of affected patients. RESULTS: Three patients developed de novo fatty liver after transplantation. The primary liver diseases among these patients were as follows: Crigler-Najjar syndrome, biliary atresia, and tyrosinemia. All of the patients who developed NAFLD were children. None of them had obesity; all had normal blood sugar values and lipid profiles (triglyceride cholesterol) at the time of and after the operation. Two patients received liver allografts from living related donors and 1 from a deceased donor. The BMI, lipid profile, and blood sugars of all donors were normal. Preoperative donor liver biopsy specimens showed normal histological findings with no evidence of a fatty liver, but the postoperative liver biopsy in recipients specimens revealed steatosis and fatty liver (20%-40% fat). Portal vein thrombosis and hepatic artery thrombosis were observed in the patients using color Doppler sonography. CONCLUSION: De novo NAFLD after liver transplantation occurred less frequently than noted in previous reports. All 3 patients experienced complicated courses. Portal vein thrombosis and hepatic artery thrombosis seemed to be important factors for development of de novo fatty liver after transplantation.

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.

Endothelial Nitric Oxide Synthase Gene T-786C Polymorphism in Renal Transplant Recipients.

BACKGROUND: Nitric oxide (NO) is a major mediator in vascular biology, regulating regional blood flow. NO and the enzymes required for its production contribute to ischemia-reperfusion injury. The T-786C functional polymorphism in the promoter region substantially reduces promoter activity of the endothelial nitric oxide synthase (eNOS) gene and compromises endothelial NO synthesis. OBJECTIVE: To examine the association between T-786C (rs 2070744) single nucleotide polymorphism (SNP) in eNOS gene and the development of acute rejection in renal transplant patients. METHODS: 60 renal transplant recipients (30 with episodes of acute rejection (ARs) and 30 without rejection (non-ARs)), between June 2008 and March 2010, were included in this study. The polymorphism was determined by PCR-restriction fragment-length polymorphism analysis. RESULTS: The distribution of the genotypes were TT/TC/CC 60%, 33.4%, 6.6%, and 43%, 46.7%, 13.3% in ARs and non-ARs, respectively (p=0.28). The frequency of T-allele was 76.7% and 66.3%; and for C-allele was 66.6% and 33.3% in ARs and non-ARs, respectively (p=0.09). There were no significant associations between these polymorphisms and acute and chronic kidney allograft rejection. CONCLUSION: We could not detect any significant association between polymorphism in T-786C of eNOS gene and the development of acute rejection.

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.

The molecular and antigenic tissue impact of viral infections on liver transplant patients with neonatal hepatitis.

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.

Graft survival rate of renal transplantation: a single center experience, (1999-2009).

BACKGROUND: Renal transplantation is the best option for treatment of the end-stage renal diseases and has more advantages than dialysis. The objective of this study is to determine the ten-year graft survival rate of renal transplantation and its associated factors in patients who have been transplanted from March 1999 to March 2009 in Nemazee Hospital Transplantation Center. METHODS: This is a historical cohort study of 1356 renal transplantation carried out during 1999 to 2009. Kaplan-Meier method was used to determine the survival rate, log rank test to compare survival curves, and Cox regression model to determine hazard ratios and for modeling of variables affecting survival. RESULTS: The 1, 3, 5, 7 and 10 years graft survival rates were 96.6, 93.7, 88.9, 87.1 and 85.5 percent, respectively.Cox regression model revealed that the donor source and creatinine level at discharge were effective factors in graft survival rate in renal transplantation. CONCLUSION: Our study showed that 10 year graft survival rate for renal transplantation in Nemazee Hospital Transplantation Center was 85.5% and graft survival rate was significantly related to recipients and donor's age,donor source and creatinine level at discharge. Our experience in renal transplantation survival rate indicates asuccess rate comparable to those noted in other reports.

Liver transplantation in the presence of old portal vein thrombosis.

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.

The effect of simvastatin on lowering panel reactive antibody titer in sensitized dialysis patients: a randomized placebo controlled clinical trial.

BACKGROUND: Patients with panel reactive antibodies (PRA) have many difficulties to find a crossmatch-negative kidney for transplantation and are at a higher risk of post-transplantation rejection. OBJECTIVE: To evaluate the effect of simvastatin on PRA and post-transplant outcome of these sensitized patients. METHODS: 82 patients with end-stage renal disease (ESRD) with a PRA ≥25% were evaluated. In a one-year follow-up, the patients were treated with simvastatin. These patients were compared with 82 matched controls receiving placebo tablets. At the end of the second and 12(th) month, PRA was rechecked in all patients. Those patients who underwent transplantation continued to take simvastatin six months after transplantation. Serum creatinine levels were checked at monthly intervals post-operation. RESULTS: The mean±SD PRA level at the end of the second month was 36.63%±31.14% and 45.34%±24.36% in cases and controls, respectively (P=0.012). Seven patients in the case group and 10 in the control group were lost to follow-up. The remaining patients continued to take simvastatin for 12 month. The mean±SD PRA level at the end of the 12(th) month was 24.02%±31.04% in cases and 43.15%±26.56% in controls (P=0.001). 25 patients underwent renal transplantation and continued to receive simvastatin 6 months after transplantation. These patients were matched with 25 controls treating with placebo. The mean±SD creatinine level 6 months after kidney transplantation was 2.05±1.14 mg/dL and 3.15±1.09 mg/dL in cases and controls consecutively (P=0.02). CONCLUSION: Simvastatin can be safely used to lower PRA and improve post-transplantation outcomes.

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.