Comparison of the effect of Everolimus, Prednisolone, and a combination of both on experimentally induced peritoneal adhesions in rats.

Postoperative intra-abdominal adhesions represent a significant post-surgical problem. Its complications can cause a considerable clinical and cost burden. Herein, our study aimed to investigate the effect of Everolimus on peritoneal adhesion formation after inducing adhesions in rats. In this experimental study, adhesion bands were induced by intraperitoneal injection of 3 ml of 10% sterile talc solution in 64 male albino rats. The first group served as the control group. The second one received oral Prednisolone (1 mg/kg/day), the third received Everolimus (0.1 mg/kg/day), and group four received both drugs with similar dosages for four consecutive weeks. The formation of adhesion bands was qualitatively graded according to the Nair classification. The rats in the control group had extensive adhesions between the abdominal wall and the organs. Regarding substantial adhesion formation, 50% (8/16) of animals in the control group had substantial adhesions, while this rate in the groups receiving Prednisolone, Everolimus, and combination treatment was 31%, 31%, and 31%, respectively. Also, 68.75% (5/11) of the Prednisolone recipients had insubstantial adhesions, the same as Everolimus recipients, while in the combination group, 66.66% (10/15) rats had insubstantial adhesions. Everolimus demonstrated satisfactory results in reducing the rates of induced peritoneal adhesion in an experimental model, similar to Prednisolone and superior to a combination regime.

Factors Associated with Chronic Rejection in Liver Transplant Recipients: A Retrospective Cohort Study From Shiraz Organ Transplant Center.

OBJECTIVES: Identification of chronic rejection risk factors in liver transplant recipients is critical for early detection and prevention of further graft loss. We investigated characteristics of liver transplant recipients who had experienced chronic rejection and the associated risk factors versus patients without chronic rejection. MATERIALS AND METHODS: Data from 3022 adult liver transplant recipients between 2011 and 2018 were analyzed; of these, 80 patients had experienced chronic rejection. The control group included 98 randomly selected liver transplant recipients who did not have chronic rejection. RESULTS: The age of the recipients and the donors was significantly lower in the group with chronic rejection versus the group without chronic rejection.The results indicated that chronic rejection was significantly associated with the sex of the recipients (hazard ratio 3.2, 95% CI 1.77-6.08; P < .001) and with the sex concordance between the recipients and donors (hazard ratio 2.93, 95% CI 1.67-5.13; P < .001, respectively). Also, in the group without chronic rejection, there were no male donors; however, the group with chronic rejection had mostly male donors (P <.001). Cold ischemia time was longer in patients with chronic rejection versus that shown in the control group (P = .031), and there was a significant difference between the 2 groups in acute rejection frequency (P < .001). CONCLUSIONS: Recipient sex and sex concordance were independent risk factors for chronic rejection. Most transplantrecipients with chronic rejection responded to medicaltreatment, and the rate of graftloss was low among our recipients.

Early hepatic artery thrombosis treatments and outcomes: aorto-hepatic arterial conduit interposition or revision of anastomosis?

BACKGROUND: Hepatic artery thrombosis (HAT) is one of the critical conditions after an orthotopic liver transplant (OLT) and leads to severe problems if not corrected promptly. However, multiple treatments have been proposed for HAT, in which surgical revascularization with either auto-hepatic conduit interposition (AHCI) or revision of the anastomosis is more familiar indeed indicated for some patients and in specific situations. In this study, we want to evaluate the success and outcomes of treating early HAT (E-HAT), which defines HAT within 30 days after OLT with either of the surgical revascularization techniques. METHOD: In this retrospective study, we collected information from the medical records of patients who underwent either of the surgical revascularization procedures for E-HAT after OLT. Patients who needed early retransplantation (RT) or died without surgical intervention for E-HAT were excluded. Demographic data, OLT surgery information, and data regarding E-HAT were gathered. The study outcomes were secondary management for E-HAT in case of improper inflow, biliary complications (BC), RT, and death. RESULTS: A total of 37 adult patients with E-HAT after OLT included in this study. These E-HATs were diagnosed within a mean of 4.6 ± 3.6 days after OLT. Two patients had their HA revised for the initial management of E-HAT; however, it changed to AHCI intraoperatively and finally needed RT. Two and nine patients from the AHCI and revision groups had re-thrombosis (12.5% vs. 47.3%, respectively, p = 0.03). RT was used to manage rethrombosis in all patients of AHCI and two patients of the revision group (22.2%). In comparison to the AHCI, revision group had statistically insignificant higher rates of BC (47.4% vs. 31.2%); however, RT for nonvascular etiologies (12.5% vs. 5.3%) and death (12.5% vs. 10.5%) were nonsignificantly higher in AHCI group. All patients with more than one HA exploration who were in the revision group had BC; however, 28.5% of patients with just one HA exploration experienced BC (p < 0.001). CONCLUSION: Arterial conduit interposition seems a better approach for the initial management of E-HAT in comparison to revision of the HA anastomosis due to the lower risk of re-thrombosis and the number of HA explorations; indeed, BC, RT, and death remain because they are somewhat related to the ischemic event of E-HAT than to a surgical treatment itself.

Severe Hepatotoxicity in Mushroom Poisoning by Lepiota brunneoincarnata from Complete Recovery to Liver Transplantation: A Case Series with Review on Liver Function Tests and Liver Histopathology.

Background: In spite of the scientific evidence supporting health advantages of mushrooms, some of them are seriously poisonous. The clinical picture of mushroom intoxication ranges from minor gastrointestinal symptoms to organ failure, such as liver failure and death. Method: We provided demographics, clinicopathological characteristics, applied treatments, and outcomes of mushroom poisoning by Lepiota species in a series of 18 cases that were referred from Kermanshah and Lorestan provinces to Abu-Ali-Sina Hospital, Shiraz, Iran. Clinical and paraclinical data were collected by taking history and reviewing of medical documents. Pathologic findings were extracted through a review of hematoxylin and eosin pathologic slides. Results: The patients were between the ages of 18 and 67 years, composed of ten females and eight males. The most frequent clinical manifestations were nausea and vomiting followed by abdominal pain. Four cases presented decreased consciousness on admission. One of them passed away. Three other cases underwent liver transplantation, two of them died after transplantation, and one fully recovered without any major issues. All instances had elevated ALT levels, which ranged from 44 to 9,140 IU/L (mean: 3259 ± 2476), with most of them also having concurrent AST elevations (mean: 1,361 ± 1,532). Only few patients had modest elevations in alkaline phosphatase. Total and direct bilirubin elevations up to 47.6 and 24 mg/dL, respectively, were found in most cases. Decreased total protein and albumin concentrations and increased BUN and creatinine levels were observed in some patients. In addition, some instances revealed increased LDH, increased WBC, decreased hemoglobin, and decreased platelet count. Most patients had increased prothrombin time; hematuria and positive stool occult blood were observed in few patients. Histopathologic examination of three explanted livers revealed massive necrosis with moderate to severe macrovesicular steatosis, significant ductular reaction, and parenchymal inflammation. Other patients followed a recovery process with a considerable drop in liver enzymes, especially ALT, during hospitalization utilizing conservative treatment. They had no liver problems or relevant issues after a two-year follow-up. Conclusion: In our study, highly elevated liver enzymes with a significantly high ALT/AST ratio were observed in cases of mushroom poisoning by Lepiota species, leading to fulminant liver failure and death in some cases. These laboratory findings were correlated with liver necrosis and macrovesicular steatosis in explanted livers.

Nonoperative management of biliopleural fistula following living-donor liver transplantation: A case report.

Key Clinical Message: Biliopleural fistula is a rare but serious complication after liver transplantation that should be managed nonoperatively with antibiotics, pleural drainage, decompression of high-pressure biliary tract, or ultimately surgery in unresponsive cases. Abstract: Bilious pleural effusion is a rare entity often iatrogenic, following hepatobiliary surgeries and biliary interventions, and has been reported only in a limited number of patients after liver transplantation. A 5-year-old girl underwent living donor liver transplantation due to progressive familial intrahepatic cholestasis. At the 7th day of the postoperative course, due to increased liver enzymes and bilirubin levels and intrahepatic bile duct dilatation on sonography, Magnetic Resonance Cholangiopancreaticography followed by a liver biopsy were performed; the findings demonstrated moderate intrahepatic bile duct dilatation and moderate cellular rejection associated with mild cholestasis, respectively. The patient was therefore administered a pulse of methylprednisolone; however, due to fever, peritonitis and also sonographic evidence of infected biloma collection adjacent to the transplanted liver, the patient underwent surgery. Laparotomy and peritoneal washout were performed and a Jackson-Pratt drain was inserted adjacent to the liver cut surface. Succeeding tachypnea on 28th post day, led to detection of right side massive pleural effusion on chest Xray and hence thoracostomy tube was inserted. A diagnosis of biliopleural fistula was established and broad-spectrum intravenous antibiotic therapy was started, followed by cholangiography, fistula closure, and bile duct stricture ballooning and internal-external biliary catheter insertion. The patient was discharged in generally good condition on the 50th posttransplant day. The diagnosis of biliopleural fistula is facilitated with the utilization of chest imaging and pleural fluid analysis, however, a high index of suspicion is required.

Prope tolerance after pediatric liver transplantation: Experience at Shiraz Organ Transplant Center.

BACKGROUND: Children receive transplants at a younger age, and the period of immunosuppression therapy may extend over decades. However, immunosuppression seems to be responsible for long-term mortality and morbidity. Pediatric liver transplant recipients can benefit from achieving immune tolerance and the opportunity of freedom from lifelong immunosuppression. This study aimed to investigate the frequency of prope tolerance among pediatric liver transplant recipients and the characteristics of these patients. METHODS: In this retrospective cohort study of pediatric liver transplant recipients, the medical records of transplant recipients treated at Shiraz Organ Transplant Center between 1994 and 2017 were reviewed. Prope tolerance was defined as normal laboratory values and stable clinical status on low-dose monotherapy. Children treated with low-dose monotherapy were categorized as the prope tolerant group. We compared the characteristics of prope tolerant recipients on low-dose monotherapy with patients on standard immunosuppression, i.e. full-dose tacrolimus plus steroids and mycophenolate mofetil. The data were analyzed with the t-test, chi-squared test, and a Cox proportional hazard model at a 5% significance level in SPSS software version 16. RESULTS: A total of 585 children with a mean age of 8.32 ± 5.23 years were enrolled. 341 patients were categorized as prope tolerant and 244 comprised the full immunosuppression regimen group. Mean age at transplantation and rejection frequency were lower in the prope tolerant group (p < 0.001, p < 0.001). Based on the underlying diseases, metabolic/genetic, biliary tract, and cryptogenic liver diseases were significantly more prevalent in the prope tolerant group (p < 0.001). However, autoimmune liver disease was found to be more prevalent in the full immunosuppression regimen group. Also, those who received living organs (p = 0.001) and recipients of organs from female donors had a greater likelihood of achieving prope tolerant. According to the multiple Cox regression results, age at transplantation (p = 0.022), rejection frequency (p < 0.001), and autoimmune liver diseases (p = 0.028) had a prognostic effect on prope tolerance. CONCLUSION: Factors as underlying disease, age at transplantation, and rejection frequency were factors that were predictive of prope tolerance in this sample of children. However, the risk of rejection should be considered during the tapering period.

Comparison of the preventive effect of colchicine versus diphenhydramine, prednisolone, and a combination therapy on intraperitoneal adhesion bands: an experimental study in rats.

BACKGROUND: Peritoneal adhesion formation is an inevitable consequence of abnormal repair of the peritoneum following different peritoneal injuries of intra-abdominal operations with the subsequent morbidity that they represent. Vast efforts have been made to elucidate the cause and prevent the development of abdominal adhesions. The aim of our study is to compare the capability of colchicine versus diphenhydramine (DPH) and methylprednisolone (MP), and also prednisolone in adhesion prevention. METHODS: Sixty-one male Wistar stock rats were divided into four groups. The first group attended as the control group. Groups 2, 3, and 4 received oral combination of MP + DPH solution (20 mg/kg), colchicine (0.02 mg/kg), and prednisolone (1 mg/ kg), respectively. Adhesion bands were induced by standardized abrasion of the peritoneum through a midline laparotomy. All rats were sacrificed on the 15th-day post medication administration and the subjects underwent an exploratory laparotomy. The presence of adhesions was evaluated with the modified using Nair's classification. RESULTS: The proportion of the control group with substantial adhesion bands (73.3%) was significantly higher than that of the MP + DPH (13.3%), colchicine (33.3%), and prednisolone (31.3%) groups. There were significant differences between the scores of the control and the MP + DPH, colchicine, and prednisolone groups (P = 0.001, 0.028, and 0.019, respectively). There was no statistically significant difference to favor colchicine against MP + DPH (P = 0.390) or MP + DPH against prednisolone (P = 0.394). CONCLUSIONS: Both colchicine and combination of DPH + MP prevented postoperative abdominal adhesions separately in our study. However, the lowest adhesion formation rate was observed in the DPH + MP group, even lower than the prednisolone group.

Cohort Profile: Shiraz Pediatric Liver Cirrhosis Cohort (SPLCCS).

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.

The Impact of HLA-G and HLA-E Polymorphisms on CMV Reinfection in Liver Transplant Recipients.

BACKGROUND: Cytomegalovirus (CMV) reinfection in transplant patients has been associated with graft loss and decreased patient survival. In this regard, the HLA-G molecule has the immunomodulatory characteristic and its soluble isoforms have important roles in immunity to viruses. The 14bp insertion/deletion polymorphism impacts HLA-G mRNA stability. Regarding the HLA-E molecule, two nonsynonymous alleles, HLA-E*0101, and HLA-E*0103 are different in their functions including the affinity of the relative peptide. OBJECTIVE: To explore the possible link between HLA-G and HLA-E polymorphisms with CMV reinfection among liver transplant recipients (LTRs). METHODS: In this study, a total of 140 liver transplantations were performed; of which 70 CMV-reactivated LTRs and 70 CMV non-reactivated ones were recruited. The cut-off value of CMV DNA was determined to be 100 copies/mL. PCR evaluated different genotypes for HLA-G and ARMS-PCR for HLA-E*0101 and *0103. RESULTS: Neither the HLA-G genotypes (-14 bp/-14bp and +14bp/+14 bp homozygous genotypes with the p-values: 0.43, and 0.13, respectively +14 bp/-14 bp heterozygous genotype with p-value: 0.49) nor the HLA-E genotypes (HLA-E*0101/0103, HLA-E*0101/0101, and HLA-E*0103/0103 with the p-values: 0.152, 0.249, and 0.391, respectively) had any association with CMV reinfection in the LTRs. CONCLUSION: No difference was observed in the HLA-E and HLA-G genotype frequencies between our studied groups. Further studies are needed to explore other genetic variations and evaluate soluble HLA-G and HLA-E levels in the transplant population.

Early Liver Transplant In Patients With Liver Cirrhosis Recovered From COVID-19 Infection.

OBJECTIVES: Coronavirus disease 2019 has resulted in significant morbidities and mortalities in nearly all parts ofthe world. There remain major concerns about management, timing, and safety of liver transplant in patients who have recovered from COVID-19. We aimed to study the clinical course and outcomes of patients with liver cirrhosis who recovered from COVID-19 and underwent liver transplant from deceased donors. MATERIALS AND METHODS: A retrospective study was conducted on liver transplant recipients who underwent liver transplant from April 1, 2020, to January 30, 2021. We evaluated all recipients of liver transplantfrom deceased donors during this period in the COVID-19 pandemic. RESULTS: There were 14 patients with decompensated liver cirrhosis who had recovered from COVID-19 as documented by reverse transcription-polymerase chain reaction test for SARS-CoV-2. Mean duration from COVID-19 to transplant surgery was 56.14 ± 29.96 days. Mortality occurred in 3 patients, and of whom 2 had been hospitalized and received medications for COVID-19 before transplant. Five patients had positive reverse transcription-polymerase chain reaction results for SARS-CoV-2 after liver transplant. CONCLUSIONS: This is a large reported series of patients with liver cirrhosis who have received liver transplant after recovery from COVID-19. We provided evidence that liver transplant from deceased donors should be considered in patients recovered from COVID-19, especially in those with deterioration of clinical status.

Metabolic syndrome, hepatic fibrosis, and steatosis diagnosed by liver stiffness measurement and controlled attenuation parameter after liver transplantation: the impact on long-term survival.

BACKGROUND: Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) are used for diagnosis of liver fibrosis and steatosis. This study aimed to noninvasively evaluate hepatic steatosis and fibrosis in liver transplant recipients using CAP and LSM and the impact on survival of patients. METHODS: In a prospective study, adult liver transplant recipients were included. CAP and LSM obtained during transient elastography (TE) were used for assessment of hepatic steatosis and fibrosis. Patients were followed during 4 years for mortality as the main outcome after liver transplantation. RESULTS: From 296 patients, 24.7% and 25% of liver transplant recipients had liver steatosis and fibrosis in CAP and LSM, respectively. In multivariable Cox regression analysis, etiology of liver disease (NASH versus non-NASH) (HR: 3.125; 95% CI: 1.594-6.134; p = 0.001), and post-transplant diabetes mellitus (PTDM) (HR: 2.617; 95% CI: 1.396-4.926; p = 0.003) were associated with hepatic steatosis after liver transplantation.  In multivariable Cox regression analysis, liver fibrosis was an independent predictor of mortality after liver transplantation (HR: 4.926; 95%CI: 1.779-13.513; p = 0.002). CONCLUSION: CAP and LS measurement during TE are useful methods for diagnosis of hepatic steatosis and fibrosis in liver transplant recipients. LS measurement might predict long-term survival of patients.

Comparison of Oral Sirolimus, Prednisolone, and Combination of Both in Experimentally Induced Peritoneal Adhesion.

INTRODUCTION: Peritoneal adhesion formation is a challenging postoperative complication. We aim to evaluate the effect of orally administered sirolimus, prednisolone, and their combination to prevent this entity. METHODS: Eighty female albino underwent intraperitoneal injection of 3 mL of 10% sterile talc solution to induce peritoneal adhesion, and were subsequently and randomly divided into four groups (each n = 20); including a control group; 1 mg/kg oral prednisolone daily in the morning; 0.1 mg/kg oral sirolimus daily; and a combination group which received both drugs, with the same dosage. On the 29th day, abdominal cavities were explored, and classification was done based on Nair classification. RESULTS: All rats were healthy on the 29th day, in which exploration was performed. The rats in the control group had extensive intra-abdominal adhesions, while 17 (85%) rats in the control group had substantial adhesion; however, the prednisolone, sirolimus, and combination group had lesser adhesion formation. Also, 14 (70%) rats of prednisolone group, 13 (65%) of sirolimus group, and 16 (80%) of combination group had insubstantial adhesion. The decrease in the grade of peritoneal adhesion bands was highly significant in the combination group (P > 0.001). CONCLUSIONS: The combination of sirolimus and prednisolone was effective for preventing peritoneal adhesions in rats.

Hepatic Computed Tomography Volumetry for Noninvasive Detection of Hepatic Steatosis and Steatohepatitis in Living Liver Donors.

OBJECTIVES: Detection of hepatic steatosis in donors is an important step for selection of a suitable liver allograft in living-donor transplant. This study aimed to investigate the role of hepatic computed tomography volumetry as a noninvasive method for detection of hepatic steatosis in living liver donors. MATERIALS AND METHODS: In a cross-sectional study, individuals who had undergone liver biopsy as a pretransplant checkup before living-donor liver transplant were included. The segmental liver volumes were measured by computed tomography scan with intravenous contrast enhancement. RESULTS: Our study included 179 individuals. Mean total volume of the liver was 1705.2 ± 256.5 cm³ in those with steatohepatitis and 1419.4 ± 241.2 cm³ in those without steatohepatitis (P < .001). Higher total volume of the liver (odds ratio of 1.005; 95% confidence interval, 1.001-1.010; P = .012) and total liver volume-to-standard liver volume ratio (odds ratio of 1.090; 95% confidence interval, 1.021-1.163; P = .009) were independent predictors of steatohepatitis. A cutoff value of 1531 cm³ for total liver volume was a predictor of presence of steatohepatitis in liver biopsies of donors (sensitivity = 83%; specificity = 71%; area under the curve = 0.809; P < .001). CONCLUSIONS: Computed tomography volumetry may be considered as an auxiliary noninvasive method for estimation of hepatic steatosis/steatohepatitis and may be used as a guide to select donor candidates for liver biopsy.

Nonalcoholic Steatohepatitis Is the Most Rapidly Growing Indication for Liver Transplantation in Iranian Patients.

OBJECTIVES: Nonalcoholic fatty liver disease is a rapidly growing disease and is hypothesized to become the most common cause of liver cirrhosis in the near future. This study aimed to investigate trends of nonalcoholic steatohepatitis as an indication for liver transplant in Iranian patients. MATERIALS AND METHODS: Liver transplant data from all adult patients (age > 18 y) who had undergone liver transplant between 1993 and 2017 at the Shiraz Organ Transplant Center (Shiraz, Iran) were reviewed. Underlying liver diseases leading to liver transplant were stratified according to year of transplant, and trends of increase or decline were analyzed. Kaplan-Meier curves were used for analysis of posttransplant survival of patients with nonalcoholic steatohepatitis and patients with modified nonalcoholic steatohepatitis. RESULTS: We evaluated 3184 liver transplant patients. Of these, 112 patients with biopsy-proven nonalcoholic steatohepatitis underwent liver transplant up to the end of 2017. Mean age of patients was 52.86 ± 9.01 years in those with nonalcoholic steatohepatitis and 51.73 ± 7.91 years in those with modified nonalcoholic steatohepatitis (P > .05).The prevalence of nonalcoholic steatohepatitis as an indication for liver transplant was 0.8% in 2011, 0.36% in 2012, 1.9% in 2013, 4.01% in 2014, 2.89% in 2015, 6.65% in 2016, and 9.97% in 2017. The prevalence of modified nonalcoholic steatohepatitis was 2.4% in 2011, 2.88% in 2012, 2.71% in 2013, 2% in 2014, 2.17% in 2015, 2.13% in 2016, and 2.28% in 2017. We found that nonalcoholic steatohepatitis as a cause of liver transplant increased significantly during recent years (P < .001). CONCLUSIONS: Nonalcoholic steatohepatitis is a rapidly growing indication for liver transplant among Iranian patients. Health care providers should consider programs for prevention and early diagnosis of patients with nonalcoholic steatohepatitis for proper treatment.

Noninvasive Estimation of Hepatic Steatosis by Controlled Attenuation Parameter in Living Donor Liver Transplant.

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.

Comparison of the characteristics of adult liver transplant recipients with prope (almost) tolerance and full immunosuppression regimen.

BACKGROUND: The liver transplant recipients are often subjected to excessive therapy by immunosuppressive drugs which produce several complications. Consequently, the minimization or even withdrawal of immunosuppression in selected patients is an attractive alternative. We investigated the frequency and characteristics of these near (or prope from Latin) tolerance in liver transplant recipients in Shiraz Organ Transplant Center. MATERIAL AND METHODS: We reviewed the medical records of over 3800 adult liver transplant recipients to select a group treated with a low-dose tacrolimus monotherapy (n = 90) between 1994 and 2017 in our transplant center. The patients with the best liver function parameters were selected; then, the clinician arbitrarily decided to withdraw steroids first and then mycophenolate mofetil and maintain each patient on a low dose tacrolimus. We compared the characteristics of prope tolerant recipients on a low-dose tacrolimus with those on standard immunosuppression, namely full-dose tacrolimus plus steroids and mycophenolate mofetil (n = 233). Data were analyzed by t-test, chi-square test using SPSS software version 16. RESULTS: Out of over 3800 liver transplant patients, 90 (2.34%) recipients were treated with a minimum dose of tacrolimus monotherapy. These recipients were compared to a selected group of 233 (6.1%) recipients treated with full-dose tacrolimus plus steroids and mycophenolate mofetil. In a prope tolerant group, there were 55 males (61.1%) and 35 females (38.9%) recipients. Mean age at the time of transplant was 39.92 ± (SD = 13.40) years with an average time from the transplantation time to completed weaning from triple immunosuppression to low-dose monotherapy of 41.35 months (SD = 17.27). The most common etiology of liver disease among both groups was viral hepatitis. CONCLUSION: The achievement of prope (almost) immune tolerance was possible only in some liver transplant recipients with a relatively low risk of rejection. Our analysis suggests that there is a difference in the underlying diseases and recipients' age and the number of rejections between the two groups.

Pediatric liver and kidney transplantation in the era of COVID-19: a follow-up study from a tertiary referral center in Iran.

BACKGROUND: We aimed to evaluate the impact of COVID-19 pandemic on pediatric transplant outcomes and determine whether to continue pediatric transplant activity or not, and how policies intended our center has been effective in preventing COVID-19 among organ transplant recipients. METHODS: We conducted a single-center, retrospective, cohort study of hospitalized pediatrics after organ transplantation at Shiraz transplant center since March to August 2020. All liver and kidney transplanted children were included the study and their laboratory and clinical related COVID-19 characteristics were followed up till 3 months after transplantation during hospitalization period and then weekly by the transplant committee. RESULTS: Fifty-one patients underwent transplantation including 11 kidney and 40 liver recipients. The mean age of the pediatric cases was 6.72 ± 5.47 years. A total of 11 patients died due to post-transplant complications, while none of the patients presented any sign or symptoms in favor of COVID-19 in the hospital course after transplantation. Six transplants including 2 kidney and 4 liver were canceled when positive PCR tests were detected in their donors before the surgery. In the 3 months of follow up, two patients presented with symptoms including high grade fever, malaise, rhinorrhea, and GI symptoms. Both patients had two negative PCR, and no radiologic or laboratory results regarding COVID-19 were also detected. One had positive influenza PCR, while the second one had a positive serologic test for EBV; CT, computed tomography CONCLUSION: Transplant programs could continue their activities during the COVID-19 pandemic with specific case selection, accurate screening methods and following protective protocols.

Clinical Outcome of Vancomycin-Resistant Enterococcus Colonization Among Liver Transplant Recipients at Shiraz Organ Transplant Center.

OBJECTIVES: Liver transplant recipients are more susceptible to vancomycin-resistant enterococci colonization than healthy individuals. We investigated the prevalence of vancomycin-resistant enterococci colonization and its effect on the outcomes of liver transplant recipients. MATERIALS AND METHODS: Patients who had undergone primary liver transplant at the Shiraz Organ Transplant Center from 2015 to 2017 were enrolled in this study. Demographic characteristics, laboratory test results, duration of stay in the intensive care unit, total duration of hospital stay, and clinical outcome data were extracted from the Shiraz Organ Transplant Center database. Posttransplant outcomes such as graft rejection, mortality, hospital stay, and kidney function tests were included for the first 90 days after transplant. RESULTS: A total of 753 liver transplant recipients (470 males and 283 females) were included in this study. Vancomycin-resistant enterococci colonization was identified in 51 patients (6.8%) after transplant at the time of intensive care unit admission. Our study found no significant difference between outcomes for patients with vancomycin-resistant enterococci colonization and outcomes for patients without colonization, including graft rejection, mortality, hospital stay, and kidney function tests. CONCLUSIONS: Our study revealed that asymptomatic vancomycin-resistant enterococci colonization in liver transplant patients has no adverse effect on the duration of posttransplant hospital stay, early mortality rate, graft rejection rate, or kidney function compared with noncolonized patients.

The Largest Single Center Report on Pediatric Liver Transplantation: Experiences and Lessons Learned.

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 ±â€Š5.55 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.

Liver Transplant for Primary Hyperoxaluria Type 1: Results of Sequential, Combined Liver and Kidney, and Preemptive Liver Transplant.

OBJECTIVES: Primary hyperoxaluria type 1 is an autosomal recessive disorder that causes overproduction and urinary excretion of oxalate. Liver transplant has been suggested as a treatment for primary hyperoxaluria type 1 since the defective enzyme is expressed in the liver. This study aimed to investigate results of combined liver and kidney, sequential, and preemptive livertransplantin patients with primary hyperoxaluria type 1. MATERIALS AND METHODS: In this cohort study, we followed patients with primary hyperoxaluria type 1 who underwent liver transplant at our centerin Shiraz, Iran. Clinical and laboratory data of patients were gathered, and major outcomes, including renal failure after liver transplant, rejection, and mortality were recorded. Survival of patients was analyzed by the Kaplan-Meier method. RESULTS: Our study included 24 patients. There were 16 male (66.6%) and 8 female (33.33%) patients. Thirteen patients were in the pediatric age group (age < 18 y), and 11 patients were adults (age ≥ 18 y). Thirteen patients underwent sequential transplant, 8 patients underwent combined liver and kidney transplant, and 3 patients underwent preemptive transplant. All patients received organs from deceased donors. There were no statistically significant differences in mortality, rejection, and hemodialysis after transplant between those with sequential transplant and those with combined liver and kidney transplant (P > .05). CONCLUSIONS: Liver transplant can be considered a treatment for patients with primary hyperoxaluria type 1. Combined liver and kidney transplant and preemptive liver transplant could be proper options for these patients.