Publications by authors named "Saman Nikeghbalian"

156 Publications

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

Exp Clin Transplant 2021 Sep 20. Epub 2021 Sep 20.

From the Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz, Iran.

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.
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http://dx.doi.org/10.6002/ect.2021.0181DOI Listing
September 2021

The potential of the incorporated collagen microspheres in alginate hydrogel as an engineered three-dimensional microenvironment to attenuate apoptosis in human pancreatic islets.

Acta Histochem 2021 Aug 24;123(7):151775. Epub 2021 Aug 24.

Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Tissue engineering is considered as a promising tool for remodeling the native cells microenvironment. In the present study, the effect of alginate hydrogel and collagen microspheres integrated with extracellular matrix components were evaluated in the decrement of apoptosis in human pancreatic islets.

Materials/methods: For three-dimensional culture, the islets were encapsulated in collagen microspheres, containing laminin and collagen IV and embedded in alginate scaffold for one week. After that the islets were examined in terms of viability, apoptosis, genes and proteins expression including BAX, BCL2, active caspase-3, and insulin. Moreover, the islets function was evaluated through glucose-induced insulin and C-peptide secretion assay. In order to evaluate the structure of the scaffolds and the morphology of the pancreatic islets in three-dimensional microenvironments, we performed scanning electron microscopy.

Results: Our findings showed that the designed hydrogel scaffolds significantly improved the islets viability using the reduction of activated caspase-3 and TUNEL positive cells.

Conclusions: The reconstruction of the destructed matrix with alginate hydrogels and collagen microspheres might be an effective step to promote the culture of the islets.
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http://dx.doi.org/10.1016/j.acthis.2021.151775DOI Listing
August 2021

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

Transpl Immunol 2021 Oct 31;68:101440. Epub 2021 Jul 31.

Abu Ali Sina Organ Transplant Center, Shiraz University of Medical Sciences, Shiraz, Iran.

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.
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http://dx.doi.org/10.1016/j.trim.2021.101440DOI Listing
October 2021

Experiences with intestinal failure from an intestinal rehabilitation unit in a country without home parenteral nutrition.

JPEN J Parenter Enteral Nutr 2021 Jul 22. Epub 2021 Jul 22.

Shiraz Transplant Center, Abu Ali Sina Hospital, Shiraz University of Medical Sciences, 7193711351, Shiraz, Iran.

Objective: For the first time, we reported experiences with an intestinal rehabilitation unit (IRU) from a country without home parenteral nutrition (HPN).

Methods: We included patients with a diagnosis of intestinal failure (IF) since the establishment of our IRU from February 2018 to February 2020. We further report on our protocols for management of enterocutaneous fistulas (ECFs), short-bowel syndrome (SBS), chronic intestinal pseudo-obstruction and motility disorders.

Results: Among a total of 349 patients who have been admitted, 100 patients had IF and were included . Mean (SD) age of patients was 46.3 ± 16.1 years. Most common cause of IF was ECFs (32%), SBS (24%), and SBS + fistula (22%). Most common causes of SBS were mesenteric ischemia (63.3%) and repeated surgery (22.4%). Median (interquartile range [IQR]) duration of parenteral nutrition (PN) for patients was 32 (18-60) days. The most common reconstructive surgery performed was resection and anastomosis (75.4%), followed by serial transverse enteroplasty procedure (10.5%) and closure of ostoma (7%). Patients were hospitalized for a median (IQR) of 33 (17.5-61) days. Most common complications were sepsis (45%), catheter infections (43%), and catheter thrombosis (20%), respectively. At the final follow-up, 61% stopped receiving PN, 23% became candidates for transplantation, and 16% died.

Conclusion: Considering that most countries lack facilities for HPN, by establishing IRUs using specific treatment protocols and autologous gastrointestinal reconstruction techniques will provide a means to manage patients with IF, thus decreasing death rates and number of patients who require intestinal transplantations due to IF.
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http://dx.doi.org/10.1002/jpen.2231DOI Listing
July 2021

Adrenocortical adenoma with myelolipomatous metaplasia: a potential diagnostic pitfall: a case report and review of the literature.

J Med Case Rep 2021 Jul 4;15(1):333. Epub 2021 Jul 4.

Department of Pathology, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Adrenal incidentalomas are often found during investigation for another tumor or unrelated problems. Except for adrenal myelolipoma (second most common primary adrenal incidentaloma following adrenocortical adenomas), adrenal lipomatous tumors are uncommon generally and are often described as case reports in the literature. Since the amount of fat is variable, without the help of advanced imaging techniques, some adrenal lipomatous tumors may be misdiagnosed before pathologic examination. Herein, we report a case of adrenal adenoma with myelolipomatous metaplasia that was excised as a periceliac mass in the setting of recurrent pancreatic cyst.

Case Report: A 45-year-old Iranian woman with hypertension and end-stage renal disease presented with recurrence of a pancreatic cyst (previous pathologic report was mucinous cyst adenoma). During exploratory laparotomy, the mentioned pancreatic cyst was tightly attached to the stomach and jejunum. There was also a periceliac round rubbery lesion (firstly diagnosed by endoscopic ultrasound) that was excised for ruling out malignancy. Histologic examination of the periceliac mass was found to be adrenocortical adenoma with foci of myelolipomatous metaplasia. The pancreatic cyst histology was just a pseudocyst.

Conclusion: Our case highlights the significance of complete evaluation of incidental findings before surgical intervention, even in the setting of another primary tumor. Myelolipoma and myelolipomatous change (metaplasia) are two different entities. Although very similar as to pathogenesis, there are still some differences.
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http://dx.doi.org/10.1186/s13256-021-02937-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255017PMC
July 2021

Surgical Management of Intestinal Failure; Initial Experiences from an Intestinal Failure, Rehabilitation and Transplant Unit in Iran.

Arch Iran Med 2021 04 1;24(4):289-295. Epub 2021 Apr 1.

Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Intestinal failure (IF) is a life-threatening medical condition. The management of IF in low- and middle-income countries without home parenteral nutrition (HPN) remains unclear. We recently established an intestinal rehabilitation unit (IRU) and aimed to provide our experience on the current management and outcomes of IF in Iran.

Methods: In this cross-sectional case series, data were collected from an established database on IF in the Shiraz Transplant Center in Abu Ali Sina hospital, affiliated to Shiraz University of Medical Sciences, Iran from January 2018 to October 2018.

Results: Overall, 30 patients with a mean age of 44.13 ± 10.32 years, which included 25 males, were recruited. Short bowel syndrome (SBS) (60%) and enterocutaneous fistulae (27%), as complication of previous surgeries, were the main causes of IF. The most common type of IF was type 3 (67 %). Mesenteric ischemia was the leading mechanism of IF (47%). Fifteen patients (50%) received autologous gastrointestinal reconstruction surgery (AGIRS), and two (7%) patients had serial transverse enteroplasty (STEP). At the end of follow-up, 15 patients recovered from IF (50%). The overall survival rate was 83.3%.

Conclusion: This series introduced the results of a multidisciplinary program for the treatment of IF in a middle-income country that lacks facilities for HPN. Our protocol of care, understanding the need for development of HPN, showed promising clinical outcomes.
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http://dx.doi.org/10.34172/aim.2021.40DOI Listing
April 2021

Continuous Renal Replacement Therapy with Low Dose Systemic Heparin in Liver Transplant Recipients.

Iran J Kidney Dis 2021 May;15(3):229-234

Taleghani Hospital, Department of Transplant and Hepatobiliary Surgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Introduction: Continuous renal replacement therapy (CRRT) is an effective dialysis method in critically ill patients. Citrate and heparin are commonly used as anticoagulants to prevent premature circuit clotting. The aim of this study was to evaluate the safety and efficacy of using low dose systemic heparin while on CRRT in liver transplant recipients.

Methods: We retrospectively evaluated and analyzed data from 29 liver transplant recipients undergoing CRRT in the postoperative course in this cross-sectional study. Numerous variables were recorded, such as coagulation parameters, duration of intensive care unit (ICU) stay, duration of dialysis, heparin dose, circuit life span, and anticoagulant complications.

Results: Out of 29 recipients, there were 16 (55%) female and 13 (45%) male. All participants underwent whole organ liver transplantation with a median age of 45 years. Overall, 98 successful dialysis sessions were recorded in this study with a mean circuit life span of 36 hours. Mean ± SD duration of CRRT for each recipient was 4.8 ± 3.1 days. The median total dose of heparin used for each recipient was 25,000 units , and the median dose of heparin per-day for each recipient was about 3,300 units. There were no episodes of anticoagulant-related bleeding complications. Thirteen (13.2%) episodes of premature circuit clotting occurred. We found a significant association between the first dose and total dose of heparin usage with first postoperative INR and PTT level (P < .05, P < .05, P < .001, and P < .05).

Conclusion: In liver transplant recipients, low dose heparin during CRRT for patency of circuit is well tolerated.
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May 2021

Post liver transplant complications of Budd-Chiari syndrome.

Indian J Gastroenterol 2021 Jun 20;40(3):281-286. Epub 2021 Mar 20.

Shiraz Transplant Research Center, Shiraz University of Medical sciences, Shiraz, Islamic Republic of Iran.

Background/purpose: Budd-Chiari syndrome (BCS) is a rare, life-threatening disease characterized by hepatic venous outflow obstruction. Liver transplantation (LT) is widely accepted as an effective therapeutic measure for irreversible liver failure due to BCS. There is debate on differences in the post LT course and complications in patients with BCS as compared to non-Budd-Chiari (NBC) patients.

Method: In this retrospective study, data on all patients who received a liver transplant for BCS at the Shiraz Organ Transplantation Center between January 1996 and September 2017 were reviewed and compared to data of a control group who had received liver transplants over the same period but due to other causes (NBC).

Results: Out of 4225 patients who received liver transplants in the study period, 108 had BCS and an age- and gender-matched control group consisted of 108 NBC cases. The mean ± standard deviation (SD) of model for end-stage liver disease (MELD) scores were 19.1 ± 3 and 20 ± 3 for BCS and NBC groups, respectively (p = 0.33). One-, 3-, 5-, and 10-year survival rates in the BCS group were as follows: 82%, 78%, 76%, and 76% compared with the NBC rates of 83%, 83%, 83%, and 76%, respectively (p = 0.556). There was no difference between the two groups in complication rates after 6 months. In the later period, vascular thrombosis was more common in BCS.

Conclusions: Whole-organ LT from deceased donors in patients with BCS had comparable outcomes with LT due to other causes of end-stage liver disease. In most instances, these patients should receive lifelong anticoagulation.
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http://dx.doi.org/10.1007/s12664-020-01139-3DOI Listing
June 2021

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

Exp Clin Transplant 2021 Aug 4;19(8):806-810. Epub 2021 Mar 4.

From the Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

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.
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http://dx.doi.org/10.6002/ect.2020.0443DOI Listing
August 2021

Hypoxia-Preconditioned Wharton's Jelly-Derived Mesenchymal Stem Cells Mitigate Stress-Induced Apoptosis and Ameliorate Human Islet Survival and Function in Direct Contact Coculture System.

Stem Cells Int 2020 17;2020:8857457. Epub 2020 Dec 17.

Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Protection of isolated pancreatic islets against hypoxic and oxidative damage-induced apoptosis is essential during a pretransplantation culture period. A beneficial approach to maintain viable and functional islets is the coculture period with mesenchymal stem cells (MSCs). Hypoxia preconditioning of MSCs (Hpc-MSCs) for a short time stimulates the expression and secretion of antiapoptotic, antioxidant, and prosurvival factors. The aim of the present study was to evaluate the survival and function of human islets cocultured with Hpc-MSCs. Wharton's jelly-derived MSCs were subjected to hypoxia (5% O: Hpc) or normoxia (20% O: Nc) for 24 hours and then cocultured with isolated human islets in direct and indirect systems. Assays of viability and apoptosis, along with the production of reactive oxygen species (ROS), hypoxia-inducible factor 1-alpha (HIF-1), apoptotic pathway markers, and vascular endothelial growth factor (VEGF) in the islets, were performed. Insulin and C-peptide secretions as islet function were also evaluated. Hpc-MSCs and Nc-MSCs significantly reduced the ROS production and HIF-1 protein aggregation, as well as downregulation of proapoptotic proteins and upregulation of antiapoptotic marker along with increment of VEGF secretion in the cocultured islet. However, the Hpc-MSCs groups were better than Nc-MSCs cocultured islets. Hpc-MSCs in both direct and indirect coculture systems improved the islet survival, while promotion of function was only significant in the direct cocultured cells. Hpc potentiated the cytoprotective and insulinotropic effects of MSCs on human islets through reducing stressful markers, inhibiting apoptosis pathway, enhancing prosurvival factors, and promoting insulin secretion, especially in direct coculture system, suggesting the effective strategy to ameliorate the islet quality for better transplantation outcomes.
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http://dx.doi.org/10.1155/2020/8857457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759420PMC
December 2020

Survival features, prognostic factors, and determinants of diagnosis and treatment among Iranian patients with pancreatic cancer, a prospective study.

PLoS One 2020 4;15(12):e0243511. Epub 2020 Dec 4.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Objectives: Investigating the survival features, and determinants of treatment and stage at presentation in Iran.

Methods: 461 patients with pancreatic ductal adenocarcinoma (PC) were prospectively enrolled from Shariati hospital, Tehran, Iran, between 2011-2018. All patients underwent endoscopic ultrasonography, computed tomography scanning, and physical examination. Validated questionnaire was completed for the participants and all were actively followed on monthly basis.

Results: Median survival time was 6.5 months, and 1-, and 5-year survival rates were 26.2%, and 1.5%. Patients who were older (p<0.001), illiterate (p = 0.004), unmarried (p = 0.003), rural inhabitant (p = 0.013), opium user (p = 0.039), and had lower body mass index (BMI) (p = 0.002) had lower overall survival. Tumors located in the head of pancreas were more commonly diagnosed at lower stages (p<0.001). Only 10.4% of patients underwent surgery who were more commonly educated (p<0.001), married (p = 0.005), had a tumor located in the head of pancreas (p = 0.016), and were diagnosed at lower stages (p<0.001). After adjustment for potential confounders and risk factors, rural inhabitance (HR: 1.33 (95% CI: 1.01-1.74)), having more symptoms (HR for each increasing symptom: 1.06 (1.02-1.11)), using opium (HR: 1.51 (1.04-2.20)), having a tumor located in the body of pancreas (HR: 1.33 (1.02-1.75)), and having an advanced tumor stage (HR: 2.07 (1.34-3.19)) remained significantly associated with increased risk of mortality. After the adjusting for potential confounders, we did not find significant relationships between smoking, alcohol intake, and BMI with the risk of death among patients with pancreatic cancer.

Conclusions: Iranian patients with PC have very poor long-term survival. Besides tumor's stage and location, socioeconomic disparities could affect the probabilities of receiving treatment and/or survival in these patients. Opium use is an independent risk factor for mortality among PC patients in Iran.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243511PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717574PMC
January 2021

Pediatric liver transplantation and COVID-19: a case report.

BMC Surg 2020 Oct 6;20(1):224. Epub 2020 Oct 6.

Shiraz Transplant Center, Abu Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Immunosuppressed patients, including individuals with organ transplantation, have been among susceptible groups with regard to COVID-19, on the other hand pediatric patients more commonly undergo a mild clinical course after acquiring COVID-19. To the best of the authors knowledge, to this date very little data exists on COVID-19 in a pediatric patient with liver transplantation.

Case Presentation: We report a three year-old boy who had liver transplantation at 18 months old. He was admitted due to dyspnea with impression of acute respiratory distress syndrome and was then transferred to the intensive care unit. Chest X-ray at admission showed bilateral infiltration. Vancomycin, meropenem, azithromycin, voriconazole and co-trimoxazole were started from the first day of admission. On day 4 of admission, with suspicion of COVID-19, hydroxychloroquine, lopinavir/ritonavir and oseltamivir were added to the antibiotic regimen. PCR was positive for COVID-19. The patient developed multi-organ failure and died on day 6 of admission.

Conclusions: For pediatric patients with organ transplantations, extreme caution should be taken, to limit and prevent their contact with COVID-19 during the outbreak, as these patients are highly susceptible to severe forms of the disease.
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http://dx.doi.org/10.1186/s12893-020-00878-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538038PMC
October 2020

A Report of 85 Cases of COVID-19 and Abdominal Transplantation From a Single Center: What Are the Associated Factors With Death Among Organ Transplantation Patients.

Transplantation 2021 01;105(1):90-99

Shiraz Transplant Center, Abu Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: In this study, we report the epidemiology of COVID-19 among recipients of organ transplantation and evaluate associated factors with death.

Methods: We screened 6969 patients who had organ transplantations in our center for COVID-19. Specific data on presentation, clinical course, treatment, and prognosis were acquired.

Results: We found 85 patients (66 liver, 16 kidney, 2 kidney-pancreas, and 1 liver-kidney recipient) who acquired COVID-19. Most common symptoms included fever (48.2%), cough (41.2%), myalgia (41.2%), and fatigue (40%). Dyspnea developed in 33% of patients. Overall, one-third of patients had an oxygen saturation of below 90% on admission. Patients were hospitalized for a median (interquartile range) of 9 (5, 13.7) days and had a 33.9% intensive care unit admission rate. Overall, 17 patients (20%) died, which included 31.3% of patients with kidney transplantations and 18.2% of patients with liver transplantations. All 4 pediatric patients in our series died. In our univariate analysis among adults, rates of leukopenia (38.4% versus 13.2%; P = 0.04), low albumin levels (53.8% versus 10.2%; P = 0.001), and shorter duration between transplantation and COVID-19 (P = 0.02), were higher among patients who died. In our least absolute shrinkage and selection operator regression model, low albumin levels (OR, 4.48; 95% confidence interval, 1.16-17.27) were associated with higher risk of death.

Conclusions: This is the largest single-center report on abdominal transplantations and COVID-19. Liver and kidney transplant recipients have an increased risk of mortality compared with the general population due to COVID-19. More specifically, pediatric patients and those with low albumin levels are at higher risks of death due COVID-19.
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http://dx.doi.org/10.1097/TP.0000000000003470DOI Listing
January 2021

Liver transplantation and COVID-19: a case report and cross comparison between two identical twins with COVID-19.

BMC Surg 2020 Aug 8;20(1):181. Epub 2020 Aug 8.

Shiraz Transplant Center, Abu Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: To this date little information exists on the effects, clinical course and outcome of the COVID-19 among patients undergoing transplantation.

Case Presentation: A 35 year old male referred with loss of sense of smell and taste after having close contact with his brother who was diagnosed with COVID-19 five days prior to his symptoms. The patient had undergone liver transplantation 3 years prior to his referral due to primary sclerosing cholangitis in association with ulcerative colitis and was using immunosuppressive medications. The patient referred to a local physician with mild symptoms of fatigue, cough, myalgia, dizziness, and nausea/vomiting with a fear of contracting the disease. Except for a CRP of 32 his other blood tests were normal. After 3 days of hospital admission the patient was discharged with a good condition. His brother had developed fever, chills, headache, mild dyspnea and an objective loss of sense of smell and taste and was sent home and advised to self-quarantine. Both patients had CT scans in favor of COVID-19.

Conclusion: Our patient who had liver transplantation and COVID-19 did not present more severe symptoms compared to his counterpart without liver transplantation and did not need to be hospitalized or be given antiviral drugs for COVID-19.
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http://dx.doi.org/10.1186/s12893-020-00837-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414266PMC
August 2020

Hepatic steatosis and liver fat contents in liver transplant recipients are associated with serum adipokines and insulin resistance.

Sci Rep 2020 07 29;10(1):12701. Epub 2020 Jul 29.

Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz, Iran.

Our data about pathogenesis of hepatic steatosis after liver transplantation is scarce. This study aimed to investigate the association between serum adipokines and insulin resistance with hepatic steatosis in liver transplant recipients. We investigated the association between insulin resistance, serum adiponectin, insulin, and leptin with hepatic steatosis in a cohort of liver transplant recipients. Homeostatic model assessment of insulin resistance 2 (HOMA 2-IR) was used for estimation of insulin resistance. Hepatic steatosis was determined using ultrasound and controlled attenuation parameter (CAP). A total of 178 patients were included. 79 patients (44.4%) had hepatic steatosis. Serum adiponectin (OR: 0.912; 95% CI 0.869-0.957; P < 0.001), serum leptin (OR: 1.060; 95% CI 1.017-1.102; P = 0.005), HOMA2-IR (OR: 1.671; 95% CI 1.049-2.662; P = 0.031), and post-transplant diabetes mellitus (PTDM) (OR: 5.988; 95% CI 1.680-21.276; P = 0.006) were independently associated with hepatic steatosis after liver transplantation. CAP values were negatively correlated with serum adiponectin (P = 0.011) and positively correlated with serum insulin (P = 0.001), leptin (P < 0.001) and HOMA2-IR (P < 0.001). Insulin resistance and alterations in adipokines might have central role in pathogenesis of hepatic steatosis after liver transplantation and can be targeted for diagnostic and therapeutic purposes.
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http://dx.doi.org/10.1038/s41598-020-69571-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391625PMC
July 2020

Reduced rate of hospital admissions for liver-related morbidities during the initial COVID-19 outbreak.

Lancet Gastroenterol Hepatol 2020 09 29;5(9):803-804. Epub 2020 Jun 29.

Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

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http://dx.doi.org/10.1016/S2468-1253(20)30207-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324093PMC
September 2020

Intestinal transplantation during COVID-19 pandemic.

Transpl Int 2020 10 21;33(10):1329-1330. Epub 2020 Jul 21.

Shiraz Transplant Center, Abu Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

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http://dx.doi.org/10.1111/tri.13684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362055PMC
October 2020

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

Ann Surg 2021 02;273(2):e70-e72

Shiraz Transplant Center, Abu Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

Objective: We described our experiences on pediatric liver transplantation (LT) from the largest LT center in the world termed the Shiraz Transplant Center.

Background: After the first successful pediatric LT in 1967, pediatric LT has become the routine treatment for children with liver failure worldwide.

Methods: Data on a total of 1141 pediatric cases of LT were collected. Specifics on baseline and anthropometric characteristics, clinicopathology, prognosis of recipients of LT, and donor characteristics are reported.

Results: Mean age of patients was 7.83 ± 5.55 years old. Most common etiologies for LT were biliary atresia (15.9%), progressive familial intrahepatic cholestasis (13.4%), and Wilson's disease (13.3%), respectively.Whole organs, living donor grafts, and split grafts were used in 47.9%, 41%, and 11.1% of patients, respectively. In-hospital complications were seen among 34.7% of patients and the most common complications were infections (26.8%), bleeding (23.4%), and vascular complications (18%).Median (interquartile range) model for end stage liver disease score was 20 (15, 25). Main causes of death among patients were sepsis (35.2%), followed by post-transplantation lymphoproliferative diseases (10.5%), and primary nonfunction of liver (9%).Patient survival showed improvement over the years (1-year survival of 73.1%, 83.4%, and 84.4%, 2-year survival of 65.2%, 77.1%, and 78.7%, 5-year survival of 58.2%, 72%, and 77.8% for 1997-2007, 2007-2013, and 2013-2019, respectively; P < 0.001).

Conclusions: This is the largest single-center report on pediatric LT in literature which provides valuable experiences in pediatric LT.
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http://dx.doi.org/10.1097/SLA.0000000000004047DOI Listing
February 2021

Guideline for Management of Mesenteric Ischemia: Shiraz Intestinal Failure Unit Protocol.

Arch Iran Med 2020 06 1;23(6):422-425. Epub 2020 Jun 1.

Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

We have recently established an intestinal rehabilitation unit (IRU) in Abu Ali Sina transplantation center affiliated to Shiraz University of Medical Sciences, Iran. Our intestinal failure rehabilitation and transplant program aims to provide state-of-the-art care for adult patients with different degrees of intestinal insufficiency and failure. In the IRU, we aimed to design an algorithmic approach to patients with small bowel ischemia and short bowel syndrome (SBS) based on our institutional experience in our country and based on other pioneering studies from other regions of the world.
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http://dx.doi.org/10.34172/aim.2020.38DOI Listing
June 2020

Significant reduction of apoptosis induced via hypoxia and oxidative stress in isolated human islet by resveratrol.

Nutr Metab Cardiovasc Dis 2020 06 20;30(7):1216-1226. Epub 2020 Apr 20.

Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology-Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background And Aims: Successful islet transplantation as a promising treatment of diabetes type 1 is threatened with the loss of islets during the pre-transplant culture due to hypoxia and oxidative stress-induced apoptosis. Therefore, optimization of culture in order to preserve the islets is a critical point. In this study, we investigated the effect of resveratrol, as a cytoprotective agent, on the cultured human islets.

Methods And Results: Isolated islets were treated with different concentrations of resveratrol for 24 and 72 h. Islets' viability, apoptosis, apoptosis markers, and insulin and C-peptide secretion, along with the production of reactive oxygen species (ROS), hypoxia inducible factor 1 alpha (HIF-1α), and its target genes in the islets were investigated. Our findings showed that the islets were exposed to hypoxia and oxidative stress after isolation and during culture. This insult induced apoptosis and decreased viability during 72 h. The presence of resveratrol significantly attenuated HIF-1α and ROS production, reduced apoptosis, promoted the VEGF secretion, and increased the insulin and C-peptide secretion. In this regard, resveratrol improved the islet's survival and function in the culture period.

Conclusions: Using resveratrol can attenuate the stressful condition for the islets in the pre-transplant culture and subsequently ameliorate their viability and functionality that lead to successful outcome after clinical transplantation.
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http://dx.doi.org/10.1016/j.numecd.2020.04.011DOI Listing
June 2020

A detailed analysis of the current status of intestinal transplantation in the middle east.

Curr Opin Organ Transplant 2020 04;25(2):169-175

Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Purpose Of Review: Intestinal transplantations are among the most complex transplantations, which are performed in few centers in the world. When patients develop intestinal failure, different treatment modalities including parenteral nutrition, autologous gastrointestinal tract reconstructive surgery, and intestinal transplantations are considered. The Middle East is a region where reports on intestinal failures and intestinal transplantations are mainly lacking. In the present review, we highlighted the status of intestinal transplantations in the Middle East and focused on existing reports from this region.

Recent Findings: Very few countries in the Middle East have the facilities for home parenteral nutrition and only two countries including Iran and Turkey perform intestinal transplantations in the region. With advances in intestinal rehabilitation units and development of autologous gastrointestinal tract reconstructive surgery, some centers have been able to reduce the number of patients in need of intestinal transplantations.

Summary: An overview of the condition of intestinal transplantations in the Middle East shows that the issue of intestinal failure and the treatment facilities still remain an unsolved problem. Although there exists a high need for intestinal transplantation, advances in reconstructive surgeries and the development of parenteral nutrition in this region can significantly reduce the need for intestinal transplantations among patients with intestinal failure.
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http://dx.doi.org/10.1097/MOT.0000000000000751DOI Listing
April 2020

Comparison of Ceftizoxime Plus Ampicillin-Sulbactam versus Gentamicin Plus Ampicillin-Sulbactam in the Prevention of Post-Transplant Early Bacterial Infections in Liver Transplant Recipients: A Randomized Controlled Trial.

Infect Drug Resist 2020 8;13:89-98. Epub 2020 Jan 8.

Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

Purpose: In this study, we aimed to compare the efficacy of combined ceftizoxime with ampicillin-sulbactam versus combined gentamicin with ampicillin-sulbactam as prophylactic antibiotic regimen in preventing early bacterial PTIs in liver TX recipients at a referral center.

Patients And Methods: All patients older than 18 years who had undergone liver TX at Abu-Ali Sina transplantation center in Shiraz, Iran from July 2018 to April 2019 were included in this study. In a single-blinded manner, the participants randomly received either combined intravenous ceftizoxime plus ampicillin-sulbactam (ceftizoxime group) or gentamicin plus ampicillin-sulbactam (gentamicin group) as prophylactic antibiotic regimen before the incision of the surgery, which was continued for 48 hrs after liver Tx. The rate and type of bacterial infections, length of hospital and intensive care unit (ICU) stay, mortality rate, and kidney function were assessed during 1 month following liver TX in the two groups.

Results: Two hundred and thirty patients were divided into two groups. One patient in the gentamicin group and five in the ceftizoxime group were excluded due to emergency exploratory laparotomy within the first 3 days after transplantation. The rate of bacterial infections during the first month after transplantation was 25.4%. This rate was significantly lower in the gentamicin group (13.16%) in comparison to the ceftizoxime group (38.18%) (<0.01), based on the univariate logistic regression analysis. Length of ICU and hospital stay and also mortality rate were significantly lower in the gentamicin group ( <0.01). There was no significant difference regarding kidney function between the two groups ( = 0.16).

Conclusion: Our results suggested that gentamicin can be considered as a promising agent in prophylactic antibiotic regimen for patients undergoing liver TX.

Trial Registration: The study was registered at the Iranian Registry of Clinical Trials (IRCT20120731010453N2; http://www.irct.ir/).
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http://dx.doi.org/10.2147/IDR.S222934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957909PMC
January 2020

Ex vivo resection and temporary portocaval shunt of unresectable hepatocellular carcinoma followed by autotransplantation of liver: a case report.

World J Surg Oncol 2020 Jan 6;18(1). Epub 2020 Jan 6.

Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Ex situ liver resection and autotransplantation is among the most advanced techniques which has been introduced in recent years.

Case Presentation: A 24-year-old male referred with chief complaints of abdominal pain, nausea, and vomiting from 1 month prior to admission. Computed tomography showed a large liver mass in the left lobe of the liver with involvement of retrohepatic inferior vena cava (IVC), in favor of hepatocellular carcinoma. After hepatectomy, the common bile duct was completely removed. A 4-cm Dacron graft was anastomosed to the inferior and top of the IVC. A temporary portocaval shunt was placed, and ex situ resection of the left lobe of the liver was done. Remnant of the liver was implanted. Reconstruction of the bile duct was done using a Roux-en-Y technique, and autotransplantation of the liver was then completed. During a 4-year follow-up, the patient had no complaints and is in good conditions.

Conclusion: With appropriate consideration of patients, despite surgical complexities, ex situ resection of unresectable HCC can provide excellent prognosis.
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http://dx.doi.org/10.1186/s12957-019-1781-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945702PMC
January 2020

Suppression of transforming growth factor-beta signaling enhances spermatogonial proliferation and spermatogenesis recovery following chemotherapy.

Hum Reprod 2019 12;34(12):2430-2442

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

Study Question: Could small molecules (SM) which target (or modify) signaling pathways lead to increased proliferation of undifferentiated spermatogonia following chemotherapy?

Summary Answer: Inhibition of transforming growth factor-beta (TGFb) signaling by SM can enhance the proliferation of undifferentiated spermatogonia and spermatogenesis recovery following chemotherapy.

What Is Known Already: Spermatogonial stem cells (SSCs) hold great promise for fertility preservation in prepubertal boys diagnosed with cancer. However, the low number of SSCs limits their clinical applications. SM are chemically synthesized molecules that diffuse across the cell membrane to specifically target proteins involved in signaling pathways, and studies have reported their ability to increase the proliferation or differentiation of germ cells.

Study Design, Size, Duration: In our experimental study, spermatogonia were collected from four brain-dead individuals and used for SM screening in vitro. For in vivo assessments, busulfan-treated mice were treated with the selected SM (or vehicle, the control) and assayed after 2 (three mice per group) and 5 weeks (two mice per group).

Participants/materials, Setting, Methods: We investigated the effect of six SM on the proliferation of human undifferentiated spermatogonia in vitro using a top-bottom approach for screening. We used histological, hormonal and gene-expression analyses to assess the effect of selected SM on mouse spermatogenesis. All experiments were performed at least in triplicate and were statistically evaluated by Student's t-test and/or one-way ANOVA followed by Scheffe's or Tukey's post-hoc.

Main Results And The Role Of Chance: We found that administration of SB431542, as a specific inhibitor of the TGFb1 receptor (TGFbR1), leads to a two-fold increase in mouse and human undifferentiated spermatogonia proliferation. Furthermore, injection of SB to busulfan-treated mice accelerated spermatogenesis recovery as revealed by increased testicular size, weight and serum level of inhibin B. Moreover, SB administration accelerated both the onset and completion of spermatogenesis. We demonstrated that SB promotes proliferation in testicular tissue by regulating the cyclin-dependent kinase (CDK) inhibitors 4Ebp1 and P57 (proliferation inhibitor genes) and up-regulating Cdc25a and Cdk4 (cell cycle promoting genes).

Limitations, Reasons For Caution: The availability of human testis was the main limitation in this study.

Wider Implications Of The Findings: This is the first study to report acceleration of spermatogenesis recovery following chemotherapy by administration of a single SM. Our findings suggest that SB is a promising SM and should be assessed in future clinical trials for preservation of fertility in men diagnosed with cancer or in certain infertility cases (e.g. oligospermia).

Study Funding/competing Interest(s): This study was supported by Royan Institute and National Institute for Medical Research Development (NIMAD, grant no 963337) granted to H.B. The authors have no conflict of interest to report.
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http://dx.doi.org/10.1093/humrep/dez196DOI Listing
December 2019

Liver stiffness correlates with serum osteopontin and TAZ expression in human liver cirrhosis.

Ann N Y Acad Sci 2020 04 7;1465(1):117-131. Epub 2019 Nov 7.

Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

The pivotal role of the extracellular matrix (ECM) as both a cause and consequence of liver fibrosis is striking. However, mechanotransducer molecules and profibrogenic factors induced by liver stiffness are still unclear. The current study aimed to investigate liver stiffness and its correlation with the expression of the transcriptional coactivator with PDZ-binding motif (TAZ) and serum osteopontin (OPN) in human cirrhosis. In this case-control study, liver tissue stiffness was determined using atomic force microscopy in cirrhotic livers (n = 38) of different etiologies and in controls (n = 10). Immunohistochemical and qRT-PCR analyses were performed to analyze TAZ expression. Besides, western blotting and ELISA were performed to assess liver Indian hedgehog and serum OPN levels, respectively. Liver stiffness, TAZ expression, and hepatic gene expression and serum protein levels of OPN were significantly increased in patients with cirrhosis compared with the control groups (all P < 0.001), specifically in autoimmune- and alcohol-related cirrhosis. In cirrhotic patients, liver stiffness was significantly associated with the expression of nuclear TAZ and OPN. The correlation between matrix stiffness as a mechanical property, TAZ as a potential mechanotransducer, and OPN as a matricellular factor suggests possible effects of mechanical features of the ECM on the expression of the aforementioned profibrogenic markers, which is predominant in autoimmune- and alcohol-related cirrhosis.
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http://dx.doi.org/10.1111/nyas.14259DOI Listing
April 2020

Changes in the distribution of etiologies of cirrhosis among patients referred for liver transplantation over 11 years in Iran.

Eur J Gastroenterol Hepatol 2020 07;32(7):844-850

Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan.

Background And Aim: Cirrhosis is a major public health problem worldwide. The prevalence of cirrhosis is various in different geographical regions. The aim of the present study was to determine the distribution of the etiologies of cirrhosis and their proportional changes through recent 11 years in Iran.

Methods: In this retrospective, observational study, the data of cirrhotic patients who have been listed for liver transplantation in the Namazi Transplant Center (Shiraz, Iran) between January 2006 and December 2016 were analyzed. Demographic and clinical data of the patients including model for end-stage liver disease score, year of registration, and the etiologic diagnosis for each patient were retrieved.

Results: The ratio of males to females was the highest (2.6:1) in patients with age over 50 years. Of 4891 patients, hepatitis B virus cirrhosis had the highest frequency (23.53%) and alcoholic cirrhosis had the lowest frequency (1.70%). The percentages of waiting list patients with hepatitis B virus (34.48%-17.48%) (P < 0.001), autoimmune hepatitis (12.64%-8.50%) (P = 0.037), and alcoholic cirrhosis (2.30%-1.10%) were decreased (P = 0.008) and the percentages of waiting list patients with cholestatic (12.64%-25.20%) and nonalcoholic steatohepatitis cirrhosis (0.77%-8.82%) were increased over 11 years (both P < 0.001). Hepatitis B virus and autoimmune hepatitis cirrhosis were the most prevalent in male and female patients, respectively.

Conclusion: The results of the present study showed an increase in the frequency of cholestasis and nonalcoholic steatohepatitis cirrhosis and therefore it should be considered in the health policy implementation.
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http://dx.doi.org/10.1097/MEG.0000000000001590DOI Listing
July 2020

Liver Transplant for Metastatic Neuroendocrine Tumors: A Single-Center Report of 15 Cases.

Exp Clin Transplant 2021 Jun 11;19(6):588-591. Epub 2019 Oct 11.

From the Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Objectives: Liver transplant has been shown to be a good treatment option for patients with nonresectable tumors that are limited to liver and that do notrespond to medicaltreatment. In this study, our aim was to share our experience in management of patients with neuroendocrine tumors and liver metastasis by liver transplant with and without more extensive surgical interventions.

Materials And Methods: We performed a 6-year (2011- 2017) retrospective study of data from the Namazi Hospital Transplant Research Center. Inclusion and exclusion criteria were determined based on pretransplant policy in our center. Our study included 15 patients with mean age of 33.3 years.

Results: Of the 15 patients included, 53.3% (n = 8) had liver transplant alone, 26.6% (n = 4) had multiorgan transplant, 6.66% (n = 1) underwentWhipple procedure and liver transplant, and 6.66% (n = 1) had segmental ileal resection and liver transplant. Six early mortalities occurred during the posttransplant hospital stay, and 2 patients with multiorgan transplant died in the followup period. In addition, 1 patient needed retransplant during follow-up due to chronic rejection.

Conclusions: In patients with neuroendocrine tumors, the therapeutic approach to the liver metastasis and the prognosis can be determined based on the natural history of the disease, severity and progression of symptoms,tumor biology, location, and differentiation. Early diagnosis and management are needed to allow less invasive treatment protocols, which could result in more favorable outcomes.
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http://dx.doi.org/10.6002/ect.2019.0154DOI Listing
June 2021

Cytoprotective effects of ginsenoside Rd on apoptosis-associated cell death in the isolated human pancreatic islets.

EXCLI J 2019 22;18:666-676. Epub 2019 Aug 22.

Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, USA.

Ginsenoside Rd (GS-Rd), one of the main pharmacologically active components of ginseng, has shown the potential to stabilize mitochondrial membrane integrity and decrease apoptotic death in neuronal and non-neuronal cells. The present study aimed to evaluate the effect of this bioactive molecule on the apoptosis-associated cell death in human pancreatic islets. In this regard human pancreatic islets were isolated and grouped for the treatment with GS-Rd. The isolated islets were treated with different concentrations of GS-Rd. After 24 and 72 h of incubation, the islets were evaluated in terms of viability, , , and insulin gene expression, BAX, BCL2, and caspase-3 protein expression, apoptosis, and glucose-induced insulin/C-peptide secretion. Our results revealed the islet survival was significantly decreased in the control group after 72 h of incubation. However, GS-Rd inhibited the progress of the islet death in the treated groups. TUNEL staining revealed that the preventive effect of this molecule was caused by the inhibition of apoptosis-associated death. In this regard, the activation of caspase-3 was down-regulated in the presence of GS-Rd. GS-Rd did not exhibit undesirable effects on glucose-induced insulin and C-peptide stimulation secretion. In conclusion, GS-Rd inhibited the progress of death of cultured human pancreatic islets by diminishing the apoptosis of the islet cells.
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http://dx.doi.org/10.17179/excli2019-1698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785759PMC
August 2019

Characterization of biopsy proven non-alcoholic fatty liver disease in healthy non-obese and lean population of living liver donors: The impact of uric acid.

Clin Res Hepatol Gastroenterol 2020 09 11;44(4):572-578. Epub 2019 Oct 11.

Avicenna Center for Medicine and Organ Transplant, Avicenna Transplant Hospital, PO Box: 71994-67985, Shiraz, Iran.

Background: Non-alcoholic fatty liver disease (NAFLD) is frequently seen among non-obese overweight individuals and lean subjects (those with normal body mass index). This study aimed to investigate prevalence and risk factors of biopsy proven NAFLD in a cluster of healthy non-obese and lean individuals.

Methods And Materials: In a retrospective study, adult (>18 years) apparently healthy individuals who had donated liver to pediatric patients between July 2012 and October 2018 were included. Non-obese and lean individuals were defined as BMI<30kg/m and BMI<25kg/m, respectively.

Results: Totally 310 patients were included. Seventy-six individuals (24.5%) had NAFL and 30 patients (9.67%) had non-alcoholic steatohepatitis (NASH) among non-obese population. In multivariate regression analysis, only higher BMI was marginally associated with NASH in non-obese compared to those without NASH (Odds ratio: 2.52, 95% CI: 0.097-6.54; P=0.05). Totally, 246 individuals were lean. 55 individuals (22.3%) had NAFL and 20 individuals (8.2%) had NASH in their liver biopsies. In univariate analysis, serum triglyceride, cholesterol, LDL, ALT, alkaline phosphatase and uric acid were associated with NAFL among lean individuals (P<0.05). In regression analysis, serum uric acid was associated with NAFL (Odds ratio: 1.70, 95% CI: 1.18-2.45; P=0.004) and NASH in lean individuals (Odds ratio: 1.98, 95% CI: 1.27-3.10; P=0.003).

Conclusion: NAFLD/NASH is prevalent even in a healthy lean population when evaluated by liver biopsy. Higher BMI and serum uric acid were two major risks of NAFLD/NASH in non-obese and lean individuals.
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http://dx.doi.org/10.1016/j.clinre.2019.09.002DOI Listing
September 2020
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