Comparison of Mir122 expression in children with biliary atresia and healthy group.

Biliary atresia (BA) is the primary cause of neonatal jaundice with various pathological mechanisms. Many BA patients may experience progressive liver dysfunction and eventually need a liver transplant. Therefore, identifying potential non-invasive biomarkers for BA is crucial. miR-122, the most abundant microRNA in the liver, plays significant roles in different liver diseases. This study aimed to assess miR-122 levels in BA patients. Eighteen patients with biliary atresia were selected at random from the Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS), along with 18 healthy controls. Blood samples were collected, and biochemical parameters (such as liver function tests) were measured. Quantitative reverse-transcription PCR (RT-PCR) was conducted on serum samples from both the case and control groups to analyze miR-122 levels. The study results indicated that serum miR-122 expression in BA patients was elevated compared to the control group, although it did not reach statistical significance. Additionally, no correlation was found between miR-122 expression and serum levels of liver enzymes or other laboratory findings in BA cases. miR-122 could be a potential target for diagnosing BA; however, further research with a larger population is necessary to determine if miR-122 could serve as a useful biomarker for diagnosing BA.

Demographic, clinical, and surgical features of patients undergoing thyroidectomy due to thyroid lesions in Southern Iran: A cross-sectional study.

Background and Aims: The incidence of thyroid cancer has witnessed a significant global increase and stands as one of the most prevalent cancers in Iran. This surge is primarily attributed to the escalating incidence of papillary thyroid cancer (PTC), with overdiagnosis emerging as an equally noteworthy factor. Consequently, this study aims to ascertain the incidence of thyroid cancer, along with its clinical presentation, demographic characteristics, and surgical features in patients undergoing thyroid surgery. Methods: This cross-sectional study involved the evaluation of patient files from referral centers in Shiraz spanning the years 2015-2020. Demographic and clinical information pertaining to thyroid cancer was extracted and subsequently analyzed using SPSS software. Results: A total of 533 documented cases of thyroid cancer undergoing surgery revealed an annual rate of 89 cases in our location. The average age of the patients was 43.9 ± 13.4 years (ranging from 13 to 92), with females constituting 429 (83.5%) of the cases, and 278 (54.1%) being malignant. Conventional PTC emerged as the most prevalent pathology, accounting for 239 (45.0%) of the cases. Patients with thyromegaly exhibited significantly higher incidences of nonmalignant tumors (p = 0.01), while those with malignant tumors were notably younger than those with nonmalignant tumors (p = 0.001). Conclusion: Our study revealed a progressive rise in the number of patients undergoing thyroidectomy over the years, with PTC constituting the majority of cases. Malignant cases were more frequently observed in younger patients, and in smaller lesion sizes, highlighting the importance of early screening and optimizing detection methods, especially in high-risk populations.

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.

Immunogenicity of Inactivated SARS-CoV-2 Vaccine (BBIBP-CorV; Sinopharm) and Short-Term Clinical Outcomes in Vaccinated Solid Organ Transplant Recipients: A Prospective Cohort Study.

BackgroundImmunocompromised patients have lower seroconversion rate in response to COVID-19 vaccination. The aim of this study is to evaluate the humoral immune response with short-term clinical outcomes in solid organ transplant recipients vaccinated with SARS-CoV-2 vaccine (BBIBP-CorV; Sinopharm).MethodsThis prospective cohort was conducted from March to December 2021 in Abu Ali Sina hospital, Iran. All transplant recipients, older than 18 years were recruited. The patients received two doses of Sinopharm vaccine 4 weeks apart. Immunogenicity was evaluated through assessment of antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 after the first and second dose of vaccine. The patients were followed up for 6 months after vaccination.ResultsOut of 921 transplant patients, 115 (12.5%) and 239 (26%) had acceptable anti S-RBD immunoglobulin G (IgG) levels after the first and second dose, respectively. Eighty patients (8.68%) got infected with COVID-19 which led to 45 (4.9%) of patients being hospitalized. None of the patients died during follow-up period. Twenty-four (10.9%) liver transplant recipients developed liver enzyme elevation, and increased serum creatinine was observed in 86 (13.5%) kidney transplant patients. Two patients experienced biopsy-proven rejection without any graft loss.ConclusionOur study revealed that humoral response rate of solid organ transplant recipients to Sinopharm vaccine was low.

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.

COVID-19 versus applied infection control policies in a Major Transplant Center in Iran.

BACKGROUND: Since Shiraz Transplant Center is one of the major transplant centers in Iran and the Middle East, this study was conducted to evaluate outcomes of the applied policies on COVID-19 detection and management. METHODS: During 4 months from March to June 2020, patient's data diagnosed with the impression of COVID-19 were extracted and evaluated based on demographic and clinical features, along with the length of hospital stay and expenses. RESULTS: Our data demonstrated that a total of 190 individuals, with a median age of 58, were diagnosed with COVID-19 during the mentioned period. Among these, 21 patients had a positive PCR test and 56 patients had clinical symptoms in favor of COVID-19. Also, 113 (59%) patients were classified as mild based on clinical evidence and were treated on an outpatient basis. Furthermore, 81 out of 450 cases (18%) of the healthcare workers at our center had either PCR of clinical features in favor of COVID-19. The mortality rate of our study was 11% and diabetes mellitus, hypertension were considered risk factors for obtaining COVID-19 infection. The direct cost of treatment and management of patients with COVID-19 amounted to 2,067,730,919 IRR, which considering the 77 patients admitted to Gary Zone per capita direct cost of treatment each patient was 26,853,648 IRR. CONCLUSION: We demonstrated that the COVID-19 pandemic had a noticeable influence on our transplant center in aspects of delaying surgery and increased hospital costs and burden. However, by implanting proper protocols, we were able to was able to provide early detection for COVID-19 and apply necessary treatment and prevention protocols to safeguard the patients under its coverage, especially immunocompromised patients.

Polymorphism Analysis of Interleukin-18 and Interleukin-37 Genes in Hepatitis B Infections with Different Outcomes: A Preliminary Report from an Iranian Population.

OBJECTIVE: Given the vital role of cytokines in influencing the outcomes of hepatitis B virus (HBV) infections, this study aimed to investigate the association between polymorphisms of interleukin (IL)-18 and IL-37 and the outcomes of HBV infection. METHODS: In this study, we enrolled 300 subjects with chronic HBV infection, including those with cirrhosis/hepatocellular carcinoma (C/HCC), chronic active hepatitis B (CAH) infection, or asymptomatic carriers (AC), and 58 individuals whose infection was spontaneously cleared (SC). Genomic DNA was extracted, and IL-18/IL-37 genotyping was performed using PCR-RFLP and ARMS-PCR. RESULTS: The frequency of genotypes and alleles of IL-18 single nucleotide polymorphisms (SNPs) at positions rs1946519, rs1946518, and rs187238 and IL-37 at position rs4241122 were not statistically different among the four studied groups (P>0.05). Furthermore, the frequency of different haplotypes was similar among the studied groups (P>0.05). CONCLUSIONS: Polymorphisms of IL-18 SNPs at positions rs1946519, rs1946518, and rs187238 and variation of IL-37 at position rs4241122 do not appear to influence the outcome of HBV infection.

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.

Impact of Octreotide on Early Complications After Liver Transplant: A Randomized, Double-Blind Placebo-Controlled Trial.

OBJECTIVES: Acute kidney injury and early allograft dysfunction are 2 common complications after liver transplant. Octreotide, through its various mechanisms, may have a role in preventing these complications. MATERIALS AND METHODS: In this randomized, double- blind placebo-controlled clinical trial, we randomly assigned 50 patients who underwent deceased donor liver transplant and fulfilled the study inclusion requirements to receive either octreotide infusion for 3 days in the first 3 days after transplant in the intensive care unit or placebo. The eligible patients were properly informed while on the transplant wait list and gave their consent to participate in the study. The rates of acute kidney injury within the first 7 days after transplant (based on KDIGO criteria), early allograft dysfunction, and nosocomial infection; total length of hospital stays and intensive care unit admissions; and intubation time were recorded and compared between the 2 groups. RESULTS: No significant differences were found between the 2 groups with regard to demographic characteristics and graft factors (P > .05). However, acute kidney injury, early allograft dysfunction, and nosocomial infection rates were significantly lower in the octreotide group compared with the control group (P < .05). Moreover, a significant difference was observed between the 2 groups with regard to length of hospital stay and intensive care unit admissions (P < .05). For infection, female patients had a higher likelihood of infection than male patients (odds ratio = 23.19). Intensive care unit admission was associated with a higher probability of early graft dysfunction (odds ratio = 1.34). In contrast, longer intubation time was associated with a decrease in the probability of early graft dysfunction (odds ratio = 0.93). CONCLUSIONS: This study showed that octreotide infusion in the first 3 days after liver transplant could improve renal and allograft function and reduce infection and length of hospital stay.

Quality of Life and Its Determinants in Liver Transplantation Candidates: A Missed Link in Liver Care Program during the Waiting Time for Liver Transplantation.

Background: The health-related quality of life (HRQOL) in the before liver transplantation (LT) stage has not been studied as much as that after the LT stage. We aimed to assess HRQOL and its determinants before the LT stage. Methods: As a cross-sectional study, HRQOL of all adult patients (n=632) referred to the LT center of Shiraz, Iran in 2018-2019 were assessed. Demographic, socioeconomic, medical, and paraclinical data were requested. Physical (PCS) and mental (MCS) aspects of HRQOL were assessed using the SF36 questionnaire. Univariable, multivariable (linear regression), and confirmatory factor analysis were performed utilizing SPSS 20 and Mplus 6.1 software. P<0.05 was considered to be significant. Results: The mean age of the patients was 47.6±12.3 years, while 414 (65.6%) were men, and the mean, score of the model for end-stage liver disease (MELD) was 18.36±5.58. The mean score of QOL, PCS, and MCS was 50.01±21.73, 46.23±23.23, and 53.78±23.91 (out of 100), respectively. Vitality had the most association with HRQOL, while role limitations had the lowest. The multivariable analysis revealed that unemployment (P<0.001), anemia (P=0.005), weight loss (P=0.005), diabetes mellitus (DM) (P=0.009), low MELD score (P=0.027), and drug use (P=0.03) were the significant determinants of HRQOL, respectively. Conclusion: The present study showed that HRQOL in the LT candidates was at the intermediate level, while their PCS and MCS are at the low and moderate levels, respectively. Furthermore, physical performance, job status, anemia, weight loss, MELD score, DM, and drug use should be considered as the significant determinants of HRQOL in the LT candidates.

Tissue presentation of human pegivirus infection in liver transplanted recipients.

Human pegivirus-1 (HPgV-1) is known for its protective role in HIV co-infected individuals. This immunomodulatory effect raised questions concerning the possible role of HPgV-1 infection and the risk of rejection in liver transplanted patients. We aimed to evaluate the possible protective effect of HPgV-1 on graft outcome of liver transplanted patients. A total of 283 patients were recruited. Formalin-fixed paraffin-embedded tissue samples were collected from the explanted liver. HBV-DNA, HCV-RNA, and HPgV-1-RNA were determined using PCR and multiplex RT-PCR assays. The clinical course of patients including the occurrence of acute cellular rejection was compared between HPgV-1-infected vs. uninfected patients. HBV-DNA, HCV-RNA and HPgV-1-RNA were detected in 42.6%, 4.9%, and 7.8% of samples, respectively. None of the HPgV-1-infected patients experienced graft rejection. Group LASSO logistic regression revealed that HPgV-1 infection was the only factor which significantly reduced the odds of graft rejection (OR = 0.5, 95% CI = 0.29-0.89). No significant association was found between the presence of HPgV-1 with HBV and HCV infections. The lack of graft rejection in HPgV-1-infected liver transplanted patients might indicate a possible role of this virus for graft surveillance. Since these are still preliminary findings, prospective studies should further elucidate the role of HPgV-1 in liver transplantation outcomes.

Isoniazid prophylaxis in liver transplant recipient with latent tuberculosis: Is it harmful for transplanted liver?

BACKGROUND: Liver transplantation (LT) is considered the only treatment for patients with end-stage liver disease and, despite its incredible impacts on the patients' health status, places them in an immunocompromised state in which opportunistic infection would find a way to present. Latent tuberculosis infection (LTBI) is the most common form of TB and can be diagnosed through tuberculin skin test (TST) or Interferon-Gamma Release Assays (IGRA). LT recipients are at significant risk of TB activation. There is no strict guideline to approaching these cases though, in most centers, Isoniazid (INH) would be prescribed prophylactically. INH is a hepatotoxic medication and can have adverse effects on the transplanted liver. There is no consensus on this issue; therefore, we aimed to survey the potential hepatotoxic effects of INH among LT recipients in Shiraz, Iran. METHODS: A retrospective cohort study was conducted among LT candidates and recipients at Abu Ali Sina Organ Transplantation Center between 1993 and 2019. All the cases underwent TST and chest X-ray to detect LTBI. All the LTBI were treated with INH from 6-9 months and followed by the level of liver enzymes for quick detection of hepatotoxicity. A control group was selected among LT recipients and matched for age, gender, MELD score, and donor age. RESULTS: Among 4895 medical records reviewed, 55 (1.12%) cases had LTBI. Neither INH-related hepatotoxicity, nor signs and symptoms that were suspicious to TB reactivation were reported. Overall, three deaths were reported, two because of myocardial infarction and one due to pneumonia. Ten patients (18.2%) experienced acute rejection as confirmed with pathology and responded to methylprednisolone. Aspartate aminotransferase (AST) was diminished from pre-LT time to the first time after transplantation; after that, it showed a steady pattern. Meanwhile, Alanine transaminase (ALT) was constant before and one stage later and decreased after that. Statistical analyses only showed significant changes in the total bilirubin titer between the case and control groups. CONCLUSION: This survey showed prophylactic management of LTBI with INH in LT candidates and recipients was associated with no hepatotoxicity or related death. It seems that INH prophylaxis is safe in LT settings and can efficiently prevent TB activation; however, careful monitoring for adverse effects and liver enzymes elevation is highly recommended.

Liver transplantation in glycogen storage disease: a single-center experience.

BACKGROUND: Glycogen storage diseases (GSDs) are inherited glycogen metabolic disorders which have various subtypes. GSDs of type I, III, IV, VI, and IX show liver involvement and are considered as hepatic types of GSDs. Thus, liver transplantation (LT) has been proposed as a final therapy for these types of GSD. LT corrects the primary hepatic enzyme defect; however, the long-term outcomes of LT in these patients have not been extensively evaluated so far. There are few reports in the English literature about the outcome of GSD patients after LT. There has been no report from Iran. The present retrospective study aimed to evaluate the long-term outcomes of eight patients with GSD types I, III, and IV who underwent LT in the affiliated hospitals of Shiraz University of Medical Sciences, from March 2013 to June 2021. During this period, there were no patients with GSD VI and IX identified in this center. RESULTS: The median time of diagnosis of the GSDs and at transplant was 1 year and 11 years, respectively. All eight transplanted patients were alive at the time of follow-up in this study. None of them required a re-transplant. All of the patients showed normalized liver enzymes after LT with no sign of hypoglycemia. CONCLUSIONS: LT is an achievable treatment for end-stage hepatic involvement of GSDs with a cure for metabolic deficiency. Our experience in these eight patients shows a favorable outcome with no mortality and no major complication.

Clinical Evaluation of an HTK Solution for Liver Transplantation: A Phase 3 Randomized Pilot Clinical Trial Study.

BACKGROUND: Organ preservation solutions are not easily accessible in Iran, similar to many resource-limited countries. We aimed to evaluate the efficacy of a locally-produced HTK solution among adult liver transplantation candidates in a pilot clinical trial study. METHODS: Adult patients undergoing liver transplantation were randomly allocated into two groups. One received the HTK solution (PharMedCina Inc., Shiraz, Iran), and the second received the commercially available HTK solution (Custodiol ®). RESULTS: Overall, 28 individuals entered the study, including 11 and 9 males (78.6% and 64.3%) in the Custodiol® and local HTK groups, respectively. Clinical characteristics, including postoperative biliary complications, reperfusion syndrome, infection and primary non-function (PNF) rates, amount of intraoperative bleeding, length of hospital and ICU stay, peak aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and duration of follow-up were similar between the two groups (P>0.05). One patient died in the locally-produced HTK group. The patient underwent re-transplantation 20 days after his first liver transplantation due to PNF. Two patients died in the Custodiol group, both due to PNF of the liver, which occurred five and three days after transplantation. The two groups did not show any difference regarding serum levels of AST, ALT, alkaline phosphatase (ALP), bilirubin, platelet count, prothrombin time and international normalized ratio, white blood cell count, blood urea nitrogen, and creatinine on the first postoperative day and on the day of discharge (P>0.05). CONCLUSION: Based on the findings of this pilot study with the current sample size, no statistically significant difference was found between our locally-produced HTK solution and Custodiol® regarding clinical outcomes.

Evaluation of the therapeutic regimen in COVID-19 in transplant patients: where do immunomodulatory and antivirals stand?

BACKGROUND: The management of COVID-19 in organ transplant recipients is among the most imperative, yet less discussed, issues based on their immunocompromised status along with their vast post-transplant medication regimens. No conclusive study has been published to evaluate proper anti-viral and immunomodulator medications effect in treating COVID-19 patients to this date. METHOD: This retrospective study was conducted in Shiraz Transplant Hospital, Iran from March 2020 to May 2021 and included COVID-19 diagnosed patients based on SARS-CoV-2 RT-PCR positive test who had been hospitalized for at least 48 h before enrolling in the study. Clinical and demographic information of patients, along with their treatment course and the medication used were evaluated and analyzed using multiple regression analysis. RESULTS: A total of 245 patients with a mean age of 49.59 years were included with a mortality rate of 8.16%. The administration of Remdesivir as an anti-viral drug (P value < 0.001) and Tocilizumab as an immunomodulator drug (P value < 0.001) could reduce the hospitalization period in the hospital and the intensive care unit, as well as the mortality rates significantly. Meanwhile, the patients treated with Lopinavir/Ritonavir experienced a lower chance of survival (OR < 1, P value = 0.04). No significant difference was observed between various therapeutic regimens in clinical complications such as bacterial coinfections, cardiovascular and gastrointestinal adverse reactions, and liver or kidney dysfunctions. CONCLUSION: The administration of Remdesivir as an anti-viral and Tocilizumab as an immunomodulatory drug in solid-organ transplant recipients could be promising treatments of choice to manage COVID-19.

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.

TLR2 and TLR4 mRNA expression levels in liver transplant patients with acute rejection.

Toll-like receptors (TLRs) have important role in transplant outcomes by activating the innate immune system and production of pro-inflammatory cytokines, leading to graft rejection. We assessed the expression level of TL2 and TLR4 in acute rejection (AR) on the 1st and 7th-day post-transplantation. TLR2 and TLR4 expressions were evaluated by real-time PCR in both the AR group (n = 50) and non-AR (n = 50), compared with the control group. Also, the correlation of the expression levels of TLRs between both the 1st and 7th day was analyzed. ROC curve analysis was used to determine the cut-off value for TLRs expression. TLR4 mRNA expression was significantly up-regulated in AR patients vs. the controls on the 1st day (p ≤ 0.05) and it was down-regulated in non-AR vs. controls on the 1st day (p ≤ 0.05). Also, TLR4 expression had decreased in both AR and non-AR groups vs. control on the 7th day (p ≤ 0.05). Both TLR2 and TLR4 expression in comparison to non-AR had increased in the AR group on the 7th day (p ≤ 0.05). TLR2 expression positively correlated between 1st and 7th day in AR (r = 0.3, (p ≤ 0.05) and non-AR group (r = 0.2, p ≤ 0.05). ROC curve analysis showed a cut-off value of TLR2 up to 0.98 with sensitivity 71.05 (95%CI = 54.1-84.6) and specificity 63.27 (95%CI = 48.3-76.6) that could distinguish between AR and non-AR group (p ≤ 0.05). The data support that both TLR2 and TLR4 expression have an effective role in AR after liver transplantation and could be used as possible biomarkers for AR to choose better therapeutic strategies based on immunological aspects.

Tenofovir in the treatment of hepatitis B virus infection after liver transplantation, a single center large population study.

AIM: This study investigated the safety and efficacy of tenofovir disoproxil fumarate (TDF) compared with lamivudine (LAM) in the prevention of recurrent HBV infection after liver transplantation (LT). BACKGROUND: Although the recurrence of hepatitis B virus after liver transplantation (LT) is now very uncommon with both nucleoside and nucleotide analogs represented with lamivudine and tenofovir disoproxil fumarate, respectively, few studies have compared the two classes. METHODS: A total of 302 HBV-related post-transplant patients who received liver transplants from deceased donors were enrolled in this retrospective study from 2011 to 2015 in the Shiraz Organ Transplant Center, Iran. The demographic data, kidney function, recurrence, resistance rate, and acute rejections at 1-, 6-, and 12-month intervals and after 12 months were compared on TDF (n=209) and lamivudine (n=93) groups. RESULTS: During a median follow-up period of 42.9 months, mean creatinine level was not significantly different between the two groups. Hepatitis B virus recurrence rate as well as acute graft rejection episode had no statistical difference in either group over the study period. CONCLUSION: Kidney function, creatinine level, disease recurrence, and acute graft rejection were comparable between tenofovir disoproxil fumarate and lamivudine in patients who received follow-up periods.

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.