Outcomes of patients with acute severe autoimmune hepatitis: Predictors of non-response to corticosteroids and need for liver transplantation.

BACKGROUND AND AIMS: Acute severe autoimmune hepatitis (AS-AIH) is an evolving concept and the outcomes and optimal treatment have been less studied. In this study, we aimed to investigate the outcomes of patients with AS-AIH and predictors of non-response to corticosteroid therapy and need for liver transplantation. METHODS: In a retrospective cohort, we included patients with AS-AIH admitted to our liver center. We defined AS-AIH based on the international autoimmune hepatitis group score as acute presentation of AIH with an international normalized ratio (INR) ≥ 1.5 and without liver cirrhosis and hepatic encephalopathy. All patients received high dose corticosteroid therapy. Treatment response was defined as liver transplant free survival at 4 months after presentation. Factors associated with response to corticosteroids and survival of patients were studied. RESULTS: In total, 61 patients with AS-AIH were included. Forty-seven patients responded to corticosteroid therapy. In the multivariate regression model, baseline INR (odds ratio [OR]: 0.184; 95% confidence interval [CI]: 0.048-0.699; p = 0.013) and delayed versus early initiation of corticosteroid (after vs. before 5 days of presentation) (OR: 0.189; 95% CI: 0.039-0.919; p = 0.039) were independent predictors of clinical non-response to corticosteroid therapy. In the multivariable Cox regression model, baseline INR level (OR: 2.542; 95% CI: 1.188-5.440; p = 0.016) and delayed initiation of corticosteroids (OR: 3.578; 95% CI: 1.084-11.812; p = 0.036) were independent predictors of liver transplant free survival at 6 months after diagnosis. CONCLUSION: Delayed initiation of corticosteroid therapy might be predictive of clinical non-response to medical therapy and need for liver transplantation in patients with AS-AIH.

Increasing Prevalence and High Survival Rate of Liver Transplanted Patients with NASH and PSC Cirrhosis.

BACKGROUND: Epidemiological studies on liver transplant (LT) patients can provide valuable information about the etiology and trends of cirrhosis. The present study aimed to investigate the prevalence and trend of different etiologies and survival rates of LT patients at the Namazi Transplant Center in Shiraz, Iran, between 2001 and 2018. METHODS: In this single-center, retrospective cohort study, the demographic and clinical characteristics of 3751 patients who underwent LT and met the study inclusion criteria, including age, gender, blood group, body mass index, model for end-stage liver disease (MELD) score, cause of cirrhosis, and diabetes, were extracted from patients' physical or electronic medical records between 2001 and 2018. RESULTS: The MELD scores of LT patients with primary sclerosing cholangitis (PSC), hepatitis B virus (HBV), and non-alcoholic steatohepatitis (NASH) cirrhosis significantly decreased over the study period (P<0.001). Among the LT patients, HBV infection had the highest frequency (21.09%), followed by cryptogenic (17.33%) and PSC (17.22%). The proportion of patients with PSC and NASH (both P<0.001) cirrhosis was significantly increased, so that PSC cirrhosis (2016: 19.4%, 2018: 18.8%) surpassed HBV (2016: 18.4%, 2018: 13.5%), autoimmune hepatitis (2016: 11.7%, 2018: 12.7%), and cryptogenic cirrhosis (2016: 16.1%, 2018:14%) as the leading indication for LT from 2016 to the end of the study period. Fortunately, these patients had a better survival rate than other common diseases (HR: 0.53, CI: 0.43‒0.66; P<0.001). CONCLUSION: The proportion of NASH and PSC cirrhosis significantly increased during the 18 years of study. However, these patients had an improved survival rate. Therefore, health organizations should pay more attention to non-communicable diseases, especially fatty liver disease and cholangitis.

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

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

Novel technique for arterial reconstruction in simultaneous pancreas-kidney transplantation, a randomized clinical trial.

INTRODUCTION: Simultaneous pancreas kidney (SPK) transplantation is an invaluable procedure to enhance the quality of life of insulin-dependent patients with advanced renal disease. The creation of vascular anastomoses of the donor's pancreas vessels to the recipient's, is of utmost importance to predict the graft outcome and surgical complications. In the study we introduce a novel technique for arterial reconstruction during SPK transplantation. METHODS: Conventionally, during the SPK transplantation, a so-called Y-graft is anastomosed between donor's superior mesenteric and splenic artery to the recipient's right iliac artery. In the study we adopted a new technique by preparing an extra extension using the donor's carotid artery, to be anastomosed to the Y-graft and the iliac artery. In this non-blinded randomized clinical trial we compared the surgical complications and early outcomes between the 2 groups of patients with the traditional and new arterial reconstruction techniques during 3 months after transplantation. RESULTS: Thirty adult patients were included in the study. The incidence of pancreatitis, vascular thrombosis and surgical site infection was lower in the new Y-graft and extension technique, which was not statistically significant. However, the calculated Cohen's d index showed the medium effect of new Y-graft and extension technique on complication after SPK transplantations. CONCLUSION: The post-operative complications tend to be lower in the novel arterial reconstruction technique, however a study on a larger patient group is encouraged to confirm our primary results. TRIAL REGISTRATION: The study was registered at the Iranian Registry of Clinical Trials on 12/05/2022; IRCT 20210625051701N2; ( http://www.irct.ir/ ).

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.

Angiotensin receptor blockers might be protective against hepatic steatosis after liver transplantation.

BACKGROUND: Hepatic steatosis is an increasing complication in liver transplant recipients. Currently, there is no pharmacologic therapy for treatment of hepatic steatosis after liver transplantation. The aim of this study was to determine the association between use of angiotensin receptor blockers (ARB) and hepatic steatosis in liver transplant recipients. METHODS: We conducted a case-control analysis on data from Shiraz Liver Transplant Registry. Liver transplant recipients with and without hepatic steatosis were compared for risk factors including use of ARB. RESULTS: A total of 103 liver transplant recipients were included in the study. Thirty five patients treated with ARB and 68 patients (66%) did not receive these medications. In univariate analysis, ARB use (P = 0.002), serum triglyceride (P = 0.006), weight after liver transplantation (P = 0.011) and etiology of liver disease (P = 0.008) were associated with hepatic steatosis after liver transplantation. In multivariate regression analysis, ARB use was associated with lower likelihood of hepatic steatosis in liver transplant recipients (OR = 0.303, 95% CI: 0.117-0.784; P = 0.014). Mean duration of ARB use (P = 0.024) and mean cumulative daily dose of ARB (P = 0.015) were significantly lower in patients with hepatic steatosis. CONCLUSION: Our study showed that ARB use was associated with reduced incidence of hepatic steatosis in liver transplant recipients.

Wunderlich Syndrome: Early Misdiagnosis with Acute Renal Colic During COVID-19 Pandemic.

Wunderlich syndrome, also known as the spontaneous non-traumatic retroperitoneal hemorrhage, is an uncommon condition characterized by acute, spontaneous, non-traumatic renal hemorrhage into the subcapsular or perirenal spaces. The majority of the cases are caused by renal cell carcinoma or renal angiomyolipoma. Other causes are arteriovenous malformation, cystic renal disease, and anticoagulation medications. The classic presentation is "Lenk's triad" of acute flank pain, palpable flank mass, and hypovolemia. The diagnosis is based on clinical suspicion and confirmed by a CT scan, which is the preferred imaging modality. Due to the rarity of these cases and the wide range of clinical manifestations, the treatment is divergent ranging from conservative management to nephrectomy. Herein, we present a case of massive right renal hemorrhage caused by warfarin toxicity that was initially misdiagnosed as acute renal colic due to the patient's refusal to refer to the clinic during Corona Virus Disease- 19 era and was later managed with a right nephrectomy.

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.

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

Liver diseases in children and adolescents are a significant and arising public health issue and should be surveyed from different dimensions (clinical and para-clinical, psychological, socio-economic) and in diverse populations. Shiraz Liver Transplant Center, Shiraz, Iran is the only center for pediatric liver transplantation and its pre-operative evaluations. This provides a unique and valuable situation for studying this vulnerable population. The Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS) was established to assess cirrhotic children, the course of their disease, and treatment over time. This cohort study aimed to prospectively evaluate the natural course and factors that contributed to complications and death of children with chronic liver disease in the region. SPLCCS was launched in September 2018 after obtaining ethical approval; until August 2022, 370 children with end-stage liver disease were enrolled and followed every six months. Here, the cohort's features, the included population's baseline characteristics, and primary outcomes are reported.

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

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

Predictors of Death in the Liver Transplantation Adult Candidates: An Artificial Neural Networks and Support Vector Machine Hybrid-Based Cohort Study.

Background: Model for end-stage liver disease (MELD) is currently used for liver transplantation (LT) allocation, however, it is not a sufficient criterion. Objective: This current study aims to perform a hybrid neural network analysis of different data, make a decision tree and finally design a decision support system for improving LT prioritization. Material and Methods: In this cohort follow-up-based study, baseline characteristics of 1947 adult patients, who were candidates for LT in Shiraz Organ Transplant Center, Iran, were assessed and followed for two years and those who died before LT due to the end-stage liver disease were considered as dead cases, while others considered as alive cases. A well-organized checklist was filled for each patient. Analysis of the data was performed using artificial neural networks (ANN) and support vector machines (SVM). Finally, a decision tree was illustrated and a user friendly decision support system was designed to assist physicians in LT prioritization. Results: Between all MELD types, MELD-Na was a stronger determinant of LT candidates' survival. Both ANN and SVM showed that besides MELD-Na, age and ALP (alkaline phosphatase) are the most important factors, resulting in death in LT candidates. It was cleared that MELD-Na <23, age <53 and ALP <257 IU/L were the best predictors of survival in LT candidates. An applicable decision support system was designed in this study using the above three factors. Conclusion: Therefore, Meld-Na, age and ALP should be used for LT allocation. The presented decision support system in this study will be helpful in LT prioritization by LT allocators.

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

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

Immunosuppressive regimens on conversion of cytomegalovirus infection to disease in liver transplant recipients.

Background: Cytomegalovirus (CMV) disease is one of the most common infectious complications after liver transplantation. It is the cause of numerous morbidity and mortalities. Intensity of immunosuppression defined as overall immunosuppressive drug dosage seems to affect infectious complications. The main purpose of this study is to investigate the intensity of immunosuppression on conversion of CMV infection to disease in this population. Methods: In this cross-sectional study, we retrospectively evaluated and analyzed the data of all recipients who underwent orthotopic liver transplantation (OLT) between March 2014 and March 2016 and had positive serum PCR for CMV after transplantation in follow- up course. Of 134 recipients, only 66 adult liver transplant recipients were eligible to be studied. Multiple variables such as MELD score, cold ischemic time, warm ischemic time, operative data, immunosuppressive drugs and regimen, plasma CMV viral load, donor and recipient CMV IgG serostatus were recorded and analyzed. Results: of the 66 patients, 50 (76%) had CMV infection and 16 (24%) had disease. There was significant association between donor CMV IgG serostatus, extra corticosteroid pulse therapy, acute cellular rejection, serum tacrolimus level and conversion of CMV infection to CMV disease (P=0.005, 0.001, 0.031, 0.031). Conclusion: It seems that the intensity of immunosuppression has influence on conversion rate of CMV infection to disease in liver recipients.

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

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

Novel Gene-Correction-Based Therapeutic Modalities for Monogenic Liver Disorders.

The majority of monogenic liver diseases are autosomal recessive disorders, with few being sex-related or co-dominant. Although orthotopic liver transplantation (LT) is currently the sole therapeutic option for end-stage patients, such an invasive surgical approach is severely restricted by the lack of donors and post-transplant complications, mainly associated with life-long immunosuppressive regimens. Therefore, the last decade has witnessed efforts for innovative cellular or gene-based therapeutic strategies. Gene therapy is a promising approach for treatment of many hereditary disorders, such as monogenic inborn errors. The liver is an organ characterized by unique features, making it an attractive target for in vivo and ex vivo gene transfer. The current genetic approaches for hereditary liver diseases are mediated by viral or non-viral vectors, with promising results generated by gene-editing tools, such as CRISPR-Cas9 technology. Despite massive progress in experimental gene-correction technologies, limitations in validated approaches for monogenic liver disorders have encouraged researchers to refine promising gene therapy protocols. Herein, we highlighted the most common monogenetic liver disorders, followed by proposed genetic engineering approaches, offered as promising therapeutic modalities.

Intestinal Transplantation in a Country Without Home Parenteral Nutrition: The Largest Report from the Middle East.

BACKGROUND: Many regions of the world, especially middle- and low-income countries, lack facilities for home parenteral nutrition and thus cannot follow existing guidelines for intestinal transplantation. Herein, we report our experiences with treatment protocols, intraoperative management, and early postoperative outcomes among patients undergoing either isolated intestinal transplantation or multivisceral transplantation in our center. METHODS: During a 1-year period from March 2019 to March 2020, a total of 9 intestinal transplantations including 6 isolated intestinal transplantations and 3 multivisceral transplantations were performed in our center. We reported on donor selection strategies, surgical treatment, anesthesiology care and protocols for total parenteral nutrition, immunosuppression regimen, and pathology evaluation. RESULTS: Mean (standard deviation) age of patients was 37.5 ± 12.5 years. The majority of patients were females (7/9). The median (interquartile range) waiting time for patients from diagnosis to transplantation was 79 (34, 164) days. Our 7-day survey of the amount of fluid therapy after transplantation revealed that the greatest need for fluid therapy was seen on the second postoperative day. After transplantation, 2 patients showed a total of 3 episodes of severe rejection, 1 of which was antibody-mediated. The 1-year survival was 66.6% and the 2-year survival was 44.5% in our study population. The median (interquartile range) time to death was 157 (26.5, 382) days. The most common cause of death was sepsis in our series (3/5). CONCLUSION: Acceptable outcomes can be obtained with intestinal transplantation in countries without home parenteral nutrition by application of specific treatment protocols.

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.

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.

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

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

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.