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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

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.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.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).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.

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.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.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.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.

Background: This study aimed to determine the prevalence of post-transplant lymphoproliferative disorder (PTLD) based on the clinical and epidemiological characteristics of donors and pediatric transplant recipients. Methods: This cross-sectional study was conducted on the patients who had experienced liver transplantation at Shiraz Transplant Center, Shiraz, Iran, from April 2007 to March 2017. Data on the epidemiological characteristics, underlying diseases, dosage of immunosuppressive drugs, and duration of drug consumption from the time of liver transplantation until the onset of PTLD for transplant recipients, and donors’ age, sex, and family relationship with recipients were collected using a data-gathering form. Log rank test was employed to determine the variations in the distribution of survival in different sex and age groups. Results: The study findings indicated that 49 out of the 1207 children who had undergone liver transplantation developed PTLD, revealing a prevalence of 4%. The results showed no significant relationship between gender and the incidence of PTLD (P = 0.13). However, the mean age of the cases with PTLD was 4.93 ± 1.07 years at the time of transplantation, while non-PTLD patients showed a higher mean age at that time (7.80 ± 5.54). The mean dose of the immunosuppressive drugs (dose/kg) consumed by the recipients was as follows: Tacrolimus = 0.2753 ± 0.23435, prednisolone = 0.6761 ± 0.62218, cellcept = 0.0724 ± 0.12963, and sirolimus = 0.1078 ± 0.08813. The average consumption period of the above-mentioned drugs from the time of transplantation until the onset of PTLD was 14.7 ± 14.409 months. Based on the results, the five-year survival rate was much lower in the patients with PTLD compared to the non-PTLD patients (31% Vs. 72.7%). The survival distribution was significantly different based on sex and age groups (P = 0.59 and P = 0.06, respectively). Conclusions: The prevalence of the clinical and epidemiological features of the PTLD in the patients under the present investigation was similar to those of the patients in other hospitals. Recognizing the clinical and epidemiological characteristics of transplant recipients with and without PTLD and donors can provide a basis for managing these patients.

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.

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.

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.

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.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. P0.05 was considered to be significant.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 (P0.001), 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.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.

Solid pseudopapillary tumor of pancreas (SPTP) is a rare tumor of the pancreas which mostly occurs in young women. Since its first description in 1969, more than 500 cases have been reported. There have been just 2 case reports and 1 review (7 cases) from Iran. In this study, we reported our experience with 22 patients with SPT from the largest pancreaticobiliary center in Southern Iran.During 6 years (2012-2017), 22 cases of SPTP were operated on in our center. All of these cases were recruited and after confirmation of the pathological diagnosis, clinical charts were evaluated and all the clinicopathologic findings as well as outcome of the surgery were evaluated.Among the 22 patients, 20 were female and 2 were males. The age range was 15-52 years and the tumor sizes were 3.5 to 17 cm. All of the tumors had preoperative diagnosis by imaging modalities and were operated on with no complication or recurrences. Just one case showed liver metastasis. All of the patients with SPTP in this study were alive and in good condition.SPTP is not very rare in our center. In young patients presenting with pancreatic mass, especially in female patients, one of the most important diagnoses is SPTP. Conservative surgery and tumor excision is satisfactory and patients show excellent prognosis even after liver metastasis.

Hepatitis B virus, which mainly affects normal liver function, leads to severe acute and chronic hepatitis, resulting in cirrhosis and hepatocellular carcinoma, but can be safely treated after liver transplant. Evaluation of determinative biomarkers may facilitate more effective treatment of posttransplant rejection. Therefore, we investigated interferon regulatory factor 1 expression in hepatitis B virus-infected liver transplant patients with and without previous rejection compared with controls.Hepatitis B virus-infected liver recipients were divided into those with (20 patients) and without a rejection (26 patients), confirmed by pathologic analyses in those who had a rejection. In addition, a healthy control group composed of 13 individuals was included. Expression levels of interferon regulatory factor 1 were evaluated during 3 follow-ups after transplant using an in-house comparative SYBR green real-time polymerase chain reaction method. Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 16.0, IBM Corporation, Armonk, NY, USA).Modifications of interferon regulatory factor 1 gene expression levels in patient groups with and without rejection were not significant between days 1, 4, and 7 after liver transplant. Interferon regulatory factor 1 mRNA expression levels were down-regulated in patients without rejection versus patients with rejection, although not significantly at day 1 (P = .234) and day 4 (P = .302) but significantly at day 7 (P = .004) after liver transplant.Down-regulation of interferon regulatory factor 1 gene expression in hepatitis B virus patients without rejection emphasized counteraction between hepatitis B virus replication and interferon regulatory factor 1 production. On the other hand, interferon regulatory factor 1 gene overexpression in patients with rejection may result in inflammatory reactions and ischemic-reperfusion injury. Therefore, a better understanding of the association between interferon regulatory factor 1 and hepatitis B virus pathogenesis in a larger population with longer follow-up is needed.

To identify the predictors of overall survival and tumor-free survival of 88 hepatocellular carcinoma patients who were treated with orthotopic liver transplant at Shiraz Organ Transplant Center.We performed this retrospective study after reviewing the transplant database of all patients who underwent orthotopic liver transplant secondary to hepatocellular carcinoma and liver cirrhosis. Hepatocellular carcinoma was diagnosed in 70 patients before liver transplant and 18 patients on histologic examination of the explanted livers. Cox regression identified independent factors that affected posttransplant survival.The overall survival rate was 83% and the tumor-free survival rate was 79.5%. Independent factors for tumor recurrence were Milan criteria, alpha-fetoprotein level before operation ≥ 400 ng/mL, tumor grade, vascular invasion, and age. Vascular invasion (odds ratio, 5; 95% confidence interval, 1.1 to 25.496; P = .049) and tumor grade (odds ratio, 14.42; 95% confidence interval, 3.652 to 56.95; P.001 were statistically significant.Vascular invasion and tumor grade were predictive factors for tumor-free survival.

Dendritic cells (DCs) are potent antigen presenting cells for triggering of the immune reaction post transplantation. These cells are centrally involved in the initiation of T cell-dependent immune responses.To compare the level of DC maturation and function in liver transplant recipients with healthy controls.In this study, twelve peripheral blood samples were selected from six liver transplant patients and six healthy controls. After the generation of DCs from monocytes, expression levels and mean fluorescent intensity (MFI) of several DC maturation markers were evaluated using flow cytometry. Secretion of IL-6, IL-12 and IL-23 proinflammatory cytokines was determined using ELISA. Gene expressions of TLR-2, TLR-4 and IL-23 were analyzed using real-time PCR.DC expression markers including CD83 (p=0.007) and CD86 (p=0.02), as well as secretion of IL-6 (p=0.02) and IL-12 (p=0.007) by DCs were significantly increased in liver transplant patients compared with healthy controls. The MFI of CD86 (p=0.009) and HLA-DR (p= 0.005) expression on DCs was also higher in patients. The expression of TLR-2 transcripts in DCs of patients was higher than that of the controls (p=0.03).Based on these findings, increased frequency of DCs expressing CD83 and CD86, higher expression of CD86, HLA-DR, and TLR-2 as well as elevated secretion of proinflammatory cytokines in DCs of liver transplant recipient's point to the more mature phenotype and active function of DCs in patients compared with controls.

This study sought to evaluate in pediatric liver transplant recipients the effects of hybrid antiviral therapy on the rate of posttransplant lymphoproliferative disorder.All pediatric patients (87 cases) who had undergone a liver transplant between April 2011 and March 2012 took part in the study and received hybrid antiviral treatment (case group). Epstein-Barr virus polymerase chain reaction was monitored intermittently. The results were compared to those of a historical control group including 117 pediatric patients who received a liver transplant between April 2009 and March 2011. Follow-up was 27 to 47 months in the control group and 12 to 26 months in the case group.Posttransplant lymphoproliferative disorder occurred in 12 patients in control group (10.2%) and 5 patients in case group (5.7%) (P = .249). Of 12 cases of posttransplant lymphoproliferative disorder, death occurred in 5 cases in the control group (41.7%), while no posttransplant lymphoproliferative disorder-associated death was seen in the case group (P = .086).Although hybrid antiviral treatment did not result in a statistically significant decrease in posttransplant lymphoproliferative disorder and posttransplant lymphoproliferative disorder-associated mortality rates, considering the limited number of posttransplant lymphoproliferative disorder cases in this study, this decrease may be interpreted as noticeable, and we advise using this strategy for pediatric patients undergoing a liver transplant.

Liver transplant can be challenging in cirrhotic patients with diabetes mellitus. In chronic liver disease, the glucose metabolism is altered; uncontrolled diabetes negatively influences the outcome of liver transplantation and poses difficulty in the management of immediate post transplantation period. Simultaneous liver-pancreas transplantation is an option to prevent early complications due to diabetes and also to improve the quality of life after transplantation in patients with Insulin-Dependent Diabetes Mellitus (IDDM) and chronic liver disease. We report the first en-bloc liver-pancreas transplant done in the transplant history of Iran. We describe the technical details of the procedure as well as the short term outcome after transplantation. In this case report, we also discuss in some details, the surgical, medical and immunological advantages of combined liver-pancreas transplantation as opposed to separate implantation of both organs.