Percutaneous Transhepatic Radiologic Intervention of Biliary Complications following Liver Transplantation: A Single-center Experience.

Background: Biliary complications are the leading cause of morbidity and mortality in patients undergo¬ing Liver Transplantation (LT). Post-biliary transplantation strictures (BSs) are a severe problem with a high risk of graft failure. However, management of these BSs has remained controversial, and consid¬erable variability has been reported in Percutaneous Transhepatic Radiological Interventions (PTRIs) related to broad differences in technical procedures. Objective: This study aimed to evaluate the efficacy of percutaneous treatments in managing post-LT BSs in a center in Shiraz. Methods: PTRIs including balloon dilatation, metallic stent, and internal or internal-external hand-made plastic stent insertion were done for 34 transplanted patients with BSs referring to the Interventional Radiology Unit of Shiraz Namazi Hospital. Technical success rate, patency rates, and complications were evaluated. Results: The. In this study, 31 strictures were successfully treated without any significant difference between the anastomotic and non-anastomotic types of stricture (success rate: 91.2%). Based on the results, 12- , 24-, and 36-month primary patency rates were 90.1%, 84.5%, and 76.8%, respectively. The secondary patency rate was 100% at 12 and 24 months and 93.3% at 36 and 60 months. The rate of minor complica¬tions (mild cholangitis and hemobilia) was 6.4%, and no major complications were detected. Conclusion: According to the findings, PTRI is an effective method for treating anastomotic and non-anas- tomotic strictures with a high success rate and low complications.

Importance of miR-UL-148D Expression Pattern in Cytomegalovirus Infected Transplant Patients.

Background: MicroRNAs (miRNAs) are endogenous, 18-22 nucleotide non-coding RNA molecules. Human cytomegalovirus (HCMV) is a ubiquitous and particular herpes virus that encodes miRNAs, which increases gradually in the presence of infection. One of the important viral miRNAs is HCMV-miRUL-148D, which plays a role in establishing and maintaining viral latency. Objective: The current study aimed to evaluate the expression levels of HCMV-miRUL-148D in active and inactive HCMV infected transplant patient groups compared to healthy individuals. Methods: Total RNA was extracted from blood samples of 60 solid organ transplant patients and 30healthy controls. In-house SYBR Green Real-Time PCR evaluated the expression levels of studied miRNAand gene. Results: The expression level of the UL-148D gene was significantly higher in the active HCMV infectedpatients (p=0.001) compared to other groups. While the miRUL-148D expression level significantly increased in the inactive HCMV-infected patients (p<0.001) compared to other groups. Conclusion: Increased miRUL-148D expression level in the inactive HCMV-infected transplant patients indicates the potential role of this miRUL-148D as a biomarker of the HCMV latent stage.

Effects of Different Cold Preservation Solutions on the Functions of Cultured Isolated Human Hepatocytes.

BACKGROUND: Hepatocyte transplantation using isolated human hepatocytes is an alternative source that can be used for the treatment of metabolic diseases and acute liver failure as a time bridge to liver transplantation. These cells can also be used for bioartificial liver systems and in vitro study of drug toxicity. OBJECTIVE: To determine which cold preservation solution is better maintain the liver function. METHODS: We prepared 4 cold preservation solutions made of different combination of antioxidants, chelating, membrane protective, and anti-apoptotic agents as well as inhibitor of cyclophilin D. For hepatocyte isolation, we used livers obtained from unused deceased donor livers and the liver of patients with Crigler-Najjar syndrome who were candidates of partial liver transplantation. After culture and cold preservation, the level of albumin, and urea production were measured as indices of liver functionality. RESULTS: We found that albumin production significantly decreased after cold preservation in solution 1. There was no significant difference in urea production after cold preservation in solution 1 compared with control 24 h. No significant differences in albumin production were found after cold storage in solution 2 and solution 4 compared with control 24 h. Urea production significantly decreased after cold storage in solutions 2 and 4 compared with control 24 h. As a whole albumin and urea production were significantly decreased after cold preservation. Although albumin and urea production were decreased after cold preservation, but the results of albumin production of two solutions were not significantly different from that of the control group (p=0.109 and 0.951). CONCLUSION: Cold preservation of cultured human hepatocytes in solution 2 and solution 4 could maintain the function of albumin production better than other cold preservation solutions in our experiments; solution 1 was more effective on urea production of cultured human hepatocytes at 4 °C for 24 h. To determine if these hepatocytes are suitable candidates for transplantation, further studies should be performed.

Association between Interleukin-21, 23 and 27 Expression and Protein Level with Cytomegalovirus Infection in Liver Transplant Recipients.

BACKGROUND: Cytokines have regulatory crosstalk with CMV infection leading to manage of post-liver transplantation virus-related outcomes. OBJECTIVE: To investigate the link between IL-21, IL-23 and IL-27 mRNA and protein level with active CMV infection, which was evaluated in reactivated and non-reactivated liver transplant recipients. METHODS: Two groups of liver transplant recipients were enrolled in this study-54 without and 15 with active CMV infection. 3 EDTA-treated blood samples were taken on day 1, 4, and 7 post-liver transplantation. Plasma and buffy coats of all samples were separated. All samples were analyzed for CMV reactivation using antigenemia technique. The separated plasma of positive samples was used for viral DNA extraction and protein evaluation. For evaluating the mRNA expression level by real-time PCR, RNA extraction and cDNA synthesis were done for all samples. Also, the protein level of studied genes was estimated by ELISA. RESULTS: The expression level of IL-21, IL-23A and IL-27A cytokine genes was increased in CMV reactivated liver transplant recipients in comparison with CMV non-reactivated ones; IL-27A expression pattern was significant (p=0.001) at all sampling times. IL-21 significantly increased on the 2nd and 3rd (p=0.028 and 0.01, respectively) sampling days in CMV reactivated compared with non-reactivated patients. The expression level of IL-23A cytokine significantly increased on the 3rd (p=0.017) sampling day in CMV reactivated compared with non-reactivated liver transplant recipients. CONCLUSION: Elevation in the expression level of IL-21, IL-23A and IL-27A mRNA and protein level in CMV reactivated patients emphasized on the antiviral role of these cytokines in CMV reactivated liver transplant recipients.

Donors' Quality of Life after Living Donor Liver Transplantation: Shiraz Organ Transplant Center Experience.

BACKGROUND: Probable effects of living donor liver transplantation on the wellbeing of the donor and psychological difficulties are necessary to be understood. OBJECTIVE: To assess the quality of life of living donors after liver donation. METHODS: 140 living donors who underwent hepatectomy between 2012 and July 2015 were enrolled in this study. Donors were asked to complete the Short Form 36-question Health Survey (SF-36) through face to face or by telephone interview. RESULTS: The mean±SD age of donors at transplantation was 32.1±7.3 years; 83 (59.3%) of donors were female. 134 (95.7%) were married. The mean±SD BMI was 23.8±3.5 (kg/m2). "Mother-to-child" was the most frequent relationship (n=79, 56.4%). 22 (15.7%) complications were reported by participants. The mean±SD score of Physical Component Summary and Mental Component Summary were 48.8±14.6 and 50.1±6.9, respectively. CONCLUSION: Most living donors sustain a near average quality of life post-donation. It seems that living donation does not negatively affect the quality of life.

The Effects of Cold Preservation Solutions Supplemented with UDCA and α-Lipoic Acid on the Viability and Function of Isolated Human Hepatocytes.

BACKGROUND: Liver transplantation is the only treatment for end-stage and genetic liver diseases. The main burden of this treatment is the shortage of both living and cadaveric liver donors. An alternative treatment is using liver cell transplantation, which can be obtained from unused livers for transplantation. These hepatocytes should be kept ready in viable and functional situation in a frozen state to be instantly used when they would be needed. In our previous experience, we had isolated hepatocytes from unused livers. OBJECTIVE: To find a preserving solution for increasing viability and function of the isolated hepatocytes that are stored to be transplanted. METHODS: 9 cadaveric donor livers, which were not used for transplantation due to various causes such as severe steatosis, were selected to isolate hepatocytes. Various cold storage solutions were tried to find the best temperature for more viability and functionality for preservation of hepatocytes. University of Wisconsin (UW) solution and Williams E media were used as control media. 2 anti-apoptotic and anti-oxidative solutions, i.e., α-lipoic acid and ursodeoxycholic acid (UDCA), were used as cold preservatives solutions. The numbers of viable hepatocytes were estimated by trypan blue method; the functionality was assessed by the cells ability to produce urea. RESULTS: The highest number of viable and functional hepatocytes was obtained from freshly isolated cells. However, after preservation, the number of these viable hepatocytes and their functionality were not significantly different in cold storage solutions comparing to the control media used. Functionality of the isolated hepatocytes stored in UW with and without UCDA solution was similar to freshly isolated hepatocytes. CONCLUSION: Preservatives with anti-apoptotic and antioxidant activity could not increase the number of viable hepatocytes. Functionality of cold storing hepatocytes could be preserved similar to freshly isolated hepatocytes by UW solution with and without UCDA.

The Genotype Frequency of CYP2C19 Enzyme after Liver Transplantation.

BACKGROUND: Liver transplant recipients are treated with various drugs, the metabolism of which is dependent on the cytochrome P450 polymorphic genotype. OBJECTIVE: To identify the polymorphic variety of CYP2C19 genotype in liver allograft before and after transplantation. METHODS: The study was conducted on 88 liver recipients. The CYP2C19 genotypes in donors and recipients were the same in 32 and different in 56 recipients. Extracted genomic DNA from the leukocytes and liver graft tissues were analyzed by TaqMan SNP genotyping assay. The distributions of homozygote, heterozygote, poor and ultra-rapid metabolizers' genotypes were investigated in both groups. RESULTS: The distributions of CYP2C19 genotypes before transplantation in the blood and liver graft were within the normal range. After transplantation, in patients with different CYP2C19 genotype in donors and recipients, the genotypes of homozygote and ultra-rapid metabolizers were significantly decreased (p=0.024); the heterozygotes and poor metabolizer genotypes were significantly increased (p=0.017). CONCLUSION: The variety in CYP2C19 genotyping must be considered in patients with different genotypes in donor and recipients to predict the dosage regimens, optimize the treatment and decrease toxicity.

Severe Cutaneous Candidiasis in a Liver Transplant Patient.

Candida infections are common diseases in immunocompromised patients. A 19-year-old boy with liver transplantation, necrotic skin lesion, jaundice, dyspnea, and ascites was admitted to Namazi Hospital, Shiraz, southern Iran. The mycological examination for the skin lesion was requested. The skin sample was cultured on Sabouraud dextrose agar and evaluated by direct microscopic smear. Identification of isolated yeast was performed with RFLP-PCR. In direct smear, pseudohyphae, blastopores and yeasts were observed. Candida species was isolated from the media and identified as Candida albicans by molecular method. He died before starting any treatments. A skin lesion may present as the only sign of a systemic fungal infection in immunocompromised people. Careful attention and follow up are therefore recommended.

Prevalence of CYP2C19 Genetic Polymorphism among Normal People and Patients with Hepatic Diseases.

BACKGROUND: Patients with hepatic diseases are treated with numerous drugs metabolized by cytochrome P450. OBJECTIVE: To evaluate the frequencies of CYP2C19 variant alleles (*2, *3, and *17), genotypes, and phenotypes, and the relationship between the frequency of these alleles and the underlying hepatic diseases among patients with advanced liver diseases who were candidates for liver transplantation. METHODS: The Study was conducted on 120 patients suffering from various hepatic disorders, candidates for liver transplantation, and 52 healthy volunteers. DNA was extracted from blood samples and analyzed by TaqMan SNP genotyping assay. The CYP2C19 genotypes were classified into poor, extensive, intermediate, and ultra-rapid metabolizer phenotypes. RESULTS: Viral hepatitis was the most common cause of liver disease among studied patients. The frequencies of CYP2C19 alleles *1, *17, and *2 were 66.7% (160/240), 20.8% (50/240) and 12.5% (30/240), respectively. Allele CYP2C19*3 was not found in the studied population. The most prevalent genotypes were CYP2C19 *1/*1 (47.5%) and *1/*17 (24.2%). The predicted CYP2C19 phenotypes were extensive metabolizer (47.5%), heterozygote extensive metabolizer (45.9%), ultra-rapid metabolizer (5%), and poor metabolizer (1.6%). There was no significant difference between the frequencies of CYP2C19 genotypes between healthy people and patients. The distribution of CYP2C19 genotype frequencies was not significantly associated with the underlying disease conditions (p=0.472). CONCLUSION: The distribution of CYP2C19 genotype frequencies in Iranian healthy people and patients with various hepatic diseases was not significantly different. This may allow the physicians to predict a tailoring dose regimens based on the individual's metabolic capacity, decrease the risk of harmful side effects of the drugs, and optimize the treatment.

Value of Histopathologic Findings of Post-reperfusion Liver Needle Biopsies.

BACKGROUND: Histopathologic changes of post-reperfusion liver needle biopsies in patients with liver transplantation have rarely been reported and most of the previous reports have been in less than 200 cases. OBJECTIVE: In this study, we evaluated 408 post-perfusion liver needle biopsies for the histopathologic changes attributable to reperfusion injury and compared them with early post-liver transplantation outcome, to find out the value of these findings. METHODS: In 408 patients who underwent liver transplantation, post-perfusion liver needle biopsy was taken within one hour of vascular anastomosis. The specimens were fixed in formalin and evaluated by a hepatopathologist blinded to the outcome of transplantation for hepatocellular necrosis, apoptosis, ballooning degeneration, cholestasis, neutrophilic infiltration, and steatosis. These were compared with cold and warm ischemic time, levels of AST, ALT, alkaline phosphatase, bilirubin, presence or absence of rejection, and duration of hospital stay. RESULTS: Hepatocellular ballooning degeneration, apoptosis, and necrosis did not show any significant correlations with early post-transplantation outcome and reperfusion injury. However, presence of neutrophilic infiltration in the post-reperfusion liver biopsy was well correlated with liver function tests and other clinical and paraclinical findings. Presence of steatosis in post-reperfusion liver needle biopsy was also associated with high liver function tests and long hospital stay. CONCLUSION: Presence of PMN leukocytes in the post-perfusion liver needle biopsy of transplanted liver is associated with poor early outcome and reperfusion injury, so it should be recorded in the pathology report and should be considered a high-risk sign for the clinicians.

Association between IRF1 Gene Expression and Liver Enzymes in HBV-infected Liver Transplant Recipients with and without Experience of Rejection.

BACKGROUND: Liver function indices and anti-viral immune regulatory markers can both improve graft outcomes, which lead to better post-transplantation management and increase the possibility of surveillance in liver transplant recipients with chronic hepatitis B virus (HBV) infection. OBJECTIVE: To determine the association between the interferon regulatory factor 1 (IRF1) mRNA levels and liver enzymes in HBV-infected liver transplant recipients with and without experience of rejection. METHODS: A total of 46 chronic HBV-infected patients who had undergone liver transplant surgery was divided into 2 groups of recipients "with rejection" and "without rejection.". Blood samples were collected form each patient on days 1, 4, and 7 post-transplantation. A SYBER GREEN real-time PCR was used to evaluate the expression level of IRF1 in liver recipients. Liver enzyme activities were also measured in all patients. RESULTS: The expression of IRF1 in the patients with rejection was up-regulated at all 3 follow-up days compared with those without rejection. The serum levels of ALT and AST were more than normal levels at 3 follow-up times in both study groups. Significant differences were found in IRF1 gene expression levels and also serum ALT levels between those with and without rejection after 7 days post-transplantation. CONCLUSION: The IRF1 expression and serum ALT levels were increased significantly in patient with rejection compared to those without rejection. IRF1, an inflammatory factor, may also intensify induction of inflammatory pathways in engrafted liver and promote liver inflammation and injuries leading to liver enzymes elevation in patients with graft rejection.

Role of Histopathologist in Liver Transplantation.

A successful liver transplantation team consists of several specialists to work closely together. The histopathologist (anatomical pathologist) is one of the key players in this multidisciplinary team. This role starts with the pre-transplantation evaluation of the recipient's liver by diagnosis or confirming the underlying liver disease and continues with the evaluation of the explanted recipient's liver for any further information about the underlying liver disease including malignancies such as hepatocellular carcinoma, cholangiocarcinoma, or any other incidental findings. The evaluation of the new donor liver begins with determining the suitability of the donor liver for transplantation during or before the operation and continues throughout the entire post-transplantation period by evaluating not only the allograft diseases but also evaluating other tissues for infections, malignancies, etc. It is worthy to note that in many of the above-mentioned situations, histopathology is the gold-standard diagnostic test. In this review, we present on various tasks of a histopathologist according to the current literature and our own experience in the largest liver transplantation center in Iran.

Association of GSTO2 (N142D) Genetic Polymorphism and Acute Rejection of Liver.

BACKGROUND: Acute rejection is the main problem in liver transplantation that occurs in the first days or months of transplantation. It includes histological and cellular rejection. Acute histological rejection is confirmed by biopsy. Glutathione S-transferase family is the most important genes in phase II detoxification working in xenobiotic and drug metabolism. GSTO2 is one of the members of this family. GSTO2 (N142D) polymorphism may influence metabolism of immunosuppressive drugs. OBJECTIVE: To determine if GSTO2 polymorphism has association with acute liver rejection. METHODS: The present study included 120 patients with histological-proven acute liver rejection and 182 patients without acute rejection. Both groups were matched for sex and age. To determine variants of GSTO2, we used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: There was a significant association between the GSTO2 genotype and acute liver rejection (NN: OR: 3.642, 95% CI: 1.179-5.444) and (ND: OR: 2.533, 95% CI: 1.672-8.149) compared to those with DD geneotype. CONCLUSION: Recipients with either NN or ND genotype for GSTO2 are more likely to develop acute liver rejection compared to those with DD genotype.

Myocardial Performance after Successful Liver Transplantation.

BACKGROUND: Myocardial performance index (MPI) or Tei index is a Doppler-derived index of combined systolic and diastolic myocardial function, calculated as the sum of isovolumetric relaxation time (IRT) and isovolumetric contraction time (ICT) divided by the ejection time (ET). OBJECTIVE: To evaluate the right and left ventricular systolic and diastolic function using MPI in children before and after liver transplantation. METHODS: A cross-sectional study was conducted on 30 children with liver cirrhosis before liver transplantation, 30 age-matched comparison group at least 6 months after liver transplantation, and 30 aged-matched children without history of heart disease in Nemazi Liver Transplant Center, Shiraz, Iran, from April 2012 to April 2014. Echocardiographic evaluation was carried out with a GE Vivid 3 echocardiographic machine, using a 3-MHz probe with tissue Doppler imaging (TDI) software using conventional and TDI method. RESULTS: The mean±SD left ventricle Tei index in patients was 0.33±0.02 before liver transplantation, 0.34±0.02 after liver transplantation, and 0.33±003 in the comparison group (p=0.36). The mean±SD right ventricular Tei index was 0.35±0.04 in patients before transplantation, 0.36±0.46 after liver transplantation, and 0.28±0.04 in the comparison group (p<0.001). In addition, when TDI was used, the mean±SD left ventricular Tei index was 0.39±0.50 in patients before transplantation, 0.37±0.42 after liver transplantation, and 0.38±006 in the comparison group (p=0.32). The tissue Doppler-derived Tei index for the right ventricle was 0.37±0.04 in patients before transplantation, 0.37±0.04 after liver transplantation, and 0.33±0.05 in the comparison group (p=0.031). The left ventricular Doppler-derived Tei index had a significant (p=0.03) correlation with Child-Turcotte-Pugh (CTP) score (r=0.57). CONCLUSION: Left ventricular MPI with Doppler echocardiography was correlated with CTP score. Right ventricular MPI was significantly increased in patients with cirrhosis and did not improve 6 months after transplantation.

Prevalence of Metabolic Syndrome in Liver Transplant Recipients in Iran.

BACKGROUND: Metabolic syndrome (MetSx) is common among liver transplant recipients. It contributes to morbidity and mortality. OBJECTIVE: To determine the prevalence of MetSx in patients undergoing liver transplantation (LTx) in Iran. METHODS: 202 liver transplant recipients of both sexes completed this study. Relevant information including age, sex, the underlying disease, systolic and diastolic blood pressure, waist circumference, fasting serum levels of blood sugar (FBS), triglyceride (TG), and HDL-cholesterol were measured. The prevalence of MetSx was evaluated at 1, 3, 6, 9, and 12 months after LTx. RESULTS: The prevalence of MetSx was 36.6% after 1 month that decreased to 28.2% after 12 months of follow-up. The lowest prevalence of MetSx (27.7%) was observed 9 months after LTx. Our data showed a decrease in TG and an increase in HDL-C level and no significant changes in blood pressure, waist circumference and FBS during the study period. CONCLUSION: The prevalence of MetSx after LTx is high when compared to the normal population. It seems that a change in diet after transplantation may affect the prevalence of MetSx.

Tolerance Induction in Liver.

Liver is an exclusive anatomical and immunological organ that displays a considerable tolerance effect. Liver allograft acceptance is shown to occur spontaneously within different species. Although in human transplant patients tolerance is rarely seen, the severity level and cellular mechanisms of transplant rejection vary. Non-paranchymal liver cells, including Kupffer cells, liver sinusoidal endothelial cells, hepatic stellate cells, and resident dendritic cells may participate in liver tolerogenicity. The mentioned cells secret anti-inflammatory cytokines such as TGF-ß and IL-10 and express negative co-stimulatory molecules like PD-L1 to mediate immunosuppression. Other mechanisms such as microchimerism, soluble major histocompatibility complex and regulatory T cells may take part in tolerance induction. Understanding the mechanisms involved in liver transplant rejection/tolerance helps us to improve therapeutic options to induce hepatic tolerance.

Polymorphism of Transcription Factor-7-Like 2 (TCF7L2) Gene and New-Onset Diabetes after Liver Transplantation.

BACKGROUND: New-onset diabetes after transplantation (NODAT) is a serious complication in transplant recipients. Transcription factor-7-like 2 (TCF7L2) is a Wnt signaling-associated transcription factor that plays an important role in ß-cell proliferation and insulin secretion. The association between TCF7L2 SNP rs7903146 and NODAT was documented in renal transplant patients. OBJECTIVE: To determine the association between TCF7L2 rs7903146 variants and the risk of NODAT after liver transplantation. METHODS: This study was conducted on 140 liver transplant recipients who had received tacrolimus-based immunosuppressive drugs. The patients were divided into NODAT (n=70) and non-NODAT (n=70) groups and were genotyped using PCR-RFLP. In addition, 100 normal subjects were considered as the comparison group. RESULTS: There was a significant difference (p<0.05) between the two study groups regarding donor and recipient age, recipient body mass index, and recipient fasting plasma glucose before the transplantation. No significant relationship was observed between TCF7L2 rs7903146 genotypes and development of NODAT. No significant difference was also found between the two groups in terms of the tacrolimus and mycophenolate mofetil daily dosage as well as tacrolimus blood level. However, the prednisolone daily dosage was significantly (p=0.01) higher in the NODAT group compared to those without NODAT. The majority of the patients in the NODAT group also had an episode of acute rejection. Furthermore, a significant difference was found between the transplant recipients and the comparison subjects regarding T allele (p<0.001, OR=1.96) and TT genotype (p<0.001, OR=3.47) frequencies. CONCLUSION: No correlation was found between TCF7L2 genotypes and development of NODAT. Acute rejection and prednisolone pulse therapy predisposed the susceptible patients to NODAT.

Parents' education level and mortality and morbidity of children after liver transplantation.

BACKGROUND: So far numerous post-transplant outcome predictors have been studied to decrease the loss of resources and grafts after organ transplantation. The role of education, as a predictor, in liver transplantation outcome has so far been studied in several articles. However, in most of the studies it was evaluated as a surrogate for socioeconomic status or other variants. The absolute impact of parents' education has rarely been studied. Adult patients are their own caregivers whereas pediatric liver transplantation recipients are mostly cared by their parents. OBJECTIVE: To evaluate the effect of level of patients' education on the mortality and morbidity of pediatric liver transplant recipients. METHODS: We studied a group of 91 children who had undergone liver transplantation in our center from March 21, 2012 to July 21, 2013. In this retrospective study, patients' medical charts and questionnaire were used to collect the necessary data. Post-transplantation mortality and complications were divided into two categories: Early (<6 months after liver transplantation), and late (≥6 months after the transplantation). Parents' educational level was also categorized into 5 groups. RESULTS: Multivariate analysis of all groups showed that paternal education is an independent predictor of the late post-transplantation complications (p=0.024). Educational level of children's mothers had no significant correlation with the late post-transplantation complications (p=0.45). Neither maternal (p=0.59) nor paternal (p=0.607) education had significant effect on the late post-transplantation mortality. CONCLUSION: Paternal educational level of liver transplanted children is associated with the late post-transplantation complications.

Restricted Crystalloid Fluid Therapy during Orthotopic Liver Transplant Surgery and its Effect on Respiratory and Renal Insufficiency in the Early Post-operative Period: A Randomized Clinical Trial.

BACKGROUND: Respiratory and renal insufficiencies are common dysfunctions during post-liver transplantation period that increase post-operative mortality and morbidity rates. Intra-operative fluid therapy is an important factor associated with pulmonary and renal insufficiency. OBJECTIVE: To evaluate the relation between intra-operative fluid therapy and early renal and respiratory insufficiency after liver transplantation. METHODS: In this randomized clinical study, 67 adult patients with end-stage liver disease who underwent orthotopic deceased donor liver transplantation were randomly allocated into two groups. The restricted fluid group, which received a controlled fluid administration of normal saline, 5 mL/kg/hr during anesthesia, and non-restricted fluid group received a controlled infusion of normal saline 10 mL/kg/hr during anesthesia. Early post-operative respiratory and renal insufficiency in both groups were assessed. The patients were monitored during the three stages of liver transplantation for their hemodynamic indices. The trial is registered with the Iranian Randomized Clinical Trial Registry, number IRCT2013101811662N4. RESULTS: The baseline demographic and clinical characteristics were similar in both studied groups. The prevalence of respiratory insufficiency in the non-restricted fluid group (15%) significantly (p=0.01) higher than that in the restricted fluid group (0%). The post-operative mean±SD serum creatinine was 1.0±0.1 mg/dL in the non-restricted fluid group and 1.1±0.2 in the restricted fluid group (p=0.43). No patients in the studied groups required post-operative continuous renal replacement therapy. CONCLUSIONS: Restricted crystalloid fluid administration during orthotropic liver transplantation though decreased post-operative chance of pulmonary insufficiency, did not increase renal dysfunction.