Significance of true-positive and false-positive pretransplantation lymphocytotoxic crossmatch in primary liver allograft outcomes.

BACKGROUND: At the time of transplantation, a recipient's serum is tested against the prospective donor's lymphocytes to identify specific reactivity and to look for a donor-specific crossmatch (CXM). Here, we investigated the relationship between the pretransplantation lymphocytotoxic CXM results and the long-term outcome of liver transplantation at a single center. METHODS: From October 1998 to April 2011, medical records, laboratory data, and pretransplantation lymphocytotoxic CXM results were collected from 1133 consecutive liver transplant recipients. RESULTS: We performed liver transplantations on 80 (7.1%) patients after a true-positive CXM (t+CXM). The t+CXM group exhibited higher initial aminotransferase levels immediately after transplantation compared with a negative CXM group. However, no significant differences in rejection, biliary or vascular complications, viral disease recurrence, or de novo malignancies were found. Although overall graft and patient survival did not differ between the groups, liver-specific graft survival was inferior in the t+CXM group. It was also found that, in 42 (3.7%) recipients, initially positive results converted to final negative results after the elimination of immunoglobulin M autoantibodies. We defined this subpopulation as a false-positive CXM. Significantly decreased posttransplantation aminotransferase levels with a higher incidence of de novo malignancies were observed in this group compared with negative controls. CONCLUSION: Our findings demonstrate that t+CXM transplants show increased aspartate aminotransferase and alanine aminotransferase peak immediately after transplantation, which influences liver-specific graft outcomes. Additionally, the presence of circulating immunoglobulin M autoantibodies against recipients' own antigens may be protective in liver grafts. However, this may be a predisposing factor for de novo malignancies.

Liver graft pretreated in vivo or ex vivo by γ-aminobutyric acid receptor regulation.

BACKGROUND: γ-Aminobutyric acid exists throughout the body, and the brain γ-aminobutyric acid receptor (GABAR) regulation reduces oxidative stress (OS). Effects of GABAR regulation in the liver are unknown. Ischemia or reperfusion injury after orthotopic liver transplantation (OLT) or shear stress after split OLT (SOLT) with a small-for-size graft causes OS-induced graft damage. Here, the strategic potential of graft pretreatment in vivo and ex vivo by GABAR regulation was investigated. MATERIALS AND METHODS: Recipient rats were divided into seven groups according to the graft pretreatments and graft types: (1) laparotomy, (2) OLT, (3) GABAR regulation in vivo and OLT, (4) GABAR regulation ex vivo and OLT, (5) SOLT, (6) GABAR regulation in vivo and SOLT, and (7) GABAR regulation ex vivo and SOLT. Survival study, biochemical assays, histopathologic or immunohistologic assessments, and Western blotting were performed at 6 h after OLT or SOLT. RESULTS: Graft pretreatment in vivo prolonged survival after SOLT. Histopathologic and biochemical profiles verified that graft pretreatment in vivo reduced graft damage after OLT or SOLT. Immunohistologically, graft pretreatment in vivo prevented apoptotic inductions after OLT or SOLT. The 4-hydroxynonenal confirmed the OS after OLT or SOLT, and graft pretreatment in vivo improved the OS. Graft pretreatment in vivo decreased ataxia-telangiectasia-mutated kinase and H2AX after OLT or SOLT. Graft pretreatment in vivo increased phosphatidylinositol 3 kinase and Akt after SOLT. In contrast, GABAR regulation ex vivo did not work. CONCLUSIONS: Graft pretreatment in vivo, not ex vivo, prevented the ischemia or reperfusion injury-mediated OS after OLT or SOLT via the ataxia-telangiectasia-mutated kinase/H2AX pathway and the shear stress-mediated OS after SOLT with small-for-size graft via the phosphatidylinositol 3 kinase/Akt pathway.

Portal uptake function in veno-occlusive regions evaluated by real-time fluorescent imaging using indocyanine green.

BACKGROUND & AIMS: Although recent advances in preoperative imaging have enabled accurate estimation of the regional liver volume with venous occlusion, the extent of functional decrease in such regions remains unclear. In this study, the portal uptake function in postoperative veno-occlusive regions and non-veno-occlusive regions was evaluated by intraoperative fluorescent imaging after intravenous injection of indocyanine green (ICG). METHODS: In 22 liver resection patients and 23 recipients and 18 donors of liver transplantation, fluorescent intensity on the remnant liver or the liver graft was evaluated in real time following intravenous injection of ICG (0.0025 mg per 1 ml of remnant liver volume). RESULTS: Plateau ICG concentrations were significantly lower in the veno-occlusive regions (C(VO)) than in the non-veno-occlusive regions (C(Non)) in liver resection patients (median [range], 0.75 [0.29-2.0]µg/ml vs. 3.0 [0.46-6.4]µg/ml, p<0.001), donors (0.69 [0.29-1.9]µg/ml vs. 2.4 [0.46-6.4]µg/ml, p<0.001), and recipients (0.75 [0.34-1.8]µg/ml vs. 1.8 [0.54-6.4]µg/ml, p<0.001). Distributions of the C(VO)/C(Non) and the ratio of the hepatic uptake rate constant in the veno-occlusive regions to that in non-veno-occlusive regions were both around 40% (mean ± standard deviation, 0.36 ± 0.17 and 0.42 ± 0.16, respectively). When the functional remnant liver volume was calculated as a sum of non-veno-occlusive regions and veno-occlusive regions multiplied by C(VO)/C(Non), its ratio to the total liver volume was correlated with the improved postoperative/preoperative ratio of prothrombin time. CONCLUSIONS: Portal uptake function in veno-occlusive regions is approximately 40% of that in non-veno-occlusive regions. Intraoperative ICG-fluorescent imaging enables real-time evaluation of the extent of the functional decrease in veno-occlusive regions, enhancing accurate estimation of the hepatic functional reserve for determining the surgical indications and procedures.

Protective mechanisms of end-ischemic cold machine perfusion in DCD liver grafts.

BACKGROUND & AIMS: The aim of this study was to identify protective mechanisms of cold machine perfusion in liver grafts donated after cardiac death. METHODS: Pig livers exposed to 60-min warm ischemia were cold stored for 7 h or treated after 6-h cold storage with 1-h hypothermic oxygenated perfusion (HOPE) through the portal vein. Different physical (perfusion pressure) and chemical (oxygen, mitochondrial transition pore inhibition) parameters were analyzed during machine perfusion to dissect key steps of mechanism. RESULTS: HOPE treatment led to a significant slowdown of mitochondrial respiration rate during 1-h machine perfusion. After reperfusion following low pressure HOPE, mitochondrial injury, nuclear injury, Kupffer cell activation and endothelial injury were significantly improved, as tested on an isolated liver perfusion model. In contrast, machine perfusion with deoxygenated perfusate showed no protection from hepatocyte injury and Kupffer cell activation. However, endothelial injury was also prevented by low pressure machine perfusion in the absence of oxygen. Perfusion with higher pressure provoked endothelial damage and Kupffer cell activation. CONCLUSIONS: The mechanisms of protection by hypothermic machine perfusion appear to be at least twofold. First, oxygenation under hypothermic conditions protects from mitochondrial and nuclear injury by downregulation of mitochondrial activity before reperfusion. Second, cold perfusion itself, under low pressure conditions, prevents endothelial damage, independently of oxygen.

Investigation of adaptation after liver transplantation using Roy's Adaptation Model.

In this study we explored the adaptation of transplant recipients in Turkey using the Roy Adaptation Model. A descriptive qualitative design was used with data collected from liver transplant recipients in either individual or group interviews between May 2009 and February 2010. Using deductive content analysis, four themes were identified in the data: physiological mode, self-concept mode, role function mode, and interdependence mode. Each theme included both adaptive and ineffective behaviors of liver transplant recipients. The findings of this study indicate that liver transplant recipients need information and support about their ineffective behaviors in all modes of the Roy Adaptation Model. The findings also support the use of a nursing model in the delivery of nursing care for liver transplantation recipients.

Remote ischemic preconditioning promotes early liver cell proliferation in a rat model of small-for-size liver transplantation.

BACKGROUND: The size of the liver donor graft is a major concern in living donor liver transplantation. Rapid regeneration is essential for the survival of these grafts. The purpose of this study was to investigate the effect of remote ischemic preconditioning (RIPC) on liver regeneration in a rat small-for-size liver transplantation model. METHODS: We established rat models of small-for-size liver transplantation (30%) in the presence or absence (control) of remote ischemic preconditioning. We observed liver mass regeneration, serum alanine aminotransferase, hepatic pathologic alterations, flow cytometry, and Ki-67 antigen immunohistochemistry. In addition, using Western blotting and reverse-transcriptase-polymerase chain reaction, we assessed the activation of cell cycle progression as well as tumor necrosis factor-α and interleukin-6 expression. RESULTS: Compared with the control group, serum alanine aminotransferase activity was significantly lower and histopathology changes were significantly attenuated in the RIPC group. Remote ischemic preconditioning induced a high level of interleukin-6 mRNA in small grafts, but suppressed the expression of tumor necrosis factor-α. The proliferation index, indicated by the S-phase and G2/M-phase ratio [(S+G2/M)/(G0/G1+S+G2/M)], was significantly increased in the RIPC group at 24 h (58.25% ± 0.506% versus 53.405% ± 1.25%; P = .007). Meanwhile, cell cycle progression and regeneration (Ki-67) were initiated early in liver grafts treated with RIPC. CONCLUSIONS: These results suggest that RIPC can protect liver cells against ischemia reperfusion injury in the small grafts and enhance liver regeneration. Interleukin-6 may be a critical mediator in the stimulatory effect on liver cell regeneration, which may make RIPC valuable as a hepatoprotective modality.

Ischaemia-reperfusion injury in liver transplantation--from bench to bedside.

Ischaemia-reperfusion injury (IRI) in the liver, a major complication of haemorrhagic shock, resection and transplantation, is a dynamic process that involves the two interrelated phases of local ischaemic insult and inflammation-mediated reperfusion injury. This Review highlights the latest mechanistic insights into innate-adaptive immune crosstalk and cell activation cascades that lead to inflammation-mediated injury in livers stressed by ischaemia-reperfusion, discusses progress in large animal experiments and examines efforts to minimize liver IRI in patients who have received a liver transplant. The interlinked signalling pathways in multiple hepatic cell types, the IRI kinetics and positive versus negative regulatory loops at the innate-adaptive immune interface are discussed. The current gaps in our knowledge and the pathophysiology aspects of IRI in which basic and translational research is still required are stressed. An improved appreciation of cellular immune events that trigger and sustain local inflammatory responses, which are ultimately responsible for organ injury, is fundamental to developing innovative strategies for treating patients who have received a liver transplant and developed ischaemia-reperfusion inflammation and organ dysfunction.

Nutritional risk and anthropometric evaluation in pediatric liver transplantation

OBJECTIVE: To analyze the nutritional status of pediatric patients after orthotopic liver transplantation and the relationship with short-term clinical outcome. METHOD: Anthropometric evaluations of 60 children and adolescents after orthotopic liver transplantation, during the first 24 hours in a tertiary pediatric intensive care unit. Nutritional status was determined from the Z score for the following indices: weight/age height/age or length/age, weight/height or weight/length, body mass index/age, arm circumference/age and triceps skinfold/age. The severity of liver disease was evaluated using one of the two models which was adequated to the patients' age: 1. Pediatric End-stage Liver Disease, 2. Model for End-Stage Liver Disease. RESULTS: We found 50.0% undernutrition by height/age; 27.3% by weight/age; 11.1% by weight/height or weight/ length; 10.0% by body mass index/age; 61.6% by arm circumference/age and 51.0% by triceps skinfold/age. There was no correlation between nutritional status and Pediatric End-stage Liver Disease or mortality. We found a negative correlation between arm circumference/age and length of hospitalization. CONCLUSION: Children with chronic liver diseases experience a significant degree of undernutrition, which makes nutritional support an important aspect of therapy. Despite the difficulties in assessment, anthropometric evaluation of the upper limbs is useful to evaluate nutritional status of children before or after liver transplantation.

Tobacco smoking and solid organ transplantation.

Smoking, both by donors and by recipients, has a major impact on outcomes after organ transplantation. Recipients of smokers' organs are at greater risk of death (lungs hazard ratio [HR], 1.36; heart HR, 1.8; and liver HR, 1.25), extended intensive care stays, and greater need for ventilation. Kidney function is significantly worse at 1 year after transplantation in recipients of grafts from smokers compared with nonsmokers. Clinicians must balance the use of such higher-risk organs with the consequences on waiting list mortality if the donor pool is reduced further by exclusion of such donors. Smoking by kidney transplant recipients significantly increases the risk of cardiovascular events (29.2% vs. 15.4%), renal fibrosis, rejection, and malignancy (HR, 2.56). Furthermore, liver recipients who smoke have higher rates of hepatic artery thrombosis, biliary complications, and malignancy (13% vs. 2%). Heart recipients with a smoking history have increased risk of developing coronary atherosclerosis (21.2% vs. 12.3%), graft dysfunction, and loss after transplantation. Self-reporting of smoking is commonplace but unreliable, which limits its use as a tool for selection of transplant candidates. Despite effective counseling and pharmacotherapy, recidivism rates after transplantation remain high (10-40%). Transplant services need to be more proactive in educating and implementing effective smoking cessation strategies to reduce rates of recidivism and the posttransplantation complications associated with smoking. The adverse impact of smoking by the recipient supports the requirement for a 6-month period of abstinence in lung recipients and cessation before other solid organs.

In vivo hypoxic preconditioning protects from warm liver ischemia-reperfusion injury through the adenosine A2B receptor.

BACKGROUND: Liver ischemia-reperfusion injury (IRI) is a known risk factor for the postoperative outcome of patients undergoing liver surgery/transplantation. Attempts to protect from organ damage require multidisciplinary strategies and are of emerging interest in view of patients with higher age and American Society of Anesthesiology status. Ischemic preconditioning has been successfully applied to prevent from IRI during liver resection/transplantation. Because even short periods of ischemia during preconditioning inevitably lead to hypoxia and formation of anti-inflammatory/cytoprotective acting adenosine, we reasoned that short nonischemic hypoxia also protects against hepatic IRI. METHODS: Mice underwent hypoxic preconditioning (HPC) by breathing 10% oxygen for 10 min followed by 10 min of 21% oxygen before left liver lobe ischemia (45 min) and reperfusion (4 hr). The interactions of hypoxia→adenosine→adenosine receptors were tested by pharmacologic antagonism at adenosine receptor (AR) sites in wild-type mice and in mice with genetic deletions at the A1, A2A, A2B, and A3 ARs. Hepatocellular damage, inflammation, and metabolic effects were quantified by enzyme activities, cytokines, liver myeloperoxidase, blood adenosine, and tissue AMP, respectively. RESULTS: Hepatoprotection by HPC was significant in wild-type and A1, A2A, and A3 AR knockout mice as quantified by lower alanine aminotransferase serum activities, cytokine levels, histologic damage scores, tissue myeloperoxidase concentrations, and preserved AMP concentrations. Protection by HPC was blunted in mice pretreated with the A2B AR antagonist MRS1754 or in A2B AR knockout mice. CONCLUSIONS: Because liver protective effects of HPC are negated when the A2B receptor is nonfunctional, the hypoxia→adenosine→A2B receptor pathway plays a critical role in the prevention of warm IRI in vivo. Hypoxic activation of this pathway warrants use of selective A2B AR agonists or even intermittent hypoxia (e.g., in deceased organ donors) to protect from liver IRI.

A comparison of intra-operative blood loss and acid-base balance between vasopressor and inotrope strategy during living donor liver transplantation: a randomised, controlled study.

Administration of vasopressors or inotropes during liver transplant surgery is almost universal, as this procedure is often accompanied by massive haemorrhage, acid-base imbalance, and cardiovascular instability. However, the actual agents that should be used and the choice between a vasopressor and an inotrope strategy are not clear from existing published evidence. In this prospective, randomised, controlled and single-blinded study, we compared the effects of a vasopressor strategy on intra-operative blood loss and acid-base status with those of an inotrope strategy during living donor liver transplantation. Seventy-six adult liver recipients with decompensated cirrhosis were randomly assigned to receive a continuous infusion of either phenylephrine at a dose of 0.3-0.4 µg.kg(-1).min(-1) or dopamine and/or dobutamine at 2-8 µg.kg(-1).min(-1) during surgery. Vascular resistance was higher over time in the phenylephrine group than in the dopamine/dobutamine group. Estimated blood loss was significantly lower in the phenylephrine group than in the dopamine/dobutamine group (mean (SD) 4.5 (1.8) l vs 6.1 (3.4) l, respectively, p=0.011). Patients in the phenylephrine group had lower lactate levels in the late pre-anhepatic and the early anhepatic phase and needed less bicarbonate administration than those in the dopamine/dobutamine group (median (IQR [range]) 40 (0-100 [0-160]) mEq vs 70 (40-163 [0-260]) mEq, respectively, p=0.018). Postoperative clinical outcomes and laboratory-measured hepatic and renal function did not differ between the groups. Increased vascular resistance and reduction of portal blood flow by intra-operative phenylephrine infusion is assumed to decrease the amount of intra-operative bleeding and thereby ameliorate the progression of lactic acidosis during liver transplant surgery.

[Acid-base disturbances during liver transplantation].

UNLABELLED: Objective of the study is to assess the contribution of different factors in the development of acid-base disturbances at the stages of liver transplantation. MATHERIALS AND METHODS: The analysis of right lobe relative liver transplantation was held in 86 recipients. 22 patients corresponded to ASA III (group 1), ASA IV - 50 patients (group 2), and ASA V - 14 patients (group 3). Blood samples were studied by pH, SB, lactate, pCO2 at the stages: up to the beginning, before v. cava inferior cross-clamping, before blood flow launch, on the 1st minute after blood flow launch, 5 min after blood flow launch. 1 hour after the blood flow launch, 2 hours after blood flow launch, at the end of operations. Cardiac index and oxygen delivery were also estimated RESULTS: The preliverless stage was characterized by a decrease in pH, SB. BE and increased lactate, oxygen delivery slightly reduced due to the reduction of oxygen blood capacity, cardiac index remained within the normal range. During liverless period, the growth rate of lactate was different in all three groups, DO2 was below the norm, CI - on the lower bound of the norm. Blood flow launch was accompanied by a peak values of pH, SBC, BE, lactate and increased pCO2. CONCLUSIONS: The main factor in the development of metabolic acidosis during preliverless stage is lactate growth as a consequence of decreased hepatic lactate clearance and blood loss. During liverless period the most significant impact contributes to reduced cardiac output, which, together with reduced oxygen blood capacity leads to a decrease in tissue DO2. Increased production of lactate, together with a decrease in its clearance due to liver shutdown from the bloodstream leads to higher rates of lactate growth in this period. When starting the blood flow in addition to the release of acidic substances, growth of endogenous CO2 leads to the peak pH values.

Performance assessment of an opto-fluidic phantom mimicking porcine liver parenchyma.

An implantable, optical oxygenation and perfusion sensor to monitor liver transplants during the two-week period following the transplant procedure is currently being developed. In order to minimize the number of animal experiments required for this research, a phantom that mimics the optical, anatomical, and physiologic flow properties of liver parenchyma is being developed as well. In this work, the suitability of this phantom for liver parenchyma perfusion research was evaluated by direct comparison of phantom perfusion data with data collected from in vivo porcine studies, both using the same prototype perfusion sensor. In vitro perfusion and occlusion experiments were performed on a single-layer and on a three-layer phantom perfused with a dye solution possessing the absorption properties of oxygenated hemoglobin. While both phantoms exhibited response patterns similar to the liver parenchyma, the signal measured from the multilayer phantom was three times higher than the single layer phantom and approximately 21 percent more sensitive to in vitro changes in perfusion. Although the multilayer phantom replicated the in vivo flow patterns more closely, the data suggests that both phantoms can be used in vitro to facilitate sensor design.

Up to 9-day survival and control of thrombocytopenia following alpha1,3-galactosyl transferase knockout swine liver xenotransplantation in baboons.

BACKGROUND: With standard miniature swine donors, survivals of only 3 days have been achieved in primate liver-transplant recipients. The recent production of alpha1,3-galactosyl transferase knockout (GalT-KO) miniature swine has made it possible to evaluate xenotransplantation of pig organs in clinically relevant pig-to-non-human primate models in the absence of the effects of natural anti-Gal antibodies. We are reporting our results using GalT-KO liver grafts. METHODS: We performed GalT-KO liver transplants in baboons using an immunosuppressive regimen previously used by our group in xeno heart and kidney transplantation. Post-operative liver function was assessed by laboratory function tests, coagulation parameters and histology. RESULTS: In two hepatectomized recipients of GalT-KO grafts, post-transplant liver function returned rapidly to normal. Over the first few days, the synthetic products of the donor swine graft appeared to replace those of the baboon. The first recipient survived for 6 days and showed no histopathological evidence of rejection at the time of death from uncontrolled bleeding, probably caused by transfusion-refractory thrombocytopenia. Amicar treatment of the second and third recipients led to maintenance of platelet counts of over 40 000 per µl throughout their 9- and 8-day survivals, which represents the longest reported survival of pig-to-primate liver transplants to date. Both of the last two animals nevertheless succumbed to bleeding and enterococcal infection, without evidence of rejection. CONCLUSIONS: These observations suggest that thrombocytopenia after liver xenotransplantation may be overcome by Amicar therapy. The coagulopathy and sepsis that nevertheless occurred suggest that additional causes of coagulation disturbance must be addressed, along with better prevention of infection, to achieve long-term survival.

Synergistic suppression of pre-perfusion of donor livers with recipient serum and cobra venom factor treatment on hyperacute rejection following liver xenotransplantation.

PURPOSE: To investigate synergistic suppression of donor liver pre-perfusion with recipient serum (RS) and cobra venom factor (CVF) treatment on hyperacute rejection (HAR) following liver xenotransplantation. METHODS: Guinea-pigs (GP, n=24) and Sprague-Dawley rats (SD, n=24) were recruited. Before transplantation, serum was collected from SD rats and used for preparation of inactivated complements. GP and SD rats were randomly assigned into four groups (n=6), respectively: RS group, CVF group, RS+CVF group and control group. Orthotopic liver xenotransplantation was performed with modified two-cuff technique. The survival time and liver function of recipients, morphological and pathological changes in rat livers were investigated. RESULTS: There was no piebald like change in the recipient livers in all experiment groups. The survival time of recipients in all experiment groups was longer than that in control group (p<0.05). Moreover, the survival time in the RS+CVF group was markedly longer than that in the RS group (p<0.01) and CVF group (p<0.05). The serum ALT level in all experiment groups were lower than that in the control group (p<0.05). Furthermore, the ALT level in the RS+CVF group was significantly lower than that in the CVF group (p<0.05) and RS group (p<0.01). The histological damages were significantly improved when compared with the control group, and the histological damages in the RS+CVF group were milder than those in the remaining groups (p<0.05) CONCLUSION: Pre-perfusion of donor liver with recipient serum and cobra venom factor treatment can exert synergistic suppressive effects on the hyperacute rejection following liver xenotransplantation.

A descriptive analysis of 188 liver transplant patient visits to an emergency department.

BACKGROUND: The aim of the study is to seek the causes of application, the demographic and clinical characteristics of liver transplant patients and to share the experiences of our Emergency Department. MATERIALS AND METHODS: One hundred eighty-eight Emergency Department visits of ninety patients who underwent liver transplant operations between 2002 and 2009 were evaluated retrospectively. RESULTS: The patients applied to the Emergency Department with the complaints of fever 28.2% and abdominal pain 30.9%. It was detected that the final diagnosis of 52.4% of the patient visits was associated with the gastrointestinal system. It was observed that the most common treatment was drug therapy by 45.2% and that antibiotics treatment was the most applied method in drug treatment. Alanine aminotransferase (ALT) median value of hospitalized patients (45.5 U/L) is significantly higher than that of discharged patients (35 U/L) (p = 0.04). From the records of the patients, positive correlations between the length of hospitalization and levels of total bilirubin, direct bilirubin, ALT and fever during the visit were detected (p = 0.001, p < 0.001, p = 0.01, p = 0.01, respectively). CONCLUSIONS: Most frequently liver transplant recipients visited the Emergency Departments with the complaints of fever and abdominal pain. The diagnosis was generally associated with gastrointestinal system disorders. The percentage of hospitalization was high and the length of stay at the hospital was long. The treatment of these patients required a multidisciplinary approach and antibiotics constituted the most used drug treatment. Also, fever and liver function tests examined at the time of admittance to the Emergency Department affected the length of hospitalization.

Corrected QT interval and QT dispersion in cirrhotic patients before and after liver transplantation.

BACKGROUND: Liver cirrhosis is associated with different types of electrophysiological changes, including QT prolongation, which may adversely affect long-term prognosis of these patients. The aim of this study is to evaluate the effect of orthotopic liver transplantation (LT) on corrected QT (QTc) interval and QT dispersion (QTd) in cirrhotic patients of various etiologies. METHODS: We enrolled 249 patients with end-stage liver disease between 2004 and 2009 at Shiraz Transplant Research Center, Shiraz, Iran. The QTc interval and QTd were measured by 12 lead ECGs for baseline and at 3 months after LT. Mean QTc interval and mean QTd were calculated. A QTc interval above 440 ms was considered abnormal. RESULTS: Within 3 months following surgery, 6 patients died. There were 105 patients (43.2%) with prolonged QTc before transplantation; in 91 (86.6%) patients, the mean QTc normalized after transplantation (baseline: 490.9 ± 45.74 ms; post-transplantation: 385 ± 48.74 ms; P < 0.0001). Fourteen patients (13.3%) had evidence of some shortening of the QTc interval although the QTc remained above the upper limit of normal. Prolongation of the QTc interval in cirrhotic patients was independent of the etiology of cirrhosis. A normal QTc was seen in 138 patients (56.7%) before transplantation, of which 4 (2.9%) developed prolonged QTc after transplantation. The mean QTd decreased significantly after transplantation (baseline: 30 ± 20 ms; post-transplantation: 30 ± 10 ms; P < 0.0001). CONCLUSION: Many cirrhotic patients have prolonged QTc intervals before LT regardless of disease etiology. In the majority of patients this value returns to normal after LT, suggesting that liver cirrhosis has independent unfavorable, but reversible electrophysiological effects.