Anhepatic Period Research Articles

Evaluation of safety parameters and changes in serum concentration in liver transplant recipients treated with doxorubicin during the anhepatic period

Because of the recurrence of hepatocellular carcinoma (HCC) at the graft after liver transplantation, circulating HCC cells may be present during the anhepatic period. Intravenous doxorubicin (DOX) is used during the anhepatic period to combat these cells; however, pharmacokinetics data have been poorly analyzed. This study aims to investigate DOX administration during the anhepatic period. We administered 5 mg/m(2) DOX immediately after liver removal and compared serum DOX concentrations at several intervals during the anhepatic period in patients who underwent liver transplantation because of liver cirrhosis and HCC (n = 3) and patients who underwent liver resection owing to HCC with portal vein tumor thrombi (n = 5). We also measured serum DOX concentrations and pharmacokinetic parameters in transplant patients that received 3-15 mg/m(2) DOX (n = 3 per dose level). We evaluated transplant patients' adverse drug reactions and survival. At 10 and 30 min after DOX administration, serum DOX concentrations were elevated two- to threefold in transplant patients versus resection patients. Dose escalation in transplant patients exhibited a prolonged T½ in the one-compartment model and T½ β in the two-compartment model, as well as a dose-dependent elevation of the area under the curve. No obvious adverse drug reactions were noted at 3-15 mg/m(2) DOX. In transplant patients, 5-year recurrence-free survival was 68.8 %; overall survival was 100.0 %. During the anhepatic period, serum DOX concentrations were elevated two- to threefold, T½ was prolonged dose dependently, and up to 15 mg/m(2) DOX could be safely administered

The Comparison of Femoral and Radial Arterial Blood Pressures During Pediatric Liver Transplantation

BackgroundOrthotopic liver transplantation (OLT) is frequently associated with dramatic hemodynamic changes; thus, it is critical to accurately monitor blood pressure. Although comparisons between femoral arterial blood pressure (FABP) and radial arterial blood pressure (RABP) have been reported in adult liver recipients, we compared FABP with RABP in pediatric recipients. MethodsThirty-five pediatric liver recipients younger than 13 years of age were included in this prospective, observational study. We measured simultaneous FABP and RABP in the femoral and radial arteries at nine time points during the procedure, including: baseline (after anesthetic induction); 1 hour thereafter; 30 minutes after the beginning of the anhepatic period as well as 0, 1, 3, 5, 15, and 60 minutes after graft reperfusion. ResultsOf the 35 pediatric liver recipients, 2 infants and 1 13-month-old child were excluded from the analysis because of radial arterial catheter malfunction. The remaining 32 patients including 16 infants and 16 children all showed significantly higher systolic and mean FABP than RABP during most stages of pediatric OLT. Overall diastolic FABP measurements were similar to diastolic RABP throughout the study. ConclusionsSystolic and mean FABP were significantly higher than RABP during most stages of pediatric OLT. Radial arterial catheter malfunctions were not uncommon during pediatric OLT. Our results indicated that it is useful to cannulate the femoral artery to accurately and reliably measure arterial blood pressure to detect hemodynamic instability during pediatric OLT.

Risk factors for in-hospital mortality of patients with high model for end-stage liver disease scores following living donor liver transplantation

Background. Living donor liver transplantation (LDLT) for patients with high model for end-stage liver disease (MELD) scores is controversial due to its poor outcome. However, there is little information regarding which factor would negatively impact the outcome of patients with high MELD scores. The aim of this study was to identify factors associated with the in-hospital mortality of patients with high MELD scores after LDLT.Material and methods. All patients with an MELD scores ≥ 20 who received LDLT from 2005 to 2011 were recruited for the present study. Pre-and intra-operative variables were retrospectively and statistically analyzed. Results. A total of 61 patients were included in the current study. The overall 3-month survival rate was 82% for patients with high MELD scores. Preoperative renal dysfunction, hyponatremia, starting albumin level < 2.8 g/dL, preoperative renal replacement for severe renal failure, anhepatic period > 100 minutes and intraoperative red blood cell (RBC) transfusion ≥ 10 units were identified as potential risk factors by univariate analysis. However, only hyponatremia, preoperative dialysis and massive RBC transfusion were independent risk factors in a multivariate analysis. The 3-month survival rates of patients with two or more independent risk factors and patients with none or one risk factor were 91 and 25%, respectively. A significant difference was observed (P < 0.001).Conclusion. Hyponatremia, preoperative dialysis and massive RBC transfusion were related to poor outcome for sicker patients. Patients with two or more of the above-mentioned risk factors and high MELD scores may exhibit extremely poor short-term survival.

Proinflammatory and Anti-Inflammatory Cytokine Balance in Patients With Cirrhotic Hepatitis During Live-Donor Liver Transplant

The immune system releases cytokines during the stress response, and the balance between proinflammatory and anti-inflammatory cytokines is important. This prospective study was done to determine which cytokines are responsible for maintaining cytokine balance during live-donor liver transplant surgery. Recipients undergoing live-donor liver transplant surgery due to cirrhotic hepatitis were allocated to a recipient group (n=44), and healthy donors were placed in the donor group (n=45). In donors, blood sampling for cytokine level analysis was performed after anesthetic induction (before the start of surgery, time point 1). In recipients, blood samples were collected before the start of surgery (time point 1), 60 minutes after the start of the anhepatic period (time point 2), and 60 minutes after reperfusion (time point 3). The proinflammatory cytokines measured were interleukin-1 β, interleukin-6, and tumor necrosis factor-α; the anti-inflammatory cytokines were interleukin-10 and interleukin-4. Cytokines were quantified using sandwich enzyme-linked immunoassays. The time course of proinflammatory and anti-inflammatory cytokine concentrations during surgery in the recipient group was evaluated. Interleukin-6, interleukin-10 and tumor necrosis factor-α showed significant changes in concentration during surgery, with interleukin-6 reaching levels 40 times higher than the preoperative value at the anhepatic stage. Interleukin-10 reached a peak at the neohepatic phase, with values 60 times higher than the preoperative value. The preoperative concentrations of interleukin-6 and interleukin-10 in the recipient group were higher than those in the donor group with a median of 4.48 vs 1.98 pg/mL (P < .001) and 2.98 vs 1.22 (P = .026). Interleukin-6 and interleukin-10 play a major role in cytokine balance before and during live-donor liver transplant surgery.

Indoleamine2, 3-dioxygenase enzyme activity detected by in vivo liver microdialysis after rat ortho topic liver transplantation

Objective To observe the activity of indoleamine 2, 3-dioxygenase (IDO) enzyme in vivo after rat liver transplantation, and the effects of liver transplantation rejection on IDO enzyme activity.Methods Ten SD rats were subjected to othotopic liver transplantations respectively in allogenic OLT group (SD→SD) and heterogenic OLT group (Wistar→SD). In the other 10 SD rats, the blood supply to the liver was obstructed for 15 min for simulating the anhepatic period in the OLT group ( sham group). An in vivo rat liver microdialysis-HPLC system was established on the day I after OLT. The concentrations of kynurenine and tryptophan in dialysate samples were continuously monitored quantitatively and reproducibly for more than 2 weeks in the same animal. Results The average concentrations of tryptophan in dialysate were 97. 14, 85.71, 53.07 nmol/L respectively in the sham, allogenic OLT and heterogenic OLT groups respectively. The concentrations of kynurenine were 3.46, 14. 58, 46.79 nmoL/L in the sham, allogenic OLT and heterogenic OLT groups respectively. The concentration of kynurenine was increased significantly on the day 7 after surgery in heterogeneic OLT group (70. 75 nmol/L). Conclusion The transplantation surgery can induce the activity of IDO enzyme in vivo and accelerate the metabolism of tryptophan in the liver allografts. Key words: Liver transplantation; Acute rejection; Immune tolerance; Tryptophane; Indoleamine 2,3-dioxygenase

Porcine Partial Liver Transplantation Without Veno-venous Bypass: An Effective Model for Small-for-Size Liver Graft Injury

Objective Partial liver transplantation is currently gaining wider acceptance, which alleviates donor organ shortage, but also reveals the problem of small-for-size (SFS) syndrome. The precise mechanism behind it remains unknown. Large animal models for SFS syndrome are being developed using veno-venous bypass (VVB), however, splenectomies have often become necessary making the models useless for clinical situations. This study establishes a clinically well-simulated and effective model of SFS graft injury without VVB. Methods In this study, 30% and 100% of liver grafts were orthotopically transplanted to pigs in groups A (n = 12) and B (n = 5), respectively, both without VVB. Intraoperative hemodynamics and metabolic parameters were assessed consecutively. The operative survival rates were evaluated during 7 days of follow-up as well as the serum biochemical profiles, the kinesis of portal pressure gradient, and the pathological findings. Results All the recipients survived the anhepatic period except one in group A who died of irretrievable acidosis. The tolerance rate for non-VVB were 91.7% (11/12) in group A and 100% (5/5) in group B with no significant differences. The 7-day survival rate in group A was significantly less than that for group B (50% versus 100%, P < .05) with more prolonged prothrombin times, increased bilirubin and alanine aminotransferase levels, and persistantly higher values of portal pressure gradient during almost the entire follow-up period. Accordingly, the pathological findings clarified more severe microvascular impairments in group A than group B. Conclusion These data suggest that the model of pigs transplanting with 30% liver grafts without VVB is safe and reproducible. The good clinical simulation on operative procedures and clinicopathological performance indicates it is a more rational model for further research on SFS syndrome.

Experience without using venoveno bypass in adult orthotopic liver transplantation

BackgroundVenoveno bypass (VVB) has been used to achieve hemodynamic stability and decrease the incidence of renal dysfunction. However, VVB has many complications. The purpose of this study is to verify the safety of total clamping of the suprahepatic inferior vena cava (IVC) without VVB during orthotropic liver transplantation (OLT) in terms of anesthetic management.MethodsTwenty-five patients without preoperative renal dysfunction who underwent primary OLT were enrolled in this study. Hemodynamic data and blood gas measurements were collected 1 hour after incision, 30 minutes after IVC total clamping and 30 minutes after reperfusion. Postoperative laboratory data, including blood urea nitrogen (BUN), creatinine (Cr) and glomerular filtration rate (GFR), were assessed at postoperative day (POD) 0-7, 30, 90, 180 and 1 year.ResultsMean blood pressure was well maintained during IVC total clamping with infusion of inotropics. There was no case of severe acidosis (pH < 7.2) during the anhepatic period. The immediate postoperative Cr and GFR were not significantly different from those of the preoperative values. BUN increased from POD 1 and decreased after POD 6, while Cr increased at POD 90 only.ConclusionsIn patients without preoperative renal dysfunction, when IVC was totally clamped, VVB does not need to be routinely performed to maintain hemodynamics during the anhepatic phase and renal function after OLT.

Factors Influencing the Concentration of Cytokines During Liver Transplantation

Not only does the underlying disease that requires surgery constitute a significant stress to the human body, but also the surgery itself serves as a stressor. Cytokine secretion is activated in response to the surgical stress during liver transplantation. We examined 44 patients to compare cytokine levels, according to the underlying diseases causing liver failure (viral hepatitis vs alcoholic hepatitis), examining whether the values differed according to the model for end-stage liver disease (MELD) score [high (≥20) vs low (<20)]. Pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)1β, and IL-6 and anti-inflammatory cytokines IL-4 and IL-10 were quantified using sandwich enzyme- linked immunoassays at three times: (1) after inducing anesthesia, (2) 60 minutes after the start of the anhepatic period, and (3) 60 minutes after reperfusion. No difference in the level of any cytokine measured in our study was detected at any time point between the viral and the alcoholic hepatitis groups. Among the high MELD group, IL-1β and IL-4 contents were higher than in the low MELD group at all time points ( P < .05). IL-10 concentrations at time 1 and TNF-α at time 2 were higher among the high MELD group ( P < .05). In conclusion, the severity of the inflammatory and stress reactions expressed as cytokine concentrations did not differ according to the underlying liver disease, but did associate with the MELD score.

Dynamic left ventricular outflow tract obstruction in living donor liver transplantation recipients -A report of two cases-

We present two cases of dynamic left ventricular outflow tract obstruction in 2 patients who were undergoing living donor liver transplantation. On the preoperative transthoracic echocardiography, the first patient showed normal ventricular function and a normal wall thickness, but severe hemodynamic deterioration developed during the anhepatic period and this was further aggravated after reperfusion in spite of volume resuscitation and catecholamine therapy. Intraoperative transesophageal echocardiography revealed the systolic anterior motion of the mitral valve leaflet together with left ventricular outflow tract obstruction. The second patient showed left ventricular hypertrophy with left ventricular outflow tract obstruction on the preoperative echocardiography. Intraoperative transesophageal echocardiography was used to guide fluid administration and the hemodynamic management throughout the procedure and a temporary portocaval shunt was established to mitigate the venous pooling during the anhepatic period. The purpose of this report is to emphasize the clinical significance of dynamic left ventricular outflow tract obstruction in patients who are undergoing living donor liver transplantation and the role of intraoperative echocardiography to detect and manage it.

Two-stage liver transplantation in a surgically complicated liver failure patient after hepatic tumor resection -A case report-

Two-stage liver transplantation, involving a total hepatectomy with a temporary portocaval shunt followed by liver transplantation, requires intensive perioperative care, especially during the prolonged anhepatic period. The pathophysiology and management of this prolonged anhepatic state is not fully elucidated and the proper management during this period is a great challenge to clinicians in the intensive care unit and anesthesiologists. We report a case and management of a total hepatectomy with a temporary portocaval shunt followed by living-donor liver transplantation in a patient with a surgically complicated liver failure after a hepatic tumor resection.

Pharmacokinetics of Propofol and Extrahepatic UGT1A6 Gene Expression in Anhepatic Rats

Objective: The metabolic enzyme of UDP-glucuronosyltransferase 1A6 (UGT1A6) has been considered to metabolize propofol intra- or extrahepatically. The aim of the present study was to investigate the pharmacokinetics of propofol and UGT1A6 mRNA expression in extrahepatic organs before and during the anhepatic status in rats. Methods: Male Sprague-Dawley rats were injected with propofol (10 mg/kg) intravenously and a blood sample was taken at 2–60 min after injection. The hepatic hilum was occluded under laparotomy and then the propofol injection and blood sampling were repeated as above 24 h later. The plasma concentrations of propofol were analyzed and UGT1A6 mRNA expression in the kidney, small intestine, lung and brain from other cohort rats at 30 and 60 min of anhepatic status were semiqualified by RT-PCR. Results: T_1/2_α,T_1/2_β and V_d of propofol were not changed significantly before and during the anhepatic status. The area under curve, derived from a time-dependent concentration response curve, was significantly increased whereas plasma clearance rate was decreased significantly in the anhepatic period when compared to that in the control period, respectively. UGT1A6 mRNA expression in extrahepatic organs was significantly increased at 30 or 60 min of the anhepatic status when compared to those in the control status. Conclusion: The pharmacokinetics of propofol during the prehepatic and anhepatic status are largely similar, which is associated with the upregulation of extrahepatic UGT1A6 gene. The marginal accumulation of propofol during anhepatic period is likely to be due to both the limited function of this metabolic pathway and physiological disturbance induced by hepatic hilum occlusion.

Advantages and Disadvantages of Vein-Venous Bypass during Liver Transplantation

Objective: to study the advantages and disadvantages of vein-venous bypass (VVB) used during liver transplantation. Subjects and methods. Fifty patients who had undergone orthotopic liver transplantation (OLT) were examined. OLT was performed without using VVB in Group 1 (n=25). In Group 2 (n=25) of OLT, during an anhepatic period (the interval of the cessation of blood flow along the inferior vena cava to the reperfusion of the implanted donor liver with venous blood), blood return was accomplished by compulsory porto-femoroaxillary shunting by means of a centrifugal pump. Results. The persistent perfusion pressure provided by VVB prolongs an anhepatic period; moreover, the functions of the kidney and heart remain stable. At the same time the longer time of an anhepatic period increases the time of cold ischemia of the grafted liver. VVB with a heat exchanger can warm a patient to normal temperature over a short period of time. Moreover, the decrease in a patient&#8217;s body temperature without using VVB is 0.5—1.5° from the start of an operation to the time of venous hepatic reperfusion. The authors failed to record intraoperative mortality from heart failure in the examinees. There were no differences in the incidence of renal dysfunction with and without VVB. Conclusion. The number of complications and the outcome of an operation do not depend on whether VVB is used or not. Liver transplantation without VVB makes it possible to reduce the time of surgery, an anhepatic period and the cost of a surgical intervention. During each liver transplantation, VVB must be linked up due to the fact that circulation can fully stop in the inferior vena cava at the stage of hepatectomy. Key words: liver transplantation, vein-venous bypass.

Coagulation and biochemical effects of balanced salt‐based high molecular weight vs saline‐based low molecular weight hydroxyethyl starch solutions during the anhepatic period of liver transplantation

The anhepatic period of liver transplantation is generally marked by a decrease in preload, and the infusion of hydroxyethyl starch (HES) solution is often an effective way to restore volume deficits in non-anaemic patients. However, the infusion of even limited amounts of HES solution during the anhepatic period may result in a worsening coagulopathy. Moreover, lactate-containing HES solution may cause some degree of biochemical derangements in compromised recipients. Therefore, we compared two different types of HES solutions: a balanced salt-based high molecular weight HES solution (670/0.75; high MW group) and a saline-based low molecular weight HES solution (130/0.4; low MW group) with respect to coagulation and biochemical profiles. First, in an in vitro study (n = 48), thromboelastography was performed to determine the effects of two HES solutions on coagulation after diluting (11%) the recipient's blood sample with each HES solution. Second, in an in vivo study, 500 ml of one of the two 6% HES solution was administered to 74 recipients (n = 37, each group) for 30 min after starting the anhepatic period. The coagulation profiles, including thromboelastography, and biochemical profiles were measured before and 30 min after the end of infusion. Less impairment in the thromboelastography profiles and aPTT was observed in the high MW group. A higher calcium concentration and less reduction in platelet count were noted in the high MW group, but lactate accumulation was greater. In conclusion, a balanced salt-based high molecular weight HES solution is a more effective volume replacement during the anhepatic period of liver transplantation with respect to coagulation than a saline-based low molecular weight HES solution, although lactate accumulation is a possible concern.

Norepinephrine in Small-For-Size Liver Grafts: An Experimental Study in Pigs

Norepinephrine plasma levels may play a role in small-for-size grafts dysfunction at the early posttransplant period. The 18 pigs used as recipients were assigned to group 1 (n = 6), group 2 (n = 6), and group 3 (n = 6) and given grafts with graft-to-recipient volume ratios of 1:1, 2:3, and 1:3, respectively. Blood serum norepinephrine was measured by high-performance liquid chromatography with electrochemical detection at the following time points: pre-anhepatic period (baseline); anhepatic period; and 30, 60, 180, and 360 min after reperfusion. Graft arterial and portal vein flows were obtained 30, 60, 180, and 360 min after reperfusion by the aid of an ultrasonic flowmeter. Aspartate transferase (AST) and international normalized ratio (INR) were measured before the procedure (baseline), and at 180 and 360 min after reperfusion. Anhepatic phase was characterized by a significant increase (6- to 8-fold) of norepinephrine in all groups (P < 0.05). In groups 1 and 2 plasma norepinephrine returned to normal values 30 min after reperfusion. In group 3, plasma norepinephrine remained significantly increased at every time point of the study compared to groups 1 and 2 (P < 0.001). Hepatic artery and portal vein flows in group 3 were significantly (P < 0.05) reduced and increased, respectively, compared to groups 1 and 2 at all times measured. Liver function tests (AST and INR) 360 min after reperfusion were significantly higher in group 3 compared to groups 1 and 2. Norepinephrine levels are increased in very small-for-size grafts and this increase may be associated with early graft dysfunction.

Minimal anhepatic technique for living donor liver transplantation using right liver graft

Minimal anhepatic technique for living donor liver transplantation using right liver graft

U-graft anastomosis for anomalous portal venous branching reconstruction in right lobe living donor liver transplantation

U-graft anastomosis for anomalous portal venous branching reconstruction in right lobe living donor liver transplantation

Comparison among three surgical techniques for orthotopic liver transplantation

目的 探讨经典原位肝移植术、改良背驮式肝移植术、原位肝移植腔静脉成形术在临床应用中的利弊.方法对2001年10月至2004年5月实施的1 55例病人的159次肝移植术式进行回顾性分析,其中经典原位肝移植术94例,改良背驮式肝移植术48例(包括改良背驮+术中门-腔静脉端侧吻合转流8例),原位肝移植腔静脉成形术17例;术中行血管架桥5例,其中因门静脉闭锁及栓塞行供肝门静脉与受体肠系膜上静脉间架桥2例,因动脉变异分支细小不能利用行供肝腹腔干与受体腹主动脉间架桥3例.159例次肝移植手术均未应用体外静脉转流技术.结果原位肝移植腔静脉成形术的手术时间、无肝期最短,术中失血输血量最少,其术中对循环和肾功能的影响与经典术式相仿.经典原位肝移植术与背驮式肝移植术相比流出道不畅发生率较低,总手术时间较短(平均少30 min),但无肝期较长(平均长8 min),术中及术后肾上腺出血发生率较高,对肾功能影响较大,三组术后ICU留置天数差异亦无显著性意义(P=0.542).结论不同的肝脏移植术式各有其优缺点,术者的经验以及对术式的熟悉程度会影响手术方式的选择,从原则上讲,手术方式的选择应根据具体病情及术中情况而决定。

Benefit of Kupffer cell modulation with glycine versus Kupffer cell depletion after liver transplantation in the rat: effects on postischemic reperfusion injury, apoptotic cell death graft regeneration and survival*

Inhibition or destruction of Kupffer cells (KC) may protect against ischemia-reperfusion (IR) induced primary graft nonfunction (PNF) in liver transplantation. Besides KC activation, PNF is characterized by microvascular perfusion failure, intrahepatic leukocyte accumulation, cell death and hepatocellular dysfunction. KCs can be inactivated by different agents including gadolinium chloride (GdCl3), methyl palmitate (MP) and glycine. The effects of three KC inactivators on IR-injury after rat liver transplantation were compared in the present study. Lewis liver donors were treated with GdCl3, MP, glycine or saline (control). Liver grafts were transplanted following 24 h storage (UW solution). KC populations and IR damage were assessed by histologic analysis, quantitative real-time polymerase chain reaction (RT-PCR) and intravital microscopy. The number of hepatic ED-1 positive macrophages was diminished after GdCl3 (114.8+/-4.4/mm2 liver tissue) and MP treatment (176.0+/-5.0), versus the glycine (263.9+/-5.5) and control (272.1+/-5.6) groups. All three treatment modalities downregulated phagocytic activity for latex particles, paralleled by reduced microvascular injury (acinar perfusion index, GdCl3: 0.75+/-0.03; MP: 0.83+/-.03; glycine: 0.84+/-0.03; 0.63+/-0.03). Quantitative RT-PCR revealed elevated myeloperoxidase mRNA after glycine versus GdCl3 and MP pretreatment (3.2- and 3.4-fold, P=0.011, respectively), without difference to controls (2.9-fold of glycine). TNFalpha-mRNA was reduced after glycine- (5.2-fold), GdCl3- (19.7-fold), MP-treatment (39.5-fold) compared with controls. However, profound prevention of intrahepatic cell death and liver graft failure was solely achieved with glycine preconditioning. Different than GdCl3 and MP, glycine modulates rather than destroys KCs. Glycine appears to preserve cell viability and to TNFalpha/leukocyte dependent organ regeneration capacity, which is related to increase graft survival following liver transplantation.

Thymoglobulin induction protects liver allografts from ischemia/reperfusion injury

Interventions that minimize hepatic ischemia/reperfusion injury (IRI) can expand the donor organ pool. Thymoglobulin (TG) induction therapy has been shown to ameliorate delayed graft function and possibly decrease IRI in cadaver renal transplants recipients. This controlled randomized trial was designated to assess the ability of TG to protect against IRI in liver transplant recipients. Twenty-two cadaveric liver transplant recipients were randomized to receive either TG (1.5 mg/kg/dose) during the anhepatic period and QOD x2 doses or no TG. No differences in recipients' demographics were present and donor characteristics were similar in terms of age, cause of death, and cold ischemia time. Maintenance immunosupression consisted of Tacrolimus (or Cyclosporine) and steroids for both groups. Donor biopsies were obtained during organ procurement, cold storage and 1 h after re-vascularization. Post-operative liver function tests were monitored. Early graft function, length of stay, patient and graft survival rates, incidence of primary non-function and rate of rejection were assessed. Patient and graft survival at 3 months was 100%. There was no incidence of primary graft non-function and no need for re-transplantation. The incidence of acute rejection was similar between the two groups. Patients in the TG group had significant decreases in alanine aminotransferase test at day 1 compared to the control group (p = 0.02). There were also near significant decreases of total bilirubin at day 5 and shorter length of hospitalization. Liver biopsy (at procurement, when cold, and post-reperfusion) of TG group demonstrated a trend for increased central ballooning. The TG allowed for more compromised liver grafts to be transplanted with less clinical evidence of IRI and improved function. Further studies on the degree of apoptosis in the liver biopsy post-reperfusion are underway.

Hepatic ischemia/reperfusion injury can be modulated with thymoglobulin induction therapy

Background Thymoglobulin induction therapy has been shown to ameliorate delayed graft function and possibly decrease ischemia reperfusion injury in cadaver renal transplant recipients. This controlled randomized trial was designed to assess whether thymoglobulin also protects liver transplant recipients from ischemia reperfusion injury. Patients and methods Twenty-two cadaver liver transplant recipients were randomized to receive either thymoglobulin (1.5 mg/kg per dose) during the anhepatic period and two doses every other day or no thymoglobulin. No differences in recipient or donor demographics were present. Maintenance immunosupression consisted of tacrolimus (or cyclosporine) and steroids for both groups. Donor biopsies were obtained during organ procurement, cold storage, and 1 hour after revascularization. Postoperative liver function tests were monitored. Early graft function, length of stay, patient and graft survival rates, incidence of primary nonfunction, and rate of rejection were assessed. Results Patient and graft survival at 3 months was 100%. There was no incidence of primary graft nonfunction and no need for retransplantation. The incidence of acute rejection was similar between the two groups. Although donor livers randomized to thymoglobulin had less optimal preimplantation biopsies, these recipients had significant decreases in ALT at day 1 compared to the control group ( P = .02), near significant decreases of total bilirubin at day 5, and shorter length of hospitalization. Conclusion Thymoglobulin allowed for more compromised liver grafts to be transplanted with less clinical evidence of ischemia reperfusion injury and improved function.