Phase Of Liver Transplantation Research Articles

Performance of the Hypotension Prediction Index in living donor liver transplant recipients.

The Hypotension Prediction Index (HPI) was recently introduced and clinically validated in different surgical conditions. This prospective observational study evaluated HPI's performance in living donor liver transplant recipients under the hypothesis that HPI would be inferior to the previously reported predictability in major surgery due to the surgical characteristics of liver transplantation. Twenty adult patients undergoing living donor liver transplantation were enrolled. HPI was monitored during the surgery with the attending anesthesiologist blinded to the HPI. The mean arterial pressure and HPI were recorded at 1-minute intervals. The area under the curve (AUC) of the receiver operating characteristic curve was calculated for the whole dataset and at each phase of liver transplantation at 5, 10, and 15 minutes to analyze HPI's performance. A total of 9173 data points were analyzed. The AUC for predicting hypotension at 5 minutes was 0.810 (95% confidence interval [CI]: 0.780-0.840). The AUCs for predicting hypotension at 10 and 15 minutes were 0.726 (95% CI: 0.681-0.772) and 0.689 (95% CI: 0.642-0.737), respectively. The AUCs for predicting hypotension at 5 minutes in the preanhepatic, anhepatic, and neohepatic phase were 0.795 (95% CI: 0.711-0.876), 0.728 (95% CI: 0.638-0.819), and 0.837 (95% CI: 0.802-0.873), respectively. The HPI's performance was inferior to that previously reported in major surgery. HPI in this observational study in living donor liver transplantation predicted hypotension with moderate-to-low accuracy, its predictive value being highest in the neohepatic phase and lowest in the anhepatic phase.

Comparison of tracheal temperature and core temperature measurement in living donor liver transplant recipients: a clinical comparative study

BackgroundBody temperature is a vital sign, and temperature monitoring during liver transplantation is important. Tracheal temperature can be measured via an endotracheal tube with a temperature sensor on the cuff of the tube. This study aimed to investigate the accuracy and trending ability of tracheal temperature measurement compared to those of the core temperature measured at the esophagus and pulmonary artery (PA) in living donor liver transplant recipients.MethodsTwenty-two patients who underwent living donor liver transplantation (LDLT) were enrolled. Patients were intubated using an endotracheal tube with a temperature sensor placed on the inner surface of the tube cuff. Tracheal, esophageal, and PA temperatures were recorded at five time points corresponding to the different phases of liver transplantation. The tracheal and esophageal, tracheal and PA, and esophageal and PA temperatures were compared using Bland–Altman analysis, four-quadrant plot/concordance analysis, and polar plot analysis.ResultsBland–Altman analysis showed an overall mean bias (95% limits of agreement) between tracheal and esophageal temperatures of -0.10 °C (-0.37 °C to 0.18 °C), with a percentage error of 0.27%; between tracheal and PA temperatures, -0.05 °C (-0.91 °C to 0.20 °C), with a percentage error of -0.15%; and between esophageal and PA temperatures, 0.04 °C (-0.27 °C to 0.35 °C), with a percentage error of 0.12%. The concordance rates between tracheal and esophageal temperatures, tracheal and PA temperatures, and esophageal and PA temperatures were 96.2%, 96.2%, and 94.94%, respectively. The polar plot analysis showed a mean angular bias (radial limits of agreement) of 4° (26°), -3° (13°), and 2° (21°).ConclusionsMonitoring core temperature at the inner surface of the endotracheal tube cuff is accurate in all phases of LDLT with good trending ability; thus, it can be an excellent alternative for monitoring during LDLTs.

346.2: Preoperative Neutrophil and Platelet-To-Lymphocyte Ratio As Predictors of Mortality and Surgical Related Complications After Liver Transplantation

Introduction: Liver transplantation (LT) is considered the only definitive treatment in patients with end-stage liver disease (ESLD). Nowadays, the 5-year overall survival (OS) after LT is 75%–85%. In addition, short-term mortality has decreased due to better perioperative care, advancements in operative techniques, as well as changes in patient selection. Despite these improvements, a subset of patients still dies within the first year after LT. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been recently reported as simple and useful markers of various inflammatory changes and are calculated based on complete blood count data. It has been suggested that both parameters in the acute phase of LT are prognostic factors for early post-transplant survival. Method: We conducted a retrospective and analytic study. Among 410 LT recipients between January 2013 and February 2022 who were operated at the HPB surgery and liver transplant department of the Hospital de Alta Complejidad “El Cruce”, we selected 120 patients after simple random sampling. Patients’ demographic data, cirrhosis etiology, model for end-stage liver disease (MELD) scores, and hematological parameters were analyzed. Latest hematological parameters prior to surgery were recorded. NLR and PLR values were calculated based on the measured hematological parameters. Time and incidence of postoperative complications were analyzed. Fisher exact test, Mann–Whitney U test and Students T-test were used when appropriate. Two-sided p value equal or less than 0.05 was considered to indicate statistical significance with a confidence interval of 95%. All analyses were conducted using MedCalc version 20.027 (https://www.medcalc.org/). Results: The mean age of the 120 patients included in the study was 58.73 ± 7.04 years; 66.67% were male. All patients received decesead donor liver transplantation. The most common indication for LT was liver cirrhosis due to hepatitis C virus (HCV) (30%) followed by alcoholic liver cirrhosis (26.67%) (table 1). The mean MELD score was found to be 24.85 ± 4.67. 23 out of 120 patients died after LT (19.16%). 5 patients (4.16%) presented surgical-related complications. Mortality was higher in patients with higher MELD scores (p = 0.011). The mean preoperative NLR was 3.54 ± 4.08 and PLR was 80.73 ± 50.59. When NLR and PLR results with cut-off values of >3,77 and ≤34,18 respectively were compared with the incidence of major complications (Dindo-Clavien ≥3) a significant result was found (p = 0.01). No statistical significance was found between NLR, PLR and age and mortality (p=0.91, 0.93 and 0.47 respectively). Conclusion: Preoperative NLR and PLR were not found useful to predict mortality after OLT in our series. However, they may be of value to anticipate poor prognosis or major incidence of complications in patients undergoing OLT. With this simple indices, high-risk patients can be identified and preventive measures can be taken.

Intraoperative lactic acid concentration during liver transplantation and cutoff values to predict early mortality: a retrospective analysis of 3,338 cases

BackgroundWe aimed to explore the distribution of intraoperative lactic acid (LA) level during liver transplantation (LT) and determine the optimal cutoff values to predict post-LT 30-day and 90-day mortality.MethodsIntraoperative LA data from 3,338 patients were collected between 2008 to 2019 and all-cause mortalities within 30 and 90 days were retrospectively reviewed. Of the three LA levels measured during preanhepatic, anhepatic, and neohepatic phase of LT, the peak LA level was selected to explore the distribution and predict early post-LT mortality. To determine the best cutoff values of LA, we used a classification and regression tree algorithm and maximally selected rank statistics with the smallest P value.ResultsThe median intraoperative LA level was 4.4 mmol/L (range: 0.5–34.7, interquartile range: 3.0–6.2 mmol/L). Of the 3,338 patients, 1,884 (56.4%) had LA levels > 4.0 mmol/L and 188 (5.6%) had LA levels > 10 mmol/L. Patients with LA levels > 16.7 mmol/L and 13.5–16.7 mmol/L showed significantly higher 30-day mortality rates of 58.3% and 21.2%, respectively. For the prediction of the 90-day mortality, 8.4 mmol/L of intraoperative LA was the best cutoff value.ConclusionsApproximately 6% of the LT recipients showed intraoperative hyperlactatemia of > 10 mmol/L during LT, and those with LA > 8.4 mmol/L were associated with significantly higher early post-LT mortality.

High-dose hydroxocobalamin in end-stage liver disease and liver transplantation.

Distributive shock is a serious complication in patients with chronic or end-stage liver disease, and can be exacerbated by vasoplegia in this patient population. Vasoplegic syndrome (VS) is a state of shock refractory to catecholamines and vasopressin that is often multifactorial in liver failure patients, and can occur in any phase of liver transplantation (LT) [i.e., pre-transplantation, intraoperative, and post-transplantation]. Methylene blue (MB) has been a well-established pharmacologic therapy for VS. However, it has been known to cause dose-related toxicity. Hydroxocobalamin (HXC) is not currently FDA approved for the management of VS, but studies have demonstrated its ability to cause an increase in systolic blood pressure by hypothesized mechanisms with only minimal side effects. To date, only three other reports have demonstrated the use of HXC in LT patients, which highlighted its use both intraoperatively and post-transplantation. Our report illustrates the utility of HXC in four LT patients with VS. Two of these cases illustrate the usefulness of HXC in the pre-transplantation period, which has never been previously reported. HXC is a useful pharmaceutical agent in the management of VS, especially if contraindications to MB exist or in cases of MB-resistant vasoplegia. Further studies with large sample sizes are necessary to ascertain the optimal dosage of HXC in LT patients.

Pharmacodynamics of cisatracurium intravenously infused during liver transplantation

Objective To evaluate the pharmacodynamics of cisatracurium intravenously infused during liver transplantation. Methods Twenty American Society of Anesthesiologists physical status Ⅲ or Ⅳ patients of both sexes, aged 18-60 yr, with body mass index of 20-30 kg/m2, scheduled for elective living donor liver transplantation, were enrolled in this study.Total intravenous anesthesia was used.The induction dose of cisatracurium for anesthesia was 0.15 mg/kg.When T1/T0 was restored to 10%, cisatracurium was injected intravenously at an initial rate of 1.5 μg·kg-1·min-1.The infusion rate was adjusted according to the monitoring results of muscle relaxation, and T1/T0 was maintained at 10%.The total amount of cisatracurium infused and infusing time were recorded during dissection phase, anhepatic phase and neohepatic phase, and the consumption of cisatracurium per unit time was calculated.Before skin incision, at 5 and 30 min of anhepatic phase, at 5 and 30 min of neohepatic phase and at the end of operation, the body temperature and stroke volume variation were recorded, blood samples were collected from the radial artery for blood gas analysis and for measurement of blood K+, Mg2+ and Ca2+ concentrations, and blood samples were collected from the internal jugular vein for determination of serum creatinine (Cr), urea nitrogen (BUN) and β2 microspheres protein (β2-MG) concentrations. Results There was no significant difference in the amount of cisatracurium per unit time between dissection phase and anhepatic phase (P>0.05). The amount of cisatracurium per unit time was significantly higher in neohepatic phase than in dissection phase and anhepatic phase (P<0.05). Compared with baseline before skin incision, blood pH value was significantly decreased at 30 min of anhepatic phase and 5 min of neohepatic phase, serum Mg2+ concentrations were decreased at 5 and 30 min of neohepatic phase and at the end of operation, the serum Cr, BUN and β2-MG concentrations were increased, the serum Ca2+ concentration was decreased at 5 min of anhepatic phase, and SVV was increased at 5 and 30 min of anhepatic phase (P< 0.05 or 0.01). Conclusion Muscle relaxation induced by cisatracurium infused intravenously in the anhepatic phase of liver transplantation is weakened. Key words: Atracurium; Liver transplantation; Infusions, intravenous; Dose-response relationship, drug

The correlation between conventional coagulation tests and thromboelastography in each phase of liver transplantation.

Thromboelastography (TEG) is gaining increasing acceptance in liver transplantation (LT) with conventional coagulation tests (CCTs) such as prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin III (ATIII), platelet count (PLT), and fibrinogen concentration. The purpose of this study was to evaluate the clinical utility of TEG in LT and investigate the correlation between TEG and CCT values during each phase of LT. Medical records of patients who underwent deceased donor LT at a single, university hospital between October 2010 and July 2015 were retrospectively reviewed. Blood samples were obtained at each phase of LT (pre-anhepatic, anhepatic, and neo-hepatic phase) according to our institutional LT protocol and utilized for analysis of TEG and CCTs. The Spearman correlation coefficient between TEG and CCT values were obtained. During the pre-anhepatic phase, the reaction time (R), PT, and aPTT did not correlate with each other, but demonstrated a negative correlation with PLT. Clot formation time (K) demonstrated a similar correlation with R and a negative correlation with fibrinogen. The maximal amplitude (MA) and α-angle (α) were positively correlated with PLT and fibrinogen and inversely correlated with aPTT. During the anhepatic phase, MA was significantly correlated with PLT and inversely correlated with aPTT; other parameters had weak or indistinct correlation. During the neo-hepatic phase, R and K were significantly correlated with aPTT and inversely correlated with PLT and fibrinogen. A correlation of MA and α with PLT, aPTT, and fibrinogen was also observed. Clot lysis at 30minutes and estimated percent lysis were inversely correlated with levels of ATIII and fibrinogen. Conventional coagulation tests and TEG show particularly poor comparability during the anhepatic period of liver transplantation. TEG can be most reliable in the anhepatic phase, during which dynamic hemostatic changes occur.

The Coagulation Profile of End-Stage Liver Disease and Considerations for Intraoperative Management.

The coagulopathy of end-stage liver disease results from a complex derangement in both anticoagulant and procoagulant processes. With even minor insults, cirrhotic patients experience either inappropriate bleeding or clotting, or even both simultaneously. The various phases of liver transplantation along with fluid and blood product administration may contribute to additional disturbances in coagulation. Thus, anesthetic management of patients undergoing liver transplantation to improve hemostasis and avoid inappropriate thrombosis in the perioperative environment can be challenging. To add to this challenge, traditional laboratory tests of coagulation are difficult to interpret in patients with end-stage liver disease. Viscoelastic coagulation tests such as thromboelastography (Haemonetics Corporation, Braintree, MA) and rotational thromboelastometry (TEM International, Munich, Germany) have helped to reduce transfusion of allogeneic blood products, especially fresh frozen plasma, but have also lead to the increased use of fibrinogen-containing products. In general, advancements in surgical techniques and anesthetic management have led to significant reduction in blood transfusion requirements during liver transplantation. Targeted transfusion protocols and pharmacologic prevention of fibrinolysis may further aid in the management of the complex coagulopathy of end-stage liver disease.

Customized nutrition intervention and personalized counseling helps achieve nutrition targets in perioperative liver transplant patients

Nutritional therapy is an integral part of care in all phases of liver transplantation (LTx). However, there are several factors that make it a challenge to manage malnutrition in these patients including, but not limited to, loss of appetite, dietary restrictions and dietary habits. Dietary habits are guided by personal choice, social, cultural and regional background with diversity ranging from veganism to vegetarianism with the latter predominant in Indian population. Therefore, it is difficult to improve nutritional intake of patients with standard dietary recommendations. We evaluated the effects of implementing personalized dietary counseling and a customized nutrition plan on its ability to enhance oral intake and, thereby improve nutritional status of patients with end stage liver disease (ESLD) being evaluated for LTx. We compared the outcomes with a matched group of patients who were prescribed standard dietary recommendations from a historic database. Primary outcome was measured by number of patients achieving ≥75% of recommended energy and protein requirements during hospitalization for LTx. Secondary outcomes included mean energy and protein intake, hours of ventilation, length of stay in Intensive Care Unit (ICU) and hospital, mortality and readmission rate in the acute phase (3months) after LTx. This was a prospective observational study, performed at a single LTx centre. All patients >18years who enrolled for LTx and consented for the study were included. The study was conducted after obtaining institutional ethics committee approval. A protocol based nutrition planning was implemented from April'14. According to this protocol, all patients being evaluated for LTx underwent a detailed nutritional assessment by a qualified Clinical Dietitian (CD) and regularly followed up with until LTx. Nutritional intervention, including a customized nutrition care plan and personalized dietary counseling, was provided based on the severity of malnutrition. To evaluate the efficacy of this protocol, we compared the nutritional adequacy (calorie and protein intake) of 65 consecutive patients who underwent LTx between August'14-October'15 (group 1) with a historic database of 65 patients who underwent LTx between January'13 and April'14 (group 2). Patients' demographics, disease severity score, baseline markers of nutritional status (subjective global assessment (SGA), and body mass index (BMI)), were recorded. First, assessment of individual patient's oral energy and protein intake was determined by the daily calorie count during hospitalization. Then the nutritional intervention (oral nutrition supplement (ONS)/enteral nutrition (EN)/parenteral nutrition (PN)) plan was customized according to their spontaneous oral intake. As part of the protocol, health related quality of life was also assessed using short form 8 (SF-8) in group 1. Statistical analyses using Pearson's correlation, Chi-Square test were applied with SPSS version 20.0. The mean age of group 1 and 2 were 52.6±9.8, 51.9±10.5 (range 25-70years) with BMI of 26.8±6.0, 26.5±5.4 respectively. According to SGA, there was significant improvement in the nutritional status of group 1 patients compared to group 2 on admission for LTx. It was indicated that 88% of group 1 individuals in comparison to 98% in group 2 were malnourished. The calorie intake of group 1 (1740.2±254.8) was significantly higher than group 2 (1568.5±321.6) (p=0.005). The marked improvement in protein intake in group 1 (63.1±12.1) when compared with group 2 (53.1±13.4) was statistically significant (p=0.008). A subset analysis showed that non-vegetarians (consuming meat and dairy products) between the groups showed that group 1 had a significantly higher calorie (p=0.004) and protein (p=0.0001) intake compared to individuals in group 2. Following implementation of study's protocol, the goal of achieving ≥75% of the prescribed calories (p=0.013) and protein (p=0.0001) was significantly higher in group 1. When compared to the standard prescription, an individualized protocol to diagnose, stratify the severity of malnutrition early, and follow up by customized nutrition planning for patients helped to achieve nutritional targets more effectively. Inspite of patients' diversity in nutritional habits and reluctance to accept change, it is clear that a qualified and dedicated transplant nutrition team can successfully implement perioperative nutrition protocol to achieve better nutritional targets.

Nutritional Therapy in Liver Transplantation.

Protein-energy malnourishment is commonly encountered in patients with end-stage liver disease who undergo liver transplantation. Malnutrition may further increase morbidity, mortality and costs in the post-transplantation setting. The importance of carefully assessing the nutritional status during the work-up of patients who are candidates for liver replacement is widely recognized. The metabolic abnormalities induced by liver failure render the conventional assessment of nutritional status to be challenging. Preoperative loss of skeletal muscle mass, namely, sarcopenia, has a significant detrimental impact on post-transplant outcomes. It is essential to provide sufficient nutritional support during all phases of liver transplantation. Oral nutrition is preferred, but tube enteral nutrition may be required to provide the needed energy intake. Herein, the latest currently employed perioperative nutritional interventions in liver transplant recipients are thoroughly illustrated including synbiotics, micronutrients, branched-chain amino acid supplementation, immunonutrition formulas, fluid and electrolyte balance, the offering of nocturnal meals, dietary counselling, exercise and rehabilitation.

Accuracy of non-invasive hemoglobin monitoring by pulse CO-oximeter during liver transplantation.

Hemoglobin level monitoring is essential during liver transplantation (LT) due to substantial blood loss. We evaluated the accuracy of non-invasive and continuous hemoglobin monitoring (SpHb) obtained by a transcutaneous spectrophotometry-based technology (Masimo Corporation, Irvine, CA) compared with conventional laboratory Hb measurement (HbL) during LT. Additionally, we made subgroup analyses for distinct surgical phases that have special features and hemodynamic problems and thus may affect the accuracy of SpHb. During LT, blood samples were obtained twice for each of the three phases of LT (pre-anhepatic, anhepatic, and neohepatic) and were analyzed by the central laboratory. The HbL measurements were compared with SpHb obtained at the time of the blood draws. A total of 282 data pairs obtained from 53 patients were analyzed. The SpHb values ranged from 6.9 to 17.7 g/dL, and the HbL values ranged from 5.4 to 17.1 g/dL. The correlation coefficient between SpHb and HbL was 0.73 (P<0.001), and change in SpHb versus change in HbL was 0.76 (P<0.001). The sensitivity value determined using a 4-quadrant plot was 79%. The bias and precision of SpHb to HbL were 0.86±1.58 g/dL; the limits of agreement were -2.25 to 3.96 g/dL. The overall correlation between SpHb and HbL remained stable in different phases of surgical procedure. SpHb was demonstrated to have a clinically acceptable accuracy of hemoglobin measurement in comparison with a standard laboratory device when used during LT. This technology can be useful as a trend monitor during all surgical phases of LT and can supplement HbL to optimize transfusion decisions or to detect occult bleeding.

The management of perioperative nutrition in patients with end stage liver disease undergoing liver transplantation.

Malnutrition is found in almost 100% of patients with end stage liver disease (ESLD) awaiting transplantation and malnutrition before transplantation leads to higher rates of post-transplant complications and worse graft survival outcomes. Reasons for protein energy malnutrition include several metabolic alterations such as inadequate intake, malabsorption, and overloaded expenditure. And also, stress from surgery, gastrointestinal reperfusion injury, immunosuppressive therapy and corticosteriods use lead to delayed bowl function recovery and disorder of nutrients absorption. In the pretransplant phase, nutritional goals include optimization of nutritional status and treatment of nutrition-related symptoms induced by hepatic decompensation. During the acute post-transplant phase, adequate nutrition is required to help support metabolic demands, replenish lost stores, prevent infection, arrive at a new immunologic balance, and promote overall recovery. In a word, it is extremely important to identify and correct nutritional deficiencies in this population and provide an adequate nutritional support during all phases of liver transplantation (LT). This study review focuses on prevalence, nutrition support, evaluation, and management of perioperative nutrition disorder in patients with ESLD undergoing LT.

Perioperative nutritional therapy in liver transplantation

Protein-energy malnutrition is frequently seen in patients with end-stage liver disease who undergo liver transplantation. This causes a deterioration of the patients' clinical condition and affects their post-transplantation survival. Accurate assessment of the nutritional status and adequate intervention are prerequisites for perioperative nutritional treatment. However, the metabolic abnormalities induced by liver failure make the traditional assessment of the nutritional status difficult. The methods that were recently developed for accurately assessing the nutritional status by body bioelectrical impedance may be implemented in pre-transplant management. Because preoperative malnutrition and the loss of skeletal muscle mass, called sarcopenia, have a significant negative impact on the post-transplantation outcome, it is essential to provide adequate nutritional support during all phases of liver transplantation. Oral nutrition is preferred, but tube enteral nutrition may be required to provide the necessary caloric intake. We herein discuss both bioelectrical impedance and the latest findings in the current perioperative nutritional interventions in liver transplant patients regarding synbiotics, micronutrients, branched-chain amino acid supplementation, the use of immune system modulating formulas, the fluid balance and the offering of nocturnal meals.

Intravenous Interferon Administered During Liver Transplantation Is Not Effective in Preventing Hepatitis C Reinfection

Post-transplant hepatitis C is a major challenge after liver transplantation (LT). Antiviral therapy is associated with lower efficacy in the post-transplant setting. The purpose of this study was to determine the safety and effect of intravenous interferon (IFN) during the anhepatic phase of LT on hepatitis C viral load. Fifteen consecutive subjects undergoing liver transplant for hepatitis C cirrhosis were enrolled in the study, ten of which received study drug and five subjects served as controls. Cases received weight-based ribavirin and subcutaneous IFN at time of incision followed by intravenous IFN at the start of the anhepatic phase. Adverse events and viral levels were recorded. Repeated measures ANOVA was employed to test for differences over time, between the groups, and time by group interaction. All subjects had genotype 1 virus. Hepatitis C viral load was lower at week 4 in cases compared to controls (769,004 ± 924,082 IU/ml and 2,329,896 ± 3,731,749 IU/ml, respectively), but did not reach statistical significance (p = 0.50). Three subjects developed adverse events related to IFN including pulmonary edema, rejection, and neutropenia. Intravenous IFN administered during the anhepatic phase of liver transplant did not prevent graft reinfection and was associated with manageable adverse events. This regimen could be further studied if direct acting antiviral agents alone are insufficient for treating post-transplant hepatitis C.

Comparison of Model Based and Clinical Blood Glucose Evolution during and after Anhepatic Status

Blood glucose (BG) control is a major difficulty during liver transplantation (LT). A model-based approach to analysis and control can enhance the efficiency of BG management during LT surgery. An existing clinically val- idated metabolic model was fitted to data from 8 LT pa- tients. The reperfusion part of the post-anhepatic phase of LT shows a clear consistent dynamic rise in blood glucose (BG) level that would enable better prediction of future BG in this phase. Model fitting errors showed that the funda- mental model captured all primary dynamics but parameter adjustment to reflect known conditions during LT surgery in specific phases would improve model quality.

One Year Follow-Up with Histology of HCV Liver Transplant Recipients who Received IV Interferon During the Anhepatic Phase of Transplant - A Controlled Pilot Study

Purpose: Post transplant recurrent Hepatitis C continues to be a challenge after liver transplantation (LT). Primary aim of this pilot study was to determine the safety of IV Interferon (IFN) & Ribavirin (RBV) administered during anhepatic phase of LT & determine their effect on HCV RNA. Secondary aims included histologic response at 48 weeks post-transplant. Methods: 15 consecutive subjects undergoing LT for HCV cirrhosis were enrolled {10 cases (received IFN), 5- controls}. All cases received RBV 1000/1200 mg PO on call to OR, 5 MU IFN α-2b SQ at time of incision & 5 MU IFN α-2b IV at start of the anhepatic phase. Adverse events within 48 weeks post LT were recorded. HCV RNA levels were obtained pre-transplant, before & after anhepatic phase, at 12, 24, 48 & 96 hrs & at week 4, 8, 12, 24 & 48 post LT. IL28B status was recorded. All subjects underwent protocol liver biopsy at 48 weeks. Immunosuppression was protocol based and all but 2 received tacrolimus. Repeated Measures ANOVA was employed to test for differences over time, between the groups, and time by group interaction. Results: All but 1 subject were male & mean age was 51 years. All had genotype 1 virus & mean MELD of study group was 18 + 6.2 (no significant difference between cases & controls). IL28B differed significantly between the 2 groups (cases - 5 CT, 2 CC, 1 TT, 1 not available; controls - 3 TT, 1 CT, 1 not available, p<0.05). We previously reported the regimen to be safe with easily manageable adverse events (n=3 subjects) and a trend for lower HCV RNA at week 4 among cases compared to controls (p >0.07; ACG 2012 # S132). There was no significant difference in Hgb, ANC, creatinine, ALT and length of stay post LT between the 2 groups. We now report follow-up 48 week data on our primary and secondary end-points. No additional adverse events were observed. The trend towards lower HCV RNA observed at week 4 among cases was lost at week 48 [HCV RNA was similar among cases and controls at 48 weeks post LT (5,866,398 + 9,441,240 vs. 5,216,657 + 4,968,923 respectively); p>0.05]. No significant difference was observed in histologic stage/grade at 48 weeks [data available in all but 2 subjects (1 case and 1 control)] between the 2 groups- all controls- stage 0 fibrosis; cases: Five- no fibrosis, One- stage 1 fibrosis, Three- stage 2 fibrosis. Conclusion: This pilot study suggests that IV IFN administered during the anhepatic phase of LT appears to be safe. There was a trend towards lower HCV RNA at week 4 post-LT among cases, although no significant virologic/ histologic effect was noted at 48 weeks. This limited data support further study of this novel approach for preventing recurrent post-LT HCV, possibly involving direct acting antiviral agents in select IL28B sub-groups.

Management of Hepatitis C Virus Infection in Liver Transplantation with Adacolumn Apheresis

Recurrent hepatitis C virus (HCV) is a major cause of liver transplant loss, hepatic failure, and retransplantation need. Posttransplantation antiviral therapy in patients with evidence of recurrent disease is the mainstay of management. Although HCV is a hepatocellular pathogen, there is increasing evidence that the virus can infect and persist in other cells. In particular, granulocytes and monocytes/macrophages are known to constitute extrahepatic sites for HCV replication and dissemination. The aim of this study was to apply Adacolumn apheresis as a possible therapeutic alternative to conventional drug therapy to manage HCV infections. Seven patients who underwent liver transplantation for HCV-related cirrhosis were eligible for the study. The patients underwent 5 1-hour sessions for 5 consecutive days. The first treatment was performed in the anhepatic phase of liver transplantation with the intent to early reduce infected granulocytes and monocytes/macrophages. The patients were evaluated over the 5 days after inclusion with 3- and 6-months follow-ups. Early apheresis treatments in the anhepatic phase and over the following 4 days after transplantation produced low viral loads in 4 patients, negative viral loads in 2 patients, and increased viremia in 1 patient. At follow-up, the viremia load was stable in 6 patients without increased transaminase levels. At the end of the treatment cycle, almost all immune cells of the 6 patients maintained CD4+/CD8+ T-cell ratios. The optimal timing of treatment initiation is unknown, but early preemptive therapy is recommended to decrease the risk for recurrent infection. Although this study investigated the responses among a small number of patients, it documented that the Adacolumn changed cellular immunity, promoting early virologic responses.

Hepatic Artery Kinking during Liver Transplantation

BackgroundHepatic artery thrombosis (HAT) represents the most common vascular complication occurring after liver transplantation (LT). Herein, we report the results of a prospective study of hepatic artery flow (HAF) measurement during abdominal wall closure after LT along with the results of an international survey of procedures adopted, in order to avoid the arterial kinking (AK) in case of long artery. MethodsSixty-four surgeons were asked regarding the different procedures used to avoid AK in the presence of long artery. We prospectively assessed the HAF during three phases of LT in 26 consecutive LT performed in patients with a long HA: after completion of the biliary anastomosis (M0), and partial abdominal wall closure with (M1w) or without (M1w/o) hepatic artery anti-kinking method (HAAK). ResultsSixty (93.7 %) surgeons replied to the survey: 44 (73.3 %) surgeons cut the artery as short as possible, of whom 38 (86.3 %) interposed an oxidized polymer or the omentum, and six (13.7 %) used other systems. Fourteen (23.3 %) surgeons did not use any interposition methods. The remaining two (3.3 %) surgeons left a long artery without HAAK. In our cohort we obtained the following HAF measures: M0 152 mL/min (89–205), M1 without HAAK 114 (66–168) and M1 with HAAK procedure 158 (91–219) (p = 0.002). ConclusionsOur survey confirms that no consensus is currently available regarding the most effective method for avoiding AK. Kinking occurs most probably when the liver is released in its final position. The utilization of an interposition method could ensure the maintenance of a correct HAF.

A Controlled Pilot Study of Interferon and Ribavirin During the Anhepatic Phase of Liver Transplantation for Prevention of Recurrent Hepatitis C

A Controlled Pilot Study of Interferon and Ribavirin During the Anhepatic Phase of Liver Transplantation for Prevention of Recurrent Hepatitis C

Indicators for global tissue perfusion in patients undergoing orthotopic liver transplantation: A pilot study

BackgroundPatients undergoing orthotopic liver transplantation are subjected to severe hemodynamic and metabolic derangements, close monitoring are always required. Mixed venous oxygen saturation (SVO2) is often used to reflect supply/demand ration for oxygen in critically ill patients. Cardiac output (CO) and serum lactate levels are also sensitive markers for detecting early hemodynamic and metabolic changes. Patients with end-stage liver disease, possess hemodynamic and metabolic derangements that can render such tools insensitive. In the current trial we evaluated SVO2, CO and serum lactate and since SVO2 can sometimes be misleading especially in hyperdynamic status we assessed oxygen delivery (DO2) and oxygen consumption (VO2).Patients and methodsTwenty patients with end-stage liver disease scheduled for live related liver transplantation were enrolled, CO, SVO2, serum lactate levels, VO2 and DO2 were recorded during the following times; dissection phase (T1), an-hepatic phase (T2) and neo-hepatic phase (T3).ResultsAll recorded parameters were comparable among the three phases of liver transplantation except for serum lactate levels that had increased significantly during T2 (7.10 ± 3.5 mmol/l, P = 0.04) and T3 (9.42 ± 4.65 mmol/l, P = 0.001) compared T1 (3.28 ± 2.7 mmol/l), however serum lactate levels and T2 and T3 were comparable. There was no evidence of any correlation among CO, SVO2, serum lactate levels, VO2 and DO2.ConclusionIncrease in serum lactate in this patient population is not necessarily due to increased production as a consequence of tissue hypoperfusion but rather may reflect improper lactate utilization since indicators of global tissue perfusion acted independently.