Perioperative Period Of Liver Transplantation Research Articles

Avatrombopag Elevates Platelet Counts and Reduces Platelet Transfusions in Patients With Chronic Liver Diseases During the Perioperative Period of Liver Transplantation

ABSTRACTBackgroundAvatrombopag has been approved for elevating platelet counts in patients with chronic liver diseases (CLDs) accompanied by thrombocytopenia (TCP). However, limited research focuses on its safety and efficacy in CLD patients during the perioperative period of liver transplantation (LT).MethodsWe retrospectively enrolled CLD patients with severe TCP who received avatrombopag during the perioperative period of LT and analyzed therapeutic efficacy, changes in platelet counts, and related adverse events. Comparisons were conducted between liver transplant recipients who received avatrombopag and those who did not use platelet‐raising drugs, focusing on intraoperative and postoperative bleeding as well as platelet transfusions.ResultsOf 93 patients who received avatrombopag, 67 cases (72%) achieved remission, with their platelet counts increasing to over 50 × 109/L without transfusion. Additionally, 38 cases (40.9%) reached platelet counts above 100 × 109/L, achieving complete remission. The overall remission rate was significantly correlated with the baseline platelet counts, suggesting that individuals with higher baselines (25−50 × 109/L vs. < 25 × 109/L) were more likely to achieve remission (82.1% vs. 57.7%, χ2 = 5.989, p = 0.014). Using propensity score‐overlap weighting to balance the baseline bias, we compared 33 liver transplant recipients who received avatrombopag to those who did not receive any platelet‐raising drugs. Recipients who used avatrombopag achieved significantly higher platelet counts both before and after propensity score‐overlap weighting ([63.76 ± 31.33] × 109/L vs. [45.73 ± 16.44] × 109/L, p = 0.004; [65.37 ± 38.41] × 109/L vs. [42.73 ± 17.27] × 109/L, p = 0.044) and required fewer intraoperative and postoperative platelet transfusions (p < 0.05). No adverse events related to avatrombopag were observed.ConclusionsAvatrombopag is safe and effective for CLD patients with TCP during the perioperative period of LT, resulting in elevated platelet counts and reduced need for platelet transfusions.

Use of N-acetyl-cysteine in the Perioperative Period of Liver Transplantation: A Scoping Review

Objective: To !nd evidence on the use of N-acetyl-cysteine (NAC) in the perioperative period of liver transplantation, since NAC, as it is the acetylated precursor of L-cysteine and reduced glutathione, contributes to the hepatic supply of glutathione, helping the liver to recover from ischemia and reperfusion injury. Methodology: "is is a scoping review of the PubMed, VHL and Web of Science databases. "e descriptors “Liver transplantation”, “N-acetyl-cysteine” and “Reperfusion Ischemia” were used, with the Boolean operator “AND”, and articles relevant to the topic were selected. Initially, 60 articles were selected, all published in the last 24 years, in Portuguese and/or English. After analysis, eight articles corresponded to the proposed objective. Results:"e groups that received NAC during TxF showed post-reperfusion hypotension, lower intraoperative pH values, higher plasma concentrations of IL-4 and a signi!cant increase in IL-10 levels !ve minutes before reperfusion. Inhibition of α-glutathione S-transferase (α-GST) was also observed after reperfusion, unlike the control group, which showed a signi!cant increase in this enzyme. Furthermore, sVCAM-1 and sICAM-1 levels were signi!cantly lower in the NAC group 24 hours after reperfusion compared with the placebo group. "e maximum AST value during the !rst 72 postoperative hours was similar in both groups, although the peak ALT was lower in the NAC group than in the placebo group. In grafts that received NAC in the perfusion solution, survival rates at 3 and 12 months were 93% and 90%, respectively, and in the control group were 82% and 70%, respectively. "e incidence of postoperative complications was 23% in the NAC group and 51% in the control group. "e incidence of EPD was lower for the NAC group, which was 15% versus 32% in the control group. Regarding the administration of NAC during the intraoperative TxF, the one-year patient survival rate was 78.4% in the NAC group compared to 80.9% in the placebo group. Conclusion: Intraoperative administration of NAC during the anhepatic phase was associated with a protective effect against reperfusion injury, however in other studies limitations were observed in protection against liver injury, in biomarkers of oxidative stress, in in$ammation and in the functioning of liver enzymes.

Gastrointestinal Tonometry in the Perioperative Period of Liver Transplantation: An Integrative Review

Introduction: Gastric tonometry is a useful tool for examining regional splanchnic perfusion as it provides an indirect assessment of the state of the liver graft. This is because splanchnic hypoperfusion is a critical parameter in the context of liver transplantation, being associated with the development of problems such as acute liver failure and multiple organ failure. Objective: To analyze the effects of gastrointestinal tonometry in the perioperative period of patients undergoing liver transplantation. Methodology: This is an Integrative Review using the PubMed and VHL databases. The following descriptors were used: “Tonometry”, “Splanchnic circulation” and “Liver transplantation” with the Boolean operator “AND”, and articles of relevance to the topic were selected. Initially, 24 articles were selected, all published in the last 20 years, in Portuguese and/or English. After analysis, 6 articles matched the proposed objective. Results:It was observed that the difference between PraCO2 at the end of surgery and in the anepathic phase was greater in patients without liver graft dysfunction. A positive correlation was found between ǻpraCO2 and peak ALT after liver transplantation. In another study, it was found that the relationship between poor graft function was the presence of elevated liver enzymes, worsening synthetic liver function, coagulopathy and encephalopathy. It has also been shown that intramucosal gastric pH can predict early graft function. In a group with liver dysfunction, patients had an intramucosal gastric pH of less than 7.3 in the perioperative period, which remained low until the 24th hour postoperatively, while the group without dysfunction had an intramucosal gastric pH of more than 7.3, except in the anepathic phase when it was below this value. Conclusion: The usefulness of gastrointestinal tonometry to monitor splanchnic circulation and liver graft function during liver transplantation has been described and although support for this statement was found in some studies, this review had limitations due to the small number of articles available, which prevents it from covering a wide range of scientific evidence

Predictive Value of Perioperative Cardiac Troponin I in Patients Undergone Liver Transplantation: A Retrospective Cohort Study.

To examine the change rule and clinical significance of cardiac troponin I (cTnI) in the perioperative period of liver transplantation in adults, as well as its association with 28-day mortality. This was a retrospective cohort study: patients who underwent elective orthotopic liver transplantation (OLT) in Beijing Chao-Yang Hospital between June 2015 and June 2020 were selected, and plasma cTnI values were collected through the electronic medical record system within 7 days after surgery. Furthermore, the baseline clinical data of these patients were collected, and the change curve of cTnI values following liver transplantation was plotted. Using univariate and multivariate logistic regression models, the relationship between the level of postoperative cTnI and short-term mortality was investigated. The primary study endpoint was mortality within 28 days after surgery. We included 414 patients who had undergone liver transplantation in this study, 48 of whom died within 28 days after surgery. cTnI, a specific marker of myocardial injury, could predict that the postoperative cardiovascular complications were higher in the death group and significantly affect the short-term prognosis of patients; however, its prognostic cut-off value was approximately 0.545 ng/mL (13×URL), indicating that a minor elevation of cTnI after liver transplantation did not significantly affect the prognosis. Moreover, a comparison of the baseline data and postoperative ICU management scores of the two groups revealed that diabetes, maximum value of cTnI >0.545 ng/mL within 7 days, and the need for postoperative renal replacement therapy (RRT) were independent prognostic factors of death within 28 days after liver transplantation. Within 7 days after surgery, an increase in cTnI to the maximum value of 0.545 ng/mL (13×URL) could have a significant impact on the short-term prognosis of patients. Diabetes and postoperative RRT were two independent prognostic factors for liver transplantation perioperative mortality.

The perioperative period of liver transplantation from unconventional extended criteria donors: data from two high-volume centres

BackgroundAs literature largely focuses on long-term outcomes, this study aimed at elucidating the perioperative outcomes of liver transplant patients receiving a graft from two groups of unconventional expanded criteria donors: brain dead aged > 80 years and cardiac dead.MethodsData of 247 cirrhotic patients transplanted at two high volume liver transplant centers were analysed. Confounders were balanced using a stabilized inverse probability therapy weighting and a propensity score for each patient on the original population was generated. The score was created using a multivariate logistic regression model considering a Comprehensive Complication Index ≥ 42 (no versus yes) as the dependent variable and 11 possible clinically relevant confounders as covariate.ResultsForty-four patients received the graft from a cardiac-dead donor and 203 from a brain-dead donor aged > 80 years. Intraoperatively, cardiac-dead donors liver transplant cases required more fresh frozen plasma units (P < 0.0001) with similar reduced need of fibrinogen to old brain-dead donors cases. The incidence of reperfusion syndrome was similar (P = 0.80). In the Intensive Care Unit, both the groups presented a comparable low need for blood transfusions, renal replacement therapy and inotropes. Cardiac-dead donors liver transplantations required more time to tracheal extubation (P < 0.0001) and scored higher Comprehensive Complication Index (P < 0.0001) however the incidence of a severe complication status (Comprehensive Complication Index ≥ 42) was similar (P = 0.52). ICU stay (P = 0.97), total hospital stay (P = 0.57), in hospital (P = 1.00) and 6 months (P = 1.00) death were similar.ConclusionSelected octogenarian and cardiac-dead donors can be used safely for liver transplantation.

Viscoelastic Management of Coagulopathy during the Perioperative Period of Liver Transplantation.

Viscoelastic testing (VET) in liver transplantation (LT) has been used since its origin, in combination with standard laboratory testing (SLT). There are only a few, small, randomized controlled trials that demonstrated a reduction in transfusion rates using VET to guide coagulation management. Retrospective analyses contrasting VET to SLT have demonstrated mixed results, with a recent concern for overtreatment and the increase in postoperative thrombotic events. An oversight of many studies evaluating VET in LT is a single protocol that does not address the different phases of surgery, in addition to pre- and postoperative management. Furthermore, the coagulation spectrum of patients entering and exiting the operating room is diverse, as these patients can have varying anatomic and physiologic risk factors for thrombosis. A single transfusion strategy for all is short sighted. VET in combination with SLT creates the opportunity for personalized resuscitation in surgery which can address the many challenges in LT where patients are at a paradoxical risk for both life-threatening bleeding and clotting. With emerging data on the role of rebalanced coagulation in cirrhosis and hypercoagulability following LT, there are numerous potential roles in VET management of LT that have been unaddressed.

Expert consensus on liver transplantation perioperative evaluation and rehabilitation for acute-on-chronic liver failure

Acute-on-chronic liver failure (ACLF) can be cured by liver transplantation; however, perioperative complications still affect posttransplant outcomes. In recent years, early rehabilitation for critical illness, liver disease, and surgery have significantly improved organ reserve function, surgery tolerance, and postoperative quality of life. They could also be applied in the perioperative period of liver transplantation in patients with ACLF. Therefore, the Transplantation Immunology Committee of Branch of Organ Transplantation Physician of Chinese Medical Doctor Association, the Organ Transplant Committee of China Association Rehabilitation Medicine, and the Guangdong Medical Doctor Association of Organ Transplantation conducted a comprehensive review of rehabilitation in end-stage liver disease, critical illness and surgical patients by summarizing current evidence and best clinical practices and proposed a practice consensus on evaluation of cardiopulmonary and physical function, rehabilitation or physiotherapies, as well as the safety concerns in perioperative liver transplant recipients. It will be a valuable resource for hepatologists, transplant surgeons, and intensivists as they care for ACLF patients during transplantation.

Role of proenkephalin in the diagnosis of severe and subclinical acute kidney injury during the perioperative period of liver transplantation

In recent decades, clinical research on early biomarkers of renal injury has been frequent and intensive, with proenkephalin (PENK) being indicated as a promising filtration biomarker (BM). From a cohort of 57 patients, blood samples were collected preoperatively and 48 h after liver transplantation (LT). The following BMs were analyzed: PENK, cystatin-C (CYS-C), and serum creatinine (Scr). Diagnosis of AKI was based on the KDIGO criteria. Of the 57 patients undergoing LT, 50 (88%) developed acute kidney injury (AKI) and were categorized as follows: no-AKI/mild-AKI - 21 (36.8%) and severe-AKI 36 (63.2%). During the preoperative period, only PENK was significantly higher in patients with severe AKI, with an AUC of 0.69 (CI 0.54–0.83), a cutoff of 55.30 pmol/l, a sensitivity of 0.86, a specificity of 0.52, and an accuracy of 0.75. In addition, subclinical AKI was determined preoperatively in 32 patients. Forty-eight hours after LT, PENK maintained its performance in determining severe AKI, with an AUC of 0.83 (CI 0.72–0.94), a cutoff of 119.05 pmol/l, a sensitivity of 0.81, a specificity of 0.90, and an accuracy of 0.84. PENK detected AKI 48 h earlier than serum creatinine. In a multivariate linear regression analysis, PENK was an independent predictor of severe AKI. This small study suggests that the filtration biomarker PENK shows promise for detecting AKI in patients undergoing LT, revealing greater accuracy and an earlier rise in patients with severe AKI. The combination of kidney functional and filtration BMs may aid in the management and prevention of AKI progression.

Commentary: 3D Laparoscopy-Assisted Operation to Adult Intussusceptions During Perioperative Period of Liver Transplantation: Case Report and Literature Review.

Commentary: 3D Laparoscopy-Assisted Operation to Adult Intussusceptions During Perioperative Period of Liver Transplantation: Case Report and Literature Review.

3D Laparoscopy-Assisted Operation to Adult Intussusceptions During Perioperative Period of Liver Transplantation: Case Report and Literature Review

Adult intussusception during the perioperative period is defined as an extremely rare condition, especially when it emerges within short intervals of laparotomy, which may be explained as an unphysiological peristaltic function of the bowel without any lead points. Accurate diagnosis and therapeutic schedule predict a satisfactory outcome. Here, we introduce the case of a 32-year-old man who had symptoms of abdominal pain, no gas emission, and defecation shortly after liver transplantation. Intussusception was definitely diagnosed by abdominal CT, and then reduction was operated successfully by three-dimensional laparoscopy-assisted operation. There were no other complaints, and no secondary lesions were detected during the postoperative rehabilitation process in the hospital and over a follow-up period of 6 months. Relevant literature has been summarized subsequently. A promising minimally invasive surgery along with minimal secondary trauma was presented by laparoscopy in this rare case, providing the potential remedy for perioperative intussusception in the adult.

Nutrition Support in Liver Transplantation and Postoperative Recovery: The Effects of Vitamin D Level and Vitamin D Supplementation in Liver Transplantation.

Vitamin D plays an important role in the arena of liver transplantation. In addition to affecting skeletal health significantly, it also clinically exerts immune-modulatory properties. Vitamin D deficiency is one of the nutritional issues in the perioperative period of liver transplantation (LT). Although vitamin D deficiency is known to contribute to higher incidences of acute cellular rejection (ACR) and graft failure in other solid organ transplantation, such as kidneys and lungs, its role in LT is not well understood. The aim of this study was to investigate the clinical implication of vitamin D deficiency in LT. LT outcomes were reviewed in a retrospective cohort of 528 recipients during 2014–2019. In the pre-transplant period, 55% of patients were vitamin-D-deficient. The serum vitamin D level was correlated with the model for end-stage liver disease (MELD-Na) score. Vitamin D deficiency in the post-transplant period was associated with lower survival after LT, and the post-transplant supplementation of vitamin D was associated with a lower risk of ACR. The optimal vitamin D status and vitamin D supplementation in the post-transplant period may prolong survival and reduce ACR incidence.

Impact of Intraoperative Norepinephrine Support on Living Donor Liver Transplantation Outcomes: A Retrospective Cohort Study of 430 Children.

Norepinephrine (NE) is often administered during the perioperative period of liver transplantation to address hemodynamic instability and to improve organ perfusion and oxygen supply. However, its role and safety profile have yet to be evaluated in pediatric living donor liver transplantation (LDLT). We hypothesized that intraoperative NE infusion might affect pediatric LDLT outcomes. A retrospective study of 430 pediatric patients (median [interquartile range] age, 7 [6.10] months; 189 [43.9%] female) receiving LDLT between 2014 and 2016 at Renji Hospital was conducted. We evaluated patient survival among recipients who received intraoperative NE infusion (NE group, 85 recipients) and those that did not (non-NE group, 345 recipients). The number of children aged over 24 months and weighing more than 10 kg in NE group was more than that in non-NE group. And children in NE group had longer operative time, longer anhepatic phase time and more fluid infusion. After multivariate regression analysis and propensity score regression adjusting for confounding factors to determine the influence of intraoperative NE infusion on patient survival, the NE group had a 169% more probability of dying. Although there was no difference in mean arterial pressure changes relative to the baseline between the two groups, we did observe increased heart rates in NE group compared with those of the non-NE group at anhepatic phase (P=0.025), neohepatic phase (P=0.012) and operation end phase (P=0.017) of the operation. In conclusion, intraoperative NE infusion was associated with a poorer prognosis for pediatric LDLT recipients. Therefore, we recommend the application of NE during pediatric LDLT should be carefully re-considered.

Study design of the DAS-OLT trial: a randomized controlled trial to evaluate the impact of dexmedetomidine on early allograft dysfunction following liver transplantation

BackgroundPerioperative ischemia/reperfusion (I/R) injury during liver transplantation is strongly associated with early allograft dysfunction (EAD), graft loss, and mortality. Hepatic I/R injury also causes remote damage to other organs including the renal and pulmonary systems. Dexmedetomidine (DEX), a selective α2-adrenoceptor agonist which is used as an adjuvant to general anesthesia, has been shown in preclinical studies to provide organ protection by ameliorating the effects of I/R injury in a range of tissues (including the liver). However, prospective clinical evidence of any potential benefits in improving outcomes in liver transplantation is lacking. This study aimed to verify the hypothesis that the application of dexmedetomidine during the perioperative period of liver transplantation can reduce the incidence of EAD and primary graft non-function (PNF). At the same time, the effects of dexmedetomidine application on perioperative renal function and lung function were studied.MethodsThis is a prospective, single-center, randomized, parallel-group study. Two hundred participants (18–65 years) scheduled to undergo liver transplantation under general anesthesia will be included in this study. For participants in the treatment group, a loading dose of DEX will be given after induction of anesthesia (1 μg/kg over 10 min) followed by a continuous infusion (0.5 μg/kg /h) until the end of surgery. For participants in the placebo group, an equal volume loading dose of 0.9% saline will be given after the induction of anesthesia followed by an equal volume continuous infusion until the end of surgery. All other supplements, e.g., opioids, sedatives, and muscle relaxant, will be identical in both arms and administered according to routine clinical practice.DiscussionThe present trial will examine whether DEX confers organoprotective effects in the liver, in terms of reducing the incidence of EAD and PNF in orthotopic liver transplantation recipients.Trial registrationClinicalTrials.gov NCT03770130. Registered on 10 December 2018. https://clinicaltrials.gov/ct2/show/NCT03770130

Effect of sedation weaning pattern on withdrawal syndrome in pediatric intensive care unit

Objective: To investigate the sedation weaning strategies in critically ill patients with mechanical ventilation in pediatric intensive care unit (PICU) and to explore the effect of different sedative weaning patterns on withdrawal syndrome. Methods: A single-center prospective cohort study was conducted from April 1, 2016 to April 30, 2017. One hundred and twelve patients who required mechanical ventilation and benzodiazepines and (or) opioids for at least 5 consecutive days in PICU of Shanghai Children's Medical Center were enrolled. Twenty patients (17.9%) had an intermittent weaning pattern, defined as a 50% or greater increase in daily benzodiazepine and (or) opioid dose after the start of weaning, and the remaining 92 cases (82.1%) had a steady weaning pattern. The demographic and clinical features, duration and dose of sedative and analgesics, and the incidence of withdrawal syndrome were evaluated. Mann-Whitney U test was used for comparison about clinical features between different weaning pattern groups and children with withdrawal syndrome or not. Logistic regression was used to explore the risk factors of withdrawal syndrome. Results: Among the 112 patients, 46 (41.1%) had withdrawal syndrome. The patients with the intermittent weaning pattern had a high score of pediatric risk of mortality Ⅲ (PRISM-Ⅲ) (10.0 (3.5, 12.0) vs. 6.0 (2.0, 10.0), U=654.50, P=0.043) and were prone to re-intubation (35.0% (7/20) vs. 7.6% (7/92), P=0.003). The patients with withdrawal syndrome had longer duration of sedation (19.5 (16.8, 24.3) vs. 10.0 (7.0, 17.3) days, U=743.50, P<0.01), higher incidence of intermittent weaning pattern (32.6% (15/46) vs. 7.6% (5/66),χ(2)=11.58, P=0.001), longer PICU hospitalization (19.0 (15.8, 25.3) vs. 12.0 (8.8, 17.0) days, U=755.00, P<0.01) and higher cost (89 (57,109) vs. 53 (32, 79) thousand yuan, U=804.00, P<0.01). Logistic regression showed that intermittent weaning pattern (odds ratio (OR)=4.85, 95% confidence interval (CI) 1.39-16.91, P=0.013), perioperative period of liver transplantation (OR=6.97, 95%CI 1.25-39.04, P=0.027) and a cumulative dose of midazolam ≥ 34.7 mg/kg (OR=8.12, 95%CI 3.09-21.37, P<0.01) were risk factors of withdrawal syndrome. Conclusions: Withdrawal syndrome is more likely to occur in children who are intermittently weaned from sedation. Steady weaning strategy may help prevent iatrogenic withdrawal syndrome.

Long-term impact of dialysis-requiring AKI during the perioperative period of liver transplantation on postdischarge outcomes.

Patients undergoing liver transplantation (LT) are prone to dialysis-requiring acute kidney injury (AKI-D). However, long-term prognoses among them need further investigation, as overall survival after LT is improving. A nationwide, population-based cohort study was conducted using the data of Korean National Health Insurance System between 2006 and 2015. The patients who received dialysis during the perioperative period of LT were in the AKI-D group, and the control group included those who did not undergo dialysis. Among the 6879 patients who underwent LT, 968 were in the AKI-D group. All-cause mortality [adjusted hazard ratio (HR): 1.52 (1.26-1.83), P<0.001], end-stage renal disease (ESRD) progression [adjusted HR: 2.93 (2.34-3.66), P<0.001], and ICU readmission [adjusted HR: 1.70 (1.44-2.01), P<0.001] within and after 90days from discharge were increased in the AKI-D group. When analyzed among those who recovered from dialysis at discharge, overall outcomes were similar to those of the AKI-D group, except the long-term mortality. AKI-D during the perioperative period of LT was associated with worse mortality, ESRD progression, and ICU readmission risk. The results of renal-recovered patients could indicate clinicians that achievement of dialysis independence is important to gain favorable long-term postdischarge survival.

Energy Balance and Nutrition Status: A Prospective Assessment of Patients Undergoing Liver Transplantation.

Energy balance (EB) and its relation to nutrition status throughout the perioperative period of liver transplantation (LTx) patients has been poorly reported in the literature, and this is the primary objective of the current study. A prospective observational study was conducted with patients undergoing LTx, who were assessed before and after the operation. Resting energy expenditure, total energy expenditure (TEE), dietary intake, and EB were evaluated, as well as anthropometry, handgrip strength, and standard phase angle (SPA). The presence of complications after the operation, length of intensive care unit and hospital stay, and death were registered. A P-value<0.05 was considered statistically significant. The average age was 54.1±11.5 years; 79.3% of the patients were male, and the mean model for end-stage liver disease (MELD) score was 16.7±4.6. Negative EB was seen in 71.4% and 77.8% of patients before and after LTx, respectively. Food intake further decreased after the operation, leading to a significantly more negative EB. The prevalence of malnutrition ranged from 17.2% to 57.7% pretransplantation and 30.8% to 86.4% postoperatively, according to the different methods used. Increased preoperative TEE (0.040) and age (0.039) were predictive factors for complications, and low SPA was a predictive factor of death (0.038). Negative EB was prevalent, and this was associated with high rates of malnutrition. These data reinforce the importance of individual nutrition assessment, including dietary intake, to tailor early nutrition interventions.

Perioperative thromboprophylaxis in liver transplant patients.

Improvements in surgical and anesthetic procedures have increased patient survival after liver transplantation (LT). However, the perioperative period of LT can still be affected by several complications. Among these, thromboembolic complications (intracardiac thrombosis, pulmonary embolism, hepatic artery and portal vein thrombosis) are relatively common causes of increased morbidity and mortality. The benefit of thromboprophylaxis in general surgical patients has already been established, but it is not the standard of care in LT recipients. LT is associated with a high bleeding risk, as it is performed in a setting of already unstable hemostasis. For this reason, the role of routine perioperative prophylactic anticoagulation is usually restricted. However, recent data have shown that the bleeding tendency of cirrhotic patients is not an expression of an acquired bleeding disorder but rather of coexisting factors (portal hypertension, hypervolemia and infections). Furthermore, in cirrhotic patients, the new paradigm of ‘‘rebalanced hemostasis’’ can easily tip towards hypercoagulability because of the recently described enhanced thrombin generation, procoagulant changes in fibrin structure and platelet hyperreactivity. This new coagulation balance, along with improvements in surgical techniques and critical support, has led to a dramatic reduction in transfusion requirements, and the intraoperative thromboembolic-favoring factors (venous stasis, vessels clamping, surgical injury) have increased the awareness of thrombotic complications and led clinicians to reconsider the limited use of anticoagulants or antiplatelets in the postoperative period of LT.

Acute kidney injury in liver transplant candidates: a position paper on behalf of the Liver Intensive Care Group of Europe.

Acute kidney injury is associated with high mortality in the perioperative period of liver transplantation. The aim of this position paper was to provide an up-to-date overview with special emphases on diagnosis, risk factors, and treatment. The Liver Intensive Care Group of Europe nominated a panel of recognized international experts who reviewed the available literature published from 1990 to January 2016 and produced clinical recommendations. The level of evidence and strength of recommendation were judged according to the Grading of Recommendations Assessment Development and Evaluation system. Diagnosis of AKI should be based on the KDIGO criteria. The preoperative risk factors are more related to the patient's predisposing factors and post-operative risk factors tend to be difficult to control. Therefore, focusing on intra-operative risk factors it would be important to maintain an adequate hemodynamics and to keep inferior vena cava clamping as short as possible. Biomarkers to identify AKI at an early stage are available; however, there is a lack of robust data that indicates their true beneficial effect. Intraoperative renal replacement therapy may be beneficial in some selective cases whereas its postoperative timing is still under debate. Perioperative liver transplant risk factors for acute kidney injury are difficult to control. Therefore, the focus should be on intra-operative hemodynamics and nephrotoxic drugs avoidance. Prospective randomized trials are needed to show the beneficial effect of early replacement therapy. In this context, the new biomarkers would be helpful in identifying kidney injury earlier.

Systemic hemodynamics in advanced cirrhosis: Concerns during perioperative period of liver transplantation.

Advanced liver cirrhosis is usually accompanied by portal hypertension. Long-term portal hypertension results in various vascular alterations. The systemic hemodynamic state in patients with cirrhosis is termed a hyperdynamic state. This peculiar hemodynamic state is characterized by an expanded blood volume, high cardiac output, and low total peripheral resistance. Vascular alterations do not disappear even long after liver transplantation (LT), and recipients with cirrhosis exhibit a persistent systemic hyperdynamic state even after LT. Stability of optimal systemic hemodynamics is indispensable for adequate portal venous flow (PVF) and successful LT, and reliable parameters for optimal systemic hemodynamics and adequate PVF are required. Even a subtle disorder in systemic hemodynamics is precisely indicated by the balance between cardiac output and blood volume. The indocyanine green (ICG) kinetics reflect the patient's functional hepatocytes and effective PVF, and PVF is a major determinant of the ICG elimination constant (kICG) in the well-preserved allograft. The kICG value is useful to set the optimal PVF during living-donor LT and to evaluate adequate PVF after LT. Perioperative management has a large influence on the postoperative course and outcome; therefore, key points and unexpected pitfalls for intensive management are herein summarized. Transplant physicians should fully understand the peculiar systemic hemodynamic behavior in LT recipients with cirrhosis and recognize the critical importance of PVF after LT.

Thrombin-activatable Fibrinolysis Inhibitor (TAFI) as a Novel Prognostic Factor After Orthotropic Liver Transplantation: A Pilot Study

BackgroundThrombin-activatable fibrinolysis inhibitor (TAFI), a liver-produced coagulation factor, has been associated with higher mortality in cirrhotic patients, but there has not been any description of its role in perioperative care in liver transplantation cases. MethodsA total of 21 patients were included. Serum TAFI levels were determined at 3 time points: preoperatively (TAFI pre), immediately postoperative (TAFI PO), and 24 hours postoperatively (TAFI 24 h). The main outcome was the physiological pattern of TAFI in the perioperative period of liver transplantation. The secondary outcomes were the association between TAFI and early allograft dysfunction (EAD) as well as that of TAFI and 6-month mortality. ResultsTAFI levels increased at the 24-hour time point, compared to the other 2 time points (TAFI pre, P = .007; TAFI PO, P = .0001). Early allograft dysfunction occurred in 2 of 21 patients, both demonstrating lower TAFI 24 h levels compared to those who did not develop this complication (3.0 ± 0.2 vs 1.5 ± 0.3; P = .0001). Three patients who died all demonstrated lower levels of TAFI pre (1.3 ± 0.1 vs 2.5 ± 0.5; P = .001) and TAFI PO (1.2 ± 0.1 vs 2.4 ± 0.4; P = .001) compared to the survivors. ConclusionsThese findings suggest that the determination of TAFI levels—both pre- and postoperatively—may be of clinical relevance in liver transplant recipients.