Management Of Liver Transplantation Research Articles

Multimodal Pain Management of Liver Transplantation: What Is New?

Liver transplantation (LT) is a life-saving treatment representing the only viable option for patients suffering from end-stage liver disease (ESLD) or acute liver failure. Patients who undergo LT require a multidisciplinary approach to postoperative pain management. However, pain management in this context is often inadequately explored. Limited options exist for proper pain control in patients with hepatic failure, mainly due to the increased risk of kidney and multi-organ failure. In LT candidates, specific analgesics may elevate the risk of side effects, such as hepatic encephalopathy, acute renal failure, and gastrointestinal bleeding, consequently increasing overall morbidity and mortality. In the case of LT, the post-operative pain might be underestimated since the demand for analgesics is typically lower than other major abdominal surgeries. Consequently, there is a lack of studies addressing post-operative pain management. This review aims to outline current strategies for pain management in LT, with a particular focus on opioid-free approaches, and to introduce forthcoming developments in this field.

Planned Extracorporeal Life Support Employment during Liver Transplantation: The Potential of ECMO and CRRT as Preventive Therapies-Case Reports and Literature Review.

Liver Transplantation (LT) has become the gold standard treatment for End-Stage Liver Disease (ESLD). One of the main strategies to manage life-threatening complications, such as cardio-respiratory failure, is Extracorporeal Membrane Oxygenation (ECMO) in the peri-transplantation period, with different configurations of the technique and in combination with other extracorporeal care devices such as Continuous Renal Replacement Therapy (CRRT). This retrospective study includes three clinical cases of planned ECMO support strategies in LT and evaluates their application compared with current literature exploring PubMed/Medline. The three LT supported with ECMO and CRRT were performed at IRCCS Polyclinic S. Orsola-Malpighi, Bologna. All three cases of patients with compromised organ function analysed produced positive outcomes. The planned use of ECMO and CRRT support in peri-transplantation has allowed the patients to overcome contraindications and successfully undergo LT. In recent years, only a few reports have documented successful LT outcomes performed with intraoperative ECMO in critically ESLD patients. However, the management of LT with ECMO and/or CRRT assistance is an emerging challenge, with the need for more published evidence on this topic to guide treatment choices in patients with severe, acute and reversible respiratory and cardiovascular failure after LT.

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.

Management of liver diseases: Current perspectives.

There is increasing incidence and prevalence of acute and chronic liver diseases (CLDs) all over the world which influence the quality of life and can give rise to life threatening complications. The burden of advanced liver disease due to hepatitis B has been controlled by antivirals but its eradication is difficult soon. Highly effective directly acting antiviral therapy has reduced the burden of hepatitis C but is partially offset by increasing IV drug abuse. Non-alcoholic fatty liver disease pandemic is on and there is recent alarming increase in alcohol related liver disease, both of which have no drug cure apart from control of the risk factors. Genetic factors have been identified in progression of all forms of CLD. Due to better management of complications of CLD, the life span of patients have increased spiking the number of hepatocellular carcinoma (HCC) and patients needing liver transplantation (LT). The present severe acute respiratory syndrome coronavirus pandemic has affected the outcome CLD including LT in addition to causing acute hepatitis. Better diagnostics and therapeutics are available for liver fibrosis, portal hypertension, HCC and post LT management and many drugs are under trial. The present review summarises the current scenario of the epidemiology and the advances in diagnosis and treatment of liver diseases including their complications like portal hypertension, HCC and LT.

Perioperative Management and Clinical Outcomes of Liver Transplantation for Children with Homozygous Familial Hypercholesterolemia.

Background and Objectives: Liver transplantation (LT) has been accepted as a life-saving option as a last resort for children with homozygous familial hypercholesterolemia (HoFH). Perioperative management of LT for HoFH poses extra challenges for clinicians largely due to premature atherosclerotic cardiovascular diseases (ASCVDs). We aimed to analyze our data of pediatric LT recipients with HoFH, with special attention paid to perioperative management and clinical outcomes. Materials and Methods: After obtaining approval from the local ethics committee, the clinical data of pediatric patients with HoFH who underwent LT at our institution between January 2014 and February 2021 were retrospectively studied. Results: Six pediatric LT recipients with HoFH were included in the analysis. Although ASCVDs were common before LT, all children with HoFH survived the perioperative period without in-hospital mortality. However, one patient experienced acute myocardial infarction two months following LT and was successfully treated with medical interventions. Post-LT metabolic improvement was shown by declines in serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in the early post-LT period (for TC: 14.7 ± 3.2 mmol/L vs. 5.5 ± 1.8 mmol/L, p < 0.001; for LDL-C: 10.6 ± 2.2 mmol/L vs. 3.6 ± 1.2 mmol/L, p < 0.001, respectively) and at the last follow-up (for TC: 14.7 ± 3.2 mmol/L vs. 4.5 ± 0.9 mmol/L, p = 0.001; for LDL-C: 10.6 ± 2.2 mmol/L vs. 2.8 ± 0.6 mmol/L, p = 0.001, respectively). Dietary restrictions could be lifted after LT. However, three patients required restarting lipid-lowering therapy after LT due to suboptimal LDL-C levels and progression of ASCVDs. Conclusions: Our data suggest that LT can be a safe and feasible therapeutic option for well-selected patients with HoFH, offering relaxed dietary restrictions and remarkable reductions in LDL-C levels. However, concerns remain regarding progression of ASCVDs after LT.

Experience Verification of 63 Cases of Liver Transplantation Anesthesia Management

Background: We reviewed the intraoperative management of previous liver transplantation (LT) cases to identify an optimal anesthetic method, which may affect patient outcomes and lead to faster postoperative recovery for future recipients. Methods: This single-center retrospective study reviewed 63 patients who underwent LT, including 51 living donor LT (LDLT), seven deceased donor LT (DDLT), and five simultaneous liver-kidney transplantation patients. We examined the patients’ backgrounds, intraoperative management (anesthetic method, water balance, and catecholamine dosage), and postoperative courses (hospitalization period, length of intensive care unit stay, renal function). Results: All patients received general anesthesia using inhalational anesthetics, either sevoflurane or desflurane, and both drugs were administered similarly. Rocuronium was administered at its usual dose despite liver failure. All patients undergoing preoperative dialysis due to acute kidney injury were successfully withdrawn from dialysis after surgery. The albumin infusion volume was 32% of the total infusion and transfusion volume. The five-year survival rate was 88% and graft failure occurred in one case. Conclusion: The anesthetic management of LT is currently conducted empirically in our institution, and we could not identify an optimal anesthetic method. However, we drew some conclusions. First, the use of human atrial natriuretic peptide as a drug infusion and appropriate transfusion management was expected to restore renal function. Second, the infusion volume of albumin was high. Third, the usual dose of rocuronium was required because excessive bleeding may cause unstable plasma drug concentration. Our results will be useful in future multi-institutional studies or meta-analyses and further improving the outcomes of future transplant recipients.

Donor Hepatic Occult Collagen Deposition Predisposes to Peritransplant Stress and Impacts Human Liver Transplantation.

Background and AimsEnvironmentally triggered chronic liver inflammation can cause collagen deposits, whereas early stages of fibrosis without any specific symptoms could hardly be detectable. We hypothesized that some of the human donor grafts in clinical liver transplantation (LT) might possess unrecognizable fibrosis, affecting their susceptibility to LT‐induced stress and hepatocellular damage. This retrospective study aimed to assess the impact of occult hepatic fibrosis on clinical LT outcomes.Approach and ResultsHuman (194) donor liver biopsies were stained for collagen with Sirius red, and positive areas (Sirius red–positive area; SRA) were measured. The body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes score was calculated using 962 cases of the donor data at the procurement. LT outcomes, including ischemia‐reperfusion injury (IRI), early allograft dysfunction (EAD), and survival rates, were analyzed according to SRA and BARD scores. With the median SRA in 194 grafts of 9.4%, grafts were classified into low‐SRA (<15%; n = 140) and high‐SRA (≥15%; n = 54) groups. Grafts with high SRA suffered from higher rates of IRI and EAD (P < 0.05) as compared to those with low SRA. Interestingly, high SRA was identified as an independent risk factor for EAD and positively correlated with the donor BARD score. When comparing low‐BARD (n = 692) with high‐BARD (n = 270) grafts in the same period, those with high BARD showed significantly higher post‐LT transaminase levels and higher rates of IRI and EAD.ConclusionsThese findings from the largest clinical study cohort to date document the essential role of occult collagen deposition in donor livers on LT outcomes. High‐SRA and donor BARD scores correlated with an increased incidence of hepatic IRI and EAD in LT recipients. This study provides the rationale for in‐depth and prospective assessment of occult fibrosis for refined personalized LT management.

Pediatric Liver Transplantation for Alagille Syndrome: Anesthetic Evaluation and Perioperative Management.

BackgroundAlagille syndrome (AGS) is an autosomal dominant hereditary disorder characterized by identifiable abnormalities in the liver, heart, face, skeleton, and eyes. Recently, liver transplantation (LT) has been proposed as a therapeutic strategy for patients with AGS complicated by end-stage liver disease, but clinical experience in performing anesthesia in LT for AGS is still scarce. We aimed to summarize our preliminary experience in the anesthetic management of LT for AGS in this study.Material/MethodsWe reviewed the cases of 11 patients with AGS who underwent LT from September 2017 to April 2019. Preoperative multi-system comorbidities, intraoperative details, and postoperative outcomes were retrospectively collected and summarized.ResultsCardiopulmonary abnormalities were common (81.8%) in AGS patients before LT, and the most frequent comorbidity was pulmonary artery stenosis. After careful anesthetic evaluation and perioperative management, all patients survived during the perioperative period without significant cardiovascular complications. However, there was an unexpectedly high prevalence of surgical complications and re-operations in AGS patients compared to biliary atresia recipients (54.5% vs. 22.4%, P=0.031; and 45.5% vs. 15.3%, P=0.028, respectively).ConclusionsPerioperative management of LT for AGS patients can be particularly challenging, requiring a full understanding of the pathophysiology, as well as a careful preoperative evaluation of the multi-system comorbidities. The high prevalence of postoperative surgical complications should be a matter of concern.

Cardiac and Liver Disease in Children: Implications for Management Before and After Liver Transplantation.

There is close interaction between the functions of the liver and heart affecting the presentation, diagnosis, and outcome of acute and chronic cardiac and liver disease. Conditions affecting both organ systems should be considered when proposing transplantation because the interaction between cardiac disease and liver disease has implications for diagnosis, management, selection for transplantation, and, ultimately, for longterm outcomes after liver transplantation (LT). The combination of cardiac and liver disease is well recognized in adults but is less appreciated in pediatric patients. The focus of this review is to describe conditions affecting both the liver and heart and how they affect selection and management of LT in the pediatric population.

Successful perioperative management of living-donor liver transplantation for a patient with severe methylmalonic acidemia: a case report

BackgroundMethylmalonic acidemia (MMAemia) is a rare hereditary disease affecting organic acid metabolism. It causes recurrent metabolic acidosis and secondary mitochondrial dysfunction, resulting in a poor prognosis. Liver transplantation (LT) has been performed to facilitate the metabolism of organic acids and improve the prognosis of MMAemia. However, there have been few reports on perioperative management of LT.Case presentationA 22-month-old female with severe MMAemia was scheduled to receive LT to relieve recurrent metabolic acidosis despite dietary and pharmacological treatment. General anesthesia was maintained without propofol or nitrous oxide, which can worsen MMAemia-induced metabolic acidosis during anesthesia for LT. Strict metabolic and respiratory management enabled the operation to be successfully performed without metabolic acidosis.ConclusionPerioperative management of LT for MMAemia is challenging for anesthesiologists because of the possibility of serious metabolic acidosis. We succeeded in preventing metabolic decompensation by avoiding the use of propofol and nitrous oxide.

Intraoperative Management of High-Risk Liver Transplant Recipients: Concerns and Challenges.

Liver transplantation (LT) offers patients with liver disease a real chance for long-term survival. In the past decade, successful survival after LT along with the Model for End-Stage Liver Disease-based allocation policy have increased willingness to accept patients with a higher risk profile and marginal organs and to prioritize the sickest patients on the waiting list. Therefore, the anesthesiologist now deals with very challenging patients. In the present review, we aimed to highlight key aspects of intraoperative LT management in high-risk patients and to place these aspects in the perspective of their impact on perioperative outcomes. Conservative standardized perioperative strategies mandate a switch toward accurate and tailored perioperative anesthetic care to maintain the steady improvement in recipient survival rates after LT. In our opinion, continuous assessment of fluid status and cardiac performance, strategies promoting graft decongestion, rational hemostatic management, and the identification of LT recipients with potential risk of vascular complications should constitute the cornerstone of intraoperative management.

Liver transplantation in Germany.

Liver transplantation (LT) is a well-accepted procedure for end-stage liver disease in Germany. In 2015, 1489 patients were admitted to the waiting list (including 1308 new admissions), with the leading etiologies being fibrosis and cirrhosis (n = 349), alcoholic liver disease (n = 302), and hepatobiliary malignancies (n = 220). Organ allocation in Germany is regulated within the Eurotransplant system based on urgency as expressed by the Model for End-Stage Liver Disease score. In 2015, only 894 LTs (n = 48 from living donors) were performed at 23 German transplant centers, reflecting a shortage of organs. Several factors may contribute to the low number of organ donations. The German transplant legislation only accepts donation after brain death (not cardiac death), whereas advances in neurosurgery and a more frequently requested "palliative care" approach render fewer patients suitable as potential donors. The legislation further requires the active consent of the donor or first-degree relatives before donation. Ongoing debates within the German transplant field address the optimal management of patients with alcoholic liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma and measures to increase living donor transplantations. As a result of irregularities at mainly 4 German transplant centers that were exposed in 2012, guiding principles updated by the German authorities have since implemented strict rules (including internal and external auditing, the 8-eyes principle, mandatory repeated testing for alcohol consumption) to prohibit any manipulations in organ allocation. In conclusion, we will summarize important aspects on the management of LT in Germany, discuss legal and organizational aspects, and highlight challenges mainly related to the relative lack of organ donations, increasing numbers of extended criteria donors, and the peculiarities of the recipient patients. Liver Transplantation 22 1136-1142 2016 AASLD.

Transoesophageal echocardiography during liver transplantation.

Liver transplantation (LT) has become the standard of care for patients with end stage liver disease. The allocation of organs, which prioritizes the sickest patients, has made the management of liver transplant candidates more complex both as regards their comorbidities and their higher risk of perioperative complications. Patients undergoing LT frequently display considerable physiological changes during the procedures as a result of both the disease process and the surgery. Transoesophageal echocardiography (TEE), which visualizes dynamic cardiac function and overall contractility, has become essential for perioperative LT management and can optimize the anaesthetic management of these highly complex patients. Moreover, TEE can provide useful information on volume status and the adequacy of therapeutic interventions and can diagnose early intraoperative complications, such as the embolization of large vessels or development of pulmonary hypertension. In this review, directed at clinicians who manage TEE during LT, we show why the procedure merits a place in challenging anaesthetic environment and how it can provide essential information in the perioperative management of compromised patients undergoing this very complex surgical procedure.

Perioperative complications in liver transplantation using donation after cardiac death grafts: A propensity-matched study

Donation after cardiac death (DCD) is an important source for expanding the donor pool for liver transplantation (LT). Although the long-term outcomes of LT using DCD grafts have been extensively studied, perioperative complications related to DCD grafts are rarely reported. The aim of this study was to determine whether DCD grafts were associated with a higher incidence of postreperfusion complications and worse outcomes in adult LT patients. After institutional review board approval, the medical records of all adult patients who underwent LT at our medical center between 2004 and 2011 were reviewed. Postreperfusion complications and posttransplant outcomes were compared between patients receiving DCD grafts and patients receiving donation after brain death (DBD) grafts. In all, 74 patients received DCD grafts during the study period, and 1369 patients received DBD grafts. An initial comparison showed that many preoperative, prereperfusion, and donor variables in the DCD group differed significantly from those in the DBD group. Propensity matching was chosen so that adjustments could be made for the differences. A postmatching analysis showed that the preoperative, prereperfusion, and donor variables no longer differed between the 2 groups. The postreperfusion requirements for blood products and vasopressors, the posttransplant ventilation times, the incidence of posttransplant acute renal injury, and the 30-day and 1-year patient and graft survival rates were comparable between the 2 groups. However, patients receiving DCD grafts experienced significantly higher rates of hyperkalemia (33.8% versus 18.9%, P < 0.05) and postreperfusion syndrome (PRS; 25.7% versus 12.3%, P < 0.05). In conclusion, after adjustments for preoperative and prereperfusion risks via propensity matching, DCD grafts remained a risk factor for postreperfusion hyperkalemia and PRS. A prophylactic regimen aimed at decreasing postreperfusion hyperkalemia and PRS is recommended for the management of LT using DCD grafts.

Prospective Evaluation of Intraoperative Hemodynamics in Liver Transplantation with Whole, Partial and DCD Grafts

The interaction of systemic hemodynamics with hepatic flows at the time of liver transplantation (LT) has not been studied in a prospective uniform way for different types of grafts. We prospectively evaluated intraoperative hemodynamics of 103 whole and partial LT. Liver graft hemodynamics were measured using the ultrasound transit time method to obtain portal (PVF) and arterial (HAF) hepatic flow. Measurements were recorded on the native liver, the portocaval shunt, following reperfusion and after biliary anastomosis. After LT HAF and PVF do not immediately return to normal values. Increased PVF was observed after graft implantation. Living donor LT showed the highest compliance to portal hyperperfusion. The amount of liver perfusion seemed to be related to the quality of the graft. A positive correlation for HAF, PVF and total hepatic blood flow with cardiac output was found (p = 0.001). Portal hypertension, macrosteatosis >30%, warm ischemia time and cardiac output, independently influence the hepatic flows. These results highlight the role of systemic hemodynamic management in LT to optimize hepatic perfusion, particularly in LDLT and split LT, where the highest flows were registered.

Aminopyrine breath test in cirrhotic patients awaiting liver transplantation: do we really need it ?

Received: 20 April 2004 Accepted: 8 June 2004 Published online: 27 October 2004 Springer-Verlag 2004 Dear Editors: We read with interest the article by Degre and colleagues on the use of the aminopyrine breath test (ABT) to predict mortality among cirrhotic patients waitlisted for liver transplantation (LT) [1]. However, their well-designed study raises questions as to the real impact of such a test in the management of LT waiting lists. Patient stratification—which is often referred to as the sickest first principle—is crucial to any resource allocation, but prediction of post-transplant survival, i.e. utility, is mandatory if an LT programme is to be cost effective. The abysmal gap between organ demand and supply and the everincreasing use of suboptimal donors mandate a policy of effective graft allocation, which is often opposite to the principle of equity. Over the recent years several quantitative tests of liver function (QTLF) have been suggested to assess the hepatic functional reserve in patients with chronic liver disease [2]. These tests include the ABT, the methionine breath test, the galactose clearance capacity, the sorbitol and the indocyanine-green clearance [2, 3]. However, none has proved superior to the traditional Child–Pugh (CP) classification, which is based on clinical and laboratory parameters. Furthermore, QTLF may vary significantly within and across CP classes as a result of enzyme-inducing agents [4] and of causes of disease [5]. To date, it is unclear whether QTLF may provide relevant prognostic information in cirrhotic patients that is superior to that of conventional prognostic parameters or risk scores [2]. The recent introduction of the model for end-stage liver disease (MELD) scoring system for patient prioritisation is based on the assumption that graft allocation should favour the most urgent patients and that the CP-driven allocation system fails to identify seriously ill patients in a timely fashion [6]. However, even though the MELD system is a reliable indicator of patients’ urgency within populations, there are differences in actual calculated risks for a given MELD score between populations [7]. Furthermore, the MELD score has been found to be poorly correlated with post-transplantation outcome, and surrogate prognostic models have been suggested [8]. The assumption that the pretransplantation patient risk is paramount and that every patient has the same right to be offered LT is not the case in most European centres, where a National Health System run programme must comply with economic and ethic issues and face shortage of available resources. Moreover, the impact of marginal donor grafts on post-transplantation outcome is to be taken into account Transpl Int (2004) 17: 651–652 DOI 10.1007/s00147-004-0772-x LETTER TO THE EDITORS