When Is a Critically Ill Cirrhotic Patient Too Sick to Transplant? Development of Consensus Criteria by a Multidisciplinary Panel of 35 International Experts.

BACKGROUND: Critically ill cirrhotic patients are increasingly transplanted, but there is no consensus about futile liver transplantation (LT). Therefore, the decision to delay or deny LT is often extensively debated. These debates arise from different opinions of futility among transplant team members. This study aims to achieve a multinational and multidisciplinary consensus on the definition of futility in LT and to develop well-articulated criteria for not proceeding with LT due to futility. METHODS: Thirty-five international experts from anesthesiology/intensive care, hepatology, and transplant surgery were surveyed using the Delphi method. More than 70% of similar answers to a question were necessary to define agreement. RESULTS: The panel recommended patient and graft survival at 1 year after LT to define futility. Severe frailty and persistent fever or <72 hours of appropriate antimicrobial therapy in case of ongoing sepsis were considered reasons to delay LT. A simple assessment of the number of organs failing was considered the most appropriate way to decide whether LT should be delayed or denied, with respiratory, circulatory and metabolic failures having the most influence in this decision. The thresholds of severity of organ failures contraindicating LT for which a consensus was achieved were a Pao2/FiO2 ratio<150 mm Hg, a norepinephrine dose >1 µg/kg per minute and a serum lactate level >9 mmol/L. CONCLUSIONS: Our expert panel provides a consensus on the definition of futile LT and on specific criteria for postponing or denying LT. A framework that may facilitate the decision if a patient is too sick for transplant is presented.

Renal dysfunction and cirrhosis.

PURPOSE OF REVIEW: Hepatorenal syndrome (HRS) does not represent the predominant phenotype of acute kidney injury (AKI) in cirrhosis. Early recognition of HRS helps initiate appropriate therapy. The aims of this review are to present redefinition of AKI, to list new biomarkers, to report recent data on vasopressors in HRS and to propose criteria for simultaneous liver and kidney transplantation (SLKT). RECENT FINDINGS: Urine output, which was not part of the definition of AKI might be reconsidered as it has an independent prognostic value. Biomarkers (NGAL and IL-18) could help identify ATN. However, cut-off values have to be clarified. Vasopressors with albumin represent first option in HRS. Continuous infusion of terlipressin has a better safety profile than intravenous boluses. SLKT should be considered whenever native kidney recovery is unlikely [i.e. prolonged renal replacement therapy (RRT) and/or GFR less than 25 ml/min for 6 weeks prior to transplantation]. SUMMARY: New definitions and recent biomarkers may help differentiate HRS from ATN at an earlier stage. Urine output should be reconsidered in the definitions. Even in patients who are not candidates for transplantation, a short trial of RRT is justified whenever needed. SLKT should be considered whenever posttransplant renal recovery is unlikely.

Critical care management of the patient with cirrhosis awaiting liver transplant in the intensive care unit.

Patients with cirrhosis who are awaiting liver transplantation (LT) are at high risk for developing critical illnesses. Current liver allocation policies that dictate a "sickest first" approach coupled with a mismatch between need and availability of organs result in longer wait times, and thus, patients are becoming increasingly ill while awaiting organ transplantation. Even patients with well-compensated cirrhosis may suffer acute deterioration; the syndrome of acute-on-chronic liver failure (ACLF) results in multisystem organ dysfunction and a marked increase in associated short-term morbidity and mortality. For patients on transplant waiting lists, the development of multisystem organ failure may eliminate candidacy for transplant by virtue of being "too sick" to safely undergo transplantation surgery. The goals of intensive care management of patients suffering ACLF are to rapidly recognize and treat inciting events (eg, infection and bleeding) and to aggressively support failing organ systems to ensure that patients may successfully undergo LT. Management of the critically ill ACLF patient awaiting transplantation is best accomplished by multidisciplinary teams with expertise in critical care and transplant medicine. Such teams are well suited to address the needs of this unique patient population and to identify patients who may be too ill to proceed to transplantation surgery. The focus of this review is to identify the common complications of ACLF and to describe our approach management in critically ill patients awaiting LT in our centers. Liver Transplantation 23 1465-1476 2017 AASLD.

Immunomodulating therapy in liver transplantation: principles and practice.

Liver transplantation has enjoyed dramatic success as a treatment option for patients suffering from chronic end-stage liver diseases. It also serves as a definitive treatment for certain genetic conditions such as familial amyloidosis and primary oxalosis, and as a potential curative therapy in selected cases of primary liver cancer. Currently, over 50,000 patients are alive with functioning liver transplants. Liver transplantation owes its success to advances in surgical technique, improvements in anesthesia and critical care, and advances in treatment of post-transplant complications including improved therapies for cytomegalovirus infections. But perhaps the most important advances in liver transplantation arise in the context of improvements in our understanding of the molecular biology of transplant immunology and the development of new agents that allow for manipulation of immunological signaling pathways. These improvements in immunosuppressive therapy have dramatically increased both graft and patient survival.