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.

Priority of candidates with hepatocellular carcinoma awaiting liver transplantation can be reduced after successful bridge therapy.

The allocation rules for patients with hepatocellular carcinoma (HCC) who are awaiting liver transplantation (LT) are a difficult issue and are continually evolving. To reduce tumor progression or down-stage advanced disease, most transplant centers have adopted the practice of treating HCC candidates with resection or locoregional therapies. This study was designed to assess the effectiveness of bridge therapy in preventing removal from the waiting list for death/sickness severity or tumor progression beyond the Milan criteria and in determining posttransplant outcomes. The removal rates for 315 adult patients with HCC who were listed for LT were analyzed and were correlated to responses to bridge therapy with a competing risk analysis. The 3-, 6-, and 12-month dropout rates were 3.5%, 6.5%, and 19.9%, respectively, and they were significantly affected by the Model for End-Stage Liver Disease score (P = 0.032), the tumor stage at diagnosis (P = 0.041), and the response to bridge therapy (P < 0.001). The stratification of candidates by the tumor stage and the response to bridge therapy showed that patients with T2 tumors who achieved only a partial response or no response to bridge therapy had the highest dropout rates, and they were followed by patients with successfully down-staged T3-T4a tumors (P = 0.037). Patients with T2 tumors who had a complete response and patients with T1 tumors had similar dropout rates (P = 0.964). The response to bridge therapy significantly affected both the recurrence rate of 176 transplant patients (P = 0.017) and the overall intention-to-treat survival rate (P = 0.001). In conclusion, the response to therapy is a potentially effective tool for prioritizing HCC patients for LT as well as select cases with different risks of tumor recurrence after transplantation.

Liver transplantation from donors aged 80 years and over: pushing the limit.

Older donors are a growing part of the total donor pool but no definite consensus exists on the limit of age for their acceptance. From November 1998 to January 2003, in a retrospective case-control multicenter study, we compared the outcome of 30 orthotopic liver transplantations (OLTs) with octogenarian donors and of 60 chronologically correlated OLTs performed with donors <40 years. The percentage of refusal was greater among older than younger donors (48.2 vs. 14.3%; p < 0.001). Cold ischemia was significantly shorter in the older than younger groups. Recipients with hepatocarcinoma and older age received octogenarian grafts more frequently. No differences were seen in post-operative complications and 6-month graft and patient survival. However, long-term survival was lower in patients transplanted with octogenarian donors (p = 0.04). Interestingly, the mortality related to hepatitis C recurrence was greater in patients with octogenarian donors. Accordingly, the long-term survival of HCV-positive patients who received older grafts was lower than those receiving younger grafts (p = 0.05). Octogenarian livers can be used safely but a careful donor evaluation and a short cold ischemia are required to prevent additional risk factors. However, hepatitis C recurrence is associated with a greater mortality in patients who received octogenarian grafts raising concerns whether to allocate these livers to HCV-positive recipients.