Abstract：
OBJECTIVE: Utility, a major principle for allocation in the context of transplantation, is questioned in patients with acute-on chronic liver failure grade 3 (ACLF-3) who undergo liver transplantation (LT). We aimed to explore long-term outcomes of patients included the three-center retrospective French experience published in 2017.
METHODS: All patients with ACLF-3 (n=73) as well as their transplanted matched controlled with ACLF-2 (n=145), 1 (n=119) and no ACLF (n=292) that have participated in the princeps study published in 2017 were included. We explored 5- and 10-year patient and graft survivals, causes of death and their predictive factors.
RESULTS: Median follow-up of patients ACLF-3 patients was 7.5 years. At LT, median MELD was 40. In patients with ACLF-3, 2, 1 and no ACLF, 5-year patients\' survivals were respectively 72.6% vs. 69.7% vs. 76.4% vs. 77.0% (p=0.31). Ten-year patients\' survival ACLF-3 was 56.8% and was not different other groups (p=0.37) Leading causes of death in ACLF-3 patients were infections (33.3%), and cardiovascular events (23.3%). After exclusion of early death, UCLA futility risk score, age-adjusted Charlson comorbidity index and Chronic Liver Failure Consortium ACLF score were independently associated with 10-year patients\' survival. Long-term grafts\' survivals were not different across the groups. Clinical frailty scale and WHO performance status improved over time in patients alive after 5 years.
CONCLUSIONS: 5- and 10-year patients\' and grafts\' survivals in ACLF-3 patients were not different from their controls. 5-year patients\' survival is higher than that of the 50%-70% threshold defining the utility of liver graft. Efforts should focus on candidates\' selection based on comorbidities as well as the prevention of infection and cardiovascular events standing as the main cause of death.
UNASSIGNED: While short-term outcomes following liver transplantation in the most severely ill cirrhotic patients (ACLF-3) are known, long-term data are limited, raising questions about the utility of graft allocation in the context of scarce medical resources. This study provides a favorable long-term update, confirming no differences in 5- and 10-year patient and graft survival following liver transplantation in ACLF-3 patients compared to matched ACLF-2, ACLF-1, and no-ACLF patients. The study highlights the risk of dying from infection and cardiovascular causes in the long-term and identifies scores including comorbidities evaluation, such as the age-adjusted Charlson Comorbidity Index, as independently associated with long-term survival. Therefore, physicians should consider the cumulative burden of comorbidities when deciding to transplant these patients. Additionally, after transplantation, the study encourages mitigating infectious risk with tailored immunosuppressive regimens and managing tightly cardiovascular risk over time.
METHODS: All patients with ACLF-3 (n=73) as well as their transplanted matched controlled with ACLF-2 (n=145), 1 (n=119) and no ACLF (n=292) that have participated in the princeps study published in 2017 were included. We explored 5- and 10-year patient and graft survivals, causes of death and their predictive factors.
RESULTS: Median follow-up of patients ACLF-3 patients was 7.5 years. At LT, median MELD was 40. In patients with ACLF-3, 2, 1 and no ACLF, 5-year patients\' survivals were respectively 72.6% vs. 69.7% vs. 76.4% vs. 77.0% (p=0.31). Ten-year patients\' survival ACLF-3 was 56.8% and was not different other groups (p=0.37) Leading causes of death in ACLF-3 patients were infections (33.3%), and cardiovascular events (23.3%). After exclusion of early death, UCLA futility risk score, age-adjusted Charlson comorbidity index and Chronic Liver Failure Consortium ACLF score were independently associated with 10-year patients\' survival. Long-term grafts\' survivals were not different across the groups. Clinical frailty scale and WHO performance status improved over time in patients alive after 5 years.
CONCLUSIONS: 5- and 10-year patients\' and grafts\' survivals in ACLF-3 patients were not different from their controls. 5-year patients\' survival is higher than that of the 50%-70% threshold defining the utility of liver graft. Efforts should focus on candidates\' selection based on comorbidities as well as the prevention of infection and cardiovascular events standing as the main cause of death.
UNASSIGNED: While short-term outcomes following liver transplantation in the most severely ill cirrhotic patients (ACLF-3) are known, long-term data are limited, raising questions about the utility of graft allocation in the context of scarce medical resources. This study provides a favorable long-term update, confirming no differences in 5- and 10-year patient and graft survival following liver transplantation in ACLF-3 patients compared to matched ACLF-2, ACLF-1, and no-ACLF patients. The study highlights the risk of dying from infection and cardiovascular causes in the long-term and identifies scores including comorbidities evaluation, such as the age-adjusted Charlson Comorbidity Index, as independently associated with long-term survival. Therefore, physicians should consider the cumulative burden of comorbidities when deciding to transplant these patients. Additionally, after transplantation, the study encourages mitigating infectious risk with tailored immunosuppressive regimens and managing tightly cardiovascular risk over time.
摘要：
目标：实用程序，在移植的背景下分配的主要原则，在接受肝移植（LT）的急性慢性肝衰竭3级（ACLF-3）患者中受到质疑。我们旨在探索患者的长期结局，包括2017年发表的三中心回顾性法国经验。
方法：所有ACLF-3患者（n=73）以及他们的移植匹配的ACLF-2对照（n=145），1（n=119）和没有ACLF（n=292）参与了2017年发表的princeps研究。我们探索了5年和10年的患者和移植物存活率，死亡原因及其预测因素。
结果：ACLF-3患者的中位随访时间为7.5年。在LT,MELD中位数为40。在ACLF-3、2、1和无ACLF的患者中，5年患者的生存率分别为72.6%和69.7%与76.4%vs.77.0%(p=0.31)。ACLF-3患者的10年生存率为56.8%，其他组没有差异（p=0.37）ACLF-3患者的主要死亡原因是感染（33.3%），和心血管事件（23.3%）。排除早期死亡后，加州大学洛杉矶分校无效风险评分，经年龄校正的Charlson合并症指数和慢性肝功能衰竭联合会ACLF评分与患者10年生存率独立相关.各组的长期移植物存活率没有差异。5年后，患者的临床虚弱量表和WHO表现状况随着时间的推移而改善。
结论：ACLF-3患者的5年和10年生存率与对照组没有差异。5年患者的生存率高于定义肝移植效用的50％-70％的阈值。应根据合并症以及预防作为主要死亡原因的感染和心血管事件来选择候选人。
虽然已知最严重的肝硬化患者（ACLF-3）肝移植后的短期结果，长期数据有限，在医疗资源稀缺的情况下，对移植分配的效用提出了质疑。这项研究提供了一个有利的长期更新，确认与匹配的ACLF-2，ACLF-1和无ACLF患者相比，ACLF-3患者肝移植后5年和10年患者和移植物存活率没有差异。该研究强调了长期死于感染和心血管原因的风险，并确定了包括合并症评估在内的分数。如年龄调整后的Charlson合并症指数，与长期生存独立相关。因此,医师在决定对这些患者进行移植时,应考虑共病的累积负担.此外,移植后,该研究鼓励通过量身定制的免疫抑制方案降低感染风险,并随着时间的推移严格控制心血管风险.
方法：所有ACLF-3患者（n=73）以及他们的移植匹配的ACLF-2对照（n=145），1（n=119）和没有ACLF（n=292）参与了2017年发表的princeps研究。我们探索了5年和10年的患者和移植物存活率，死亡原因及其预测因素。
结果：ACLF-3患者的中位随访时间为7.5年。在LT,MELD中位数为40。在ACLF-3、2、1和无ACLF的患者中，5年患者的生存率分别为72.6%和69.7%与76.4%vs.77.0%(p=0.31)。ACLF-3患者的10年生存率为56.8%，其他组没有差异（p=0.37）ACLF-3患者的主要死亡原因是感染（33.3%），和心血管事件（23.3%）。排除早期死亡后，加州大学洛杉矶分校无效风险评分，经年龄校正的Charlson合并症指数和慢性肝功能衰竭联合会ACLF评分与患者10年生存率独立相关.各组的长期移植物存活率没有差异。5年后，患者的临床虚弱量表和WHO表现状况随着时间的推移而改善。
结论：ACLF-3患者的5年和10年生存率与对照组没有差异。5年患者的生存率高于定义肝移植效用的50％-70％的阈值。应根据合并症以及预防作为主要死亡原因的感染和心血管事件来选择候选人。
虽然已知最严重的肝硬化患者（ACLF-3）肝移植后的短期结果，长期数据有限，在医疗资源稀缺的情况下，对移植分配的效用提出了质疑。这项研究提供了一个有利的长期更新，确认与匹配的ACLF-2，ACLF-1和无ACLF患者相比，ACLF-3患者肝移植后5年和10年患者和移植物存活率没有差异。该研究强调了长期死于感染和心血管原因的风险，并确定了包括合并症评估在内的分数。如年龄调整后的Charlson合并症指数，与长期生存独立相关。因此,医师在决定对这些患者进行移植时,应考虑共病的累积负担.此外,移植后,该研究鼓励通过量身定制的免疫抑制方案降低感染风险,并随着时间的推移严格控制心血管风险.
