Tanaka Tomohiro, Roberts Emily K, Platt Jonathan
Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
Department of Health Management and Policy, College of Public Health, University of Iowa, Iowa City, Iowa, USA.
Hepatol Commun. 2025 Feb 19;9(3). doi: 10.1097/HC9.0000000000000651. eCollection 2025 Mar 1.
Prior studies show severe acute-on-chronic liver failure (ACLF) at liver transplantation (LT) negatively impacts short-term, but not long-term, post-LT outcomes. However, not accounting for ACLF's time-varying effect on the waitlist may underappreciate its dynamic nature. Moreover, excluding those who died or dropped off the waitlist raises concerns about selection bias.
This US nationwide retrospective cohort study estimated the effect of severe ACLF (grade 3) (ACLF-3) on post-LT outcomes, including adult, first-time deceased donor LT candidates listed from June 2013 to May 2023. A marginal structural model (MSM) to address selection bias and time-varying exposure (ACLF-3) was applied, with extended Cox proportional hazard models using a Heaviside step function to assess the hazard of death after LT.
Among 31,267 eligible candidates for LT (baseline cohort), 11.3% (n = 3518) had ACLF-3 at listing; 13.6% (n = 4243) died or dropped out while on the LT waitlist. Of the 27,024 patients who received LT (transplanted cohort), 12.3% (n = 3333) had ACLF-3 at LT. ACLF-3 at LT (but not at waitlisting) was associated with a higher hazard of death, with the hazard ratio of 1.80 (95% CI: 1.09-2.97) within 1 year after LT but not thereafter. This marginal structural model effect size was 9% higher than conventional multivariable Cox proportional hazard models. Sensitivity analyses corroborated these findings.
Compared to previous studies, ACLF-3 at LT in our marginal structural model was associated with a discernible increase in short-term mortality after transplant, presumably due to our addressing of selection bias, while long-term survival was similar to those without severe ACLF at LT. However, potential vulnerability to posttransplant complications warrants further investigation.
先前的研究表明，肝移植（LT）时的严重急性慢性肝衰竭（ACLF）对LT后的短期结局有负面影响，但对长期结局无影响。然而，未考虑ACLF对等待名单的时变效应可能会低估其动态性质。此外，排除那些在等待名单上死亡或退出的人会引发对选择偏倚的担忧。
这项美国全国性回顾性队列研究估计了严重ACLF（3级）（ACLF-3）对LT后结局的影响，研究对象包括2013年6月至2023年5月登记在册的成年首次接受已故捐赠者LT的候选人。应用边际结构模型（MSM）来解决选择偏倚和时变暴露（ACLF-3），并使用Heaviside阶跃函数的扩展Cox比例风险模型来评估LT后死亡风险。
在31267名符合LT条件的候选人（基线队列）中，11.3%（n = 3518）在登记时患有ACLF-3；13.6%（n = 4243）在LT等待名单上死亡或退出。在27024名接受LT的患者（移植队列）中，12.3%（n = 3333）在LT时患有ACLF-3。LT时（而非登记时）的ACLF-3与更高的死亡风险相关，LT后1年内的风险比为1.80（95%CI：1.09-2.97），之后则无此关联。这种边际结构模型效应大小比传统多变量Cox比例风险模型高9%。敏感性分析证实了这些发现。
与先前的研究相比，我们的边际结构模型中LT时的ACLF-3与移植后短期死亡率的显著增加相关，这可能是由于我们解决了选择偏倚问题，而长期生存率与LT时无严重ACLF的患者相似。然而，移植后并发症的潜在易感性值得进一步研究。
