Department of Hepatology and Liver Transplantation, Hospital Universitario Reina Sofía, IMIBIC, Córdoba, Spain; Department of Medicine, University of Córdoba, Córdoba, Spain; Centro de investigación biomédica en red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain.
Department of Computer Science and Numerical Analysis, University of Córdoba, Córdoba, Spain.
Lancet Gastroenterol Hepatol. 2023 Mar;8(3):242-252. doi: 10.1016/S2468-1253(22)00354-5. Epub 2022 Dec 14.
The Model for End-stage Liver Disease (MELD) and its sodium-corrected variant (MELD-Na) have created gender disparities in accessing liver transplantation. We aimed to derive and validate the Gender-Equity Model for liver Allocation (GEMA) and its sodium-corrected variant (GEMA-Na) to amend such inequities.
In this cohort study, the GEMA models were derived by replacing creatinine with the Royal Free Hospital glomerular filtration rate (RFH-GFR) within the MELD and MELD-Na formulas, with re-fitting and re-weighting of each component. The new models were trained and internally validated in adults listed for liver transplantation in the UK (2010-20; UK Transplant Registry) using generalised additive multivariable Cox regression, and externally validated in an Australian cohort (1998-2020; Royal Prince Alfred Hospital [Australian National Liver Transplant Unit] and Austin Hospital [Victorian Liver Transplant Unit]). The study comprised 9320 patients: 5762 patients for model training, 1920 patients for internal validation, and 1638 patients for external validation. The primary outcome was mortality or delisting due to clinical deterioration within the first 90 days from listing. Discrimination was assessed by Harrell's concordance statistic.
449 (5·8%) of 7682 patients in the UK cohort and 87 (5·3%) of 1638 patients in the Australian cohort died or were delisted because of clinical deterioration within 90 days. GEMA showed improved discrimination in predicting mortality or delisting due to clinical deterioration within the first 90 days after waiting list inclusion compared with MELD (Harrell's concordance statistic 0·752 [95% CI 0·700-0·804] vs 0·712 [0·656-0·769]; p=0·001 in the internal validation group and 0·761 [0·703-0·819] vs 0·739 [0·682-0·796]; p=0·036 in the external validation group), and GEMA-Na showed improved discrimination compared with MELD-Na (0·766 [0·715-0·818] vs 0·742 [0·686-0·797]; p=0·0058 in the internal validation group and 0·774 [0·720-0·827] vs 0·745 [0·690-0·800]; p=0·014 in the external validation group). The discrimination capacity of GEMA-Na was higher in women than in the overall population, both in the internal (0·802 [0·716-0·888]) and external validation cohorts (0·796 [0·698-0·895]). In the pooled validation cohorts, GEMA resulted in a score change of at least 2 points compared with MELD in 1878 (52·8%) of 3558 patients (25·0% upgraded and 27·8% downgraded). GEMA-Na resulted in a score change of at least 2 points compared with MELD-Na in 1836 (51·6%) of 3558 patients (32·3% upgraded and 19·3% downgraded). In the whole cohort, 3725 patients received a transplant within 90 days of being listed. Of these patients, 586 (15·7%) would have been differently prioritised by GEMA compared with MELD; 468 (12·6%) patients would have been differently prioritised by GEMA-Na compared with MELD-Na. One in 15 deaths could potentially be avoided by using GEMA instead of MELD and one in 21 deaths could potentially be avoided by using GEMA-Na instead of MELD-Na.
GEMA and GEMA-Na showed improved discrimination and a significant re-classification benefit compared with existing scores, with consistent results in an external validation cohort. Their implementation could save a clinically meaningful number of lives, particularly among women, and could amend current gender inequities in accessing liver transplantation.
Junta de Andalucía and EDRF.
终末期肝病模型（MELD）及其钠校正变体（MELD-Na）导致了获得肝移植的性别差异。我们旨在制定并验证性别公平肝脏分配模型（GEMA）及其钠校正变体（GEMA-Na），以纠正这种不公平。
在这项队列研究中，通过用皇家自由医院肾小球滤过率（RFH-GFR）替代 MELD 和 MELD-Na 公式中的肌酐，对 GEMA 模型进行了推导和验证，同时对每个成分进行了重新拟合和重新加权。新模型通过广义加性多变量 Cox 回归在英国（2010-20 年；英国移植登记处）接受肝移植的成年人名单中进行了训练和内部验证，并在澳大利亚队列（1998-2020 年；皇家阿尔弗雷德王子医院[澳大利亚国家肝移植单位]和奥斯汀医院[维多利亚肝移植单位]）中进行了外部验证。该研究包括 9320 名患者：5762 名用于模型训练，1920 名用于内部验证，1638 名用于外部验证。主要结局是在登记后 90 天内因临床恶化而导致死亡或被取消资格。通过 Harrell 的一致性统计来评估判别能力。
英国队列中 7682 名患者中的 449 名（5.8%）和澳大利亚队列中 1638 名患者中的 87 名（5.3%）在 90 天内因临床恶化而死亡或被取消资格。与 MELD 相比，GEMA 在预测等待名单纳入后 90 天内因临床恶化导致的死亡或取消资格方面显示出更好的判别能力（Harrell 的一致性统计 0.752[95%CI 0.700-0.804] vs 0.712[0.656-0.769]；p=0.001 在内部验证组和 0.761[0.703-0.819] vs 0.739[0.682-0.796]；p=0.036 在外部验证组），而 GEMA-Na 与 MELD-Na 相比显示出更好的判别能力（0.766[0.715-0.818] vs 0.742[0.686-0.797]；p=0.0058 在内部验证组和 0.774[0.720-0.827] vs 0.745[0.690-0.800]；p=0.014 在外部验证组）。GEMA-Na 在女性中的判别能力高于总体人群，无论是内部（0.802[0.716-0.888]）还是外部验证队列（0.796[0.698-0.895]）。在汇总验证队列中，与 MELD 相比，GEMA 在 3558 名患者中的 1878 名（52.8%）中导致评分至少变化 2 分（25.0%升级，27.8%降级）。与 MELD-Na 相比，GEMA-Na 在 3558 名患者中的 1836 名（51.6%）中导致评分至少变化 2 分（32.3%升级，19.3%降级）。在整个队列中，3725 名患者在登记后 90 天内接受了移植。在这些患者中，586 名（15.7%）将通过 GEMA 与 MELD 相比得到不同的优先级；468 名（12.6%）患者将通过 GEMA-Na 与 MELD-Na 相比得到不同的优先级。如果使用 GEMA 而不是 MELD，可以避免 15 分之一的死亡，如果使用 GEMA-Na 而不是 MELD-Na，可以避免 21 分之一的死亡。
GEMA 和 GEMA-Na 与现有评分相比显示出更好的判别能力和显著的重新分类获益，在外部验证队列中得到了一致的结果。它们的实施可以挽救大量具有临床意义的生命，特别是在女性中，并可以纠正目前在获得肝移植方面的性别不平等。
安达卢西亚联合委员会和 EDRF。
