首次及进一步失代偿对因代谢相关脂肪性肝病导致的代偿期酒精性肝硬化患者的影响。
Impact of first and further decompensation in patients with compensated ACLD due to MASLD.
作者信息
Pennisi Grazia, Di Maria Gabriele, Wai-Sun Wong Vincent, de Ledinghen Victor, Sebastiani Giada, Viganò Mauro, Fracanzani Anna Ludovica, Miele Luca, Bugianesi Elisabetta, Ekstedt Mattias, D'Ambrosio Roberta, Ravaioli Federico, Schepis Filippo, Marra Fabio, Aghemo Alessio, Svegliati-Baroni Gianluca, Persico Marcello, Valenti Luca, Berzigotti Annalisa, George Jacob, Armandi Angelo, Nasr Patrik, Kechagias Stergios, Liguori Antonio, Saltini Dario, Mendoza Yuly P, Calvaruso Vincenza, Enea Marco, Lin Huapeng, Infantino Giuseppe, Masarone Mario, Pugliese Nicola, Tulone Adele, Di Marco Vito, Cammà Calogero, Petta Salvatore
机构信息
Section of Gastroenterology and Hepatology, Dipartimento Di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE), University of Palermo, Italy.
Dipartimento Di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE), University of Palermo, Italy.
出版信息
J Hepatol. 2025 Jun 21. doi: 10.1016/j.jhep.2025.06.014.
BACKGROUND&AIM: The first and further decompensation mark the natural history and the risk of mortality in patients with cirrhosis. We assessed the cumulative incidence of first and further (acute and non-acute) decompensation and evaluated their impact on liver-related death (LR-D) in patients with compensated advanced chronic liver disease (cACLD) due to metabolic dysfunction-associated steatotic liver disease (MASLD).
METHODS
International multicenter retrospective study (17 centers) on 6,061 consecutive patients with clinical (liver stiffness measurement [LSM] >10 kPa) or biopsy-proven (F3-F4 fibrosis) diagnosis of cACLD due to MASLD. First and further decompensation were defined according to Baveno VII criteria. Competing risk analysis by cumulative incidence functions and Cause-specific Cox models with baseline and time-dependent variables were performed. A multistate model was built to better assess the clinical course of cACLD due to MASLD.
RESULTS
The cumulative incidence of the first decompensation was 3.5% (95% CI 3.0-4.1) at 5 years, increasing 18.9-fold (95% CI 10.8-32.9) the cause-specific hazard of LR-D using Cause-specific Cox model; the cumulative incidence of further decompensation was 43.9% (95% CI 37.2-50.2) at 5 years among patients with first decompensation, additionally increasing 1.52-times (95% CI 1.02-2.34) the cause-specific hazard of LR-D. Ascites, followed by variceal bleeding, were the most common events in both first and further decompensation. Hepatocellular carcinoma (HCC) further independently increased the cause-specific hazard of LR-D by 2.95 (95% CI 2.02-4.31) and 1.43 (95% CI 1.03-2.00) folds in the whole cohort of cACLD due to MASLD and in those who experienced first decompensation, respectively.
CONCLUSIONS
The first and further decompensations represent tipping points in the clinical course of patients with cACLD due to MASLD, increasing 18.9-times and additionally 1.52-times the cause-specific hazard of LR-D. HCC is an independent predictor of LR-D in patients with cACLD due to MASLD, resulting in an additional cause-specific hazard of LR-D when associated with both first and further decompensation.
背景与目的
首次失代偿及后续失代偿标志着肝硬化患者的自然病程及死亡风险。我们评估了首次及后续（急性和非急性）失代偿的累积发生率，并评估了它们对代谢功能障碍相关脂肪性肝病（MASLD）所致代偿期晚期慢性肝病（cACLD）患者肝相关死亡（LR-D）的影响。
方法
对6061例因MASLD导致cACLD且经临床（肝脏硬度测量[LSM]>10 kPa）或活检证实（F3-F4纤维化）的连续患者进行国际多中心回顾性研究（17个中心）。首次及后续失代偿根据巴韦诺VII标准定义。采用累积发生率函数进行竞争风险分析，并使用具有基线和时间依赖性变量的特定病因Cox模型。构建多状态模型以更好地评估MASLD所致cACLD的临床病程。
结果
5年时首次失代偿的累积发生率为3.5%（95%CI 3.0-4.1），使用特定病因Cox模型使LR-D的特定病因风险增加18.9倍（95%CI 为10.8-32.9）；在首次失代偿的患者中，5年时后续失代偿的累积发生率为43.9%（95%CI 37.2-50.2），使LR-D的特定病因风险额外增加1.52倍（95%CI 1.02-2.34）。腹水，其次是静脉曲张出血，是首次及后续失代偿中最常见的事件。在整个MASLD所致cACLD队列以及经历首次失代偿的患者中，肝细胞癌（HCC）分别使LR-D的特定病因风险进一步独立增加2.95倍（95%CI 2.02-4.31）和1.43倍（95%CI 1.03-2.00）。
结论
首次及后续失代偿是MASLD所致cACLD患者临床病程中的转折点，使LR-D的特定病因风险分别增加18.9倍和额外增加1.52倍。HCC是MASLD所致cACLD患者LR-D的独立预测因素，与首次及后续失代偿相关时会导致LR-D额外的特定病因风险。
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