用于肝硬化中肝细胞癌风险分层的PAaM的3期验证
Phase 3 Validation of PAaM for Hepatocellular Carcinoma Risk Stratification in Cirrhosis.
作者信息
Fujiwara Naoto, Lopez Camden, Marsh Tracey L, Raman Indu, Marquez Cesia A, Paul Subhojit, Mishra Sumit K, Kubota Naoto, Katz Courtney, Kanzaki Hiroaki, Gonzalez Michael, Quirk Lisa, Deodhar Sneha, Selvakumar Pratibha, Raj Prithvi, Parikh Neehar D, Roberts Lewis R, Schwartz Myron E, Nguyen Mindie H, Befeler Alex S, Page-Lester Stephanie, Srivastava Sudhir, Feng Ziding, Reddy K Rajender, Khaderi Saira, Asrani Sumeet K, Kanwal Fasiha, El-Serag Hashem B, Marrero Jorge A, Singal Amit G, Hoshida Yujin
机构信息
Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Gastroenterology and Hepatology, Graduate School of Medicine, Mie University, Mie, Japan.
Biostatistics Program, Public Health Science Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
出版信息
Gastroenterology. 2025 Mar;168(3):556-567.e7. doi: 10.1053/j.gastro.2024.10.035. Epub 2024 Nov 8.
BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) risk stratification is an urgent unmet need for cost-effective HCC screening and early detection in patients with cirrhosis to improve poor HCC prognosis.
METHODS
Molecular (prognostic liver secretome signature with α-fetoprotein) and clinical (aMAP [age, male sex, albumin-bilirubin, and platelets] score) variable-based scores were integrated into PAaM (prognostic liver secretome signature with α-fetoprotein plus age, male sex, albumin-bilirubin, and platelets), which was subsequently validated in 2 phase 3 biomarker validation studies: the statewide Texas HCC Consortium and nationwide HCC Early Detection Strategy prospective cohorts, following the prospective specimen collection, retrospective blinded evaluation design. The associations between baseline PAaM and incident HCC were assessed using Fine-Gray regression, with overall death and liver transplantation as competing events.
RESULTS
Of 2156 patients with cirrhosis in the Texas HCC Consortium, PAaM identified 404 (19%) high-risk, 903 (42%) intermediate-risk, and 849 (39%) low-risk patients with annual HCC incidence rates of 5.3%, 2.7%, and 0.6%, respectively. Compared with low-risk patients, high- and intermediate-risk groups had sub-distribution hazard ratios for incident HCC of 7.51 (95% CI, 4.42-12.8) and 4.20 (95% CI, 2.52-7.01), respectively. Of 1328 patients with cirrhosis in the HCC early detection strategy, PAaM identified 201 high-risk (15%), 540 intermediate-risk (41%), and 587 low-risk (44%) patients, with annual HCC incidence rates of 6.2%, 1.8%, and 0.8%, respectively. High- and intermediate-risk groups were associated with sub-distribution hazard ratios for incident HCC of 6.54 (95% CI, 3.85-11.1) and 1.77 (95% CI, 1.02-3.08), respectively. Subgroup analysis showed robust risk stratification across HCC etiologies, including metabolic dysfunction-associated steatotic liver disease and cured hepatitis C infection.
CONCLUSIONS
PAaM enables accurate HCC risk stratification in patients with cirrhosis from contemporary etiologies.
背景与目的
肝细胞癌（HCC）风险分层对于肝硬化患者进行具有成本效益的HCC筛查和早期检测以改善HCC不良预后而言，是一项迫切未得到满足的需求。
方法
将基于分子（α-甲胎蛋白预后性肝脏分泌组特征）和临床（aMAP[年龄、男性、白蛋白-胆红素和血小板]评分）变量的评分整合到PAaM（α-甲胎蛋白预后性肝脏分泌组特征加年龄、男性、白蛋白-胆红素和血小板）中，随后在两项3期生物标志物验证研究中进行验证：全州范围的德克萨斯HCC联盟和全国范围的HCC早期检测策略前瞻性队列，采用前瞻性标本收集、回顾性盲法评估设计。使用Fine-Gray回归评估基线PAaM与HCC发生之间的关联，将全因死亡和肝移植作为竞争事件。
结果
在德克萨斯HCC联盟的2156例肝硬化患者中，PAaM识别出404例（19%）高危、903例（42%）中危和849例（39%）低危患者，HCC年发病率分别为5.3%、2.7%和0.6%。与低危患者相比，高危和中危组发生HCC的亚分布风险比分别为7.51（95%CI，4.42 - 12.8）和4.20（95%CI，2.52 - 7.01）。在HCC早期检测策略的1328例肝硬化患者中，PAaM识别出201例（15%）高危、540例（41%）中危和587例（44%）低危患者，HCC年发病率分别为6.2%、1.8%和0.8%。高危和中危组发生HCC的亚分布风险比分别为6.54（95%CI，3.85 - 11.1）和1.77（95%CI，1.02 - 3.08）。亚组分析显示，在包括代谢功能障碍相关脂肪性肝病和治愈的丙型肝炎感染在内的各种HCC病因中，PAaM均具有强大的风险分层能力。
结论
PAaM能够对当代病因所致肝硬化患者进行准确的HCC风险分层。
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