Phase 3 validation of PAaM for hepatocellular carcinoma risk stratification in cirrhosis

IF 25.7 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastroenterology Pub Date : 2024-11-08 DOI:10.1053/j.gastro.2024.10.035

Naoto Fujiwara, Camden Lopez, Tracey L. Marsh, Indu Raman, Cesia A. Marquez, Subhojit Paul, Sumit K. Mishra, Naoto Kubota, Courtney Katz, Hiroaki Kanzaki, Michael Gonzalez, Lisa Quirk, Sneha Deodhar, Pratibha Selvakumar, Prithvi Raj, Neehar D. Parikh, Lewis R. Roberts, Myron E. Schwartz, Mindie H. Nguyen, Alex S. Befeler, Yujin Hoshida

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Abstract

Background and 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 alpha-fetoprotein) and clinical (aMAP score) variable-based scores were integrated to develop PAaM, which was subsequently validated in two phase 3 biomarker validation studies: the statewide Texas HCC Consortium (THCCC) and nationwide HCC Early Detection Strategy (HEDS) prospective cohorts, following the prospective specimen collection, retrospective blinded evaluation (PRoBE) 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 2,156 cirrhosis patients in THCCC, 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 to low-risk patients, high- and intermediate-risk groups had sub-distribution hazard ratios (sHRs) for incident HCC of 7.51 (95% confidence interval [CI], 4.42-12.8) and 4.20 (95%CI, 2.52-7.01), respectively. Of 1,328 cirrhosis patients in HEDS, PAaM identified 201 (15%) high-risk, 540 (41%) intermediate-risk, and 587 (44%) low-risk patients, with annual HCC incidence rates of 6.2%, 1.8%, and 0.8%, respectively. High- and intermediate risk groups were associated with sHRs 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 (MASLD) and cured hepatitis C infection.

Conclusion

PAaM enables accurate HCC risk stratification in patients with cirrhosis from contemporary etiologies.

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PAaM 对肝硬化患者肝细胞癌风险分层的 3 期验证

背景和目的肝细胞癌（HCC）风险分层是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不良预后的一项尚未满足的迫切需求。方法将基于分子（带有甲胎蛋白的预后肝脏分泌组特征）和临床（aMAP评分）变量的评分整合在一起，开发出了PAaM，随后在两项三期生物标记物验证研究中进行了验证：全州范围的德克萨斯州HCC联盟（THCCC）和全国范围的HCC早期检测策略（HEDS）前瞻性队列，采用的是前瞻性标本采集、回顾性盲法评估（PRoBE）设计。结果在THCCC的2156例肝硬化患者中，PAaM发现了404例（19%）高危患者、903例（42%）中危患者和849例（39%）低危患者，其HCC年发病率分别为5.3%、2.7%和0.6%。与低危患者相比，高危和中危组的HCC发病亚分布危险比（sHR）分别为7.51（95%置信区间[CI]，4.42-12.8）和4.20（95%CI，2.52-7.01）。在 HEDS 的 1328 例肝硬化患者中，PAAM 发现了 201 例（15%）高危患者、540 例（41%）中危患者和 587 例（44%）低危患者，其每年的 HCC 发病率分别为 6.2%、1.8% 和 0.8%。高风险组和中度风险组发生 HCC 的 sHR 分别为 6.54（95%CI，3.85-11.1）和 1.77（95%CI，1.02-3.08）。亚组分析表明，不同病因的HCC风险分层效果都很好，包括代谢功能障碍相关性脂肪性肝病（MASLD）和治愈的丙型肝炎感染。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gastroenterology 医学-胃肠肝病学

CiteScore

45.60

自引率

2.40%

发文量

4366

审稿时长

26 days

期刊介绍： Gastroenterology is the most prominent journal in the field of gastrointestinal disease. It is the flagship journal of the American Gastroenterological Association and delivers authoritative coverage of clinical, translational, and basic studies of all aspects of the digestive system, including the liver and pancreas, as well as nutrition. Some regular features of Gastroenterology include original research studies by leading authorities, comprehensive reviews and perspectives on important topics in adult and pediatric gastroenterology and hepatology. The journal also includes features such as editorials, correspondence, and commentaries, as well as special sections like "Mentoring, Education and Training Corner," "Diversity, Equity and Inclusion in GI," "Gastro Digest," "Gastro Curbside Consult," and "Gastro Grand Rounds." Gastroenterology also provides digital media materials such as videos and "GI Rapid Reel" animations. It is abstracted and indexed in various databases including Scopus, Biological Abstracts, Current Contents, Embase, Nutrition Abstracts, Chemical Abstracts, Current Awareness in Biological Sciences, PubMed/Medline, and the Science Citation Index.