用生理机制模拟肝脏健康变化,可预测脂肪肝进展。
A Physiology-Informed Digital Twin Framework for Simulating Liver Health Progression

- 基于肝脏代谢等生理机制构建数字孪生模型
- 在五年内模拟出符合临床特征的生物标志物轨迹
- 适合个性化肝病预警与非侵入式监测研究
我们提出一种生理信息驱动的人类肝脏数字孪生框架HEPATWIN,用于长期模拟肝脏功能及早期疾病进展。该模型整合碳水化合物、脂质和蛋白质代谢、胆红素结合、胆汁生成与解毒等关键肝功能过程,在系统层面生成可临床观测的生物标志物轨迹。不同于纯数据驱动方法,HEPATWIN融合肝脏生理机制与个体化输入(如饮食、活动、基线生物标志物),模拟疾病随时间演变。为确保与临床进展模式一致,引入阶段跃迁驱动的校准机制,使模拟输出匹配不同疾病阶段(如非酒精性脂肪肝、纤维化、肝硬化)的群体生物标志物分布。基于NIDDK NAFLD数据集验证表明,HEPATWIN生成的纵向生物标志物估计值处于临床可接受范围,并可实现多年跨度的轨迹预测。此外,模拟生物标志物仍具备足够临床信号,支持下游NASH检测,性能媲美使用真实实验室数据的模型。结果表明,生理信息驱动的数字孪生在个性化、非侵入式器官健康评估方面具有潜力,尤其适用于肝脏健康监测。
原文摘要 · Abstract (English)
We present a physiology-informed digital twin of the human liver designed for longitudinal simulation of liver function and early-stage disease progression. The model, referred to as HEPATWIN, integrates key hepatic processes, including carbohydrate, lipid, and protein metabolism, bilirubin conjugation, bile production, and detoxification, within a unified systems-level framework to generate clinically observable biomarker trajectories. Unlike purely data-driven approaches, HEPATWIN incorporates mechanistic representations of liver physiology and patient-specific inputs such as diet, activity, and baseline biomarkers to simulate disease evolution over time. To ensure consistency with clinical progression patterns, we introduce a stage-transition-driven calibration mechanism that aligns simulated outputs with population-level biomarker distributions across disease stages, including NAFLD, fibrosis, and cirrhosis. Validation using the NIDDK NAFLD dataset demonstrates that HEPATWIN produces longitudinal biomarker estimates within clinically acceptable ranges and can forecast trajectories over multi-year horizons. Furthermore, simulated biomarkers retain sufficient clinical signal to support downstream NASH detection with competitive performance relative to models using ground-truth laboratory data. These results highlight the potential of physiology-informed digital twins for personalized, non-invasive diagnosis and prediction of organ health in general and liver health monitoring in particular.
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