Yuan Hai-Yang, Tong Xiao-Fei, Ren Ya-Yun, Li Yang-Yang, Wang Xin-Lei, Chen Li-Li, Chen Sui-Dan, Jin Xiao-Zhi, Wang Xiao-Dong, Targher Giovanni, Byrne Christopher D, Wei Lai, Wong Vincent W-S, Tai Dean, Sanyal Arun J, You Hong, Zheng Ming-Hua
MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Liver Research Center, Beijing Friendship Hospital, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Capital Medical University, Beijing, China.
Liver Int. 2024 Oct;44(10):2572-2582. doi: 10.1111/liv.16025. Epub 2024 Jul 4.
Lifestyle intervention is the mainstay of therapy for metabolic dysfunction-associated steatohepatitis (MASH), and liver fibrosis is a key consequence of MASH that predicts adverse clinical outcomes. The placebo response plays a pivotal role in the outcome of MASH clinical trials. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence analyses can provide an automated quantitative assessment of fibrosis features on a continuous scale called qFibrosis. In this exploratory study, we used this approach to gain insight into the effect of lifestyle intervention-induced fibrosis changes in MASH.
We examined unstained sections from paired liver biopsies (baseline and end-of-intervention) from MASH individuals who had received either routine lifestyle intervention (RLI) (n = 35) or strengthened lifestyle intervention (SLI) (n = 17). We quantified liver fibrosis with qFibrosis in the portal tract, periportal, transitional, pericentral, and central vein regions.
About 20% (7/35) and 65% (11/17) of patients had fibrosis regression in the RLI and SLI groups, respectively. Liver fibrosis tended towards no change or regression after each lifestyle intervention, and this phenomenon was more prominent in the SLI group. SLI-induced liver fibrosis regression was concentrated in the periportal region.
Using digital pathology, we could detect a more pronounced fibrosis regression with SLI, mainly in the periportal region. With changes in fibrosis area in the periportal region, we could differentiate RLI and SLI patients in the placebo group in the MASH clinical trial. Digital pathology provides new insight into lifestyle-induced fibrosis regression and placebo responses, which is not captured by conventional histological staging.
生活方式干预是代谢功能障碍相关脂肪性肝炎（MASH）治疗的主要手段，肝纤维化是MASH的关键后果，可预测不良临床结局。安慰剂反应在MASH临床试验结果中起关键作用。具有人工智能分析功能的二次谐波产生/双光子激发荧光（SHG/TPEF）显微镜可以对称为qFibrosis的纤维化特征进行连续尺度的自动定量评估。在这项探索性研究中，我们使用这种方法来深入了解生活方式干预引起的MASH纤维化变化的影响。
我们检查了接受常规生活方式干预（RLI）（n = 35）或强化生活方式干预（SLI）（n = 17）的MASH个体的配对肝活检（基线和干预结束时）的未染色切片。我们在门静脉区、门周区、过渡区、中央周围区和中央静脉区用qFibrosis对肝纤维化进行定量。
RLI组和SLI组分别约有20%（7/35）和65%（11/17）的患者出现纤维化消退。每次生活方式干预后，肝纤维化倾向于无变化或消退，这种现象在SLI组中更为突出。SLI诱导的肝纤维化消退集中在门周区。
使用数字病理学，我们可以检测到SLI导致的更明显的纤维化消退，主要在门周区。根据门周区纤维化面积的变化，我们可以在MASH临床试验的安慰剂组中区分RLI和SLI患者。数字病理学为生活方式诱导的纤维化消退和安慰剂反应提供了新的见解，这是传统组织学分期无法捕捉到的。
