Non-Alcoholic Steatohepatitis (NASH) is a common cause of chronic liver disease, and the degree of liver fibrosis is an important factor determining its clinical prognosis. Lifestyle intervention is the cornerstone of NASH treatment and can improve liver fibrosis. However, the specific effects of lifestyle intervention on micro-level liver fibrosis reversal are not clear. Dr. Minghua Zheng’s team at the First Affiliated Hospital of Wenzhou Medical University used quantitative digital pathology technology qFibrosis to assess liver fibrosis characteristics in depth and explore the impact of the intensity of lifestyle intervention on NASH fibrosis. The relevant results were selected for poster presentation at the 58th Annual Meeting of the European Association for the Study of the Liver (EASL2023) and the 2023 EASL Congress.
Using Second Harmonic Generation/Two-Photon Excitation Fluorescence (SHG/TPEF) imaging microscopy, combined with artificial intelligence algorithms, fibrosis characteristics were continuously and automatically quantitatively assessed. qFibrosis is the overall output parameter obtained through AI analysis, quantifying the overall level of fibrosis in liver biopsy samples, including parameters such as the length, width, and area of collagen fibers in different liver lobules (portal tract, periportal, Zone 2, central vein, peri-central vein). Professor Zheng’s team examined 72 liver biopsy samples from NASH patients who received routine lifestyle intervention (RLI, n=24) or intensified lifestyle intervention (SLI, n=12) before and after the intervention. Statistical analysis was performed on qFibrosis, clinical, and biochemical characteristics of the RLI and SLI groups.
As shown in the figure below, the proportions of fibrosis reversal in the RLI and SLI groups were 21% (5/24) and 50% (6/12), respectively. In both groups, 50% of patients showed no change in fibrosis. Numerical analysis revealed that after lifestyle intervention, fibrosis progression in NASH patients tended to stagnate or improve, with a more pronounced effect in the SLI group.
In-depth analysis of NASH patients with no change or reversal of fibrosis based on routine pathology was conducted using qFibrosis technology (table). In patients with routine pathological fibrosis reversal, the SLI group showed significantly reduced fibrosis parameters in the portal tract (PT), central vein (CV), and peri-central vein (peri-CV) regions compared to the RLI group (P<0.001), while fibrosis parameters in Zone 2 of the periportal region increased (P<0.001). In patients with routine pathological fibrosis stability, the SLI group showed a significant reduction in fibrosis parameters in Zone 2 of the periportal region compared to the RLI group (P<0.001).
In conclusion,Fibrosis reversal in NASH patients is more pronounced with intensified lifestyle intervention, especially in the portal tract and central vein regions. qFibrosis provides new insights into fibrosis reversal induced by lifestyle intervention, which cannot be captured by the current fibrosis staging systems.
Researchers’ Remarks
With the improvement of people’s living standards, the prevalence of NASH is increasing year by year, and awareness of the disease is growing both domestically and internationally. The development of new drugs for NASH is progressing rapidly. To date, no suitable new drugs have been approved. Therefore, lifestyle intervention for NASH patients, such as scientifically guided dietary advice provided by doctors, can play a significant role. “Control your diet, get moving” is crucial for people’s health.
qFibrosis, as a novel pathological assessment tool, is based on Second Harmonic/Two-Photon Excitation Fluorescence imaging technology. It does not require staining of tissue samples and combines digital pathology with artificial intelligence. Compared to semi-quantitative traditional pathological assessment, it can quantitatively capture collagen protein morphology characteristics in different areas of liver tissue, with higher repeatability and reproducibility. Due to its quantitative, accurate, and repeatable advantages, this technology has been applied and validated in various liver diseases both domestically and internationally, such as viral liver diseases like HBV and HCV, as well as NASH. It has gained wide recognition, being used to verify drug efficacy in multiple retrospective or prospective Phase II and III clinical trials, helping to determine inclusion criteria. It has even been announced by the U.S. FDA for use as the sole primary endpoint in NASH Phase IIb clinical trials. We hope that qFibrosis technology will continue to make greater contributions to liver disease research.
In addition, due to the relatively small sample size and single-center nature of the current study, we will further solidify the sample size and representativeness in collaboration with Professor You Hong’s team at Beijing Friendship Hospital, Affiliated with Capital Medical University. The related research results will be presented at the European Fatty Liver Summit in September this year.
Zheng Minghua is the Chief Physician, Professor, and Ph.D. supervisor of the Liver Disease Center of the First Affiliated Hospital of Wenzhou Medical University.
Tag: EASL2023,Vioce of China,NASH
