Special Interview with Prof. Ralf Weiskirchen, RWTH Aachen University Hospital

Hepatoma Research recently had the pleasure of interviewing Prof. Ralf Weiskirchen from the Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH Aachen University Hospital, Germany. As an internationally recognized expert in liver fibrosis and molecular hepatology, Prof. Weiskirchen shared his perspectives on the rapidly evolving understanding of liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD/MASH), the mechanisms linking fibrosis to hepatocellular carcinoma (HCC), and the emerging research directions that may shape the future of fibrosis diagnosis and therapy.

During the interview, Prof. Weiskirchen emphasized that liver fibrosis should no longer be regarded simply as the accumulation of extracellular matrix during chronic liver injury. Instead, fibrosis is now understood as a highly dynamic and biologically regulated process involving extensive interactions among hepatocytes, hepatic stellate cells, macrophages, endothelial cells, cholangiocytes, immune cells, and numerous signaling molecules. In MASLD/MASH, metabolic stress, insulin resistance, oxidative stress, mitochondrial dysfunction, and chronic inflammation collectively drive fibrosis progression, while individual patients may experience markedly different disease trajectories. He further highlighted that the extracellular matrix itself actively regulates cell signaling, immune responses, and tissue remodeling, fundamentally changing current concepts of fibrosis biology, biomarker development, and therapeutic intervention.

Discussing the relationship between liver fibrosis and hepatocellular carcinoma, Prof. Weiskirchen explained that fibrosis actively creates a microenvironment favorable for carcinogenesis rather than merely reflecting previous liver injury. Chronic inflammation, extracellular matrix remodeling, activated hepatic stellate cells, altered tissue stiffness, immune dysregulation, and continuous hepatocyte regeneration collectively establish a fibrotic niche that promotes malignant transformation and tumor progression. He noted that understanding this complex interaction between fibrosis and cancer development may provide valuable opportunities for identifying biomarkers for HCC risk prediction and discovering novel therapeutic targets capable of modifying both the tumor and its surrounding microenvironment.

Prof. Weiskirchen also introduced several research directions currently pursued by his laboratory. His team focuses on understanding the molecular mechanisms regulating hepatic stellate cell activation, persistence, and inactivation, aiming to distinguish pathological fibrogenesis from physiological wound healing. He highlighted the importance of identifying molecular switches capable of promoting fibrosis resolution and healthy tissue remodeling, an approach with considerable translational potential for patients already presenting with established fibrosis. In parallel, his group is actively developing novel biomarkers - including circulating proteins, extracellular matrix remodeling products, extracellular vesicles, non-coding RNAs, imaging-derived parameters, and multi-marker approaches - to enable dynamic monitoring of fibrosis activity rather than relying solely on static fibrosis staging.

Looking toward the future, Prof. Weiskirchen identified several priorities that are expected to transform liver fibrosis research over the coming years. These include the development of reliable non-invasive diagnostic strategies integrating serum biomarkers, imaging technologies, digital pathology, genetics, and artificial intelligence; the advancement of personalized combination therapies targeting metabolism, inflammation, fibrosis, and the gut-liver axis; deeper investigation into fibrosis regression and tissue repair; and improved prediction of HCC risk among patients with MASLD/MASH. He further emphasized that meaningful progress will require close integration of basic science, clinical research, multi-omics technologies, computational biology, and multidisciplinary collaboration to accelerate the translation of mechanistic discoveries into clinical practice.

We sincerely thank Prof. Weiskirchen for sharing his valuable expertise and forward-looking perspectives. His insights into liver fibrosis, MASLD/MASH, hepatocarcinogenesis, biomarker development, and translational research provide important guidance for advancing precision hepatology and improving clinical management of chronic liver diseases. We look forward to continuing our collaboration with Prof. Weiskirchen to promote high-quality research and international academic exchange in liver fibrosis and liver cancer.

Interview Question

Q1. In recent years, our understanding of liver fibrosis in the context of MASLD/MASH has been evolving rapidly. From your perspective, what has been the most important change in our understanding of the development and progression of liver fibrosis?
Q2. There has been growing interest in how chronic fibrosis creates a microenvironment that promotes hepatocarcinogenesis. In your view, what is the key biological link between liver fibrosis and the development of hepatocellular carcinoma?
Q3. Your research group has made important contributions to liver fibrosis research. Which current research directions or emerging technologies do you believe have the greatest potential to advance the field and ultimately improve patient care?
Q4. Looking ahead, what do you think will be the most important developments in liver fibrosis and MASLD/MASH research over the next several years?
Q5. Given the remarkable complexity of fibrotic niches and the heterogeneous responses observed among patients, do you see artificial intelligence and machine learning playing a meaningful role in liver fibrosis research and precision medicine in the future?

About the Interviewee:

Editor: Vivienne Yan
Production Editor: Xingyue Luo
Respectfully Submitted by the Editorial Office of Hepatoma Research