Topic: Novel Molecular Mechanisms and Therapeutic Targets in Metabolic Dysfunction-Associated Steatohepatitis (MASLD): From Bench to Bedside

With population aging and lifestyle changes, the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has been steadily increasing. MASLD is now the most common chronic liver disease worldwide, with a prevalence of up to 80% among individuals with obesity and diabetes. Without effective intervention, MASLD can progress to metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, and eventually hepatocellular carcinoma (HCC). Therefore, there is an urgent need to enhance precise prevention strategies and develop effective treatments for MASLD.

As the body’s central metabolic organ, the liver regulates diverse metabolic processes through intricate networks involving cytokines, adhesion molecules, and cellular interactions. MASLD is closely associated with insulin resistance, abnormal lipid accumulation, inflammatory responses, mitochondrial dysfunction, and oxidative stress. Due to its multifactorial pathogenesis, targeting a single signaling pathway is unlikely to sufficiently halt disease progression. Additionally, clinical trial endpoints for MASLD are often complex and require long-term follow-up, presenting further challenges.

Despite recent advances in MASLD prevention and treatment, significant gaps remain. This Special Issue invites submissions that explore novel molecular mechanisms, clinical studies, and therapeutic potentials for MASLD. We welcome original research articles, reviews, mini-reviews, clinical trials, case reports, commentaries, methodological studies, and perspectives focused on, but not limited to, the following topics:

1. Novel epidemiological findings, molecularmechanisms, and therapeutic targets of MASLD, with particular emphasis on multi-omics integration studies.

2. Molecularmechanisms driving the progression of MASLD to MASH, liver fibrosis, and

3. Clinical characteristics andmolecular mechanisms of MASLD coexisting with other chronic diseases, such as type 2 diabetes mellitus, obesity, and viral hepatitis.

4. Exploration of prospectivenon-invasive diagnostic and prognostic biomarkers for MASLD, especially through multi-omics approaches.

5. Preclinical andclinical cohort studies investigating innovative drugs for MASLD or MASH, such as Resmetirom, Tirzepatide, Semaglutide, and Mazdutide, as well as their molecular mechanisms.

6. Interpretation of the latest treatment guidelines and majorpublic health policies related to MASLD.

7. The role and potential benefitsof gut microbiota modulation and nutritional interventions in MASLD.