Regular exercise is fundamental for people with metabolic dysfunction-associated steatotic liver disease (MASLD), yet exercise maintenance is generally poor. This generative co-design process aimed to embed the voices and opinions of people with lived experience of MASLD and their care stakeholders to (i) frame barriers and enablers to exercise maintenance and (ii) highlight priorities for exercise-focused research agendas in MASLD.

A generative co-design framework was applied. Two virtual co-design sessions were undertaken: Session 1 – Framing the issue, where initial discovery was conducted with people with lived experience of MASLD; and Session 2 – Generative design and sharing ideas with lived experience partners and healthcare stakeholders. Sessions were audio-recorded and transcribed, and key determinants and considerations were discerned by two independent researchers.

Lived experience partners (n = 5, 53 ± 16 years, 40% male) ranked five equally important barriers to exercise maintenance: musculoskeletal and pain issues, lack of access to exercise equipment/facilities, cost, competing priorities, and low energy levels, which influenced core positive and negative determinants. Alongside lived experience partners, healthcare stakeholders (hepatologists [n = 3], exercise professionals [n = 3], 67% male) identified three core needs with eight considerations. Some disconnects in priorities were observed. Lived experience partners emphasized affordability, accessibility, and considerations for comorbidities, while healthcare partners advocated for research on natural history, prevention, behavior change, cost-effectiveness, and health system change.

This co-design methodology highlights unique consumer-informed research questions. Exercise interventions and their associated implementation trials will benefit from being co-designed with both people with MASLD and care stakeholders.

The gut microbiota is crucial in maintaining host health and liver function. Fecal microbiota transplantation (FMT) has shown promising potential in treating chronic liver diseases. To help clinicians quickly master and standardize the clinical application of FMT for chronic liver disease, the Liver Related Digestive Diseases Group of the Chinese Society of Hepatology of the Chinese Medical Association has developed the “Expert Consensus on the Clinical Application of FMT for Chronic Liver Disease.” This consensus addresses the key aspects of FMT, including the indications, contraindications, efficacy, safety, donor selection, transplantation routes, precautions, and the prevention and management of adverse reactions for chronic liver conditions, such as chronic hepatitis, cirrhosis, and liver cancer, thereby offering reference and guidance to clinicians implementing FMT in the treatment of chronic liver disease.

Familial hypobetalipoproteinemia (FHBL), caused by apolipoprotein B (APOB) variants, disrupts APOB-containing lipoprotein synthesis, leading to reduced serum total cholesterol, low-density lipoprotein cholesterol, and APOB. Heterozygous carriers are often asymptomatic, while homozygotes exhibit severe manifestations like malabsorption, vitamin deficiencies, and hepatic steatosis. In recent years, FHBL has attracted increasing attention due to its association with liver disease and its role as a unique monogenic model of steatotic liver disease independent of cardiometabolic risk factors. Mechanistically, lipid overload, endoplasmic reticulum stress, oxidative damage, and impaired autophagy may drive hepatocellular injury and fibrosis. Challenges include insufficient diagnosis, sparse epidemiological data, and unclear disease progression. Enhanced genetic testing, mechanistic research, and longitudinal studies are critical to improving diagnosis, risk assessment, and therapies for FHBL-associated liver disease.

Metabolic dysfunction-associated steatohepatitis (MASH) represents a critical step in the progression from simple fatty liver disease to more severe conditions such as cirrhosis and hepatocellular carcinoma, and it remains difficult to treat. Arctigenin (ATG), a monomer of Fructus Arctii, exhibits anti-inflammatory activity. Therefore, we aimed to examine its potential protective role against MASH and explore the underlying mechanisms.

Male C57BL/6 mice were divided into four groups: control, MASH, low-dose ATG (30 mg/kg/day), and high-dose ATG (120 mg/kg/day). MASH was induced through a choline-deficient, L-amino acid-defined high-fat diet for eight weeks, with concurrent preventive ATG administration. Liver injury, lipid metabolism, inflammation, oxidative stress, and fibrosis were assessed. Network pharmacology was employed to identify the potential protective mechanisms of ATG. Key factors were evaluated in vitro to verify the ATG targets.

ATG administration prevented the progression of MASH in a dose-dependent manner. High-dose ATG significantly reduced hepatic macrophage and neutrophil infiltration, serum enzyme levels, and lipid peroxidation, while enhancing antioxidant enzyme activity. Mechanistic network pharmacology identified modulation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome as the central pathway underlying ATG’s bioactivity. Functional analyses in lipopolysaccharide-stimulated RAW264.7 cells confirmed that ATG inhibited NLRP3 expression, pyroptosis-related protein cleavage (hereinafter referred to as GSDMD-N), and pro-inflammatory chemokine production in a concentration-dependent manner. Notably, ATG disrupted NLRP3/GSDMD-N axis activity in macrophages without causing cellular toxicity.

ATG may inhibit the inflammatory cascade primarily by targeting macrophage NLRP3 inflammasomes, thereby preventing the progression of MASH.

Myosteatosis is associated with poor outcomes in various liver diseases. However, standardized methods for assessing, defining, and diagnosing myosteatosis in the context of liver diseases remain unclear. Furthermore, the underlying mechanisms by which myosteatosis leads to pathophysiological progression and adverse health outcomes remain elusive. Therefore, in this review, we elaborate on the currently available measures, definitions, and diagnostic criteria of myosteatosis in the existing literature. We thoroughly clarify the recent evidence and data regarding the possible involvement of myosteatosis in the progression and deterioration of various liver diseases and resulting complications, including liver cirrhosis, chronic viral hepatitis, non-alcoholic/metabolic-associated fatty liver disease, primary sclerosing cholangitis, liver transplantation, and hepatocellular carcinoma. Additionally, it synthesizes insights from basic research on the pathogenesis of myosteatosis, which involves multifactorial mechanisms, including insulin resistance, mitochondrial dysfunction, and chronic inflammation. Finally, from an operational and pragmatic perspective, several regimens, including physical, nutritional, and pharmacological therapies, have been discussed as potential treatments for myosteatosis.