Metformin is a highly effective medication for managing type 2 diabetes mellitus. Recent studies have shown that it has significant therapeutic benefits in various organ systems, particularly the liver. Although the effects of metformin on metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis are still being debated, it has positive effects on cirrhosis and anti-tumoral properties, which can help prevent the development of hepatocellular carcinoma. Furthermore, it has been proven to improve insulin resistance and dyslipidaemia, commonly associated with liver diseases. While more studies are needed to fully determine the safety and effectiveness of metformin use in liver diseases, the results are highly promising. Indeed, metformin has a terrific potential for extending its full therapeutic properties beyond its traditional use in managing diabetes.

Sarcopenia is associated with increased morbidity and mortality in patients with cirrhosis, but its definition in current literature is very heterogeneous. We performed a systematic review and meta-analysis to assess the association between mortality and sarcopenia evaluated by computed tomography (CT) in patients with cirrhosis, both overall and stratified for the criteria used to define sarcopenia. Medline, Embase, Scopus, and Cochrane Library were searched up to January 2023. We included studies assessing sarcopenia presence with CT scans and providing data on the risk of mortality. Adjusted hazard ratios (HRs) and 95% CIs were pooled using a random-effects model. Thirty-nine studies comprising 12,827 patients were included in the meta-analysis. The summary prevalence of sarcopenia was 44% (95% CI 38-50%). The presence of sarcopenia (any definition) was an independent predictor of mortality with an adjusted HR of 2.07 (95% CI 1.81-2.36), and the result was consistent in all subgroup analyses. The prognostic role of the EASL/AASLD criteria was confirmed for the first time with an HR of 1.86 (95% CI 1.53-2.26) (n = 14 studies). The cut-offs used to define sarcopenia based on psoas muscle parameters varied among studies, thus, a subgroup analysis was not feasible. There was no substantial heterogeneity for the main estimates and no significant risk of publication bias. Sarcopenia on CT is associated with a 2-fold higher risk of mortality in patients with cirrhosis. The cut-offs proposed by EASL/AASLD are prognostically relevant and should be the recommended criteria used to define sarcopenia in clinical practice. Sarcopenia assessed by the reference standard (computed tomography scan) is an independent predictor of mortality in patients with cirrhosis, with a 2-fold increase in the risk of death in all sensitivity analyses. This finding is particularly valid in patients from Europe and North America, and in transplant candidates. Stratifying for the parameters and cut-offs used, we confirmed for the first time the prognostic impact of the definition proposed by EASL/AASLD, supporting their use in clinical practice. Psoas muscle assessment is promising, but data are still limited and too heterogeneous to recommend its routine use at present.

Chronic liver disease (CLD), including non-alcoholic fatty liver disease (NAFLD) and its advanced form, non-alcoholic steatohepatitis (NASH), affects a significant portion of the population worldwide. NAFLD is characterised by fat accumulation in the liver, while NASH is associated with inflammation and liver damage. Osteosarcopenia, which combines muscle and bone mass loss, is an emerging clinical problem in chronic liver disease that is often underappreciated. The reductions in muscle and bone mass share several common pathophysiological pathways; insulin resistance and chronic systemic inflammation are the most crucial predisposing factors and are related to the presence and gravity of NAFLD and to the worsening of the outcome of liver disease. This article explores the relationship between osteosarcopenia and NAFLD/MAFLD, focusing on the diagnosis, prevention and treatment of this condition in patients with CLD.

Gut microbiota has become an area of increasing interest for its potential role in metabolic dysfunction-associated steatotic liver disease (MASLD) and its more advanced form, metabolic dysfunction-associated steatohepatitis (MASH)—now recognized as the most frequent liver disease worldwide. Research suggests that imbalances in the intestinal microbiota, including dysbiosis and increased intestinal permeability, may contribute to the pathogenesis of MASLD and progression to MASH. These changes affect insulin resistance and trigger inflammatory responses by disrupting the gut–liver axis. This review examined the current evidence connecting gut microbiota to MASLD and MASH, exploring how microbial shifts might influence liver health. Emerging strategies—such as probiotics, prebiotics, and targeted dietary changes—that may help prevent or manage these conditions are also discussed. Finally, key areas where further studies are required to understand the role of microbiota and its therapeutic potential are highlighted.

Metabolic dysfunction-associated steatotic liver disease (MASLD)—and its worse form, metabolic-associated steatohepatitis (MASH), characterised by inflammation and liver damage—corresponds to the liver’s involvement in metabolic syndrome, which constitutes an economic burden for healthcare systems. However, the biomolecular pathways that contribute to steatotic liver disease are not completely clear. Abnormalities of bone metabolism are frequent in people affected by metabolic liver disease, with reduced bone density and an increased risk of fracture. Receptor activator of NF-κB (RANK), receptor activator of NF-κB ligand (RANKL), and osteoprotegerin(OPG) are critical regulators of bone metabolism, performing pleiotropic effects, and may have potential involvement in metabolic disorders like MASLD, resulting in a topic of great interest and intrigue. This narrative review aims to investigate this potential role and its implications in MASLD development and progression and in hepatocellular carcinoma, which represents its worst complication.

Introduction: Liraglutide 3.0 mg, a glucagon-like peptide-1 (GLP-1) analogue, is a medication approved for obesity treatment. This study aimed to investigate the relationship between psychiatric symptoms, including depression, anxiety, and binge eating, and their impact on therapy adherence. Methods: A clinical audit was carried out on a cohort of 54 adults with obesity treated with liraglutide 3.0 mg. We retrospectively analyzed the connection between psychiatric symptoms assessed through the State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and Binge Eating Scale (BES). Adherence to therapy was assessed by the maximum dosage (MD) and treatment duration (TD). Results: Notably, a discontinuation rate of 59% was encountered. However, among those who continued the treatment, we observed a negative association between anxiety symptoms (STAI score) and MD, depression symptoms (BDI score) and TD, and a higher likelihood of binge eating (BES score > 17) and TD. Moreover, presence of psychiatric symptoms did not compromise drug's effectiveness in achieving weight loss, which was 4.43% (± 5.5 SD) in the whole sample and 5.3% (± 6.3 SD) in the subgroup evaluated at 12 weeks. Conclusion: We observed a high discontinuation rate in real-life clinical setting, where Liraglutide 3.0 therapy is paid out-of-pocket. While psychiatric symptoms might play a role in diminishing adherence to therapy, they do not prevent drug's effectiveness to promote weight loss. This finding underscores the potential advantages of liraglutide 3.0 mg therapy for individuals contending with obesity while simultaneously managing mental health challenges. Level of evidence: Level V, descriptive studies.