Background & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) imposes significant healthcare burdens. Early detection of advanced fibrosis and cirrhosis in MASLD is essential due to their unfavourable outcomes. This multi-level random-effects meta-analysis aimed to provide the best evidence for the diagnostic accuracy of two-dimensional shear wave elastography (2D-SWE) in detecting liver fibrosis in biopsy-proven MASLD. Approach & Results: Systematic search in PubMed/MEDLINE, Embase, Scopus, Web of Science, LILACS, and Cochrane Library electronic databases for full-text articles published in any language up to the 26^th of February 2024. Included studies reported liver stiffness measurement (LSM) by 2D-SWE and used histological diagnosis as gold standard. A linear mixed-effects multiple thresholds model was employed, and summary estimates for sensitivity (Se), specificity (Sp), and summary area under the curve (sAUC) were computed. 20 observational studies (SuperSonic Imagine, General Electric Healthcare, Canon Medical Systems) fulfilled the inclusion criteria, comprising 2223 participants with biopsy-proven MASLD. The prevalence of mild fibrosis (F1), significant fibrosis (F2), advanced fibrosis (F3), and cirrhosis (F4) was 30.0%, 18.5%, 17.9%, and 10.9%, respectively. The sAUCs [95%CI] in detecting ≥F1, ≥F2, ≥F3, and F4 for all ultrasound machines considered together were 0.82 [0.16-0.98], 0.82 [0.76-0.88], 0.86 [0.77-0.93], and 0.89 [0.80-0.95], respectively. The optimal cut-off values were 6.432 kPa for ≥F1, 8.174 kPa for ≥F2, 9.418 kPa for ≥F3, and 11.548 kPa for F4, respectively. Conclusions: Our meta-analysis identified optimised cut-offs for fibrosis staging by 2D-SWE in etiology-specific chronic liver diseases (MASLD), with excellent diagnostic performance, underscoring the potential for standardising cut-off values. Export

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.

In recent decades, following the spread of obesity, metabolic dysfunction has come to represent the leading cause of liver disease. The classical clinical presentation of the cirrhotic patient has, therefore, greatly changed, with a dramatic increase in subjects who appear overweight or obese. Due to an obesogenic lifestyle (lack of physical activity and overall malnutrition, with an excess of caloric intake together with a deficit of proteins and micronutrients), these patients frequently develop a complex clinical condition defined as sarcopenic obesity (SO). The interplay between cirrhosis and SO lies in the sharing of multiple pathogenetic mechanisms, including malnutrition/malabsorption, chronic inflammation, hyperammonemia and insulin resistance. The presence of SO worsens the outcome of cirrhotic patients, affecting overall morbidity and mortality. International nutrition and liver diseases societies strongly agree on recommending the use of food as an integral part of the healing process in the comprehensive management of these patients, including a reduction in caloric intake, protein and micronutrient supplementation and sodium restriction. Based on the pathophysiological paths shared by cirrhosis and SO, this narrative review aims to highlight the nutritional interventions currently advocated by international guidelines, as well as to provide hints on the possible role of micronutrients and nutraceuticals in the treatment of this multifaceted clinical condition.

The role of moderate alcohol consumption in the evolution of NAFLD is still debated. The aim of this study is to evaluate the impact of current and lifelong alcohol consumption in patients with NAFLD. From 2015 to 2020, we enrolled 276 consecutive patients fulfilling criteria of NAFLD (alcohol consumption up to 140 g/week for women and 210 g/week for men). According to their current alcohol intake per week, patients were divided in: abstainers, very low consumers (C1: <70 g/week) and moderate consumers (C2). We created a new tool, called LACU (Lifetime Alcohol Consuming Unit) to estimate the alcohol exposure across lifetime: 1 LACU was defined as 7 alcohol units per week for 1 drinking year. Patients were divided into lifelong abstainers and consumers and the latter furtherly divided into quartiles: Q1-Q4. Stratification according to alcohol intake, both current and cumulative as estimated by LACU, showed that very low consumers (C1 and Q1-Q3) displayed lower frequency of cirrhosis and hepatocellular carcinoma compared to abstainers and moderate consumers (C2 and Q4). We can speculate that up to one glass of wine daily in the context of a Mediterranean diet may be a long-term useful approach in selected NAFLD patients.

Background: Non-alcoholic fatty liver disease (NAFLD) is a global epidemic involving 20-40% of the general population. NAFLD is rapidly becoming the leading cause of hepatocellular carcinoma (HCC) worldwide. Knowledge about NAFLD-HCC peculiar features is needed to understand this emerging disease better. Objective: To review the current literature about the epidemiological, pathogenic and clinical features characterising the NAFLD and distinguishing it from HCC of other etiologies. Methods: A systematic review of the literature (PubMed and Medline) using the following string ("Non-alcoholic Fatty Liver Disease"[Mesh] and "Carcinoma, Hepatocellular"[Mesh]). Particular relevance was given to papers published in the last five years as well as previously published manuscript very relevant to this topic according to the experience of the authors. Results: A total of 244 original papers in humans in English literature were analysed. Inherent difficulties in the identification of high-risk subjects and the possibility of occurrence in non-cirrhotic livers are peculiar characteristics of NAFLD-HCC hampering surveillance programs. The consequently delayed diagnosis limits access to surgical procedures and impacts on survival. After correction for tumour burden, however, the survival is not different from that of viral HCC, suggesting that NAFLD-HCC is not intrinsically a more aggressive malignancy. Conclusions: A great deal of effort is needed to improve the clinical outcome of NAFLD-HCC, especially in terms of prevention, surveillance protocols, and identification of drug modifying the natural history of the underlying liver disease. The outcome of these efforts will significantly impact global HCC-related costs and mortality.