Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition marked by excessive lipid accumulation in hepatic tissue. This disorder can lead to a range of pathological outcomes, including metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. Despite extensive research, the molecular mechanisms driving MASLD initiation and progression remain incompletely understood. Oxidative stress and lipid peroxidation are pivotal in the “multiple parallel hit model”, contributing to hepatic cell death and tissue damage. Gut microbiota plays a substantial role in modulating hepatic oxidative stress through multiple pathways: impairing the intestinal barrier, which results in bacterial translocation and chronic hepatic inflammation; modifying bile acid structure, which impacts signaling cascades involved in lipidic metabolism; influencing hepatocytes’ ferroptosis, a form of programmed cell death; regulating trimethylamine N-oxide (TMAO) metabolism; and activating platelet function, both recently identified as pathogenetic factors in MASH progression. Moreover, various exogenous factors impact gut microbiota and its involvement in MASLD-related oxidative stress, such as air pollution, physical activity, cigarette smoke, alcohol, and dietary patterns. This manuscript aims to provide a state-of-the-art overview focused on the intricate interplay between gut microbiota, lipid peroxidation, and MASLD pathogenesis, offering insights into potential strategies to prevent disease progression and its associated complications.

Hepatocellular carcinoma (HCC) represents a worldwide health matter with a major care burden, high prevalence, and poor prognosis. Its pathogenesis mainly varies depending on the underlying etiological factors, although it develops from liver cirrhosis in the majority of cases. This review summarizes the role of the most interesting soluble factors as biomarkers for early diagnosis and as recommended targets for treatment in accordance with the new challenges in precision medicine. In the premalignant environment, inflammatory cells release a wide range of cytokines, chemokines, growth factors, prostaglandins, and proangiogenic factors, making the liver environment more suitable for hepatocyte tumor progression that starts from acquired genetic mutations. A complex interaction of pro-inflammatory (IL-6, TNF-α) and anti-inflammatory cytokines (TGF-α and -β), pro-angiogenic molecules (including the Angiopoietins, HGF, PECAM-1, HIF-1α, VEGF), different transcription factors (NF-kB, STAT-3), and their signaling pathways are involved in the development of HCC. Since cytokines are expressed and released during the different stages of HCC progression, their measurement, by different available methods, can provide in-depth information on the identification and management of HCC.

Novel foods, including edible insects, are emerging because of their nutritional characteristics and low environmental impacts and could represent a valid alternative source of food in a more sustainable way. Edible insects have been shown to have beneficial effects on human health. Insect-derived bioactive peptides exert antihypertensive, antioxidant, anti-inflammatory, and antimicrobial properties and have protective effects against common metabolic conditions. In this review, the roles of edible insects in human health are reported, and the possible applications of these peptides in clinical practice are discussed. A special mention is given to the role of antimicrobial peptides and their potential applications in controlling infections in orthodontic procedures. In this context, insects’ antimicrobial peptides might represent a potential tool to face the onset of infective endocarditis, with a low chance to develop resistances, and could be manipulated and optimized to replace common antibiotics used in clinical practice so far. Although some safety concerns must be taken into consideration, and the isolation and production of insect-derived proteins are far from easy, edible insects represent an interesting source of peptides, with beneficial effects that may be, in the future, integrated into clinical and orthodontic practice.

Background and Aims: Adaptive immunity is gaining a significant role in progression of metabolic dysfunction‐associated steatotic liver disease (MASLD). B‐cell activity can be assessed by serum‐free light chains (sFLCs) k and λ levels. The objective of the present investigation is to examine the utility of sFLCs as non‐invasive biomarkers for the stratification of MASLD.Methods: We enrolled a consecutive cohort from an outpatient liver unit. Diagnosis of metabolic dysfunction‐associated steatohepatitis (MASH) was made with liver biopsy according to current guidelines. Compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH) were defined according to Baveno VII criteria. sFLCs were measured by turbidimetry using an immunoassay.Results: We evaluated 254 patients, 162/254 (63.8%) were male. Median age was 54 years old, and the median body mass index was 28.4 kg/m². A total of 157/254 (61.8%) subjects underwent liver biopsy: 88 had histological diagnosis of MASH, 89 were considered as simple metabolic dysfunction‐associated steatotic liver (MASL) and 77/254 (30.3%) patients with compensated metabolic dysfunction‐associated cirrhosis. By using Baveno VII criteria, 101/254 (39.7%) patients had cACLD; among them, 45/101 (44.5%) had CSPH. Patients with cACLD showed higher sFLC levels compared with patients without cACLD (p < .01), and patients with CSPH showed higher sFLC levels than patients without CSPH (p < .01). At multivariable analysis, sFLCs were associated with cACLD (p < .05) independently from γ‐globulins and other known dysmetabolic risk factors. κFLC was associated with CSPH (p < .05) independently from γ‐globulins and other known dysmetabolic risk factors.Conclusion: sFLCs could be a simple biomarker for stratification of cACLD in MASLD patients.

Background and Aims: Liver fibrosis is a major determinant of liver‐related events (LREs) in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD). Effective stratification based on fibrosis severity is essential for accurate prognosis. The Enhanced Liver Fibrosis (ELF) test, a non‐invasive test measuring direct fibrosis markers, offers a potential alternative to traditional methods like FIB‐4, liver stiffness measurement (LSM) and liver biopsy. This study aims to evaluate the prognostic value of the ELF test in comparison with these established methods. Methods: We retrospectively analysed 289 MASLD patients (30.4% female, median age 49 years [IQR 39–58], 28% with type 2 diabetes) from the PROMETEO cohort (NCT04371042). We excluded patients with prior or current evidence of decompensated cirrhosis. At baseline, patients underwent liver biopsy, FIB‐4, ELF and LSM assessments. The primary outcome was development of Liver Related Events (LRE), a composite of liver‐related death, hepatocellular carcinoma, liver transplantation, ascites, encephalopathy or variceal bleeding. Results: Over a median follow‐up of 64 months [IQR 39–81], 41 patients (14.2%) experienced LREs. Event rates increased markedly across ELF categories (1% for ELF < 9.8, 27.8% for ELF ≥ 9.8 to < 11.3 and 72.7% for ELF ≥ 11.3). ELF demonstrated discriminative performance comparable to histological fibrosis stage and LSM, with the highest overall AUC among evaluated tests. In adjusted Cox models, higher ELF categories remained strongly associated with LRE risk, although confidence intervals were wide due to the limited number of events. Conclusions: In this biopsy‐proven MASLD cohort, ELF provided prognostic stratification for liver‐related events comparable to liver histology and LSM. Given the limited number of outcome events, these findings support the non‐inferiority of ELF rather than definitive superiority. Larger prospective studies are needed to confirm these results and refine risk prediction strategies.

Multiple myeloma (MM) is the second most common hematologic malignancy. It is still largely incurable, but treatment has changed greatly with proteasome inhibitors, immunomodulatory drugs, monoclonal and bispecific antibodies, autologous stem cell transplantation and chimeric antigen receptor T cells. Most patients now achieve a complete response. As a result, conventional criteria, based on monoclonal protein, serum free light chains and bone marrow plasma cell counts, can no longer distinguish different depths of response. Measurable residual disease (MRD) has therefore become the reference endpoint. The International Myeloma Working Group defines MRD negativity as the absence of clonal plasma cells among at least 100,000 bone marrow cells. MRD negativity predicts progression-free and overall survival, independently of cytogenetic risk and disease stage. The US Food and Drug Administration has also accepted it as an early endpoint for accelerated approval. This review examines the three main technologies now used to assess MRD in MM. Next-generation flow cytometry is standardized through the EuroFlow two-tube, eight-color protocol. It gives same-day results and can be applied to all patients without a baseline sample. Next-generation sequencing of clonal immunoglobulin gene rearrangements is more sensitive and can be used on stored samples. It can also follow clonal evolution and the appearance of resistance mutations. Mass spectrometry is performed on peripheral blood. It detects the patient-specific clonotypic immunoglobulin with much higher sensitivity than electrophoretic methods and allows frequent, minimally invasive monitoring. For now, however, it complements marrow-based testing and does not replace it. For each method, we discuss analytical principles, sensitivity, standardization, pre-analytical requirements, clinical validation and limitations, and we briefly consider the growing contribution of artificial intelligence. The review also covers the role of cytogenetics and fluorescence in situ hybridization in baseline risk assessment. Finally, we discuss the limits of MRD testing in a disease that is often unevenly distributed between marrow, extramedullary sites and peripheral blood. Current evidence suggests that combining marrow-based and blood-based assays may identify residual disease most accurately. This combined approach has not yet been validated prospectively, and for now it should be used within clinical trials.