Livers, Volume 5, Issue 1 (March 2025) – 5 articles

Liver fibrosis is a very complicated dynamic process where several immune cells are involved. Both innate and adaptive immunity are implicated, and their interplay is always present. Multi-directional interactions between liver macrophages, hepatic stellate cells (HSCs), immune cells, and several cytokines are important for the induction and perpetuation of liver fibrosis. Detailed studies of proteomics and transcriptomics have produced new evidence for the role of individual cells in the process of liver fibrosis and cirrhosis. Most of these cells are controlled by the various immune checkpoints whose main function is to maintain the homeostasis of the implicated immune cells. Recent evidence indicates that several immune checkpoints are involved in liver fibrosis. In particular, the role of the programmed cell death protein 1 (PD-1), the programmed death-ligand 1 (PD-L1), and the role of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) have been investigated, particularly after the availability of checkpoint inhibitors. Their activation leads to the exhaustion of CD4+ve and CD8+ve T cells and the promotion of liver fibrosis. In this review, the current pathogenesis of liver fibrosis and the immunological abnormalities are discussed. The recent data on the involvement of immune checkpoints are identified as possible targets of future interventions. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the novel terminology encompassing liver disease associated with metabolic dysfunction, replacing the previous terminology of non-alcoholic fatty liver disease (NAFLD). This disease is strongly associated with metabolic disorders such as obesity, type 2 diabetes, and dyslipidemia. MASLD and dyslipidemia are deeply interconnected, driven by shared pathophysiological mechanisms. Emerging evidence suggests that statins, a class of lipid-lowering medications, may have beneficial effects on MASLD beyond their primary role in reducing cholesterol levels through several mechanisms, including anti-inflammatory, antioxidant, anti-fibrosis, and immunomodulatory effects. This review aims to summarize the efficacy of statins in the management of MASLD and provide insights into their potential mechanisms of action. It discusses the pathophysiology of MASLD and the role of statins in targeting key aspects of the disease. Additionally, the review examines the clinical evidence supporting the use of different statins in MASLD treatment and highlights their specific effects on liver enzymes, inflammation, and fibrosis. Furthermore, an algorithm for statin therapy in MASLD is proposed based on the current knowledge and available evidence. Full article

The authors of this study focused their research on developing cap geometries for the FibroScan^® elastograph (FibroScan, EchoSens, Paris, France) measuring head aimed at a non-invasive assessment of liver condition for transplantation using a pig animal model. Numerical models were created to simulate the propagation of a mechanical wave through a biological medium induced by the FibroScan^® elastograph measuring head. The designed caps were intended to replicate the skin–muscle–rib–liver structures to minimize the risk of damage caused by mechanical wave excitation when directly applied to liver tissue. The construction process of numerical models for the liver and surrounding tissues is presented, along with simulations reflecting the mechanical and acoustic properties of the wave propagation process. The results obtained from in vivo measurements on pigs were validated through a numerical analysis, confirming a high level of agreement between the test results and the numerical model. Full article

Chronic liver disease poses significant challenges to healthcare systems, which frequently struggle to meet the needs of end-stage liver disease patients. Early detection and management are essential because liver damage and fibrosis are potentially reversible. However, the implementation of population-wide screenings is hindered by the asymptomatic nature of early chronic liver disease, along with the risks and costs associated with traditional diagnostics, such as liver biopsies. This study pioneers the development of innovative, minimally invasive methods capable of improving the outcomes of liver disease patients by identifying liver disease biomarkers using quantification methods with translational potential. A targeted mass spectrometry assay based on stable isotope standard protein epitope signature tags (SIS-PrESTs) was employed for the absolute quantification of 108 proteins in just two microliters of plasma. The plasma profiles were derived from patients of various liver disease stages and etiologies, including healthy controls. A set of potential biomarkers for stratifying liver fibrosis was identified through differential expression analysis and supervised machine learning. These findings offer promising alternatives for improved diagnostics and personalized treatment strategies in liver disease management. Moreover, our approach is fully compatible with existing technologies that facilitate the robust quantification of clinically relevant protein targets via minimally disruptive sampling methods. Full article

Background: This study addresses a particular aspect of the biological behavior of the Spike subunit S1 of SARS-CoV-2. Researchers observed S1 acting freely in the human organism during and after COVID-19 and vaccination. One of its properties is that it interacts one-to-one with human proteins. S1 interacts with 12 specific human proteins in the liver. Methods: We used these proteins as seeds to extract their functional relationships from the human proteome through enrichment. The interactome representing the set of metabolic activities in which they are involved shows several molecular processes (KEGG), including some linked to HBV (hepatitis B) and HCC (hepatocellular carcinoma) with many genes/proteins involved. Reports show that, in some COVID patients, HBV reactivated or progressed to cancer. Results: We analyzed the interactome with several approaches to understand whether the two pathologies have independent progressions or a common progression. All our efforts consistently showed that the molecular processes involving both HBV and HCC are significantly present in all approaches we used, making it difficult to extract any useful information about their fate. Through BioGRID, we extracted experimental data in vivo but derived it from model cell systems. The lack of patient data in STRING results prevents diagnosis or prediction of real disease progression; therefore, we can consider them “aseptic” model data. Conclusion: The interactome tells us that genes involved in HCC and HVB-related pathways have the potential to activate disease processes. We can consider them as a gold standard. It is the comparison with similar molecular interactions found in individual human phenotypes that shows us whether the phenotype favors or hinders their progression. This also suggests how to use these features. These sets of proteins constitute a molecular “toolkit”. In fact, if we compare them with similar molecular sets of the patient, they will provide us with information on the level of the phenotypic state that is driving the disease. The information derived from the composition of an entire group of proteins is broader and more detailed than a single marker. Therefore, these protein compositions can serve as a reference system with which doctors can compare specific cases for personalized molecular medicine diagnoses. Full article