Chronic liver diseases (CLD) stem from various causes and lead to a gradual progression that ultimately may result in fibrosis and eventually cirrhosis. This process is typically prolonged and asymptomatic, characterized by the complex interplay among various cell types, signaling pathways, extracellular matrix components, and immune responses. With the prevalence of CLD increasing, diagnoses are often delayed, which leads to poor prognoses and in some cases, the need for liver transplants. Consequently, there is an urgent need for the development of novel, non-invasive methods for the diagnosis and monitoring of CLD. In this context, serum biomarkers—safer, repeatable, and more acceptable alternatives to tissue biopsies—are attracting significant research interest, although their clinical implementation is not yet widespread. This review summarizes the latest advancements in serum biomarkers for detecting hepatic fibrogenesis and advocates for concerted efforts to consolidate current knowledge, thereby providing patients with early, effective, and accessible diagnoses that facilitate personalized therapeutic strategies.

The activation of members of the Epidermal Growth Factor Receptor (EGFR) family (including ErbB) triggers pathways that have significant effects on cellular processes and have profound consequences both in physiological and pathological conditions. Within the nervous system, the neuregulin (NRG)/ErbB3 signaling plays a crucial role in promoting the formation and maturation of excitatory synapses. Noteworthy is ErbB3, which is actively involved in the process of cerebellar lamination and myelination. All members of the ErbB-family, in particular ErbB3, have been observed within the nuclei of various cell types, including both full-length receptors and alternative variants. One of these variants was detected in Schwann cells and in glioblastoma primary cells where it showed a neuregulin-dependent expression. It binds to promoters’ chromatin associated with genes, like ezrin, involved in the formation of Ranvier’s node. Its nucleolar localization suggests that it may play a role in ribosome biogenesis and in cell proliferation. The regulation of ErbB3 expression is a complex and dynamic process that can be influenced by different factors, including miRNAs. This mechanism appears to play a significant role in glioblastoma and is often associated with a poor prognosis. Altogether, the targeting of ErbB3 has emerged as an active area of research in glioblastoma treatment. These findings highlight the underappreciated role of ErbB3 as a significant receptor that can potentially play a pivotal role in diverse pathologies, implying the existence of a shared and intricate mechanism that warrants further investigation.

Increasing evidence underlines the role of B-cells in the development of hepatic fibrogenesis following viral infections and metabolic dysfunction, through different mechanisms depending on the etiology. Circulating biomarkers of B-cell activation—such as B-cell activating factor (BAFF), immunoglobulin G (IgG) subclasses, and free light chains (FLCs)—may be associated with different results between viral and metabolic hepatic fibrosis, supporting their use as diagnostic tools. We conducted a case-control study including 100 patients with liver fibrosis, 50/100 of metabolic etiology and 50/100 of viral etiology. A reference group of 30 healthy donors was included as control. Serum levels of BAFF were measured using ELISA, while IgG subclasses (IgG1, IgG2, IgG3, IgG4), κ-FLC, λ-FLC, and the κ/λ ratio were quantified by turbidimetric methods. In univariate analysis, κ-FLC, λ-FLC, and BAFF levels were significantly elevated in both patient groups, with the highest concentrations consistently observed in metabolic fibrosis. IgG2 was selectively increased in metabolic fibrosis, whereas IgG3 was specifically elevated in viral fibrosis. Multivariate analysis confirmed these findings, showing a clear clustering of the three groups and identifying increased BAFF and κ-FLC as key features of metabolic fibrosis, while elevated IgG3 emerged as the most distinctive marker of viral etiology. These results reveal distinct B-cell-related immunological signatures in metabolic and viral hepatic fibrosis supporting the role of BAFF, FLCs, and IgG subclasses as biomarkers of etiological differentiation, and provide novel insights into the immune mechanisms driving fibrosis progression, potentially contributing to the identification of new therapeutic targets.

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.