Hepatitis B virus-infection related cryoglobulinemic vasculitis. Clinical manifestations and the effect of antiviral therapy: A review of the literature

Objective: Hepatitis B virus (HBV) infection causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Furthermore, about 20% of the patients develop extrahepatic manifestations such as cryoglobulinemic vasculitis (CV), polyarteritis nodosa, non-rheumatoid arthritis, glomerulonephritis and non-Hodgkin lymphoma. This review analyzed literature data on clinical manifestations of HBV-related CV and the impact of antiviral therapy with analoques nucleotide. Methods: A PubMed search was performed to select eligible studies in the literature, up to July 2022. Results: Some studies have analyzed clinical manifestations in HBV-related CV and have investigated the role of antiviral therapy with nucleotides analogues (NAs). Clinical manifestations of CV vary from mild to moderate (purpura, asthenia and arthralgias) to severe (leg ulcers, peripheral neuropathy, glomerulonephritis, and non-Hodking lymphoma). NAs therapy leads to suppression of HBV-DNA; therefore, it is capable of producing clinical response in the majority of patients with mild to moderate symptoms. Conclusion: Antiviral therapy with NAs is the first choice for HBV suppression and control of mild to moderate disease. In severe vasculitis (glomerulonephritis, progressive peripheral neuropathy and leg ulcers), rituximab alone or with plasma-exchange is always indicated in combination with antiviral therapy

The Role of Interleukin 23/17 Axis in Psoriasis Management: A Comprehensive Review of Clinical Trials

Luca Potestio,* Fabrizio Martora,* Giuseppe Lauletta, Ylenia Vallone, Teresa Battista, Matteo Megna Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy*These authors contributed equally to this workCorrespondence: Luca Potestio, Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, Napoli, 80131, Italy, Tel +39 - 081 – 7462457, Fax +39 - 081 - 7462442, Email [email protected]: Psoriasis pathogenesis is influenced by genetic factors and characterized by a complex interplay between genetic predisposition and various environmental triggers. These triggers set off metabolic processes involving inflammation, cell signaling, immune response dysregulation, and antigen presentation. Several types of innate and adaptive immune cells are involved in psoriasis. Among the cytokine cascade which leads to psoriasis development, the interleukin (IL)-23/Th17 axis, especially IL-17 production, emerges as crucial. Recognizing the pivotal role of this axis has facilitated the development of selective and effective biological drugs, such as anti-IL17 and anti-IL23 monoclonal antibodies. These drugs aim to achieve the complete or near-complete disappearance of psoriatic lesions, as indicated by PASI100 and PASI90 responses, respectively. In this context, the aim of our review was to delve into the functioning of the IL-23/Th17 axis, its dysregulation in psoriasis pathogenesis, and the therapeutic potential of its inhibition. Currently, 4 anti-IL17 (secukinumab, ixekizumab, bimekizumab and brodalumab) and 3 anti-IL23 (guselkumab, risankizumab and tildrakizumab) have been approved. All these drugs showed high levels of effectiveness in both clinical trials and real-life experiences, with an excellent profile in terms of safety. Certainly, furthers studies will allow for better characterization of biologics’ profile, in order to administer the right drug for the right patients at the right moment.Keywords: psoriasis, management, clinical trial, IL-17/23 axi

Management of mixed cryoglobulinemia with rituximab: evidence and consensus-based recommendations from the Italian Study Group of Cryoglobulinemia (GISC)

Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones producing pathogenic immune complexes, called cryoglobulins. It is often secondary to hepatitis C virus (HCV), autoimmune diseases, and hematological malignancies. CV usually has a mild benign clinical course, but severe organ damage and life-threatening manifestations can occur. Recently, evidence in favor of rituximab (RTX), an anti-CD 20 monoclonal antibody, is emerging in CV: nevertheless, questions upon the safety of this therapeutic approach, especially in HCV patients, are still being issued and universally accepted recommendations that can help physicians in MCS treatment are lacking. A Consensus Committee provided a prioritized list of research questions to perform a systematic literature review (SLR). A search was made in Medline, Embase, and Cochrane library, updated to August 2021. Of 1227 article abstracts evaluated, 27 studies were included in the SLR, of which one SLR, 4 RCTs, and 22 observational studies. Seventeen recommendations for the management of mixed cryoglobulinemia with rituximab from the Italian Study Group of Cryoglobulinemia (GISC) were developed to give a valuable tool to the physician approaching RTX treatment in CV

Detection and quantitation of HCV core protein in single hepatocytes by means of laser capture microdissection and enzyme-linked immunosorbent assay

Immunohistochemistry provides valuable information concerning the localization and distribution of hepatitis C virus (HCV)-related proteins in histological sections of liver tissue, but does not readily permit their quantitation in individual cells and the staining intensity of cell immunodeposits cannot be calibrated with the current number of antigen molecules. We specifically detected and quantitated HCV core protein in single hepatocytes by coupling laser capture microdissection (LCM) with a sensitive enzyme-linked immunosorbent assay (ELISA). Quantitation of HCV core protein per cell was carried out on liver tissue cells obtained by LCM from fixed and stained frozen sections of 10 HCV-positive patients with chronic active hepatitis (CAH). Macromolecules from captured cells were solubilized in an extraction buffer and directly assayed for core protein using a sandwich ELISA. Calibration was achieved by developing a standard curve based on known concentrations of HCV core protein. Precision, linearity and sensitivity were verified for known numbers of microdissected tissue cells. In this study, the concentration of HCV core protein in single hepatocytes ranged from 7 to 56 pg/ cell. Specificity was verified on 10 replicates of 10 HCVnegative liver tissues. Immunohistochemical staining of HCV core protein was compared with the results of the soluble immunoassay for the adjacent liver tissue sections. Independent scoring of HCV immunostaining failed to parallel the LCM quantitative immunoassay. LCM-based immunoassay significantly expands our ability to investigate function- related antigens in apparently pure cell populations in HCV infection

Hepatitis C virus infection and mixed cryoglobulinemia

Hepatitis C virus (HCV) chronic infection is recognized as the major cause of mixed cryoglobulinemia (MC). Its persistence represents a continuous stimulus for host immune system with production of circulating immune complexes (ICs), one-third of them with cryoprecipitate property. Several factors contribute to the biological activities of ICs, many of which are not completely known. Among them, complement factors play a crucial role in the cold-insoluble ICs-mediated vasculitis, involving primarily small blood vessels in different tissues including skin, kidney, peripheral, and central nervous system. Liver represents the major target of HCV infection with inflammatory infiltrates, resembling secondary lymphoid follicles. Cytokine like CXCL13 contribute to B-cell homing in intraportal lymphoid aggregates, in which B-cell clonal selection may arise. B-cell clonal expansion starts as an antigen-driven event and expands towards indolent and malignant B-cell proliferation. Occurrence of intrahepatic Bcell clonalities correlates with extrahepatic clinical manifestations of HCV infection. In this context, cryoglobulinemic patients should be considered a peculiar HCV-infected population that needs a clinical multidisciplinary approach and more articulated therapeutic measures