Predictors of long-term cryoglobulinemic vasculitis outcomes after HCV eradication with direct-acting antivirals in the real-life

Gragnani, Laura; Lorini, Serena; Marri, Silvia; Vacchi, Caterina; Madia, Francesco; Monti, Monica; Ferri, Clodoveo; Zignego, Anna Linda

doi:10.1016/j.autrev.2021.102923

Cited by 15 publications

(14 citation statements)

References 46 publications

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“…As expected, the majority of MCs patients had a viral etiology, mostly HCV- and very rarely the HBV-related disease, reflecting the current epidemiology of these hepatotropic viruses in Italy. In addition, the higher female/male subject ratio, observed in the overlap syndrome subgroup compared to other subgroups, is in keeping with the coexistence of MCs with other ASDs, which are characterized by a marked prevalence of female sex, as well as by a younger mean age compared to HCV-related MCs [ 34 ], while the finding of different mean disease duration among MCs subsets, particularly between HCV-related and essential MCs, could be not completely reliable since this parameter is difficult to assess in real-life studies, as previously suggested [ 35 ].…”

Section: Discussionmentioning

confidence: 85%

“…In this context, the MCs patients represent one of the most “frail” population due its diffuse vascular multiorgan involvement, advanced mean age, frequent chronic steroid administration, and possibly long disease duration [ 6 ]. Although the actual disease duration in MCs is hard to assess in real life [ 35 ], we found an increased prevalence of COVID-19 in patients with a long-lasting cryoglobulinemic syndrome. It is conceivable that a longer disease duration may contribute to generally worse health condition, thus increasing the patient’s vulnerability and morbidity of SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 89%

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COVID-19 and Mixed Cryoglobulinemia Syndrome: Long-Term Survey Study on the Prevalence and Outcome, Vaccine Safety, and Immunogenicity

et al. 2023

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Purpose Mixed cryoglobulinemia syndrome (MCs) is a rare immunoproliferative systemic disorder with cutaneous and multiple organ involvement. Our multicenter survey study aimed to investigate the prevalence and outcome of COVID-19 and the safety and immunogenicity of COVID-19 vaccines in a large MCs series. Methods The survey included 430 unselected MCs patients (130 M, 300 F; mean age 70 ± 10.96 years) consecutively collected at 11 Italian referral centers. Disease classification, clinico-serological assessment, COVID-19 tests, and vaccination immunogenicity were carried out according to current methodologies. Results A significantly higher prevalence of COVID-19 was found in MCs patients compared to Italian general population (11.9% vs 8.0%, p < 0.005), and the use of immunomodulators was associated to a higher risk to get infected ( p = 0.0166). Moreover, higher mortality rate was recorded in MCs with COVID-19 compared to those without ( p < 0.01). Patients’ older age (≥ 60 years) correlated with worse COVID-19 outcomes. The 87% of patients underwent vaccination and 50% a booster dose. Of note, vaccine-related disease flares/worsening were significantly less frequent than those associated to COVID-19 ( p = 0.0012). Impaired vaccination immunogenicity was observed in MCs patients compared to controls either after the first vaccination ( p = 0.0039) and also after the booster dose ( p = 0.05). Finally, some immunomodulators, namely, rituximab and glucocorticoids, hampered the vaccine-induced immunogenicity ( p = 0.029). Conclusions The present survey revealed an increased prevalence and morbidity of COVID-19 in MCs patients, as well an impaired immunogenicity even after booster vaccination with high rate of no response. Therefore, MCs can be included among frail populations at high risk of infection and severe COVID-19 manifestations, suggesting the need of a close monitoring and specific preventive/therapeutical measures during the ongoing pandemic. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-023-01444-4.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 89%

COVID-19 and Mixed Cryoglobulinemia Syndrome: Long-Term Survey Study on the Prevalence and Outcome, Vaccine Safety, and Immunogenicity

et al. 2023

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“…Clinical worsening and relapse are associated with high rheumatoid factor levels before treatment [40 & ,44]. Moreover, pretreatment presence of peripheral neuropathy, weakness and sicca symptoms and renal involvement have been found to be reliable predictors of poor clinical response in HCV-related CV patients [45]. During follow-up after SVR, some data showed that circulating B-cells clones can persist in blood of patients, also in absence of clinical or biochemical relapses, suggesting that those clones could have switched to a quiescent state [46].…”

Section: Therapy and Prognosismentioning

confidence: 99%

“…Clinical worsening and relapse are associated with high rheumatoid factor levels before treatment [40 ▪ ,44]. Moreover, pretreatment presence of peripheral neuropathy, weakness and sicca symptoms and renal involvement have been found to be reliable predictors of poor clinical response in HCV-related CV patients [45].…”

Section: Therapy and Prognosismentioning

confidence: 99%

Cryoglobulinemic vasculitis: a 2023 update

Moretti,

Ferro,

Baldini

et al. 2023

Current Opinion in Rheumatology

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Purpose of review Cryoglobulinemic vasculitis (CV) is an immune complex mediated small vessel vasculitis characterized by the presence of cryoglobulins in serum, often associated with hepatitis C infection, systemic autoimmune diseases or hematological conditions. The focus of this review is to provide an update on new insights into pathogenesis, epidemiology and therapies of infectious and noninfectious type II and type III CV. Recent findings The introduction of new antiviral drugs for treatment of hepatitis C infection implied major changes in HCV-related CV, allowing to shed new lights on CV pathogenesis and mechanisms of relapse and, therefore, to increase the relevance of autoimmune diseases in CV epidemiology. Specific B-cell clones are involved in the production of pathogenic immune complexes that leads to small-vessel vasculitis. Therefore, both antiviral treatments [direct-acting antivirals (DAAs) and oral nucleot(s)ide analogues] and targeted anti-CD20 therapies (rituximab) prove to be safe and effective options, leading to a better prognosis. Association of Sjögren syndrome and CV defines a specific phenotype of patients, characterized by severe manifestations and poor outcome. Summary Removing viral stimulation on B-cells through direct-acting antivirals and blocking B-cells proliferation and differentiation with rituximab are the goals of treatment of CV. However, further research is needed to identify prognostic factors of refractory and relapsing disease.

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“…In this respect, the identification of reliable markers predictive of clinical response after HCV eradication represents a prime concern to clarify. A recently published study dealing with this specific topic suggested that neuropathy, weakness, and sicca syndrome, together with standardised disease severity indexes might predict the long-term clinical response of HCV-MC patients before initiating antiviral treatment (57). Despite the remarkable results achieved in the last thirty years, some aspects of the complex HCV-related hepatic and extra-hepatic disorders still remain to be addressed.…”

Section: Mixed Cryoglobulinaemia and Hepatitis C Virus: A Paradigm Of...mentioning

confidence: 99%

Mixed cryoglobulinaemia and hepatitis C virus: a paradigm of a virus-related autoimmune and lymphoproliferative disorder

Ferri

Bombardieri

2021

Clinical and Experimental Rheumatology

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Predictors of long-term cryoglobulinemic vasculitis outcomes after HCV eradication with direct-acting antivirals in the real-life

Cited by 15 publications

References 46 publications

COVID-19 and Mixed Cryoglobulinemia Syndrome: Long-Term Survey Study on the Prevalence and Outcome, Vaccine Safety, and Immunogenicity

COVID-19 and Mixed Cryoglobulinemia Syndrome: Long-Term Survey Study on the Prevalence and Outcome, Vaccine Safety, and Immunogenicity

Cryoglobulinemic vasculitis: a 2023 update

Mixed cryoglobulinaemia and hepatitis C virus: a paradigm of a virus-related autoimmune and lymphoproliferative disorder

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