Hematological and Genetic Markers in the Rational Approach to Patients With HCV Sustained Virological Response With or Without Persisting Cryoglobulinemic Vasculitis

Abstract

BACKGROUND and AIMSDirect acting antivirals (DAAs) usually lead to improvement/remission of cryoglobulinemic vasculitis (CV) although symptoms may persist/recur after a sustained virological response (SVR). We evaluated haematological and genetic markers in HCV-SVR vasculitis patients with and without persisting/recurring symptoms to early predict the CV outcome. APPROACH and RESULTSNinety-eight HCV-CV patients were prospectively enrolled after a DAA-induced SVR:Group A: 52 with complete clinical response; Group B: 46 with symptom maintenance/recurrence. Monoclonal B-cell lymphocytosis, t(14;18) translocation and abnormal free light chains k/λ ratios were detected by flow-cytometry or nested-PCR or nephelometry in 4% Group A vs 17% Group B (p= 0.04) patients, 17% Group A vs 40% Group B patients (p= 0.02) and 17% Group A vs 47% Group B (p= 0.003) patients, respectively.At least one out of three clonality markers was altered/positive in 29% of Group A vs 70% of Group B patients (p<0.0001).When available, pre-therapy samples were also tested for t(14;18) translocation (detected in 12/37 (32%) Group A and 21/38 (55%) Group B) and k/λ ratios (abnormal in 5/35 (14%) Group A and 20/38 (53%) Group B) (p=0.0006), while at least one clonality marker was detected/altered in 16/37 (43%) Group A and 30/38 (79%) Group B (p=0.002).CV-associated single nucleotide polymorphisms were tested by Real-Time PCR. Amongst them, notch4 rs2071286 T minor allele and TT genotype showed a higher frequency in Group B vs Group A (46% vs 29%, p=0.01 and 17% vs 2%, p=0.006, respectively). CONCLUSIONHematological or genetic analyses could be used to foresee the CV clinical response after DAA-therapy and could be valuable to assess a rational flow-chart to manage CV during the follow-up.

Persistence of Cryoglobulinemic Vasculitis after DAA Induced HCV Cure

“…According to an Egyptian study on 1000 patients with chronic hepatitis C by Tawfik et al [24], 369 patients presented with skin manifestations, and 286 of these 369 (77.5%) patients had cryoglobulinemia. In this and other reports, purpura was the most prevalent skin manifestation that presented in over 50% of patients with HCV-related CryoVas [19,27,28]. Skin necrosis and Raynaud's phenomenon were reported in 10% and 18% of the patients, respectively [19,27].…”

“…Two thousand articles were initially identified through database-searching on PubMed, Embase, Cochrane, Web of Science, and clinicaltrials.gov. Ultimately, 19 studies [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] meeting the prespecified inclusion criteria were selected (Figure 2).…”

“…Relapse after CR/PR was mentioned in eight studies and ranged from 0-18% of the treated patients. Genetics as predictive factors for persistence or relapse CryoVas and persistent B-cell clones were focused on in three [28][29][30] and two studies [26,31], respectively, without providing information about the overall response or relapse. Nephrology complications, neurology complications, and dermatological complications were discussed in four, another four, and six studies, respectively.…”

HCV-related lymphoproliferative disorders in the direct-acting antiviral era: From mixed cryoglobulinaemia to B-cell lymphoma

“…Despite this positive impact, B clones may persist in the serum after DAA-induced SVR, but so far, their persistence has not been correlated with reactivation of vasculitis (35). While the mechanisms behind CryoVas relapses after DAA remain unclear, biomarkers such as monoclonal B-cell lymphocytosis, t(14;18) translocation, and abnormal free light chains κ/λ ratios have been proposed as biological elements to foresee clinical response (36).…”

Letter to the Editor: The Potential Mechanism by the Protection Effects of Exercise Training on Ischemia/Reperfusion–Induced Injury and Metastasis

“…We read with great interest the recently published article by Yazdani et al (1) demonstrating the protection effects of exercise training on liver ischemia/reperfusion (I/R)-induced injury and metastasis. It is a meaningful study proposing exercise training as a nonpharmacological method for preventing cancer metastasis, given that we all know that cancer metastasis and recurrence are the main contributors of poor postoperative prognosis.…”