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Hematological and Genetic Markers in the Rational Approach to Patients With HCV Sustained Virological Response With or Without Persisting Cryoglobulinemic Vasculitis
Author(s) -
Gragnani Laura,
Lorini Serena,
Marri Silvia,
Basile Umberto,
Santarlasci Veronica,
Monti Monica,
Madia Francesco,
Petraccia Luisa,
Stasi Cristina,
Marello Niccolò,
Napodano Cecilia,
Annunziato Francesco,
Zignego Anna Linda
Publication year - 2021
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.31804
Subject(s) - medicine , gastroenterology , group b , vasculitis , group a , immunology , genotype , cryoglobulinemia , biology , hepatitis c virus , virus , biochemistry , disease , gene
Background and Aims Direct‐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 hematological and genetic markers in patients with HCV‐SVR vasculitis with and without persisting/recurring symptoms to early predict the CV outcome. Approach and Results Ninety‐eight patients with HCV‐CV 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 κ/λ ratios were detected by flow cytometry or nested‐PCR or nephelometry in 4% Group A versus 17% Group B ( P  = 0.04) patients, 17% Group A versus 40% Group B patients ( P  = 0.02), and 17% Group A versus 47% Group B ( P  = 0.003) patients, respectively. At least 1 out of 3 clonality markers was altered/positive in 29% of Group A versus 70% of Group B patients ( P  < 0.0001). When available, pretherapy samples were also tested for t(14;18) translocation (detected in 12/37 [32%] Group A and 21/38 [55%] Group B) and κ/λ ratios (abnormal in 5/35 [14%] Group A and 20/38 [53%] Group B) ( P  = 0.0006), whereas 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. Among them, notch4 rs2071286 T minor allele and TT genotype showed a higher frequency in Group B versus Group A (46% vs. 29%, P  = 0.01, and 17% vs. 2%, P  = 0.006, respectively). Conclusions Hematological or genetic analyses could be used to foresee the CV clinical response after DAA therapy and could be valuable to assess a rational flowchart to manage CV during follow‐up.

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