Late relapses of hepatitis C virus-cured mixed cryoglobulinaemia associated with infection or cancer

Long‐lasting persistence of large B‐cell clones in hepatitis C virus‐cured patients with complete response of mixed cryoglobulinaemia vasculitis

“…Thus, IgG, especially in the form of immune complexes, could be the autoantigenic trigger responsible for the survival and reactivation of B‐cell clones beyond HCV. In this regard, it is of interest that relapses of MCV in HCV‐cured patients have been observed in concomitance with respiratory infections or the occurrence of lung cancer, or shortly after influenza vaccination . In the cohort reported here, one complete responder had recurrence of purpura and of cryoglobulinaemia in concomitance with an acute respiratory infection; also notably, a lung cancer was diagnosed during antiviral therapy in a patient who had dramatic progression of vasculitis despite the clearance of HCV.…”

“…[4][5][6] The eradication of HCV infection with direct-acting antivirals (DAAs) is associated in most cases with healing of MCV [7][8][9] and with regression of NHL, 10 but cryoglobulins persist in almost half of HCV-cured MC patients 8 and clinical relapses have been observed in some of them. 9,11 We previously reported 12 that circulating B-cell clones may persist for at least some months after the eradication of HCV, suggesting that this might be the cause for HCV-independent persistence or relapse of MC. Here, we describe the long-term immunological and clinical outcomes of antiviral therapy with DAAs in patients with MCV with or without NHL, and correlate these outcomes with the presence and persistence of circulating B-cell clones.…”

“…These clonal B‐cells display peculiar characteristics such as low expression of CD21 (CD21 low B‐cells) and features of functional exhaustion . The eradication of HCV infection with direct‐acting antivirals (DAAs) is associated in most cases with healing of MCV and with regression of NHL, but cryoglobulins persist in almost half of HCV‐cured MC patients and clinical relapses have been observed in some of them …”

Clinico‐immunological outcomes of HCV‐cured cryoglobulinemia: Lower relapse rate with interferon‐based than interferon‐free therapy

“…To our knowledge, despite a large body of studies [1][2][3][4] only nine cases of relapse of MCV after an initial clinical response have been reported in HCV-cured patients treated with IFN-based therapy. 11,12 Relapses consisted in transient purpura in six patients, while in three cases were persistent and were associated with NHL in two of them. 11 Previous studies on the outcomes of MCV after IFN-free therapy through relatively short median follow-up periods of 6 or 15 months failed to report relapses of vasculitis.…”

“…The overall response rate of MCV are similar in patients who attained a SVR after either IFN‐based, 88%‐97%, 3,4 or IFN‐free therapy, average 93% 5‐9 . However, recent studies reported that 4%‐11% of DAA‐treated patients with clinical response of MCV have relapse of vasculitis despite remaining in SVR, 7,9,10 while very few relapses of vasculitis have been described in IFN‐treated patients who did not have virological relapse 11,12 . Also, serum cryoglobulins have been reported to persist for at least several months in 20%‐50% of SVR patients after DAAs 5,7,8 while, to our knowledge, such observation is lacking in reports on IFN‐based therapy.…”