Letter to the editor: High rate of clinical and immunological response in patients with HCV‐associated cryoglobulinemia
Authors: Sofiia Gavrisheva, Dzhamal Abdurakhmanov, Svetlana Milovanova, Elena Nikulkina, Teona Rozina, Elena Tanashchuk, Ekaterina Nabatchikova, Nikolay Bulanov, Tatiana Krasnova, Sergey Moiseev
Journal: Hepatology (2022)

To the editor, We have read with interest the article by Kondili et al.[1] The results of this study indicate that long‐term monitoring of patients with HCV‐associated cryoglobulinemic vasculitis (CV) is required after treatment with direct‐acting antivirals (DAAs). Despite the high rate of clinical improvement, the symptoms of CV fluctuated during the follow‐up, and nearly a half of the patients had a deterioration of initial response. Several studies demonstrate the importance of long‐term follow‐up in patients with HCV‐CV.[2,3] In the past we have shown persistent cryoglobulinemia and CV after HCV eradication.[3] Here, we report data on nine symptomatic (CV) patients and 20 patients with asymptomatic cryoglobulinemia, treated with DAAs ± ribavirin (Table 1). The activity of HCV‐CV was assessed using the Birmingham Vasculitis Activity Score, version 3 (BVAS.v3). The median follow‐up period was 26 (15–36) months after treatment cessation. TABLE 1 - Baseline characteristics of study population Baseline characteristic All patients (n = 29) Male sex, n (%) 8 (27.6) Age, median (IQR) 53.0 (48.0–59.0) Cirrhosis, n (%) 27 (93.1) HCV genotype, n (%)a 1b 19 (65.5) 2 3 (10.4) 3 6 (20.7) Treatment‐naive, n (%) 17 (58.6) Monoclonal gammopathy, n (%) 3 (10.4) Rheumatiod factor (IU/ml), median (IQR)b 17.0 (0–201.3) Serum C4 (mg/dl), median (IQR)c 11.0 (8.9–15.6) IgG (g/L), median (IQR)d 18.0 (14.9–23.3) ESR (mm/h), median (IQR)e 20.0 (17.0–42.5) Clinical manifestations, n (%)f Skin purpura 9 (100) Arthralgia 5 (55.6) Neuropathy 4 (44.5) Renal involvement 4 (44.5) BVAS.v3 score, median (IQR) 5.0 (2.0–5.0) Abbreviations: ESR, erythrocyte sedimentation rate; IQR, interquartile range.aData on HCV genotype were available for 28 patients.bReference ranges for rheumatoid factor levels were 0–14 IU/ml.cReference ranges for serum C4 levels were 16–38 mg/dl.dReference ranges for IgG levels were 7–16 g/L.eReference ranges for ESR levels were 0–20 mm/h.fData for nine symptomatic patients are presented. All patients achieved sustained virological response at 12 weeks. Cryoglobulins disappeared at the end of treatment in 11 (37.9%) patients (in four [44.4%] symptomatic and seven [35%] asymptomatic patients). During follow‐up eight more patients achieved cryoglobulin elimination, and one patient had recurrence of cryoglobulinemia. The overall cryoglobulinemia elimination rate was 62.1%. Of the nine symptomatic patients, clinical response was complete (defined by a BVAS.v3 score of 0) in four (44.4%) patients and partial response (defined by a BVAS.v3 score < 50% of the baseline score) in two (22.2%) patients. During the follow‐up one more patient achieved complete clinical response, and the overall rate of clinical response was 77.7%. Skin purpura (66.7% reduction), joint manifestation (60% reduction), and renal impairment (75% reduction) were most likely to resolve, with a lower rate of response in neurological symptoms (25%). Our study had a longer observational period than the study by Kondili et al. We also demonstrated high rates of virological, clinical, and immunological responses in DAA‐treated patients with HCV‐CV and cryoglobulinemia, which increased during the follow‐up. In the article by Kondili et al., nearly 50% of patients had deterioration of the clinical response, whereas in our cohort only one patient (3.5%) experienced transitory clinical relapse and a recurrence of cryoglobulinemia after treatment cessation. These differences may be explained by the lower rate of neuropathy in our cohort, which is usually a less reversible manifestation of CV. Our findings are in line with the study by Bonacci et al., in which clinical relapse was observed in five (9%) patients with HCV‐CV during long‐term follow‐up.[3] But in our cohort nearly half of the patients (with partial or no clinical and immunological response) still needed further follow‐up and alternative treatments. CONFLICT OF INTEREST Nothing to report.