Long Term Follow-Up of Patients with Cryoglobulinemia After Successful Treatment of Chronic C Virus Hepatitis

Mixed cryoglobulinemia is one of the most important extrahepatic manifestations of chronic hepatitis C infection.

We screened 111 HCV-infected patients and identified 40 with cryoglobulinemia, who later achieved sustained virologic response (SVR). We prospectively followed them regarding laboratory findings and clinical symptoms for a median [IQR] of 5 [3–10] years.

Prior to antiviral treatment, the median serum cryoglobulin level was 297 (IQR: 61–1144) mg/L. In 25 patients type II, while in 15 type III cryoglobulinemia were found with significant difference in cryoglobulin levels (669 [297–2713] vs. 57 [33–123], respectively) (p < 0.001). Only 23 patients had clinical symptoms at the diagnosis, of whom 21 had cryoglobulinemic vasculitis and 2 non-Hodgkin's lymphoma (NHL), and 17 patients were asymptomatic. Cryoglobulin levels were monitored yearly after SVR. Median times to cryoglobulin disappearance were significantly different between type II and type III disease forms (36 vs. 12 months, pLog-Rank: 0.002). Improvement or complete cessation of complaints were parallel to the cryoglobulin disappearance. Vasculitis, in most cases (n = 16) and one NHL were cured spontaneously during follow-up observation. However, some patients required specific treatment, such as immunosuppression [n = 5] for vasculitis and combined chemotherapy [n = 1] for aggressive NHL. Relapses of cryoglobulinemia and related symptoms were detected in 2 patients. Importantly, polyneuropathy did not show improvement by any means.

Our results support that the monitoring of cryoglobulins is important even after SVR, especially in case of type II forms. Long-term complications such as severe vasculitis or NHL may still occur.