Background Mixed cryoglobulinemia is one of the most important extrahepatic manifestations of chronic hepatitis C infection. Aims and Methods 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. Results 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. Conclusions 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.

Background and aims: Acute decompensation (AD) of cirrhosis is a critical clinical event with heterogeneous outcomes, ranging from stable decompensated (SD) cirrhosis to acute-on-chronic liver failure (ACLF). Disturbances in the primary and secondary hemostasis have been implicated in the progression of cirrhosis. This study aimed to evaluate changes in primary hemostasis, i.e., VWF parameters, multimer distribution and ADAMTS13 activity in patients who could clinically improve after AD. Methods: Thirty-five cirrhotic patients hospitalized with AD were prospectively assessed at baseline and at 3-month follow-up when they reached an SD state. Clinical and laboratory characteristics, including the MELD score, were evaluated at both time points. VWF level and its different activities were measured using automated immunoassays, ADAMTS13 activity by chemiluminescent assay, and VWF multimer distribution using electrophoresis and densitometry. Results: At AD, at least one organ failure occurred in 13 patients, with 4 patients identified as ACLF grade 1. The MELD score was 22 (IQR 18–25) at AD, while at 3 months (SD) it was 17 (12–20) (p < 0.001). VWF parameters similarly decreased [VWF antigen 530% vs. 409% (p = 0.009), VWF activity 332% vs. 301% (p = 0.038), VWF collagen-binding 399% vs. 308% (p = 0.017)], while ADAMTS13 activity increased from 55% to 84% (p < 0.001). Ultra-large VWF multimers (ULMWM) were detected in six patients during AD but were absent in all SD samples, while ADAMTS13 activity normalized. Conclusions: Our findings demonstrate that the VWF–ADAMTS13 axis in cirrhosis is a dynamically changing marker, and the temporary appearance of ULMWM during AD exposes thrombogenic potential in cirrhosis.