Background and aims: Hepatitis C virus (HCV) infection is associated with extrahepatic manifestations such as cryoglobulinemia and accounts for up to 90% of all cases of mixed cryoglobulinemia (MC). The present study aimed to evaluate the effect of sofosbuvir–­daclatasvir therapy on symptomatic HCV-related MC and sustained virologic response (SVR) achievement.
Patients and methods: This prospective cohort study was carried out on 120 patients with chronic HCV infection, clinically suspected to have MC, but only 63 of whom were positive for cryoglobulins. HCV-MC patients were treated with sofosbuvir 400 mg and daclatasvir 60 mg once daily for 3 months. The serum cryoglobulins levels, complement 3 (C3), complement 4 (C4) (using ELISA assay kits) and rheumatoid factor (RF) (using immunoturbidimetric assay kit), were measured in the included HCV infected patients (to confirm HCV-MC diagnosis), in addition to quantitave HCV-RNA assays, using real time PCR. All these measurements have been done before stating therapy and 12, 24 weeks post-therapy for assessments of immunological recovery, viral load and SVR.
Results: Significant increase in the serum cryoglobulin levels and RF with significant decrease in C3 and C4 serum levels were detected in only 63 out of 120 included HCV infected patients, upon whom the study has been completed. They showed significant decrease in their mean cryoglobulin levels from 41.47 µg/mL ±12.32 SD to 5.12 µg/mL ±3.59 SD then to 5.09 µg/mL ±3.02 SD, 12 to 24 weeks post-therapy respectively (p <0.001), with significant decline in RF concentrations and rise in C3 and C4 serum levels approaching the normal values. There were improvements in the presenting HCV-MC clinical manifestations in variable degrees, ranging from 5 (71.42%) in patients with glomerulonephritis to 62 (98.4%) in patients with purpura. Eighty-seven percent of the included patients showed complete response (clinical, virological and immunological recovery) and 13% showed partial response (virological and immunological recovery without clinical improvement of cryoglobulinemia associated manifestations).
Conclusion: A combined therapy of sofosbuvir 400 mg and daclatasvir 60 mg once daily for 3 months was associated with a significant decrease in serum cryoglobulin levels and appears as a reasonable treatment option for HCV-associated MC.
Keywords: directly acting antiviral drugs, mixed cryoglobulinemia, HCV

摘要视频链接：Sofosbuvir–daclatasvir improves hepatitis C virus–induced MC