Treatment of chronic hepatitis C-associated cryoglobulinemia vasculitis at the era of direct-acting antivirals

Abstract

Hepatitis C virus (HCV) infection is responsible for both hepatic and extrahepatic manifestations. Before the era of direct-acting antivirals (DAA), cryoglobulinemia was related to HCV infection in 70–90% of cases. Observed in 30% to 40% of patients with hepatitis C, mixed cryoglobulinemia is mainly asymptomatic. Conversely, symptomatic cryoglobulinemia vasculitis (CV) can occur in 5–10% of patients with HCV-associated cryoglobulinemia. CV is a small-vessel systemic vasculitis, and organ damage results from circulation and precipitation of cryoglobulins and complement activation. A wide range of clinical symptoms can be observed during CV, and manifestations are potentially life-threatening. The most frequent manifestations occurring in CV are cutaneous, with recurrent purpura, articular with joint pains, neurologic with peripheric neuropathy, and renal with membranoproliferative glomerulonephritis. DAA have drastically changed chronic HCV therapy. DAA induce sustained virological response (SVR) rates greater than 95%, and also improve extrahepatic manifestations such as CV. We review recent studies investigating the clinical and immune effects of DAA therapy on HCV-CV.

HCV-related lymphoproliferative disorders in the direct-acting antiviral era: From mixed cryoglobulinaemia to B-cell lymphoma

“…Less than 5% of patients discontinue DAA treatment (79). Of note is that in the DAA era the mortality rate of HCV-CryoVas is less than 3% compared with 40 to 60% in the IFN era (79).…”

“…Less than 5% of patients discontinue DAA treatment (79). Of note is that in the DAA era the mortality rate of HCV-CryoVas is less than 3% compared with 40 to 60% in the IFN era (79). However, achievement of an SVR is necessary but not sufficient to achieve a complete immunological response, as 6 to 12 months following DAA therapy cryoglobulins remain present in about 50% of patients (Figure 5B).…”

Human hepatitis viruses-associated cutaneous and systemic vasculitis

“…Occasionally, extrahepatic-related autoimmune comorbidities such as cryoglobulinemia vasculitis can lead to the diagnosis of HCV infection[ 76 ]. Sustained eradication of HCV by IFN-α or DAA agents has shown to be beneficial for outcomes following these manifestations[ 78 , 79 ]. Notably, a prospective study with 9895 HCV-infected cases receiving DAA medications revealed that viral clearance is responsible for a significant decrease in HCV extrahepatic mortality[ 80 ].…”

“…Anti-HCV therapy can follow the existing guideline as cryoglobulinemia does not specifically influence the choice of antiviral drug[ 138 ]. DAA agents alone induce SVR with less adverse events and are more effective than the combined IFN-α and ribavirin regimen in cryoglobulinemic vasculitis[ 79 ]. In a prospective multicenter study carried out in these patients, all achieved SVR with a 90% complete clinical response after DAA therapy for 12 wk or more[ 139 ].…”

“…In a prospective multicenter study carried out in these patients, all achieved SVR with a 90% complete clinical response after DAA therapy for 12 wk or more[ 139 ]. Altogether, patients with HCV-associated cryoglobulinemic vasculitis had higher SVR (74%-100%) and clinical remission (61%-100%) rates after receiving DAA medications[ 79 ]. Higher complete response rates (75%-100%) were observed in cutaneous and musculoskeletal presentations, while lower responses (30%-70%) were identified in peripheral nerve and renal involvement[ 139 ].…”