Direct-acting antiviral agents in the therapy of hepatitis C virus-related mixed cryoglobulinaemia: a single-centre experience

Abstract

BackgroundThe efficacy and safety of direct-acting antiviral agents (DAAs) were evaluated in a cohort of prospectively enrolled patients with hepatitis C virus (HCV)-related mixed cryoglobulinaemia (MC), an immune complex-mediated vasculitis of small and medium vessels in which the pathogenetic role of HCV has been clearly established.MethodsTwenty-two patients received DAAs. Clinical and laboratory features were recorded at baseline, every 4 weeks until the end of treatment (EoT), and 12 weeks afterwards. Primary efficacy endpoints were (a) sustained virological response 12 weeks after therapy completion (SVR12), (b) regression of symptomatology (clinical response) and (c) cryoglobulin disappearance or cryocrit reduction ≥50% (immunological response). Complete response (CR) was defined as the occurrence of all three primary endpoints; partial response (PR) was defined as the occurrence of SVR12, with or without either immunological or clinical response; and no response was defined as missing the achievement of all three endpoints.ResultsAll patients reached SVR12. Compared with basal values, mean cryocrit values were significantly decreased at EoT and SVR12. A significant reduction of alanine transaminase and a parallel increase of complement component C4 levels were also detected. Rheumatoid factor activity was significantly reduced at EoT but not at SVR12. At SVR12, a CR was established in 14 patients (63.7%) and a PR in 8 patients (36.3%). In one patient with small lymphocytic lymphoma, the tumour progressed despite viral clearance. Mild adverse events were recorded in nine patients (40.9%).ConclusionsThe response rates induced by the use of DAAs in patients with MC were remarkably higher than those previously achieved with pegylated interferon-α/ribavirin, with or without rituximab. A much longer follow-up is desirable to achieve useful information in terms of persistent viral clearance and clinical response.

Interferon‐free therapy in hepatitis C virus mixed cryoglobulinaemia: a prospective, controlled, clinical and quality of life analysis

“…Thus, the presence of cryoglobulinaemia was a prognostic factor of non‐response independent from the severity of liver disease, or other well‐known prognostic factors . In this study, both intention to treat and per protocol analyses confirmed the excellent virological outcome reported by previous studies on CV or MC patients treated with DAAs, hindering a valuable logistic regression analysis to identify outcome predictors. In other words, using DAAs, it was not possible to find significant differences in SVR rates between cryoglobulinaemic patients and controls.…”

“…Data regarding these new IFN‐free regimens for the treatment of CV patients are still limited, and based on uncontrolled studies and short follow‐ups. These studies are generally consistent with high rates of symptom remission in patients with sustained virological response (SVR), as well as a high tolerance of therapy …”

Impact of mixed cryoglobulinemia on patients with spontaneous hepatitis C virus clearance: A 13‐year prospective cohort study

“…Namely, approximately half of CHC‐associated cryoglobulin disappeared after SVR. Thus, for patients with spontaneous HCV clearance, the MC prevalence of 34.6% is close to the proposed range based on the CHC studies (half of 40%‐60%), but is much higher than that of essential MC (0.001%) . The persistence of MC after viral clearance suggests that HCV antigens are not an unfailing component of cryoprecipitating immune complexes .…”

“…As mentioned, 40%‐60% of CHC patients exhibit circulating cryoglobulins . The clearance rate of cryoglobulin ranged from 35% to 59% in CHC patients who achieved an SVR by using DAAs and ranged from 43.6% to 57% in those who achieved an SVR by using interferon‐based therapy. Namely, approximately half of CHC‐associated cryoglobulin disappeared after SVR.…”

Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

“…Eradicating hepatitis C infection results in numerous health benefits, including reduced rates of allcause mortality, cirrhosis, hepatic decompensation, and HCC. (33,37,(98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108)(109)(110) Successful treatment also confers improvement in extrahepatic manifestations of HCV disease, including cryoglobulinemic vasculitis (111)(112)(113)(114)(115)(116) and HCV-related non-Hodgkin lymphoma and other lymphoproliferative disorders, (117)(118)(119)(120)(121)(122)(123)(124)(125) as well as improved productivity and quality of life. (34,35,(126)(127)(128)(129)(130)(131) Given these and other benefits associated with virologic cure, the HCV guidance panel strongly recommends antiviral treatment for all adults with acute or chronic HCV infection (except those with a short life expectancy that cannot be remediated).…”