Evolution of Cryoglobulinemia in Direct-Acting Antiviral-Treated Asian Hepatitis C Patients With Sustained Virological Responses: A 4-Year Prospective Cohort Study

Abstract

BackgroundHow cryoglobulinemia evolves after sustained virological response (SVR) following direct-acting antiviral (DAA) treatment in Asian hepatitis C virus (HCV)-infected patients remains elusive.MethodsA prospective cohort study was conducted in 422 Taiwanese patients (358 completed DAA therapy and 353 experienced SVRs). Serum cryoglobulins were surveyed at baseline and every 3-6 months posttherapy.ResultsOf 422, 227 (53.8%) had cryoglobulinemia, 8 (1.89%) had cryoglobulinemic vasculitis. Of 227, 54 (23.8%), 57 (25.1%) and 116 (51.1%) had 1, 2 and 3 cryoglobulins, respectively; those with 3 cryoglobulins had the highest alanine aminotransferase, immunoglobulin G (IgG) and fibrosis-4 index. During a 4-year follow-up, among SVR patients, cryoglobulinemia rates decreased from 56.4% to 15.4%, single cryoglobulin rates increased (21.6% to 63.9%) and 3 cryoglobulin rates decreased (55.7% to 11.1%). Compared with baseline values, among SVR patients with baseline cryoglobulinemia, complement component 4 levels increased, and IgG and IgM levels decreased until 48 weeks posttherapy for those without posttherapy cryoglobulinemia. All 8 cryoglobulinemic vasculitis patients exhibited SVRs; 5 (62.5%) achieved complete clinical response 12 weeks posttherapy, of whom, 2 (40%) experienced clinical relapse 24~48 weeks posttherapy. Baseline IgM levels were associated with posttherapy cryoglobulinemia in SVR patients (cut-off values at 12, 24, 48 weeks and 4 years posttherapy: 130, 105, 118 and 168 mg/dL, respectively).ConclusionsAmong DAA-treated SVR patients, in 4 years, cryoglobulinemia rates decreased from 56.4% to 15.4%, multiple cryoglobulin rates decreased, cryoglobulinemia signals reversed, 62.5% of cryoglobulinemic vasculitis patients achieved complete clinical response (40% had relapse), and baseline IgM levels indicated posttherapy cryoglobulinemia.

Cryoglobulinemic vasculitis: a 2023 update

“…Cryocrit and RF show a significant decrease and C4 levels increase after therapy [40 ▪ ], with persistent cryoglobulinemia associated with advanced liver fibrosis [41,42]. Cryoglobulins reduction has persisted over a 4-years follow-up period in an Asian cohort [43]. Clinical worsening and relapse are associated with high rheumatoid factor levels before treatment [40 ▪ ,44].…”

Unveiling Mixed Cryoglobulinemia in Suspected Sepsis Without a Source

“…In this regard, it has been shown that the immune response triggered by chronic HCV infection leads to the formation of cryoglobulins, causing vasculitis and various clinical manifestations such as skin lesions, joint pain, and kidney involvement [ 3 ]. Before the advent of direct-acting antivirals (DAAs), HCV infection was a common cause of MC [ 7 ]. However, with the introduction of DAAs for the treatment of HCV, the landscape of mixed cryoglobulinemia has seen an etiological shift toward autoimmune and lymphoproliferative disorders, HCV-related MC treated with DAA has shown dramatic amelioration and prevented further organ damage [ 7 ].…”

“…Before the advent of direct-acting antivirals (DAAs), HCV infection was a common cause of MC [ 7 ]. However, with the introduction of DAAs for the treatment of HCV, the landscape of mixed cryoglobulinemia has seen an etiological shift toward autoimmune and lymphoproliferative disorders, HCV-related MC treated with DAA has shown dramatic amelioration and prevented further organ damage [ 7 ]. In this article, we summarize the clinical course and diagnostic approach of a case of MC type III secondary to HCV infection.…”