Predictors of Long-Term Response to High-Dose Interferon Therapy in Type II Cryoglobulinemia Associated With Hepatitis C Virus Infection

Abstract

We have prospectively studied patients with type II cryoglobulinemia since 1985 to assess the efficacy of treatment with interferon-α at cumulative doses ranging from 234 to 849 MU. In the present study we retrospectively evaluated in this cohort parameters associated with complete response to therapy in 31 consecutive patients with type II cryoglobulinemia associated with hepatitis C virus (HCV) infection. Prevalence of complete response of cryoglobulinemia (disappearance of symptoms and signs of vasculitis and decrease of cryocrit below 10% of the initial value) was 62%, with a median response duration of 33 months and a range of 3 to 100 months. Three patients were putatively cured, as they remained in complete remission for more than 5 years off therapy. Eighteen patients (58%) had liver disease evidenced by histopathology and/or raised transaminase levels. Prevalence of normalization of transaminase levels was 100%, with a median response duration of 36 months. Relapse of hypertransaminasemia occurred in 100% and 8% of patients receiving less than or greater than 621 MU, respectively. By logistic regression analysis, the only pretherapy parameter that associated significantly (P = .0393) with complete response of cryoglobulinemia was the solitary anti-C22 (HCV core) antibody pattern, which was observed in 29% of patients. Association with older age and low cryocrit approached statistical significance (P = .06), while no significant correlations were found with serum IgM levels, duration of disease, HCV genotype, NS5a gene mutations, liver histology, HLA-DR phenotype, or WA cross-idiotype. Complete responses were also associated, on univariate statistical analysis, with low pretherapy HCV viremia. Responses were accompanied by decrease of viremia, of anti-HCV antibody levels and cryocrit. The usefulness of a high dose regimen is underscored by the higher rates of sustained responses of cryoglobulinemia and transaminase levels compared with previous studies.

Prospective study of guideline‐tailored therapy with direct‐acting antivirals for hepatitis C virus‐associated mixed cryoglobulinemia

“…This outcome is of particular relevance because these manifestations of MC vasculitis appear to be associated with increased mortality and high health care costs. (15,48) Finally, while a correlation between decrease of cryocrit and response of MC vasculitis has been reported in patients treated with IFNbased therapy, (11) we failed to clearly show this trend.…”

Treatment of hepatitis C virus infection in patients with mixed cryoglobulinemic syndrome and cryoglobulinemic glomerulonephritis

“…Complete clinical response usually but not always correlates with SVR, which is synonymous with cure. 58,59 However, IFN-based therapies are less likely to lead to SVR in patients with HCV-MCS than in the general HCV-infected population. 60 IFN-a monotherapy achieved SVR in 4%-27% of patients with HCV-MCS and a moderate complete clinical response rate of 27%-62%.…”

“…60 IFN-a monotherapy achieved SVR in 4%-27% of patients with HCV-MCS and a moderate complete clinical response rate of 27%-62%. 58,59,[61][62][63] The combination of pegylated IFN-a with RBV is more efficacious, resulting in SVR rates of 18%-54% and complete clinical response rates of 44%-77%, although relapse rates are still as high as 60%, and because of this improvement in renal manifestations is only seen in 50%. 45,[63][64][65][66][67] Patients whose HCV relapses after IFN-based treatment typically have recurrence of HCV-MCS symptoms.…”

“…99 SVR after IFN-based therapy leads to clinical remission in 88%-97% of patients who are cured of the virus. 58,59,[100][101][102] The discrepancy between IFN-and DAA-treated patients may be explained by the longer treatment courses with IFN, thus at the time of SVR measurement, patients had been virus-free for longer and were more likely to have clinically responded. Additionally, it is possible that many patients treated with DAA-based therapy had failed prior rounds of IFN-based therapy and thus had HCV-MCS for an extended period of time prior to being cured.…”

“…The link between cryoglobulin decline and clinical response is less clear in DAA treated patients than in the IFN-treated population, of whom nearly all clinical responders had disappearance of cryoglobulins. 58,59 In some recent series of patients treated with DAAs, clearance of cryoglobulins lagged substantially behind viral clearance and clearance of cryoglobulins did not necessarily ensure complete resolution of clinical symptoms. 86,96,103 Bonacci et al demonstrated that 73% of immunologic responders also had clinical improvement but immunologic parameters normalized only in 37% of patients with clinical response.…”