Interferon-alpha in mixed cryoglobulinemia patients: a randomized, crossover-controlled trial

Ferri, Clodoveo; Marzo, E; Longombardo, G.; Lombardini, Fabrizio; Civita, L. La; Vanacore, Renato; Liberati, Anna Marina; Gerli, Roberto; Greco, Francesco; Moretti, A; Monti, Monica; Geñtilini, Paolo; Bombardieri, Stefano; Zignego, Anna Linda

doi:10.1182/blood.v81.5.1132.1132

Cited by 265 publications

(63 citation statements)

References 26 publications

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“…Interferon-a has been shown to be clinically ef®cacious in the management of HCV-associated MC in several large randomized studies. 6 Unfortunately, our patient falls into the worse prognostic group with high viral load (> 2´10 6 HCV copies ¤ mL blood), genotype I, more than 40 years of age, and evidence of liver ®brosis. Other reasons for treatment failure in this case may be due to the delay in reaching a ®nal diagnosis due to false-negative serology and inadequate duration of treatment (6±12 months minimum).…”

Section: Discussionmentioning

confidence: 84%

Long-term follow-up of a patient with cutaneous vasculitis secondary to mixed cryoglobulinaemia and Hepatitis C virus

Kapur¹,

Tympanidis²,

Colville

et al. 2002

Clinical and Experimental Dermatology

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We describe the clinical course of a patient with mixed cryoglobulinaemia and multisystem disease over a 21-year period. She consistently tested negative for hepatitis C virus (HCV) serology, but active HCV infection (genotype Ia) was confirmed using reverse transcription-polymerase chain reaction. After initial improvement following treatment with interferon-alpha and ribavirin, unfortunately she developed severe neutropenia necessitating discontinuation of both drugs within 4 weeks. She died 1 month later.

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Section: Discussionmentioning

confidence: 84%

Long-term follow-up of a patient with cutaneous vasculitis secondary to mixed cryoglobulinaemia and Hepatitis C virus

Kapur¹,

Tympanidis²,

Colville

et al. 2002

Clinical and Experimental Dermatology

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“…Early studies using IFN monotherapy showed that, in spite of a clinical-immunological response during treatment, both infection and vasculitis generally relapsed after treatment. [32][33][34][35] The MC response improved with the increased efficacy of antiviral therapy, passing from recombinant IFN 32 to PEG-IFN plus RBV. This latter combination, in some studies, was able to lead to a clinical response ranging from 62.5% to 78% of patients, 17,36 suggesting that it should be the first therapeutic option for patients with HCV-MCS.…”

Section: Discussionmentioning

confidence: 99%

Long‐term effect of HCV eradication in patients with mixed cryoglobulinemia: A prospective, controlled, open‐label, cohort study

et al. 2015

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Limited data are available about the efficacy of antiviral treatment in hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC), especially concerning the long-term effects of HCV eradication. The aim of this study was to evaluate the influence of MC on the virological response and the long-term effects of viral eradication on MC. We prospectively enrolled 424 HCV 1 patients belonging to the following groups: MC syndrome (MCS)-HCV (121 patients with symptomatic MC), MC-HCV (132 patients with asymptomatic MC), and HCV (158 patients without MC). Pegylated interferon plus ribavirin treatment was administered according to standard protocols. Posttreatment follow-up ranged from 35 to 124 months (mean 92.5 months). A significant difference was observed in the rate of sustained virological response between the HCV group and both the MC-HCV (P 5 0.009) and MC-HCV1MCS-HCV (P 5 0.014) groups. Multivariate logistic regression analysis identified cryoglobulinemia as an independent prognostic factor of nonresponse. The clinical-immunological response in MCS-HCV correlated with the virological one. All patients with sustained virological response also experienced a sustained clinical response, either complete or partial. In the majority of sustained virological response patients all MCS symptoms persistently disappeared (36 patients, 57%); in only two (3%) did definite MCS persist. All virological nonresponders were also clinical nonresponders, in spite of a transient improvement in some cases. No evolution to lymphoma was observed. For the first time we have evaluated both the effects of interferon-based therapy on HCV patients with and without MC and with and without symptoms, as well as the long-term effects of viral eradication on MC. Conclusion: MC is a negative prognostic factor of virological response. Clearance of HCV led to persistent resolution or improvement of MCS, strongly suggesting the need for a next generation of highly effective antiviral drugs. (HEPATOLOGY 2015;61:1145-1153 M ixed cryoglobulinemia (MC) is an autoimmune/lymphoproliferative disorder characterized by circulating immune complexes named cryoglobulins (CGs) that reversibly precipitate at low temperatures. The CGs are comprised of polyclonal immunoglobulin Gs (including anti-hepatitis C virus [HCV] immunoglobulin) and mono-or polyclonal immunoglobulin M with rheumatoid factor activity, sustained by the clonal expansion of rheumatoid factor B cells.

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“…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.…”

Section: Antiviral Therapy: Historical Use Of Ifn and Ribavirin In Hcmentioning

confidence: 99%

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

Rutledge

Chung

Sise

2018

Hemodialysis International

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Cryoglobulinemia is a common extrahepatic manifestation of infection with hepatitis C virus (HCV). When signs and symptoms of systemic vasculitis or glomerulonephritis occur in the presence of circulating cryoglobulins, this syndrome is called "mixed cryoglobulinemia syndrome" (MCS). Historically, interferon-based therapies in HCV have been associated with lower rates of viral cure in patients with MCS than in the general HCV-infected population. The advent of direct-acting antiviral therapies have revolutionized the treatment of HCV, dramatically increasing rates of cure. Early studies of first-generation protease inhibitors (telaprevir and boceprevir) in combination with interferon and ribavirin demonstrated HCV cure rates of 67% and complete clinical response rates of vasculitis symptoms in 60% of patients with MCS; however, regimens were poorly tolerated by patients, 22% discontinued treatment early. More recently, all-oral, interferon-free regimens have become available and combination therapies are now being approved for patients with and without renal impairment. Patients with HCV-MCS achieved sustained virologic response in 297 out of 313 patients (95%) treated with direct-acting antiviral therapy, and 85% had a complete or partial clinical response of MCS symptoms. Current direct-acting antiviral therapies are well tolerated in patients with HCV-MCS and only 1.6% discontinued treatment early. Patients with cryoglobulinemic glomerulonephritis also had an excellent cure rate (94%). The majority improved; 17/52 (33%) experienced full remission and 15/52 (29%) experienced partial remission. There were no reports of worsening kidney function in patients treated with direct-acting antiviral therapies. Less than 5% of patients with HCV-MCS treated with IFN-free direct-acting antiviral therapy required immunosuppression. However, patients with severe vasculitis appear to still require concomitant immunosuppression.

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Interferon-alpha in mixed cryoglobulinemia patients: a randomized, crossover-controlled trial

Cited by 265 publications

References 26 publications

Long-term follow-up of a patient with cutaneous vasculitis secondary to mixed cryoglobulinaemia and Hepatitis C virus

Long-term follow-up of a patient with cutaneous vasculitis secondary to mixed cryoglobulinaemia and Hepatitis C virus

Long‐term effect of HCV eradication in patients with mixed cryoglobulinemia: A prospective, controlled, open‐label, cohort study

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

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