Response to interferon alpha  treatment and disappearance of cryoglobulinaemia in patients infected by hepatitis C virus

Cresta, Pascale; Musset, Lucile; Cacoub, Patrice; Frangeul, Lionel; Vitour, Damien; Poynard, Thierry; Opolon, P; Nguyen, Duc T.; Golliot, Franck; Jc, Piette; Jm, Huraux; Lunel, F.

doi:10.1136/gut.45.1.122

Cited by 65 publications

(34 citation statements)

References 33 publications

(26 reference statements)

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“…However, the improvement is generally temporary [12], and the response is mild in patients with neuropathy [11,39]. Moreover, during acute immunological flare-ups, antiviral treatment is usually either insufficient to control vasculitic manifestations [36] or may even be detrimental, albeit able to reduce viremia [6].…”

Section: Introductionmentioning

confidence: 99%

Rituximab in cryoglobulinemic peripheral neuropathy

et al. 2009

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Type II mixed cryoglobulinemia is sustained by an oligoclonal production of IgM sharing rheumatoid activity and can be associated with renal, cutaneous, rheumatologic or neurological manifestations. Peripheral neuropathy is a major cause of morbidity in hepatitis C virus-associated mixed cryoglobulinemia and is often refractory to any treatment. Rituximab induces a selective depletion of IgM-producing B cells, and both case reports on monoclonal IgM-related polyneuropathy as well as studies on small series of patients with interferon alpha-resistant mixed cryoglobulinemia have suggested that it may be beneficial. Thirteen patients affected by type II mixed cryoglobulinemia with polyneuropathy were treated. Rituximab was administered intravenously at a dose of 375 mg/m(2) on days 1, 8, 15 and 22. Two more doses were given 1 and 2 months later. No other immunosuppressive drugs were added. Response was evaluated by assessing the changes in the clinical neurological condition, in electromyographic indices and in laboratory parameters (including cryocrit, viral load, complement levels and rheumatoid factor) over at least 12 months. Sensory symptoms disappeared or improved following treatment. A significant improvement in the clinical neuropathy disability score was observed. Electromyography examination revealed that the amplitude of compound motor action potential had increased. Viral load did not significantly change. Side effects were negligible. In this open prospective study, rituximab appeared to be effective and safe in the treatment of patients with type II cryoglobulinemia-associated neuropathy.

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Section: Introductionmentioning

confidence: 99%

Rituximab in cryoglobulinemic peripheral neuropathy

et al. 2009

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“…The first studies of the effects of IFN monotherapy showed the remission of symptoms in the majority of patients, but this benefit was often transient and relapses were very frequent after treatment discontinuation [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. However, the presence of cryoglobulinemia did not affect the response to IFN in patients with chronic HCV infection [34][35][36] [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. After a mean follow-up of 18.6 months (range of 6-33) following the discontinuation of antiviral therapy, seven patients (78%) showed a SVR and were complete clinical responders, and one a partial virological and a complete clinical response.…”

Section: Antiviral Therapymentioning

confidence: 99%

Recommendations for the management of mixed cryoglobulinemia syndrome in hepatitis C virus-infected patients

Pietrogrande¹,

Vita²,

Zignego³

et al. 2011

Autoimmunity Reviews

184

155

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Objective: The objective of this review was to define a core set of recommendations for the treatment of HCVassociated mixed cryoglobulinemia syndrome (MCS) by combining current evidence from clinical trials and expert opinion. Methods: Expert physicians involved in studying and treating patients with MCS formulated statements after discussing the published data. Their attitudes to treatment approaches (particularly those insufficiently supported by published data) were collected before the consensus conference by means of a questionnaire, and were considered when formulating the statements. Results: An attempt at viral eradication using pegylated interferon plus ribavirin should be considered the first-line therapeutic option in patients with mild-moderate HCV-related MCS. Prolonged treatment (up to 72 weeks) may be considered in the case of virological non-responders showing clinical and laboratory improvements. Rituximab (RTX) should be considered in patients with severe vasculitis and/or skin ulcers, peripheral neuropathy or glomerulonephritis. High-dose pulsed glucocorticoid (GC) therapy is useful in severe conditions and, when necessary, can be considered in combination with RTX; on the contrary, the majority of conference participants discouraged the chronic use of low-medium GC doses. Apheresis remains the elective treatment for severe, life-threatening hyper-viscosity syndrome; its use should be limited to patients who do not respond to (or who are ineligible for) other treatments, and emergency situations. Cyclophosphamide can be considered in combination with apheresis, but the data supporting its use are scarce. Despite the limited available data, colchicine is used by many of the conference participants, particularly in patients with mild-moderate MCS refractory to other therapies. Careful monitoring of the side effects of each drug, and its effects on HCV replication and liver function tests is essential. A lowantigencontent diet can be considered as supportive treatment in all symptomatic MCS patients. Although there are no data from controlled trials, controlling pain should always be attempted by tailoring the treatment to individual patients on the basis of the guidelines used in other vasculitides. Conclusion: Although there are few controlled randomised trials of MCS treatment, increasing knowledge of its pathogenesis is opening up new frontiers. The recommendations provided may be useful as provisional guidelines for the management of MCS.

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“…In our patients with symptomatic cryoglobulinemia, genotype 1 was most prevalent (73%) followed by genotype 2 (15%) and genotype 3 (8%) and this is representative of the North American population with hepatitis C infection [15]. It is well recognized that infection with genotype 2 or 3 serves as the strongest positive predictive factor for viral clearance in response to antiviral therapy in patients with and without cryoglobulinemia [16][17][18]. In our population of 38 treated patients, of those 16 who achieved SVR, 11 (69%) were genotype 1 and 5 (38%) had genotypes 2 or 3.…”

Section: Discussionmentioning

confidence: 87%

“…Zuckerman et al also reported that after treating nine patients with interferon plus ribavirin for 6 months, in which only two patients (22%) achieved SVR a substantial symptomatic improvement was observed in all [11]. Cresta et al observed that in their series of patients treated with interferon monotherapy, 12 patients with symptomatic cryoglobulinemia had symptomatic improvement despite only 1 achieving a SVR [16]. It is optimal to achieve a SVR to cure the infection and thus to eliminate the possibility of relapse; however, we observed in our patient population in all treatment groups that some degree of symptomatic response was evident regardless of virological response.…”

Section: Discussionmentioning

confidence: 94%

Symptomatic and Virological Response to Antiviral Therapy in Hepatitis C Associated with Extrahepatic Complications of Cryoglobulimia

Joshi¹,

Kuczynski²,

Heathcote³

2007

Dig Dis Sci

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Mixed cryoglobulins are detected in 50% of patients with hepatitis C; fortunately, few have vasculitis affecting skin, peripheral nerves, kidneys, and synovia. This study was designed to identify the natural history of symptomatic cryoglobulinemia and evaluate the response to antiviral therapy. Patients with hepatitis C complicated by symptomatic cryoglobulinemia were assessed for their disease manifestations and response to antiviral therapy. Of 83 patients identified, 56 patients with a minimum of 12 months follow-up were reviewed. Manifestations included dermatologic (75%), rheumatologic (57%), neurologic (34%), and renal (proteinuria 25%). Antiviral therapy was given to 38, of whom 9 were retreated for symptomatic and/or virological nonresponse. Antiviral therapy included interferon monotherapy (n = 8), pegylated-interferon monotherapy (n = 5), consensusinterferon (n = 2), interferon + ribavirin (n = 18), and pegylated-interferon + ribavirin (n = 14). Treatment provided sustained symptomatic response in 31 (82%) and virological response in 16 (42%) patients. Symptomatic cryoglobulinemia responds well to antiviral therapy, even when virological response is not achieved.

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Response to interferon alpha treatment and disappearance of cryoglobulinaemia in patients infected by hepatitis C virus

Cited by 65 publications

References 33 publications

Rituximab in cryoglobulinemic peripheral neuropathy

Rituximab in cryoglobulinemic peripheral neuropathy

Recommendations for the management of mixed cryoglobulinemia syndrome in hepatitis C virus-infected patients

Symptomatic and Virological Response to Antiviral Therapy in Hepatitis C Associated with Extrahepatic Complications of Cryoglobulimia

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