Symptomatic Mixed Cryoglobulinemia Research Articles

Serological profile of asymptomatic HCV positive patients with low level of cryoglobulins.

Clinical spectrum of hepatitis C virus (HCV)-related cryoglobulinemia varies from an asymptomatic presentation to severe vasculitis and lymphoma. A recent study in HCV-negative patients suggests that low cryoglobulins (CGs) levels are responsible for severe renal and neurological complications. The aim of this study was to identify a panel of serological biomarkers associated with low levels of CGs in HCV-positive patients. We studied a population of 79 untreated patients with chronic HCV infection: 13 naïve patients without CGs; 28 patients with asymptomatic mixed cryoglobulinemia (MC) and low levels of CGs (16/28 with polyclonal type III and 12/28 with microheterogeneous type III CGs); 38 patients with symptomatic MC and high levels of type II CGs. Serum samples were collected and examined for rheumatoid factor (RF) IgG and IgM, free light chains (FLCs) and C3 and C4 complement components. We found that RF-IgG and IgM, free k chains and k+λ were increased while C4 component was reduced, both in symptomatic and asymptomatic patients. Our results suggest that, even in absence of MC symptoms, the low levels of CGs may represent a trigger of activation for immune system in course of HCV infection. The identification of a correlated biomarkers panel could improve the clinical management of these patients and pave the way for target treatment strategies. © 2018 BioFactors, 45(3):318-325, 2019.

FRI-216 - Sofosbuvir/Ribavirin treatment in patients with genotype 2, Hepatitis C Virus infection and symptomatic mixed cryoglobulinemia: an interim analysis on safety, efficacy and impact on quality of life

FRI-216 - Sofosbuvir/Ribavirin treatment in patients with genotype 2, Hepatitis C Virus infection and symptomatic mixed cryoglobulinemia: an interim analysis on safety, efficacy and impact on quality of life

Mixed Cryoglobulinemia and HCV: An Overview

Chronic Hepatitis C Virus (HCV) is a worldwide public health problem affecting over 170 million people, or about 3% of the world’s population. In Egypt, the situation is quite worse, with the overall prevalence (percentage of people) positive for antibody to HCV being 14.7% [1]. HCV predominantly affects the liver but it can also produce a number of extra hepatic manifestations. It has been reported that 74% of patients with hepatitis C have at least one extra hepatic manifestation, the most common conditions including essential mixed cryoglobulinemia (40%), arthralgia or joint pain (23%), paresthesia (17%), myalgia (15%), pruritus (15%), and sicca syndrome (11%) [2]. Cryoglobulinemia is a haematological disorder caused by abnormal proteins deposited in small and medium-sized blood vessels called cryoglobulins aggregated together with cooling of the blood and then dissolve again when rewarmed. These can lead to vascular insufficiency in the affected organs(eg. Jointsm types II and III have rheumatoid factor whereas it is absent in type I (Table 1). The most common and severe form Is Mixed Cryoglobulinemia (MC), a systemic vacuities involving small and medium-sized arteries and veins. MC is characterized by the deposition of immune complexes containing mainly rheumatoid factor, IgG, HCV RNA, and complement on endothelial surfaces, resulting in vascular inflammation, albeit through poorly understood mechanisms. Moreover, HCV can trigger impairment in lymph proliferation with cryoglobulin production [3]. A triad of purpura, arthralgia, and asthenia is the most characteristic clinical features of this syndrome, involvement of the renal & peripheral nervous systems commonly occur [4]. In a large prospective study of 1614 patients chronically infected with HCV, mixed cryoglobulinemia was the predominant extra-hepatic biologic manifestation, identified in 40% of patients. Using multivariate analysis, four independent factors were found to be significantly associated with the presence of cryoglobulins: female sex, alcohol consumption more than 50 g/d, HCV genotype II or III, and extensive liver fibrosis. Cryoglobulin-positive patients were examined for arthralgias, arterial hypertension, purpura, and systemic vasculitis. Considering the high frequency of positive cryoglobulins in patients with HCV, severely symptomatic mixed cryoglobulinemia with vasculitis was rare, noted in only 2 to 3% of cryoglobulin-positive patients [3,5].

Triple antiviral therapy in hepatitis C virus infection with or without mixed cryoglobulinaemia: a prospective, controlled pilot study.

Mixed cryoglobulinaemia is strongly related to hepatitis C virus infection. Treatment with peg-interferon and ribavirin has been indicated as first-line therapy for mild/moderate hepatitis C virus-related mixed cryoglobulinaemia. To evaluate the safety and efficacy of triple boceprevir-based antiviral therapy in patients with or without mixed cryoglobulinaemia previously treated with peg-interferon and ribavirin, and with advanced liver disease. Thirty-five hepatitis C virus-positive patients (17 with asymptomatic mixed cryoglobulinaemia, 5 with symptomatic mixed cryoglobulinaemia, and 11 without mixed cryoglobulinaemia) were treated with triple boceprevir-based antiviral therapy. In 19/22 cryoglobulinaemic subjects (86%), the addition of boceprevir induced cryocrit disappearance. Cryocrit behaviour was related to virological response, with improvement of symptoms upon undetectable viraemia and reappearance after virological breakthrough. The rate of sustained virological response was lower in cryoglobulinaemic patients than in patients without mixed cryoglobulinaemia (23.8% vs 70% respectively, p=0.01). Boceprevir-based therapy was safe and effective in cryoglobulinaemic patients. The correlation between direct inhibition of hepatitis C virus replication and clinical improvement in mixed cryoglobulinaemic patients is definitive proof of the key pathogenetic role played by viral replication. Further studies are needed to confirm and clarify the reduced virological response in patients with mixed cryoglobulinaemia.

Antiviral therapy of symptomatic HCV‐associated mixed cryoglobulinemia: Meta‐analysis of clinical studies

Hepatitis C virus (HCV) infection may be associated with extra-hepatic illness including mixed cryoglobulinemia. Evidence on HCV-related mixed cryoglobulinemia in the non-transplantation setting exists even if its appropriate management remains unclear. The cornerstone of treatment for symptomatic HCV-associated mixed cryoglobulinemia is antiviral therapy but little is known about its activity. A systematic review of the literature with a meta-analysis of clinical studies was performed in order to assess efficacy and safety of combination antiviral therapy for symptomatic HCV-associated mixed cryoglobulinemia in non-immunosuppressed individuals. The random effects model of DerSimonian and Laird was used, with heterogeneity and sensitivity analyses. The primary outcome was sustained virological response (as a measure of efficacy), and the secondary outcome was the rate of patients stopping (or dose reducing) antiviral agents (as a measure of tolerability). Ten clinical studies (300 unique patients) were identified; the rate of baseline kidney involvement ranged between 4% and 39%. The summary estimate of frequency of sustained viral response was 0.42 with a 95% confidence interval (CI) of 0.31; 0.54 (random effects model). Significant heterogeneity occurred (P = 0.00001; I(2) = 77.6%). Stratified analysis showed higher efficacy in those studies using combination therapy with pegylated-than conventional IFN; the summary estimate of sustained viral response being 0.52 (95% CI, 0.40; 0.63) and 0.32 (95% CI, 0.15; 0.49), respectively. There was good association between viral and clinical response, weighted K 0.634 (95% CI, 0.455; 0.814), by a meta-analysis at individual level on a subset of reports (n = 3; 74 unique patients). The summary estimate of frequency of patients stopping (or dose reducing) antiviral agents was 0.15 (95% CI, 0.08; 0.21); no heterogeneity occurred (P = 0.05; I(2) = 51%). In summary, combination antiviral therapy (pegylated IFN plus ribavirin) gives satisfactory response in more than the half of patients with symptomatic mixed cryoglobulinemia associated with HCV. HCV-related mixed cryoglobulinemia is uncommon in developed countries and this clearly hampers randomized controlled clinical trials aimed to evaluate efficacy and safety of antiviral therapy in non-immunosuppressed individuals.

Clinical Spectrum, Treatment, and Outcome of Patients with Type II Mixed Cryoglobulinemia without Evidence of Hepatitis C Infection

The clinical spectrum, etiologies, and best therapeutic approaches of type II mixed cryoglobulinemia (MC) not associated with hepatitis C virus (HCV) infection have been poorly described to date. We studied the clinical presentation and outcome of patients with type II MC with no evidence of HCV. This was a multicenter retrospective study on the clinical presentation and outcome of patients with type II MC without evidence of HCV infection. Only patients with symptomatic MC were included. Thirty-three patients were included (median followup 67.2 mo). Extensive investigations for associated diseases were performed at presentation. MC was related to an autoimmune disease in 14 patients, to a lymphoid malignancy in 4 patients, and to an infectious disease in 2 patients, while MC was classified as essential (primary) in 13. Essential MC tended to be more severe than secondary disease with, in particular, more frequent renal and peripheral nerve involvement. Most patients were treated with steroid with or without immunosuppressive agents, mainly cyclophosphamide. These treatments were unable to induce sustained remission. One patient was successfully treated with lenalidomide. Seven patients with nonmalignant MC were treated with rituximab; 2 had a sustained complete remission, 3 improved greatly but relapsed within 5 months, and 2 experienced a disease flare. An important proportion of non HCV-related type II MC remains essential. Efforts should be made to find other etiologies than HCV, because treatments with steroid and immunosuppressants are not satisfactory, especially in severe forms. In these situations anti-CD20 therapy may present the best option but should be used with caution. New agents such as lenalidomide remain to be evaluated.

Symptomatic Mixed Cryoglobulinemia during HIV Primary Infection: A Case Report

We report a patient who developed during HIV primary infection a symptomatic mixed cryoglobulinemia. The patient suffered from arthralgias, vascular purpura of the legs, and proteinuria. Cryoglobulinemia progressively disappeared in several months after HAART.

Hepatitis C: crioglobulinemia y linfoma no-Hodgkin

Hepatitis C virus infection plays a major role in the pathogenesis of mixed cryoglobulinemia, promoting activation and expansion of B cells. These molecular rearrangements induce synthesis of cryoglobulins and the appearance of cryoglobulinemic vasculitis. Clearance of the virus promotes resolution of the clinical manifestations and immunological disorders seen in mixed cryoglobulinemia in a large percentage of patients, but not in all. In some cases, cryoglobulinemia could appear after sustained response. Several steps in the pathogenesis of mixed cryoglobulinemia are strongly related to HCV infection and when the virus is eliminated, the disease course improves. However, independent steps related to other factors do not improve following viral clearance. In some types of low-grade non-Hodgkin lymphoma (lymphomoplasmocytic lymphoma, marginal zone lymphoma) sustained response following antiviral treatment induces remission of the neoplasm. HCV has a minor role in aggressive lymphomas and clearance of the virus may not induce remission, but could decrease the hepatotoxicity associated with the chemotherapy.Therefore, in chronic hepatitis C, the combination of peginterferon + ribavirin is strongly recommended in treating symptomatic mixed cryoglobulinemia and HCV-related non-Hodgkin lymphomas.

Cryoglobulinemia in chronic hepatitis C: clinical aspects and response to treatment with interferon alpha and ribavirin

The main extra-hepatic manifestation of hepatitis C is mixed cryoglobulinemia (MC). The aim of this study was to evaluate its prevalence among patients with chronic hepatitis C (CHC), to correlate its presence to host and virological variables and to the response to combined therapy with interferon-alpha and ribavirin. 202 CHC naive patients (136 with chronic hepatitis and 66 with cirrhosis) were consecutively evaluated for the presence of cryoglobulins. Cryoprecipitates were characterized by immunoelectrophoresis and classified according to the Brouet's criteria. The prevalence of MC was 27% (54/202), and 24% of them (13/54) showed major clinical manifestation of the disease. Even though type III MC was more frequent (78%), symptomatic MC was more common in type II MC. The presence of cirrhosis (RR=2.073; IC95%=1.029-4.179; p=0.041), and age of the patients (RR=1.035; IC95%=1.008-1.062; p=0.01) were independently associated with the presence of cryoglobulins. No relationship was found with viral load and genotype. 102 patients were treated with interferon alpha and ribavirin. Among these, 31 had MC. Sustained virological response (around 30%) was similar in patients with and without MC (p=0.971). MC represents a prevalent complication in patients with CHC, specially older and cirrhotic patients. Only 24% of these patients show clinical manifestation of the disease, specially those with type II MC. The presence of MC did not affect the response to therapy.

Hepatitis C virus and non-Hodgkin's lymphoma 10 years later

Hepatitis C virus is associated with chronic liver disease as well as with lymphoproliferative disorders such as mixed cryoglobulinemia and, likely, non-Hodgkin's lymphomas. The association between hepatitis C virus infection and B-cell lymphoma is controversial since it shows a strong regional variation. In fact, the prevalence of hepatitis C virus infection in non-Hodgkin's lymphoma shows a prevalence ranging between 7.4 and 37.0%. However, the intimate pathogenetic mechanism involved in hepatitis C virus-associated lymphomas remains considerably unknown. Hepatitis C virus may exert its oncogenic potential via an indirect mechanism or utilise other pathways directly. It is reasonable to assume that several different pathogenetic mechanisms operate in the wide spectrum of hepatitis C virus-related lymphoproliferative disorders, which include the intermediate to high-grade lymphoma, and the more common indolent, low-grade lymphoma, preceded by long standing symptomatic mixed cryoglobulinemia Type II. In this review, the etiopathogenetic role of hepatitis C virus in non-Hodgkin's lymphoma is discussed on the basis of molecular, clinical and epidemiological considerations. The management of hepatitis C virus-associated non-Hodgkin's lymphoma is similar to that of conventional lymphoma, although viral reactivation or the underlying chronic liver disease can complicate chemotherapy. Whether to treat low-grade hepatitis C virus-related lymphomas with anti-viral therapy is still debatable, but encouraging data emerge from some recent studies.

CD4+CD25+ regulatory T-cell deficiency in patients with hepatitis C-mixed cryoglobulinemia vasculitis

AbstractPatients who are chronically infected with hepatitis C virus (HCV) often develop mixed cryoglobulinemia (MC), a B-cell proliferative disorder with polyclonal activation and autoantibody production. We investigated if MC is associated with a deficit of CD4+CD25+ immunoregulatory T (Treg) cells, which have been shown to control autoimmunity. Because Treg cells express higher amounts of CD25 than activated CD4+ T cells, we analyzed blood CD4+CD25high Treg cells in 69 untreated patients chronically infected with HCV. Treg cell frequency in patients without MC (8.8% ± 2.3%) or with asymptomatic MC (7.4% ± 2.1%) was comparable to that of healthy controls (7.9% ± 1.3%). In contrast, it was significantly reduced in symptomatic MC patients (2.6% ± 1.2%, P < .001) even when compared to a panel of untreated HCV- patients with different inflammatory disorders (6.2% ± 0.8%, P < .0001). In symptomatic MC patients, the purified remaining CD4+CD25+ T cells retained suppressive activity in vitro. These results, together with experimental data showing that depletion of Treg cells induces autoimmunity, suggest a major role of Treg cell deficiency in HCV-MC vasculitis and this is the first report of a quantitative Treg cell deficiency in virus-associated autoimmunity. (Blood. 2004; 103:3428-3430)

Treatment recommendations in Waldenstrom's macroglobulinemia: Consensus Panel Recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia

This presentation represents consensus recommendations for the treatment of patients with Waldenstrom's macroglobulinemia (WM), which were prepared in conjunction with the second International Workshop held in Athens, Greece during September 2002. The faculty adopted the following statements for the management of patients with Waldenstrom's macroglobulinemia: (1) Alkylating agents, nucleoside analogues, and rituximab are reasonable choices for first line therapy of WM. (2) Both cladribine and fludarabine are reasonable choices for the therapy of WM. (3) Combinations of alkylating agents, nucleoside analogues, or rituximab should at this time be encouraged in the context of a clinical trial. (4) In WM, rituximab can cause a sudden rise in serum IgM and viscosity levels in certain patients, which may lead to complications, therefore close monitoring of these parameters and symptoms of hyperviscosity is recommended for WM patients undergoing rituximab therapy. (5) For relapsed disease, it is reasonable to use an alternate first line agent or re-use of the same agent; however, since autologous stem cell transplantation may have a role in treating patients with relapsed disease it is recommended that for patients in whom autologous transplantation is seriously being considered, exposure to alkylator or nucleoside analogue drugs should be limited. (6) Combination chemotherapy for patients who can tolerate myelotoxic therapy, thalidomide alone or with dexamethasone, can reasonably be considered to have relapsed. (7) Autologous stem cell transplantation may be considered for patients with refractory or relapsing disease. (8) Allogeneic transplantation should only be undertaken in the context of a clinical trial. (9) Plasmapheresis should be considered as interim therapy until definitive therapy can be initiated. (10) Rituximab should be considered for patients with IgM-related neuropathies. (11) Corticosteroids may be useful in the treatment of symptomatic mixed cryoglobulinemia. (12) Splenectomy is rarely indicated but has been used to manage painful splenomegaly and hypersplenism. Semin Oncol 30:121-126. © 2003 Elsevier Inc. All rights reserved.

Hepatitis C and B-cell lymphoma: the hemato-hepatologist linkage

Hepatitis C virus (HCV)-lymphotropism may be responsible for the development of mixed cryoglobulinemia (MC) and other lymphoproliferative disorders associated with HCV infection. An association between HCV infection and B-cell lymphoma has been largely demonstrated in several geographical areas with prevalence ranging between 7.4 and 37%. However, the intimate pathogenetic mechanism involved in HCV-associated lymphomas remains considerably unknown. HCV may exerts its oncogenic potential via an indirect mechanism or utilizes other pathways directly. It is reasonable to assume that several different pathogenetic mechanisms operate in the wide spectrum of HCV-related lymphomas which includes the ‘idiopathic’, non-cryoglobulinemic, intermediate to high-grade lymphoma, and the more common indolent, low-grade lymphoma, preceded by long standing symptomatic MC type II. In most cases, HCV has no significant impact on response to chemotherapy or survival of lymphoma patients. Treatment with chemotherapy is relatively safe, and interruption of treatment regimens is usually not required. Whether to treat low-grade HCV-related lymphomas with anti-viral therapy is still debatable, but encouraging data emerge from recent studies.

Sustained response to interferon-alpha or to interferon-alpha plus ribavirin in hepatitis C virus-associated symptomatic mixed cryoglobulinaemia.

Hepatitis C virus (HCV) infection has been associated with mixed cryoglobulinaemia. To investigate the efficacy of anti-viral therapy on the eradication of HCV and its clinical manifestations in patients with HCV-associated symptomatic mixed cryoglobulinaemia. 18 out of 32 patients with symptomatic mixed cryoglobulinaemia (MC group) received a 12-month course of interferon (3 MU three times a week, subcutaneously). Nonresponders or relapsers to this therapy were treated with interferon plus ribavirin (1200 mg/day, orally) for 12-months. 226 patients with HCV infection and without cryoglobulins were studied in comparison (Hepatitis C group). Serial quantification of serum HCV-RNA and cryoglobulins were performed. In the MC group, 10 out of 18 patients (55%) receiving interferon showed an end of treatment response, but at the end of follow-up, only five (28%) patients had a sustained response. In the hepatitis C group, 91 patients (47%) showed an end of treatment response but only 42 (20%) a sustained response. In the MC group alanine transaminase, cryocrit and rheumatoid factor decreased significantly in responders, with an improvement or disappearance of the MC-associated clinical manifestations. Alanine transaminase, cryocrit and rheumatoid factor increased in the relapsers and the clinical manifestations reappeared. Nonresponders and relapsers to interferon in the MC group were retreated with interferon plus ribavirin. Five out of eight nonresponders showed a end of treatment response but it was sustained in three of them. In the relapsers, treatment with combined therapy achieved a sustained response in four out of the five patients (80%). Interferon as monotherapy or combined with ribavirin is a safe and effective treatment in patients with HCV-associated MC. The presence of cryoglobulins does not affect the response to anti-viral treatment in patients with HCV infection. The eradication of HCV is associated with an improvement or disappearance of MC-associated clinical manifestations.

Hepatitis C virus-associated mixed cryoglobulinaemia

Symptomatic mixed cryoglobulinaemia may dominate the course of hepatitis C virus infection. While conventional treatment of mixed cryoglobulinaemia relied on immunosuppression, the discovery of the close association to HCV infection has prompted treatment studies with interferon-alpha. Although symptomatic improvement is achieved in most patients during therapy, the rate of sustained response is low.

Natural Interferon-α Versus Its Combination With 6-Methyl-Prednisolone in the Therapy of Type II Mixed Cryoglobulinemia: A Long-Term, Randomized, Controlled Study

Type II mixed cryoglobulinemia (MC) is an often progressive vasculitis characterized by circulating cold-precipitable proteins that usually consists of polyclonal IgG and monoclonal IgM kappa with rheumatoid factor (RF) activity. Its etiology is unknown, although recent evidence strongly suggests that hepatitis C virus (HCV) plays a major role. Plasmapheresis, corticosteroids, and cytotoxic drugs have been used in the therapy of MC patients. Recently, favorable results with recombinant interferon-alpha (rIFN alpha) have been reported. To further assess its effectiveness, we studied the effects of natural human interferon-alpha (nIFN alpha), alone and in combination with 6-methyl-prednisolone (PDN), in a prospective, randomized, controlled trial in patients with symptomatic MC. Sixty-five patients were enrolled onto the trial, 52 (80%) of whom presented serum anti-HCV antibodies and specific genomic RNA sequences. Fifteen patients received nIFN alpha (3 MU) intramuscularly (IM) three times weekly, whereas 17 patients also received 16 mg/d of PDN orally on non-IFN days. Moreover, 18 patients received 16 mg/d of PDN only, and 15 were untreated. Treatment was discontinued after 1 year and patients were monitored for 8 to 17 months (mean, 13). A complete response was achieved in eight of 15 patients (53.3%) treated with nIFN alpha and nine of 17 (52.9%) treated with nIFN alpha plus PDN, as compared with three of 18 patients (16.7%) who received PDN only (P < .05) and one of 15 (6.7%) untreated controls (P < .01). Partial response occurred in two of 15 (13.3%) patients treated with nIFN alpha, three of 17 (17.6%) who received nIFN alpha plus PDN, one of 18 (5.5%) who received PDN only, and one of 15 (6.7%) controls. A complete response in six patients (66.7%) was achieved within 3 months in the group that received nIFN alpha plus PDN, as compared with two patients (25%) of those who received nIFN alpha alone (P < .02). In anti-HCV-positive patients, the clinical response occurred in step with reduced or undetectable levels of HCV RNA and transaminase normalization. Quantification of circulating HCV RNA represented a good predictive response marker. The probability of relapse within 3 months after treatment was 100% (three of three patients) and 75% (six of eight patients), respectively, in patients who received PDN alone or nIFN alpha alone as compared with none of those who received nIFN alpha plus PDN (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Natural interferon-alpha versus its combination with 6-methyl- prednisolone in the therapy of type II mixed cryoglobulinemia: a long- term, randomized, controlled study

Type II mixed cryoglobulinemia (MC) is an often progressive vasculitis characterized by circulating cold-precipitable proteins that usually consists of polyclonal IgG and monoclonal IgM kappa with rheumatoid factor (RF) activity. Its etiology is unknown, although recent evidence strongly suggests that hepatitis C virus (HCV) plays a major role. Plasmapheresis, corticosteroids, and cytotoxic drugs have been used in the therapy of MC patients. Recently, favorable results with recombinant interferon-alpha (rIFN alpha) have been reported. To further assess its effectiveness, we studied the effects of natural human interferon-alpha (nIFN alpha), alone and in combination with 6- methyl-prednisolone (PDN), in a prospective, randomized, controlled trial in patients with symptomatic MC. Sixty-five patients were enrolled onto the trial, 52 (80%) of whom presented serum anti-HCV antibodies and specific genomic RNA sequences. Fifteen patients received nIFN alpha (3 MU) intramuscularly (IM) three times weekly, whereas 17 patients also received 16 mg/d of PDN orally on non-IFN days. Moreover, 18 patients received 16 mg/d of PDN only, and 15 were untreated. Treatment was discontinued after 1 year and patients were monitored for 8 to 17 months (mean, 13). A complete response was achieved in eight of 15 patients (53.3%) treated with nIFN alpha and nine of 17 (52.9%) treated with nIFN alpha plus PDN, as compared with three of 18 patients (16.7%) who received PDN only (P &lt; .05) and one of 15 (6.7%) untreated controls (P &lt; .01). Partial response occurred in two of 15 (13.3%) patients treated with nIFN alpha, three of 17 (17.6%) who received nIFN alpha plus PDN, one of 18 (5.5%) who received PDN only, and one of 15 (6.7%) controls. A complete response in six patients (66.7%) was achieved within 3 months in the group that received nIFN alpha plus PDN, as compared with two patients (25%) of those who received nIFN alpha alone (P &lt; .02). In anti-HCV-positive patients, the clinical response occurred in step with reduced or undetectable levels of HCV RNA and transaminase normalization. Quantification of circulating HCV RNA represented a good predictive response marker. The probability of relapse within 3 months after treatment was 100% (three of three patients) and 75% (six of eight patients), respectively, in patients who received PDN alone or nIFN alpha alone as compared with none of those who received nIFN alpha plus PDN (P &lt; .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Hépatite C et facteurs rhumatoïdes

Hepatitis C is associated with most of symptomatic mixed cryoglobulinemia (MC). MC contain rheumatoid factors (RF) so we have looked for RF in 111 patients with chronic hepatitis C. Most of them had FR in correlation with age, the length of infection and the presence of pseudo follicular lymphoid aggregates in the liver.