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Patrice Cacoub

Publications and source records attributed to Patrice Cacoub.

At least 55 records · Page 3Linked to original sources
PubMed2004

[A pluridisciplinary point of view of hepatitis C virus infections].

Various complementary actors are implied in the management of HCV infections: virologists, general practitioners, hepato-gastroenterologists and hospital residents, and they should all cooperate together. The role of biologist is crucial in assisting the practitioners in the choice of examinations to be prescribed for the diagnosis of HCV infections (search for RNA HCV), in establishing a prognosis and in deciding on the therapeutic strategy (genotyping, Fibrotest and Actitest). The role of the general practitioner is important at all stages of the management. The practitioner's involvement is also crucial in the recognition and follow-up of the concomitant diseases. THE ROLE OF THE SPECIALIST: The hepatologist, together with the general practitioner, are inseparable partners in the management of a patient suffering from hepatitis C. The specialist should only see patients exhibiting hepatitis C who are participating in a treatment program, since the indication for treatment is usually decided on by the specialist. The hepatologist should be informed of the various concomitant diseases and the treatments (replacement therapy or others) prescribed for them. CRUCIAL QUESTIONS: For the management of an HCV infection, in general 3 questions require an answer: who should be screened for such infections, what explorations should be performed in the case of positive serology and what follow-up is required during and after anti-HCV treatment?

Gastroenterology↗
PubMed2004

Thrombotic thrombocytopenic purpura with severe ADAMTS-13 deficiency in two patients with primary antiphospholipid syndrome.

Arterial thrombotic events, thrombocytopenia, and hemolytic anemia with schistocytes may be encountered in the setting of both thrombotic thrombocytopenic purpura (TTP) and primary antiphospholipid syndrome (APS). We report 2 cases of TTP occurring in patients with definite primary APS. We also describe the results of tests for ADAMTS-13 activity in 20 consecutive patients with primary APS, as well as tests for antiphospholipid antibodies in 26 patients who had TTP, severe ADAMTS-13 deficiency, and ADAMTS-13-inhibiting antibodies. In both of the patients with primary APS and TTP, ADAMTS-13 activity was undetectable, and ADAMTS-13-inhibiting antibodies were present. None of the 26 patients with TTP and severe ADAMTS-13 deficiency was positive for the lupus anticoagulant. One of these patients had a low level of anticardiolipin antibodies (22 IgG phospholipid units). In the 20 patients with primary APS, mean ADAMTS-13 activity was 116% (range 44-250%), and no severe deficiency (< 5%) was observed. Our findings suggest that primary APS must be added to the list of autoimmune disorders that can be complicated by TTP.

ADAM Proteins↗
PubMed2004

Clonal B cell populations in the blood and liver of patients with chronic hepatitis C virus infection.

OBJECTIVE: The association of hepatitis C virus (HCV) infection with type II mixed cryoglobulinemia is well established, but the role of HCV in B cell lymphoma remains controversial. The objective of this study was to determine the frequency of circulating and liver-infiltrating monoclonal B cells in patients with HCV infection. METHODS: One hundred sixty patients were studied prospectively, including 115 HCV-positive patients and 45 HCV-negative patients with other nonimmune chronic liver disease(s). B cell clonality was determined by DNA amplification of the IgH rearrangements, followed by polyacrylamide gel electrophoresis. RESULTS: A clonal B cell population was detected in the blood of 21 (26%) of 81 HCV-positive patients whose cryoglobulin status was known, including 12 of 25 patients with type II cryoglobulinemia, 2 of 12 patients with type III cryoglobulinemia, and 7 of 44 patients without cryoglobulins. A clonal IgH rearrangement was detected in 26 (32%) of 81 liver biopsy specimens from HCV- infected patients, including 16 patients with a circulating clonal population. A clonal B cell population was not observed in the blood of 40 patients with non-HCV liver diseases and was present in only 1 (3%) of 30 liver biopsy specimens. Logistic regression analysis showed that HCV-infected patients with clonal B cell proliferation in both the blood and liver were older (P = 0.004) and had longer duration of HCV infection (P = 0.009), higher serum cryoglobulin levels (P = 0.001) that were more frequently symptomatic (P < 0.03), and liver disease that was more severe than that in patients without a clonal B cell population in the blood or liver (P = 0.05). In 4 of 16 patients with a clonal B cell population in both the blood and liver, a definite B cell malignancy was finally diagnosed. CONCLUSION: Clonal B lymphocytes are frequently detected in the blood and liver of patients with chronic HCV infection, in the absence of overt B cell malignancy. These clones are usually, but not always, associated with the presence of type II cryoglobulins. A high percentage of patients with B cell clonality in both the blood and liver were finally diagnosed as having a definite B cell malignancy.

Adult↗
PubMed2004

Predominance of type 1 (Th1) cytokine production in the liver of patients with HCV-associated mixed cryoglobulinemia vasculitis.

BACKGROUND/AIMS: Patients with hepatitis C virus (HCV) mixed cryoglobulinemia (MC) vasculitis have a higher mortality rate and more frequent incidence of cirrhosis than their cryoglobulin-negative counterparts. To compare the cytokine profile of liver-infiltrating T cells in HCV-infected patients with or without MC vasculitis. METHODS: Hepatic biopsy specimens were obtained from HCV infected patients with and without MC vasculitis. Using intracellular staining and flow cytometry, we assessed the ability of freshly isolated liver T cells from these biopsies to produce IFN-gamma, TNF-alpha, IL-2, IL-4, and IL-10 in response to stimulation with PMA and ionomycin. RESULTS: HCV-MC vasculitis patients compared to HCV-MC negative controls have an enhanced hepatic T cells production of Th1-type cytokines [i.e. TNF-alpha(30.3 +/- 13% vs. 15.5 +/- 5%, P = 0.01), IL-2 (20.2 +/- 9% vs. 10 +/- 4%, P = 0.01) and IFN-gamma (22.2 +/- 11% vs. 9.4 +/- 4%, P = 0.008)], whereas IL-10, a representative Th2-type cytokine, was significantly lower (7.2 +/- 4% vs. 17 +/- 7%, P = 0.01). CONCLUSIONS: T cell from the liver of HCV-MC vasculitis patients display a significantly augmented liver Th1 profile compared to MC-negative controls. This enhanced production of type-1 cytokines may account for a more severe course of liver disease.

Adult↗
PubMed2004

Hepatitis C virus-associated extrahepatic manifestations: a review.

The hepatitis C virus (HCV) infection is a worldwide disease that is characterized by a preferential chronic evolution with mild to severe liver disease, including cirrhosis and, in lesser proportion, hepatocarcinoma. Out of these complications, HCV is frequently reported to complicate extrahepatic manifestations. Among those associated to HCV infection with a high degree of certainty, mixed cryoglobulinemia and its complications (skin, neurological, renal, rheumatological involvement) are the most prevalent (50%) in HCV-infected patients. The other diseases include noncryoglobulinemic systemic vasculitis, splenic lymphoma with villous lymphocytes, fatigue, porphyria cutanea tarda, sicca syndrome, and autoantibodies production. The extrahepatic manifestations that share mild-degree certainty of association with HCV infection include B-cell non-Hodgkin lymphoma, autoimmune thrombocytopenia, pruritus, and type II diabetes mellitus. The other diseases such as autoimmune thyroiditis, lichen planus are more questionable for their eventual association with HCV and others (pulmonary fibrosis with or without polymyositis, progressive encephalomyelitis, Mooren's corneal ulcers, erythema nodosum, chronic polyradiculonevritis) are mostly case reports. Howerver, even in cases of tight association, the mechanisms through which HCV may promote or induce extrahepatic manifestations remain unclear and merit further investigations.

Autoimmune Diseases↗
PubMed2004

Influence of antiviral therapy in hepatitis C virus-associated cryoglobulinemic MPGN.

BACKGROUND: The influence of hepatitis C virus (HCV) treatment on the course of HCV cryoglobulinemic membranoproliferative glomerulonephritis (MPGN) is controversial. METHODS: Twenty-five patients with nephrotic-range proteinuria, mixed cryoglobulinemia, MPGN proved by renal biopsy, and HCV infection were studied for their response to antiviral treatment. RESULTS: After first-line treatment with prednisone, furosemide, or plasmapheresis, antiviral therapy with standard or pegylated interferon alfa and ribavirin was introduced in 18 patients. These patients were compared with 7 patients who did not receive antiviral treatment. Mean duration of antiviral treatment was 18 +/- 10 months, with a follow-up of at least 6 months after treatment withdrawal. HCV RNA clearance (sustained virological response) was achieved in 12 of 18 patients. Compared with values before antiviral therapy, a decrease in proteinuria was observed in sustained virological responders at the end of combination therapy, as well as at the end of follow-up (mean, 2.85 +/- 2.2 [SD] versus 1 +/- 1.4 and 0.4 +/- 0.8 g/d, respectively; P < 0.05). In sustained virological responders, cryoglobulin levels at the end of treatment (0.29 +/- 0.4 g/L) and end of follow-up (0.25 +/- 0.4 g/L) were decreased (P < 0.05) compared with pretreatment values (1.38 +/- 2.2 g/L). Conversely, no changes in serum cryoglobulinemia levels were observed in nonresponders or controls. Serum creatinine levels remained stable in the 18 patients with antiviral therapy, regardless of response to treatment. CONCLUSION: Anti-HCV treatment improved HCV-associated cryoglobulinemic glomerulonephritis.

Aged↗
PubMed2004

Cardiovascular involvement, an overlooked feature of Erdheim-Chester disease: report of 6 new cases and a literature review.

Erdheim-Chester disease (ECD) is a rare, non-Langerhans form of histiocytosis of unknown origin. It is characterized by xanthomatous or xanthogranulomatous infiltration of tissues by spumous ("foamy") histiocytes. As of this writing, 178 cases have been reported. ECD is characterized by heterogeneous systemic manifestations. Bone pain is the most frequent symptom. About half of all patients have extraskeletal manifestations. Cardiovascular manifestations of ECD remain underestimated. We report 6 new cases of ECD associated with periaortic fibrosis. In 4 of these cases, the whole aorta had a "coated" aspect. A literature review revealed 66 cases of ECD with cardiovascular involvement. We therefore analyzed 72 ECD patients with cardiovascular involvement: 40 (55.6%) had periaortic "fibrosis," 32 (44.4%) had pericardial involvement, and 22 (30.6%) had myocardial involvement. Six had a right atrial tumor. Symptomatic valvular heart disease (3 aortic and 3 mitral regurgitations) was found in 6 patients. Nineteen patients (26.4%) had heart failure, leading to death in 8 cases. Six patients had renovascular hypertension related to perirenal artery stenosis. Data concerning follow-up were available for 58 (80.6%) patients. Of these, 35 (60.3%) patients died, confirming the severe prognosis of ECD. Cardiovascular complications were responsible for the death of 11 of the 35 patients (31.4%).

Adult↗
PubMed2004

Longterm course of mixed cryoglobulinemia in patients infected with hepatitis C virus.

OBJECTIVE: To describe epidemiological, clinical, and immunological characteristics and the longterm course of persistent mixed cryoglobulinemia (MC) in patients infected with hepatitis C virus (HCV). METHODS: Retrospective study of HCV infected patients (HCV RNA positive) who had persistent positive MC, with 2 immunochemical typings of MC carried out after 24-month minimum interval. RESULTS: In total, 125 patients were studied, aged 52 +/- 13 years at diagnosis of MC, with duration of HCV infection of 18 +/- 10 years. At entry, 60 patients had type II MC, 53 patients had type III, and 12 patients had the oligoclonal type. At the second immunochemical typing, after a mean interval of 45 +/- 20 months, MC was type II in 72 patients, type III in 39 patients, and the oligoclonal type in 14 patients. The proportion of cases of MC with the same immunochemical type was higher among patients with type II (78%) than type III (59%) or oligoclonal MC (17%) (p < 0.01). The MC that changed turned more to type II (55.5%) than type III (29%) or the oligoclonal type (15.5%) (p = 0.0002). MC vasculitis (purpura, arthralgia, peripheral neuropathy, renal involvement) and other extrahepatic manifestations (polyarteritis nodosa, lymphoma) in 60/125 patients was associated with advanced age (p < 0.01), a longer duration of infection (p < 0.05), type II MC (odds ratio = 5, p < 0.01), and a higher MC serum level (p < 0.01). CONCLUSION: During chronic active HCV infection, type II MC is more stable over time than type III and oligoclonal MC. The oligoclonal type appears to be an intermediate stage in the course of type III changing to type II MC. Symptomatic persistent HCV MC was associated with advanced age, longer duration of HCV infection, type II MC, and a higher MC serum level.

Adult↗
PubMed2003

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

Patients 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(+)CD25(high) 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.

Adult↗
PubMed2003

Mortality due to hepatitis C-related liver disease in HIV-infected patients in France (Mortavic 2001 study).

OBJECTIVE: To determine mortality due to end-stage liver disease (ESLD) in a nationwide cohort of HIV-infected patients 5 years after the introduction of highly active antretroviral therapy (HAART) and to compare this with that observed before and during the early years of HAART. DESIGN: and methods: All departments of internal medicine and infectious diseases from the GERMIVIC Study Group prospectively recorded all deaths in HIV-infected patients during 2001. Sixty-five departments, following a total of 25 178 HIV-infected patients, participated in the study. Results were compared with those of previous surveys conducted using similar methodology in 1995 and 1997. RESULTS: Among 265 deaths observed during 2001, 129 (48.7%) were related to AIDS, 38 (14.3%) to ESLD, and 98 (36.7%) to other causes. Mortality due to ESLD represented 28% of non AIDS-related deaths; 36 of the 38 patients (95%) dying from ESLD had chronic hepatitis C virus (HCV) infection. In 2001, deaths due to ESLD (14.3%) were significantly more frequent than in 1995 (1.5%; P < 0.01) and 1997 (6.6%; P < 0.01). During this interval, the prevalence of hepatocellular carcinoma as a cause of death increased (1995, 4.7%; 1997, 11%; 2001, 25%; P < 0.05), as did alcohol consumption (P < 0.01). CONCLUSIONS: In the post-HAART era, ESLD due to HCV is a growing cause of mortality in HIV-infected patients. Increased longevity attributable to HAART, and a higher prevalence of alcohol consumption, are probably involved in this trend.

Adult↗
PubMed2003

High ferritin and low glycosylated ferritin may also be a marker of excessive macrophage activation.

OBJECTIVE: A high serum ferritin concentration with a low percentage of glycosylated ferritin (< 20%) have been reported to be a specific marker of active adult Still's disease (ASD). However, high ferritin levels are found during hemophagocytosis syndrome (HS). We investigated the ferritin level and the percentage of glycosylation in a HS series of various causes. METHODS: Diagnosis of HS was confirmed by erythrophagocytosis pictures on a bone marrow cytology or biopsy in all patients. Serum ferritin concentration was determined on a heterogenous immunoassay module. Glycosylated ferritin was separated using concanavalin A (Con-A) sepharose 4B chromatography. The nonglycosylated ferritin unbound to Con-A was recovered in the supernatant and quantified with the same procedure. Percentages of glycosylated ferritin less than 20% are considered to be usual in ASD, between 20 and 40% usual in inflammatory syndrome, and between 50 and 80% normal. RESULTS: In all cases tested during the acute phase of the disease, ferritin blood level was high and the percentage of glycosylated ferritin was low, less than 20%. CONCLUSION: The combination of high ferritin level and low percentage of glycosylation may be a marker of excessive macrophage activation.

Adult↗
PubMed2003

Hepatitis C virus infection in systemic lupus erythematosus: a case-control study.

OBJECTIVE: Viruses might be one of the elements that trigger systemic lupus erythematosus (SLE). Steroid therapy may influence the natural history of virus infections. The most frequent extrahepatic manifestations of hepatitis C virus (HCV) including arthralgia, myalgia, sicca syndrome, and antinuclear antibodies, may mimic a connective tissue disease, particularly SLE. Reports on the association between SLE and HCV infection are scarce. We investigated the association of HCV infection and SLE. METHODS: Retrospective case-control monocentric study of 19 patients with SLE and anti-HCV antibodies versus 42 randomized SLE patients without anti-HCV antibodies, matched for age and sex, coming from our cohort of 700 patients with SLE. SLE and HCV-infection features were reviewed. RESULTS: Mode of infection was blood product transfusion, drug addiction, or unknown. Prevalence of lupus clinical manifestations, antinuclear, anti-dsDNA, anti-extractable nuclear antigen antibodies, and complement levels was not different between HCV positive and negative SLE patients. Prevalence of cryoglobulin was higher in SLE patients with anti-HCV antibodies (p < 0.04), but none had a mixed cryoglobulinemia syndrome. ALT activity was increased in 11 HCV positive patients and 13 had detectable HCV RNA. Liver biopsy showed cirrhosis in 2 and mild fibrosis and activity in 5. One patient treated with interferon-alpha had a sustained virological response without SLE flare. Steroid therapy did not seem to alter HCV course. CONCLUSION: SLE in HCV positive patients shows higher prevalence of cryoglobulin without mixed cryoglobulinemia syndrome. HCV infection has moderate signs of biochemical and liver pathological severity. SLE by itself or treated with steroids does not seem to worsen HCV infection.

Adolescent↗
PubMed2002

Prevalence of monoclonal gammopathy in patients presenting with acquired angioedema type 2.

PURPOSE: Acquired angioedema type 1 is characterized by a C1 inhibitor deficiency in patients with lymphoproliferative disorders, whereas acquired angioedema type 2 is characterized by anti-C1 inhibitor antibodies, and has not been thought to be associated with lymphoproliferative disease. We studied the clinical features, complement profiles, and associated diseases in 19 new patients with diagnosed acquired angioedema type 2. SUBJECTS AND METHODS: Plasma concentrations and functional activity of complement components were measured by conventional techniques. Functional C1 inhibitor activity was assessed by a chromogenic assay. Autoantibodies to C1 inhibitor were detected using an enzyme-linked immunosorbent assay. RESULTS: The 11 men and 8 women (median age, 60 years) presented with recurrent attacks of angioedema. All patients had detectable anti-C1 inhibitor antibodies in serum. A monoclonal gammopathy was detected in 12 patients (63%) at the time of diagnosis, 11 of whom had an immunoglobulin peak of the same heavy- and light-chain isotypes as the acquired anti-C1 inhibitor antibody. Three of these 12 patients developed a malignant lymphoproliferative disease. CONCLUSION: As with type 1 disease, a large proportion of patients with acquired angioedema type 2 have a lymphoproliferative disorder.

Age Distribution↗
PubMed2002

Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection.

BACKGROUND: Some epidemiologic studies suggest a link between hepatitis C virus (HCV) infection and some B-cell non-Hodgkin's lymphomas. We undertook this study after a patient with splenic lymphoma with villous lymphocytes had a hematologic response after antiviral treatment of HCV infection. METHODS: Nine patients who had splenic lymphoma with villous lymphocytes and HCV infection were treated with interferon alfa-2b (3 million IU three times per week) alone or in combination with ribavirin (1000 to 1200 mg per day). The outcomes were compared with those of six similarly treated patients with splenic lymphoma with villous lymphocytes who tested negative for HCV infection. RESULTS: Of the nine patients with HCV infection who received interferon alfa, seven had a complete remission after the loss of detectable HCV RNA. The other two patients had a partial and a complete remission after the addition of ribavirin and the loss of detectable HCV RNA. One patient had a relapse when the HCV RNA load again became detectable in blood. In contrast, none of the six HCV-negative patients had a response to interferon therapy. CONCLUSIONS: In patients with splenic lymphoma with villous lymphocytes who are infected with HCV, treatment with interferon can lead to regression of the lymphoma.

Adult↗
PubMed2002

Human leukocyte antigen class II alleles may contribute to the severity of hepatitis C virus-related liver disease.

Whether the host's immune response genes influence the severity of hepatitis C virus (HCV) liver disease is controversial. Human leukocyte antigen (HLA) class II alleles were analyzed in 233 HCV RNA-positive patients with chronic active hepatitis (197 patients with Knodell index of fibrosis F0-F3 and 36 patients with index of F4). The 2 groups did not differ by sex, duration of infection, mode of contamination, alcohol consumption, or HCV genotype. Patients with cirrhosis were older than those without (56+/-12 vs. 46+/-14 years; P<10-4) and had a lower DRB1*11 allele frequency (5.6% vs. 14.5%; P=.037), whereas DRB1*03 and DQB1*0201 frequencies appeared to be higher (DRB1*03, 18.1% vs. 9.6%; DQB1*0201, 37.5% vs. 23.4%; P=.04, corrected P value is not significant). Mean index of fibrosis was higher in DR3-positive than in DR11-positive patients (2.14 vs. 1.58; P=.05). By multivariate analysis, cirrhosis was associated with male sex and age >50 years. HLA class II alleles may weakly contribute to the severity of HCV liver disease. Of persons infected with HCV, only 15%-20% spontaneously clear the virus, and the rest become chronically infected.

Adolescent↗