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P Cacoub

Publications and source records attributed to P Cacoub.

At least 19 recordsLinked to original sources
PubMed2006

[Update in Hepatitis C virus associated extrahepatic manifestations].

INTRODUCTION: Since the discovery of the hepatitis C virus, many manifestations, so called extra-hepatic manifestations (EHM), are largely reported with more or less relationship proofs. ACTUALITIES AND MAIN POINTS: This article proposes a review of the main extra-hepatic manifestations associated with the Hepatis C Virus infection and which remain a topical subject, more than fifteen years after the discovery of this virus. Mixed cryoglobulin and its vasculitic manifestations are still one of the more frequent Hepatis C Virus associated-extra-hepatic manifestations. Its management may be critically changed due to the increasing use of anti-CD20 therapy. Among other HCV-EHM, the following extra-hepatic manifestations are still of interest: the chronic fatigue syndrome, the sicca syndrome, the non-insulin-dependent diabetes mellitus, malignant B cell proliferations, mainly the Hepatis C Virus-related splenic lymphoma with villous lymphocytes and the production of auto-antibodies. PERSPECTIVES AND PROJECTS: The mechanisms underlying these HCV-associated EHM are ill-elucidated and still remain of great interest as proved by current studies. The use of anti-CD20 antibodies in the treatment of cryoglobulinemic vasculitis is also under investigation.

Autoantibodies↗
PubMed2006

Hepatitis B virus-human immunodeficiency virus co-infection in France: a cross-sectional multicentre study.

This prospective, multicentre study was conducted between September and October 2003 in 38 French departments of internal medicine, infectious disease and hepatogastroenterology and included 406 consecutive HBV-infected patients (positive HBsAg), half of whom were HIV-infected (53%). The aim was to outline the main characteristics of hepatitis B virus (HBV)-human immunodeficiency virus (HIV) co-infected patients in French hospitals. HBV-HIV co-infected patients (85% were receiving HAART; mean CD4 count 447+/-245/microl, HIV RNA load<400 copies/ml, 67% of patients), compared to HIV-negative patients, were more often male, injecting drug users, HBeAg-positive and HCV-HIV co-infected (P<10(-4)). They underwent liver biopsy less often (31% vs. 51%, P<10(-4)), particularly those with severe immunodeficiency. They received anti-HBV treatment more often (75% vs. 45.7%, P<10(-4)), mainly lamivudine and tenofovir. Significant improvements in the management of such patients are awaited mainly in the appraisal of liver disease by either liver biopsy or non-invasive alternatives to liver biopsy.

Adult↗
PubMed2006

Hepatitis C virus-associated B-cell proliferation--the role of serum B lymphocyte stimulator (BLyS/BAFF).

OBJECTIVE: B lymphocyte stimulator (BLyS) is known to support B-cell proliferation (BCP) in B-cell haemopathies and autoimmune diseases. We assume that BLyS may play a role in the initiation and expression of hepatitis C virus (HCV)-associated BCP. We assessed BLyS serum levels in HCV-infected patients and in various forms of HCV-associated BCP [i.e. mixed cryoglobulin (MC), rheumatoid factor (RF) and systemic vasculitis]. METHODS: A total of 76 HCV-infected patients (HCV RNA+) were compared with 13 healthy volunteers. Epidemiological, clinical, immunochemical and virological data were prospectively collected. BLyS serum levels were assessed by an ELISA sandwich method. RESULTS: Of the 76 patients, 38 females, 38 males, mean age 53 +/- 15 yrs; 47 (62%) patients had type II (27 patients) or type III MC (20 patients); 27 (35.5%) patients had HCV-systemic vasculitis. BLyS serum levels tended to be higher in HCV-infected patients than in healthy controls (1.8 +/- 0.9 vs 1.5 +/- 0.2 ng/ml), were higher in patients with MC than without (2.03 +/- 1.02 vs 1.5 +/- 0.5 ng/ml; P = 0.008), and even higher in type II than type III MC (2.3 +/- 1.2 vs 1.7 +/- 0.6 ng/ml; P = 0.03). There was a correlation between BLyS and MC serum levels (R = 0.4; P = 0.004). BLyS serum levels were higher in patients with a positive RF than in those without (2.06 +/- 1.09 vs 1.6 +/- 0.56 ng/ml, P = 0.035), and with systemic vasculitis than in those without (2.24 +/- 1.16 vs 1.6 +/- 0.6 ng/ml; P = 0.006). CONCLUSION: BLyS serum levels are significantly correlated with B-cell proliferation during chronic HCV infection. These results strongly suggest a role for BLyS in the induction and expression of HCV-BCP.

Adult↗
PubMed2006

[Serum markers of non-invasive fibrosis in chronic hepatitis C virus infection].

MATTER: Liver biopsy is recommended for the management of patients infected by hepatitis C virus (HCV) and is currently the gold standard in assessing liver histology. It's an invasive test prone to complications with a morbidity rate of 0.3 to 0.6% and a mortality rate up to 0.05%. Since the last decade, researchers developed non invasifs biomarkers of liver fibrosis as an alternative to liver biopsy. These scores are based on different algorithms with various combinations of biomarkers issued from extra-cellular matrix, serum and cells. CURRENT EVENTS: The diagnostic performance of these scores, estimated by the AUROC for significant fibrosis (>F2), in patients with chronic hepatitis C reach 0.78 to 0.90 for the most accurate. In HIV-HCV co-infected patients and patients with hepatitis C cirrhosis the diagnostic performance of these scores reach 0.74 to 0.88 and 0.73 to 0.97 respectively. PERSPECTIVES: Liver fibrosis biomarkers constitutes an alternative to liver biopsy due to their non invasive approach, their easy reproducibility and accuracy. However, these scores must be used only after a validation in multicentric independent studies. The future is based on the comparison and validation of these scores after laboratory methods standardization.

Alanine Transaminase↗
PubMed2006

Anti-C1q antibodies in hepatitis C virus infection.

Autoantibodies against C1q have been described in many immune-complex diseases including hypocomplementaemic urticarial vasculitis and systemic lupus erythematosus (SLE). No study has focused on the role of anti-C1q antibodies in hepatitis C virus (HCV) infection. The aim of this study was (i) to evaluate the prevalence of anti-C1q antibodies in HCV infection; and (ii) to analyse the association of anti-C1q antibodies with clinical and biological features of HCV-mixed cryoglobulinaemia (MC) vasculitis. We searched for anti-C1q antibodies using an enzyme-linked immunosorbent assay (ELISA) test in 111 HCV patients (75 had cryoglobulin and 23 systemic vasculitis), 60 SLE patients and 109 blood donors. Anti-C1q antibodies were detected in 26% of HCV patients compared to 10% of healthy donors (P < 0.01), and 38% in patients with SLE. Although there was a higher prevalence of anti-C1q antibodies among HCV patients with type III cryoglobulin (50%, P < 0.01), the overall prevalence of anti-C1q antibodies was similar in HCV patients being cryoglobulin-positive or cryoglobulin-negative (26%versus 25%, P = 0.98). A significant association was found between anti-C1q antibodies and low C4 fraction of complement (P < 0.05). No association was found between anti-C1q antibodies and HCV genotype, severity of liver disease or with specific clinical signs of HCV-MC vasculitis. This study shows an increased prevalence of anti-C1q antibodies in HCV-infected patients. Anti-C1q antibodies were associated with low C4 levels. No association was found between anti-C1q antibodies and HCV-MC vasculitis, nor between anti-C1q antibodies and cryoglobulinaemia.

Aged↗
PubMed2006

Multicentre study of hepatitis B virus genotypes in France: correlation with liver fibrosis and hepatitis B e antigen status.

The clinical significance of hepatitis B virus (HBV) genotypes is still under debate. The aims of this study were to assess the distribution of HBV genotypes in France and to identify the associations between HBV genotypes and patient demographics, severity of liver disease and HBeAg status in patients referred to tertiary care centres. This was a French, multicentre, retrospective study on 262 patients with chronic HBV infection. HBV genotypes were determined using INNO-LiPA. Liver fibrosis damage was evaluated by histological analysis of biopsy samples. Patients were mainly male (74%), of Caucasian (65%), Asian (17%) or African (18%) ethnicity and 36% were HBeAg positive. All A-G genotypes were found, the most frequent being genotypes D (27%) and A (24%), followed by E (13%) and C (12%), and B (7%). Mixed genotypes were detected in 16% of the cases. Genotype A was associated with sexual contact (P < 0.001) and genotype D with transfusion (P < 0.001) and HBe antibody positivity (P = 0.03).The distribution of HBV genotypes differed with regard to the ethnicity, and may reflect migration patterns. Genotypes A and D were the most frequent in France. Genotype A was associated with HBeAg positivity and genotype D with HBe antibody positivity. In our European patients, we find no clear association between a given HBV genotype and liver disease severity.

Adult↗
PubMed2006

Treatment of hepatitis C virus and human immunodeficiency virus coinfection: from large trials to real life.

To analyse the barriers for anti-hepatitis C virus (anti-HCV) treatment in human immunodeficiency virus (HIV)-HCV coinfected patients, we surveyed 71 physicians specializing in infectious disease (39%), internal medicine (27%), HIV/AIDS information and care (17%), haematology (10%) and hepatology (6%). A standard data collection form was used to identify patients observed in 7 days in November 2004. Three hundred and eighty patients with the following characteristics were included: male gender 71%; mean age 41.5 years; HIV diagnosed 12 years ago; routes of transmission via injection drug use (78%); undetectable HIV viral load (235/373, 63%) or <10 000 copies/mL (86/373, 23%). HCV RNA was positive in 325 of 369 (88%) patients; HCV genotype was 1 or 4 in 65% and liver biopsy had been carried out in 56%. There were several explanations for the nontreatment of HCV in 205 of the 380 (54%) patients, with 2.4 reasons per patient: anti-HCV treatment was deemed questionable (n = 109) because of minor hepatic lesions, alcohol consumption, or active drug use; no liver biopsy had been performed (n = 68); treatment was contraindicated (n = 62), mainly for psychiatric reasons; there was physician conviction of poor patient compliance (n = 62) and patient refusal (n = 33). Patients having received anti-HCV treatment (n = 91) compared with those who had never received any (n = 205) were more commonly of European origin, had better control of their HIV infection, were followed by a hepatologist more often, had a liver biopsy more often and had more commonly a high HCV viral load (P < 0.001). In 'real life' in France in 2004, more than half of the HIV-HCV coinfected patients have never received anti-HCV treatment. The main reasons are a treatment that may be deemed questionable (minimal hepatic lesions, alcohol, active drug use), a lack of available liver biopsy, a psychiatric contraindication and physician conviction of poor patient compliance.

Adult↗
PubMed2006

A case-control study of risk factors for hepatitis C infection in patients with unexplained routes of infection.

Twenty to 40% of hepatitis C virus (HCV)-infected patients do not have a recognized parenteral risk factor, suggesting that still-unidentified modes of transmission exist. In order to investigate potential routes of HCV transmission for patients with no recognized parenteral risk factor, we conducted a multicentre case-control study. A total of 450 HCV-seropositive patients with no history of transfusion or intravenous drug use and 757 controls were recruited from the general population and matched for sex, age, geographical residence and number of chronic diseases. All subjects answered an interviewer-administered questionnaire on potential risk factors for HCV. Eighty per cent of cases had chronic hepatitis or cirrhosis. Respective percentages of genotypes 1, 2, 3, 4 and 5 were 65, 14, 11, 5 and 4. Among the 66 items considered, multivariate analysis identified 15 independent risk factors for HCV infection: nosocomial [admission to medical (odds ratio, OR = 2.1) or surgical ward (OR = 1.7), digestive endoscopy (OR = 1.9), abortion (OR = 1.7)], outpatient treatments [cutaneous ulcer and wound care (OR = 10.1), diathermy (OR = 3.0), gamma globulin (OR = 1.7), intravenous (OR = 1.7) or intramuscular (OR = 1.4) injections, varicose vein sclerotherapy (OR = 1.6), acupuncture (OR = 1.5)] and lifestyle-associated [intranasal cocaine use (OR = 4.5), practice of contact sports (OR = 2.3), beauty treatments (OR = 2.0), professional pedicure/manicure (OR = 1.7)]. These factors could explain 73% of community-acquired hepatitis C. In conclusion, for patients with unexplained routes of HCV infection, our data incriminate previously unidentified risk factors (abortions, some dermatological procedures, outpatient injections, contact sports, beauty treatments, professional pedicure/manicure) and confirm those already recognized (hospitalization, digestive endoscopy, acupuncture and intranasal cocaine use).

Adult↗
PubMed2006

Comparison of serum hepatitis C virus (HCV) RNA and core antigen levels in patients coinfected with human immunodeficiency virus and HCV and treated with interferon plus ribavirin.

Trak-C (Ortho-Clinical Diagnostics) is an enzyme-linked immunosorbent assay-based method capable of quantifying hepatitis C virus (HCV) core antigen (CA) in serum and could be an alternative to molecular detection and quantification of HCV RNA. We have evaluated the Trak-C assay in comparison with an HCV RNA quantitative assay (Versant HCV v3.0; Bayer Diagnostics) in the follow-up of 348 treated, human immunodeficiency virus (HIV)/HCV-coinfected patients included in the ANRS HC02 RIBAVIC trial. ANRS HC02 RIBAVIC is a therapeutic, multicenter, randomized protocol comparing the efficacy of alpha interferon 2b (IFN-alpha2b) (3 million units three times a week)-ribavirin (800 mg/day) to that of pegylated IFN-alpha2b (1.5 mug/kg of body weight/week)-ribavirin (800 mg/day) during 48 weeks of treatment of HIV/HCV-coinfected patients naïve to HCV treatment. Patients were assessed for virological analysis at day 0 and weeks 4, 12, 24, 48, and 72. Correlation of HCV RNA and HCV CA at the initiation of treatment was excellent (r = 0.92). HCV RNA and CA kinetics were similar during follow-up of HCV treatment from day 0 to week 72 whatever the group of response and genotype. The positive and negative predictive values of response to the treatment at week 4 were 59 and 94%, respectively, for HCV RNA load reduction of >2 log and 54 and 94%, respectively, for HCV CA below the threshold value (4.18 log(10) pg/ml . 10(4)). Trak-C, a new assay able to quantify CA in HIV/HCV-coinfected patients, correlates well with quantitative HCV RNA assays and is cheaper and easier to perform than molecular technology. HCV CA could be a valuable alternative test for therapeutic follow-up of coinfected patients treated with IFN plus ribavirin in developing countries.

Antiviral Agents↗
PubMed2006

Anti-cyclic citrullinated peptide antibodies in hepatitis C virus associated rheumatological manifestations and Sjogren's syndrome.

OBJECTIVE: To investigate the diagnostic reliability of anti-CCP antibodies (anti-CCP Ab) in distinguishing hepatitis C virus (HCV) associated rheumatological manifestations and Sjögren's syndrome from rheumatoid arthritis. METHODS: 147 HCV infected patients (HCV RNA positive) were compared with 64 patients with definite rheumatoid arthritis in a retrospective study. Anti-CCP Ab were detected using the Immunoscan ELISA kit (second generation) and rheumatoid factor (RF) by the FIDIStrade mark Rheuma kit. RESULTS: Among the 147 HCV infected patients (77 women; mean (SD) age 58 (16) years), 77 (52%) had a mixed cryoglobulin (MC), 38 (26%) an MC associated systemic vasculitis, 35 (24%) arthralgia/arthritis, and seven (5%) definite Sjögren's syndrome. HCV infected patients with arthralgia were more often RF positive than those without arthralgia (54% v 27%; p = 0.003), but less often than patients with rheumatoid arthritis (54% v 81%; p = 0.009). Anti-CCP Ab were detected in only two HCV infected patients with arthralgia (5.7%), in none without arthralgia or with Sjögren's syndrome, and in 78% of patients with rheumatoid arthritis. With a specificity of 93.5% and a positive predictive value of 96% for rheumatoid arthritis, anti-CCP Ab were the most specific biological marker. CONCLUSIONS: Anti-CCP antibodies are very rarely found in HCV infected patients with rheumatological manifestations or Sjögren's syndrome. They are reliable serological markers to distinguish these from patients with rheumatoid arthritis.

Adult↗
PubMed2005

Chronic Chlamydia pneumoniae infection in patients with symptomatic atherothrombosis.

OBJECTIVES: The aim of the present study was to search for an association between chronic Chlamydia pneumoniae infection, indicated by elevated antibody titers against the pathogen, atherothrombosis and the occurrence of arterial ischemic events. METHODS: We studied 52 patients presenting at baseline with at least one symptomatic episode of atherothrombosis. A screening for fasting blood glucose and a lipid profile was performed on all patients who had no known history of diabetes or hypercholesterolemia. RESULTS: The prevalence of IgG and IgA anti-C. pneumoniae antibodies at baseline was 90% (95% CI: 79-97) and 81% (67-90), respectively. Forty-two of the 52 patients (81%) experienced a new arterial ischemic event after a mean follow-up of 9 years [heart: 19 (37%); brain: 12 (23%); lower limbs: 8 (15%); and other: 13 (25%)]. Occurrence of a new arterial ischemic event was related to age (p=0.003), sex (p=0.009), and tobacco smoking (p=0.06). Prevalences of IgA and IgG anti-C. pneumoniae were significantly higher in patients with atherothrombosis at baseline than that in controls. CONCLUSION: Our study confirmed the links between C. pneumoniae and atherothrombosis. However, neither IgA nor IgG antibodies for C. pneumoniae was a significant predictive factor for new ischemic arterial events in patients with atherothrombosis.

Adult↗
PubMed2005

[Interest of performing systematically the protein profile in an internal medicine department. National survey and prospective study on 229 admissions].

INTRODUCTION: Despite a wide national use, the usefulness of the protein profile has only been evaluated in a small number of studies, essentially in patients with unknown diagnoses. METHODS: We conducted a survey on 339 french internal medicine departments to evaluate how the protein profile was used in these services. Concomitantly we achieved a prospective study on 229 patients in our department, with a mean follow up of 9 months, to evaluate how did the protein profile influence the diagnosis process. RESULTS: We received 183 responses to our national survey: the protein profile was available in 110/183 (60%) departments with 94/110 (85%) using it during hospitalisation and 20/94 (21.3%) using it systematically. Among the 229 protein profile analysed in our department, 44 (19.2%) were considered useful with 20 (8.7%) of them allowing the diagnosis of a new pathology. If the profile had not been done systematically, the physicians of our department would have performed the profile in 102/229 (44.5%) cases, whereas seven (3%) useful profiles would not have been done. CONCLUSION: We think that the profile has a consistent interest in hospitalized patients with a known or unknown pathology but performing systematically such a test appears to be of limited benefit.

Blood Proteins↗
PubMed2005

Management of chronic hepatitis C in French departments of internal medicine and infectious diseases.

This prospective, multicentre study was conducted during 2-30 April 2001 in the internal medicine/infectious diseases services in France and included data from 1858 hepatitis C virus (HCV)-infected patients, half of whom were HIV co-infected. The aims were to outline the type of pre-therapeutic evaluation of HCV infection performed (HCV RNA, genotype, liver biopsy); determine the proportion and characteristics of patients receiving antiviral treatment; and determine if any changes in these parameters had occurred between 1995 and 2001. Patients whom had a complete pre-therapeutic evaluation (39%, 709/1834) and received antiviral treatment (38%, 690/1830) were more likely to have abnormal liver biochemistry, cirrhosis and cryoglobulinaemia (P < 0.001). Injecting drug users and HIV-co-infected patients were less likely to have a complete pre-therapeutic evaluation or receive antiviral treatment (P < 0.001). A complete pre-therapeutic evaluation was more often performed in 2001 than in 1995 (39% vs. 6%, P < 0.001), including qualitative HCV RNA testing (91% vs. 68%, P < 0.001), genotyping (59% vs. 7%, P < 0.001) and a liver biopsy (60% vs. 29%, P < 0.001). The frequency of anti-HCV treatment approximately doubled between 1995 and 2001 (20% vs. 38%, P < 0001). Although adherence to consensus recommendations regarding pre-therapeutic evaluation is not ideal, a substantial improvement has occurred since 1995. Nevertheless, means of increasing the availability of antiviral therapies, particularly for patients with HIV co-infection or injecting drug use, require further study.

Adult↗
PubMed2005

Genetic heterogeneity of the hypervariable region I of Hepatitis C virus and lymphoproliferative disorders.

B-cell lymphoproliferative disorders (BCLD) have been associated with chronic hepatitis C virus (HCV) infection. The HCV glycoprotein E2 (gpE2) hypervariable region I (HVR-I) may be a potential antigenic candidate to promote B-cell proliferation. The purpose of this study was to analyze the influence of HVR-I sequence variability in the development of BCLD. HVR-I sequences were studied in 29 chronically HCV-infected patients with (n=15) or without (n=14) BCLD. After PCR amplification of the gpE2 region, analysis of the 81 bp HVR-I encoding fragment was performed on 7-18 clones per patient. HVR-I sequence complexity was slightly lower in patients with BCLD (mean 0.347) than without (0.468) (P=0.2), though, sequence diversities were similar (0.0370 vs 0.0954, P=0.239). Phylogenetic analysis did not reveal any BCLD-associated clustering. In our population, neither the recently described insertion between positions 1 and 2 of HVR-I nor residues at positions 4 and 13 were particularly linked to BCLD. As previously described, we confirm the high degree of conservation of HVR-I residues T-2, G-6 and G-23 in our patients. Contrary to recent findings, our analysis based on multiple clones per patient analysis did not reveal any particular motif associated with BCLD.

Adult↗
PubMed2005

[Prevalence of asymptomatic atherothrombotic lesions and risk of vascular events in patients with documented coronary artery disease].

Coronary arteries are the most frequent location of atherosclerosis. Coronary artery disease is the first cause of death related to atherothrombosis. In addition, patients with a prior history of acute coronary syndromes exhibit a 10% annual risk of recurrence. Although there seems to be a close correlation between the extension of CAD and the severity of atherosclerotic lesions in extra coronary arterial beds, the prevalence of these extracoronary asymptomatic lesions depends on their location. Hence, the prevalence of renal artery disease defined as stenosis > or = 50% or of peripheral artery disease defined as an ABI < 0.9 is estimated to be 20% up to 30%, whereas the prevalence of both carotid artery disease defined as stenosis > or = 70% or aortic aneurysm is estimated to be 5%. Conversely, the annual absolute risk of stroke among CAD patients is estimated at 1% while it remains unknown for vascular events related to PAD or aortic lesions. These data suggest that a systematic screening for asymptomatic extracoronary atherosclerotic lesions among CAD patients cannot be justified without a better knowledge of the prevalence of these lesions. In addition, the identification of the predicting factors for the presence and the development of these asymptomatic lesions is warranted. Finally, the potential benefit in terms of therapeutic intervention of such screening needs to be evaluated. These important issues warrant further clinical studies with appropriate design.

Coronary Artery Disease↗