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Biomedical subjects

P Cacoub

Publications and source records attributed to P Cacoub.

At least 91 records · Page 5Linked to original sources
PubMed2000

Natural history of HCV infection.

Chronic hepatitis C virus (HCV) infection affects 170 million individuals worldwide. These individuals are at risk of developing both hepatological and non-hepatological manifestations. HCV is usually only fatal when it leads to cirrhosis, the final stage of liver fibrosis. Therefore, an estimate of fibrosis progression represents an important surrogate end-point for the evaluation of the vulnerability of an individual patient. In untreated patients, the median expected time to cirrhosis is 30 years; 33% of patients have an expected median time to cirrhosis of less than 20 years and 31% will only progress to cirrhosis after more than 50 years, if ever. Several factors are associated with fibrosis progression rate: duration of infection, age, male gender, consumption of alcohol, HIV co-infection and low CD4 count. Non-hepatological manifestations are frequent with more than 70% of HCV patients experiencing fatigue or at least one extrahepatic clinical manifestation involving primarily the joints, skin and muscles. Several immunological abnormalities are frequently observed, including cryoglobulins (40%),anti-nuclear antibodies (10%) and anti-smooth muscle antibodies (7%). In contrast severe extrahepatic manifestations are rare, with 1% for systemic vasculitis.

Antibodies, Antinuclear↗
PubMed2000

Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d'Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l'Hepatite C.

From January 1996 to January 1997, 321 patients with an average age of 46 +/- 16 years and chronically infected with hepatitis C virus (HCV) were prospectively enrolled in a study designed to determine the prevalence of extrahepatic manifestations associated with HCV infection in a large cohort of HCV patients, to identify associations between clinical and biologic manifestations, and to compare the results obtained in human immunodeficiency virus (HIV)-positive versus HIV-negative subsets. In a cross-sectional study, clinical extrahepatic manifestations, viral coinfections with HIV and/or hepatitis B virus, connective tissue diseases, and a wide panel of autoantibodies were assessed. Thirty-eight percent (122/321) of patients presented at least 1 clinical extrahepatic manifestation including arthralgia (60/321, 19%), skin manifestations (55/321, 17%), xerostomia (40/321, 12%), xerophthalmia (32/321, 10%), and sensory neuropathy (28/321, 9%). Main biologic abnormalities were mixed cryoglobulins (110/196, 56%), thrombocytopenia (50/291, 17%), and the presence of the following autoantibodies: antinuclear (123/302, 41%), rheumatoid factor (107/280, 38%), anticardiolipin (79/298, 27%), antithyroglobulin (36/287, 13%) and antismooth muscle cell (27/288, 9%). At least 1 autoantibody was present in 210/302 (70%) of sera. By multivariate logistic regression analysis, 4 parameters were significantly associated with cryoglobulin positivity: systemic vasculitis (p = 0.01, odds ratio OR[ = 17.3), HIV positivity (p = 0.0006, OR = 10.2), rheumatoid factor positivity (p = 0.01, OR = 2.8), and sicca syndrome (p = 0.03, OR = 0.27). A definite connective tissue disease was noted in 44 patients (14%), mainly symptomatic mixed cryoglobulinemia and systemic vasculitis, HIV coinfection (23%) was associated with 3 parameters: anticardiolipin (p = 0.003, OR = 4.18), thrombocytopenia (p = 0.01, OR = 3.56), and arthralgia or myalgia (p = 0.017, OR = 0.23). HIV-positive patients presented more severe histologic lesions (p = 0.0004). Extrahepatic clinical manifestations in HCV patients involve primarily the skin and joints. The most frequent immunologic abnormalities include mixed cryoglobulins, rheumatoid factor, antinuclear, anticardiolipin, and antithyroglobulin antibodies. Cryoglobulin positivity is associated with systemic vasculitis and rheumatoid factor and HIV positivity. HIV coinfection is associated with arthralgia or myalgia, anticardiolipin antibodies, and thrombocytopenia.

Adolescent↗
PubMed2000

Mixed cryoglobulinemia in hepatitis C patients. GERMIVIC.

Cryoglobulins are immunoglobulins that persist in the serum, precipitate with cold temperature and resolubilize when rewarmed. Types II and III are mixed cryoglobulins (MC), composed of different immunoglobulins, with a monoclonal component in type II and only polyclonal immunoglobulins in type III. Mixed cryoglobulins are associated with connective-tissue disease, malignant hematological disorder (type B lymphoproliferation) or obvious infectious process. Mixed cryoglobulinemia syndrome is characterized by the clinical triad of purpura, arthralgia and asthenia associated with type II or type III MC. The disorder is the consequence of an immune-complex-type vasculitis as supported by clinical features, analysis of the cryoglobulins, the usually depressed level of complement during the active phase of the disease, and the deposition of immunoglobulins and complement in the lesions. Such cryoglobulinemia vasculitis may involve numerous organs, particularly the peripheral nervous system and the kidneys. MC is frequently associated with clinical and biological evidence of liver disease. There has been some controversy about which comes first, MC or chronic liver disease, but it seems fairly clear that MC is often a manifestation of underlying chronic active or persistent hepatitis. In MC patients, the hepatotropic antigen(s) capable of triggering production of antibodies which can later form immune complexes has been sought for many years. In the last ten years, numerous studies have demonstrated that infection with hepatitis C virus is involved in the pathogenesis of most mixed cryoglobulinemia. This review analyzes the main published data on hepatitis C virus-mixed cryoglobulinemia, the role of liver alterations, the predictive factors associated with MC production in HCV patients and its symptomatic nature or not, and the different types of vasculitis associated with HCV chronic infection.

Arthralgia↗
PubMed2000

Lymphoproliferative diseases and hepatitis C virus infection.

The putative role of hepatitis C virus (HCV) infection in the pathophysiology of lymphoproliferative diseases (LPD) is supported by north-American and south-European studies reporting high HCV seroprevalence in patients with B-cell-non-Hodgkin lymphoma (NHL). However, controversial data were reported from other areas. The review of available reports to data on HCV-associated LPD points to some features: predominance of low-grade malignant lymphoma, frequent involvement of extranodal sites, absence of particular HCV genotype distribution (except in Italy for genotype 2), important geographical seroprevalence discrepancies. In our experience in 43 cases of HCV-associated LPD in France, we noted a predominance of B-cell NHL (31/43 cases), and the frequency of LPD among HCV-infected patients approximates 2.5%. Pathophysiology hypotheses are discussed, particularly in view of the lympho tropism of HCV. HCV is frequently associated with type II mixed cryoglobulinemia, a benign monoclonal lymphoproliferation which sometimes evolves to overt B-cell lymphoma. The recent finding of HCV binding on CD81, a surface-expressed protein present on lymphocyte membrane, enhances the putative role of HCV in lymphomagenesis. Further investigations are needed to characterize interaction between B lymphocytes and HCV, and to determine putative cofactors involved in the multistep process leading to clonal lymphoproliferation in HCV patients.

Antigens, CD↗
PubMed2000

Treatment of autoimmune and extra-hepatic manifestations of HCV infection.

Hepatitis C virus (HCV) infects mononuclear cells and may, like other viruses, cause immunological disorders. Immunological abnormalities observed in HCV infections are usually nonspecific (e.g. cryoglobulinemia, immune complex deposits, autoantibodies). There is a clear association between cryoglobulinemia and hepatitis C and cryoglobulinemia related symptoms are usually improved by treatment with interferon alpha, although patients usually relapse after treatment end. The relationships between hepatitis C and other immunological abnormalities are unclear. The association between chronic hepatitis C and anti-smooth muscle or anti-nuclear antibodies does not appear to be significantly different from that in other hepatic disorders, particularly hepatitis B. Conversely, patients with hepatitis C have significantly more often anti-liver kidney microsomal (LKM1) antibodies than patients with other causes of liver diseases. When clinical, histological and biological findings are indicative of HCV infection with chronic hepatitis, interferon alpha or combination therapy with ribavirin are treatments options. Conversely, when clinical context and results of laboratory tests are in favor of an autoimmune disorder or of overlap-syndromes (i.e. both autoimmune and viral hepatitis), interferon should not be given in first intention, since revelation or exacerbation of autoimmune hepatitis have been reported under interferon. An important prevalence of anti-HCV antibodies has also been reported in patients with sialadenitis, lichen planus and thyroiditis. It has been clearly demonstrated that interferon may induce or worsen such immunological diseases, but there are very few studies showing improvement of these manifestations under interferon. In conclusion, interferon may be appropriate in patients with HCV infection and extrahepatic manifestations linked to immune complex deposition, whereas, in other cases, careful assessment of patients with autoimmune processes is necessary before choosing any treatment strategy.

Antiviral Agents↗
PubMed2000

[Systemic sarcoidosis during interferon-alpha therapy for chronic hepatitis C virus infection].

A 62-year-old white woman with chronic hepatitis C virus infection was diagnosed with systemic sarcoidosis during treatment with interferon-alpha. Seventeen cases of sarcoidosis associated with interferon treatment have been reported, with only 8 inpatients with chronic hepatitis C virus infection. Our patient, with no past history of sarcoidosis, developed subcutaneous sarcoid nodules, arthritis, uveitis, pneumonitis and heart involvement two months after she was started on treatment with interferon-alpha. Her symptoms resolved when she began corticosteroid therapy and interferon-alpha was stopped. This case report suggests that exogenous interferon-alpha may trigger or contribute to the development of this multisystem granulomatous disorder in which interferon-gamma and CD4 + T-lymphocyte are mainly involved. Patients should be monitored during and following interferon-alpha therapy, since the autoimmune diseases induced by interferon therapy do not always improve after cessation of treatment.

Anti-Inflammatory Agents↗
PubMed2000

[Hyperferritinemia].

Many causes provoke elevated serum ferritin levels including not only iron overload, but also many pathological situations where hyperferritinemia or modified isoferritin profiles have no direct relationship with body iron stores. There are five general categories of hyperferritinemia: hemochromatosis, inflammatory syndromes, cytolysis, hemophagocytosis, Still's disease, and other etiologies.

Ferritins↗
PubMed2000

[Spinal cord involvement revealing systemic sarcoidosis].

Spinal neurosarcoidosis is rare (0.43 p. 100 of all sarcoidosis) and can be the initial manifestation of the disease. A 43-year-old right handed African man developed a progressive dorsal neck pain, slowly worsened paresthesia weakness in the legs and a gait disturbance. Magnetic resonance imaging (MRI) scan of the cervical and thoracic spinal cord (sagittal T(1)- weighted image) revealed diffuse enlargement of the cord from C2 to T7 with intense intramedullary enhancement from C2 to T3 after administration of contrast material on sagittal T(1)- weighted image. Cranial MRI scan was normal. Radiographs of the chest revealed bilateral symmetric hilar mediastinal lymphadenopathy with no pulmonary infiltrates. Bronchial biopsy demonstrated non caseating granulomas with langerhans giant cells. The serum angiotensin converting enzyme level was elevated. The patient received corticosteroid with good progressive response. His neurologic symptoms improved markedly and twenty months post-treatment MRI showed no abnormality on enhanced T(1)- weighted images. Two years later he had no relapse. Only 6 to 10 p. 100 of patients with neurosarcoidosis have spinal cord involvement, which may account for the first clinical manifestation of the disease. Most patients with neurosarcoidosis have associated extraneurologic abnormalities. The diagnosis is supported usually by extraneurologic biopsies. Spinal cord biopsy needs to be considered on case-by-case basis.

Adrenal Cortex Hormones↗
PubMed2000

[Edematous syndrome revealing an exudative lymphocytic gastritis: efficacy of omeprazole].

Lymphocytic gastritis is characterized by intense lymphocytic infiltration of gastric epithelium. Excessive gastric protein loss is uncommon. We describe the case of a 49-year-old white woman suffering from generalized edema and abdominal pain. She had severe serum hypoproteinemia, hypoalbuminemia and hypogammaglobulinemia. There was no renal, cardiac or hepatic origin of protein loss, and no protein-losing enteropathy. Endoscopic examination showed diffuse varioliform gastritis and histology confirmed lymphocytic gastritis with > 30% intraepithelial lymphocytes without Helicobacter pylori. The protein loss stopped within two weeks of the beginning of omeprazole and extensive edema disappeared. Four years later, the patient was still free from edema. Inflammatory involvement of the gastric mucosa probably caused protein losing in this patient. Recognition of this exsudative gastropathy is important because long term remission is obtained with omeprazole.

Abdominal Pain↗
PubMed2000

[Horton's disease and corticosteroid-responsive hearing loss].

BACKGROUND: Temporal arteritis (TA) is a inflammatory panarteritis of the elderly, which may diffuse to all large arteries. Five to 10% of the patients present nonclassical signs with respiratory, vascular, cardiologic, neurologic or hepatic manifestations. We reviewed eighteen cases of TA and deafness in the literature and report two new cases. CASE REPORTS: Our two patients developed sudden, bilateral and corticosteroid responsive hearing loss. One patient developed hearing loss before the diagnosis of TA. CONCLUSION: The mechanism of deafness is probably explained by vertebrobasilar or terminal cochleovestibular arteritis. While the diagnosis of TA is usually easy, it may be difficult in other circumstances. Sensorineural hearing loss may be the first symptom of TA. Prompt recognition and treatment may lead to partial or total improvement of hearing loss in 55% of the cases.

Aged↗
PubMed2000

Amyloidosis and cardiac involvement.

BACKGROUND: Amyloidosis is a rare disease characterized by the extracellular accumulation of a protein polysaccharide complex: amyloid. Cardiac involvement may occur with or without clinical manifestations, and is considered as a major prognostic factor. AIM OF THE STUDY: Firstly, to analyze the clinical, electrocardiographic, radiological and echocardiographic features in a group of patients with extracardiac biopsy-proven amyloid infiltration and evidence of echocardiographic amyloid heart disease. Secondly, to compare the survival of amyloidosis patients, with or without cardiac involvement. PATIENTS AND METHODS: We retrospectively analyzed the main echocardiographic features of 47 patients with biopsy proven amyloidosis. No clinical, electrocardiographic, radiological or scintigraphic criterium were selective for cardiac involvement. Thirty patients with echographic features of amyloid heart disease were identified and compared to 17 patients without echographic features of amyloid heart disease. RESULTS: Amyloid disease with heart involvement was AL in 25/30 (83%) patients and occurred more commonly in middle age men (mean age: 53+/-11 years). The main clinical presentation was congestive heart failure (59%), but 37% of patients had no clinical cardiac features. The electrocardiogram was abnormal in 86% and the cardiac silhouette was enlarged on chest roentgenogram in 27% of patients. The main echocardiographic findings were: diffuse ventricular wall thickening in 21 patients (70%) and isolated septal wall thickening in 9 patients (30%); restrictive pattern of left ventricular (LV) diastolic function in 17 patients (57%); pericardial effusion in 12 patients (40%); impaired LV systolic function in 8 patients (27%); atrial enlargement in 8 patients (27%); characteristic granular sparkling of LV myocardium in 8 patients (27%); mitral and/or aortic valve thickening in 4 patients (13%). Cardiac symptoms developed in 72% of the non symptomatic patients having echocardiographic evidence of cardiac involvement. Twenty-five patients died during the study period and the death was due to cardiac disease in 76%. Median survival time was 36 months from time of amyloidosis diagnosis, and it was 23 months from time of amyloid myocardiopathy diagnosis. It shortened to 6 months when congestive heart failure appeared. CONCLUSION: Patients with a histologically proven amyloidosis should be examined by echocardiography, because cardiac involvement is frequently found in patients with no clinical symptoms, and non symptomatic patients having echocardiographic evidence of cardiac involvement will almost always develop cardiac symptoms. Survival actuarial study confirms the significant adverse influence of cardiac involvement in amyloidosis.

Amyloidosis↗
PubMed2000

[Efficacy of colchicine in recurrent acute idiopathic pericarditis].

Acute idiopathic pericarditis is complicated by recurrence in 15 to 30% of cases. The preventive treatment of recurrences is not well codified. Aspirin, non-steroidal anti-inflammatory drugs and corticoids are the commonest prescribed treatments. The objective of this study was to assess the value of colchicine in the prevention of recurrences of acute idiopathic pericarditis. Twenty-eight cases of recurrent acute pericarditis (2 episodes, 1 month between each episode) admitted to a department of internal medicine between 1989 and 1999 were reviewed. Analysis was concentrated on the 13 idiopathic forms. The subjects were 7 women and 6 men with an average age of 41 years (10-62) at the time of the first episode of acute pericarditis. These 13 patients were treated with colchicine (1 to 2 mg/day) after failure of conventional treatment (aspirin 13/13, NSAID 13/13, steroids 9/13 and pericardiocentesis 3/13). Ten patients were followed up regularly (6 months after starting colchicine) and were improved with respect to number, duration and intensity of their recurrences. The average duration of colchicine therapy was 17 +/- 14 months (6-48). Progressive withdrawal of NSAID and steroids was obtained in 8/10 cases. The authors conclude that colchicine is useful in the prevention of recurrence of acute pericarditis. It may be proposed as treatment of choice, especially in the idiopathic forms.

Acute Disease↗
PubMed2000

[Epidemiologic and virologic study of hepatitis C virus infections in Morocco].

OBJECTIVES: We prospectively studied 783 consecutive Moroccan patients to define: 1) the prevalence of anti-hepatitis C virus (HCV) antibody (Ab), 2) the prevalence of other viral infections: HBs Ag, anti-HAV IgM, anti-HGV, HGV RNA, 3) the risk factors of spreading HCV infection, and 4) the distribution of HCV genotypes. RESULTS: 60/783 (7.7%) patients had anti-HCV Ab (48 H/12 F), 26 (3.3%) HBs Ag, and 3 (0.3%) IgM anti-HAV. Anti-HGV Ab was found in 11/60 (18.3%) anti-HCV positive patients, and 6/38 (15.8%) anti-HCV negative patients. 2/22 (9%) serum anti-HCV positive and anti-HGV negative patients were positive for HGV RNA. The 60 HCV positive patients rarely had other viral infections: 3 (5%) HBs Ag, 11 (18.3%) anti-HGV positive, 2 (9%) HGV RNA positive, and none had anti-HBc, IgM anti-HAV, or anti-HIV. HCV positive patients had more often undergone transfusion of blood products (21.7 vs 5.5%; P < 0.0001), and dental treatment (55% vs 8.3%; p < 0.0001). Patients with anti-HCV Ab frequently had hepatitis lesions on liver biopsy, i.e. chronic active hepatitis (n = 44) or cirrhosis (n = 16). HCV RNA was positive in 45/60 (75%) anti-HCV positive patients. HCV genotypes were: 1b (n = 21, 47%), 2a/2c (n = 13, 29%), 1a (n = 6, 13%), et 3 (n = 1, 2%). CONCLUSIONS: In our Moroccan population, the prevalence of HCV was high (7.7%). Other viral infections (HBV, HAV, HGV) were rare.

Adult↗
PubMed1999

[Transmitted transfusion virus: a new hepatotropic virus...in search for a disease].

AN UBIQUITOUS VIRUS: The family of hepatitis viruses now has a new member discovered in 1997 by a Japanese team. The TTV (transmitted transfusion virus) is a small ubiquitous DNA virus probably largely distributed throughout the world. Prevalence in blood donors is about 2 to 10%. TRANSMISSION AND PERSISTENCE: TTV is generally transmitted via the parenteral route but can probably be transmitted via orofecal and matemo-fetal routes. The natural history of TTV has been studied in retrospective studies, particularly in hemophiliacs. After a post-transfusional peak, the virus appears to persist for long periods in the organism without causing liver damage nor any change in transaminase levels. PATHOGENICITY: Although no proof is yet available, the TTV does probably not have any intrinsic pathogenic power. It would rather be a ìsurrogate virusî transmitted at the same time as another virus yet to be discovered and which causes the rare cases of non A-non-G post-transfusional hepatitis.

Blood↗
PubMed1999

Octreotide treatment of chronic intestinal pseudoobstruction secondary to connective tissue diseases.

Chronic intestinal pseudoobstruction (CIPO) is a rare syndrome that may occur in association with connective tissue diseases (CTD). Effective management is a major challenge. We report 3 cases in which subcutaneous octreotide was efficacious in the treatment of digestive symptoms in CIPO. In 2 of the 3 cases, previous treatment with domperidone, cisapride, or erythromycin had been unsuccessful. All 3 patients underwent a regimen of oral antibiotics along with octreotide to stimulate small bowel motility. The effects of octreotide were evident within 48 hours after the first injection in all patients. In 2, the efficacy seemed to decrease after 1 week and 6 months respectively, but increasing the dosage led to another remission. CIPO in CTD is a severe condition that can evolve regardless of the underlying disease activity. Octreotide appears to be efficacious in improving both clinical symptoms and manometric patterns. When its therapeutic effect diminishes, increasing the dosage can be useful.

Adult↗