[Acute hepatitis. Biological hepatic anomalies in asymptomatic persons].
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Biomedical subjects
Publications and source records attributed to Catherine Buffet.
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OBJECTIVES: The aim of this study was to ascertain the reasons for the prescription of serological tests for viral hepatitis B (HBV) and C (HCV) in the Greater Parisian area, and to assess standards of prescription with respect to current guidelines. PATIENTS AND METHODS: The population studied comprised patients affiliated to the three main health insurance schemes in the Greater Parisian area, for whom at least one serological test for HBV or HCV was reimbursed on May 14th or 15th, 2002. Data was collected from prescribing and laboratory heads. RESULTS: The sample consisted of 1 046 prescription orders for HBV and/or HCV tests. The mean age of patients was 39 years, and 68% were females. The main medical indications declared by the prescribing physicians were: screening for HBV or HCV (40%), tests for pregnant women (19%), suspected hepatitis B or C (13%), pre- and post-vaccination tests for HBV (7%), medically assisted procreation (6%), follow-up of diagnosed chronic hepatitis (4%). Assessment of the standards of prescription orders showed a lack of compliance with guidelines for 71% of HBV tests, and 56% of HCV tests. CONCLUSIONS: The implementation of guidelines for the prescription of serological tests for HBV and HCV needs to be improved in clinical practice.
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Autoimmune hepatitis is a disorder of unknown aetiology. Imatinib belongs to a new class of anticancer agents with high selectivity toward a specific molecular target. Its main indications are chronic myeloid leukaemia and gastrointestinal tumours. We report here, for the first time to our knowledge, imatinib mesylate-induced hepatitis with autoimmune features.
Autoimmune thyroid disease is a common side-effect of interferon-alpha (IFN-alpha) treatment of viral hepatitis C. We have described three patients with hepatitis C for whom IFN-alpha and ribavirin were prescribed and who developed two successive phases of silent thyroiditis followed by hyperthryroidism relapse due to Graves' disease. These three men had no known history of familial or personal thyroid disease. Destructive thyrotoxicosis appeared 4-6 months after starting IFN-alpha, followed by Graves' hyperthyroidism within 8 to 11 months. The thyrotropin (TSH) level was normal before IFN-alpha was started. The diagnosis of destructive thyroiditis was confirmed by anti-TSH receptor antibody (TSHRAb) negativity and the absence of radionuclide ((123)I or (99)Tc) uptake on thyroid scintiscans. Eight to eleven months after starting treatment, TSHRAb positivity and intense scintigraphic uptake confirmed the appearance of Graves' disease. IFN-alpha was continued in only one patient. Hence, hyperthyroidism induced by IFN-alpha could correspond to the first phase of silent thyroiditis, to Graves' disease or to the succession of both. Rigorous diagnostic procedures with repeated scintiscans and TSHRAb titering are necessary to avoid a false diagnosis and inappropriate therapy.
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AIMS: Steatosis may increase oxidative stress, which is counteracted by cellular enzymatic (cytosolic and mitochondrial superoxide dismutases (Cu/Zn-SOD and Mn-SOD), glutathione peroxidase (GPx), catalase) and non-enzymatic antioxidant systems. We aimed to determine, in patients with non-alcoholic fatty liver disease (NAFLD), the level of antioxidant defenses (1) in liver biopsies, to demonstrate the existence of oxidative stress; (2) in erythrocytes and plasma, to determine whether their antioxidant defenses reflect liver oxidative stress. METHODS: Erythrocyte and plasma antioxidant defenses were prospectively studied in two groups of 16 patients: patients with NAFLD and controls. Liver biopsies were performed in eight NAFLD patients; liver antioxidant enzyme activities were measured and compared with those in 12 control livers used for transplantation. RESULTS: Cu/Zn-SOD, GPx and catalase activities were significantly higher in NAFLD livers than in controls whereas no significant differences were observed in Mn-SOD activity, and thiobarbituric acid-reactive substance (TBARS) concentration. No differences were observed in erythrocyte antioxidant enzyme activities (GPx, catalase, Cu/Zn-SOD), erythrocyte TBARS concentration, and plasma alpha-tocopherol concentration. CONCLUSIONS: Liver antioxidant enzyme activities were high in patients with NAFLD, reflecting an oxidative stress possibly involved in inflammation and fibrogenesis. However, erythrocyte and plasma antioxidant defenses did not reflect intrahepatic peroxidation.
In this report, we describe an unusual and unreported complication with the new licensed form of pegylated interferon alpha2a (PEG-IFN-alpha2a). We report the first case of severe autoimmune cytopenias, an Evans' syndrome, in a patient with chronic hepatitis C, 2 months after PEG-IFN-alpha2a initiation. Haemolytic anaemia and thrombocytopenia developed, complicated by gastric bleeding and brain haemorrhage. Outcome was favourable under immunosuppressive treatment. Treatment with PEG-IFN-alpha2a requires careful follow-up, as IFNalpha can induce or exacerbate autoimmune diseases.
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Female sex is a protective factor for the progression of fibrosis in patients with chronic hepatitis C virus (HCV) infection. Experimental data suggest that estrogens may have an antifibrotic effect. The objective of this study was to evaluate the influence of past pregnancies, oral contraceptives, menopause, and hormone replacement therapy (HRT) on liver fibrosis progression in HCV-infected women. Four hundred seventy-two HCV-infected women received a survey regarding prior pregnancies, menopause, and the use of oral contraceptives and HRT. The impact of these variables on liver fibrosis and its progression were evaluated using multivariate analyses considering all putative confounding factors. Two hundred one women completed the survey (43% response rate), 157 of whom had an estimated date of HCV infection (96 postmenopausal women, 96 women with previous pregnancies, and 105 women with past use of oral contraceptives). Through multivariate analyses, the estimated rate of fibrosis progression was higher in postmenopausal (P < .05) and nulliparous (P = .02) women and was associated with greater histological activity (P < .001). Prior use of oral contraceptives had no significant influence. Among postmenopausal women, the estimated rate of fibrosis progression (+/-SE) was lower in women who received HRT compared with untreated patients (0.099 +/- 0.016 vs. 0.133 +/- 0.006 METAVIR units/yr; P = .02) and was similar to that of premenopausal women (0.093 +/- 0.012 METAVIR units/yr; P value not significant). In conclusion, menopause appears to be associated with accelerated liver fibrosis progression in HCV-infected women, an effect that may be prevented by HRT. Pregnancies may have a beneficial impact on the long-term progression of liver fibrosis.
BACKGROUND: The choice between reusable and single-use devices for ERCP depends on various medical and economic criteria. This study evaluated the reliability and the safety (risk of cross-contamination) of reusable devices. A cost analysis of the use of reusable devices also was conducted. METHODS: All patients referred for ERCP that required use of a sphincterotome or a retrieval basket were eligible for inclusion in a clinical study of 4 different devices (3 types of sphincterotome, 1 type of retrieval basket). All devices were steam sterilized. Before each use, each device was subjected to bacteriologic and virologic tests (hepatitis C virus, hepatitis B virus markers). Devices were examined before and after each procedure. The numbers of safe and efficient procedures that could be performed with each device were assessed. Three strategies were compared in a cost analysis: internal reprocessing (strategy 1), external reprocessing (strategy 2), and single-use (strategy 3). Inputs used were the results of the clinical study, hospital data for 1 year of endoscopic activity, and market prices. RESULTS: A total of 342 patients underwent the following procedures: sphincterotomy (248 patients), stent insertion (59 patients), use of basket without sphincterotomy (14 patients), and diagnostic ERCP/unsuccessful cannulation (21 patients). At the time of ERCP, 36 patients had viral or bacterial infection. Fifty instruments were used (20 single-lumen sphincterotomes, 10 double lumen sphincterotomes, 20 retrieval baskets). Overall, the median number of efficient uses per device was 10. The median number of efficient uses by each type of device was the following: single-lumen sphincterotome, 12; double-lumen sphincterotome, 8; and, retrieval baskets, 10. All virologic and bacteriologic tests for all instruments were negative. The cost-optimization analysis found that strategy 1 is cost effective (euro37,283/y) compared with strategy 2 (euro40,101/y) and especially with Strategy 3 (euro115,210/y). CONCLUSIONS: Reuse of the sphincterotomes and baskets evaluated in this study during ERCP is safe in terms of infectious hazards. Because they endure numerous uses, reusable instruments are cost effective, especially when compared with single-use accessories.
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AIMS OF THE STUDY: To evaluate the diagnosis, treatment and outcome of patients with pancreatic metastases. PATIENTS AND METHODS: We retrospectively reviewed the records of patients with pancreatic metastasis managed in the Paris area between 1990 and 2000. RESULTS: The series analyzed included 22 patients, 10 men and 12 women, mean age 61 years (range: 35-76). The primary tumors were renal-cell carcinoma (N=10), colorectal cancer (N=4), lung cancer (N=4), breast cancer (N=2), cutaneous melanoma (N=1) and ileal carcinoid (N=1). The mean interval between primary treatment and presentation was 73.5 months (range: 2-151). Diagnosis was established because of clinical symptoms (N=15) or during surveillance (N=7). Computed tomography (N=19) and endoscopic ultrasound (EUS) (N=18) mainly showed solitary and hypodense/or hypoechoic masses. Histological diagnosis was obtained before surgery by EUS-guided fine needle aspiration (N=6), ultrasound-guided biopsy (N=3) or duodenoscopy (N=3). Among 10 patients with primary renal-cell carcinoma, 7 were treated by surgery. Median global survival was 33 months. Median survival was 61 months in the event of surgical treatment and 20 months in the other patients (ns). Mean survival depended on the type of primary tumor, 61 months for renal-cell carcinoma and 33 for colorectal cancer (P=0.06). CONCLUSIONS: Most pancreatic metastases develop from renal-cell carcinoma and can occur several years after nephrectomy. Histological diagnosis is often obtained before surgery. Surgical resection must be discussed as it can allow long-term survival.
BACKGROUND AND AIMS: The molecular mechanism of hereditary persistence of alpha-fetoprotein (HPAFP) has been previously described in a large Scottish family, consisting of a -119G>A substitution in the distal hepatocyte nuclear factor 1 (HNF-1) binding site of the alpha-fetoprotein (AFP) gene promoter. We report here the molecular mechanisms of HPAFP in 2 new unrelated families. METHODS: Family 1 was of Bengali origin, and family 2 was Italian. Four of 5 subjects (family 1) and 3 of 9 (family 2) showed HPAFP. The AFP gene promoter was studied in all available family members. RESULTS: All subjects with high AFP levels had mutated promoter sequences. Family 1 showed the reported -119G>A substitution. Family 2 showed -55C>A and -65C>T substitutions in the proximal putative HNF-1 binding region of the promoter. The -55C>A mutation increased the similarity of the proximal HNF-1 binding region to a consensus binding region. Gel shift assays confirmed its increased affinity toward HNF-1, and transfection experiments revealed an increased level of gene transcription. The -65C>T substitution theoretically created a CCAAT box. However, gel shift and transfection experiments failed to show any biological effect of this substitution that is associated with the -55C>A mutation. CONCLUSIONS: Two different mutations localized in either HNF-1 binding sites of the AFP gene promoter may result in HPAFP. This highlights the importance of HNF-1 in AFP gene expression. Unexplained persistent AFP should lead to family study and/or AFP gene promoter sequencing to avoid inappropriate explorations and treatment decisions.