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O Chazouillères

Publications and source records attributed to O Chazouillères.

At least 19 recordsLinked to original sources
PubMed2005

HHV-6-related acute liver failure in two immunocompetent adults: favourable outcome after liver transplantation and/or ganciclovir therapy.

Fulminant hepatitis of unknown origin remain a significant cause of mortality, for which liver transplantation is often considered as the only therapeutic option. In retrospective studies, human herpesvirus 6 (HHV-6) infections have been associated with such diseases, but the diagnosis of HHV-6 infection of the liver is rarely established during the acute phase of liver failure. Using real-time polymerase chain reaction (PCR), we diagnosed two cases of severe acute liver failure (ALF) related to HHV-6 occurring in immunocompetent young adults. Both cases had a favourable outcome, one after valganciclovir therapy, one after liver transplantation associated with ganciclovir. Viral origin was evidenced in each case by the detection of high amounts of HHV-6 DNA in liver tissue by the PCR assay. The decrease of intrahepatic viral load after therapeutic intervention was also monitored by quantitative PCR and paralleled in the two cases the clinical improvement. Diagnosis of HHV-6 infection must be systematically evoked in case of unexplained ALF, since it might lead to specific therapeutic interventions, in addition of liver transplantation.

Administration, Oral↗
PubMed2003

Retreatment with interferon and ribavirin vs interferon alone according to viraemia in interferon responder-relapser hepatitis C patients: a prospective multicentre randomized controlled study.

Low pretreatment viral load has consistently been shown to be an independent predictor of sustained response (SR) in patients with chronic hepatitis C infection. We assessed the efficacy of interferon (IFN) plus ribavirin vs IFN alone in low viraemic patients (<2 millions copies/mL) who had relapsed to a previous course of IFN and the efficacy of 24 vs 48 week combination therapy in high viraemic patients. Two hundred and ninety-seven patients were randomly assigned to one of the four regimens after stratification on pretreatment viral load. All patients received IFN-alpha2b (6 million units thrice weekly for 24 weeks and 3 million units thrice weekly for 24 weeks). Patients with low viraemia received either IFN-alpha2b alone for 48 weeks (R1: 42 patients) or IFN-alpha2b plus ribavirin (600 mg/day) for 24 weeks and IFN-alpha2b alone for the next 24 weeks (R2: 48 patients). Patients with high viral load received either IFN-alpha2b plus ribavirin for 24 weeks and then IFN-alpha2b alone for the next 24 weeks (R3: 104 patients) or IFN-alpha2b plus ribavirin for 48 weeks (R4: 103 patients). In low viraemic patients the rate of SR was 37.7% in group R1 and 59.6% in group R2 (P < 0.05). In high viraemic patients, the rate of SR was 44.7% in group R3 and 51.4% in group R4 (P: NS). Thirty-one patients discontinued treatment (10.4%) without difference regarding treatment regimen. In the regimen using ribavirin we found no difference in terms of SR between patients receiving a dose of ribavirin below 10.6 mg/kg/day (55%) or over 10.6 mg/kg/day (58%). Histological improvement occurred in 70.2% of patients regardless of the regimen. Logistic regression showed that genotype 2 and 3, Knodell score <6 and alanine aminotransferase pretreatment level >3 x upper limit of normal were significantly and independently correlated with SR. In low viraemic patients who relapsed to a previous IFN treatment, combination therapy using high-dose IFN and low-dose ribavirin is better than high-dose IFN alone. In high viraemic patients there was no benefit in increasing the duration of combination therapy from 24 to 48 weeks. In this study, it was found that low dose of ribavirin can be used safely and there is no effect of ribavirin dose on SR.

Adult↗
PubMed2003

A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy.

A-Type lamins, arising from the LMNA gene, are intermediate filaments proteins that belong to the lamina, a ubiquitous nuclear network. Naturally occurring mutations in these proteins have been shown to be responsible for several distinct diseases that display skeletal and/or cardiac muscle or peripheral nerve involvement. These include familial partial lipodystrophy of the Dunnigan type and the mandibuloacral dysplasia syndrome. The pathophysiology of this group of diseases, often referred to as laminopathies, remains elusive. We report a new condition in a 30-yr-old man exhibiting a previously undescribed heterozygous R133L LMNA mutation. His phenotype associated generalized acquired lipoatrophy with insulin-resistant diabetes, hypertriglyceridemia, hepatic steatosis, hypertrophic cardiomyopathy with valvular involvement, and disseminated whitish papules. Immunofluorescence microscopic analysis of the patient's cultured skin fibroblasts revealed nuclear disorganization and abnormal distribution of A-type lamins, similar to that observed in patients harboring other LMNA mutations. This observation broadens the clinical spectrum of laminopathies, pointing out the clinical variability of lipodystrophy and the unreported possibility of hypertrophic cardiomyopathy and skin involvement. It emphasizes the fact that the diagnosis of genetic alterations in A-type lamins requires careful and complete clinical and morphological investigations in patients regardless of the presenting signs.

Adult↗
PubMed2001

Hepatitis C virus induced hypobetalipoproteinemia: a possible mechanism for steatosis in chronic hepatitis C.

BACKGROUND/AIMS: Steatosis could be the result of HCV (hepatitis C virus)-induced hypobetalipoproteinemia in patients with chronic hepatitis C. The aim of this study was to assess serum levels of main constituents of betalipoproteins and their relationship with steatosis in patients with chronic hepatitis C without known risk factors for steatosis. PATIENTS: One-hundred male patients with untreated biopsy proven non-cirrhotic chronic hepatitis C were included. Twenty-nine of these patients were further treated with interferon. RESULTS: Cholesterol concentration was significantly lower in patients compared to three control groups: reference male population, patients with chronic hepatitis B or with non-alcoholic fatty liver. In multivariate analysis, low apolipoprotein B concentration was an independent factor related with the degree of steatosis. Hypobetalipoproteinemia and degree of steatosis were significantly associated with infection with genotype 3. Among treated patients, only sustained virological responders had a significant increase of cholesterol (5.6 +/- 1 vs. 4.7 +/- 1.3 mmol/l; P = 0.03) and apolipoprotein B concentrations (113 +/- 19 vs. 75 +/- 14 mg/dl; P = 0.05). CONCLUSION: In chronic hepatitis C, hypobetalipoproteinemia is prevalent and associated with steatosis, especially in patients infected with genotype 3. The correction of hypobetalipoproteinemia following HCV eradication suggests that HCV itself could induce hypobetalipoproteinemia and steatosis.

Adult↗
PubMed2001

Apolipoprotein E polymorphism, a marker of disease severity in primary biliary cirrhosis?

BACKGROUND/AIMS: To determine whether the apolipoprotein E (apo-E) polymorphism is associated with the risk of primary biliary cirrhosis (PBC), the severity of the disease and its response to ursodeoxycholic acid (UDCA) therapy. METHODS: The apo-E genotype was determined in 72 PBC patients. Genotype and allele distributions were compared with those found in the French general population. Laboratory parameters obtained before and after 1- and 4-year UDCA treatment were compared according to the apo-E allele carrier status. RESULTS: Apo-E allele and genotype distributions were similar between PBC patients and the general population. At the time of diagnosis, the epsilon4 allele carriers were younger (P < 0.05), had higher bilirubin (P < 0.05) and IgG (P < 0.001) levels and a lower prothrombin index (P < 0.01) than epsilon2 (homozygous + heterozygous) or epsilon3 homozygous allele carriers. After 4-year UDCA therapy, the decrease in serum alkaline phosphatase and in alanine and aspartate aminotransferase activities was lower in percentage in the epsilon4 than in other epsilon allele carriers (P < 0.01). CONCLUSIONS: Although apo-E polymorphism does not appear to confer susceptibility to PBC, it probably influences PBC progression and response to UDCA. The epsilon4 allele may identify patients with high risk of severe disease and poor response to treatment.

Alanine Transaminase↗
PubMed2001

Sequential treatment with lamivudine and interferon monotherapies in patients with chronic hepatitis B not responding to interferon alone: results of a pilot study.

Sustained viral suppression using monotherapy with interferon alfa (IFN-alpha) or lamivudine can only be achieved in a small percentage of patients with chronic hepatitis B. The concomitant administration of lamivudine and IFN-alpha does not enhance efficacy. We postulated that the optimal timing of therapy might be sequential treatment with lamivudine and IFN-alpha. The aim of this study was therefore to assess the efficacy of sequential treatment in patients resistant to IFN-alpha alone. Fourteen male patients, with a median age of 40 years, nonresponders to IFN-alpha with hepatitis B virus (HBV) DNA > 100 pg/mL (branched DNA [bDNA] Chiron) and positive hepatitis B e antigen (HBeAg) in 11 of 14 patients, were treated with lamivudine 100 mg/d alone for 20 weeks, then with both IFN-alpha2b 5 MU 3 times per week and lamivudine for 4 weeks, and lastly with IFN-alpha alone for 24 weeks. At the end of lamivudine therapy, all patients had undetectable serum HBV DNA, and none exhibited an emergence of HBV polymerase mutant or breakthrough. Sustained serum HBV-DNA clearance 6 months after the end of sequential treatment was achieved in 8 of 14 patients, HBeAg-to-anti-HBe seroconversion in 5 of 11 patients, and HBeAg and hepatitis B surface antigen (HBsAg) seroconversions in 3 of 14 patients (anti-HBs > 100 IU/mL). All sustained responders had normalized their alanine transaminase (ALT) values and exhibited histologic improvements. In conclusion, the results of this pilot study suggest that sequential treatment with lamivudine and IFN-alpha can induce a sustained virologic response, including HBs seroconversion, in patients with chronic hepatitis B not responding to IFN-alpha alone, without the selection of drug-resistant mutants. This therapeutic schedule warrants further evaluation in clinical trials.

Adult↗
PubMed2001

Polyspecificity of antimicrosomal thyroid antibodies in hepatitis C virus-related infection.

OBJECTIVES: The outcome of dysthyroidism and the presence of antithyroid antibodies in patients with chronic hepatitis C virus (HCV) infection receiving interferon-alpha therapy is clearly established. However, the prevalence and the specificity of antithyroid antibodies in HCV patients before interferon-alpha therapy remain controversial. The aim of the present study is to clarify within a large population of HCV patients the prevalence of antithyroid antibodies before interferon-alpha therapy and to determine whether their immunodominant antigen is the same as described in autoimmune thyroiditis. METHODS: Sera from 99 patients with chronic hepatitis C before (n = 99) and after (n = 37) interferon-alpha treatment were investigated for the presence of antimicrosomal and antithyroperoxidase antibodies assessed by indirect immunofluorescence and ELISA, respectively. Dot blotting on human thyroid lysate was designed to further characterize these autoantibodies. Data were compared to those obtained with sera of patients with autoimmune thyroiditis (n = 75) and healthy subjects (n = 96). RESULTS: In HCV patients, antimicrosomal antibodies were found with a higher proportion before interferon-alpha therapy (12.1%) than after therapy (8%). Thyroperoxidase constitutes the main antigen in only 4% before treatment, a prevalence similar to that observed in healthy controls. CONCLUSIONS: The prevalence of antithyroid antibodies is low in patients with chronic hepatitis C before interferon-alpha therapy. Thyroperoxidase may not be their main target. Further studies are required to determine whether HCV infection leads to a breakdown of tolerance to a thyroid self-protein other than thyroperoxidase.

Adult↗
PubMed2000

Fetal microchimerism in primary biliary cirrhosis.

BACKGROUND/AIMS: Recent studies have suggested a role of fetal microchimerism in the pathogenesis of scleroderma. The present study investigated the potential role of fetal microchimerism in primary biliary cirrhosis (PBC), a closely related disease. METHODS: A quantitative nested polymerase chain reaction was used to detect Y-chromosome sequences in the peripheral blood or the liver of PBC women and controls having male children and no transfusion or miscarriage history. RESULTS: Male microchimerism was found in the peripheral blood from 45% (9 of 20) of PBC women and 25% (5 of 20) of healthy controls matched for the number of male children and age of the youngest son (p=0.28), and in the liver-biopsy specimens from 33% (5 of 15) of PBC women and 32% (8 of 25) of controls. The level of chimerism did not differ between patients and controls either in blood or in liver. Microchimerism was not related to the severity of the disease but was more frequent in PBC patients with anticentromere antibodies (p=0.049). CONCLUSIONS: Fetal microchimerism does not seem to play a major role in most cases of PBC. However, the association with anticentromere antibodies suggests a possible role in the subgroup of patients with CREST syndrome or scleroderma.

Adult↗
PubMed2000

Prognostic value of serum hyaluronan in patients with compensated HCV cirrhosis.

BACKGROUND/AIM: Serum hyaluronan (HA) levels increase according to the degree of liver fibrosis in patients with chronic viral hepatitis C. Patients with liver disease and markedly high serum HA levels have cirrhosis with typical signs of hepatic sinusoidal capillarization, a factor of aggravation of cirrhosis The aim of this study was to evaluate the prognostic value of serum HA for severe complications in asymptomatic patients with HCV cirrhosis. METHODS: Six hundred and sixty-eight patients with anti-HCV antibodies and increased serum alanine aminotransferase were referred to our hospital for evaluation, including liver biopsy. At entry, serum HA levels were measured in 91 patients (64 men, 27 women, 56 +/-11 years old) out of 103 who had asymptomatic, biopsy-proven cirrhosis According to the criteria of Child-Pugh, 82 were classified A and 9 B. The follow-up period was 6 to 82 months (median: 38 months), and 51 of these patients received alpha-interferon therapy during the first year. Severe complications were defined as death or liver transplantation, ascites, bleeding from esophageal varices, encephalopathy, or hepatocellular carcinoma. RESULTS: Serum HA levels at entry were higher in the cirrhotic patients in whom severe complications occurred during the follow-up period (520+/-426 microg/l vs 197+/-146 microg/l, p<0.0001). The patients with serum hyaluronan levels >350 microg/l displayed higher probabilities of occurrence of severe complications (p<0.0001). Other factors associated with the occurrence of complications or death were: serum bilirubin >18mol/l (p = 0.03), platelet count <112x10(9)/l (p= 0.02), prothrombin time <63% (p<0.0001), serum albumin <36 g/l (p=0.002), alkaline phosphatase >81 IU/l (p=0.01), and no interferon treatment (p= 0.0003). Multivariate analysis identified five independent factors predictive of severe clinical complications, namely: hyaluronan (p=0.006), prothrombin time (p=0.04), bilirubin (p=0.04), albumin (p=0.04), and no therapy (p=0.03). CONCLUSION: Serum HA level is predictive for occurrence of severe complications in HCV cirrhosis, and can be used as a prognostic marker, in addition to the parameters of the Child-Pugh score, particularly in patients with compensated cirrhosis.

Aged↗
PubMed2000

Chronic cholestatic diseases.

Chronic cholestatic diseases, whether occurring in infancy, childhood or adulthood, are characterized by defective bile acid transport from the liver to the intestine, which is caused by primary damage to the biliary epithelium in most cases. In this article, approaches to diagnosis and management of the main specific disorders are provided and some of the recent developments in this field are discussed. Major advances in the understanding of the cellular and molecular physiology of bile secretion have led to identification of genetic defects responsible for the different types of progressive familial intrahepatic cholestasis (PFIC). The potential role of the genes involved in PFIC in some adult cholestatic disorders remains to be determined. The majority of adult patients with chronic cholestasis have primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). Recently, variant forms of PBC have been described. The term autoimmune cholangitis is used to describe patients having chronic non-suppurative cholangitis with negative antimitochondrial antibodies (AMA) but positive antinuclear and/or antismooth muscle antibodies. Autoimmune cholangitis and AMA-positive PBC are quite similar in terms of clinical presentation, survival and response to ursodeoxycholic acid (UDCA) therapy. In contrast, autoimmune cholangitis must be distinguished from PBC-autoimmune hepatitis (AIH) overlap syndrome in which biochemical and histological characteristics of both PBC and AIH coexist. Combination of UDCA and corticosteroids is required in most patients with overlap syndrome to obtain a complete clinical and biochemical response. Long-term UDCA treatment improves survival without liver transplantation in PBC patients. Among the putative mechanisms of the beneficial effects of UDCA, description of anti-apoptotic properties and effect on endotoxin disposal in biliary cells have provided new insights. In patients with incomplete response to UDCA, combination of UDCA with antiinflammatory or immunosuppressive drugs is under evaluation. Variant forms of PSC have also been described, including PSC-AIH overlap syndrome, especially in children or young adults, and small-duct PSC, which is characterized by normal cholangiogram in patients having chronic cholestasis, histologic features compatible with PSC and inflammatory bowel disease. Development of cholangiocarcinoma (CC) is a major feature of PSC, occurring in 10-15% of patients. Early diagnosis of CC is a difficult challenge, although positron emission tomography seems a promising tool. Unlike PBC, effective medical therapy is not yet available in PSC, reflecting the lack of knowledge about the exact pathogenesis of the disease. Currently, liver transplantation is the only effective therapy for patients with advanced disease, although recurrence of PSC in the graft may occur.

Adult↗
PubMed2000

Comparison of a new method for the direct and simultaneous assessment of LDL- and HDL-cholesterol with ultracentrifugation and established methods.

BACKGROUND: Automated electrophoresis combined with enzymatic cholesterol staining might improve routine assessment of LDL- and HDL-cholesterol (LDLC and HDLC), as an alternative to the Friedewald equation and precipitation. A new method (Hydrasys; SEBIA) that adapts the cholesterol esterase/cholesterol oxidase reaction within urea-free gels was evaluated. METHODS: Fresh sera from 725 subjects (512 dyslipidemics) were analyzed by electrophoresis, in parallel with sequential ultracentrifugation, beta-quantification, calculation, and precipitation. RESULTS: Electrophoresis was linear up to 4 g/L cholesterol, with a detection limit of 0.042 g/L cholesterol/band. Within-run, between-run, between-batch, and between-operator imprecision (CVs) were 1.6%, 2.0%, 1.5%, and 2.7% for LDLC, and 3.9%, 4.3%, 5.5%, and 4.9% for HDLC, and remained unchanged up to 6.3 g/L plasma triglycerides (TGs). Precision decreased with very low HDLC (<0.25 g/L). Serum storage for 3-7 days at +4 or -80 degrees C did not interfere significantly with the assay. Agreement with beta-quantification was stable for LDLC up to 5.07 g/L (r = 0.94), even at TG concentrations >4 g/L (r = 0.91). Bias (2.88% +/- 12%) and total error (7.84%) were unchanged at TG concentrations up to 18.5 g/L. Electrophoresis predicted National Cholesterol Education Program cut-points with <0.04 g/L error, exactly and appropriately classified 79% and 96% of the subjects, and divided by 2.4 (all subjects) and 5.8 (TGs >1.5 g/L) the percentage of subjects underestimated by calculation. One-half of the patients with TGs >4 g/L had LDLC >1.30 g/L. For HDLC, correlation was better with precipitation (r = 0.87) than ultracentrifugation (r = 0.76). Error (-0.10% +/- 26%) increased when HDLC decreased (<0.35 g/L). Direct assessment of the LDLC/HDLC ratio detected 45% more high-risk subjects than the calculation/precipitation combination. CONCLUSIONS: Electrophoresis provides reliable quantification of LDLC, improving precision, accuracy, and concordance over calculation, particularly with increasing plasma TGs. Implementation of methods to detect low cholesterol concentrations could extend the applications for HDLC assessment.

Adolescent↗
PubMed1999

Clinical and biochemical expression of the histopathological lesions of primary biliary cirrhosis. UDCA-PBC Group.

BACKGROUND/AIMS: This study aimed to assess the relationships which may link elementary histological lesions with symptoms and biochemistries in primary biliary cirrhosis. METHODS: We studied 103 patients with primary biliary cirrhosis who participated in a double-blind, placebo-controlled trial of UDCA treatment and in whom liver biopsy specimens obtained at entry were reassessed. Relationships between histological features, fatigue, pruritus and biochemistries were calculated by using exact tests for 2 ordinal variables. RESULTS: The degrees of severity of fatigue and pruritus were significantly and exclusively related to the presence of florid interlobular bile duct lesions (p<0.01 and p<0.02, respectively). The only laboratory parameter associated with the presence of interlobular bile duct florid lesion was IgM level. The most discriminant biochemical test for interlobular bile duct paucity was gamma glutamyltranspeptidase activity. The degree of severity of both lymphocytic hepatocellular piecemeal necrosis and lobular inflammation and necrosis was mainly associated with increased gammaglobulin and IgG levels and to a lesser extent with increased IgM and aspartate aminotransferase levels. The extent of fibrosis was mainly associated with gammaglobulin levels and to a lesser degree with serum albumin, bilirubin and IgG levels. CONCLUSIONS: Symptoms and biochemistries classically used to assess primary biliary cirrhosis reflect in part the degree of severity of the main elementary histological lesions. We propose that the picture of primary biliary cirrhosis results from the clinical and biochemical expression of three distinct processes, e.g., bile duct inflammation and destruction, parenchymal inflammation and necrosis, and fibrosis. The various combinations of these processes may explain why the spectrum of primary biliary cirrhosis varies from typical primary biliary cirrhosis to mixed type of primary biliary cirrhosis and autoimmune hepatitis and suggests that the response to therapies may depend on the predominance of each process in a given patient.

Adrenal Cortex Hormones↗
PubMed1999

[Chronic cholestatic disorders in the adult].

Many hepatobiliary diseases can result in cholestasis. The main causes of chronic cholestasis in adults are primary biliary cirrhosis, which is characterized by portal triad inflammation and segmental necrosis of interlobular bile ducts, and primary sclerosing cholangitis, in which the intra and/or extrahepatic bile ducts undergo inflammation and fibrosis. The diagnosis is based on the presence of evidence of cholestasis and of symptoms specific for each condition. A number of drugs, sarcoidosis, total parenteral nutrition, chronic liver transplant rejection, and graft-versus-host disease can also cause chronic cholestasis. The treatment of these conditions has benefited greatly from rational use of ursodeoxycholic acid.

Adult↗