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Biomedical subjects

Michel Beaugrand

Publications and source records attributed to Michel Beaugrand.

At least 19 recordsLinked to original sources
PubMed2006

Risk factors for hepatocellular carcinoma in patients with alcoholic or viral C cirrhosis.

BACKGROUND & AIMS: Influence of being overweight and diabetes mellitus on the occurrence of hepatocellular carcinoma (HCC) in patients with cirrhosis has not been evaluated prospectively. The aim of this study was to show the predictive value of these factors in a cohort of 771 patients with well-compensated alcohol- or hepatitis C (HCV)-related cirrhosis who were screened prospectively for HCC. METHODS: The predictive value for HCC occurrence was assessed by using the log-rank test and the Cox proportional hazards model. At enrollment, the mean age was 61.4 +/- 10 years and 431 patients were men. Cirrhosis was caused by alcohol (n = 478), HCV (n = 220), or the association of both factors (n = 73). The mean body mass index (BMI) was 25.4 kg/m(2) and 231 patients were diabetic. RESULTS: During a mean follow-up period of 4.2 +/- 3 years, 220 patients developed HCC. In univariate analysis, a BMI of 25 kg/m(2) or more, diabetes, male sex, age older than 60 years, and HCV infection were risk factors for HCC. In multivariate analysis, predictive factors were a BMI between 25-30 kg/m(2) (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.4-2.7), BMI of 30 kg/m(2) or more (HR, 2.8; 95% CI, 2.0-4.0), diabetes (HR, 1.6; 95% CI, 1.2-2.1), age 60-70 years (HR, 2.4; 95% CI, 1.3-4.3), age older than 70 years (HR, 3.0; 95% CI, 1.7-5.5), male sex (HR, 2.0; 95% CI, 1.4-2.7), HCV (HR, 1.6; 95% CI, 1.1-2.2), and mixed (HR, 2.6; 95% CI, 1.7-4.0) etiology. We found a positive linear relationship between BMI level and HCC incidence during follow-up evaluation. CONCLUSIONS: Overweight and diabetes mellitus are associated with an increased risk of HCC occurrence in patients with HCV- or alcohol-related cirrhosis.

Age Factors↗
PubMed2006

Liver stiffness measurement selects patients with cirrhosis at risk of bearing large oesophageal varices.

BACKGROUND/AIMS: Periodic endoscopic screening for oesophageal varices is recommended in patients with cirrhosis, but might be limited to a subgroup of patients if a simple non-invasive test was available to select those at risk of bleeding. METHODS: We studied in 165 patients with cirrhosis the relation between the presence of oesophageal varices assessed by endoscopy, and liver stiffness measurement by Fibroscan, a non-invasive parameter related to liver fibrosis. The results were compared to those of other parameters reflecting portal hypertension, splenic size, platelet count, and platelet count/spleen size ratio. RESULTS: Liver stiffness measurement was correlated to the grade of oesophageal varices (r = 0.6, p < 0.0001). AUROC values of liver stiffness measurement were 0.84 (95% CI: 0.78-0.90) for the presence of oesophageal varices and 0.83 (0.76-0.89) for varices grade > or = II. Liver stiffness measurement value < 19 kPa was highly predictive of the absence of oesophageal varices grade > or = II (Se: 84%, PPV: 47%, NPV: 93%). CONCLUSIONS: Liver stiffness measurement allows to predict the presence of large oesophageal varices in patients with cirrhosis, and may help to select patients for endoscopic screening.

Elasticity↗
PubMed2006

Genetic polymorphisms in antioxidant enzymes modulate hepatic iron accumulation and hepatocellular carcinoma development in patients with alcohol-induced cirrhosis.

Manganese superoxide dismutase (MnSOD) converts the superoxide anion into H(2)O(2), which, unless it is detoxified by glutathione peroxidase 1 (GPx1), can increase hepatic iron and can react with iron to form genotoxic compounds. We investigated the role of Ala/Val-MnSOD and Pro/Leu-GPx1 polymorphisms on hepatic iron accumulation and hepatocellular carcinoma development in patients with alcoholic cirrhosis. Genotypes were determined in 162 alcoholic patients with cirrhosis but without hepatocellular carcinoma initially, who were prospectively followed up for hepatocellular carcinoma development. We found that patients with two Val-MnSOD alleles (slow H(2)O(2) production) and two Pro-GPx1 alleles (presumably quick H(2)O(2) detoxification) had a lower risk of hepatocellular carcinoma development than other patients (chi(2) trend test, P = 0.001; log-rank, P = 0.0009). Indeed, hepatocellular carcinoma percentage was 0% in subjects with this "2Val-MnSOD/2Pro-GPx1" genotype versus 16%, 27%, and 32% in "2Val-MnSOD/1or2Leu-GPx1," "1or2Ala-MnSOD/2Pro-GPx1," and "1or2Ala-MnSOD/1or2Leu-GPx1" patients, respectively. The percentage of patients with stainable hepatic iron increased progressively with these genotypic associations: 22%, 28%, 50%, and 53%, respectively (chi(2) trend test, P = 0.005). Stainable iron was a risk factor for hepatocellular carcinoma (log-rank, P = 0.0002; relative risk, 3.40). In conclusion, polymorphisms in antioxidant enzymes modulate hepatic iron accumulation and hepatocellular carcinoma development in French alcoholic patients with cirrhosis.

Alleles↗
PubMed2006

Diagnosis of hepatic fibrosis and cirrhosis by transient elastography in HIV/hepatitis C virus-coinfected patients.

BACKGROUND: Chronic hepatitis C in HIV-infected patients is an increasing cause of death dependent on the development of liver fibrosis, which is currently assessed by liver biopsy despite its limitations. Liver stiffness measurement, a new noninvasive method, allows the evaluation of liver fibrosis. The aim of this prospective study was to assess the accuracy of liver stiffness measurement for the detection of fibrosis and cirrhosis in HIV/hepatitis C virus (HCV)-coinfected patients and to compare its accuracy with other noninvasive methods. METHODS: We studied 72 consecutive HIV patients with chronic hepatitis C who had a simultaneous liver biopsy and liver stiffness measurement by transient elastography (FibroScan; Echosens, Paris, France) for the assessment of liver fibrosis. RESULTS: Liver stiffness values ranged from 3.0 to 46.4 kilopascal. Liver stiffness was significantly correlated to fibrosis stage (Kendall tau-b = 0.48; P < 0.0001). The area under the receiver operating characteristic (AUROC) curve of liver stiffness measurement was 0.72 for F > or = 2 and 0.97 for F = 4. For the diagnosis of cirrhosis, AUROC curves of liver stiffness measurement were significantly higher than those for platelet count (P = 0.02), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (P = 0.0001), Aspartate aminotransferase-to-Platelet Ratio Index (APRI) (P = 0.01), and FIB-4 (P = 0.004). CONCLUSION: Liver stiffness measurement is a promising noninvasive method for the assessment of fibrosis in HIV-infected patients with chronic HCV infection. Its use for the follow-up of these patients should be further evaluated.

Diagnostic Techniques, Digestive System↗
PubMed2006

Assessment of biliary fibrosis by transient elastography in patients with PBC and PSC.

Noninvasive measurement of liver stiffness with transient elastography has been recently validated for the evaluation of hepatic fibrosis in chronic hepatitis C. The current study assessed the diagnostic performance of liver stiffness measurement (LSM) for the determination of fibrosis stage in chronic cholestatic diseases. One hundred one patients with primary biliary cirrhosis (PBC, n=73) or primary sclerosing cholangitis (PSC, n=28) were prospectively enrolled in a multicenter study. All patients underwent liver biopsy (LB) and LSM. Histological and fibrosis stages were assessed on LB by two pathologists. LSM was performed by transient elastography. Efficiency of LSM for the determination of histological and fibrosis stages were determined by a receiver operating characteristics (ROC) curve analysis. Analysis failed in six patients (5.9%) because of unsuitable LB (n=4) or LSM (n=2). Stiffness values ranged from 2.8 to 69.1 kPa (median, 7.8 kPa). LSM was correlated to both fibrosis (Spearman's rho= 0.84, P < .0001) and histological (0.79, P < .0001) stages. These correlations were still found when PBC and PSC patients were analyzed separately. Areas under ROC curves were 0.92 for fibrosis stage (F) > or =2, 0.95 for F > or =3 and 0.96 for F=4. Optimal stiffness cutoff values of 7.3, 9.8, and 17.3 kPa showed F > or =2, F > or =3 and F=4, respectively. LSM and serum hyaluronic acid level were independent parameters associated with extensive fibrosis on LB. In conclusion, transient elastography is a simple and reliable noninvasive means for assessing biliary fibrosis. It should be a promising tool to assess antifibrotic therapies in PBC or PSC.

Adolescent↗
PubMed2006

Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver diseases.

A proper diagnosis of cirrhosis is essential for the management of patients with chronic liver diseases. We assessed the accuracy of liver stiffness measurement by Fibroscan for the diagnosis of cirrhosis in 1,257 patients with chronic liver diseases of various causes enrolled in a prospective multicenter study as well as clarified causes of discrepancies between liver histology and Fibroscan. One hundred thirty-two patients had unsuitable biopsy specimens, and 118 had unreliable liver stiffness measurements. Because 232 patients overlapped with a previous study, analysis was performed in the 775 new patients then derived in the whole population (1,007; 165 cirrhosis). Diagnostic accuracy was assessed by receiver operator curve (ROC) analysis. Liver samples were re-analyzed in case of discrepancies. The area under the ROC (AUROC) was 0.95 (95% CI, 0.93-0.96) for the diagnosis of cirrhosis in either 775 or 1,007 patients. The cutoff value with optimal diagnosis accuracy was 14.6 kPa in 1,007 patients (positive and negative predictive values, 74% and 96%) with discrepancies among the etiological groups. Eighty patients were misclassified: (1) among 45 patients without cirrhosis with liver stiffness 14.6 kPa or greater, 27 (60%) had extensive fibrosis and 10 (22%) significant perisinusoidal fibrosis; and (2) among 35 patients with cirrhosis and liver stiffness less than 14.6 kPa, 10 (29%) had a macronodular pattern and 25 (71%) either none or mild activity. In conclusion, Fibroscan is a reliable method for the diagnosis of cirrhosis in patients with chronic liver diseases, better at excluding than at predicting cirrhosis using a threshold of 14.6 kPa. False-negatives are mainly attributable to inactive or macronodular cirrhosis.

Adult↗
PubMed2006

Significance of hepatitis B virus genotypes A to E in a cohort of patients with chronic hepatitis B in the Seine Saint Denis District of Paris (France).

The aim of this study was to examine the genetic variability of the hepatitis B virus (HBV) and its significance. HBV genotypes, core promoter and precore mutants were characterized in 109 consecutive patients with biopsy-proven HBV chronic hepatitis. Genotypes A (26.6%), B (12.8%), C (18.3%), D (18.3%), and E (14.7%) indicate a wide genotypic distribution. Patients were from Asia (30.3%), Europe (28.4%), Sub Saharan Africa (23.9%), the Caribbean (10.1%), North Africa (5.5%), and Madagascar (1.8%). HBV genotypes A and D (HBV/A and /D) infected all subgroups except Asian patients. HBV/B or /C were found in 97% of Asian patients, whereas HBV/E only infected sub-Saharan African and Caribbean patients. Differences according to genotypes were: an increased prevalence of anti-HBe antibodies in patients infected with HBV/D (P = 0.003), higher serum transaminases in patients infected with HBV/A and/D (P = 0.043), more severe liver fibrosis in patients infected with HBV/A, /C and/D (P = 0.02). Precore and core promoter mutants were found in 87% of anti-HBe positive patients, and were associated with HBV/D (P = 0.04) and severe liver fibrosis (P = 0.002). It is concluded that HBV genotypes A, B, C, D, and E circulate in the Seine Saint Denis District, reflecting the geographical origin of patients. HBV/A, /C and/D seem to be associated with more severe hepatic disease.

Adult↗
PubMed2006

Molecular epidemiology of hepatitis C virus subtype 3a in injecting drug users.

Hepatitis C virus subtype 3a (HCV-3a) originates from Asia and has spread widely among injecting drug users as well as other patient groups in industrialized countries. HCV subtype 3a infection remains highly prevalent and frequently transmitted in the population of intravenous drug users. The objective of this study was to understand better the mechanisms of the worldwide HCV-3a epidemics in drug users. Ninety-three sera from HCV-3a-infected IDUs from France, the United States, Brazil, Argentina, and Australia were studied. Phylogenetic analyses of the non-structural 5B region showed no specific clustering according to the continent of the patient's origin. Non-exclusive clusters of viral sequences from South America, Australia, and California were observed, but topologies were not supported by strong bootstrap values. The results suggest that HCV-3a has been transmitted from a common origin through a unique worldwide epidemic that rapidly spread among drug users. Regional transmission occurred in the recent past, leading to an embryonic genetic diversification of HCV-3a among local injecting drug user population.

Argentina↗
PubMed2006

Ethanol versus radiofrequency ablation for the treatment of small hepatocellular carcinoma in patients with cirrhosis: a retrospective study of efficacy and cost.

OBJECTIVE: To compare cost effectiveness of radio-frequency (RF) ablation versus percutaneous ethanol (Pe) ablation for treatment of small hepatocellular carcinoma. METHODS: 57 patients with 72 hepatocellular carcinomas (HCC) treated with ethanol ablation were retrospectively compared with 60 new patients who had 72 HCC treated with RF ablation. All patients had Child-Pugh A cirrhosis and HCC less than 3.5 cm in diameter. Therapeutic efficacy was evaluated with tri-phase spiral computed tomography. Cost of hospital stay, supplies and follow-up including complications were calculated. Survival was estimated by Kaplan-Meier method and prognostic value of treatment methods by Log Rank test and multivariate Cox proportional hazard model. RESULTS: The two groups had similar baseline characteristics. The rate of severe complications associated with RF was 15% (9/60) vs 6,9% (9/60) with Pe (P=0,11) The two-year overall survival, disease free survival and local tumor free survival in the ethanol and radiofrequency groups were 70.8% vs. 91.2% (Odd Ratio=3.7, P=0.006), 48.6% vs. 71.1% (Odd Ratio=2.2, P=0.01), and 68.5% vs. 80.7%, (Odd Ratio=1.9; P=0.09), respectively. The treatment method was the sole significant factor related to overall and tumor free survival. Costs per patient of ethanol and radiofrequency treatments were 1534 euro and 1196 euro, respectively. CONCLUSION: This retrospective study suggests that RF is the most cost effective strategy, with higher 2-year disease free survival rate.

Adult↗
PubMed2006

Liver stiffness measurement versus clinicians' prediction or both for the assessment of liver fibrosis in patients with chronic hepatitis C.

OBJECTIVES: The goal of this study was to estimate the additional value of liver stiffness measurement (LSM) with physicians' assessment of fibrosis based on epidemiological, clinical, and biological parameters. METHODS: One hundred forty-two unselected patients with chronic hepatitis C were included. Liver biopsy and LSM were performed simultaneously. First, four physicians (two junior residents with limited experience in hepatology and two senior hepatologists) independently predicted the stage of fibrosis according to the METAVIR classification, using clinical, epidemiological, and biological data. For the second step, they were informed of LSM values and could modify their first evaluation if necessary. Finally, the two successive evaluations were compared with the histological fibrosis score. RESULTS: Providing LSM values improved agreement between physicians and resulted in a better correlation between clinical impression and histological liver fibrosis. The diagnostic performances were only significantly improved with transient elastography for the diagnosis of cirrhosis where assessment improved in three of the four physicians (AUROC [area under receiver operating characteristic curve]: 0.76 vs 0.87, 0.80 vs 0.87, and 0.83 vs 0.89, all p < 0.05). Moreover, these performances were nearly similar for junior and senior physicians when LSM was provided with the AUROC ranging from 0.69 to 0.72 for significant fibrosis and 0.87 to 0.90 for cirrhosis. CONCLUSIONS: Providing LSM values to physicians results in a better estimation of liver fibrosis and a more accurate diagnosis of cirrhosis. Moreover, it allows physicians with limited experience to predict liver fibrosis as well as experienced hepatologists.

Adult↗
PubMed2005

[Non-surgical treatment of hepatocellular carcinoma. An overview].

Surgery is often not a treatment option in patients with hepatocellular carcinoma with the numerous limitations of liver transplantation or surgical resection due to coexisting cirrhosis in the later case. Non-surgical treatments deal with 3 types of methods: local ablation with curative purpose, transarterial treatments with many technical variants and systemic treatment. Local treatments rely on chemical or thermic agents to achieve ablation of liver lesions, which not exceed initially 3 cm in diameter. The use of radiofrequency ablation allows now larger limits. Intra-arterial treatment usually combines intra-arterial chemotherapy with embolisation of hepatic artery in a procedure called chemoembolisation. Its antitumoral effect mainly due to ischemia is well documented but the influence on survival remains controversial. Finally systemic treatments have yet to be demonstrated useful: new agents and new randomised trials are still needed.

Antineoplastic Agents↗
PubMed2005

Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C.

Liver fibrosis is the main predictor of the progression of chronic hepatitis C, and its assessment by liver biopsy (LB) can help determine therapy. However, biopsy is an invasive procedure with several limitations. A new, noninvasive medical device based on transient elastography has been designed to measure liver stiffness. The aim of this study was to investigate the use of liver stiffness measurement (LSM) in the evaluation of liver fibrosis in patients with chronic hepatitis C. We prospectively enrolled 327 patients with chronic hepatitis C in a multicenter study. Patients underwent LB and LSM. METAVIR liver fibrosis stages were assessed on biopsy specimens by 2 pathologists. LSM was performed by transient elastography. Efficiency of LSM and optimal cutoff values for fibrosis stage assessment were determined by a receiver-operating characteristics (ROC) curve analysis and cross-validated by the jack-knife method. LSM was well correlated with fibrosis stage (Kendall correlation coefficient: 0.55; P < .0001). The areas under ROC curves were 0.79 (95% CI, 0.73-0.84) for F > or =2, 0.91 (0.87-0.96) for F > or =3, and 0.97 (0.93-1) for F=4; for larger biopsies, these values were, respectively, 0.81, 0.95, and 0.99. Optimal stiffness cutoff values of 8.7 and 14.5 kPa showed F > or =2 and F=4, respectively. In conclusion, noninvasive assessment of liver stiffness with transient elastography appears as a reliable tool to detect significant fibrosis or cirrhosis in patients with chronic hepatitis C.

Adult↗
PubMed2005

Serum albumin and platelet count but not portal pressure are predictive of death in patients with Child-Pugh A hepatitis C virus-related cirrhosis.

AIM: The presence of esophageal varices has been reported to be a prognostic factor in patients with compensated hepatitis viral C induced cirrhosis. We studied the prognostic value of hepatic venous pressure gradient in addition to epidemiological and clinical parameters in these patients. METHODS: Among patients with Child-Pugh A hepatitis C induced cirrhosis, prospectively followed in two Parisian centres, 100 had measurement of occluded and free hepatic venous pressures. We evaluated hepatic venous pressures as a predictive factor of death by Cox models (survival) and Fine and Gray models (liver-deaths). RESULTS: Median hepatic occluded pressure and gradient were 21.5 (15-24) and 13 mm Hg (9-15), respectively. The median duration of follow-up was 85 months (range: 70-112); 38 deaths or liver transplantation were registered. Hepatic venous pressure gradient was not significantly related to survival in the studied population but as a continuous variable was predictive of death from liver disease. On multivariable analysis serum albumin <40 g/L and platelet count <90,000 /mm(3) were the only selected prognostic factors. CONCLUSION: Hepatic venous pressure gradient has a limited value for assessing the prognosis of patients with Child-Pugh A hepatitis C virus induced cirrhosis; prognosis is accurately predicted by serum albumin and platelet count.

Aged↗
PubMed2005

Genetic dimorphism in superoxide dismutase and susceptibility to alcoholic cirrhosis, hepatocellular carcinoma, and death.

BACKGROUND AND AIMS: A genetic dimorphism encodes for either alanine (Ala) or valine (Val) in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD), and modulates its mitochondrial import. However, the role of this dimorphism in the susceptibility of alcoholic patients to develop cirrhosis is controversial, and its influence on the occurrence of hepatocellular carcinoma (HCC) and death in patients with alcoholic cirrhosis is unknown. METHODS: We compared MnSOD genotypes in 94 control subjects and 264 patients with alcoholic cirrhosis. Patients were included at the time of the first liver biopsy examination showing cirrhosis, and were followed-up prospectively. RESULTS: Alcohol consumption was similar, whatever the patients' genotype. At inclusion, the percentage of Val/Val homozygotes was lower in patients than in controls (16% vs. 31%), whereas the percentage of Ala/Ala homozygotes was higher in patients than in controls (30% vs. 21%) ( P = .008). During follow-up evaluation, only 9% of Val/Val patients developed HCC, vs. 30% and 29% of Ala/Val and Ala/Ala patients, respectively ( P = .02). Only 28% of Val/Val patients died or were transplanted, vs. 49% and 50% of Ala/Val and Ala/Ala patients, respectively ( P = .03). Because of the progressive decrease in surviving Ala patients, the genotypic distribution in patients surviving for 5 or 10 years no longer differed from the genotypic distribution in controls. CONCLUSIONS: The presence of at least 1 Ala MnSOD allele increases the risk for developing cirrhosis in French alcoholics, and increases the rates of HCC development and death in cirrhotic patients.

Carcinoma, Hepatocellular↗
PubMed2005

Local/regional and systemic treatments of hepatocellular carcinoma.

Screening programs for patients with cirrhosis are designed to detect hepatocellular carcinoma at an early stage when effective treatment is feasible and may provide long-term survival benefits. However, only a minority of these patients will be considered candidates for liver transplantation or surgical resection and hence, most cases will be evaluated for other medical options. While systemic therapy has never been shown to bear a relevant antitumoral activity with an impact on survival, there are several locoregional options that can achieve a high rate of objective responses (this includes complete necrosis or partial reduction in tumor burden). Percutaneous ablation by any of the available methods (ethanol injection, radiofrequency, microwave, acetic acid injection, laser) is extremely useful in patients with small solitary tumors. Results indicate that 90% of tumors < 2 cm will be completely ablated using the percutaneous approach. However, when tumor size exceeds 3 cm and/or the number of nodules is greater than 3, the rate of treatment success is significantly reduced. In patients with large/multifocal disease, the sole option that has been shown to provide treatment efficacy with moderate improvement in survival is chemoembolization. New therapeutic agents should target biological mechanisms in a tailored strategy, and the demonstration of beneficial results for patients should be obtained by large, randomized, controlled trials comparing active intervention versus no treatment.

Antineoplastic Agents, Hormonal↗
PubMed2005

Partial splenic embolization in patients with cirrhosis: efficacy, tolerance and long-term outcome in 32 patients.

BACKGROUND: Although partial splenic embolization (PSE) has been proposed in patients with cirrhosis in cases when thrombocytopenia or neutropenia may cause clinical manifestations or if there are contra-indications to other therapeutic procedures, there are limited data on long-term outcome. We provide a retrospective review of results and the tolerance of all PSE procedures in patients with cirrhosis in our department. PATIENTS AND METHODS: Thirty-two consecutive patients with cirrhosis were included over a 6 year period. Indications for PSE were as follows: (1) severe cytopenia preventing necessary antiviral treatment (n=14), percutaneous destruction of hepatocellular carcinoma (n=8) or major surgery (n=3), severe purpura (n=3); (2) painful splenomegaly (n=4). After superselective catheterization, embolization was performed with up to 50% reduction of splenic blood flow. RESULTS: Thrombocyte and leucocyte counts increased markedly (185% and 51% at 1 month; 95% and 30% at 6 months). Thirty-one and 20 patients had platelet count >80,000/mm3 at months 1 and 6 vs only one before PSE. Overall, the aim of PSE was achieved in 27 patients (84%) (planned treatment: 20/25; disappearance of purpura and splenic pain: 7/7). Severe complications occurred in five patients (16%): transient ascites (n=2), splenic and/or portal vein thrombosis (n=2) that resolved after anticoagulation therapy, and splenic abscess (n=2) leading to death. These two patients had splenic necrosis >70%. CONCLUSION: In patients with cirrhosis, PSE may resolve cytopenia and the clinical complications related to hypersplenism or splenomegaly. However, due to a high risk of severe complications, particularly splenic abscess, the indications of PSE should be very limited and the extent of necrosis should be strictly controlled during the PSE procedure.

Abscess↗