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Biomedical subjects

Raoul Poupon

Publications and source records attributed to Raoul Poupon.

At least 19 recordsLinked to original sources
PubMed2005

Impact of steatosis on progression of fibrosis in patients with mild hepatitis C.

In patients with mild hepatitis C, the usefulness of antiviral therapy is subject of debate, as a low risk for progression of fibrosis is assumed. Several studies have shown that steatosis is a strong and independent predictor of the severity as well as the progression of fibrosis in chronic hepatitis C. Therefore, this study assessed the impact of steatosis on the progression of fibrosis between paired liver biopsies in untreated patients with mild hepatitis on index biopsy. One hundred thirty-five untreated patients (mean age, 38 years; M/F sex ratio, 1.43) with one known risk factor of infection (68 transfusions, 67 injecting drug use) had 2 liver biopsies after a median interval of 61 months (18-158). All had METAVIR score of A1F1 or lower at first liver biopsy. Unequivocal progression of fibrosis was considered if patients had a fibrosis score of 3 or 4 at the second liver biopsy. The probability of progression of fibrosis was estimated by using the Kaplan-Meier method. During follow-up, progression of fibrosis occurred in 21 patients (16%) after a median delay of 65 months. Cumulative probabilities of the progression of fibrosis at 4 and 6 years were 5.2% and 19.8%, respectively. In multivariate analysis, steatosis was the only independent factor predictive of progression of fibrosis (RR, 4.8; CI, 1.3-18.3). Probability of progression of fibrosis was significantly related to the percentage of hepatocytes with steatosis. In conclusion, steatosis is a major determinant of the progression of fibrosis in mild hepatitis C, regardless of the genotype. Our results argue for antiviral treatment in the subgroup of patients with mild hepatitis and steatosis.

Adult↗
PubMed2005

Gefitinib, an EGFR inhibitor, prevents hepatocellular carcinoma development in the rat liver with cirrhosis.

Epidermal growth factor receptor (EGFR) binds transforming growth factor alpha (TGF-alpha) which is mitogenic for hepatocytes. Diverse lines of evidence suggest that activation of the TGF-alpha /EGFR pathway contributes to hepatocellular carcinoma (HCC) formation. Herein, we developed an experimental model of cirrhosis giving rise to HCC and tested the antitumoral effect of gefitinib, a selective EGFR tyrosine kinase inhibitor, in this model. Rats received weekly intraperitoneal injections of diethylnitrosamine (DEN) followed by a 2-week wash-out period that caused cirrhosis in 14 weeks and multifocal HCC in 18 weeks. Hepatocyte proliferation was increased in diseased tissue at 14 weeks compared with control liver and at even higher levels in HCC nodules compared with surrounding diseased tissues at 18 weeks. Increased proliferation was paralleled by upregulation of TGF-alpha messenger RNA expression. A group of DEN-treated rats received daily intraperitoneal injections of gefitinib between weeks 12 and 18. In rats treated with gefitinib, the number of HCC nodules was significantly lower than in untreated rats (18.1 +/- 2.4 vs. 3.7 +/- 0.45; P < .05), while EGFR was activated to a lesser extent in the diseased and tumoral tissues of these animals compared with untreated rats. HCC nodules from both untreated and gefitinib-treated animals displayed insulin-like growth factor 2 overexpression that contributed to tumor formation in treated animals. In conclusion, the blockade of EGFR activity by gefitinib has an antitumoral effect on the development of HCC in DEN-exposed rats, suggesting that it may provide benefit for the chemoprevention of HCC.

Alkylating Agents↗
PubMed2005

Chronic liver injury during obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) are at risk for the development of fatty liver as a result of being overweight. Several data suggest that OSA per se could be a risk factor of liver injury; ischemic hepatitis during OSA has been reported, and OSA is an independent risk factor for insulin resistance. Therefore, we investigated liver damage and potential mechanisms in 163 consecutive nondrinking patients with nocturnal polysomnographic recording for clinical suspicion of OSA. Serum levels of liver enzymes were measured in all patients. Liver biopsy was offered to patients with elevated liver enzymes. Intrahepatic hypoxia was assessed by the expression of vascular endothelial growth factor (VEGF) on liver biopsy specimens. Severe OSA (apnea-hypopnea index [AHI] > 50/hr) was seen in 27% of patients; 52% had moderate OSA (AHI 10-50/hr), and 21% had no OSA. Overall, 20% had elevated liver enzymes. Independent parameters associated with elevated liver enzymes were body mass index (BMI) (OR: 1.13; CI: 1.03-1.2) and severe OSA (OR: 5.9; CI: 1.2-29). Liver biopsy was performed in 18 of 32 patients with elevated liver enzymes and showed steatohepatitis in 12 cases, associated with fibrosis in 7 cases. Patients with severe OSA were more insulin-resistant according to homeostasis model assessment, had higher percentage of steatosis as well as scores of necrosis and fibrosis, despite similar BMI. Hepatic immunostaining used as an indirect marker of hypoxia was not different between patients with or without severe OSA. In conclusion, severe OSA is a risk factor for elevated liver enzymes and steatohepatitis independent of body weight. Promotion of insulin resistance is probably involved. Further studies are needed to determine whether hypoxia contributes directly to liver injury.

Adult↗
PubMed2005

The effect of ursodeoxycholic acid therapy on the natural course of primary biliary cirrhosis.

BACKGROUND AND AIMS: We used a multistate modeling approach to assess the effect of ursodeoxycholic acid (UDCA) therapy on the natural course of primary biliary cirrhosis (PBC), which remains controversial. METHODS: Our population included 262 patients with PBC who had received 13-15 mg/kg UDCA daily for a mean of 8 years (range, 1-22 years). Data were analyzed using a multistate Markov model, with histologic stage progression, death, and orthotopic liver transplantation (OLT) as main end points. Survival without OLT was compared with that predicted by the updated Mayo model and with the expected survival in the control population. RESULTS: Forty-five patients developed cirrhosis, 20 underwent OLT, and 16 died by the censor date. Ten deaths were due to liver disease. The overall survival rates were 92% at 10 years and 82% at 20 years. Survival rates without OLT were 84% and 66% at 10 and 20 years, respectively, which were slightly lower than the survival rate of an age- and sex-matched control population (relative risk [RR], 1.4; P = .1) but better than the spontaneous survival rate as predicted by the updated Mayo model (RR, .5; P < .01). The survival rate of patients in stage 1 and 2 was similar to that in the control population (RR, .8; P = .5), whereas the probability of death or OLT remained significantly increased in treated patients in late histologic stages (RR, 2.2; P < .05). CONCLUSIONS: Treatment with UDCA alone normalizes the survival rate of patients with PBC when given at early stages. However, there is a continued need for new therapeutic options in patients with advanced disease.

Adult↗
PubMed2005

[Hepatitis C: epidemiology, management and treatment].

Hepatitis C virus (HCV) is a major public health problem and a leading cause of chronic liver disease in western countries. The aim of this review is to provide an update on the epidemiology, diagnosis, management and therapy of the infection. It is estimated that about 400,000 persons in France have ongoing HCV infection. The estimated incidence is around 4000 cases per year. All patients with suspected chronic HCV infection should be tested for HCV RNA, as seropositivity without detectable viremia is frequent. The HCV genotype should be determined systematically prior to specific treatment in order to determine the optimal duration of therapy and the likelihood of response. Liver biopsy should be performed when the results are likely to influence the decision to treat. Treatment decisions should be individualized, being based on the severity of liver disease, the potential for serious adverse effects, the likelihood of a treatment response, and any comorbidity. The peginterferon-ribavirin combination is the treatment of choice, affording sustained viral clearance in up to 85% of patients infected by genotypes 2 and 3, and up to 50% in patients with genotype 1 infection.

Antiviral Agents↗
PubMed2004

Quality of life in patients with primary biliary cirrhosis.

The impact of primary biliary cirrhosis (PBC) on health-related quality of life (HRQOL) is poorly documented. We assessed quality of life in a group of 276 unselected patients with PBC using the Nottingham Health Profile (NHP). This is a generic scale that assesses six major areas commonly associated with HRQOL. Data were compared with those of a sex- and age-matched control group. The associations between NHP scores and the severity of PBC were tested. Patients (86% women) had a median age of 62 years (range 33-87). Most patients were treated with UDCA. PBC patients showed a strong statistically significant difference in energy compared to controls (respectively, 40.6 vs. 22.9, P < .0001) and had worse scores for emotional reactions (22.2 vs. 16.1, P < .005). No other differences were observed. No associations of the dimension subscores were found with biochemical liver tests, histological stages, or duration of the disease. Among the signs or symptoms, fatigue was the finding most often associated with the dimension subscores. In conclusion, patients with PBC feel that their overall quality of life is worse than that of the control population. This difference is mainly due to the decrease in the subscores of energy and emotional reactions, both associated with fatigue. These effects must be taken into account by clinicians when treating these patients, as they constitute the clinical outcomes that have the most impact on patients' lifestyle and adherence to treatment.

Adult↗
PubMed2004

Improved survival after variceal bleeding in patients with cirrhosis over the past two decades.

Over the past two decades, new treatment modalities have been introduced for the management of variceal bleeding. The aim of this retrospective study in a single center was to assess whether these treatments have improved the prognosis for cirrhotic patients with variceal bleeding. We reviewed the clinical records of all patients with cirrhosis admitted to our Liver Intensive Care Unit due to variceal bleeding during the years 1980, 1985, 1990, 1995, and 2000. Whereas balloon tamponade was still the first-line treatment in 1980, patients treated in 2000 received a vasoactive agent, an endoscopic treatment, and an antibiotic prophylaxis in, respectively, 90%, 100%, and 94% of cases. The in-hospital mortality rate steadily decreased over the study period: 42.6%, 29.9%, 25%, 16.2%, and 14.5% in 1980, 1985, 1990, 1995, and 2000, respectively (P < .05). Mortality decreased from 9% in 1980 to 0% in 2000 in Child-Turcotte-Pugh class A patients, from 46% to 0% in class B patients, and from 70% to 32% in class C patients. This improved survival was associated with a decrease of rebleeding (from 47% in 1980 to 13% in 2000) and bacterial infection rates (from 38% to 14%). On multivariable analysis, endoscopic therapy and antibiotic prophylaxis were independent predictors of survival. In conclusion, in-hospital mortality of patients with cirrhosis and variceal bleeding decreased threefold over the past two decades, in concurrence with an early and combined use of pharmacological and endoscopic therapies and short-term antibiotic prophylaxis.

Adult↗
PubMed2004

Immune response to lipopolysaccharide in primary biliary cirrhosis and autoimmune diseases.

A bacteriological aetiology is suspected to be the triggering factor in primary biliary cirrhosis. We studied lipid A, the toxic and immunogenic moiety of gram-negative bacteria lipopolysaccharide, which accumulates abnormally in Kupffer cells, hepatocytes, and biliary epithelial cells in primary biliary cirrhosis patients. Anti-lipid A antibody levels from serum samples from 36 primary biliary cirrhosis patients, drawn before and after ursodeoxycholic acid treatment, were compared to those from patients with other liver diseases (n=236), non-hepatic diseases (n=249), and healthy subjects (n=75). In primary biliary cirrhosis patients, the prevalence of IgM anti-lipid A antibodies was higher before than after ursodeoxycholic acid therapy (64% vs 22%, respectively; P<0.001). Patients with anti-lipid A antibodies had significantly higher IgM levels than those without antibodies (8.7+/-1.1 g/l vs 4.4+/-0.8 g/l, P<0.02). Total IgM levels were correlated with anti-lipid A antibody levels (r=0.65, P<0.02). After therapy, the serum IgM levels decreased significantly (P<0.03). These results indicate that bacterial antigens may participate in the observed increase of serum IgM levels, and support an aetiological role of a gut-derived endotoxin antigen in the pathogenesis of primary biliary cirrhosis.

Adult↗
PubMed2004

[Fatal Dieulafoy's type ulcer in a case of gastric AL-amyloidosis].

Dieulafoy's ulcer is a particular form of gastric ulcer confined to a persistent caliber artery and may lead to severe hemorrhage. We report a case of fatal gastric bleeding in a woman with benign biclonal gammapathy. Autopsy found a typical Dieulafoy's ulcer centered by a persistent caliber artery which wall was thickened by AL-amyloid deposits. Amyloidosis involved the gastric wall, but also middle caliber arteries of the liver, the lung, the pancreas, the kidney and the myocardium. AL-amyloidosis is a rare and late complication of monoclonal gammapathy and may be asymptomatic. Pathogenesis of Dieulafoy's ulcer remains unclear. In our case, local ischemia may have facilitated gastric ulceration, and amyloid deposits may have contributed to arterial rupture.

Aged↗
PubMed2004

[Biliary function and its regulation].

Biliary function is essential for intestinal absorption of fat, homeostasis of cholesterol and elimination of diverse metabolic end-products. Bile is elaborated in hepatocyte canaliculi and modified by cholangiocytes through both secretion and absorption processes. The main determinant of bile formation is an osmotic filtration process resulting from active transport of bile acids and other osmotic solutes. Most of the membrane transporters ensuring bile formation have now been identified. The expression of these membrane transporters is regulated in particular through transcriptional mechanisms under the control of nuclear receptors activated by ligands, such as bile acids, which act as endogenous steroids synthesized from cholesterol in hepatocytes. Monogenic cholestatic diseases illustrate the key role of membrane transporters in biliary function. Bile acids are potent modulators of transporters and thus trigger an adaptative response to cholestasis. The extent of this adaptative response could explain the compelling phenotypic variability of cholestatic diseases in childhood and adults. The firstline medical treatment is currently ursodeoxycholic acid. In case of failure of this medical treatment, liver transplantation is required. Recent progress in the molecular pathogenesis of bile formation and cholestatic liver diseases is expected to provide the design for drugs targeted to the molecular abnormalities responsible of cholestatic diseases.

Animals↗