Search PubMed⌕ Search

Biomedical subjects

Raoul Poupon

Publications and source records attributed to Raoul Poupon.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2004

Biochemical markers of liver fibrosis and lymphocytic piecemeal necrosis in UDCA-treated patients with primary biliary cirrhosis.

BACKGROUND/AIM: We have previously shown that the histological stage and severity of lymphocytic piecemeal necrosis (LPN) are independent predictive factors of cirrhosis development in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cirrhosis (PBC). Our aim during this study was to determine whether biochemical parameters classically used in PBC management and measured under UDCA could be considered as reliable surrogate markers for these histological prognostic indices in clinical practice. METHOD: The study included 153 patients with PBC who had undergone a control liver biopsy after 2 years of UDCA therapy. The relationships between histological and biological features were assessed by variance analysis and logistic regression. The diagnostic value of independent markers was assessed in terms of their sensitivity, specificity, positive predictive value (PPV) and negative value (NPV) and receiver-operating characteristic curves. RESULTS: Two variables were independently associated with extensive fibrosis (i.e. advanced histological stages): serum levels of bilirubin and hyaluronic acid (HA). A fibrosis index ([bilirubin (micromol/l)/14]+[HA (microg/l)/143]) higher than 1.5 exhibited good PPV and specificity (>74%) but rather poor NPV and sensitivity (<64%) regarding a diagnosis of extensive fibrosis. The only independent marker of LPN was aspartate aminotransferase (AST) activity. AST activity of more than twice the upper limit of normal showed acceptable PPV (>70%) but very low sensitivity (<25%) for a diagnosis of LPN. CONCLUSIONS: Serum bilirubin and HA levels measured under UDCA therapy are of acceptable diagnostic value for extensive fibrosis, but none of the biochemical tests commonly employed in the management of PBC can be considered as surrogate markers of LPN. Taken together with our previous results, these findings suggest that liver biopsy may be necessary to screen UDCA-treated patients who might require additional therapies.

Aspartate Aminotransferases↗
PubMed2004

Genetic and acquired thrombotic factors in chronic hepatitis C.

OBJECTIVES: During the progression of chronic liver disease towards cirrhosis, morphological studies have shown a close association between parenchymal remodeling and obliterative lesions of intrahepatic small portal and hepatic veins. These lesions are highly suggestive of intrahepatic thrombotic events, which may have a key role in the pathogenesis of hepatic fibrosis. The aim of the study was to investigate thrombotic risk factors in chronic hepatitis C patients with different extent of liver fibrosis. METHODS: The following thrombotic factors were evaluated in 68 hepatitis C patients with prothrombin activity >/= 80% (34 consecutive patients with extensive fibrosis and/or cirrhosis compared with 34 consecutive patients without extensive fibrosis and/or cirrhosis): factor V Leiden, G20210A prothrombin mutation, antithrombin, protein C and S deficiencies, hyperhomocysteinemia, elevated factor VIII level, and lupus anticoagulant. RESULTS: Three thrombotic risk factors were significantly more frequent in patients with extensive fibrosis and/or cirrhosis than in those without extensive fibrosis: protein C deficiency present in 14 patients (41%) as compared with three patients (9%), p= 0.004; elevated factor VIII level present in 19 patients (56%) as compared with six patients (18%), p= 0.002; and hyperhomocysteinemia present in 10 patients (29%) as compared with two patients (6%), p= 0.023. The association of two or three prothrombotic factors was present in 19 patients (56%) with extensive fibrosis and/or cirrhosis as compared with one patient (3%) without extensive fibrosis and/or cirrhosis, p < 0.001. CONCLUSION: Multiple thrombotic risk factors coexist frequently in patients with extensive fibrosis and early stage of cirrhosis. Their association with local inflammation could favor thrombotic events in the liver micro-circulatory bed.

Adult↗
PubMed2003

Early change in bilirubin levels is an important prognostic factor in severe alcoholic hepatitis treated with prednisolone.

Early identification of patients with severe (discriminant function >or=32) biopsy-proven alcoholic hepatitis (AH) who are not responding to corticosteroids would be clinically relevant. Our goal was to develop simple criteria that will help physicians to promptly identify nonresponders to corticosteroids. A total of 238 patients were included. We used 6 months survival as an end point because of the rule requiring 6 months for listing alcoholic patients for transplantation. Overall survival at 1 and 6 months was 85% +/- 2.3% and 64.3% +/- 3.3%, respectively. An early change in bilirubin levels (ECBL) at 7 days (defined as bilirubin level at 7 days lower than bilirubin level on the first day of treatment) was observed in 73% of patients. At 7 days, in patients with ECBL, bilirubin decreased (84 +/- 75 micromol/L [4.94 +/- 4.40 mg/dL]), whereas it increased in patients without ECBL (76.5 +/- 77 micromol/L [4.50 +/- 4.54 mg/dL], P <.0001). Ninety-five percent of patients with ECBL continued to have improved liver function during treatment. At 6 months, survival of patients with ECBL was significantly higher than that of patients without ECBL, 82.8% +/- 3.3% versus 23% +/- 5.8%, P <.0001. On multivariate analysis, ECBL, discriminant function and creatinine were independent prognostic variables, and ECBL had the most important prognostic value. In conclusion, ECBL is a very simple predictive factor for identifying nonresponders. A recommendation to discontinue corticosteroids after 7 days in patients without ECBL, suggested by our results, awaits additional confirmation.

Adult↗
PubMed2003

ABCB4 gene mutation-associated cholelithiasis in adults.

BACKGROUND & AIMS: We recently put forward arguments in favor of ABCB4 gene (adenosine triphosphate-binding cassette, subfamily B, member 4) defects as a risk factor for symptomatic cholelithiasis in adults. In this study, we characterized ABCB4 gene mutations in a series of patients with symptomatic cholelithiasis to determine the genetic basis and the clinical phenotype of ABCB4 gene mutation-associated cholelithiasis. METHODS: We analyzed the entire ABCB4 gene coding sequences in a first group of 32 patients who had a clinical history compatible with the syndrome previously described, in a second group of 28 patients who presented with a classic gallstone disease that justified a cholecystectomy, and in a third group of 33 patients without a history of cholelithiasis. RESULTS: We identified both heterozygous and homozygous ABCB4 gene point mutations in 18 of 32 (56%) patients who presented with clinical criteria of the syndrome, whereas no mutation was detected in the 2 other groups of patients (P < 0.001). Three independent clinical features were strongly associated with point mutations: recurrence of symptoms after cholecystectomy (odds ratio, 8.5); intrahepatic hyperechoic foci, intrahepatic sludge, or microlithiasis (odds ratio, 6.1); and age <40 years at the onset of symptoms (odds ratio, 3.0). ABCB4 gene point mutations were detected exclusively in the patients who showed 2 or 3 of these clinical features. CONCLUSIONS: Our results show that ABCB4 gene mutations represent a major genetic risk factor in a symptomatic and recurring form of cholelithiasis in young adults.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2003

Combined analysis of the effect of treatment with ursodeoxycholic acid on histologic progression in primary biliary cirrhosis.

BACKGROUND/AIMS: This study aimed at evaluating the effect of ursodeoxycholic acid (UDCA) treatment on histologic progression in primary biliary cirrhosis (PBC). METHODS: Using combined individual histologic findings from four clinical trials, we selected the patients in whom paired liver-biopsy specimens were available with a time interval of about 36 months between biopsies. A total of 367 patients were selected (UDCA: 200 vs. placebo: 167). RESULTS: Overall, there was no significant difference in the progression of the histologic stage between the two groups. By contrast, in the subgroup of patients with initial stages I-II (n=177) there was a significant decrease in the histologic stage progression in the UDCA group relative to the placebo group (P<0.03). Overall, there was a significant delay in the progression of periportal necroinflammatory lesions (P=0.03), and an improvement in the degree of ductular proliferation (P=0.02) in the UDCA group compared with the placebo group. There was no significant difference in the progression of other specific lesions. CONCLUSIONS: A 2-year UDCA treatment reduces periportal necroinflammation and improves ductular proliferation, and when initiated at the earlier stages I-II of the disease also delays the progression of histologic stage. These data support the early initiation of the drug to prevent these histologic features of PBC.

Adult↗
PubMed2003

Autoimmune overlapping syndromes.

The overlap syndrome raises several questions. First could these patients have two coincident autoimmune diseases? Such possibility cannot be discarded in particular in the setting of consecutive occurrence of the two conditions (eg, PBC followed by AIH) and this is consistent with the fact that autoimmune diseases are associated with one another in about 5% to 10% of cases. Furthermore, it is presumed that they share similar genetic susceptibility. A second possibility could be that overlap syndrome represents the middle of a continuous spectrum of two autoimmune liver diseases. The systematic study of the relationships between elementary histologic lesions and biochemistries in "pure" PBC patients pleads strongly for such a hypothesis. Pure PBC is characterized by 2 different groups of elementary lesions that are not interrelated: first, florid bile duct lesions and bile duct paucity and second, lymphocytic piecemeal necrosis and lobular necro-inflammatory changes. Furthermore, the first set of lesions is selectively associated with biochemical cholestasis and IgM levels, whereas the second set of lesions is selectively associated with serum transaminase activities and IgG levels. These observations are consistent with the assumption that two main mechanisms are involved in the progression of liver injury in PBC. The first is bile duct destruction leading to chronic cholestasis and fibrosis of biliary pattern. The second is lymphocytic piecemeal necrosis of hepatocytes, which tends to lead to cirrhosis, the pattern of which resembles cirrhosis following various forms of chronic active hepatitis. The author has therefore speculated that the picture of pure PBC results always forms the clinical and biochemical expression of the two main histologic lesions, and combination of these processes might explain why the spectrum of PBC varies from typical PBC to AIH or PBC overlap. A third hypothesis is that an exaggerated hepatitic response in PBC is associated with the HLA haplotype commonly seen in AIH, eg, B8, DR3, DR4. Further studies are obviously needed to confirm such an attractive hypothesis. Other possible explanation for the concurrent occurrence of features of both conditions in the same individual includes the selective modulation of HLA class 1, class 2 expression and Rantes by cholestasis itself and in particular bile acids. It is conceivable that the degree of interface and lobular inflammation in PBC and PSC may be modulated by chemokines, their receptors, and the parenchymal concentrations of individual bile acids that are all, at least in part, genetically determined.

Autoimmune Diseases↗