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Biomedical subjects

P Mathurin

Publications and source records attributed to P Mathurin.

At least 55 records · Page 3Linked to original sources
PubMed1996

Meta-analysis of interferon randomized trials in the treatment of viral hepatitis C: effects of dose and duration.

The aims of this study were to evaluate the benefits of higher doses or of longer duration in comparison with a standard interferon regimen (3 MU three times per week for 6 months) in chronic hepatitis C, and to assess the efficacy of interferon in acute hepatitis C. Meta-analysis made use of the Peto et al. and the Der Simonian and Laird methods, with heterogeneity and sensitivity analyses. In chronic hepatitis, a total of 17 trials versus controls and of 16 trials comparing different interferon regimens were included. Standard regimen, 3 MU three times per week for 6 months, was associated with an increase of the complete alanine transaminase (ALT) response rate and sustained (ALT) response rate by 45% (95% confidence interval: 35% to 55%; P < .001) and 21% (13% to 28%; P < .001), respectively, with the natural course being less than 2% of spontaneous responses. There was a significant dose effect (6 vs. 3 MU three times per week) upon the sustained response rate at 12 months, with a mean 17% increase (7% to 28%; P < .001), but not at 6 months. There was a significant duration effect (12 vs. 6 months) upon the sustained response rate both at the dose of 3 MU with a mean of 16% (9% to 23%; P < .001), and at the dose of 6 MU three times per week with a mean of 20% (7% to 33%; P = .003). In acute hepatitis C, 3 months of interferon treatment showed significant efficacy versus controls (4 trials), upon the complete ALT response (69% vs. 29%; P < .001), the sustained response rate during the 12 months following treatment (53% vs. 32%; P = .02), and hepatitis C virus (HCV)-RNA clearance (41% vs. 4%; P < .001). The best efficacy/risk ratio was in favor of 3 MU three times per week for at least 12 months in patients with chronic hepatitis C who had never been treated with interferon. Patients with acute hepatitis should be treated with at least 3 MU three times per week for 3 months.

Acute Disease↗
PubMed1996

Glue embolisation of a ruptured pancreaticoduodenal artery aneurysm.

Embolisation of a mycotic aneurysm of the anterior pancreaticoduodenal arcade was performed in an emergency situation using a microcatheter and tissue adhesive, after unsuccessful surgical therapy. The polymerising agent occluded the outflow vessel, the aneurysm and the feeding artery successfully.

Aneurysm, Infected↗
PubMed1996

Treatment of chronic hepatitis C by interferon for longer duration than six months.

The efficacy of various regimens using interferon-alpha (IFN-alpha) in the treatment of hepatitis C virus (HCV) infection was analyzed in a meta-analysis of 33 randomized clinical trials (RCTs). The results of the meta-analysis showed increased complete and sustained ALT response rates in patients receiving IFN 3 MU three times a week for six months compared with patients receiving placebo or no treatment. The dose effect (6 MU three times a week versus 3 MU three times a week) on complete ALT response rate at the end of treatment was significant, with a mean 10% improvement at both six and 12 months. There also was a significant dose effect on sustained response for 12 months treatment, with a mean 17% improvement. There was a significant treatment duration effect on sustained response rate at 3 MU three times a week and 6 MU three times a week, with a mean improvement of 16% (> or = 12 months vs six months) with 3 MU three times a week. Due to adverse events, we conclude that the best efficacy-risk ratio favors IFN treatment with 3 MU three times a week for at least 12 months. The results of our RCT comparing three IFN regimens showed that patients receiving 3 MU three times a week for up to 18 months exhibited significant improvements in histological activity score, normalization of serum ALT concentrations, and sustained response compared with patients receiving a lower dose or shorter duration of treatment with IFN. Together, these results support the conduct of another RCT to evaluate the hypothesis that long-term, continuous IFN treatment may significantly reduce the incidence of cirrhosis in patients with HCV infection.

Chronic Disease↗
PubMed1996

Hepatorenal syndrome. Long-term treatment with terlipressin as a bridge to liver transplantation.

In patients with hepatorenal syndrome (HRS), 4-hr administration of a vasopressin analog has recently been shown to benefit renal blood flow and renal function. However, long-term effects and tolerance of this treatment have not been reported. We report a case of HRS that was controlled by the vasopressin analog, terlipressin. Because HRS repeatedly relapsed when treatment was discontinued, terlipressin, 2 mg/day was administered for 67 days, until liver transplantation could be performed in a patient with normal renal function. Except for limited cutaneous necrosis at an injection point, prolonged treatment with this vasopressin analog was well tolerated.

Adult↗
PubMed1996

Survival and prognostic factors in patients with severe alcoholic hepatitis treated with prednisolone.

BACKGROUND & AIMS: Corticosteroids have been shown to significantly decrease short-term mortality in patients with severe alcoholic hepatitis. However, independent factors associated with a favorable outcome and long-term survival are unknown. The aim of this study was to examine prognostic factors and long-term survival in patients with biopsy-proven severe alcoholic hepatitis. METHODS: Of 183 patients studied, 61 had been randomized in a previous trial; 32 of them were treated with prednisolone (group I) and 29 were not treated (group II); 61 were treated from the end of this randomized trial (group III); and 61 were simulated (group IV). RESULTS: At 1 year, survival in group I (69%; confidence interval [CI], 57%-81%) and group III (71%; CI, 55%-87%) was better than in the nontreated groups (group II, 41%; CI, 23%-59%; P = 0.01) (group IV, 50%; CI, 37%-63%; P = 0.05). At 2 years, survival was not significantly different. Treated patients with marked liver polymorphonuclear infiltrate had better 1-year survival (76%; CI, 64%-88%) than the others (53%; CI, 35%-71%; P = 0.05). Treated patients with polymorphonuclear counts of > 5500/mm3 had better 1-year survival (77%; CI, 65%-89%) than the others (40%; CI, 14%-66%; P = 0.003). In the 93 treated patients, liver polymorphonuclear infiltrate (P < 0.03) and polymorphonuclear count (P < 0.001) were independently correlated with 1-year survival. CONCLUSIONS: Prednisolone reduced mortality by at least 1 year. Liver polymorphonuclear infiltrate and polymorphonuclear count were independent prognostic factors.

Female↗
PubMed1996

Binding of apolipoprotein A-I and acetaldehyde-modified apolipoprotein A-I to liver extracellular matrix.

Apolipoprotein A-I (Apo A-I), a protein produced mainly by hepatocytes, is decreased in the sera of alcoholic patients with liver fibrosis and cirrhosis. To explain this decrease, we investigated possible interactions between liver extracellular matrix (ECM) and Apo A-I. Using a solid-phase binding assay, we evaluated the binding of Apo A-I to the different liver matrix components. Apo A-I bound significantly to fibronectin (FN) (optical density [OD] = 1.11 +/- .26, P = .01) and collagen (C) I (OD = 0.91 +/- 0.22, P = .02) in comparison with bovine serum albumin (BSA) (OD = 0.26 +/- 0.16). Binding of Apo A-I to fibronectin was concentration dependent and saturable. Apo A-I bound also to ECM in vivo because Apo A-I was detected by immunofluorescence on fibrous septa in liver biopsy specimens of alcoholic patients. Because a negative correlation between Apo A-I and liver fibrosis is amplified in alcoholic patients, we investigated whether the in vitro formation of Apo A-I/acetaldehyde complex (adducts) increased the binding of Apo A-I to the ECM. We showed that the amount of Apo A-I that bound to FN was significantly higher with acetaldehyde-modified Apo A-I (OD = 2.18 +/- 0.19, P = .01) than with native Apo A-I. This increase was probably related to the formation and binding of Apo A-I dimers, because immunoblot of in vitro acetaldehyde-modified Apo A-I showed the formation of dimeric Apo A-I. In conclusion, FN binds both native and acetaldehyde-modified Apo A-I. Because FN is deposited early and in excess during liver fibrosis, a storage mechanism of Apo A-I on newly deposited fibronectin would explain, in part, the decrease observed in alcoholic patients with liver fibrosis.

Acetaldehyde↗
PubMed1996

Marked increase in serum CA 19-9 level in patients with alcoholic cirrhosis: report of four cases.

We report four cases of marked increase in serum carbohydrate antigen (CA 19-9) levels in patients with severe alcoholic cirrhosis without any evidence of gastric or pancreatic carcinoma. Brief reports were obtained from two hepatology units of four cirrhotic patients, three of them with alcoholic hepatitis. In the four cases, improvement of liver function and disappearance of jaundice were associated with a decrease to normal serum CA 19-9 levels. These observations show that a marked increase in serum CA 19-9 level in patients with severe hepatic dysfunction is not diagnostic of pancreatic or gastric carcinoma.

Alcoholism↗
PubMed1996

Histological features predictive of liver fibrosis in chronic hepatitis C infection.

AIMS: To assess which pathological features are associated with a sensitive marker of liver fibrogenesis and thus of the potential development of fibrosis in hepatitis C. METHODS: The degree of liver fibrogenesis was evaluated by quantification of type I collagen mRNA and transforming growth factor (TGF) beta 1 mRNA (a major profibrogenic cytokine) in liver biopsy specimens from 28 patients with chronic hepatitis C and five controls, using a quantitative reverse transcription polymerase chain reaction (RT-PCR) assay. Results of mRNA quantification were correlated with histological lesions scored semiquantitatively in the same specimens. RESULTS: Type I collagen mRNA was more strongly expressed in patients than in controls and correlated with the degree of fibrosis, but not with any of the necro-inflammatory lesions (portal inflammation, piecemeal necrosis, and lobular necrosis). TGF beta 1 mRNA concentration was higher in patients than in controls and correlated with histological grade of activity and lobular necrosis. This result was confirmed by in situ hybridisation experiments which showed that TGF beta 1 mRNA was mainly expressed in areas of focal lobular necrosis in chronic hepatitis C. CONCLUSION: This study shows that fibrosis, rather than necro-inflammatory lesions or activity scores, is associated with fibrogenesis and thus with potential aggravation of the fibrous deposit in chronic hepatitis C. Lobular necrosis is an important predictor of prognosis in chronic hepatitis C, as shown by its strong association with TGF beta 1 mRNA expression.

Adult↗
PubMed1996

Role of liver extracellular matrix in transcriptional and post-transcriptional regulation of apolipoprotein A-I by hepatocytes.

Apolipoprotein A-I, a protein produced mainly by hepatocytes, is of major importance in prevention of atherosclerosis. Its serum level varies according to the degree of liver fibrosis and the mechanism of this regulation is unknown. The aim of this study was to investigate the role of extracellular matrix in the regulation of apolipoprotein A-I by the liver. Primary mouse hepatocytes were cultured on different extracellular matrix components. The apolipoprotein A-I mRNA level was quantified in these different culture conditions by a sensitive quantitative RT-PCR procedure and compared according to the extracellular matrix component used as substrate. A significant decrease in the apolipoprotein A-I mRNA level was observed when cells were plated on fibronectin by comparison with cells cultured on all other components. Potential binding of apolipoprotein A-I to the different matrix components was also studied in vitro. We demonstrated that apolipoprotein A-I significantly bound to fibronectin in a concentration-dependent, saturable and specific manner. Thus, fibronectin, a major liver extracellular matrix component, can interact with apolipoprotein A-I both by downregulating its mRNA level in liver cells and by binding this molecule after its secretion in the extracellular space. Since fibronectin is the first matrix component to be produced in excess and deposited in liver fibrosis, it could be involved in the decrease in serum apolipoprotein A-I in alcoholic patients with liver fibrosis and cirrhosis.

Animals↗
PubMed1995

A comparison of three interferon alfa-2b regimens for the long-term treatment of chronic non-A, non-B hepatitis. Multicenter Study Group.

BACKGROUND: We studied the effects of long-term treatment with interferon on histologic features of the liver and serum alanine aminotransferase concentrations in patients with chronic non-A, non-B hepatitis. METHODS: Consecutive patients who met the inclusion criteria were enrolled in the study. The diagnosis of chronic non-A, non-B hepatitis was established on the basis of the liver-biopsy findings and an abnormal serum alanine aminotransferase value (greater than 1.5 times the normal value) for at least one year. All patients were treated for six months with 3 million units of interferon alfa-2b given subcutaneously three times a week and were then randomly assigned to the same treatment for an additional 12 months (group 1), a regimen of 1 million units three times a week for 12 months (group 2), or no further treatment (group 3). Patients in group 3 who had elevated serum alanine aminotransferase concentrations for three consecutive months underwent the initial regimen once again. Follow-up continued for two years after the discontinuation of treatment. Histologic improvement was defined as a decrease of at least one grade in the score for necroinflammatory activity (0, no activity; 1, mild; 2, moderate; or 3, severe) between the first liver biopsy and a biopsy performed at 18 months. RESULTS: Of the 329 patients initially treated, 303 were randomized: 103 to group 1, 101 to group 2, and 99 to group 3. Of the 286 patients tested, 252 (88.1 percent) had antibodies to hepatitis C virus. In an intention-to-treat analysis, 46 of the patients in group 1 (44.7 percent) had normal serum alanine aminotransferase values at 18 months, as compared with 27 of the patients in group 2 (26.7 percent, P = 0.008) and 30 of those in group 3 (30.3 percent, P = 0.04). Between 19 and 42 months, 23 of the patients in group 1 (22.3 percent) continued to have normal serum alanine aminotransferase values (measured every six months), as compared with 10 of the patients in group 2 (9.9 percent, P = 0.02) and 8 of those in group 3 (8.1 percent, P = 0.005). Among the 176 patients with repeated liver biopsies at 18 months, more patients in group 1 had improved histologic-activity scores (69.6 percent) than in group 2 (47.6 percent, P = 0.02) or group 3 (38.6 percent, P < 0.001). CONCLUSIONS: Among patients with chronic non-A, non-B hepatitis, a regimen of 3 million units of interferon alfa-2b given three times a week for 18 months produced better histologic findings and serum alanine aminotransferase values than regimens involving a lower dose or a shorter duration of treatment.

Alanine Transaminase↗
PubMed1995

Ischemic hepatitis due to obstructive sleep apnea.

The case of an obese patient who developed massive centrilobular liver cell necrosis, severe coagulopathy, acute renal failure, and encephalopathy is presented. Hypovolemia and heart failure were absent, but the acute liver disease was associated with severe arterial hypoxemia due to obstructive sleep apnea that was shown by the nocturnal blood oxygen desaturation, the results of the polysomnographic study, and normal baseline pulmonary function tests. In this obese patient, liver cell necrosis was caused by severe liver cell hypoxia secondary to severe arterial hypoxemia as a consequence of obstructive sleep apnea associated with a Pickwickian syndrome. This observation is consistent with the hypothesis that liver ischemia was directly related to severe arterial hypoxemia.

Female↗
PubMed1995

A multidimensional case-control study of dietary, alcohol, and tobacco habits in alcoholic men with chronic pancreatitis.

This study compared diet, type of alcoholism, and smoking in three groups of alcoholic men, with chronic pancreatitis (n = 56), with histological cirrhosis (n = 50), and without pancreatitis or cirrhosis (controls; n = 50) by a multidimensional analysis. Only patients in whom the first symptom of pancreatitis or cirrhosis was present for < 1 year before the interview were included. Patients with pancreatitis consumed more nonalcohol calories than cirrhotics (p < 0.05). The percentage of calories taken as proteins (p < 0.0003) and lipids (p < 0.0001) was higher and the percentage of calories taken as alcohol (p < 0.0003) was lower in patients with pancreatitis than in cirrhotics and control patients. There was no difference among the three groups for total calories/basal energy expenditure ratio, total nonalcohol calories/basal energy expenditure ratio, mineral and vitamin intake, or tobacco consumption. The duration of excessive alcohol consumption and the total alcohol consumption in patients with pancreatitis was similar to that of controls but lower than that of cirrhotics (p < 0.002 and p < 0.05, respectively). Three parameters were found to be independently different in the three groups by discriminant analysis: percentage of calories taken as lipids (p < 0.0001), duration of excessive alcohol consumption (p < 0.002), and percentage of calories taken as proteins (p < 0.08). These three parameters explained 24% of the variance. We conclude that the reasons alcoholic men develop chronic pancreatitis may be explained partly by dietary habits.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Prevalence of cholelithiasis according to alcoholic liver disease: a possible role of apolipoproteins AI and AII.

Moderate alcohol intakes decreases the risk of gallstones; in contrast, the prevalence of gallstones is increased in patients with alcoholic cirrhosis. The aims of this prospective study were to assess the prevalence of cholelithiasis among drinkers according to the histological severity of liver disease, and to estimate the importance of serum apolipoproteins AI and apolipoprotein AII as risk factors for gallstones. Among the 320 drinkers included, 53 patients had cholelithiasis. The prevalence increased (p < 0.0001) from 5% in patients with normal liver (1 of 22) and 6% in patients with steatosis only (3 of 47) to 13% in patients with fibrosis (7 of 54), reaching 27% among patients with biopsy-proven cirrhosis (28 of 103). Among patients with clinically obvious cirrhosis on whom biopsy was not performed mainly because of the severity of liver disease, the prevalence of cholelithiasis reached a maximum of 46% (6 of 13). Among drinkers with nonsevere liver disease, patients with cholelithiasis were older (59 +/- 9 years, mean +/- SD vs. 45 +/- 11, p = 0.003) with lower apolipoprotein AI (118 +/- 37 vs. 163 +/- 45 mg/dl; p = 0.002) and apolipoprotein AII (30 +/- 12 vs. 53 +/- 20 mg/dl; p = 0.0002) in comparison with patients without cholelithiasis. These differences persisted after considering by multiple logistic regression analysis, sex, and ideal body weight. Alcohol consumption during the last 5 years was lower in patients with cholelithiasis (83 g/day) in comparison with patients without cholelithiasis (142 g/day; p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Laparoscopic treatment of recurrence and embolization failure of varicocele].

Varicocele is a benign pathology, for which the less invasive treatment is percutaneous embolisation. Literature reports results from 70 to 85% (1,2). Laparoscopic treatment seems to be a good alternative for patients suffering from a recurrence, or patients who can not be embolised. We report our experience concerning the first 13 patients treated with laparoscopic technic. In all 13 cases it was possible to practice the technic, and patients were cured.

Adolescent↗
PubMed1994

Prednisone-interferon combination in the treatment of chronic hepatitis B: direct and indirect metanalysis.

The aim of this study was to review all published randomized clinical trials evaluating the efficacy of a combination of prednisone and interferon in treatment of chronic hepatitis B and to subject these studies to metanalysis. Two types of metanalyses were carried out: direct metanalysis, comparing the prednisone-interferon combination with interferon on its own; and indirect metanalysis, comparing the treatment efficacy of prednisone-interferon and of interferon with control results. At the end of follow-up, four assessable end points were analyzed: HBeAg, hepatitis B virus DNA, HBsAg loss and serum ALT normalization rate. The direct metanalysis included seven trials comparing prednisone-interferon with interferon treatment. No significant differences were observed between the two types of therapy, for all the criteria given. However, in patients with low ALT levels, the prednisone-interferon combination gave significantly better results than interferon alone--HBeAg loss was 48% in the former group vs. 18.4% with interferon alone (p < 0.01). Fifteen trials compared interferon with control values; all end points were significantly improved. Seven trials compared prednisone-interferon with control results and showed all end points to be significantly improved by treatment. Indirect metanalysis showed that the differences in odds ratios for prednisone-interferon/control group and interferon/control group studies were negative for all assessable end points. In conclusion, the use of corticosteroids did not produce any significant increase in the efficacy of interferon treatment in adults with chronic hepatitis B and high initial ALT levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1994

[Hyperthyroidism: a possible factor of cholestasis associated with hyperemesis gravidarum of prolonged evolution].

We report two cases of hyperemesis gravidarum with hyperthyroidism and jaundice. The cessation of vomiting associated with supportive care was followed by complete recovery in 5 weeks. Hyperthyroidism occurs in 60% of hyperemesis gravidarum, but jaundice is uncommon. The association of jaundice and hyperthyroidism suggests that hyperthyroidism is a possible factor of cholestasis in patients with hyperemesis gravidarum.

Adult↗