We report the cases of two adult patients in whom fulminant hepatitis developed after 17 and 103 ... more We report the cases of two adult patients in whom fulminant hepatitis developed after 17 and 103 days of ketoconazole administration. Histologic administration showed massive, predominantly centrilobular necrosis. Clinical manifestations of hypersensitivity and eosinophilia were absent in both patients, which suggests that ketoconazole hepatotoxicity is not mediated through an immunoallergic mechanism.
The protein C system is essential in limiting the activation of coagulation in vivo. We report th... more The protein C system is essential in limiting the activation of coagulation in vivo. We report the case of a 45 year old man with portal vein thrombosis complicated by ruptured oesophageal varices. Low concentration of plasma protein C was found in the patient and subsequently in one brother with a history of venous thromboembolism, and also in one son
We report the cases of two renal transplant recipients suffering from idopathic portal hypertensi... more We report the cases of two renal transplant recipients suffering from idopathic portal hypertension, a condition characterised by increased portal venous pressure in the absence of both histological lesion of the liver and obstruction of the portal vein. In these two patients, perisnusoidal fibrosis, invisible by light microscopy, was demonstrated by electron microscopy; it is suggested that partial obstruction of
Peliosis hepatis, an uncommon liver lesion characterised by blood-filled cavities bordered by hep... more Peliosis hepatis, an uncommon liver lesion characterised by blood-filled cavities bordered by hepatocytic plates, was found in 12 patients three to 17 months after renal transplantation. Hepatomegaly and portal hypertension were present in five of the six patients with major peliosis hepatis, and were absent in the other six with minor hepatic lesions. Alterations of centrilobular vein walls in some
Controlled trials have yielded inconsistent results with regard to the efficacy of corticosteroid... more Controlled trials have yielded inconsistent results with regard to the efficacy of corticosteroids in the treatment of alcoholic hepatitis. Three meta-analyses suggest that they may be effective in patients with encephalopathy who have severe liver disease. We conducted a randomized, double-blind trial comparing 28 days of prednisolone treatment (40 mg per day) with placebo in 61 patients with biopsy-proved alcoholic hepatitis and either spontaneous hepatic encephalopathy (n = 19) or a discriminant-function value higher than 32. The discriminant function used was as follows: 4.6 (prothrombin time-control time [in seconds]) + serum bilirubin (in micromoles per liter)/17. Fifty-seven of the patients had evidence of cirrhosis on biopsy. The primary end point was death within two months. One patient was lost to follow-up after 56 days. Treatment was discontinued in two patients because of drug toxicity. By the 66th day after randomization, 16 of 29 placebo recipients had died (mean [+/- SE] survival, 45 +/- 8 percent), as compared with 4 of 32 prednisolone recipients (survival, 88 +/- 5 percent) (log-rank test, 10.9; P = 0.001). The survival advantage for prednisolone persisted after stratification according to center and the presence of encephalopathy, and after adjustment for prognostic factors in a proportional-hazards model. Treatment with prednisolone improves the short-term survival of patients with severe biopsy-proved alcoholic hepatitis.
This study compared diet, type of alcoholism, and smoking in three groups of alcoholic men, with ... more 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)
This controlled trial was designed to evaluate the prophylactic effect of nadolol on gastrointest... more This controlled trial was designed to evaluate the prophylactic effect of nadolol on gastrointestinal bleeding in cirrhotic patients with large oesophageal varices who had never bled. Nadolol or placebo was given randomly to two groups of 53 patients. The percentage of patients free of gastrointestinal bleeding 1 year after inclusion in the study was 83 +/- 6% (mean +/- S.D.) in the nadolol group and 80 +/- 6% in the placebo group. In the nadolol and placebo groups, 40 and 47 patients, respectively, were compliant, i.e., took nadolol or placebo continuously. The percentage of patients who were free of bleeding 1 year after inclusion was 97 +/- 3% in the subgroup of compliant nadolol patients. This percentage was significantly higher than that of patients who were free of bleeding in the placebo group (P less than 0.03) as well as in the subgroup of compliant placebo patients (77 +/- 6%; P less than 0.02). We concluded that, although there was no overall significant effect of nadolol on the risk of bleeding in cirrhotic patients in good condition with large oesophageal varices, this study suggests that nadolol reduced the risk of bleeding in compliant patients.
Three patients suffered from fulminant hepatitis within 23, 59 and 22 weeks after having ingested... more Three patients suffered from fulminant hepatitis within 23, 59 and 22 weeks after having ingested a total dose of 16, 26 and 15 g, respectively, of amodiaquine for the prophylaxis of malaria. Amodiaquine administration was continued for 44, 21 and 25 days after the onset of jaundice, respectively. One patient underwent emergency orthotopic liver transplantation and survived. The other two died. Fulminant hepatitis threatens patients in whom amodiaquine administration is protracted for several months and not interrupted when jaundice occurs.
We report a case of chronic active hepatitis caused by benzarone, a benzofuran derivative used in... more We report a case of chronic active hepatitis caused by benzarone, a benzofuran derivative used in Europe for the treatment of peripheral venous disorders. Jaundice and serum alanine aminotransferase activity increased while drug administration was continued, but promptly decreased when it was eventually interrupted. Liver lesions were those of chronic active hepatitis. Anti-smooth muscle antibodies were present at a titer of 1:500 and disappeared 8 months after withdrawal of benzarone.
To improve blood pressure control among hypertensive ( > 140/90 mmHg) excessive alcohol dr... more To improve blood pressure control among hypertensive ( > 140/90 mmHg) excessive alcohol drinkers. Fourteen worksite physicians were randomised onto an intervention group and a control group. The intervention was based on training the worksite physicians and follow up of those hypertensive subjects defined as excessive drinkers. Follow up was based on self monitoring of alcohol consumption by the subject, in view of the results of their gamma glutamyl transferase (GGT) activity determination. Fourteen workplaces in France - mainly in the industrial sector. Altogether 15 301 subjects were screened by the 14 physicians: 129 of these were included in the study. This was the difference between the initial systolic blood pressure (SBP) and the SBP one year later (delta BP). Secondary criteria were the difference between the initial and final diastolic blood pressure (delta DBP) and delta BP at two years; antihypertensive treatment; state alcohol consumption (delta AC); delta GGT; and body mass index (delta BMI). The decrease in SBP levels was significantly larger in the intervention group than in the control group: at one year, delta SBP values were -11.9 (15.6) mmHg and -4.6 (13.8) respectively (p < 0.05). This benefit was still observed after two years of follow up (-13.8 (17.4) mmHg v -7.5 (14.2) mmHg (p < 0.05)). No difference was observed in DBP. The percentage of treated subjects did not differ between groups. At one year, delta AC was larger in the intervention group (-2.8 (5.2) U/d) than in the control group (-1.6 (3.4) (p < 0.1)). delta GGT and delta BMI did not differ between the two groups. A weak positive correlation was observed between delta AC and delta SBP (r = 0.16). An intervention aimed at the hypertensive excessive drinkers in a working population was found to be effective in reducing SBP on a long term basis (two years). The mechanisms of reduction in alcohol consumption and improved drug compliance cannot be ascertained in this pragmatic study. From a public health point of view, reducing the excess cardiovascular risk among a "hard to reach" population seems feasible with a strategy specifically designed for this high risk group.
We report the case of a young woman in whom investigations for acute Budd-Chiari syndrome disclos... more We report the case of a young woman in whom investigations for acute Budd-Chiari syndrome disclosed an hormone-secreting but clinically nonfunctioning adrenocortical carcinoma. We supply a very brief review of the literature.
In a 25-month period, 100 cirrhotic patients, in our intensive care unit (ICU) needed endotrachea... more In a 25-month period, 100 cirrhotic patients, in our intensive care unit (ICU) needed endotracheal intubation and mechanical ventilation. The overall mortality rate was 89%; the mortality rate was 100% among patients with septic shock and/or superimposed acute hepatitis and/or severe cirrhosis defined with clinical signs: jaundice and/or ascites and/or spontaneous hepatic encephalopathy and/or severe malnutrition. With these prognostic indices, using Bayes theorem, the probability of fatal evolution ranges from 95%-100% (alpha = 5%). These results allow a group of patients with high cost and poor prognosis to be defined.
In 27 patients who had bled from esophagogastric varices, large-sized and/or actively bleeding ga... more In 27 patients who had bled from esophagogastric varices, large-sized and/or actively bleeding gastric varices were endoscopically obturated with the tissue adhesive butyl cyanoacrylate. Active bleeding was stopped in six patients. Rebleeding occurred in 10 patients; in four patients, rebleeding was due to ruptured gastric varices, occurred early and was successfully treated by reinjection of gastric varices; in one patient, rebleeding was attributed to ulceration on an injected gastric varix. Eight patients died: two of rebleeding (from esophageal varices or undetermined source), four of sepsis and/or liver failure and two at home of undetermined cause. No specific complication due to injection of gastric varices was observed. The results obtained in this series of patients with gastric varices obturated by injection of butyl cyanoacrylate are much more satisfactory than those obtained in previously published series of patients with gastric varices treated by injection of sclerosants.
We report the cases of two adult patients in whom fulminant hepatitis developed after 17 and 103 ... more We report the cases of two adult patients in whom fulminant hepatitis developed after 17 and 103 days of ketoconazole administration. Histologic administration showed massive, predominantly centrilobular necrosis. Clinical manifestations of hypersensitivity and eosinophilia were absent in both patients, which suggests that ketoconazole hepatotoxicity is not mediated through an immunoallergic mechanism.
The protein C system is essential in limiting the activation of coagulation in vivo. We report th... more The protein C system is essential in limiting the activation of coagulation in vivo. We report the case of a 45 year old man with portal vein thrombosis complicated by ruptured oesophageal varices. Low concentration of plasma protein C was found in the patient and subsequently in one brother with a history of venous thromboembolism, and also in one son
We report the cases of two renal transplant recipients suffering from idopathic portal hypertensi... more We report the cases of two renal transplant recipients suffering from idopathic portal hypertension, a condition characterised by increased portal venous pressure in the absence of both histological lesion of the liver and obstruction of the portal vein. In these two patients, perisnusoidal fibrosis, invisible by light microscopy, was demonstrated by electron microscopy; it is suggested that partial obstruction of
Peliosis hepatis, an uncommon liver lesion characterised by blood-filled cavities bordered by hep... more Peliosis hepatis, an uncommon liver lesion characterised by blood-filled cavities bordered by hepatocytic plates, was found in 12 patients three to 17 months after renal transplantation. Hepatomegaly and portal hypertension were present in five of the six patients with major peliosis hepatis, and were absent in the other six with minor hepatic lesions. Alterations of centrilobular vein walls in some
Controlled trials have yielded inconsistent results with regard to the efficacy of corticosteroid... more Controlled trials have yielded inconsistent results with regard to the efficacy of corticosteroids in the treatment of alcoholic hepatitis. Three meta-analyses suggest that they may be effective in patients with encephalopathy who have severe liver disease. We conducted a randomized, double-blind trial comparing 28 days of prednisolone treatment (40 mg per day) with placebo in 61 patients with biopsy-proved alcoholic hepatitis and either spontaneous hepatic encephalopathy (n = 19) or a discriminant-function value higher than 32. The discriminant function used was as follows: 4.6 (prothrombin time-control time [in seconds]) + serum bilirubin (in micromoles per liter)/17. Fifty-seven of the patients had evidence of cirrhosis on biopsy. The primary end point was death within two months. One patient was lost to follow-up after 56 days. Treatment was discontinued in two patients because of drug toxicity. By the 66th day after randomization, 16 of 29 placebo recipients had died (mean [+/- SE] survival, 45 +/- 8 percent), as compared with 4 of 32 prednisolone recipients (survival, 88 +/- 5 percent) (log-rank test, 10.9; P = 0.001). The survival advantage for prednisolone persisted after stratification according to center and the presence of encephalopathy, and after adjustment for prognostic factors in a proportional-hazards model. Treatment with prednisolone improves the short-term survival of patients with severe biopsy-proved alcoholic hepatitis.
This study compared diet, type of alcoholism, and smoking in three groups of alcoholic men, with ... more 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)
This controlled trial was designed to evaluate the prophylactic effect of nadolol on gastrointest... more This controlled trial was designed to evaluate the prophylactic effect of nadolol on gastrointestinal bleeding in cirrhotic patients with large oesophageal varices who had never bled. Nadolol or placebo was given randomly to two groups of 53 patients. The percentage of patients free of gastrointestinal bleeding 1 year after inclusion in the study was 83 +/- 6% (mean +/- S.D.) in the nadolol group and 80 +/- 6% in the placebo group. In the nadolol and placebo groups, 40 and 47 patients, respectively, were compliant, i.e., took nadolol or placebo continuously. The percentage of patients who were free of bleeding 1 year after inclusion was 97 +/- 3% in the subgroup of compliant nadolol patients. This percentage was significantly higher than that of patients who were free of bleeding in the placebo group (P less than 0.03) as well as in the subgroup of compliant placebo patients (77 +/- 6%; P less than 0.02). We concluded that, although there was no overall significant effect of nadolol on the risk of bleeding in cirrhotic patients in good condition with large oesophageal varices, this study suggests that nadolol reduced the risk of bleeding in compliant patients.
Three patients suffered from fulminant hepatitis within 23, 59 and 22 weeks after having ingested... more Three patients suffered from fulminant hepatitis within 23, 59 and 22 weeks after having ingested a total dose of 16, 26 and 15 g, respectively, of amodiaquine for the prophylaxis of malaria. Amodiaquine administration was continued for 44, 21 and 25 days after the onset of jaundice, respectively. One patient underwent emergency orthotopic liver transplantation and survived. The other two died. Fulminant hepatitis threatens patients in whom amodiaquine administration is protracted for several months and not interrupted when jaundice occurs.
We report a case of chronic active hepatitis caused by benzarone, a benzofuran derivative used in... more We report a case of chronic active hepatitis caused by benzarone, a benzofuran derivative used in Europe for the treatment of peripheral venous disorders. Jaundice and serum alanine aminotransferase activity increased while drug administration was continued, but promptly decreased when it was eventually interrupted. Liver lesions were those of chronic active hepatitis. Anti-smooth muscle antibodies were present at a titer of 1:500 and disappeared 8 months after withdrawal of benzarone.
To improve blood pressure control among hypertensive ( > 140/90 mmHg) excessive alcohol dr... more To improve blood pressure control among hypertensive ( > 140/90 mmHg) excessive alcohol drinkers. Fourteen worksite physicians were randomised onto an intervention group and a control group. The intervention was based on training the worksite physicians and follow up of those hypertensive subjects defined as excessive drinkers. Follow up was based on self monitoring of alcohol consumption by the subject, in view of the results of their gamma glutamyl transferase (GGT) activity determination. Fourteen workplaces in France - mainly in the industrial sector. Altogether 15 301 subjects were screened by the 14 physicians: 129 of these were included in the study. This was the difference between the initial systolic blood pressure (SBP) and the SBP one year later (delta BP). Secondary criteria were the difference between the initial and final diastolic blood pressure (delta DBP) and delta BP at two years; antihypertensive treatment; state alcohol consumption (delta AC); delta GGT; and body mass index (delta BMI). The decrease in SBP levels was significantly larger in the intervention group than in the control group: at one year, delta SBP values were -11.9 (15.6) mmHg and -4.6 (13.8) respectively (p < 0.05). This benefit was still observed after two years of follow up (-13.8 (17.4) mmHg v -7.5 (14.2) mmHg (p < 0.05)). No difference was observed in DBP. The percentage of treated subjects did not differ between groups. At one year, delta AC was larger in the intervention group (-2.8 (5.2) U/d) than in the control group (-1.6 (3.4) (p < 0.1)). delta GGT and delta BMI did not differ between the two groups. A weak positive correlation was observed between delta AC and delta SBP (r = 0.16). An intervention aimed at the hypertensive excessive drinkers in a working population was found to be effective in reducing SBP on a long term basis (two years). The mechanisms of reduction in alcohol consumption and improved drug compliance cannot be ascertained in this pragmatic study. From a public health point of view, reducing the excess cardiovascular risk among a "hard to reach" population seems feasible with a strategy specifically designed for this high risk group.
We report the case of a young woman in whom investigations for acute Budd-Chiari syndrome disclos... more We report the case of a young woman in whom investigations for acute Budd-Chiari syndrome disclosed an hormone-secreting but clinically nonfunctioning adrenocortical carcinoma. We supply a very brief review of the literature.
In a 25-month period, 100 cirrhotic patients, in our intensive care unit (ICU) needed endotrachea... more In a 25-month period, 100 cirrhotic patients, in our intensive care unit (ICU) needed endotracheal intubation and mechanical ventilation. The overall mortality rate was 89%; the mortality rate was 100% among patients with septic shock and/or superimposed acute hepatitis and/or severe cirrhosis defined with clinical signs: jaundice and/or ascites and/or spontaneous hepatic encephalopathy and/or severe malnutrition. With these prognostic indices, using Bayes theorem, the probability of fatal evolution ranges from 95%-100% (alpha = 5%). These results allow a group of patients with high cost and poor prognosis to be defined.
In 27 patients who had bled from esophagogastric varices, large-sized and/or actively bleeding ga... more In 27 patients who had bled from esophagogastric varices, large-sized and/or actively bleeding gastric varices were endoscopically obturated with the tissue adhesive butyl cyanoacrylate. Active bleeding was stopped in six patients. Rebleeding occurred in 10 patients; in four patients, rebleeding was due to ruptured gastric varices, occurred early and was successfully treated by reinjection of gastric varices; in one patient, rebleeding was attributed to ulceration on an injected gastric varix. Eight patients died: two of rebleeding (from esophageal varices or undetermined source), four of sepsis and/or liver failure and two at home of undetermined cause. No specific complication due to injection of gastric varices was observed. The results obtained in this series of patients with gastric varices obturated by injection of butyl cyanoacrylate are much more satisfactory than those obtained in previously published series of patients with gastric varices treated by injection of sclerosants.
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