Efficacy and safety of combination therapy with interferon-alpha2b and ribavirin for chronic hepatitis C in HIV-infected patients.

OBJECTIVES: To evaluate the efficacy and safety of a combination therapy of interferon-alpha2b (IFN) and ribavirin for the treatment of chronic hepatitis C in HIV-seropositive patients. DESIGN: Open prospective trial. METHODS: Twenty patients co-infected with hepatitis C virus (HCV) and HIV, with a mean CD4 cell count of 350 +/- 153 x 10(6)/l were treated with IFN (3 MU three times per week) in combination with ribavirin (500 mg or 600 mg twice a day) for 6 months. Tolerance and efficacy were monitored at weeks 12 (month 3) and 24 (month 6). The primary endpoint was a complete virological response, as defined by the lack of detectable HCV RNA in serum. RESULTS: Baseline values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were 121 +/- 72 IU/l and 75 +/- 67 IU/l, respectively. The total Knodell score was 10.4 +/- 2.4, with nine patients showing histological evidence of active cirrhosis (45%). All patients exhibited circulating HCV RNA. The treatment was well tolerated, with no impact on the course of HIV infection. After 6 months of combination therapy with IFN and ribavirin, 10 patients (50%) exhibited no further detectable HCV RNA viraemia, seven of whom achieved undetectable viraemia at month 3. Levels of ALT and AST decreased after 6 months of treatment from a mean of 121 +/- 72 to 51 +/- 40 IU/l and from a mean of 129 +/- 58 IU/l to 68 +/- 61 IU/l, respectively (P < 0.0002 and P < 0.0001). CONCLUSION: Our results indicate that combination therapy with IFN and ribavirin is effective in 50% of cases in clearing serum HCV RNA and may thus provide effective means of therapy in HIV-HCV-coinfected patients as initial treatment or in patients who have previously failed IFN monotherapy.

Single-dose pharmacokinetics of amprenavir, a human immunodeficiency virus type 1 protease inhibitor, in subjects with normal or impaired hepatic function.

Amprenavir (141W94) is extensively metabolized by P450 cytochromes, specifically, CYP3A4. Because hepatic insufficiency reduces P450-mediated metabolism, the concentrations in plasma of drugs metabolized through this pathway are often increased in subjects with liver disease. Following administration of a single, oral dose of 600 mg of amprenavir, pharmacokinetic parameters were determined for 10 subjects with severe cirrhosis, 10 subjects with moderate cirrhosis, and 10 healthy volunteers. Model-independent methods for determining the area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC(0-infinity)) showed an increase in amprenavir AUC(0-infinity) of 2.5-fold in the group with moderate cirrhosis and 4.5-fold in the group with severe cirrhosis compared with that in the control group of healthy volunteers (P < 0.05). AUC(0-infinity) was linearly related to the severity of liver disease, as assessed by the Child-Pugh score. Of the laboratory data used to calculate the Child-Pugh score, only the mean total bilirubin concentration showed a significant relationship with AUC(0-infinity). The relationship between the total bilirubin concentration and the AUC(0-infinity) of amprenavir was well characterized by a simple E(max) model, suggesting that the total bilirubin concentration may be a useful parameter for predicting the amprenavir AUC in subjects with hepatic insufficiency. Finally, the sera of cirrhotic subjects showed significant decreases in the levels of alpha(1)-acid glycoprotein, the primary plasma binding protein for amprenavir. On the basis of the results of this study, for an exposure equivalent to a clinical dose of 1,200 mg twice daily in subjects without cirrhosis, subjects with Child-Pugh scores of 5 to 8 should receive a twice-daily 450-mg dose of amprenavir, and subjects with Child-Pugh scores of 9 to 15 should receive a twice-daily 300-mg dose of amprenavir.

Concurrent emergence of hepatitis B e antigen-negative hepatitis B virus variant and autoimmune hepatitis cured by adenine arabinoside monophosphate.

We report the case of a hepatitis B virus chronic carrier in whom features of severe autoimmune hepatitis developed concurrently with the emergence of a hepatitis Be antigen-negative variant. Corticosteroid administration failed to normalize serum transaminase activity and resulted in increased viral multiplication. Adenine arabinoside monophosphate treatment allowed simultaneous inhibition of hepatitis B virus multiplication and remission of autoimmune features. This observation indicates that hepatitis Be antigen-negative variants can induce autoimmune hepatitis and adds support to the hypothesis that autoimmune hepatitis can be triggered by hepatotropic viruses. Patients with both features should first be treated with adenine arabinoside monophosphate. This observation indicates that hepatitis Be antigen-negative variants can induce autoimmune hepatitis and adds support to the hypothesis that autoimmune hepatitis can be triggered by hepatotropic viruses. Patients with both features should first be treated with adenine arabinoside monophosphate.

[Hemorrhagic colitis and hemolytic uremic syndrome caused by Escherichia coli O157:H7]. / Colite hémorragique et syndrome hémolytique et urémique dus à Escherichia coli O157:H7.

We report the case of an Escherichia coli O157:H7 infection in a patient with hemorrhagic colitis. Initial diagnosis was ischemic colitis because of the age of the patient and clinical presentation. After one week, a hemolytic-uremic syndrome occurred and serologic antibodies to the lipopolysaccharide O157 of Escherichia coli O157:H7 were positive, leading to the diagnosis of hemorrhagic colitis caused by this bacteria. Escherichia coli O157:H7 colonic infection is not well known, specially in France where only two cases has been reported in adults. This bacteria and the toxin produced (Shiga-like toxin) should be searched in cultures of stools and colonic biopsies in case of bloody diarrhea, in particular when a hemolytic-uremic syndrome is associated. As clinical, pathological and endoscopic findings in Escherichia coli O157:H7-associated colitis may be similar to the ischemic colitis pattern, differential diagnosis may be difficult.

Endoscopic ultrasonography immediately prior to laparoscopic cholecystectomy: a prospective evaluation.

BACKGROUND AND STUDY AIMS: In patients who are highly likely to have common bile duct (CBD) stones, it seems necessary to image the biliary tract before laparoscopic cholecystectomy, and endoscopic ultrasonography (EUS) is one way of doing this. The aim of this study was to compare immediate preoperative EUS to intraoperative cholangiography for imaging the CBD and for the diagnosis of CBD stones, in a population with a high risk of choledocholithiasis (as assessed by clinical, biochemical, and ultrasound criteria). PATIENTS AND METHODS: From January 1993 to August 1995, EUS was carried out in the operating room in 50 patients (11 men, 39 women; mean age 57 years) before laparoscopic cholecystectomy for symptomatic choledocholithiasis. A diagnosis of CBD stones by EUS or intraoperative cholangiography was always confirmed by instrumental exploration. An absence of stones in the CBD was established by a negative EUS and intraoperative cholangiography, as well as normal findings at clinical monitoring three months after laparoscopic cholecystectomy. RESULTS: EUS visualized the CBD in 100% of cases. Intraoperative cholangiography was successful in 94% of cases (n = 47 of 50), and after conversion to open laparotomy in eight patients. CBD stones were found in 12 patients (24%). The sensitivity, specificity, and positive and negative predictive values for EUS were 100%, 97%, 92%, and 100%, respectively. CONCLUSIONS: Immediate preoperative EUS may make it possible to select the best form of treatment in patients with CBD stones, avoiding inappropriate laparoscopic instrumental CBD exploration.

Dieulafoy's ulcer: combined endoscopic and laparoscopic treatment.

Dieulafoy's disease is a rare, but dangerous cause of upper gastrointestinal hemorrhage. We report here the case of a patient in whom the failure of endoscopic therapy necessitated a surgical approach by combining endoscopy and laparoscopy. The intraoperative endoscopic examination located the site of the lesion precisely, allowing a limited adapted wedge resection to be carried out laparoscopically.

[A new hereditary cause of portal vein thrombosis: the abnormal resistance to activated protein C by the Arg 506-->Gln mutation of the gene of factor V]. / Une nouvelle cause héréditaire de thrombose portale: la résistance anormale à la protéine C activée par mutation Arg506-->Gln du gène du facteur V.

We report 2 cases of portal vein thrombosis associated with a single point mutation in the factor V gene that replaces arginine in residue 506 with glutamine. This mutation induces abnormal resistance to anticoagulant activity of activated protein C and increases the risk of deep vein thrombosis. Both patients had a personal and familial history of deep vein thrombosis. Intraabdominal neoplasia or infection, myeloproliferative disorder, antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria and coagulation inhibitor deficiency (antithrombin, proteins C and S) were excluded by exhaustive investigation. However, an abnormal resistance to activated protein C was found, and DNA analysis showed the factor V Arg506 to Gln mutation in both cases. Anticoagulant treatment was begun. A study of family history made in one case, showed the same genetic disease in one of the relatives. Resistance to activated protein C with factor V gene mutation should be investigated in patients with portal vein thrombosis. A study of family history, and anticoagulant treatment are justified for symptomatic patients.

["Dysphagia lusoria". Physiopathological discussion apropos of a clinical case]. / "Dysphagia lusoria". Discussion physio-pathologique à propos d'un cas clinique.

We report the observation of a patient suffering from dysphagia lusoria, a dysphagia caused by an anomalous form of the right subclavian artery. The diagnosis was confirmed by aortic arch angiography and cine-oesophagogram. Oesophageal manometric study revealed segmental hypoperistalsis and anti-peristalsis. Dysphagia disappeared with cisapride. This observation suggests that dysphagia lusoria is caused by oesophageal motility disorders and not by vascular compression.

Clinical pharmacokinetics of lansoprazole.

Lansoprazole, a benzimidazole derivative with antisecretory and antiulcer activities, inhibits the acid pump activity at the final stage of the enzyme process and therefore reduces the acid secretion of parietal cells. Lansoprazole is converted to active metabolites in the acid environment of these cells. It is rapidly absorbed from a gastric acid-resistant formulation and is approximately 97% bound in human plasma. Single dose pharmacokinetics of lansoprazole appear to be linear over the range from 15 to 60mg. Food and time of dose influence absorption after single doses, but do not modify the antisecretory effect of multiple doses. Lansoprazole is extensively metabolised following oral administration into sulphone and 5-hydroxylated metabolites by the cytochrome P450 enzymes CYP3A4 and CYP2C18. Two other metabolites have been identified in plasma: sulphide and hydroxylated sulphone. Mean plasma elimination half-life (t1/2) is between 1.3 and 2.1 hours in healthy volunteers. 15 to 23% of the total dose is found in urine as free and conjugated hydroxylated metabolites, while unchanged lansoprazole is not detected. The pharmacokinetic profile of the drug is not modified by multiple administration. In healthy elderly volunteers, area under the plasma concentration-time curve (AUC) and t1/2 are significantly greater after single administration occurs to the same extent as in young volunteers. Renal failure has no influence on the pharmacokinetics of lansoprazole, but severe hepatic failure causes a significant decrease in clearance and an increase in the AUC and t1/2 of lansoprazole. This is accompanied by modifications in the AUC of metabolites, but severe hepatic failure has minimal effect on accumulation of the drug after multiple administration. The pharmacokinetics of lansoprazole in patients with acid-related disorders do not differ from those in healthy volunteers. Studies of interactions of lansoprazole with warfarin, prednisone, theophylline, phenazone (antipyrine), diazepam, phenytoin and oral contraceptives suggest minimal risk of any clinically significant interaction.

[Prospective comparison of ultrasound endoscopy and computed tomography in the assessment of locoregional invasiveness of malignant ampullar and pancreatic tumors verified surgically]. / Comparaison prospective de l'échoendoscopie et de la tomodensitométrie dans le bilan d'extension loco-régionale de tumeurs malignes ampullaires et pancréatiques vérifiées chirurgicalement.

OBJECTIVE: To compare, in a prospective study, results of endoscopic ultrasonography and computed tomography in staging of pancreatic and ampullary carcinoma tumours, assessed surgically. METHOD: From January 1990 to May 1993, 37 patients with pancreatic tumours had per-operative endoscopic ultrasonography and computed tomography. All patients underwent surgery and surgical and histological staging were performed. RESULTS: All the tumours were visualized by endoscopic ultrasonography, and 92% were correctly localized; 63% of the tumours were visualized by computed tomography. In lymph node involvement diagnosis (23 patients), endoscopic ultrasonography. In major portal vessel involvement diagnosis (14 patients), endoscopic ultrasonography sensitivity and specificity were respectively 71.4% and 95.65%, and 21.4% and 100% for computed tomography. In a vessel-by-vessel analysis, endoscopic ultrasonography was superior to computed tomography for veinous involvement diagnosis (sensitivity: 68.4% vs 26.3%), and the results were similar for arterial involvement diagnosis (sensitivity: 55.5% vs 66.6%). CONCLUSION: Endoscopic ultrasonography is more accurate than computed tomography in detection of metastatic lymph nodes and portal involvement, and their results are similar in detection of arterial involvement.