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A double blind study compared the efficacy of metronidazole in two doses (20 mg/kg, 10 mg/ kg) with placebo in patients with Crohn's disease. One hundred and five patients participated but only 56 completed the 16 week study -21 were withdrawn for deterioration of symptoms, 17 for adverse experiences, and 11 for protocol violation. Significant improvement in disease activity as measured by the Crohn's disease activity index (metronidazole 20 mg/ kg, 97 units; metronidazole 10 mg/kg, 67 units; placebo -1 unit, p=0002) and serum orosomucoid (metronidazole 20 mg/kg/day, 49; 10 mg/kg/day, 38; placebo, -9, p=0001)) were detected. Changes in C reactive protein concentrations did not achieve significance when all three groups were considered but were significant when all metronidazole treated patients were grouped and compared with the placebo treated patients (0-8 v -0-9, p<005). Although patients receiving metronidazole 20 mg/kg/day had a greater improvement in disease activity than those receiving 10 mg/kg/ day (difference 30 units (95% confidence intervals -27-87), the small sample size may have precluded the detection of statistical significance. Preliminary analysis suggests that metronidazole was more effective in patients with disease confined to the large intestine or affecting both small and large bowel than in those with small bowel disease only. There were no differences in remission rates between metronidazole and placebo treated patients. We conclude that metronidazole warrants further assessment in the treatment of patients with active Crohn's disease.

Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are "auto-anticoagulated" and thus protected from thrombotic events. Warfarin and non-vitamin K-antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population.

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