RIFAXIMIN IN THE TREATMENT OF CHRONIC HEPATIC-ENCEPHALOPATHY - RESULTS OF A MULTICENTER STUDY OF EFFICACY AND SAFETY

Hepatic encephalopathy (HE) is a metabolic-neurophysiologic syndrome that occurs in patients with liver disease. One of the main pathogenic mechanisms is represented by circulating toxins produced from the intestinal metabolism of nitrogenous compounds. The therapeutic approach to HE includes drugs that eliminate ammonia-producing bacteria. The aim of this study was to evaluate the efficacy and safety of rifaximin, a nonabsorbable antibacterial agent, in the treatment of chronic HE in a large population of cirrhotic patients. One hundred thirty-six cirrhotic patients (100 men, 36 women; mean age, 59.5 years) with clinical and biochemical signs of mild HE were studied under three different treatment protocols: one open study in which rifaximin (1200 mg/day) was administered for 21 days to 80 patients; and two randomized controlled studies, one in which rifaximin (1200 mg/day, 20 patients) and neomycin (3000 mg/day, 15 patients) were administered for 21 days and one in which rifaximin (1200 mg/day, 9 patients) and lactulose (40 gm/day, 12 patients) were administered for 21 days. In the open study, after 5 days of treatment, ammonia reached normal values in each patient; after 7 days, electroencephalographic abnormalities were present only in a few cases; and after 15 days, no patients showed neurologic signs of HE. In the rifaximin versus neomycin study, blood ammonia levels and neurologic signs significantly decreased during both treatments, but rifaximin induced an earlier disappearance of clinical and biochemical signs of HE. In the rifaximin versus lactulose study, both drugs were efficacious in reducing the neurologic signs of HE, but some patients treated with lactulose presented mild side effects at the beginning of the therapy, which disappeared in the course of treatment. This study confirms the usefulness of rifaximin in the management of cirrhotic patients with mild HE; the absence of significant side effects suggests its use even in more severe cases of HE, either alone or in association with other drugs.