Rifaximin,but not growth factor 1,reduces brain edema in cirrhotic rats

AIM:To compare rifaximin and insulin-like growth factor(IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion.METHODS:Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups:Cirrhosis;Cirrhosis + IGF-1;Cirrhosis + rifaximin;Controls;Controls + IGF-1;and Controls + rifaximin.An oral glutamine-challenge test was performed,and plasma and cerebral ammonia,glucose,bilirubin,transaminases,endotoxemia,brain water content and ileocecal cultures were measured and liver histology was assessed.RESULTS:Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups,and improved some liver function parameters(bilirubin,alanine aminotransferase and aspartate aminotransferase).These effects were associated with a significant reduction in cerebral water content.Blood and cerebral ammonia levels,and area-underthe-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals.By contrast,IGF-1 administration failed to improve most alterations observed in cirrhosis.CONCLUSION:By reducing gut bacterial overgrowth,only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema,alterations associated with hepatic encephalopathy.

Efficacy of combination therapy with natriuretic and aquaretic drugs in cirrhotic ascites patients: A randomized study

AIM To assess the effects of a combination therapy with natriuretic and aquaretic drugs in cirrhotic ascites patients.METHODS A two-center,randomized,open-label,prospective study was conducted. Japanese patients who met the criteria were randomized to trial group and the combination diuretic group(received 7.5 mg of tolvaptan) or the conventional diuretic group(received 40 mg of furosemide) for 7 d in addition to the natriuretic drug which was used prior to enrolment in this study. The primary endpoint was the change in body weight from the baseline. Vital signs,fluid intake,and laboratory and urinary data were assessed to determine the pharmacological effects after administration of aquaretic and natriuretic drugs.RESULTS A total of 56 patients were randomized to receive either tolvaptan(n = 28) or furosemide(n = 28). In the combination and conventional diuretic groups,the average decrease in body weight from the baseline was 3.21 ± 3.17 kg(P < 0.0001) and 1.75 ± 2.36 kg(P = 0.0006),respectively,when measured on the final dosing day. Following 1 wk of treatment,a significantly greater reduction in body weight was observed in the combination diuretic group compared to that in the conventional diuretic group(P = 0.0412).CONCLUSION Compared to a conventional diuretic therapy with only a natriuretic drug,a combination diuretic therapy with natriuretic and aquaretic drugs is more effective for patients with cirrhotic ascites.