title: Clinical effects of rifaximin in patientswith hepatic encephalopathy intolerant or nonresponsive to previous lactulose treatment: An open-label, pilot study.
abstract: BACKGROUND
  Hepatic encephalopathy (HE) is a metabolic-neurophysiologicsyndrome that occurs in patients with advanced hepatic disease. One of the main pathogenic mechanisms is represented by circulating toxins produced by the intestinal metabolism of nitrogenous compounds. The therapeutic approach to HE is mainly based on drugs that eliminate ammonia-producing bacteria.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the effects of the nonabsorbable antibiotic rifaximin in patients with HE who were intolerant or nonresponsive to treatment with an oral, nonabsorbable disaccharide (lactulose).
  
  
  METHODS
  This uncontrolled, open-label, pilot study was conducted at the University of Bologna, Bologna, Italy. Patients aged ≥ 18 years with histologically proven liver cirrhosis and HE were studied. All patients were intolerant or nonresponsive to previous treatment with lactulose. Rifaximin tablets were administered to patients at a dosage of 400 mg TID for 10 days. The portal systemic encephalopathy (PSE) index was evaluated at enrollment and at the end of the treatment period. Tolerability was assessed using hematology, biochemistry, and urinalysis and by recording adverse effects (AEs).
  
  
  RESULTS
  Twenty-six patients (18 men, 8 women; mean [SD] age, 55.8 [8.0] years) were enrolled (intolerants, n = 17; nonresponders, n = 9). All patients completed the study. Significant improvement was shown in most of the 5 components of the PSE index after rifaximin administration in both intolerants and nonresponders. At the end of the 10-day treatment period, the PSE index was significantly reduced in both intolerants and nonresponders. Rifaximin was well tolerated; no clinically relevant AEs were observed during the treatment period.
  
  
  CONCLUSIONS
  This pilot study of patients with liver cirrhosis and HE who were intolerant or nonresponsive to previous treatment with an oral, nonabsorbable disaccharide suggests that treatment with rifaximin may be considered as an adjuvant or an alternative treatment in reducing HE.
authors.affiliation: Department of Internal Medicine and Gastroenterology, Alma Mater Studiorum,University of Bologna, Bologna, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sama
authors.affiliation: Department of Internal Medicine and Gastroenterology, Alma Mater Studiorum,University of Bologna, Bologna, Italy.
authors.forename: Antonio Maria
authors.initials: AM
authors.lastname: Morselli-Labate
authors.affiliation: Department of Internal Medicine and Gastroenterology, Alma Mater Studiorum,University of Bologna, Bologna, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pianta
authors.affiliation: Department of Internal Medicine and Gastroenterology, Alma Mater Studiorum,University of Bologna, Bologna, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Lambertini
authors.affiliation: Department of Internal Medicine and Gastroenterology, Alma Mater Studiorum,University of Bologna, Bologna, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Berardi
authors.affiliation: Department of Internal Medicine and Gastroenterology, Alma Mater Studiorum,University of Bologna, Bologna, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Martini
keywords: antibiotics; disaccharides; drug therapy; hepatic encephalopathy; liver cirrhosis; rifaximin