Rifaximin and Its Microbial Resistance as a Secondary Prophylaxis of Hepatic Encephalopathy in Patients With HCV Related Cirrhosis

Methodology Inclusion and exclusion criteria Fully conscious patients were enrolled from the National Hepatology and Tropical Medicine Research Institute (NHTMRI), Cairo, Egypt between January 2015 and December 2018. The inclusion criteria were cirrhosis due to HCV infection, age 18 to 75 years, experiencing at least one episode of OHE, and a MELD score ≤ 25.13 Patients with neurological or communication problems, hepatocellular carcinoma, diabetes mellitus, active infection, serum creatinine > 2 mg/dl, Hg < 8 g/dL, serum Na < 125 mmol/L or serum K < 2.5 mmol/L were excluded. Patients with previous intake of rifaximin as prophylaxis or any antibiotic within the last month were also excluded.

Study Design The protocol of this open label, parallel, prospective interventional study was approved by the institutional review board (IRB) of NHTMRI and that of the Faculty of Pharmacy, Cairo University (CL(1173)). All patients and/or patients' caregivers for those with weak/impaired cognitive and/or thinking ability due to previous episode of HE were consulted and explained for provided written informed consent before study enrolment.

The patients were randomly assigned into either intervention group (rifaximin group) or control group (lactulose only group). Both groups received lactulose syrup 30-45 ml three times daily while rifaximin 400 mg three times daily was added to the intervention group for 6 months. Other conventional therapy including diuretics, proton pump inhibitors, ursodeoxycholic acid and silymarin were given to the patients in both groups according to the hospital protocol.

Study Follow-up All recruited patients were assessed clinically and biochemically at baseline and every 2 weeks for 6 months. Conn score, asterixis grade, complete blood picture with differential, serum bilirubin (total and direct), serum aspartate transaminase (AST) and alanine transaminase (ALT), alkaline phosphatase, gamma-glutamyltransferase (GGT), serum albumin, prothrombin time and concentration, urea and serum creatinine, serum sodium (Na) and potassium (K), urine and stool analysis were measured.

Efficacy outcomes The primary efficacy endpoint was the time to the first breakthrough episode of OHE (defined as the time from the first dose of the study drug to an increase from a baseline Conn score of 0 or 1 to a score of 2 or more or from a baseline Conn score of 0 to a Conn score of 1 plus a 1-unit increase in the asterixis grade.13 The secondary efficacy endpoint was the time to the first hospitalization involving HE (defined as hospitalization because of the disorder or hospitalization during which an episode of HE occurred).14 The percentage of patient's survival during the study was also considered a secondary outcome.