Aim: The aim of the present investigation was to test study benzodiazepines (BZDs) profile in patients with viral cirrhosis under different combinations of rifaximine and of a novel symbiotic. Methods: Our study groups consisted of 30 patients with a confirmed diagnosis of HCV-related Child B liver cirrhosis. Patients were randomly allocated into three groups: rifaximine 400mg t.i.d. for 2 weeks; (B) SCM-III (Lactobacillus acidophilus, Lactobacillus helveticus and Bifidobacteria in a ion- and vitamin-enriched medium, Named srl, Italy) 10ml t.i.d. for 2 weeks; (C) rifaximine 400mg t.i.d. for 1 week followed by SCM-III 10ml t.i.d. for 5 weeks. At weekly interval, blood samples were withdrawn to test BZD-like substances, ammonia and endotoxin. Results: Rifaximine treatment brought about a significant early drop of BZDs ( [Formula: see text] versus pre-treatment and versus control) till fourth week of observation when a gradual increase took place with return to pre-treatment values at the sixth week. Symbiotic treatment was comparably effective while given to patients but significantly elevated BZDs level were noted starting from the third week. Similar phenomena were noted for endotoxin and ammonia although symbiotic seemed more effective against endotoxin and rifaximine against ammonia increase. However, the sequential treatment rifaximine-symbiotic brought about a sustained normalization of BZDs, ammonia and endotoxin throughout the 6-week study. Conclusion: The present pilot study suggests that a rifaximine-symbiotic regimen could be an effective tool in compensated liver cirrhosis to limit some triggering factors of hepatic encephalopathy while being amenable to long-term use and devoid of significant side effects.