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Rifaximin improved outcomes of lactulose therapy for hepatic encephalopathy

Patients with overt hepatic encephalopathy experienced better results and less mortality when treated with lactulose and rifaximin than those who received lactulose alone in a recent study.

In a prospective, double blind trial, researchers randomly assigned 120 adults with cirrhosis and overt hepatic encephalopathy (HE) 30 mL to 60 mL lactulose three times daily with either 400 mg rifaximin three times daily (n=63) or placebo (n=57), in addition to standard treatments. Patients received the medication via nasogastric tube for 10 days or until complete HE recovery, with follow-up until hospital discharge or in-hospital death.

The cohort included 22 patients with grade 2, 40 with grade 3 and 58 with grade 4 HE at admission. Complete HE reversal was observed in 76% of rifaximin recipients, compared with 50.8% of placebo recipients. Multivariate analysis indicated independent associations between treatment nonresponse and nonreceipt of rifaximin (P=.0001) and total leukocyte count at baseline (P=.024).

Hospital stay was significantly shorter among those who received rifaximin (5.8 ± 3.4 days compared with 8.2 ± 4.6 days; P=.001). Mortality following treatment was significantly less frequent in the rifaximin group (23.8% of cases vs. 49.1%; P<.05). Death due to sepsis was more common among the placebo group (P=.01), while death due to GI bleed and hepatorenal syndrome occurred similarly between groups. No serious adverse events related to treatment occurred.

“We conclude that a combination of rifaximin and lactulose is more effective than lactulose alone for treatment of overt HE in patients with cirrhosis,” the researchers wrote. “Traditionally, nonabsorbable disaccharides have been used as the first-line therapy for patients with HE, even if their effectiveness in comparison with placebo has not been proven. Rifaximin offers an attractive choice as the risk of bacterial resistance appears to be lower with rifaximin than with systemic antibiotics.”

Disclosure: The researchers report no relevant financial disclosures.