Rifaximin Bests Lactulose in Preventing OHE Recurrence

Rifaximin monotherapy resulted in significantly fewer recurrences of overt hepatic encephalopathy (OHE) compared with lactulose (LAC) monotherapy in patients with a history of OHE, according to research presented at the American College of Gastroenterology scientific meeting.

This abstract was awarded ACG Outstanding Research Award in the Liver Category and was also noted as a Newsworthy Abstract. The research was presented by Jasmohan S. Bajaj, MD, MS, FACG, from Virginia Commonwealth University School of Medicine in Richmond, Virginia.

The investigators set out to evaluate the efficacy and safety of the two drugs used as monotherapy in OHE. They noted in the abstract that nonadherence to lactulose can precipitate the recurrence of OHE, indicating that other strategies are needed.

The team analyzed data post hoc from 2 randomized trials (phase 3 double-blind; phase 4 open-label) of adults with cirrhosis and a history of OHE during the previous 6 months. Only patients who were treated with rifaximin 550 mg twice daily with no lactulose, or with lactulose, titrated to 2-3 soft stools per day, plus placebo were included in the analysis. The primary efficacy endpoint was time to first breakthrough OHE episode.

Of the subjects included, 125 patients received rifaximin and 145 patients received lactulose. The majority of patients were male (60.0%; 68.3%), with a mean age of 57.  The median MELD score was 12 in both groups, and about half (51.2%; 46.2%) were Child-Pugh class B.

Among patients receiving rifaximin monotherapy, 23.2% had an OHE episode vs 49.0% of those treated with lactulose monotherapy. (P< 0.0001). Over 6 months of treatment, with a number needed to treat (NNT) of 4, rifaximin lowered the risk of an OHE episode by 60% compared to lactulose.

The study also found a a lower mortality rate in the rifaximin monotherapy group vs those treated with lactulose monotherapy (1.6% vs 4.8%; P< 0.001), with a NNT of 19 (HR, 0.048; 95% CI, 0.01-0.29). Through follow-up (14±2 days posttreatment), 2 (1.6%) patients in the rifaximin group died compared to 10 (6.9%) patients in the lactulose group. Of patients who died during the study, 2 had baseline Child-Pugh class A (lactulose group), 9 class B (rifaximin [n=2]; lactulose [n=7]), and 1 class C (lactulose group up); only 2 patients (1 in each group) had a baseline MELD score of 19 or more. More lactulose-treated patients discontinued early from study vs rifaximin-treated (62.1% vs 36.0%), most commonly due to OHE recurrence. Rifaximin monotherapy was well tolerated.

Rifaximin monotherapy may be an appropriate management approach in select patient populations.

Bajaj JS, Rahimi RS, Allen C, et al. 9 - Rifaximin monotherapy is more effective than lactulose monotherapy for reducing the risk of overt hepatic encephalopathy (OHE) recurrence and all-cause mortality: an analysis of two randomized trials