Rifaximin cuts systemic inflammation, mucin degradation to resolve hepatic encephalopathy

Rifaximin suppresses the oralization of mucin-degrading bacteria and systemic inflammation, contributing to the prevention of recurrent hepatic encephalopathy (HE), a new trial has found.

The placebo-controlled, double-blind mechanistic study randomized 38 cirrhotic patients with HE to receive either 550-mg rifaximin-α (n=19) or placebo (n=90). Intervention lasted for 90 days, after which outcomes such as HE status, systemic inflammation, health-related quality of life (HRQoL), and infection, among others, were evaluated. Outcome assessments were also performed at 30 days.

Treatment with rifaximin led to the resolution of overt HE, such that none of the treated patients experienced an HE episode, whereas 21 percent of placebo controls did. HE grade was normalised to 0 90 days after treatment with rifaximin, while the median postintervention HE grade in controls was 0.5 (p=0.014). Treatment likewise significantly improved scores in the Psychometric HE Scale (p=0.009) but not HRQoL.

Mechanistically, the researchers observed that such HE resolution could be due to rifaximin’s suppression of systemic inflammation. Plasma levels of tumour necrosis factor-α was significantly lowered vs placebo at days 30 and 90 (p<0.001 for both), while interleukin-10 concentrations had dropped significantly at day 30 (p=0.005). Rifaximin likewise cut the likelihood of infections by 80 percent.

Moreover, rifaximin treatment led to the reduction of mucin-degrading bacterial genera, such as Veillonella, Akkermansia, and Hungatella, all three of which are also known to be orally originating.

“Rifaximin suppresses gut bacteria that translocate from the mouth to the intestine which causes the intestinal wall to become leaky by breaking down the protective mucus barrier. This resolves encephalopathy and reduces inflammation in the blood preventing the development of infection,” the researchers said.