Rifaximin and lactulose combo effectively, decreases mortality in hepatic encephalopathy

China: Metabolic disorders induce hepatic encephalopathy (HE), which causes severe liver disease and mismanaged central nervous system. Improving HE is clinically essential to improve functional capacity, quality of life, and patient prognosis.

The US Food and Drug Administration (FDA) approved Rifaximin, an oral antimicrobial agent, in 2010 for the prevention and management of HE. Lactulose reduces aminogenic substrates in the intestinal lumen and colon pH by organic acid production through bacterial fermentation and the osmotic cathartic mechanism.

Rifaximin and lactulose should be used in combination to treat HE. But data is scanty to support whether this combination is additionally strengthening compared to lactulose alone in HE.

Against the above scenario, Jian Fu, Department of Infection, Hainan General Hospital, China, and colleagues aimed to conduct a systemic review and meta-analysis of randomized controlled trials (RCT) to investigate the effectiveness of rifaximin plus lactulose versus lactulose alone in HE patients.

For the study, the researchers included 7 RCTs with 843 enrolled patients. Relative risks (RR) with 95 % confidence intervals were used to calculate pooled effect estimates for treatment effectiveness.

The research article was published in PLOS ONE.

The conclusive points from the study include:

• Three RCTs were conducted in Pakistan, 2 in India, and 2 in China.

• There was an increased incidence of effective rate with the use of rifaximin plus lactulose compared to lactulose alone. (RR, 1.30).

• The combination of rifaximin plus lactulose reduced mortality as compared to lactulose alone. (RR, 0.57)

• In subgroup analysis, the beneficial effect of rifaximin plus lactulose was mainly present in studies conducted in China and Pakistan. The data included HE patients with mean age < 50 years, males < 70 %, and cirrhosis as etiological factors; these were low-quality studies.

• The combination was not associated with the incidence of effective rate from data pooled from studies in India. These studies were of high quality and included overt HE males≥ 70 % involving many etiological factors.

• Young patients with mild HE and women predilection could benefit from rifaximin plus lactulose.

• One study reported the adverse event associated with the combination.

The first author and the co-author Yi Gao wrote," Rifaximin plus lactulose reduces HE progression, severity and sepsis-related deaths by lowering levels of gut-related endotoxins."

The researchers added, "Rifaximin plus lactulose should be applied in clinical practice, especially in India, China, and Pakistan. However, large-scale RCTs should be conducted to ascertain the long-term benefits of this combination versus lactulose alone in patients with HE."

References:

Fu J, Gao Y, Shi L (2022) Combination therapy with rifaximin and lactulose in hepatic encephalopathy: A systematic review and meta-analysis. PLoS ONE 17(4): e0267647