Lactulose improves cognition, quality of life, and gut microbiota in minimal hepatic encephalopathy: A multicenter, randomized controlled trial.

Abstract

OBJECTIVE:

Lactulose is effective in the treatment and prevention of overt hepatic encephalopathy (OHE), but there are limited data on its use on microbiota in relations to minimal hepatic encephalopathy (MHE) recovery. The present study aimed to assess the efficacy of lactulose in recovery of MHE in aspects of cognitive function, quality of life, and impact on intestinal microbiota.

METHODS:

This multicenter, open-label randomized controlled trial was conducted in 11 teaching hospitals in China. Participants were randomly allocated on a 2:1 basis to receive lactulose (Gp-L) or no therapy as control (Gp-NL) for 60 days. The primary endpoint was the MHE reversal rate. Gut microbiota were compared between MHE patients and healthy volunteers, as well as lactulose-responders and non-responders.

RESULTS:

A total of 98 cirrhotic patients were included in the study, with 31 patients in the Gp-NL group and 67 patients in the Gp-L group. At day 60, the MHE reversal rate in Gp-L (64.18%) was significantly higher than that in Gp-NL (22.58%) (P = .0002) with a relative risk of 0.46 (95% confidence interval 0.32-0.67). Number needed to treat was 2.4. Further, there was significantly more improvement in physical functioning in Gp-L (4.62 ± 6.16) than in Gp-NL (1.50 ± 5.34) (P = .0212). Proteobacteria was significantly higher in MHE patients compared with healthy volunteers (12.27% vs 4.65%, P < .05). Significant differences were found between lactulose responders and non-responders in Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria.

CONCLUSIONS:

Treatment with lactulose significantly improves MHE recovery rate, and gut microbiota change in MHE patients can modulate the effectiveness of this therapy. Chinese Clinical Trial Register (ChiCTR) (ID: ChiCTR-TRC-12002342).

• Authors: Ji Yao Wang, Jasmohan S Bajaj, Jiang Bin Wang, Jia Shang, Xin Min Zhou, Xiao Lin Guo, Xuan Zhu, Li Na Meng, Hai Xing Jiang, Yu Qiang Mi, Jian Ming Xu, Jin Hui Yang, Bai Song Wang, Ning Ping Zhang
• Journal: Journal of digestive diseases (J Dig Dis) Vol. 20 Issue 10 Pg. 547-556 (Oct 2019) ISSN: 1751-2980 [Electronic] Australia
• PMID: 31448533 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2019 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Chemical References

• Gastrointestinal Agents
• Lactulose

Topics

• Adult
• Cognition (drug effects)
• Female
• Gastrointestinal Agents (therapeutic use)
• Gastrointestinal Microbiome (drug effects)
• Hepatic Encephalopathy (drug therapy, etiology, microbiology)
• Humans
• Lactulose (therapeutic use)
• Liver Cirrhosis (complications)
• Male
• Middle Aged
• Quality of Life
• Time Factors
• Treatment Outcome