Lactulose in cirrhosis: Current understanding of efficacy, mechanism, and practical considerations

Abstract

HE is a complication of cirrhosis characterized by neuropsychiatric and motor dysfunction, and results in decreased quality of life and increased mortality. Lactulose is a synthetic disaccharide used to treat HE since 1966, though many questions about its use remain unanswered. Lactulose reverses minimal HE, prevents overt HE, improves quality of life, increases the rate of recovery from overt HE, and improves survival rates. Lactulose's clinical effect appears to be derived from its impact on intestinal microbes, likely a result of its enteric acidifying effect, positive pressure on beneficial taxa, and improvement of gut barrier function. There are several practical considerations with lactulose including (1) a need to avoid excessive bowel movements and subsequent dehydration, (2) treatment titration protocols need further investigation, (3) baseline or treatment-induced gastrointestinal side effects limit adherence in some cases, and (4) the utility of monitoring stool consistency or pH remains unknown. Further research is needed to optimize our use of this effective treatment for HE.

FIGURE 1

Clinical benefits of lactulose. Lactulose has multiple clinical benefits for patients with cirrhosis and HE.

FIGURE 2

Mechanisms by which lactulose treats HE. Lactulose puts positive pressure on probiotic bacteria, which consume ammonia and produce SCFAs as part of their metabolism. These SCFAs supply energy to the intestinal epithelia and also create an acidic environment which place negative pressure on ammonia-producing and potentially pathogenic organisms. Figure created in biorender.com. Abbreviation: SCFA, short-chain fatty acid.

FIGURE 3

Use of mobile technology to titrate lactulose. Patients taking lactulose require monitoring to avoid excessive bowel movements and subsequent dehydration. Such monitoring can be achieved with just-in-time text messages or other mobile technology.

FIGURE 4

Aims of future lactulose research. While lactulose is clearly effective in treating HE, there are several lingering uncertainties about its mechanism and ideal use. These uncertainties should be the focus of future research.