Abstract
Background
Nonabsorbable disaccharides (lactulose or lactitol) are considered the treatment of choice for hepatic encephalopathy.
Objectives
To assess the beneficial and harmful effects of nonabsorbable disaccharides for patients with hepatic encephalopathy.
Search methods
Trials were identified through The Cochrane Hepato-Biliary Group Controlled Trials Register (March 2003), The Cochrane Central Register of Controlled Trials (Issue 1, 2003), MEDLINE (1966 to 2003/03), EMBASE (1980 to 2003/03), manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies.
Selection criteria
Randomised trials comparing lactulose or lactitol versus no intervention, placebo, or antibiotics and trials comparing lactulose versus lactitol for hepatic encephalopathy.
Data collection and analysis
The primary outcome measures included no improvement of hepatic encephalopathy and all-cause mortality. Binary outcomes are reported as relative risks (RR) based on a random effects model. Subgroup analyses were performed with regard to methodological quality and form of hepatic encephalopathy.
Main results
Thirty trials assessed nonabsorbable disaccharides versus placebo, no intervention, or antibiotics or assessed lactulose versus lactitol. We could not extract data from all trials. Compared with placebo or no intervention, nonabsorbable disaccharides had no statistically significant effect on mortality (RR 0.41, 95% CI 0.02 to 8.68, four trials), but appeared to reduce the risk of no improvement of hepatic encephalopathy (RR 0.62, 95% CI 0.46 to 0.84, six trials). However, this result may reflect bias due to low methodological quality of the majority of included trials. Trials of high methodological quality found no significant effect of nonabsorbable disaccharides on the risk of no improvement (RR 0.92, 95% CI 0.42 to 2.04, two trials). We found no statistically significant difference between lactulose and lactitol on mortality (two trials) or risk of no improvement (four trials). However, our meta-analyses were underpowered to establish whether these treatments have comparable effect. Nonabsorbable disaccharides appeared to be inferior to antibiotics on reducing the risk of no improvement (RR 1.24, 95% CI 1.02 to 1.50, 10 trials).
Authors’ conclusions
This systematic review questions the beneficial effects of nonabsorbable disaccharides and highlights that there is insufficient high-quality evidence to support this treatment. We found that antibiotics appeared to be superior to nonabsorbable disaccharides in improving hepatic encephalopathy, but it is unclear whether this difference in treatment effect is clinically important to patients. Nonabsorbable disaccharides should not serve as comparator in randomised trials on hepatic encephalopathy.
Plain language summary
There is insufficient evidence to confirm or exclude whether nonabsorbable disaccharides have an effect on patients with hepatic encephalopathy
Nonabsorbable disaccharides (lactulose or lactitol) are considered the treatment of choice for hepatic encephalopathy. When all the identified trials were combined, nonabsorbable disaccharides appeared to have a modest effect on improving encephalopathy. However, this effect was not seen when only trials of high quality were analysed. Antibiotics appeared to be superior to nonabsorbable disaccharides in improving hepatic encephalopathy, but it is unclear whether this difference in treatment effect is important to patients. Too few patients have been randomised to establish whether lactulose and lactitol have comparable effect.
