Lactulose in Hepatic Encephalopathy:
Does it work or not!

Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomised trials
Objective To assess the effects of non-absorbable disaccharides (lactulose and lactitol) in patients with hepatic encephalopathy.
Conclusions There is insufficient evidence to support or refute the use of non-absorbable disaccharides for hepatic encephalopathy. Antibiotics were superior to non-absorbable disaccharides in improving hepatic encephalopathy, but it is unclear whether this difference is clinically important. Non-absorbable disaccharides should not serve as comparator in randomised trials on hepatic encephalopathy.
(Bodil Als-Nielsen et al In BMJ  2004;28: 1046 (1 May),doi:10.1136 bmj.38048. 506134.EE (published 30 March 2004)

It’s not lactulose!
Als-Nielsen et al systematically reviewed randomised trials using lactulose or lactilol for hepatic encephalopathy, which has been warranted for some time. We agree that non-absorbable disaccharides have been introduced into clinical practice without any convincing evidence base but question the authors’ conclusion, that there is insufficient evidence to determine whether non-absorbable disaccharides are of benefit to patients with hepatic encephalopathy. Surely, this comprehensive review shows clearly that lactulose is ineffective for treatment of hepatic encephalopathy, rather than there being insufficient evidence.
Furthermore, the results of this study have several important implications.
Firstly, what should comprise standard medical treatment for hepatic encephalopathy? Lactulose should no longer be included, but strict attention should be paid to treating the precipitating factors, with correction of dehydration, electrolyte and acid base imbalance, constipation, and infection.
Secondly, we make a plea for placebo controlled trials: no restriction should be imposed on the conduct of placebo controlled studies on ethical grounds.
Thirdly, the interorgan metabolism of ammonia should be revisited and the recent studies showing the important roles of the small intestine, muscle, and kidneys in regulating the blood concentrations of ammonia considered.
(Debbie L Shawcross, research fellow and Rajiv Jalan, senior lecturer in BMJ  2004;329:112 (10 July)

Lactulose should not be part of standard treatment of hepatic encephalopathy
We do not agree that our Cochrane review clearly shows that lactulose is ineffective. The fact that we found no evidence of effect does not imply that there is evidence of no effect. It is difficult to prove that a treatment has no effect.
A survey of 989 abstracts of Cochrane reviews showed that inappropriate claims of no effect were made in 240 (22.5%) abstracts. In our review, we found that high quality trials found no significant effect of lactulose on the risk of no improvement of hepatic encephalopathy (relative risk 0.92, 95% confidence interval 0.42 to 2.04). The confidence interval indicates that we cannot exclude that lactulose may benefit (reduce the risk of no improvement by up to 58%). On the other hand, lactulose may also harm (increase the risk of no improvement by up to 104%). Our meta-analysis is based on only two trials with a total of 46 patients. Accordingly, our analysis has low power to detect clinically beneficial or harmful effect.
A consequence of claiming no effect would be that further research assessing the effect of lactulose is unnecessary. We find that a large, randomised, parallel, double blind trial is warranted. It would be interesting to compare lactulose, another laxative (magnesium or sorbitol) prepared to appear and taste like non-absorbable disaccharides, and a placebo of similar taste and appearance but without a cathartic effect (such as glucose).
We agree that lactulose should not be part of standard treatment of hepatic encephalopathy, and that placebo controlled trials are mandatory in this field, where none of the current treatments has proved clinically effective.
(Bodil Als-Nielsen, research fellow In BMJ  2004;329:112 (10 July)