Lactulose reduced falls in cirrhosis without provoking encephalopathy

Design

24-week two-stage sequential multiple assignment randomised trial (SMART), win-ratio analysis

Population

230 adults with cirrhosis and portal hypertension without prior overt hepatic encephalopathy, four US centres

Primary outcome

hierarchical composite of death or transplantation, injurious falls, incident encephalopathy and non-injurious falls

Effect

lactulose then TeleTai-Chi vs usual care: injurious falls 4% vs 12%, win ratio 2.7 (95% CI 1.3–5.5); lactulose users vs non-users win ratio 2.3 (1.3–4.0)

Patients with cirrhosis fall, and they have said themselves that reducing that risk matters to them. LiveSMART enrolled 230 adults with cirrhosis and portal hypertension but no prior overt hepatic encephalopathy across four US centres in a 24-week two-stage sequential multiple assignment randomised trial. In stage one, weeks 1 to 12, participants were randomised to lactulose or enhanced usual care — education on nutrition and fall prevention. In stage two, weeks 13 to 24, they were randomised again to TeleTai-Chi or exercise education. The primary outcome was a hierarchical composite of death or transplantation, injurious falls, incident encephalopathy and non-injurious falls, analysed by win ratio.

Lactulose followed by TeleTai-Chi, against enhanced usual care, reduced injurious falls (4% vs 12%) and non-injurious falls (19% vs 32%), with no difference in overt encephalopathy (2% vs 0%) and no deaths or transplants in either arm; win ratio for the composite 2.7 (95% CI 1.3 to 5.5). Comparing lactulose users with non-users, injurious falls were 3.5% against 8.5%, non-injurious falls 15.0% against 26.5%, overt encephalopathy 1.8% against 2.6%, win ratio 2.3 (1.3 to 4.0), with no difference in adverse events.

The interesting part is what did not happen. The usual objection to lactulose in a patient who has never had overt encephalopathy is that it is burdensome and unnecessary — and covert encephalopathy is the plausible mechanism for the falls. Treating it prophylactically reduced falls without an excess of overt episodes or adverse events.

• Ask patients with cirrhosis and portal hypertension specifically about falls and near-falls
• Consider lactulose for fall risk in portal hypertension even without prior overt encephalopathy
• Titrate to stool frequency and review tolerance — adherence is the practical limit
• Add a supervised exercise or balance component where one can be arranged

Why it matters

It gives a reason to start lactulose before the first overt episode rather than after it.

Don't overread it

The user-versus-non-user analysis is observational within the trial; the randomised comparison is the sequential one.

The statistics, in plain English

A win ratio compares every patient in one arm with every patient in the other on a ranked hierarchy of outcomes — a value of 2.3 means wins outnumbered losses by roughly two to one. The interval of 1.3 to 4.0 excludes 1.0, so the advantage is unlikely to be chance, but the width reflects 230 patients and few events. The lactulose user-versus-non-user comparison is not the randomised contrast and is vulnerable to the differences between people who take lactulose and people who do not.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.