Lactulose, Tai chi prevent falls in patients with cirrhosis, portal hypertension

The LIVE-SMART trial presented at AASLD 2025 shows that lactulose and Tai chi may prevent falls in individuals with cirrhosis and portal hypertension.

“Falls are common, morbid, and predictable in patients with cirrhosis,” said the researchers. “Falls matter to patients as these reduce quality of life.” In one study, ~70 percent of participants considered falls as a ‘very extremely important’ patient-reported outcome. [Hepatology 2019;69:1787-1797]

This two-stage Sequential Multiple Assignment Randomized Trial comprised individuals who had cirrhosis and portal hypertension without prior overt hepatic encephalopathy from four centres in the US. In stage 1, participants were randomized 1:1 to receive enhanced usual care (EUC; education on nutrition and falls prevention) with or without lactulose therapy for 12 weeks. Stage 2 then ensued, in which participants were rerandomized to either Tai chi or EUC (exercise education) for an additional 12 weeks.

The intention-to-treat (ITT) population included 230 participants (mean age 61.8 years, 60 percent women). Of these, 64 comprised the EUC arm, 61 were on the lactulose arm, 53 received both EUC and Tai chi, and 52 had lactulose and Tai chi. [abstract 5003, AASLD 2025]

About 54 percent had metabolic-dysfunction-associated steatohepatitis, a quarter had alcohol-associated liver disease, and 54 percent had ascites. The average MELD-Na* score was 9.9. Twenty-three percent reported having any falls in the past 6 months.

The primary outcome was a hierarchical composite of death or transplantation for acute-on-chronic liver failure, injurious falls, overt hepatic encephalopathy, and non-injurious falls, compared between study groups using an ITT win ratio (WR). A WR >1 denotes a reduction in event risk.

At 12 weeks, in the ITT cohort, a comparison between lactulose and EUC yielded a WR of 2 (p=0.03); between Tai chi and no Tai chi, the WR was 2.3 (p=0.06). Similar patterns were observed in the per-protocol (PP) population (WR, 2.2; p=0.02 and WR, 4.2; p=0.004, respectively).

Week 24 saw similar WRs in the comparisons between lactulose and no lactulose (2.3; p=0.003 [ITT] and 2.3; p=0.005 [PP]) and between lactulose/Tai chi and EUC/EUC (2.7; p=0.006 and 2.4; p=0.02, respectively).

Compared with EUC, the survival probability was better with lactulose (p=0.0021) and with both lactulose and Tai chi (p=0.0081).

Events by arm

At week 24, compared with no lactulose, lactulose therapy was associated with reductions in any event in the composite outcome (18.58 percent vs 36.75 percent; hazard ratio [HR], 0.44; p=0.002), any fall (16.81 percent vs 34.19 percent; HR, 0.43; p=0.002), and any event including any transplant (18.58 percent vs 37.61 percent; HR, 0.43; p=0.002).

Similar patterns were observed for the comparison between lactulose/Tai chi and EUC/EUC for any event in the composite outcome (HR, 0.40; p=0.011), any fall (HR, 0.41; p=0.02), and any event including any transplant (HR, 0.40; p=0.01).

The researchers noted similar trends when looking at the outcomes between baseline and week 12 and between weeks 12 and 24.

Reducing fall risk a care priority

There was no difference in the incidence of adverse events between the lactulose and no-lactulose arms, as well as between the Tai chi and no-Tai chi arms. Only two cases of severe diarrhoea were reported among those who did not receive lactulose or Tai chi.

“Patients have identified reducing fall risk as a care priority … This is the largest trial of lactulose and the first trial of Tai chi for patients with cirrhosis. Lactulose and Tai chi are two effective interventions to reduce falls and fall-related harms in patients with cirrhosis and portal hypertension,” the researchers concluded.