Patient Acceptance of Lactulose Varies Between Indian and American Cohorts: Implications for Comparing and Designing Global Hepatic Encephalopathy Trials.

Background: Lactulose is the first-line drug for hepatic encephalopathy (HE), but its acceptance widely differs between Western and Eastern studies. Patient preference for lactulose between different parts of the world has not been examined systematically.

Aim: To define the preferences and reasons behind acceptance of lactulose in patients from USA and India.

Methods: A discrete-choice questionnaire with six hypothetical scenarios was constructed. Situations 1-3 studied preference for lactulose vs no-lactulose, while 4-6 studied preference for high-dose vs low-dose lactulose varying the overt HE prevention at 6 months and adverse event rates in each situation. This was administered to outpatient cirrhotics without prior/current experience with lactulose after dedicated education.

Results: 100 patients (50 Indian, 50 USA) with similar MELD scores were included. A significantly higher proportion of Indian respondents agreed to lactulose in all situations compared to Americans. While their acceptance of lactulose decreased in the situation with the least difference in overt HE prevention, it was consistently higher than Americans. In the high-dose vs low-dose scenario, the relative proportion of American respondents accepting high-dose increased with the higher presented protection against overt HE. On the other hand, Indian respondents remained largely consistent with low-dose lactulose option.

Conclusions: There are significant variations in the acceptance of lactulose in Indian and American populations. The acceptance increases with a more favorable perceived benefit/risk profile, which is strongly influenced by socio-cultural factors. These results have important implications when designing, comparing and interpreting HE trials from different parts of the world.