Aliment Pharmacol Ther 31, 1012–1017

Background  Lactulose is considered first‐line therapy for hepatic encephalopathy. However, the effect of adherence with lactulose on recurrence of hepatic encephalopathy outside clinical trials remains unclear.

Aim  To determine the association of lactulose use with recurrence of hepatic encephalopathy episodes.

Methods  Patients with cirrhosis who were initiated on lactulose after an index hepatic encephalopathy episode in a liver‐transplant centre were retrospectively reviewed. Recurrence of hepatic encephalopathy, precipitating factors and adherence on lactulose were investigated using chart review and electronic pharmacy records. Patients with/without hepatic encephalopathy recurrence were compared, and predictors of recurrence were analysed.

Results  A total of 137 patients with cirrhosis (age 55 ± 6years, MELD 17 ± 7) who were initiated on lactulose after the index hepatic encephalopathy episode were included. Of these, 103 patients developed recurrent hepatic encephalopathy 9 ± 1 months after their index episode; 39 (38%) of these were not adherent on lactulose, 56 (54%) were adherent and 8 (8%) had lactulose‐associated dehydration leading to recurrence. Recurrent hepatic encephalopathy precipitants in lactulose‐adherent patients were sepsis (19%), GI bleeding (15%), hyponatremia (4%) and TIPS (7%). Overall, all patients who did not suffer recurrence were adherent on lactulose. In contrast, the adherence rate for those who recurred was only 64% (P = 0.00001). On multivariate regression, lactulose non‐adherence (OR 3.26) and MELD score (OR 1.14) were the factors that predicted recurrence.

Conclusion  Lactulose non‐adherence and lactulose‐associated dehydration were associated with nearly half of recurrent hepatic encephalopathy episodes.