Predictors of the recurrence of hepatic encephalopathy in lactulose-treated patients

Abstract

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.