EBM Consult

HELP Trial: Lactulose vs Polyethylene Glycol 3350 for Hepatic Encephalopathy


  • The HELP Trial was a prospective, randomized, single-center clinical trial of 50 patients with known cirrhosis and were admitted for hepatic encephalopathy (HE) to receive either lactulose or PEG 3350 and found that PEG led to more rapid resolution of HE (based on improvements in HESA score) than lactulose.

HELP Trial Abstract

  • Rahimi RS, et al. Lactulose vs polyethylene glycol 3350-electrolyte solution for treatment of overt hepatic encephalopathy. The HELP Randomized Clinical Trial. JAMA Intern Med 2014;doi:10.1001.
    Study Design Prospective, Randomized, Single-Center Clinical Trial
    Sample Size n = 50
    Patients Cirrhotics who were admitted for acute hepatic encephalopathy
    • PEG, 4-L dose (n = 25) or
    • Standard-of-care lactulose (n = 25)
    Primary Endpoint

    An improvement of 1 or more in HE grade at 24 hours, determined using the hepatic encephalopathy scoring algorithm (HESA), ranging from 0 (normal clinical and neuropsychological assessments) to 4 (coma).

    Secondary Endpoint Time to resolution of HE and overall length of stay.
    • Thirteen of 25 patients in the standard therapy arm (52%) had an improvement of 1 or more in HESA score compared with 21 of 23 evaluated patients receiving PEG (91%) (P < .01)
    • The mean (SD) HESA score at 24 hours for patients receiving standard therapy changed from 2.3 (0.9) to 1.6 (0.9) compared with a change from 2.3 (0.9) to 0.9 (1.0) for the PEG-treated groups (P = .002).
    • The median time for HE resolution was 2 days for standard therapy and 1 day for PEG (P = .01).
    • Adverse events were uncommon, and none was definitely study related.
    Conclusions PEG led to more rapid HE resolution than standard therapy, suggesting that PEG may be superior to standard lactulose therapy in patients with cirrhosis hospitalized for acute HE.
    ClinicalTrials.gov NCT01283152