title: Lactulose vs polyethylene glycol 3350--electrolyte solution for treatment of overt hepatic encephalopathy: the HELP randomized clinical trial.
abstract: OBJECTIVE
  Hepatic encephalopathy (HE) is a common cause of hospitalization in patients with cirrhosis. Pharmacologic treatment for acute (overt) HE has remained the same for decades.
  
  
  OBJECTIVE
  To compare polyethylene glycol 3350-electrolyte solution (PEG) and lactulose treatments in patients with cirrhosis admitted to the hospital for HE. We hypothesized that rapid catharsis of the gut using PEG may resolve HE more effectively than lactulose.
  
  
  METHODS
  The HELP (Hepatic Encephalopathy: Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution) study is a randomized clinical trial in an academic tertiary hospital of 50 patients with cirrhosis (of 186 screened) admitted for HE.
  
  
  METHODS
  Participants were block randomized to receive treatment with PEG, 4-L dose (n = 25), or standard-of-care lactulose (n = 25) during hospitalization.
  
  
  METHODS
  The primary end point was 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 outcomes included time to HE resolution and overall length of stay.
  
  
  RESULTS
  A total of 25 patients were randomized to each treatment arm. Baseline clinical features at admission were similar in the groups. Thirteen of 25 patients in the standard therapy arm (52%) had an improvement of 1 or more in HESA score, thus meeting the primary outcome measure, compared with 21 of 23 evaluated patients receiving PEG (91%) (P < .01); 1 patient was discharged before final analysis and 1 refused participation. 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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01283152.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas2Parkland Memorial Hospital, Parkland Health and Hospital System, Dallas, Texas3Now with Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medic.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Rahimi
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas2Parkland Memorial Hospital, Parkland Health and Hospital System, Dallas, Texas4Department of Clinical Science, University of Texas Southwestern Medical Center, Dallas.
authors.forename: Amit G
authors.initials: AG
authors.lastname: Singal
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas2Parkland Memorial Hospital, Parkland Health and Hospital System, Dallas, Texas.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Cuthbert
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas2Parkland Memorial Hospital, Parkland Health and Hospital System, Dallas, Texas5Now with Department of Internal Medicine, Medical University of South Carolina, Charles.
authors.forename: Don C
authors.initials: DC
authors.lastname: Rockey
mesh_terms: D000368:Aged; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006501:Hepatic Encephalopathy / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007792:Lactulose / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D013501:Surface-Active Agents / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D007792:Lactulose