Polyethylene Glycol Plus Lactulose Associated With Early Resolution of Hepatic Encephalopathy

hepatic encephalopathy
Diagnosis Hepatic Encephalopathy. Neurological hammer, stethoscope and liver laboratory test lie on note with title of Hepatic Encephalopathy. Concept for neurology and gastroenterology
Investigators assessed the safety and efficacy of polyethylene glycol plus lactulose vs lactulose alone for the treatment of acute-on-chronic liver failure.

Hepatic encephalopathy (HE) was effectively resolved with polyethylene glycol (PEG) plus lactulose treatment among patients with acute-on-chronic liver failure (ACLF). These findings, from a randomized trial, were published in the Journal of Clinical Gastroenterology.

Patients (N=60) with ACLF and HE with a West Haven Criteria grade ³2 were recruited in 2018 at the Liver Clinic of the Post Graduate Institute of Medical Education and Research in India. Patients were randomly assigned in a 1:1 ratio to receive 2 doses of PEG (118 g/dose) dissolved in 1 L of water on day 1 and 30 to 60 ml/3 times per day of lactulose from day 2 (n=29) or lactulose alone (n=31). HE resolution and outcomes up to 90 days were assessed.

The PEG and lactulose alone cohorts were 93.1% and 83.87% men, aged mean 42.38±10.28 and 43.5±10.62 years, and body mass index (BMI) was 22.52±3.58 and 23.14±3.37 kg/m2, respectively. No significant group differences were observed at baseline.

The patients had ethanol (78%), nonalcoholic steatohepatitis (15%), hepatitis B and C (5%), and autoimmune hepatitis (2%) liver disease etiologies.

HE Scoring Algorithm (HESA) scores improved by ³1 point at 24 hours among 62.1% of the PEG recipients and 32.2% of the lactulose alone recipients (P =.020). The mean HESA score was lower among PEG recipients at 24 (mean, 1.69 vs 2.12; P =.014) and 48 (mean, 1.11 vs 1.70; P =.001) hours.

HE was resolved at 1 week among 65.4% of PEG recipients and 21.4% of lactulose only recipients (P =.002). HE resolution had a decreased latency period among the PEG treatment group (mean, 5.8 vs 8.3 days; P =.026).

More than half of PEG recipients (58.6%) were successfully treated without recurrence compared with 17.1% of lactulose only recipients (P =.038).

Survival was higher among the PEG recipients at 28 days (93.1% vs 67.7%; P =.014); the difference in survival was no longer significant at day 90 (68.9% vs 48.3%; P =.940). Causes of death included sepsis (35%), progressive liver failure (25%), and variceal bleeding (6%).

Mortality at 28 days was associated with baseline HESA score (hazard ratio [HR], 6.01; 95% CI, 1.27-28.5; P =.024), baseline Model for End-Stage Liver Disease (MELD) Sodium score (HR, 1.26; 95% CI, 1.01-1.53; P =.022), and age (HR, 1.06; 95% CI, 1.00-1.13; P =.033).

HESA score >2.5 (area under the receiver operating characteristic curve [AUC ROC], 0.78; 95% CI, 0.63-0.92; P =.003) and MELD sodium score >28.5 (AUC ROC, 0.71; 95% CI, 0.57-0.84; P =.020) were predictors for mortality.

More PEG recipients reported excessive diarrhea (20.6% vs 9.6%). There were no differences reported for abdominal discomfort, serum sodium, creatinine, blood urea nitrogen, or coagulation function.

This study may have been limited by choosing to modify PEG dosing by dissolving 1 sachet in 1 L of water instead of 2 L, as has been done in previous studies.

These data indicated that early initiation of PEG among patients with HE and ACLF was associated with increased HE resolution and improved survival at 28 days compared with lactulose alone.


Ahmed S, Premkumar M, Dhiman RK, et al. Combined PEG3350 plus lactulose results in early resolution of hepatic encephalopathy and improved 28-day survival in acute-on-chronic liver failure. J Clin Gastroenterol. 2022;56(1):e11-e19. doi:10.1097/MCG.0000000000001450