Intravenous BCAA Infusion Does Not Lead to a Sustained Recovery From Overt HE in ACLF – An Open Label Randomized Clinical Trial.

Hepatic encephalopathy (HE) in acute-on-chronic liver failure (ACLF) is associated with significant morbidity and mortality. We conducted a prospective, randomized controlled clinical trial to study the efficacy of intravenous branched chain amino acids (IV-BCAA) with lactulose versus lactulose alone for improvement in HE at 24 h, day 3, and day 7. The primary outcome was an improvement in encephalopathy by ≥ 1 grade at 72 h. European association for study of liver (EASL) defined ACLF patients with overt HE were assessed and randomized into the experimental arm (IV-BCAA - 500 mL/day for 3 days + Lactulose; n = 39) and the comparator arm (Lactulose alone; n = 37). Six patients developed COVID-19 after randomization and were excluded (4-experimental arm and 2-comparator arm). Of 222 screened patients, 70 (35 in each arm) were included in the analysis. Baseline characteristics, including HE grade (2.9 ± 0.7 vs 2.8 ± 0.7; P = 0.86) and (chronic liver failure) CLIF-C ACLF score (54.2 ± 5.6 vs 54.8 ± 5.7; P = 0.65), were similar. Overall survival was 40% at 28 days (48.5% vs 31.4%; P = 0.14). Improvement in hepatic encephalopathy scoring algorithm (HESA) by ≥ 1 grade at 24 h occurred in 14 patients (40%) in the BCAA arm and 6 patients (17.1%) in the control group (P = 0.03) which translated to a shorter intensive care unit (ICU) stay. The median change in HESA at 24 h was greater in the BCAA arm than the control arm (P = 0.006), which was not sustained at days 3 or 7. Ammonia levels did not correlate with the grade of HE (Spearman's correlation coefficient (ρ) = - 0.0843; P = 0.29). Intravenous BCAA does not lead to a sustained improvement in HE grade in ACLF. NCT04238416 (clinicaltrials.gov). • Hepatic encephalopathy (HE) in acute-on-chronic liver failure (ACLF) is associated with high morbidity and mortality. • Oral branched-chain amino acids (BCAA) are helpful in HE in cirrhosis but role of intravenous BCAA in ACLF is unknown. • We describe the use of intravenous BCAA for HE in ACLF. • IV BCAA given in a short 3-day course helps in early resolution of HE which translated to shorter ICU stay. • The improvement in HE by IV BCAA was not sustained at day 3 or day 7 and there was no 28-day survival benefit. [ABSTRACT FROM AUTHOR]