Intravenous branched chain amino acid infusion is associated with early but ill-sustained recovery of overt hepatic encephalopathy in acute-on-chronic liver failure: a pilot protocol

ABSTRACT

Background and Aim: Hepatic encephalopathy (HE) in acute-on-chronic liver failure (ACLF) is associated with significant morbidity and mortality. There is limited evidence regarding HE management in patients with ACLF. 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 24h, day 3 & day 7. Duration of ICU stay and survival at days 7 and 28 was compared. Methods: CANONIC ACLF patients with HE grades>=2 were randomized into two groups - experimental arm (IV-BCAA - 500mL/day for 3 days + Lactulose;n=39) and comparator arm (Lactulose alone;n=37). Six patients developed COVID-19 after randomization & were excluded (4-experimental arm & 2-comparator arm). HE Grade was assessed by West Haven Classification and Hepatic Encephalopathy Scoring Algorithm (HESA). ACLF severity was determined by CLIF-C ACLF and MELD scores. All patients received standard of care. Results: Both groups were similar in baseline characteristics including grade of HE (2.85 ± 0.75 vs 2.82 ± 0.66;P = 0.864) and CLIF-C ACLF score (54.19 ± 5.55 vs 54.79 ± 5.74;P = 0.655). Overall survival was 40% at 28 days (48.5% vs 31.4%;P=0.143). Significant improvement in HESA score by 1 grade at 24h was seen in 14 patients (40%) in BCAA arm and 6 patients (17.14%) in control group (P=0.034) which translated to shorter ICU stay in the BCAA arm. Median change in HESA score at 24h was significantly more in BCAA arm than control arm (P=0.006), however, this was not sustained at day 3 or 7. Ammonia levels did not correlate with HE grade (Spearman correlation coefficient (-0.0843;P=0.295). Conclusion: Intravenous BCAA leads to early but ill-sustained improvement in grade of HE and reduced ICU stay in ACLF.