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: Hepatic encephalopathy (HE) in acute-on- chronic liver failure (ACLF) is associated with significant morbidity and mortality. There is paucity of data regarding HE management in patients with ACLF and most of the evidence is extrapolated from patients with cirrhosis. 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 scores at 24h, day 3 & day 7. Duration of ICU stay and survival at days 7 and 28 was compared. Method(s) CANONIC ACLF patients with HE grades >= 2 were assessed for eligibility and 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). Grade of HE 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 for HE and ACLF management. Result(s) 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 a shorter ICU stay in the BCAA arm (Table 1). 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 the grade of HE (Spearman's correlation coefficient(rho) = -0.0843;P=0.295). Conclusion(s) Intravenous BCAA leads to early but ill-sustained improvement in grade of HE and reduced ICU stay in ACLF.