Intravenous BCAA Infusion Does Not Lead to a Sustained Recovery From Overt HE in ACLF - An Open Label Randomized
Rohit Mehtani1, Madhumita Premkumar1, Shankey Garg2
1Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Insights
Intravenous branched-chain amino acids (IV-BCAA) with lactulose showed a rapid but not sustained improvement in hepatic encephalopathy (HE) in acute-on-chronic liver failure (ACLF) patients. This treatment did not improve overall survival at 28 days.
Area of Science:
- Hepatology
- Gastroenterology
- Clinical Nutrition
Background:
- Hepatic encephalopathy (HE) significantly increases morbidity and mortality in acute-on-chronic liver failure (ACLF).
- Effective treatments for HE in ACLF are crucial for improving patient outcomes.
- Understanding the role of specific nutritional interventions like IV-BCAA is important.
Purpose of the Study:
- To evaluate the efficacy of intravenous branched-chain amino acids (IV-BCAA) combined with lactulose versus lactulose alone for improving HE in ACLF patients.
- To assess the impact of IV-BCAA on HE grade at 24 hours, day 3, and day 7.
- To determine the effect on overall survival and intensive care unit (ICU) stay.
Main Methods:
- A prospective, randomized controlled trial was conducted involving European association for study of liver (EASL) defined ACLF patients with overt HE.
- Patients were randomized into two groups: IV-BCAA (500 mL/day for 3 days) plus lactulose, or lactulose alone.
- The primary outcome was an improvement of at least one grade in HE, assessed using the hepatic encephalopathy scoring algorithm (HESA), at 72 hours.
Main Results:
- Of 70 analyzed patients, baseline characteristics were similar between the IV-BCAA and control groups.
- A significant improvement in HESA by ≥1 grade at 24 hours was observed in the IV-BCAA arm (40%) compared to the control group (17.1%) (P=0.03).
- This improvement in HE was not sustained at days 3 or 7, and no significant difference in overall 28-day survival was found (48.5% vs 31.4%; P=0.14).
Conclusions:
- Intravenous BCAA treatment does not lead to a sustained improvement in HE grade in ACLF patients.
- While IV-BCAA may offer short-term benefits in HE management, it does not impact long-term survival.
- Further research is needed to explore sustained therapeutic strategies for HE in ACLF.
Background:
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.
Patients And Methods:
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).
Results:
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).
Conclusion:
Intravenous BCAA does not lead to a sustained improvement in HE grade in ACLF.
Trial Registration No:
NCT04238416 (clinicaltrials.gov).
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