Comparison of Dietary Protein with an Oral, Branched Chain‐Enriched Amino Acid Supplement in Chronic Portal‐Systemic Encephalopathy: A Randomized Controlled Trial

Hepatology
Q1
Mar 1984
Citations:240
Influential Citations:7
Interventional (Human) Studies
80
Low RoB
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Methods
Design: randomized, double-blind, controlled trial at six hospitals. Participants: 37 hospitalized adults with cirrhosis and chronic portal-systemic encephalopathy who required dietary protein restriction (≤40 g/day). Baseline: stable hepatic encephalopathy (Grade 0–1). Ages: mean 60 years (range 30–75) in the protein group and 57 years (range 38–76) in the BCAA group. Exclusions included GI bleeding, bacterial infection, hepatorenal syndrome, or acute alcoholic/fulminant hepatitis. Randomization via sealed envelopes; assessments by blinded clinicians and neurologist; duration: 4 weeks.
Intervention
Basal dietary protein: 20 g/day for all during Week 1. After randomization, dietary protein group received 40 g/day in Week 2, 60 g/day in Week 3, and 80 g/day in Week 4. The branched-chain amino acid (BCAA) group received the same basal 20 g/day dietary protein plus an oral A662 BCAA-enriched amino acid solution in Weeks 2–4, dosed at 20 g/day in Week 2, 40 g/day in Week 3, and 60 g/day in Week 4. A662 was dissolved in a flavored maltodextrin solution and taken orally. Regimens lasted 4 weeks.
Results
Nitrogen balance improved to positive in both groups; Week 4: protein group +6.6 g/day vs BCAA group +3.9 g/day (not statistically different). Encephalopathy progression (Stage 2+): 7/12 in protein group vs 1/14 in BCAA group (p<0.05). PSE Index at end of therapy rose in the protein group and fell in the BCAA group; difference between groups at termination highly significant (p<0.005). Mental state grade increased in the protein group (0.6→1.4; p<0.05) and decreased non-significantly in the BCAA group (0.8→0.5). Asterixis worsened with protein but remained low with BCAA. Plasma BCAA levels rose with A662; BCAA/AAA molar ratio increased from 1.48 to 2.95 (p<0.001). Conclusion: Oral BCAA supplements are nutritionally effective, producing positive nitrogen balance to a similar degree as dietary protein while reducing the frequency of encephalopathy; they may be a viable alternative for patients with PSE who cannot tolerate dietary protein.
Limitations
Small sample size; premature termination due to availability issues with A662; protocol violations (admitting patients who could tolerate >40 g/day protein; continued lactulose/neomycin); missing data and incomplete EEG/ammonia measurements across centers; multicenter variability; not all outcomes available for all participants; death of one patient in the BCAA group potentially related to comorbidity.

Abstract

A randomized study was conducted in 37 hospitalized patients at six cooperating hospitals in which protein‐intolerant cirrhotic patients were fed increasing amounts of either dietary protein or a branched‐chain enriched amino acid solution (BCAA) unt...