TOPLINE:

Amino acid imbalance — characterized by decreased levels of branched-chain amino acids (BCAAs) and increased levels of tyrosine — was found to be an independent prognostic factor in patients with cirrhosis. Both the ratio of BCAAs to tyrosine and the individual amino acid levels significantly predicted mortality risk.

METHODOLOGY:

• Amino acid imbalance is a common metabolic disturbance in cirrhosis and is usually assessed using Fischer’s ratio or the ratio of BCAAs to tyrosine. Although it has been linked to cirrhosis-related complications, its prognostic significance has not been adequately studied.
• Researchers conducted a multicenter retrospective cohort study to evaluate the prognostic impact of amino acid imbalance in patients with cirrhosis admitted to hospitals in Japan between June 2004 and July 2023.
• Serum concentrations of BCAAs and tyrosine, as well as the BCAA-to-tyrosine ratio, were measured under fasting conditions on the day of admission or the following day.
• Based on recommended cutoffs, a BCAA-to-tyrosine ratio ≤ 4.4 and a total BCAA concentration < 344 μmol/L were classified as low, whereas a tyrosine concentration > 99 μmol/L was classified as high.
• The primary outcome was all-cause mortality, with follow-up visits occurring at least every 3 months after discharge.

TAKEAWAY:

• Among 541 included patients (median age, 66 years; 50.3% female) and followed up for a median 3.5 years, 51.6% had a low BCAA-to-tyrosine ratio.
• Compared with those with a high ratio, patients with a low ratio had an increased prevalence of ascites and significantly poorer liver function (eg, worse Child-Pugh and Model for End-Stage Liver Disease scores and other factors).
• Patients with a low BCAA-to-tyrosine ratio had significantly poorer survival than those with a high ratio, with 1-, 3-, and 5-year survival rates of 88.0%, 73.3%, and 62.5% vs 94.1%, 89.8%, and 87.0%, respectively (P < .001).
• BCAA-to-tyrosine ratio independently predicted mortality (hazard ratio, 0.82; P =.004), as did older age, male sex, and a higher Child-Pugh score (P < .001 for all).
• Individual amino acid levels were also independently predicted mortality, with low BCAA levels (P = .019) and high tyrosine levels (P = .002) both linked to poorer survival.

IN PRACTICE:

“These findings highlight the importance of assessing amino acid imbalances, including both BCAA and tyrosine levels, to improve risk stratification and identify patients who may benefit from nutritional interventions in clinical practice,” the authors wrote.

SOURCE:

The study was led by Yuki Utakata, Department of Gastroenterology, Chuno Kosei Hospital, Seki, Japan. It was published online in Alimentary Pharmacology & Therapeutics.

LIMITATIONS:

The study was limited to patients with cirrhosis in Gifu, Japan, potentially affecting generalizability. Its retrospective design may have introduced selection bias and unmeasured confounding factors. Cut-off values were based on Japanese reference values, and changes in amino acid levels over time were not assessed. 

DISCLOSURES:

This study was supported by the Japan Society for the Promotion of Science KAKENHI grant. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.