Liver Dysfunction Markers and Heart Failure Mortality: A Meta-Analysis

A systematic review and meta-analysis published April 2, 2025, in BMC Cardiovascular Disorders has identified serum albumin as a significant predictor of prognosis for patients living with heart failure with preserved ejection fraction (HFpEF).

The research evaluated the prognostic value of various liver function markers to determine their ability to predict mortality and morbidity in this specific patient population.

Heart failure with preserved ejection fraction accounts for 50% of all heart failure cases. Its prevalence is increasing globally, driven by an aging population and common risk factors such as obesity and hypertension.

Study Scope and Methodology

The researchers conducted a systematic search across multiple databases, including PubMed, Scopus, Web of Science and Embase, to identify studies assessing the link between liver markers and adverse outcomes in HFpEF patients.

The final analysis included 20 studies encompassing a total of 30,623 patients. The primary outcome measured by the researchers was a composite of death or heart failure-related hospitalization.

The study focused on five specific liver biomarkers: serum albumin, bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP).

Findings on Serum Albumin

Serum albumin emerged as the primary marker with a significant association with patient outcomes. In a meta-analysis of 16 studies, the research found that serum albumin was significantly associated with a reduced risk of adverse outcomes, yielding a hazard ratio (HR) of 0.71 (95% CI: 0.61–0.83).

The researchers noted high heterogeneity in the initial results, with an I² statistic of 87%. However, after outliers were excluded, the heterogeneity decreased to 23%, and the association remained statistically significant with an HR of 0.75 (95% CI: 0.69–0.82).

Analysis of Other Liver Biomarkers

While serum albumin showed a clear prognostic link, other markers did not reach statistical significance in this analysis.

The study found no significant associations between adverse outcomes and the following markers:

• Aspartate aminotransferase (AST)
• Alanine aminotransferase (ALT)
• Alkaline phosphatase (ALP)
• Bilirubin

The authors suggested that the lack of statistical significance for these specific markers may have been caused by the limited number of studies available for their evaluation.

Clinical Context of Liver Dysfunction in HFpEF

Liver dysfunction is a common occurrence in patients with HFpEF. Because the liver is sensitive to changes in systemic circulation and venous congestion, its function can reflect the overall severity of heart failure.

The research indicates that liver dysfunction can worsen heart failure symptoms and negatively impact the overall prognosis for patients.

By identifying serum albumin as a reliable predictor, clinicians may have a clearer tool for assessing the risk of hospitalization or death in patients with preserved ejection fraction.