Binding and transport functions of human serum albumin and its clinical implications in liver disease: a narrative review.

Background and Objective: Human serum albumin (HSA), a multifunctional plasma protein derived from the liver, plays a crucial role in the pathophysiology and management of liver diseases. Increasing research reveals that the non-colloid functions of HSA, especially its binding and transport of both endogenous and exogenous substances, are clinically important, beyond its well-characterized colloid effects such as maintaining oncotic pressure. In chronic liver diseases such as cirrhosis, impaired function of HSA disrupts its ligand-binding and detoxification processes, thereby leading to various complications. Common hepatic complications include metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH), hyperbilirubinemia, and iron overload. This narrative review aims to explore the clinical applications of the binding and transport functions of HSA in the diagnosis and treatment of liver diseases, with the objective of offering insights into the comprehensive management of these conditions. Methods: A computerized search was performed in PubMed and Embase, restricting the results to articles published in English and Chinese from January 2000 to March 2025. The search keywords use Medical Subject Headings and related entry terms, including terms related to "serum albumin, human", "recombinant human albumin", "antineoplastic agents", "analgesics", "anti-bacterial agents", "diuretics", "antiviral agents", "fatty acids", "ferritins", "bilirubin", "protein conformation", and "Amino Acid Sequence". Additionally, inverse searches were conducted based on the identified papers in these databases to uncover further relevant studies that were not captured by the automated search process. Key Content and Findings: HSA-ligand binding exerts substantial effects on drug pharmacokinetic profiles from a clinical perspective, thereby impacting therapeutic efficacy of antiviral and antimicrobial agents, along with management strategies for hepatocellular carcinoma (HCC). Additionally, the concept of effective albumin concentration (eAlb) is proposed and highlights albumin's physiological function beyond its absolute serum levels with marked eAlb depletion in cirrhosis restored by albumin treatment. The adoption of recombinant HSA (rHSA) as a substitute for HSA remains constrained, pending further validation of its ligand-binding properties compared with HSA. Conclusions: This review elucidates structural, mechanistic, and clinical perspectives of HSA, and characterizes HSA as a prognostic biomarker as well as a therapeutic target, while emphasizing the critical need for standardized guidelines for optimal albumin use in liver disease.