The evolving role of liver biopsy in chronic liver disease: a pathological and clinical perspective

Abstract Background Liver biopsy has traditionally been regarded as the reference standard for evaluating chronic liver disease because it provides direct tissue-level assessment of necroinflammatory activity, fibrosis, architectural remodeling, and disease-specific patterns of injury. However, its role has changed substantially with the widespread use of serum-based biomarkers, elastography, imaging, and other non-invasive tests that now guide risk stratification and follow-up in many clinical settings. Objective This narrative review provides an integrated pathological and clinical perspective on the contemporary role of liver biopsy in chronic liver disease, emphasizing its selective indications, diagnostic value, technical and interpretive limitations, disease-specific applications, and evolving relationship with emerging technologies. Methods A structured literature search was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar, focusing primarily on publications from January 1, 2010, to March 31, 2026. Recent guidelines, systematic reviews, meta-analyses, landmark studies, and pathology-focused articles were prioritized. The review examined the role of liver biopsy across metabolic dysfunction-associated steatotic liver disease, autoimmune hepatitis, cholestatic liver diseases, chronic viral hepatitis, metabolic and deposition-related disorders, drug-induced liver injury, and other selected chronic liver disease settings. Main findings Liver biopsy is no longer required routinely for all patients with chronic liver disease, particularly when non-invasive assessment provides sufficient information for fibrosis risk stratification. Its greatest value lies in selected cases where tissue assessment can clarify diagnostic uncertainty, identify overlap or competing pathology, assess clinically meaningful inflammatory activity or fibrosis, or influence treatment and follow-up decisions. Nevertheless, biopsy findings should be interpreted critically because sampling error, specimen inadequacy, technical artifacts, interobserver variability, procedural risk, and the nonspecific nature of many histologic patterns may limit diagnostic confidence. Emerging approaches, including digital pathology, AI-assisted interpretation, molecular profiling, and spatial/single-cell technologies, may enhance the precision and biological depth of tissue-based assessment, but they currently remain adjunctive tools requiring validation, standardization, feasibility assessment, and expert clinicopathologic oversight. Conclusion In the modern era, the value of liver biopsy is best defined by precision rather than frequency. When applied selectively and interpreted within an integrated clinical, biochemical, serologic, imaging, non-invasive, and pathological framework, liver biopsy remains a high-value diagnostic tool that complements non-invasive assessment and supports individualized patient care.