ABSTRACT Hepatic diseases progress silently, leading to fibrosis, cirrhosis, and hepatocellular carcinoma. Although liver biopsy remains the gold standard for fibrosis assessment, it is limited by invasiveness and sampling variability. Non‐invasive liver tests (NILTs) can mitigate biopsy‐related risks. However, some NILTs are costly, and economic/implementation evidence remains limited due to small samples and variability across healthcare systems. This systematic review aimed to evaluate economic studies comparing the costs and benefits of NILTs versus liver biopsy in chronic liver disease. Comprehensive searches were conducted up to February 21, 2024, identifying cost and economic evaluation studies comparing NILTs and biopsy for fibrosis detection in individuals with hepatitis B, hepatitis C, alcoholic liver disease (ALD), and non‐alcoholic fatty liver disease (NAFLD). Sources included PubMed, Embase, and Scopus, supplemented by searches in economic databases. Two reviewers independently screened, appraised, and extracted data. Of 478 studies identified, 17 met inclusion criteria, primarily from Europe and published after 2012. Most studies used cost‐utility analyses adopting a public healthcare perspective and a lifetime horizon. Chronic viral hepatitis and NAFLD were the most studied conditions, with Fibroscan, Enhanced Liver Fibrosis (ELF), and FibroTest as the predominant NILTs. Outcomes included Quality‐Adjusted Life Years (QALYs) and diagnostic accuracy. Incremental Cost‐Effectiveness Ratios (ICERs) ranged from US$28 868 to US$150 000, influenced by factors such as test cost, screening age, and sequential strategies. Despite heterogeneity, most studies conclude that NILTs are cost‐effective, particularly in combination, supporting their broader adoption in the management of chronic liver disease. Trial Registration: PROSPERO: CRD42023404278
Key Points Increase in NILTs use: Noninvasive liver tests (NILT) are increasingly used to detect fibrosis, offering a safer alternative to invasive testing. Main conditions and interventions: Chronic viral hepatitis and NAFLD were most commonly studied; key interventions included FibroScan, ELF, and FibroTest. Predominant effectiveness measures: The most frequent measures were quality‐adjusted life years (QALYs) and correct diagnosis. Strong recommendations in favour of NILTs: Most studies favoured NILT, particularly combinations of tests, to improve cost‐effectiveness in chronic liver disease management. Limitations and suggestions for future research: Most clinical data came from nonrandomized studies, and evidence for alcoholic liver disease is limited. Future work should prioritise prospective, randomised studies, especially evaluating combinations of NILT.