Considerations and clinical utility of referral pathways for early detection of liver disease in at-risk populations.

Metabolic dysfunction-associated steatotic liver disease is the most prevalent chronic liver condition, affecting over one-third of the global population, with cirrhosis present in up to 3.3% of cases. Early detection of advanced liver disease in at-risk populations can enable timely intervention, prevent progression, and reduce complications. This review focuses on the current recommendations for early detection of advanced liver disease, evaluates the evidence for the performance of non-invasive tests in the target population for screening, and examines the multifaceted burden of screening, including economic implications and psychological impacts. Additionally, we discuss future directions, such as integrating liver health into a multidisciplinary care framework. Current guidelines recommend case-finding, targeting individuals with type 2 diabetes, metabolically complicated obesity, or persistent elevated liver enzymes. The Fibrosis-4 index is widely endorsed as a first-line non-invasive test, yet the diagnostic performance in primary care settings seems suboptimal, particularly for pre-cirrhotic disease. Sequential strategies incorporating novel non-invasive tests may improve accuracy and cost-effectiveness. Confirmation typically involves vibration-controlled transient elastography. Key challenges include a large eligible population, uncertainties in optimal screening intervals, patient adherence to follow-up, and limited real-world cost-effectiveness data. Integrating liver health assessment into cardiometabolic care pathways, reflex testing, telehealth, and patient education may enhance uptake. While challenges remain, early detection of advanced liver disease is already likely cost-effective. Ongoing advances in screening pathways and treatment options are expected to further strengthen the case for widespread implementation.