Risk-stratified hepatocellular carcinoma surveillance in non-cirrhotic patients with MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as the leading global liver disorder and is poised to become the primary cause of hepatocellular carcinoma (HCC). Research indicates that nearly 50% of HCC cases in MASLD patients occur without cirrhosis, often presenting with more advanced and larger tumors. Despite this, current guidelines primarily focus on HCC screening in cirrhotic patients, with limited guidance for non-cirrhotic MASLD individuals. This narrative review seeks to identify key risk factors for HCC development, consolidate available screening methods, and propose a practical, risk-stratified algorithm for HCC surveillance in non-cirrhotic MASLD patients. We conducted a comprehensive review of studies published between 2017 and 2023 using PubMed, Embase, and CNKI, focusing on HCC risk factors and emerging screening strategies for non-cirrhotic MASLD cohorts. Key risk factors for HCC development in these patients include male sex, age over 65, hypertension, diabetes, mild alcohol consumption, smoking, dyslipidemia, elevated alanine aminotransferase levels, and a platelet count ≤ 150 × 10⁹/L. Among the screening methods evaluated, circulating free DNA, alpha-fetoprotein (AFP) combined with protein induced by vitamin K absence or antagonist-II (PIVKA-II), and the GALAD score (incorporating Glypican-3, AFP, alpha-1-Antitrypsin, and des-gamma-carboxy prothrombin) demonstrated the highest performance. Based on these findings, we proposed a risk-stratified HCC surveillance algorithm that integrates GALAD and PIVKA-II into the existing sonography and AFP screening protocols. This review aims to provide clinicians with actionable recommendations for HCC screening in non-cirrhotic MASLD patients.