Noninvasive strategies for metabolic dysfunction-associated steatotic liver disease assessment and referral in Japan

Abstract

To establish practical, evidence-based strategies for noninvasive assessment and referral of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) in Japan, we must address the urgent clinical need for accurate risk stratification and timely specialist intervention. A panel of 11 Japanese hepatology experts conducted a modified Delphi process to evaluate consensus recommendations regarding the use of noninvasive tests (NITs), including the fibrosis-4 index, enhanced liver fibrosis test, Mac-2-binding protein glycosylation isomer, type IV collagen 7S, cytokeratin-18 fragments, and imaging modalities such as ultrasound elastography and magnetic resonance elastography, for MASLD assessment and clinical referral. Practical algorithms were developed based on current Japanese data and panel consensus. The expert panel validated the utility of NITs as reliable tools for identifying patients with MASLD at risk for advanced fibrosis. Sequential use of NITs improved diagnostic accuracy and referral appropriateness while minimizing unnecessary specialist consultations. The proposed algorithms offer stepwise guidance for primary care physicians, supporting efficient, evidence-based decision-making. However, prospective longitudinal studies remain necessary for full prognostic validation of NITs in MASLD management. Noninvasive testing algorithms enable effective risk stratification and referral for MASLD in real-world Japanese practice with anticipated benefit for patient outcomes and healthcare systems. Broader adoption and further validation are warranted.

Keywords: Fibrosis-4 index; Enhanced liver fibrosis test; Mac-2-binding protein glycosylation isomer; Type 4 collagen 7S; Cytokeratin-18 fragment; Elastography

Core Tip: MASLD is highly prevalent, progressing to MASH, fibrosis, cirrhosis, and hepatocellular carcinoma. Although liver biopsy is traditional, noninvasive tests (NITs) such as the fibrosis-4 index, enhanced liver fibrosis test, Mac-2-binding protein glycosylation isomer, type IV collagen 7S, cytokeratin-18 fragments, and imaging (elastography/magnetic resonance elastography) now enable accurate and accessible assessment of liver fibrosis. This review summarized expert consensus on the appropriate use of NITs in Japan, providing evidence-based referral strategies and practical algorithms for primary care and non-hepatologists. Delphi panel results confirmed the utility of NITs but also highlighted the need for further longitudinal studies to establish their prognostic value.