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

Figure 2 Stepwise approach for evaluating metabolic dysfunction-associated steatotic liver disease using the fibrosis-4 index and the cytokeratin 18 fragment biomarker. A: High-risk group (orange). Patients with fibrosis-4 (FIB-4) > 2.67 should be referred to a hepatologist regardless of cytokeratin 18 fragment (CK-18F) levels due to the high risk of advanced fibrosis; B: Low-risk group (green). Patients with FIB-4 < 1.3 and CK-18F < 260 U/L are considered to have minimal fibrosis and inflammation. Follow-up with repeat FIB-4 and CK-18F testing every 1-2 years is recommended; C: Referral consideration group (pink). Patients with CK-18F ≥ 260 U/L may have progressive inflammation. Consider referring to a hepatologist for pathologic evaluation; D: Intermediate-risk group (yellow). Patients with FIB-4 of 1.30-2.67 and CK-18F < 260 U/L may include cases of full-blown metabolic dysfunction-associated steatohepatitis with advanced fibrosis. ¹Indicates further evaluation with the enhanced liver fibrosis test, Mac-2-binding protein glycosylation isomer, type IV collagen 7S, vibration-controlled transient elastography, or magnetic resonance elastography will be necessary to confirm fibrosis status. ²Indicates a fibrosis-4 index of 2.0 is considered intermediate risk for patients age 65 or older. CK-18F: Cytokeratin 18 fragment; FIB-4: Fibrosis-4.