Dynamic Changes in Metabolic Syndrome and Risk of Hepatocellular Carcinoma: Evidence From a Nationwide Japanese Cohort

ABSTRACT Aim Metabolic syndrome (MetS) is a known risk factor for hepatocellular carcinoma (HCC), but the impact of cumulative MetS burden and changes in MetS status over time remains unclear. This study aimed to assess these associations using a large‐scale Japanese health dataset. Methods We analysed medical data from 2.71 million Japanese individuals collected between 2005 and 2020. The study evaluated the incidence of HCC in relation to MetS, preMetS (an early stage of MetS), and five MetS components: triglycerides ≥ 150 mg/dL, HDL‐C < 40 mg/dL in men or < 50 mg/dL in women, fasting blood glucose ≥ 100 mg/dL, blood pressure ≥ 130/85 mmHg, and waist circumference ≥ 90 cm in men or ≥ 80 cm in women. For the dynamic analysis, participants were classified into four groups based on MetS status during two predefined periods, 2010–2011 and 2012–2013: MetS‐free, MetS‐developed, MetS‐persistent, and MetS‐recovered. As Type 2 diabetes (T2D) is an extreme metabolic state and a strong independent risk factor for HCC, this study assessed the impact of MetS on HCC risk excluding T2D. Results Among the 2.71 million individuals, 63 435 developed HCC. Compared with the non‐MetS group, both the MetS group (HR 1.42, 95% CI 1.39–1.45) and the preMetS group (HR 1.26, 95% CI 1.22–1.29) had significantly increased HCC risk. A higher number of MetS components was associated with progressively increased HCC incidence. Individuals who developed or maintained MetS over time had a higher risk of HCC than MetS‐free individuals, whereas those who recovered from MetS had a reduced risk. Conclusion MetS and even preMetS are significant risk factors for HCC. Importantly, improvement in MetS status may help prevent HCC. These findings suggest that early identification and management of MetS could play a key role in liver cancer prevention.