Abstract
BACKGROUND: Discrepancies and uncertainties persist across various guidelines regarding specific age categories and their association with the risk of hepatocellular carcinoma (HCC). Simultaneously, a more nuanced examination is warranted to ascertain whether the association between age and HCC risk adheres strictly to a linear pattern. AIMS: To elucidate the relationship between age and risk of HCC in individuals with hepatitis B virus (HBV)-related cirrhosis. METHODS: A retrospective study conducted across two medical centers enrolled individuals with HBV-related cirrhosis, treating baseline age as a categorical variable to assess the risk of developing HCC. Restricted cubic spline regression was employed to scrutinize potential non-linear associations between age and HCC risk. RESULTS: Of the 434 patients recruited, over a median antiviral treatment duration of 43 months, HCC developed in 45 patients. Baseline age exhibited an independent association with on-treatment HCC risk, demonstrating a non-linear parabolic-like pattern with a threshold value of 59. Below the threshold, age was linked to an increased risk of HCC (aHR 1.104; p = 0.004), while this heightened risk persisted above the threshold. In comparison to the middle-aged group, the youth group was less prone to HCC development (HR 0.3; p = 0.001). These associations remained robust even after adjustments for covariates. CONCLUSIONS: The interplay between baseline age and on-treatment HCC risk exhibited a non-linear, parabolic-like trajectory. Early initiation of antiviral therapy is recommended to mitigate the escalating risk of HCC in individuals with HBV-related cirrhosis. Additionally, enhanced monitoring for HCC is advised for individuals initiating antiviral therapy above the age of 50 years. TRIAL REGISTRATION: CR-HepB (China Registry of Hepatitis B) is a nationwide hospital-based electronic platform in China, used to demonstrate the clinical pattern and treatment profile of chronic HBV infection, evaluate long-term efficacy and safety of antiviral therapy and provide real-world evidence for policy-making in China.Up to 2018, 47 hospitals have joined the CR-HepB and our hospital is one of the branch centers. CLINICALTRIALS: gov ID: NCT03108794. Registration Date: June 30, 2012.