Abstract

Alpha-fetoprotein (AFP) checkup with abdominal ultrasonography for hepatocellular carcinoma (HCC) surveillance remains controversial. We evaluated a serial AFP-increase and high AFP levels in the prediction of HCC. At-risk patients with chronic liver disease underwent HCC surveillance with trimonthly AFP measurement were included and categorized into HCC and non-HCC groups. Their AFP levels at 12, 9, and 6months (-6M) before the outcome date were evaluated. Group-based trajectory analysis and multivariable regression analysis were performed to identify AFP trajectories as risk predictors for HCC. Overall, 2776 patients were included in the HCC (n=326) and non-HCC (n=2450) groups. Serial AFP levels were significantly higher in the HCC than the non-HCC groups. Trajectory analysis identified AFP-increase group (11%) increased 24-fold risks of HCC compared with the AFP-stable (89%) group. Compared with patients without the AFP-increase, a serial 3-month AFP-increase ≥10% elevated HCC risk by 12.1-fold (95% CI: 6.5-22.4) in 6months, and the HCC risks increased 13-60 fold in patients with cirrhosis, hepatitis B, or C receiving antiviral therapy, or AFP levels <20ng/ml. Combining serial AFP-increase ≥10% and AFP ≥20ng/ml at -6M significantly increased 41.7-fold (95% CI: 13.8-126.2) HCC risks. In patients who underwent biannual AFP checkups, those with both 6-month AFP-increase ≥10% and AFP ≥20ng/ml increased 22.1-fold (95% CI: 12.52-39.16) HCC risks in 6months. Most HCCs were detected at an early stage. Serial 3-6-month AFP-increase of ≥10% previously and AFP level of ≥20ng/ml significantly increased HCC risks in 6months.

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