There are limited data on the downstream effects of hepatocellular carcinoma (HCC) surveillance, including the frequency of false-positive results. We aimed to quantify the incidence of indeterminate nodules (INs) and the follow-up testing needed to resolve these findings among patients enrolled in a structured HCC surveillance program. We retrospectively analyzed adult patients with cirrhosis enrolled in a structured HCC surveillance program in a large tertiary care center. Outcomes included surveillance benefits, defined as early HCC detection, and harm, defined as INs prompting additional diagnostic evaluation. Among 999 patients followed for a median of 2.2 years, HCC surveillance imaging was consistently completed every 6, 9, and 12 months in 46%, 51%, and 68% of patients, respectively. Of 256 (25.6%) patients with abnormal imaging, 69 (27.0%) were diagnosed with HCC and 187 (73.0%) with INs. Most HCC (n = 54, 78.3%) were found within Milan criteria. Among those with an IN, 78.1% returned to ultrasound surveillance after a median of 2 (interquartile range [IQR], 1-3) negative computed tomography (CT)/magnetic resonance imaging (MRI) scans, and 21.9% continued CT/MRI imaging (median, 1; IQR, 1-2). Eleven patients underwent diagnostic liver biopsy. Hypoalbuminemia, thrombocytopenia, and larger nodule size were independently associated with HCC diagnosis. In conclusion, 1 in 4 patients enrolled in an HCC surveillance program had abnormal surveillance imaging, but three-fourths of the lesions were INs, resulting in downstream harm. Improved risk-stratification tools are needed to identify nodules that are benign to reduce follow-up diagnostic evaluation.
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