68Ga-FAPI-04 PET/CT in the Diagnosis of Hepatocellular Carcinoma Associated with Cirrhosis: Diagnostic Value, Correlation Between PET Parameters of the Tumor and Its Size, and PIVKA-II Levels

<b>Background/Objectives:</b> Hepatocellular carcinoma remains a major cause of death from cancer globally. While ¹⁸F-FDG PET/CT is commonly used for tumor imaging, its sensitivity is limited, especially due to high liver background uptake. Recently, ⁶⁸Ga-FAPI PET/CT, which targets fibroblast activation protein in tumor stroma, has emerged as a promising diagnostic tool. In this study, we aimed to assess the diagnostic performance of ⁶⁸Ga-FAPI-04 PET/CT in HCC patients with and without liver cirrhosis and to explore the relationship between PET metrics, tumor size, and PIVKA-II serum marker. <b>Methods:</b> In this prospective single-center study, 59 patients with confirmed HCC (37 with cirrhosis, 22 without) underwent ⁶⁸Ga-FAPI-04 PET/CT. The standard dose (1.5-2.0 MBq/kg) was administered intravenously, and imaging was carried out 60 min post-injection. Semi-quantitative parameters including SUVmax, SUVmean, and tumor-to-background ratio were calculated. Diagnostic performance was assessed using histopathology and multimodal imaging. Statistical analyses included the Mann-Whitney U test and Spearman correlation. <b>Results:</b> The overall sensitivity for HCC detection was 89.8%, with a specificity of 60% and accuracy of 87%. Sensitivity and specificity showed a tendency to be lower in cirrhotic compared with non-cirrhotic patients, with a notably higher background liver uptake in cirrhosis (SUVmax 3.60 vs. 1.3, <i>p</i> < 0.001), resulting in lower TBR values (3.7 vs. 7.0, <i>p</i> < 0.001). A strong correlation between SUVmax and tumor size was seen in non-cirrhotic HCC, while a moderate association between SUVmax and PIVKA-II levels was observed in cirrhotic patients. <b>Conclusions:</b>⁶⁸Ga-FAPI-04 PET/CT demonstrates high sensitivity for HCC detection and may serve as a complementary imaging modality, particularly when interpreted through conventional cross-sectional imaging. Image interpretation in cirrhotic livers may be challenging due to increased background uptake and reduced TBR. Associations between PET-derived parameters, tumor size, and serum PIVKA-II levels should be considered hypothesis-generating and require validation in larger, multicenter studies with clinical outcome data.