⁶⁸Ga-FAPI PET/CT reveals fibroblast activation beyond biochemical fibrosis scores in chronic liver disease

Purpose To evaluate the role of ⁶⁸Ga-FAPI PET/CT in assessing fibroblast activity in patients with chronic liver disease (CLD). We studied FAPI liver uptake and its relationship with functional disease severity (Child-Pugh score) and biochemical fibrosis indices (APRI and FIB-4). Methods This prospective study included 10 control subjects without liver disease and 33 patients with CLD across Child–Pugh classes A–C. Biochemical evaluation included liver function tests, APRI, and FIB-4 scores. Participants underwent ⁶⁸Ga-FAPI PET/CT, and SUVmax, SUVmean, FAPI-avid liver volume (FLV), and total liver FAPI activity (TLFA) were quantified. Correlation and regression analyses were done between PET parameters, biochemical markers, and Child–Pugh classes. Diagnostic performance was assessed using receiver operating characteristic analysis and effect size estimation. Discordance analysis was done for PET-derived fibroblast activity, Child–Pugh classes, and biochemical fibrosis indices. Result CLD patients demonstrated significantly raised PET-derived parameters and deranged biochemical markers compared to controls ( p < 0.05). Biochemical markers worsened progressively across Child–Pugh classes ( p < 0.05), whereas SUVmax showed a non-significant increasing trend. Compared with controls, Child–Pugh A patients had significantly higher SUVmax, FIB-4, and APRI indices with high discrimination (AUC = 1.00, 1.00, and 0.965, respectively). No significant association was noted between PET parameters, Child–Pugh class, or biochemical fibrosis indices. Only 17% of SUVmax variance was explained by biochemical parameters. Discordance analysis showed High SUVmax in 37.5% and 58.3% of patients with intermediate FIB-4 and mild–moderate APRI categories, respectively. All patients with advanced fibrosis had persistently raised FAPI uptake. Conclusion ⁶⁸Ga-FAPI PET/CT shows significant fibroblast activation in early CLD with intrahepatic heterogeneity. It shows concordance with the severity of biochemical fibrosis indices at extremes. PET-derived fibroblast activity shows discordance with functional disease severity and intermediate-grade biochemical fibrosis. These findings suggest a complementary role for FAPI PET in characterizing FAP-associated stromal activity beyond conventional biochemical fibrosis indices in CLD.