CRAFITY and AFP/PIVKA-II Kinetics Predict Prognosis in Hepatocellular Carcinoma on Immunotherapy

The CRAFITY score, integrating baseline C-reactive protein (CRP) and alpha-fetoprotein (AFP), has been validated as a prognostic biomarker in hepatocellular carcinoma (HCC) treated with immunotherapy, but many patients present with non-elevated AFP, limiting its accuracy. This study evaluated a composite model incorporating the CRAFITY score with AFP/PIVKA-II kinetic changes.

We retrospectively enrolled 69 patients with unresectable HCC (BCLC stage B/C) receiving immunotherapy between September 2021 and June 2023. Baseline CRP, AFP, and PIVKA-II, as well as 4-week changes, were recorded. The CRAFITY-100 RULE combined CRAFITY (0-2) with AFP/PIVKA-II kinetics (0-3), yielding three risk levels (I-III). Clinical outcomes included objective response (OR) and overall survival (OS).

Of the cohort, 10 (14.5%), 29 (42%), and 30 (43.5%) patients had CRAFITY scores 0, 1, and 2, respectively, but this score did not clearly stratify OS (median 24, 12, and 15 months; p = 0.267). In contrast, the CRAFITY-100 RULE classified 5 (7.3%), 35 (50.7%), and 29 (42%) patients into levels I-III, respectively, with significantly different survival (median OS 24, 15, and 7 months; p = 0.048). OR rates were lowest at level III (17%). Time-dependent ROC analysis confirmed superior discrimination of CRAFITY-100 RULE over CRAFITY scores at 6 months (AUROC 0.673 vs. 0.604) and 12 months (0.732 vs. 0.656).

The CRAFITY-100 RULE provided clearer stratification and higher discrimination. This simple model integrating baseline and dynamic biomarkers may assist clinical decision-making in unresectable HCC treated with immunotherapy.