PIVKA-II as a surrogate biomarker for therapeutic response in Non-AFP-secreting hepatocellular carcinoma
Abstract Background Alpha-fetoprotein (AFP) is a key biomarker for hepatocellular carcinoma (HCC), but 30–40% of cases are AFP-negative. Prothrombin induced by vitamin K absence II (PIVKA-II) is more sensitive for HCC detection, though its role in systemic therapy remains underexplored. This study a...
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BMC
2025-02-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-025-13568-4 |
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| author | San-Chi Chen Hsiang-Ling Ho Chien-An Liu Yi‑Ping Hung Nai-Jung Chiang Ming‑Huang Chen Yee Chao Muh-Hwa Yang |
| author_facet | San-Chi Chen Hsiang-Ling Ho Chien-An Liu Yi‑Ping Hung Nai-Jung Chiang Ming‑Huang Chen Yee Chao Muh-Hwa Yang |
| author_sort | San-Chi Chen |
| collection | DOAJ |
| description | Abstract Background Alpha-fetoprotein (AFP) is a key biomarker for hepatocellular carcinoma (HCC), but 30–40% of cases are AFP-negative. Prothrombin induced by vitamin K absence II (PIVKA-II) is more sensitive for HCC detection, though its role in systemic therapy remains underexplored. This study aimed to evaluate PIVKA-II in non-AFP-secreting HCC treated with systemic therapy. Methods Patients with unresectable HCC undergoing systemic therapy were enrolled. Baseline imaging and PIVKA-II levels were recorded. After 8–12 weeks of treatment, response was evaluated through imaging and repeat PIVKA-II measurements. Results A total of 116 treatment assessments from 61 cases were analyzed. Baseline PIVKA-II levels correlated with tumor size, but not tumor number or liver function. PIVKA-II regression (≥ 50% reduction) and progression (≥ 50% increase) were defined using ROC analysis. Imaging showed 71.0% objective response in the regression group, 50.0% stable disease in the stable group, and 83.7% progressive disease in the progression group (p < 0.001). This association held for targeted therapies, immune checkpoint inhibitors, and chemotherapy. Progression-free survival (PFS) for the regression, stable, and progression groups was non-reached, 6.7, and 3.2 months (p = 0.0002), and overall survival (OS) was non-reached, non-reached, and 18.5 months (p = 0.02). Conclusions This study is the first to establish the “50–50 rule” for PIVKA-II response in non-AFP-secreting HCC treated with systemic therapy, highlighting its value as a surrogate marker for radiological outcomes and prognosis. |
| format | Article |
| id | doaj-art-4813a67c995948b9b8e71b9fce39062f |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-4813a67c995948b9b8e71b9fce39062f2025-02-09T12:41:27ZengBMCBMC Cancer1471-24072025-02-012511810.1186/s12885-025-13568-4PIVKA-II as a surrogate biomarker for therapeutic response in Non-AFP-secreting hepatocellular carcinomaSan-Chi Chen0Hsiang-Ling Ho1Chien-An Liu2Yi‑Ping Hung3Nai-Jung Chiang4Ming‑Huang Chen5Yee Chao6Muh-Hwa Yang7Institute of Clinical Medicine, National Yang Ming Chiao Tung UniversityDepartment of Pathology and Laboratory Medicine, Taipei Veterans General HospitalDepartment of Radiology, Taipei Veterans General HospitalInstitute of Clinical Medicine, National Yang Ming Chiao Tung UniversitySchool of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityInstitute of Clinical Medicine, National Yang Ming Chiao Tung UniversityDepartment of Internal Medicine, Central Clinical & HospitalInstitute of Clinical Medicine, National Yang Ming Chiao Tung UniversityAbstract Background Alpha-fetoprotein (AFP) is a key biomarker for hepatocellular carcinoma (HCC), but 30–40% of cases are AFP-negative. Prothrombin induced by vitamin K absence II (PIVKA-II) is more sensitive for HCC detection, though its role in systemic therapy remains underexplored. This study aimed to evaluate PIVKA-II in non-AFP-secreting HCC treated with systemic therapy. Methods Patients with unresectable HCC undergoing systemic therapy were enrolled. Baseline imaging and PIVKA-II levels were recorded. After 8–12 weeks of treatment, response was evaluated through imaging and repeat PIVKA-II measurements. Results A total of 116 treatment assessments from 61 cases were analyzed. Baseline PIVKA-II levels correlated with tumor size, but not tumor number or liver function. PIVKA-II regression (≥ 50% reduction) and progression (≥ 50% increase) were defined using ROC analysis. Imaging showed 71.0% objective response in the regression group, 50.0% stable disease in the stable group, and 83.7% progressive disease in the progression group (p < 0.001). This association held for targeted therapies, immune checkpoint inhibitors, and chemotherapy. Progression-free survival (PFS) for the regression, stable, and progression groups was non-reached, 6.7, and 3.2 months (p = 0.0002), and overall survival (OS) was non-reached, non-reached, and 18.5 months (p = 0.02). Conclusions This study is the first to establish the “50–50 rule” for PIVKA-II response in non-AFP-secreting HCC treated with systemic therapy, highlighting its value as a surrogate marker for radiological outcomes and prognosis.https://doi.org/10.1186/s12885-025-13568-4PIVKA-IIDes-γ-carbonylated prothrombin (DCP)Alpha-fetoprotein (AFP)Hepatocellular carcinoma (HCC)Biomarker |
| spellingShingle | San-Chi Chen Hsiang-Ling Ho Chien-An Liu Yi‑Ping Hung Nai-Jung Chiang Ming‑Huang Chen Yee Chao Muh-Hwa Yang PIVKA-II as a surrogate biomarker for therapeutic response in Non-AFP-secreting hepatocellular carcinoma BMC Cancer PIVKA-II Des-γ-carbonylated prothrombin (DCP) Alpha-fetoprotein (AFP) Hepatocellular carcinoma (HCC) Biomarker |
| title | PIVKA-II as a surrogate biomarker for therapeutic response in Non-AFP-secreting hepatocellular carcinoma |
| title_full | PIVKA-II as a surrogate biomarker for therapeutic response in Non-AFP-secreting hepatocellular carcinoma |
| title_fullStr | PIVKA-II as a surrogate biomarker for therapeutic response in Non-AFP-secreting hepatocellular carcinoma |
| title_full_unstemmed | PIVKA-II as a surrogate biomarker for therapeutic response in Non-AFP-secreting hepatocellular carcinoma |
| title_short | PIVKA-II as a surrogate biomarker for therapeutic response in Non-AFP-secreting hepatocellular carcinoma |
| title_sort | pivka ii as a surrogate biomarker for therapeutic response in non afp secreting hepatocellular carcinoma |
| topic | PIVKA-II Des-γ-carbonylated prothrombin (DCP) Alpha-fetoprotein (AFP) Hepatocellular carcinoma (HCC) Biomarker |
| url | https://doi.org/10.1186/s12885-025-13568-4 |
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