Disease Diagnosis | Revolutionizing Early Liver Cancer Screening and Management with iXLAB Algo-GADA

"Multicenter Study in Evaluating the Combination of Multiple Indicators in Hepatocellular Carcinoma (HCC) Screening", led by Peking University and involving Peking University People's Hospital, Peking University Shenzhen Hospital, the First Affiliated Hospital of Zhejiang University School of Medicine, the First Affiliated Hospital of Fujian Medical University, the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology, Shenzhen Third People's Hospital, the Second Affiliated Hospital of Chongqing Medical University, the Second Hospital of Shanxi Medical University, Qinghai Provincial People's Hospital, and the First Hospital of Sanming City, in collaboration with Snibe, has successfully concluded!

Background

Globally, primary liver cancer ranks as the fourth most common cancer and the fourth leading cause of cancer-related mortality. Nearly half of the global new HCC cases and deaths occur in Asia, particularly in regions with high hepatitis B virus (HBV) prevalence. HBV infection is the main cause of HCC in these regions, and the five-year survival rate of liver cancer patients is alarmingly low, under 20%, which represents a significant public health challenge worldwide.

In the WHO-published Global Health Sector Strategy (GHSS), a 90% reduction in the incidence of new viral hepatitis infections and a 65% reduction in mortality rates by 2030 is set as a strategic goal. Early diagnosis is crucial to improve survival rates, with imaging methods currently being the primary approach for screening and diagnosis of liver cancer. However, the accuracy of imaging-based screening can be limited by factors such as the experience of operators and the patient’s obesity level. Furthermore, imaging methods have limited sensitivity in detecting small or early-stage liver cancer, with detection rates below 65%. Therefore, new clinical tools are essential for more effective early screening and diagnosis of liver cancer.

Project Overview

The "Multicenter Study in Evaluating the Combination of Multiple Indicators in HCC Screening" is led by Peking University, with support from Snibe and participation from 10 clinical institutions. The project follows a "1+1+10 Industry-Academia-Research-Medicine" collaboration model and aims to evaluate the clinical value of combining alpha-fetoprotein (AFP), Protein induced by vitamin K absence-II (PIVKA-II), and patient demographics (e.g., age and sex) for early liver cancer screening, and to establish an auxiliary diagnostic model.

• This is a prospective clinical trial (Registration Number: ChiCTR2300071404), officially launched on June 25, 2022.

After over two years of research, the study successfully included a total of 28,273 cases, with 4,609 external independent validation cases from Zhengzhou University First Affiliated Hospital and Shanxi Medical University First Hospital.

• The study was approved by the Biomedical Ethics Committee of Peking University (Approval No. IRB00001052-22082), the ethics committees of all 10 participating institutions, and received the approval of the Ministry of Science and Technology's Human Genetics Office (Approval No. 2023 CJ1465).

Results

This multicenter study, based on big data from chronic HBV populations in China, established the GADA model, which incorporates factors such as patient sex, age, and serum markers like AFP and PIVKA-II for analysis.

• Validation across 10 hospitals showed that the GADA model has excellent diagnostic efficacy for HBV-related liver cancer, with an area under the ROC curve (AUC) of 0.920 (95% CI: 0.916-0.923), and high sensitivity (82.92%) and specificity (85.55%).?
• External validation from Zhengzhou University and Shanxi Medical University also demonstrated the model's excellent diagnostic performance.

Based on the GADA model, Peking University collaborated with Snibe to develop the iXLAB Algo-GADA software for early screening of liver cancer. This software integrates data collection, processing, ?and reporting, providing an intelligent auxiliary diagnostic system for dynamic screening and monitoring of high-risk populations, such as chronic HBV patients. It marks a significant step toward "smart" healthcare in the prevention and treatment of chronic liver diseases.

• At present, the software has obtained the computer software copyright of the State Intellectual Property Office of the People's Republic of China (Certificate No. 13305554).

Key Advantages of the Multicenter Study

Conclusion

The multicenter study established the GADA model, an effective auxiliary diagnostic system, which incorporates sex, age, AFP, and PIVKA-II levels for early liver cancer diagnosis. It holds a unique, independently patented technology, making it a promising tool for improving liver cancer diagnosis worldwide. With an AUC of 0.920, and sensitivity and specificity rates of 82.92% and 85.55%, the model represents a significant step in the fight against liver cancer.

In this multicenter study, AFP and PIVKA-II reagent kits were all provided by Snibe.

References:

[1] Rumgay H, Arnold M, Ferlay J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol. 2022; 77(6): 1598-1606.