Editor’s Note: Primary liver cancer is currently the fourth most common malignant tumor and the second leading cause of cancer death in China, posing a serious threat to the health and well-being of the population. Reducing the burden associated with liver cancer remains a major challenge in the fields of public health and chronic disease prevention in China. Optimizing screening strategies for liver cancer populations is an important ongoing focus and direction. On April 15, 2024, the National Health Commission released the “Primary Liver Cancer Diagnosis and Treatment Guidelines (2024 Edition),” recommending the aMAP, aMAP-2, and aMAP-2 Plus series of liver cancer risk scoring developed by the research team of Professor Jinlin Hou/Professor Rong Fan from Southern Medical University’s Southern Hospital for screening and monitoring high-risk liver cancer populations. At the recent 2024 Greater Bay Area Hepatology Summit and the Conference on the Elimination of Viral Hepatitis, Professor Rong Fan delivered an outstanding report titled “Precision Screening for Liver Cancer Patients in China.” Our publication has specially invited Professor Rong Fan to provide an in-depth discussion on this hot topic of concern.
Liver cancer incidence and mortality rates in China are relatively high. What challenges and issues do you see in the current screening methods for liver cancer patients in China in terms of technology and precision?
Professor Rong Fan:Indeed, the incidence and mortality rates of liver cancer in China are significantly high, presenting considerable challenges in the medical field. The issues and challenges in the screening of liver cancer patients, particularly concerning technology and precision, should not be overlooked.
Firstly, the rate of early diagnosis of liver cancer is relatively low, at less than 30%, which is a critical issue we face. Increasing the early diagnosis rate is crucial for reducing mortality rates among liver cancer patients. However, the current technologies and methods for liver cancer screening still have certain limitations, resulting in many early-stage liver cancer patients not being detected in time.
Secondly, China has a large base of chronic liver disease patients, including those with hepatitis B, hepatitis C, fatty liver, and cirrhosis. These patients are all at high risk for liver cancer and require regular screening. However, due to limited resources, comprehensive screening for all patients is not feasible, necessitating efforts to improve the efficiency and precision of screening.
Regarding these issues and challenges, our team has already made some progress in our preliminary work. We have developed a series of tools for assessing liver cancer risk, which help us better identify high-risk individuals, thereby significantly enhancing the efficiency of screening. By promoting and utilizing these tools, we hope to advance early screening and diagnosis of liver cancer, reducing the mortality rate.
When devising precise screening strategies for liver cancer patients in China, how should we consider the impact of factors such as genetic background, lifestyle, and dietary habits?
Professor Rong Fan: These factors indeed need to be carefully considered when formulating precise screening strategies for liver cancer patients in China.
Firstly, the causes of liver cancer in our country are significantly different from those in other countries. The most notable difference is that over 80% of liver cancer cases in China are caused by hepatitis B. This characteristic requires special attention to the screening and monitoring of hepatitis B patients. The progression from hepatitis to cirrhosis and then to liver cancer, often referred to as the “hepatic trilogy,” is particularly pronounced in hepatitis B patients. Therefore, timely detection and treatment of hepatitis B, along with regular liver cancer screening for these patients, are crucial for improving early diagnosis rates and reducing mortality.
Secondly, the awareness and cure rates of hepatitis B in China are still relatively low, which means we need to intensify efforts to identify more hepatitis B patients and include them in liver cancer screening programs. By increasing awareness of hepatitis B and strengthening antiviral treatments and liver cancer screenings for these patients, we can more effectively reduce the incidence and mortality rates of liver cancer.
Moreover, considering the lifestyle and dietary habits of the Chinese population, such as high-fat, high-salt, low-fiber diets, and lack of exercise, these factors may increase the risk of liver cancer. Therefore, in formulating screening strategies, we also need to focus on these high-risk groups and reduce the incidence of liver cancer through health education and lifestyle interventions.
Professor Jinlin Hou led the creation of three liver cancer prediction models— aMAP, aMAP-2, and aMAP-2 Plus. What advantages do these models offer in stratifying and effectively predicting liver cancer risk in China?
Professor Rong Fan: In 2020, Professor Hou Jinlin led an international collaboration to establish a hepatitis cooperation network covering chronic liver disease patients worldwide, involving 29 countries across five continents and 9,684 centers with 17,374 participants. This collaboration resulted in the creation of the world’s first cross-disease, cross-racial liver cancer risk prediction model: the aMAP score. This scoring system allows us to precisely predict liver cancer risk, enabling 50% of low-risk patients to avoid frequent liver cancer screenings, thus effectively saving medical resources.
Building on the foundation of the aMAP score, we conducted further research and optimization, integrating sequential multi-time point data on alpha-fetoprotein (AFP) and circulating free DNA (cfDNA) to enhance and update the original aMAP score, resulting in two more precise prediction models: aMAP-2 and aMAP-2 Plus. These models offer more refined and comprehensive risk predictions for liver cancer, providing us with stronger tools for our screening efforts.
Additionally, we pioneered a sequential liver cancer screening strategy comprising three steps: aMAP, aMAP-2, and aMAP-2 Plus. These steps are akin to a pyramid, each an extension of the previous one and a deeper exploration into risk prediction. The aMAP score is the cornerstone of this pyramid. Its indicators are simple and easily obtained, including age, gender, platelet count, albumin, and total bilirubin, helping clinicians to quickly screen the chronic liver disease population. The aMAP-2 score builds on this by incorporating longitudinal AFP data, enhancing prediction accuracy and better identifying high-risk individuals. Lastly, aMAP-2 Plus integrates multi-time point cfDNA data, further broadening the predictive scope to cover a wider range of liver cancer risk factors.
Our goal is to use this interconnected, progressive screening approach to allow 90% of the low-risk liver cancer population to avoid frequent screenings, focusing medical resources on the remaining 10% who are at very high risk. This ensures they receive timely and effective attention and treatment, improving screening efficiency and reducing overall medical costs. We hope that through precise predictions and effective screening, we can improve early diagnosis rates and reduce mortality for liver cancer in China, bringing hope to many more patients.
With the continuous development and innovation in medical technology, what new screening methods or technologies are being researched or applied in the precision screening of liver cancer?
Professor Rong Fan: As medical technology continues to advance and innovate, the field of precision screening for liver cancer is seeing a surge of new methods and technologies. These innovations extend beyond traditional biology into emerging omics fields, such as proteomics, metabolomics, and radiomics.
In proteomics, scientists are working to identify specific proteins closely associated with the onset and progression of liver cancer, which could serve as biomarkers for early screening. Meanwhile, research in metabolomics is deepening, with analyses of metabolic changes in liver cancer patients shedding light on the mechanisms of disease onset, offering new approaches for early diagnosis.
Additionally, the advancement of radiomics provides new tools for precision screening of liver cancer. High-resolution medical imaging technologies, such as MRI and CT, combined with computer-assisted diagnostic systems, enable precise localization and diagnosis of liver cancer lesions.
In addition to these traditional research areas, some emerging technologies are being explored and applied. For example, using Whole Genome Sequencing (WGS) multi-dimensional variant detection technology combined with traditional methods, we can screen for nodules in the liver against a background of cirrhosis, thereby establishing a liver nodule screening model. This model can assist in clinical diagnostics by helping to distinguish between benign and malignant liver nodules, providing effective reference indices for clinical use.
However, these new technologies and methods also face challenges in terms of accessibility and cost. Many new technologies, while highly accurate in diagnosis, are difficult to disseminate nationwide due to high equipment costs and complex operations. Therefore, reducing the costs and increasing the accessibility of new technologies are pressing issues that need to be addressed.
In this regard, the three series of scoring models we proposed earlier have significant practical value. These scoring models can serve as a foundation for the dissemination of new technologies, identifying populations at very high risk for liver cancer and then promoting new techniques and methods among these groups. This approach not only enhances the early diagnosis rate of liver cancer but also reduces the waste of medical resources, achieving a seamless integration of early work with advanced technologies.
