The clinical management of hepatocellular carcinoma in China: Progress and challenges

Article information

Clin Mol Hepatol. 2023;29(2):339-341
Publication date (electronic) : 2023 March 16
doi :
Liver Research Center, Beijing Friendship Hospital, Capital Medical University; The National Clinical Research Center for Digestive Diseases, Beijing, China
Corresponding author : Jidong Jia Liver Research Center, Beijing Friendship Hospital, Capital Medical University; The National Clinical Research Center for Digestive Diseases, Beijing 100050, China Tel: +86-010-63139246, Fax: +86-010-63139246, E-mail:
Editor: Yuri Cho, National Cancer Center, Korea
Received 2023 February 28; Revised 2023 March 13; Accepted 2023 March 13.

Primary liver cancer, which mainly comprises hepatocellular carcinoma (HCC), poses a significant public health burden, especially in China and other Asian countries/territories [1,2]. The major etiology of HCC in China is chronic hepatitis B virus (HBV) infection, which confers a more malignant phenotype in terms of higher serum level of alpha-fetoprotein (AFP) and rapid progression [3,4]. Primary prevention through universal vaccination against hepatitis B has successfully reduced HCC incidence and mortality in China [5]. In prospective randomized clinical trials, screening and surveillance of HCC in high-risk populations identified more cases at early stages and improved the clinical outcomes compared with no surveillance [6,7]. High-quality research from China on the diagnosis, staging, and treatment of HCC has provided important evidence for developing guidelines [8-10].

In an article published in the current issue of Clinical and Molecular Hepatology, Dr. Xie and colleagues [11] from Zhongshan Hospital, Fudan University, Shanghai, China, provided an excellent overview of the advances in the clinical management of HCC in China. This review article depicted the key points of the 2022 updated guidelines and the big picture of real-world clinical HCC management in China, while focusing on the rationale and evidence supporting the recommendations. First, the surveillance of HCC by AFP measurement and ultrasonography every six months is recommended in the high-risk population, and the diagnosis of suspected nodules can be confirmed by enhanced multiphasic CT/MRI. Second, the China Liver Cancer Staging System (CNLC) is recommended for use because it is better reflective of individual subgroup survival, facilitating allocation of therapeutic modalities. Third, the University of California San Francisco criteria for liver transplant are adopted and offer HCC patients more transplant opportunities than the Milan criteria but yield a similar post-transplant outcome. Last, this article also discussed multimodal and high-intensity anti-tumor strategies for HCC patients in real-life practices in China, such as the addition of immunotherapy-based systemic therapy to local modalities, which may improve the chance of receiving curative therapy and long-term survival for patients with nonearly-stage HCC.

Although great progress has been achieved, control and management of HCC remain significant challenges in China. First, the total burden of HCC is high, although the age-standardized incidence and mortality rates are declining [12]. The high burden is mainly due to the huge number of people living with chronic HBV infection, who carry a high risk of HCC development and require long-term antiviral therapy to reduce progression to cirrhosis and HCC. However, the diagnosis and treatment rates of chronic HBV infection are low despite the increasing trend [13,14]. Second, due to poor adherence to long-term HCC surveillance [15], most patients with HCC are in intermediate or advanced stage, which carries a very poor survival rate since such patients are not eligible for curative therapy [16]. Third, compliance with clinical HCC management guidelines must be improved. Real-life practice of HCC management is highly heterogeneous and subject to personal opinion, local expertise, or available resources rather than clinical study evidence and guideline recommendations. Last, survival disparity exists between populations with different insurance types, which may reflect the different socioeconomic statuses of the patients [17].

To meet the aforementioned challenges, consensus on the primary, secondary, and tertiary prevention methods of primary liver cancer has been published in China in 2018, 2021, and 2022, respectively [18-20]. Universal infant HBV vaccination combined with a triple elimination program to prevent mother-to-child transmission of human immunodeficiency virus, syphilis, and HBV [21], together with large-scale diagnosis and treatment of CHB will eventually reduce the incidence of HCC. Population-based cancer screening and surveillance programs, including those for HCC, in rural areas are wellplanned and pending implementation [22]. HCC surveillance will increase the opportunity for curative treatment [23]. Furthermore, the advent and validation of novel serum biomarkers and models may also facilitate surveillance and identification of early-stage HCC [24]. Finally, the timely updating and advocating of evidence-based HCC guidelines will help improve the quality of care in real-world practice to improve clinical outcomes of HCC patients in China.


Authors’ contributions

Drafting of the manuscript: Shan Shan; Critical revision of the manuscript: Jidong Jia.

Conflicts of Interest

The authors have no conflicts to disclose.


This work was supported by the National Natural Science Foundation of China (No. 82000569 and 82270603).



hepatocellular carcinoma


hepatitis B virus




China Liver Cancer Staging System


1. International Agency for Research on Cancer. Data visualization tools for exploring the global cancer burden in 2020. IARC web site, <>. Accessed 26 Feb 2023.
2. Torimura T, Iwamoto H. Optimizing the management of intermediate-stage hepatocellular carcinoma: Current trends and prospects. Clin Mol Hepatol 2021;27:236–245.
3. Dhanasekaran R, Nault JC, Roberts LR, Zucman-Rossi J. Genomic medicine and implications for hepatocellular carcinoma prevention and therapy. Gastroenterology 2019;156:492–509.
4. Liu Z, Mao X, Jiang Y, Cai N, Jin L, Zhang T, et al. Changing trends in the disease burden of primary liver cancer caused by specific etiologies in China. Cancer Med 2019;8:5787–5799.
5. Qu C, Chen T, Fan C, Zhan Q, Wang Y, Lu J, et al. Efficacy of neonatal HBV vaccination on liver cancer and other liver diseases over 30-year follow-up of the Qidong hepatitis B intervention study: a cluster randomized controlled trial. PLoS Med 2014;11:e1001774.
6. Yang B, Zhang B, Xu Y, Wang W, Shen Y, Zhang A, et al. Prospective study of early detection for primary liver cancer. J Cancer Res Clin Oncol 1997;123:357–360.
7. Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol 2004;130:417–422.
8. Xu RH, Wei W, Krawczyk M, Wang W, Luo H, Flagg K, et al. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma. Nat Mater 2017;16:1155–1161.
9. Wei X, Jiang Y, Zhang X, Feng S, Zhou B, Ye X, et al. Neoadjuvant three-dimensional conformal radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus: A randomized, open-label, multicenter controlled study. J Clin Oncol 2019;37:2141–2151.
10. Shao G, Bai Y, Yuan X, Chen X, Gu S, Gu K, et al. Ramucirumab as second-line treatment in Chinese patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib (REACH-2 China): A randomised, multicentre, doubleblind study. EClinicalMedicine 2022;54:101679.
11. Xie D, Shi J, Zhou J, Fan J, Gao Q. Clinical practice guideline and real-life practice in hepatocellular carcinoma: Chinese perspective. Clin Mol Hepatol 2023;29:206–216.
12. Yu S, Wang H, Hu T, Yu C, Liu H, Chen X, et al. Disease burden of liver cancer attributable to specific etiologies in China from 1990 to 2019: An age-period-cohort analysis. Sci Prog 2021;104:368504211018081.
13. Li M, Zhao L, Zhou J, Sun Y, Wu X, Ou X, et al. Changing clinical care cascade of patients with chronic hepatitis B in Beijing, China. Lancet Reg Health West Pac 2021;16:100249.
14. Cui F, Blach S, Manzengo Mingiedi C, Gonzalez MA, Sabry Alaama A, Mozalevskis A, et al. Global reporting of progress towards elimination of hepatitis B and hepatitis C. Lancet Gastroenterol Hepatol 2023;8(4):332–342.
15. Ji M, Liu Z, Chang ET, Yu X, Wu B, Deng L, et al. Mass screening for liver cancer: results from a demonstration screening project in Zhongshan City, China. Sci Rep 2018;8:12787.
16. Lin J, Zhang H, Yu H, Bi X, Zhang W, Yin J, et al. Epidemiological characteristics of primary liver cancer in mainland China from 2003 to 2020: A representative multicenter study. Front Oncol 2022;12:906778.
17. Wu J, Liu C, Wang F. Disparities in hepatocellular carcinoma survival by insurance status: A population-based study in China. Front Public Health 2021;9:742355.
18. Prevention of Infection Related Cancer (PIRCA) Group, Specialized Committee of Cancer Prevention and Control, Chinese Preventive Medicine Association, ; Non-communicable & Chronic Disease Control and Prevention Society, Chinese Preventive Medicine Association, ; Health Communication Society, Chinese Preventive Medicine Association. [Strategies of primary prevention of liver cancer in China: expert consensus (2018)]. Zhonghua Yu Fang Yi Xue Za Zhi 2019;53:36–44. Chinese.
19. Nan Y, Xu X, Gao Y, Wang R, Li W, Yang M, et al, ; Chinese Society of Hepatology, Chinese Medical Association. Consensus on the secondary prevention of primary liver cancer. Hepatol Int 2021;15:1289–1300. Erratum in: Hepatol Int 2022;16:484-485.
20. Chinese Society of Hepatology, Chinese Medical Association. [The consensus on tertiary prevention of primary liver cancer (2022 version)]. Zhonghua Gan Zang Bing Za Zhi 2022;30:832–845. Chinese.
21. Liu Z, Chen Z, Cui F, Ding Y, Gao Y, Han G, et al. Management algorithm for prevention of mother-to-child transmission of hepatitis B virus (2022). J Clin Transl Hepatol 2022;10:1004–1010.
22. Li J, Li H, Zeng H, Zheng R, Cao M, Sun D, et al. A study protocol of population-based cancer screening cohort study on esophageal, stomach and liver cancer in rural China. Chin J Cancer Res 2020;32:540–546.
23. Sohn W, Kang D, Kang M, Guallar E, Cho J, Paik YH. Impact of nationwide hepatocellular carcinoma surveillance on the prognosis in patients with chronic liver disease. Clin Mol Hepatol 2022;28:851–863.
24. Yu JH, Cho SG, Jin YJ, Lee JW. The best predictive model for hepatocellular carcinoma in patients with chronic hepatitis B infection. Clin Mol Hepatol 2022;28:351–361.

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