Dear Editor,
Hepatocellular carcinoma (HCC) ranks the fourth most common cancer globally, with approximately 905,000 new cases and 830,000 deaths in 2020 [
1]. It was evaluated that the surveillance participation rate in population aged 35 to 74 in China is 37.5–62.3% [
2]. Despite the existence of national surveillance guidelines, implementing a comprehensive nationwide HCC surveillance program remains challenging due to China’s extremely large population and uneven development across regions, with about 466,000 new cases annually, accounting for almost half of the global HCC incidence [
3]. While hepatitis B virus (HBV) infection remains the primary risk factor in China, other etiologies including hepatitis C, alcohol abuse, and nonalcoholic fatty liver disease are becoming increasingly prevalent.
Early detection of HCC through regular surveillance can significantly improve outcomes, as curative interventions are feasible in early-stage disease [
4]. International guidelines recommend semi-annual abdominal ultrasound with or without alpha-fetoprotein (AFP) for high-risk patients [
5,
6]. A guideline from China also suggested that HCC surveillance including ultrasound and AFP should be performed every 6 months for patients at high-risk [
7]. However, a metaanalysis revealed that only 37% of HCC cases are diagnosed via surveillance globally [
8], with patient nonadherence emerging as a major barrier, largely due to lack of awareness and education.
To assess patients’ understanding of HCC surveillance, we conducted an 8-item questionnaire survey on 292 highrisk patients with chronic HBV infection (136 with cirrhosis and 156 without cirrhosis) at two Chinese outpatient clinics from July 2022 to June 2023. The complete questionnaire is available in
Table 1. The results revealed significant misconceptions about HCC surveillance among these patients, highlighting both overestimation and underestimation of its value.
Most patients overestimated surveillance effectiveness, with 61.6% believing it could prevent HCC development. This misconception may lead to unrealistic expectations and potential disappointment. Additionally, 41.8% expected surveillance to reduce 5-year mortality by 60% or more, far exceeding the actual benefit demonstrated in clinical studies [
4]. 76.0% failed to recognize that abdominal ultrasound has a high rate of missed diagnosis of HCC. These misconceptions about HCC surveillance are illustrated in
Figure 1.
Conversely, underestimation of surveillance importance was also prevalent. Alarmingly, 60.6% thought surveillance was only necessary when symptomatic, despite early-stage HCC often being asymptomatic. This belief could lead to delayed diagnosis and missed opportunities for curative treatment. Moreover, 38.4% of high-risk patients believed they didn’t need regular surveillance at all, a concerning finding that underscores the urgent need for patient education.
Our study revealed a strong correlation between educational level and survey performance. Among patients with junior high school education or lower, 61.5% answered 3 or fewer questions correctly, compared to only 11.3% of those with a bachelor’s degree. This disparity highlights the need for tailored educational interventions, particularly for patients with lower educational levels. The detailed breakdown of correct answers by educational level is presented in
Supplementary Figure 1.
The timing of surveillance also showed misconceptions, with 17.5% of patients believing that annual or less frequent surveillance would be adequate, contrary to the recommended 6-month interval. This could result in delayed diagnosis and poorer outcomes, as demonstrated by recent studies [
9,
10].
These findings have significant clinical implications. First, they highlight the urgent need for comprehensive education programs on HCC surveillance, tailored to different educational levels. Such programs should address both overestimation and underestimation of surveillance benefits, emphasizing its importance while setting realistic expectations. Second, healthcare providers should actively engage in long-term care and education for high-risk patients, rather than passively waiting for them to seek surveillance. This may require improvements in healthcare delivery systems, including reminder systems and patient navigation programs [
11]. Third, the development of more accurate and accessible HCC surveillance tools is crucial. While ultrasound remains the primary surveillance tool, its limitations in certain patient populations necessitate research into alternative or complementary methods [
10].
Our study has several limitations that warrant consideration. First, its two-center design in tertiary hospitals may limit generalizability to other healthcare settings or regions in China. Second, the questionnaire, while comprehensive, may not capture all aspects of patients’ understanding of HCC surveillance and we failed to ask the participants about their actual surveillance of HCC, due to the small number of doctors assisting in the study. The closed-ended questions might have led to response bias. Third, our cross-sectional design prevents us from assessing how patients’ knowledge changes over time or after educational interventions. Fourth, we didn’t explore the reasons behind patients’ misconceptions. Lastly, while we found a correlation between educational level and survey performance, other factors such as socioeconomic status, healthcare access, and previous medical experiences were not accounted for. Additionally, our study focused solely on patients with HBV infection, and the findings may not fully represent the perceptions of all HCC high-risk groups. Future multicenter, longitudinal studies with mixed-methods approaches could address these limitations and provide a more comprehensive understanding of HCC surveillance perceptions among high-risk populations.
In conclusion, our study reveals a critical gap in knowledge about HCC surveillance among high-risk patients with chronic HBV infection in China. Addressing this gap through targeted education, improved healthcare delivery, and enhanced surveillance strategies could significantly improve early detection rates and ultimately reduce HCCrelated mortality. Future research should focus on developing and evaluating effective educational interventions, optimizing surveillance protocols for diverse patient populations, and exploring novel surveillance technologies to overcome current limitations.
FOOTNOTES
-
Authors’ contribution
Lei Cai: study concept, design, drafting, and statistical analysis; Chao Li: data extraction, Interpretation of data, and critical revision of the manuscript; Li-Yang Sun: interpretation of data, drafting, and critical revision of the manuscript; Yong-Kang Diao: interpretation of data and critical revision of the manuscript; Mingda Wang: interpretation of data and critical revision of the manuscript; Tian Yang: study concept, design, drafting, and statistical analysis.
-
Conflicts of Interest
The authors have no conflicts to disclose.
SUPPLEMENTAL MATERIAL
Supplementary material is available at Clinical and Molecular Hepatology website (
http://www.e-cmh.org).
Supplementary Figure 1.
(A) Considerate number of high-risk patients (38.4%) held that they didn’t need regular hepatocellular carcinoma (HCC) surveillance. (B) 17.5% participants mistakenly believed that the interval of HCC surveillance should be longer than 6 months. (C) Percentage of participants with different levels of education who correctly answered 3, 4 to 5 and 6 to 7 questions, respectively, in their respective populations.
Figure 1.Patients’ perceptions of hepatocellular carcinoma (HCC) surveillance. (A) Most patients held that regular HCC surveillance could prevent the development of HCC. (B) Most patients believed that abdominal ultrasound always detects HCC if present. (C) 41.8% of patients believed that the 5-year mortality of HCC patients would be reduced by 60% or more with regular surveillance, which exceeds the actual benefit demonstrated in clinical studies. (D) 60.6% patients believed that surveillance was only necessary when patients had complaints. (E) 30.8% patients didn’t think that most cases of HCC were diagnosed at advanced stage. (F) 36.3% of participants believed wrongly that over 20% of HCC patients are available for radical curative treatment.
Table 1.
Questionnaire about hepatocellular carcinoma
Dear Participant,
Thank you very much for taking the time to participate in this questionnaire. The purpose of this survey is to better understand your knowledge and attitudes towards hepatocellular carcinoma (HCC), the most common form of liver cancer, and its surveillance, which will help inform preventive and treatment measures. Your responses are invaluable to our research.
Please be assured that all your answers will remain strictly confidential and will only be used for academic research purposes. The questionnaire will take approximately 10 minutes to complete. We appreciate your time and support!
1. Basic Information of Participant
Table 1.
|
Age |
□ 18-30 years □ 31-45 years |
|
□ 46-60 years □ 61 years and above |
|
Gender |
□ Male □ Female |
|
Occupation |
□ Student □ Medical worker |
|
□ Service industry □ Company employee |
|
□ Freelancer □ Retired |
|
□ Other: ___________ |
|
Area of Residence |
□ Urban □ Suburban □ Rural |
|
Education Level |
□ Junior high school or below |
|
□ High school |
|
□ College or above |
|
Family history of liver cancer |
□ Yes □ No |
|
Chronic liver disease |
□ Yes □ No |
|
Previous major illness |
□ Yes (Please specify: ___________) □ No |
|
Regular health check-up habit |
□ Yes □ No |
2. Knowledge and Attitude Towards HCC Surveillance
Table
|
Do you think regular HCC surveillance can prevent HCC development? |
□ Yes □ No |
|
Do you think the abdominal ultrasound can detect HCC during each surveillance? |
□ Yes □ No |
|
Do you know the exact reduction of 5-year mortality when regular surveillance is performed for high-risk population? |
□ Hardly □ 40% |
|
□ 60% □ 80% |
|
Do you think HCC surveillance is only necessary when symptoms (e.g., abdominal pain, bloating, jaundice, etc.) appear? |
□ Yes □ No |
|
Do you think most HCC cases are diagnosed at an advanced stage? |
□ Yes □ No |
|
Do you know the exact probability for patients without regular HCC surveillance of receiving radical treatment after being diagnosed with HCC? |
□ 20% □ 40% |
|
□ 60% □ 80% |
|
Do you believe you need regular HCC surveillance? |
□ Yes □ No |
|
What do you think is the appropriate interval for HCC surveillance? |
□ Every 3 months □ Every 6 months |
|
□ Every 12 months □ Every 24 months |
Abbreviations
REFERENCES
- 1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-249.
- 2. Jie HE, Wanqing CHEN, Hongbing SHEN, Ni LI, Chunfeng QU, Jufang SHI, et al. China guideline for liver cancer screening (2022, Beijing). J Clin Hepatol 2022;38:1739-1758.
- 3. Wang FS, Fan JG, Zhang Z, Gao B, Wang HY. The global burden of liver disease: the major impact of China. Hepatology 2014;60:2099-2108.
- 4. Tzartzeva K, Obi J, Rich NE, Parikh ND, Marrero JA, Yopp A, et al. Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis. Gastroenterology 2018;154:1706-1718.e1.
- 5. Galle PR, Forner A, Llovet JM, Mazzaferro V, Piscaglia F, Raoul JL, et al. ASL clinical practice guidelines: management of hepatocellular carcinom. J Hepatol 2018;69:182-236.
- 6. Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018;67:358-380.
- 7. Xie D, Shi J, Zhou J, Fan J, Gao Q. Clinical practice guidelines and real-life practice in hepatocellular carcinoma: a Chinese perspective. Clin Mol Hepatol 2023;29:206-216.
- 8. Zhao C, Xing F, Yeo YH, Jin M, Le R, Le M, et al. Only onethird of hepatocellular carcinoma cases are diagnosed via screening or surveillance: a systematic review and metaanalysis. Eur J Gastroenterol Hepatol 2020;32:406-419.
- 9. Lee SW, Choi J, Kim SU, Lim YS. Entecavir versus tenofovir in patients with chronic hepatitis B: enemies or partners in the prevention of hepatocellular carcinoma. Clin Mol Hepatol 2021;27:402-412.
- 10. Rich NE, Phen S, Desai N, Mittal S, Yopp AC, Yang JD, et al. Cachexia is prevalent in patients with hepatocellular carcinoma and associated with worse prognosis. Clin Gastroenterol Hepatol 2022;20:e1157-e1169.
- 11. Singal AG, Lim JK, Kanwal F. AGA clinical practice update on interaction between oral direct-acting antivirals for chronic hepatitis C infection and hepatocellular carcinoma: expert review. Gastroenterology 2019;156:2149-2157.
Citations
Citations to this article as recorded by
- Persisting challenges in the early detection of hepatocellular carcinoma
Ashwini Arvind, Kennedy Redmon, Amit G Singal
Expert Review of Anticancer Therapy.2025; 25(3): 229. CrossRef
