Introduction
Liver cancer is a major burdensome cancer worldwide, and China contributes more than half the global burden of liver cancer [
1]. Effective interventions have been established in the past two decades in China, including universal neonatal hepatitis B virus (HBV) vaccination, regional dietary aflatoxin control, and appropriate regulations to address primary prevention as well as secondary prevention measures such as screening and early detection [
1]. Although this has resulted in positive changes such as a decline in HBV infection over time, the current burden of liver cancer in China is still significant [
2]. The 5-year survival rate of liver cancer was much lower than the average of all cancers in 2012–2015 (12.1% vs. 40.5%) [
3].
Liver cancer also imposes a substantial economic burden. A multicenter survey (n = 12,342) reported that the per-case average medical expenditure for liver cancer diagnosis and treatment in China doubled from 2002 to 2011 [
4]. An earlier systematic review focused on the economic burden of liver cancer in China from 1996 to 2015; among the 32 studies included, only two were conducted at the population level (one at the provincial level and the other at the municipal level) [
5]. In an updated review published in 2020 [
2], an additional population-level economic burden analysis was included; this is the only national study, to our knowledge, to provide cost data for liver cancer at the national level. In this broad expenditure analysis of hospital care for all cancers in China, which used a Chinese hospital information database, the direct medical cost of liver cancer in 2015 was estimated at CNY8.1 billion [
6]; however, the study did not present costs due to disability and premature death for liver cancer.
Because liver cancer presents a significant burden, it must be addressed through evidence-based interventions to achieve the United Nations’ Sustainable Development Goals (SDG) 2030 [
7] of reducing premature mortality from non-communicable diseases by one-third and the Chinese goal of increasing the 5-year cancer survival rate by 15% by 2030 [
8]. Detailed baseline data on the population-level economic burden of liver cancer are essential in providing a benchmark for future interventions and for evaluating and monitoring primary and secondary liver cancer interventions in China for these goals. Thus, the current study aimed to quantify the comprehensive economic burden of liver cancer in China from 2019 to 2030 at the population level. A prevalence-based approach was previously used to evaluate the population-level economic burden of lung cancer [
9,
10]. This study further developed the methodology and integrated detailed local population-specific parameters for liver cancer. The findings will be informative for future policymaking on liver cancer control and related budget allocation in China.
Discussion
To our knowledge, this is the most comprehensive and detailed analysis of the population-level economic burden of liver cancer conducted in China. This study provides benchmark data on the population-level economic burden, which is essential to inform policymaking in liver cancer control and related budget allocation. Using a prevalence-based approach and integrating multisource data, this study found that the economic burden of liver cancer in China was substantial in 2019 (CNY76.7/US$11.1 billion, of which 71.8% were indirect costs, accounting for 0.047% of China’s GDP) and would continue to increase (CNY234.3/US$34.0 billion in 2030). However, the burden in 2030 would be <CNY144.4/US$20.9 billion if China achieved the ‘Healthy China 2030’ goal or the SDG.
The proportion of the economic burden of one disease to the local GDP (GDP percent) is used as an indicator to compare different economies. Our study suggests that China’s GDP proportion attributable to cancer is lower than that of Japan (0.102%, 607.2 billion Japanese Yen in 2014) [
28] and Korea (0.117%, US$2.27 billion in 2015) [
29], based on the available literature. For other Western countries, such as the US, where the main causes of liver cancer are quite different from Asia [
30], the overall financial cost per hospitalization for liver cancer was US$59,465 in 2011 [
31], and a recent systematic review showed no other studies of the population-level economic burden of liver cancer in the US to date [
32]. As expected, the GDP percent for liver cancer (0.085%) is lower than that of lung cancer (0.205%). The main reason may be the differences in disease burden.
Our study included direct non-medical expenditure and indirect costs, which are rarely reported in existing studies on the economic burden of China’s population, in addition to direct medical expenditure. Using large-scale inpatient medical records and assuming ratios of outpatient payments to inpatient payments, a previous study reported a national expenditure of hospital care as CNY8.1 billion for liver cancer [
6], which is ~ 2/5 of the direct medical expenditure in our study. The differences are likely due to the different data sources of per-case expenditures, which were greater from tertiary hospitals in our study than from tertiary or lower-level hospitals in the study by Cai et al. [
6] Our analysis also suggests a high proportion of indirect cost in the total burden for liver cancer (71.8%), which is higher than that of lung cancer (55.7%) [
10]. The difference is probably due to the relatively lower survival rate of liver cancer (12.1%) [
3].
The findings suggest that the overall economic burden of liver cancer in China will continue to increase (CNY234.3 billion in 2030), but the extent of the increase could be largely delayed if appropriate interventions are implemented in China. Population aging, continuing urbanization, and increasing liver cancer burden contribute to the increase in the projected economic burden of liver cancer over the next decade in China. However, if the goals of SDG 2030 (a), SDG 2030 (b) and Healthy China 2030 can be achieved through application of policy approaches and interventions, the economic burden would decline by 38.4%, 58.7% and 38.7%, respectively. These reductions highlight the need for actions to reduce the economic burden by aiming to reduce mortality and increase the survival rate of liver cancer. These actions require further advances in clinical treatment, primary prevention (e.g. various HBV vaccination interventions and antiviral therapy) and secondary prevention (e.g. liver cancer screening in high-risk populations, early detection or surveillance). The shifting burden from indirect cost (IDIS and IPD) to direct expenditure (DM and DNM) in the breakdown of the estimated economic burden indicates that due to the aging population and urbanization, the survival period of patients is prolonged, and the number of patients and the corresponding cost increase. In Japan [
28], decreased IPD was the primary factor contributing to the total economic burden, mainly due to the decreased fatality rate and increased age at death. Therefore, the urgent need to formulate and implement relevant control measures is growing because appropriate interventions could weaken this dynamic growth trend and reduce the economic burden.
In the sensitivity analysis, a change in the annual productivity/earnings growth rate has a greater influence on the overall economic burden than a change in the annual growth rate of direct expenditure because it mainly affected IPD, which accounts for the largest proportion of the overall burden. Regarding the impact of working age, when assuming shortened age ranges of three types (in which the maximum age limit is 69 rather than below the sex-specific life expectancy), the overall burden would be considerably reduced. The overall burden was found to be most sensitive (doubled) to data sources of the disease burden when using a set of parameters from GLOBOCAN, in which higher incidence and mortality estimates were adopted. Considering variable trends in the pathogenic factors of liver cancer (HBV, hepatitis C virus, and non-virus-related factors), our future trend estimation, which used future disease burden data from the GBD website, reflects the changes in etiology to a certain extent.
The current analysis can be regarded as a preliminary estimate of the economic burden at the population level, but it has limitations. First, the precision of the current estimate relies on the per-case data from a previous hospital-based survey that involved individual-level and hospital-level (high-level) selection bias, which may cause an overestimation of the medical economic burden; however, this is the best publicly available data to date. Second, when patients were diagnosed at very late stages, some refused treatment. The extent remains unknown, and we used a simplified estimation based on the consultation rate. Furthermore, the treatment costs incurred outside hospitals, such as drugs purchased in retail pharmacies, cannot be accessed and considered in medical expenditures. Both estimations affect medical expenditure and indirect costs. Third, the current combination of expenditure and cases was not well matched. If death occurred within 1 year after diagnosis, the cost was regarded as the EOL phase according to the definition, which we did not consider this situation. Finally, this study is based on a variety of assumptions and databases, and other uncertainties may exist.
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