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. 2025 Nov 24;139(3):415–423. doi: 10.1097/CM9.0000000000003828

Burden of liver cancer and underlying etiologies in China from 1990 to 2021: A systematic analysis from the Global Burden of Disease Study 2021

Menglong Li 1, Huiming He 1, Xinyu Zhao 2,3, Mengying Guan 1, Nourhan M Khattab 1, Galal Elshishiney 1, Hong You 2,3,✉, Yifei Hu 1,4,5,✉
Editor: Yanjie Yin
PMCID: PMC12875693  PMID: 41481853

Abstract

Background:

Liver cancer continues to pose a global health challenge. In 2020, China accounted for nearly half of new liver cancer cases worldwide, with a low 5-year survival. This study aims to evaluate the evolving landscape of the liver cancer burden in China.

Methods:

Data on prevalence, incidence, death, and disability-adjusted life year (DALY) attributed to liver cancer and its six etiologies in China between 1990 and 2021 were extracted from the Global Burden of Disease Study 2021. Temporal trends in liver cancer burden were determined by percent changes and average annual percent change (AAPC). Decomposition analysis was conducted to understand the contributions of population aging, population growth, and epidemiological change to the observed trends.

Results:

In 2021, there were 265,539 prevalence cases of liver cancer in China accounting for 35.9% of the global total (739,300 prevalence cases). From 1990 to 2021, the prevalence cases, incidence cases, deaths, and DALYs attributed to liver cancer in China increased by 99.99%, 103.91%, 81.24%, and 48.41%, respectively, primarily driven by population aging, then population growth. Males experienced higher burden and percentage changes in prevalence, incidence, and DALYs than females. Meanwhile, decreasing trends were observed in overall age-standardized incidence, death, and DALY rates (AAPC: –0.32%, –0.79%, and –1.03%) and generally across sex groups and the six etiologies. Notably, there were increasing trends in age-standardized incidence rate of liver cancer due to alcohol use (AAPC: 0.36%) and metabolic dysfunction-associated steatotic liver disease (MASLD) (AAPC: 0.44%). In 2021, hepatitis B, hepatitis C, and alcohol use were the main causes of liver cancer burden in China. There were age differences in the burden of liver cancer. The overall 5-year relative survival rate was 12.27% in 2021.

Conclusions:

Liver cancer cases increased dramatically over the past 30 years, primarily driven by population aging and growth, posing challenges to the control of liver cancer. Targeted interventions by sex, etiology, and age are needed to address the burden effectively.

Keywords: Alcohol, Liver cancer, Global Burden of Disease, Hepatitis B, Hepatitis C, Hepatoblastoma, Metabolic dysfunction-associated steatotic liver disease, Underlying etiologies

Introduction

Liver cancer remains a formidable global health challenge, causing substantial morbidity and mortality worldwide.[1,2] In 2020, it ranked as the third leading cause of cancer-related deaths globally, with hepatocellular carcinoma as the predominant form among adults.[3–7] China shouldered a substantial proportion of the global liver cancer burden, accounting for 45.3% of new liver cancer cases worldwide in 2020,[4] and 38.7% of the total liver cancer deaths in 2019.[4,8] The high incidence and mortality of liver cancer in China posed significant challenges to the prevention, management, and treatment of this disease, resulting in a 5-year relative survival of 14.4%.[9,10]

The major etiologies of liver cancer are often linked to hepatitis B and hepatitis C virus (HBV/HCV), alcohol consumption, metabolic dysfunction-associated steatotic liver disease (MASLD), and other causes.[2,11–13] Shifts in the etiologies of liver cancer have led to changes in its overall burden, as evidenced by the decreasing incidence trends due to hepatitis B and the increasing trends caused by alcohol use and MASLD.[2,11,14,15] Efforts to reduce the liver cancer burden must encompass multifaceted strategies, including prioritizing hepatitis B vaccination programs, hepatitis C screening, and interventions targeting modifiable risk factors such as alcohol consumption and obesity-related liver disease.[4,6,11,16] Early detection through surveillance and screening programs is crucial for timely diagnosis and improved outcomes.[11,16]

The Chinese government has launched a hepatitis B vaccination plan since 1992, which was expanded into a comprehensive fully financed nationwide initiative in 2005.[17] Since then, China has introduced various screening programs aimed at detecting liver cancer, including the Early Detection and Early Treatment of Cancer in Rural Cancer (2005–present), the Program of Early Detection and Early Treatment of Cancer in Huaihe River (2007–present), and the Cancer Screening Program in Urban China (2012–present).[17,18] According to the “Healthy China, 2030” plan, the 5-year survival for cancer in China is targeted to increase by 15% by 2030.[19] Therefore, updating the assessment of liver cancer burden is essential to inform targeted interventions in China.

In this study, we focused on the current status and temporal trends in the burden of liver cancer and its underlying etiologies by sex in China from 1990 to 2021. This study aimed to evaluate the evolving landscape of liver cancer to inform liver cancer prevention and control in China.

Methods

Data source

This study was conducted using data from the Global Burden of Diseases Study (GBD) 2021, a systematic effort offering estimates on the burden of 371 diseases, encompassing 204 countries and territories and 811 subnational locations.[2,20–23] Input data sources included population-based cancer registries, vital registration systems, and verbal autopsy studies.[2,20] The International Classification of Diseases, 10th revision (ICD-10) codes used for liver cancer in this study were C22.0–22.8, and a proportion of C22.9. The six etiologies assessed included hepatitis B, hepatitis C, alcohol use, MASLD (non-alcoholic steatohepatitis [NASH] in GBD framework), other causes, and hepatoblastoma.[2] Crosswalk adjustment factors were set for model inputs for liver cancer etiology proportions in Meta-regression with Bayesian priors, Regularization, and Trimming (MR-BRT) estimation procedure.[21] The estimation of burden attributed to six etiologies was determined using DisMod-MR 2.1, a Bayesian meta-regression method, according to the etiology proportions.[2,12]

This study used publicly available data from the GBD 2021, comprising deidentified information rather than individual-level data. Therefore, the institutional review board waived the requirement for ethical approval and informed consent.

Disease burden

Data on the number of cases, age-specific rates, and age-standardized rates (ASRs) of prevalence, incidence, death, and disability-adjusted life year (DALY) attributed to liver cancer and its six etiologies in China between 1990 and 2021 by sex and age were extracted with 95% uncertainty intervals (UIs) from the Institute for Health Metrics and Evaluation (IHME), which can be accessed for download at https://vizhub.healthdata.org/gbd-results/.

Prevalence or incidence rates were calculated by dividing the number of prevalence or incidence by the corresponding population, whereas death rates were calculated by dividing the estimated number of deaths by the corresponding population. DALYs were calculated by summing years of life lost (YLLs) and years lived with disability (YLDs). YLLs were determined by multiplying the estimated number of deaths by the difference between the standard life expectancy for the individual’s age and the age at death. YLDs were calculated by multiplying prevalence by a specific disability weight in a Bayesian regression model. All measures were presented per 100,000 individuals.[2,20–23] Five-year relative survival was estimated using the formula (1–mortality/incidence)×100.[24,25]

Statistical analysis

In this study, we employed ASR to present a comparable overview across sex and the six etiologies and used percent change and average annual percent change (AAPC) to assess temporal trends in prevalence, incidence, death, and DALYs of liver cancer from 1990 to 2021. ASR was derived using the direct method to the GBD standard population.[2,20–22] AAPC was derived with 95% confidence interval (CI) from log-linear Joinpoint models.[23,26,27]

In addition, we conducted a decomposition analysis of changes in prevalence cases, incidence cases, deaths, and DALYs using the methods developed by Gupta to understand the drivers of these changes across three explanatory components: population aging, population growth, and age-specific rates (epidemiological change).[26,28] All statistical tests were two-tailed. Increasing trends are defined as when the percent change and its 95% UI or AAPC and its 95% CI are both greater than zero. Conversely, decreasing trends are defined as both are less than zero. Otherwise, the trends are defined as stable. The analyses were performed using SAS (version 9.4, SAS Institute Inc., Cary, NC, USA), Joinpoint Regression Program (version 5.0.2, the National Cancer Institute, Rockville, MD, USA), and R (version 4.3.2, R Foundation, Vienna, Austria).

Results

Burden of liver cancer in China, 2021

In 2021, there were 265,539 prevalence cases of liver cancer in China, accounting for 35.9% of the global total (739,300 prevalence cases) and 96.4% of the East Asia total. There were 196,636 incidence cases of liver cancer, with an age-standardized incidence rate of 9.52 per 100,000 in China, which is higher than the global estimate of 6.15 per 100,000 and only lower than that in high-income Asia Pacific (12.63 per 100,000). At the same time, liver cancer accounted for 172,068 deaths in China, with an age-standardized death rate of 8.35 per 100,000, higher than the global average (5.65 per 100,000). China also experienced a total of 4,890,023 DALYs attributed to liver cancer, with an age-standardized DALY rate of 239.91 per 100,000, which is 1.6 folds higher than the global average [Figure 1].

Figure 1.

Figure 1

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Number, age-standardized prevalence, incidence, death, and DALY rates of liver cancer by regions in 2021. ASR: Age-standardized rate, per 100,000; DALY: Disability-adjusted life year; N: Number.

Trends in liver cancer burden by sex in China, 1990–2021

As shown in Table 1, from 1990 to 2021, the number of liver cancer incidence cases and deaths increased by 103.91% (95% UI: 52.37–168.23%) and 81.24% (95% UI: 36.07–137.11%), respectively, slightly lower than the global change [Supplementary Table 1, http://links.lww.com/CM9/C623]. However, age-standardized incidence and death rates presented decreasing trends, with AAPCs of –0.32% (95% CI: –0.35% to –0.27%) and –0.79% (95% CI: –0.86% to –0.71%), respectively. Both numbers and ASRs of liver cancer measures were higher among males than females, with generally higher percentage changes in prevalence, incidence, and DALYs among males, except for deaths. Almost all ASRs of liver cancer measures for both sexes decreased from 1990 to 2021 in China, but the age-standardized prevalence rate for males showed an increasing trend, consistent with global patterns [Supplementary Table 1, http://links.lww.com/CM9/C623]. The decreasing trends measured by AAPCs were more pronounced among females than males.

Table 1.

Change in number, age-standardized prevalence, incidence, death, and DALY rates of liver cancer by sex between 1990 and 2021 in China.

Indices N (95% UI) Percent change (95% UI) ASR, per 100,000 (95% UI) AAPC (95% CI)
1990 2021 1990–2021 1990 2021 1990–2021
Prevalence
Total 132,779 (108,924, 155,564) 265,539 (212,435, 331,149) 99.99 (51.57, 164.33) 13.51 (11.20, 15.77) 13.29 (10.75, 16.41) –0.04 (–0.09, 0.00)
Male 95,779 (78,334, 116,603) 198,826 (150,846, 266,673) 107.59 (47.68, 186.78) 18.94 (15.48, 23.02) 20.00 (15.38, 26.47) 0.19 (0.14, 0.23)
Female 37,000 (29,627, 44,601) 66,713 (51,940, 84,332) 80.31 (32.40, 153.43) 7.86 (6.34, 9.48) 6.64 (5.19, 8.32) –0.53 (–0.57, –0.50)
Incidence
Total 96,434 (80,971, 113,769) 196,636 (158,273, 243,558) 103.91 (52.37, 168.23) 10.58 (8.94, 12.43) 9.52 (7.72, 11.78) –0.32 (–0.35, –0.27)
Male 70,209 (56,752, 85,768) 143,788 (108,927, 193,831) 104.80 (43.93, 183.39) 15.06 (12.20, 18.24) 14.34 (10.93, 19.18) –0.14 (–0.18, –0.11)
Female 26,225 (20,941, 31,755) 52,848 (41,045, 67,026) 101.52 (48.49, 181.03) 6.04 (4.82, 7.28) 4.89 (3.82, 6.18) –0.68 (–0.71, –0.65)
Death
Total 94,937 (79,884, 111,527) 172,068 (139,621, 212,496) 81.24 (36.07, 137.11) 10.75 (9.12, 12.61) 8.35 (6.80, 10.29) –0.79 (–0.86, –0.71)
Male 68,304 (55,235, 83,128) 122,463 (93,115, 164,816) 79.29 (26.19, 149.31) 15.19 (12.32, 18.36) 12.40 (9.46, 16.55) –0.63 (–0.70, –0.56)
Female 26,633 (21,350, 32,258) 49,605 (38,617, 62,668) 86.25 (37.23, 159.58) 6.33 (5.08, 7.64) 4.57 (3.57, 5.76) –0.98 (–1.10, –0.89)
DALY
Total 3,294,864 (2,763,029, 3,879,589) 4,890,023 (3,905,089, 6,124,599) 48.41 (10.75, 96.81) 334.52 (281.08, 393.14) 239.91 (191.98, 299.37) –1.03 (–1.09, –0.98)
Male 2,462,152 (2,000,446, 3,012,119) 3,702,093 (2,805,347, 4,985,654) 50.36 (5.05, 108.19) 483.97 (392.36, 591.53) 368.19 (279.67, 490.95) –0.85 (–0.92, –0.78)
Female 832,712 (666,725, 1,010,058) 1,187,930 (924,053, 1,513,173) 42.66 (3.96, 99.91) 177.47 (142.84, 214.58) 111.91 (87.16, 141.96) –1.44 (–1.54, –1.37)
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AAPC: Average annual percent change; ASR: Age-standardized rate; CI: Confidence interval; DALY: Disability-adjusted life year; N: Number; UI: Uncertainty interval.

Trends in liver cancer burden by six etiologies in China, 1990 to 2021

The burden and trends of liver cancer from the six etiologies in China from 1990 to 2021, ranked by prevalence, incidence, deaths, and DALYs, were shown in Supplementary Tables 2 and 3, http://links.lww.com/CM9/C623, and Figure 2. In 2021, the rankings for the six etiologies of liver cancer due to hepatitis B, hepatitis C, alcohol use, MASLD, other causes, and hepatoblastoma remained consistent across prevalence, incidence, deaths, and DALYs. The top three etiologies by incidence cases, deaths, and DALYs were due to hepatitis B, hepatitis C, and alcohol use, and these rankings remained unchanged from 1990 and 2021. Moreover, the age-standardized incidence, death, and DALY rates of liver cancer due to hepatitis B and hepatitis C decreased from 1990 to 2021, whereas the age-standardized incidence rate of liver cancer due to alcohol use showed an increasing trend (AAPC: 0.36%, 95% CI: 0.32% to 0.39%). Significant increases in prevalence cases, incidence cases, deaths, and DALYs as well as age-standardized prevalence and incidence rates were observed for liver cancer due to MASLD. For liver cancer due to other causes, there were significant increases in prevalence cases, incidence cases, and deaths, but significant decreases were observed in all ASRs. Hepatoblastoma exhibited significant decreasing trends in all numbers and ASRs of prevalence, incidence, death, and DALY.

Figure 2.

Figure 2

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Trends in prevalence (A), incidence (B), death (C), and DALY (D) of liver cancer by six etiologies in China, 1990–2021. AAPC: Average annual percent change; ASR: Age-standardized rate, per 100,000; CI: Confidence interval; DALY: Disability-adjusted life year; MASLD: Metabolic dysfunction-associated steatotic liver disease; UI: Uncertainty interval.

Decomposition analysis of changes in liver cancer burden in China, 1990–2021

Decomposition analysis indicated that the total changes in prevalence cases, incidence cases, deaths, and DALYs attributed to liver cancer were primarily driven by population aging, followed by population growth in China, compared with 1990. Conversely, epidemiological change (age-specific rates) had a contrasting impact in most scenarios, especially for deaths and DALYs and among females [Figure 3, Supplementary Table 4, http://links.lww.com/CM9/C623]. Specifically, the contributions of population aging and population growth to percent changes in prevalence cases, incidence cases, deaths, and DALYs of liver cancer in 2021 were as follows: 73.23% and 27.41% for prevalence cases, 93.16% and 28.31% for incidence cases, 93.18% and 26.77% for deaths, and 66.51% and 23.83% for DALYs [Figure 3, Supplementary Table 4, http://links.lww.com/CM9/C623]. However, epidemiological change contributed a change of –0.65% in prevalence cases, –17.57% in incidence cases, –38.70% in deaths, and –41.93% in DALYs in 2021 [Figure 3].

Figure 3.

Figure 3

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Decomposition analysis of changes in prevalence cases, incidence cases, deaths and DALYs of liver cancer in China (A) and by sex (B, C) and three etiologies, (D, E, F) compared with 1990. DALY: Disability-adjusted life year; N: Number.

Similar patterns were observed for both males and females and for liver cancer due to hepatitis B, hepatitis C, and alcohol use. Generally, changes in liver cancer burden were attributed to population growth, population aging, and epidemiological changes, with females affected more than males [Figure 3, Supplementary Tables 4 and 5, http://links.lww.com/CM9/C623]. For the increase in liver cancer burden due to hepatitis C, population aging showed the most significant effect, with population growth showing a similar effect compared with liver cancer due to hepatitis B and alcohol use [Figure 3, Supplementary Tables 6–9, http://links.lww.com/CM9/C623].

Burden of liver cancer by age in China, 2021

Numbers and rates for the burden of liver cancer by age and sex in 2021 were presented in Figure 4. As a severe disease, liver cancer shows similar patterns across the four measures. For age-specific prevalence rate, males have three peaks at ages 50–54 years, 65–69 years, and 85–89 years, with the highest rate occurring in the 85–89 years group at 86.79 per 100,000 (95% UI: 68.63–111.19). Females also have two peaks, mainly at ages 70–74 years and 85–89 years, with the peak in the 85–89 years group at 45.98 per 100,000 (95% UI: 33.40–58.93). The prevalence rate in the <5 years group was notably high, exceeding that of the 25–29 years and younger age groups in males, and the 40–44 years and younger age groups in females [Figure 4A]. The incidence rates of males were higher than those of females across all age groups, except for the 90–94 years group, where incident cases were lower for males (944.31 per 100,000) compared with females (1007.15 per 100,000). The incidence rate for males peaked in the 90–94 years group, reaching 116.75 per 100,000 (95% UI: 87.13–153.82). For females, the incidence rate decreased rapidly after the age of 85–89 years (55.67 per 100,000). The total incidence rate fell between the rates of males and females across all age groups, and followed a similar trend to the female incidence rate, peaking in the 85–89 age group at 74.59 per 100,000 (95% UI: 60.11–89.92) [Figure 4B]. The death rate caused by liver cancer generally increased with age, reaching its peak in the 90–94 years group (males: 164.10 per 100,000, 95% UI: 125.19–216.56; females: 67.03 per 100,000, 95% UI: 47.91–86.86) [Figure 4C]. The pattern of DALY rate mirrored the prevalence rate, with the peak for males in the 90–94 years group at 1441.51 per 100,000 (95% UI: 1098.87–1901.41) and the peak for females in the 80–84 years group at 652.02 per 100,000 (95% UI: 493.25–812.15) [Figure 4D].

Figure 4.

Figure 4

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Number and rate of prevalence (A), incidence (B), death (C), and DALY (D) of liver cancer by age in 2021. DALY: Disability-adjusted life year; N: Number.

Five-year relative survival of liver cancer in China, 2021

In 2021, the 5-year relative survival for liver cancer in China was estimated at 12.27%, with males showing a higher rate (13.48%) than females (6.64%). Moreover, the 5-year relative survival decreased with age, estimated at 48.53%, 26.11%, and 5.89% among people aged <20 years, 20–54 years and 55 years and older, respectively.

Discussion

This study presented the temporal trends in the number and ASRs of incidence, prevalence, death, and DALY attributed to liver cancer and its six etiologies from 1990 to 2021 in China. Increasing trends were observed in prevalence cases, incidence cases, deaths, and DALYs attributed to liver cancer, primarily driven by population aging, then population growth. Epidemiological changes showed an opposite effect. Stratified by six etiologies, liver cancer due to hepatitis B, hepatitis C, alcohol use, MASLD, and other causes generally showed increasing trends in prevalence cases, incidence cases, deaths, and DALYs. Conversely, the burden of hepatoblastoma showed a decreasing trend. Overall decreasing trends in age-standardized death and DALY rates were determined across both sexes and six etiologies. However, increasing trends were observed in age-standardized incidence rates of liver cancer due to alcohol use and MASLD, and age-standardized prevalence rates of males and liver cancer due to hepatitis C, alcohol use, and MASLD. Differences in liver cancer burden patterns were observed across age groups, and 5-year relative survival decreased by age with an overall rate of 12.27%.

In 2021, there were about 265,539 prevalence cases, 196,636 incidence cases, 172,068 deaths, and 4,890,023 DALYs from liver cancer in China at the national level. The deaths in this study were half lower than that from the national mortality surveillance system (367,720 deaths) in 2020[26] and from national cancer registries (316,500 deaths) in 2022,[29] with similar sex disparity patterns. In this study, males experienced 2.5- to 3.1-fold of these numbers compared with females. At the same time, consistently higher age-standardized incidence, prevalence, death, and DALY rates were observed in males than in females, underscoring the influence of complex factors. Behavioral differences significantly contribute to these disparities. Traditionally, males are more likely to engage in high-risk behaviors such as smoking, heavy drinking, and less frequent healthcare utilization compared with females.[10,30–32] These behaviors increase their susceptibility to diseases and lead to poorer health outcomes.[6,33,34] In addition, occupational exposures disproportionately affect males due to their higher representation in hazardous industries such as construction, manufacturing, and mining, which increases their exposure to environmental pollutants and physical harm.[13,16,35]

Substantial increases were observed in prevalence cases, incidence cases, deaths, and DALYs attributed to liver cancer in 2021 compared with 1990. There were increases primarily driven by population aging, then population growth, while epidemiological change showed a contrasting effect in some years, consistent across both sexes. China experienced a dramatical demographic transition and population aging during the past 50 years and older individuals were more susceptible to liver cancer due to cumulative exposure to risk factors over their lifetime.[5,13,36,37] This made population aging a dominant factor in the increase of liver cancer burden in China, which contributed to increases ranging from 66.51% to 93.18%. Population growth resulted in an expanding number of people at risk, contributing an increase of 23.83–28.31%. However, the impact of epidemiological changes reflected the contribution of the decreasing age-specific rates and improvements in the management and treatment of liver cancer. Understanding these driving factors can lead to the formulation of more effective control strategies to lower age-specific rates and address the growing demands of patients.

Although age-standardized incidence, death, and DALY rates of liver cancer in China showed significant decreases to 9.52, 8.35, and 239.91 per 100,000 in 2021, liver cancer continued to be a major health concern, primarily caused by hepatitis B, hepatitis C, and alcohol use. Hepatitis B has historically been the leading cause, particularly in east and southeast Asia.[10,12,14,38,39] Despite efforts in China to reduce hepatitis B-related liver cancer through vaccination and transmission prevention, challenges persist in decreasing mortality and improving diagnosis.[6,14,17,18,22,40] Lacking a specific vaccine for hepatitis C posed a challenge to early prevention of liver cancer. Moreover, the advanced stage at diagnosis and direct-acting antiviral therapy challenges may lead to a lower 5-year relative survival.[4,7,11] Gender differences exist in liver cancer causes, with males being more affected by alcohol-related liver cancer, while females are more susceptible to HCV-induced liver cancer.[15,35] In addition, hormonal factors may influence the prevalence of HBV-related liver cancer in postmenopausal females.[41] Alcohol-related liver diseases and MASLD were increasingly prevalent, and the rise of MASLD-related liver cancer underscores the importance of addressing lifestyle factors to combat this growing issue.[42,43] Lifestyle interventions, such as alcohol tax and dietary changes, are key in reducing the incidence of liver cancer.[16,44]

Significant differences were observed in the burden of liver cancer patterns across different age groups. Hepatoblastoma primarily affects children under 5 years of age,[38] which contributed to a peak in the young population <20 years old in 2021. This study also showed a significant decrease in all burden measures for hepatoblastoma from 1990 to 2021. The peak number of incidence, prevalence, death, and DALY were mainly showed in individuals aged 50–69 years, with age-specific incidence, death, and DALY rates peaking at the 90–94 years group. These findings highlight the dual nature of liver cancer epidemiology: a notable peak in childhood due to hepatoblastoma, and a significant peak in older adults. The overall decrease in the burden of hepatoblastoma from 1990 to 2021 suggests improvements in maternal and infant nutrition leading to fewer preterm and low birth weight infants and advancements in early detection, treatment, and preventive measures.[45] However, the persistent burden among older adults highlights ongoing challenges in managing liver cancer in this demographic, potentially influenced by factors such as an aging population and accumulated risk exposures over a lifetime. Addressing these age-specific patterns is crucial for developing targeted public health strategies to mitigate the impact of liver cancer across different age groups.

There were several limitations in this study. First, the lack of access to subnational data limited the discussions across regions and the difference between urban and rural areas in China. Second, the quality of the source data, delays in cancer statistics, and challenges in accessing and integrating all relevant metadata may affect the accuracy of the estimates of disease burden at the national level within the GBD framework and potentially lead to reporting bias. However, advances in statistical methods used in GBD studies and multiple rounds of internal validation have enhanced the comparability and robustness of estimates across different measures and etiologies. Third, the absence of comprehensive data on health policies for liver cancer prevention and treatment, as well as insufficient information on cancer staging and etiologies, impedes a detailed analysis and understanding of disparities in the liver cancer burden.

In conclusion, this study provides a comprehensive overview of the liver cancer burden in China across sex and six etiologies from 1990 to 2021. Increasing trends were observed in prevalence cases, incidence cases, deaths, and DALYs attributed to liver cancer, primarily driven by population aging, followed by population growth. In 2021, the burden of liver cancer was mainly caused by hepatitis B, hepatitis C, and alcohol use. This study also identified a dual pattern of liver cancer burden: a childhood peak and an adulthood peak among the elderly. These insights into variations by sex, etiology, and age enhance the national understanding of epidemiological changes in the liver cancer burden. These findings may inform more targeted interventions to address liver cancer in China.

Funding

This study was supported by grants from the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission (No. 2024-3-028) and the National Natural Science Foundation of China (No. 72061137007).

Conflicts of interest

None.

Supplementary Material

cm9-139-415-s001.docx (59.8KB, docx)
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Footnotes

Menglong Li and Huiming He contributed equally to this work.

How to cite this article: Li ML, He HM, Zhao XY, Guan MY, Khattab NM, Elshishiney G, You H, Hu YF. Burden of liver cancer and underlying etiologies in China from 1990 to 2021: A systematic analysis from the Global Burden of Disease Study 2021. Chin Med J 2026;139:415–423. doi: 10.1097/CM9.0000000000003828

References

  • 1.Bray F Laversanne M Sung H Ferlay J Siegel RL Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024;74:229–263. doi: 10.3322/caac.21834. [DOI] [PubMed] [Google Scholar]
  • 2.Tan EY Danpanichkul P Yong JN Yu Z Tan DJH Lim WH, et al. Liver cancer in 2021: Global Burden of Disease Study. J Hepatol 2025;82:851–860. doi: 10.1016/j.jhep.2024.10.031. [DOI] [PubMed] [Google Scholar]
  • 3.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. doi: 10.3322/caac.21660. [DOI] [PubMed] [Google Scholar]
  • 4.Rumgay H Arnold M Ferlay J Lesi O Cabasag CJ Vignat J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol 2022;77:1598–1606. doi: 10.1016/j.jhep.2022.08.021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Cao W, Qin K, Li F, Chen W. Socioeconomic inequalities in cancer incidence and mortality: An analysis of GLOBOCAN 2022. Chin Med J 2024;137:1407–1413. doi: 10.1097/CM9.0000000000003140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Xu Y Xia C Li H Cao M Yang F Li Q, et al. Survey of hepatitis B virus infection for liver cancer screening in China: A population-based, cross-sectional study. Chin Med J 2024;137:1414–1420. doi: 10.1097/cm9.0000000000003171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Llovet JM Kelley RK Villanueva A Singal AG Pikarsky E Roayaie S, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2021;7:6. doi: 10.1038/s41572-020-00240-3. [DOI] [PubMed] [Google Scholar]
  • 8.Cao M Xia C Cao M Yang F Yan X He S, et al. Attributable liver cancer deaths and disability-adjusted life years in China and worldwide: Profiles and changing trends. Cancer Biol Med 2024;21:679–691. doi: 10.20892/j.issn.2095-3941.2024.0149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Zeng H Zheng R Sun K Zhou M Wang S Li L, et al. Cancer survival statistics in China 2019–2021: A multicenter, population-based study. J Natl Cancer Cent 2024;4:203–213. doi: 10.1016/j.jncc.2024.06.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Qin Y, Tang C, Li J, Gong J. Liver cancer in China: The analysis of mortality and burden of disease trends from 2008 to 2021. BMC Cancer 2024;24:594. doi: 10.1186/s12885-024-12334-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Pinheiro PS Jones PD Medina H Cranford HM Koru-Sengul T Bungum T, et al. Incidence of etiology-specific hepatocellular carcinoma: Diverging trends and significant heterogeneity by race and ethnicity. Clin Gastroenterol Hepatol 2024;22:562–571.e568. doi: 10.1016/j.cgh.2023.08.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Liu Y Zheng J Hao J Wang RR Liu X Gu P, et al. Global burden of primary liver cancer by five etiologies and global prediction by 2035 based on global burden of disease study 2019. Cancer Med 2022;11:1310–1323. doi: 10.1002/cam4.4551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Wang Z, Li Z, Ye Y, Xie L, Li W. Oxidative stress and liver cancer: Etiology and therapeutic targets. Oxid Med Cell Longev 2016;2016:7891574. doi: 10.1155/2016/7891574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Zhang CH, Cheng Y, Zhang S, Fan J, Gao Q. Changing epidemiology of hepatocellular carcinoma in Asia. Liver Int 2022;42:2029–2041. doi: 10.1111/liv.15251. [DOI] [PubMed] [Google Scholar]
  • 15.Tan DJH Setiawan VW Ng CH Lim WH Muthiah MD Tan EX, et al. Global burden of liver cancer in males and females: Changing etiological basis and the growing contribution of NASH. Hepatology 2023;77:1150–1163. doi: 10.1002/hep.32758. [DOI] [PubMed] [Google Scholar]
  • 16.Li Q Cao M Lei L Yang F Li H Yan X, et al. Burden of liver cancer: From epidemiology to prevention. Chin J Cancer Res 2022;34:554–566. doi: 10.21147/j.issn.1000-9604.2022.06.02. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Shi JF Cao M Wang Y Bai FZ Lei L Peng J, et al. Is it possible to halve the incidence of liver cancer in China by 2050? Int J Cancer 2021;148:1051–1065. doi: 10.1002/ijc.33313. [DOI] [PubMed] [Google Scholar]
  • 18.Cao M Li H Sun D He S Yu Y Li J, et al. Cancer screening in China: The current status, challenges, and suggestions. Cancer Lett 2021;506:120–127. doi: 10.1016/j.canlet.2021.02.017. [DOI] [PubMed] [Google Scholar]
  • 19.The Central Committee of the Communist Party of China . Healthy China, 2030 (in Chinese). Available from: http://www.gov.cn/zhengce/2016-10/25/content_5124174.htm. [Accessed on September 1, 2024].
  • 20.Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021: A systematic analysis for the Global Burden of Disease Study 2021. Lancet 2024;403:2100–2132. doi: 10.1016/s0140-6736(24)00367-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: A systematic analysis for the Global Burden of Disease Study 2021. Lancet 2024;403:2133–2161. doi: 10.1016/s0140-6736(24)00757-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Burden of disease scenarios for 204 countries and territories, 2022-2050: A forecasting analysis for the Global Burden of Disease Study 2021. Lancet 2024;403:2204–2256. doi: 10.1016/s0140-6736(24)00685-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Duan J Ding R Li M Qi J Yin P Wang L, et al. Subnational Evidence for the attributable burden of respiratory infections in China’s population under 20: Challenges from particulate matter pollution. Environ Health 2024. doi: 10.1021/envhealth.4c00137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Asadzadeh Vostakolaei F, Karim-Kos HE, Janssen-Heijnen ML, Visser O, Verbeek AL, Kiemeney LA. The validity of the mortality to incidence ratio as a proxy for site-specific cancer survival. Eur J Public Health 2011;21:573–577. doi: 10.1093/eurpub/ckq120. [DOI] [PubMed] [Google Scholar]
  • 25.Chen W Zheng R Baade PD Zhang S Zeng H Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin 2016;66:115–132. doi: 10.3322/caac.21338. [DOI] [PubMed] [Google Scholar]
  • 26.Qi J Li M Wang L Hu Y Liu W Long Z, et al. National and subnational trends in cancer burden in China, 2005-20: An analysis of national mortality surveillance data. Lancet Pub Health 2023;8:e943–e955. doi: 10.1016/s2468-2667(23)00211-6. [DOI] [PubMed] [Google Scholar]
  • 27.Li ML Qi JL Ma YQ Shu W Xiao HD Wang LJ, et al. National age-specific mortality trends for cervical and breast cancers in urban–rural areas of China from 2009 to 2021: A population-based analysis. Mil Med Res 2024;11:55. doi: 10.1186/s40779-024-00561-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Das Gupta P. Standardization and decomposition of rates: A user’s manual. 1993. Available from: https://www.census.gov/content/dam/Census/library/publications/1993/demo/p23-186.pdf. [Accessed on September 1, 2024]. [PubMed]
  • 29.Han B Zheng R Zeng H Wang S Sun K Chen R, et al. Cancer incidence and mortality in China, 2022. J Nat Cancer Cent 2024;4:47–53. doi: 10.1016/j.jncc.2024.01.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015: A systematic analysis from the Global Burden of Disease Study 2015. Lancet 2017;389:1885–1906. doi: 10.1016/s0140-6736(17)30819-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Novak JR, Peak T, Gast J, Arnell M. Associations between masculine norms and health-care utilization in highly religious, heterosexual men. Am J Mens Health 2019;13:1557988319856739. doi: 10.1177/1557988319856739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Rumgay H Shield K Charvat H Ferrari P Sornpaisarn B Obot I, et al. Global burden of cancer in 2020 attributable to alcohol consumption: A population-based study. Lancet Oncol 2021;22:1071–1080. doi: 10.1016/s1470-2045(21)00279-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Marti-Aguado D, Clemente-Sanchez A, Bataller R. Cigarette smoking and liver diseases. J Hepatol 2022;77:191–205. doi: 10.1016/j.jhep.2022.01.016. [DOI] [PubMed] [Google Scholar]
  • 34.Yoo JE Han K Shin DW Kim D Kim BS Chun S, et al. Association between changes in alcohol consumption and cancer risk. JAMA Netw Open 2022;5:e2228544. doi: 10.1001/jamanetworkopen.2022.28544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Biswas A Harbin S Irvin E Johnston H Begum M Tiong M, et al. Sex and gender differences in occupational hazard exposures: A scoping review of the recent literature. Curr Environ Health Rep 2021;8:267–280. doi: 10.1007/s40572-021-00330-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Macias RIR Monte MJ Serrano MA González-Santiago JM Martín-Arribas I Simão AL, et al. Impact of aging on primary liver cancer: Epidemiology, pathogenesis and therapeutics. Aging (Albany NY) 2021;13:23416–23434. doi: 10.18632/aging.203620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Luo Y, Su B, Zheng X. Trends and challenges for population and health during population aging - China, 2015–2050. China CDC Wkly 2021;3:593–598. doi: 10.46234/ccdcw2021.158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Berkemeyer S. Primary liver cancers: Connecting the Dots of cellular studies and epidemiology with metabolomics. Int J Mol Sci 2023;24:2409. doi: 10.3390/ijms24032409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Song C Lv J Liu Y Chen JG Ge Z Zhu J, et al. Associations between hepatitis B virus infection and risk of all cancer types. JAMA Netw Open 2019;2:e195718. doi: 10.1001/jamanetworkopen.2019.5718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Younossi ZM, Wong G, Anstee QM, Henry L. The global burden of liver disease. Clin Gastroenterol Hepatol 2023;21:1978–1991. doi: 10.1016/j.cgh.2023.04.015. [DOI] [PubMed] [Google Scholar]
  • 41.Montella M D’Arena G Crispo A Capunzo M Nocerino F Grimaldi M, et al. Role of sex hormones in the development and progression of hepatitis B virus-associated hepatocellular carcinoma. Int J Endocrinol 2015;2015:854530. doi: 10.1155/2015/854530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Díaz LA, Arab JP, Louvet A, Bataller R, Arrese M. The intersection between alcohol-related liver disease and nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2023;20:764–783. doi: 10.1038/s41575-023-00822-y. [DOI] [PubMed] [Google Scholar]
  • 43.Huang DQ, Singal AG, Kono Y, Tan DJH, El-Serag HB, Loomba R. Changing global epidemiology of liver cancer from 2010 to 2019: NASH is the fastest growing cause of liver cancer. Cell Metab 2022;34:969–977.e962. doi: 10.1016/j.cmet.2022.05.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Hallsworth K, Adams LA. Lifestyle modification in NAFLD/NASH: Facts and figures. JHEP Rep 2019;1:468–479. doi: 10.1016/j.jhepr.2019.10.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Wu Z, Xia F, Wang W, Zhang K, Fan M, Lin R. Worldwide burden of liver cancer across childhood and adolescence, 2000-2021: A systematic analysis of the Global Burden of Disease Study 2021. EClinicalMedicine 2024;75:102765. doi: 10.1016/j.eclinm.2024.102765. [DOI] [PMC free article] [PubMed] [Google Scholar]

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