Abstract
Background
Hepatoblastoma accounts for the majority of liver malignancies in children with a high socioeconomic burden worldwide. Comprehensive and accurate burden data assessment is crucial for health policy planning.
Materials and methods
Epidemiological data of hepatoblastoma was extracted from the Global Burden of Diseases Study 2021. The incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were assessed and Joinpoint regression analysis was conducted to evaluate the time trends. Age-standardized rates (ASR) were used to compare the burden among different sociodemographic index (SDI) and GBD regions. The Bayesian age-period-cohort model was applied to predict the disease burden.
Results
In 2021, there were 4048.42 new cases (95% UI: 3252.45-5000.45) and 2416.17 deaths (95% UI: 1922.47-3019.03) worldwide, of which 35.0% of new cases and 40.9% of deaths occurred in low SDI countries, and the corresponding ASR of morbidity and mortality was 0.09 (95% UI: 0.06–0.12) and 0.06 (95% UI: 0.04–0.08). Western Sub-Saharan contributed the highest ASR of incidence (0.10) and death (0.07) across the 21 GBD regions. The morbidity (1.23) and mortality rate (0.74) of the under 1 year-old group were higher than those of other age groups. Compared with 1990, the incidence, mortality, and DALYs of hepatoblastoma decreased significantly, with estimated annual percentage change (EAPC) of −2.03, −2.54, and − 2.53. The high SDI regions exhibited an upward trend in incidence with EAPC of 0.73. Joinpoint regression analysis indicated a gradual but fluctuating decline in ASR of incidence, prevalence, death and DALYs. The global burden was predicted to decrease while an increased incidence and mortality in low SDI countries.
Conclusion
The morbidity and mortality burden of hepatoblastoma has steadily decreased over the last 31 years. However, the increased incidence in high SDI areas and the higher mortality in low SDI areas pose a significant challenge. Effective differentiated intervention should be facilitated to reduce the impact of hepatoblastoma.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12889-025-24407-3.
Keywords: Hepatoblastoma, Global burden of disease study, Epidemiology, Sociodemographic index
Introduction
Primary liver Cancer in the pediatric age-group was extremely rare, which accounts for only 1% of all malignancies [1, 2]. Although the morbidity exhibited a downward trend, hepatoblastomas are still the most common liver Cancer in children, with 90% of cases occurring within the first 5 years of life [2, 3]. Hepatoblastomas usually present as an asymptomatic abdominal mass with normal liver enzymes [4]. The treatment such as neoadjuvant chemotherapy and surgical resection has advanced, however, the overall prognosis remains unsatisfactory [5]. Thus, considerable planning was required for an increasing survival by policy makers to ensure adequate resource allocation.
Despite the cause of hepatoblastoma is mostly unknown, an increase in incidence has been reported recently owing to the higher number of survivors of premature birth and infants with birth weight lower than 1500 g, especially in developed countries [6, 7]. With better medical care, it has been reported that the 5-year survival rate of children with Cancer has reached approximately 80% in high-income countries [8]. However, the survival rate was only 40% in low-income countries [9]. It is difficult to establish an adequate national medical insurance system, thus resulting in a lower survival rate and higher burden of childhood cancer in low-income countries [10]. It is important for pediatricians and government officials to have knowledge about the epidemiology, incidence and mortality trend difference between regions.
Nowadays, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) study provides a chance to gain a deeper understanding of hepatoblastoma. The GBD study 2021, conducted by the Institute for Health Metrics and Evaluation, permits a more precise estimate of health loss caused by hepatoblastoma across different regions in 204 countries and territories. The GBD study is also a systematic, scientific effort to quantify the comparative magnitude of health loss due to diseases, injuries, and risk factors by age, sex, and geographies for specific points in time. It employs a robust methodology to estimate the burden of disease, including the use of statistical tools like DisMod-MR 2.1 for disease modeling, geographical restrictions and assumption methods for missing data, garbage code handling for cause-of-death analyses, and supplementary data sources and covariates to enhance data comprehensiveness and reliability [11, 12].
Quantifying hepatoblastoma trends and understanding how they vary between countries is critical. Besides, the under-five mortality rate is a valid indicator of the quality of national economic and healthcare systems. Children in the early phases of childhood are the main targets of public health policies [13]. In a recent study, the incidence, mortality, and DALYs of hepatoblastoma were reported to decrease significantly from 1990 to 2021. Human development level was positively associated with the average annual percentage change of incidence, and high-income regions showed an upward trend in incidence [14]. However, further exploration of global trends and regional differences, especially age and gender composition, is an important factor in determining the disease burden of hepatoblastoma. Thus, based on the latest data of GBD 2021, we systematically analyzed the global, regional, and national burden of hepatoblastoma from 1990 to 2021 to provide a more comprehensive perspective to make global and regional targeted intervention and health policies.
Methods
Data source
Hepatoblastoma was diagnosed according to the International Classification of Diseases tenth edition (ICD-10) with code C22.2. The global, regional, and national burden data of hepatoblastoma was obtained from the GBD study 2021, which provides a comprehensive evaluation of the health impacts of 371 Diseases along with 88 risk factors across 204 countries and territories. The 204 countries and territories were classified into 21 regions based on epidemiological similarities and geographical proximity, including North and Middle East Africa, Central Sub-Saharan Africa, Southern Sub-Saharan Africa, Western Sub-Saharan Africa, Eastern Sub-Saharan Africa; Caribbean, Southern Latin America, Andean Latin America, Tropical Latin America, High-income North America, Central Latin America; East Asia, Southeast Asia, Central Asia, High-income Asia Pacific, South Asia; Eastern Europe, Central Europe, Western Europe; Oceania and Australasia. The countries and territories were also divided into five groups based on their SDI (low SDI, low-middle SDI, middle SDI, high-middle SDI, and high SDI). SDI is a composite indicator of development status strongly correlated with health outcomes. The SDI value is usually between 0 and 1, with higher values indicating higher socio-economic, demographic, and development levels in the region. The incidence, prevalence, mortality, and DALYs (disability-adjusted life years) data was download from the Global Health Data Exchange query tool (http://ghdx.healthdata.org/gbd-results-tool). The analysis of this study is based on the latest epidemiological data and improved standardized techniques. This study complies with the Declaration of Helsinki and was exempted from ethical approval by the Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University because all data used were obtained from public databases.
Estimation of hepatoblastoma burden
The annual incidence, prevalence, mortality, and DALYs data and its corresponding age-standardized rate for hepatoblastoma were download online and reported with 95% uncertainty intervals (UIs). The uncertainty analysis of each step in the computation process is stored in 1000 draws, and the 1000 draws are used for every step in the data process, with final estimates computed using the mean estimate across 1000 draws. The 95% UIs were calculated as the 2.5th and 97.5th percentile of the distribution of 1000 draws at each step in the process, with the uncertainty propagated through each step. The global maps were generated to visualize the distribution of hepatoblastoma burden with R (version 4.2.3) using the “ggplot2” and “sf” packages. To summarize the age distribution of the burden, patients were divided into 4groups: under 1 year-old group, 1–2 years-old group, 2–4 years-old group, and 5–9 years-old group. The comparative magnitude of health loss caused by hepatoblastoma across different regions stratified by gender and age was also explored.
Temporal trend analysis
The age-standardized rate and average annual percentage change (APC) were utilized to analyze hepatoblastoma temporal trends. We used the joinpoint regression model, which consists of linear statistical models by connecting several different lines, to assess the temporal trends of incidence, prevalence, mortality, and DALYs. This model can identify significant changes in data trends over time, distinguishing real shifts in trends from random variability. The results are presented as APC value accompanied by corresponding 95% confidence intervals (CIs) to determine the statistical significance of the trends. An upward trend in the age-standardized rate could be identified if the APC and its 95% CI are both > 0, and if they were both < 0, the age-standardized rate was deemed to present a decreasing trend. The analysis was performed using the “Joinpoint” R package. Besides, the temporal trend analysis of gender disparity among different SDI regions were also analyzed for comparison the burden of hepatoblastoma. The R package “dplyr” and “ggplot2” were utilized for data manipulation and visualization.
Bayesian Age-Period-Cohort (BAPC) model for forecasting
The future burden of hepatoblastoma from 2022 to 2035 were projected by used the Bayesian age-period-cohort (BAPC) model. The BAPC model is a log-linear Poisson model that provides a comprehensive approach to understanding future trends in disease burden, considering the effects of age, period, and cohort. It combines prior information on unknown parameters with sample information to estimate the posterior distribution and infer these unknown parameters We employed the BAPC model within the integrated nested Laplacian approximation (R packages BAPC and INLA) to project the incidence and mortality of hepatoblastoma.
Statistical analysis
Descriptive analysis was performed to describe the overall burden of hepatoblastoma and by age, sex, SDI, and 21 regions using age-standardized rates. All data analyses were conducted using the open-source software R (version 4.2.3) and JD_GBDR (V2.27, Jing ding Medical Technology Co., Ltd.). A two-tail p value < 0.05 was considered statistically significant.
Results
Global and National levels of hepatoblastoma burden
Over the past 31 years, the global absolute number (incidence, prevalence, deaths, and DALYs) of hepatoblastoma has decreased significantly. In 2021, the newly incident cases were 4048.42 (95% UI: 3252.45-5000.45) and the number of deaths caused by hepatoblastoma was 2416.17 (95% UI: 1922.47-3019.03). Compared to 1990, the incident cases were 7063.70 (95% UI: 5798.84-8280.72) and 4828.29 (95% UI: 3938.60-5670.55) for deaths, the percentage change decreased by 42.69% and 49.96% respectively. The similar trends were also observed in prevalence (decreased 39.79%), deaths (decreased 49.96%), and DALYs (decreased 49.93%) (Table S1). The global age-standardized rate of incidence, deaths, and DALYs were 0.06 (95% UI: 0.05–0.08), 0.04 (95% UI: 0.03–0.05), and 3.27 (95% UI: 2.61–4.10) with EAPCof − 2.03, −2.54, and − 2.53 (Table 1). To further clarify the differences in hepatoblastoma burden between countries, the map was generated with the data of age-standardized rate (Fig. 1). At the country level, the highest age-standardized incidence rates of hepatoblastoma were in the Republic of Mali 0.36 (95% UI: 0.21–0.54), followed by the Republic of the Gambia 0.28 (95% UI: 0.18–0.42) and Mongolia 0.27 (95% UI: 0.17–0.40). Meanwhile, the top three countries with the highest mortality burden caused by hepatoblastoma were the Republic of Mali 0.25 (95% UI: 0.15–0.38), followed by the Republic of the Gambia 0.19 (95% UI: 0.13–0.29) and Republic of Guinea 0.18 (95% UI: 0.10–0.28).
Table 1.
The age-standardized incidence, prevalence, deaths, dalys of hepatoblastoma, and estimated annual percent change between 1990 and 2021
| Incidence | Prevalence | Deaths | DALYs | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1990 | 2021 | EAPC | 1990 | 2021 | EAPC | 1990 | 2021 | EAPC | 1990 | 2021 | EAPC | |
| Global |
0.11 (0.09, 0.13) |
0.06 (0.05, 0.08) |
−2.03 (−2.17, −1.89) |
0.91 (0.33, 1.20) |
0.52 (0.28, 0.68) |
−1.84 (−1.98, −1.70) |
0.08 (0.06, 0.09) |
0.04 (0.03, 0.05) |
−2.54 (−2.68, −2.40) |
6.90 (5.64, 8.09) |
3.27 (2.61, 4.10) |
−2.53 (−2.67, −2.39) |
| SDI | ||||||||||||
| Low SDI |
0.16 (0.11, 0.20) |
0.09 (0.06, 0.12) |
−1.88 (−1.98, −1.79) |
1.21 (0.26, 1.81) |
0.69 (0.17, 1.02) |
−1.71 (−1.81, −1.62) |
0.11 (0.08, 0.14) |
0.06 (0.04, 0.08) |
−1.94 (−2.03, −1.85) |
9.79 (6.67, 12.76) |
5.27 (3.71, 7.16) |
−1.93 (−2.02, −1.84) |
| Low-middle |
0.10 (0.06, 0.12) |
0.06 (0.05, 0.07) |
−1.38 (−1.48, −1.28) |
0.74 (0.18, 1.09) |
0.48 (0.21, 0.62) |
−1.17 (−1.28, −1.06) |
0.07 (0.05, 0.08) |
0.04 (0.03, 0.05) |
−1.50 (−1.60, −1.41) |
5.94 (4.00, 7.48) |
3.47 (2.78, 4.24) |
−1.49 (−1.59, −1.40) |
| Middle SDI |
0.13 (0.12, 0.15) |
0.05 (0.04, 0.06) |
−3.62 (−3.92, −3.32) |
1.06 (0.38, 1.36) |
0.41 (0.29, 0.54) |
−3.36 (−3.65, −3.07) |
0.09 (0.08, 0.11) |
0.03 (0.02, 0.03) |
−4.40 (−4.67, −4.13) |
8.16 (7.11,9.43) |
2.29 (1.84, 2.86) |
−4.40 (−4.67, −4.13) |
| High-middle |
0.11 (0.09, 0.13) |
0.05 (0.04, 0.07) |
−2.81 (−3.19, −2.43) |
0.90 (0.53, 1.13) |
0.48 (0.37, 0.60) |
−2.53 (−2.89, −2.17) |
0.07 (0.06, 0.08) |
0.02 (0.02, 0.02) |
−5.13 (−5.58, −4.68) |
6.36 (5.45, 7.48) |
1.66 (1.37, 2.01) |
−5.10 (−5.55, −4.66 |
| High SDI |
0.05 (0.05, 0.06) |
0.06 (0.06, 0.07) |
0.73 (0.44, 1.03) |
0.47 (0.41, 0.51) |
0.59 (0.53, 0.65) |
0.82 (0.51, 1.14) |
0.02 (0.02, 0.03) |
0.02 (0.01, 0.02) |
−1.19 (−1.26, −1.12) |
2.05 (1.90, 2.22) |
1.41 (1.29, 1.52) |
−1.15 (−1.21, −1.08) |
DALYs disability-adjusted life years, SDI sociodemographic index, EAPC estimated annual percentage change
Fig. 1.
The global burden of hepatoblastoma in 204 countries and territories in 2021. Geographical distribution of age-standardized rates (rate per 100,000 population) of hepatoblastoma for (A) incidence; (B) prevalence; (C) deaths; (D) Disability-adjusted life-years (DALYs)
Hepatoblastoma burden and SDI regions
To analyze the regional differences, the age-standardized rate of incidence, prevalence, deaths, and DALYs were compared across different SDI regions. In 2021, 35.0% of new cases and 40.9% of deaths occurred in the low SDI regions (Table S1). Among the five SDI regions, the highest age-standardized rate of morbidity and mortality also occurred in the low SDI regions, with 0.09 (95% UI: 0.06–0.12) and 0.06 (95% UI: 0.04–0.08), respectively. Only the high SDI regions exhibited an upward trend in incidence and prevalence from 1990 to 2021, with an estimated annual percentage change (EAPC) value of 0.73 (95% CI: 0.44–1.03) and 0.82 (95% CI: 0.51–1.14). The most obvious decrease in incidence and prevalence was identified in the middle SDI regions with an EAPC value of − 3.62 and − 3.36. The global death and DALYs burden presented a downward trend, with an EAPC value of − 2.54 (95% CI: −2.68 - −2.40) and − 2.53 (95% CI: −2.67 - −2.39). The largest changes in the burden of death and DALYs were found in high-middle SDI regions with an EAPC value of − 5.13 and − 5.10.
Regional hepatoblastoma burden
Across the 21 GBD regions, the highest incidence of hepatoblastoma in 2021 was reported in Western Sub-Saharan, with an age-standardized rate of 0.10 (95% UI: 0.07–0.14), followed by High-income North America (0.09). The number of new cases was 823.63 (95% UI: 590.15-1092.90) and 179.17 (95% UI: 159.52-200.12) respectively. Southern Latin America had the lowest age-standardized rate (0.01). Five GBD regions showed an increased EAPC of incidence from 1990 to 2021, with the High-income North America experiencing a substantial increase to 2.10 (95% CI: 1.83–2.36). In 2021, the Western Sub-Saharan has the highest age-standardized mortality rate of 0.07 (95% CI: 0.05–0.09) and 570.57 (95% UI: 412.61-754.29) deaths. The mortality burden showed a decreasing trend in 17 (81.0%) GBD regions, with the most significant decrease occurring in East Asia (EAPC = − 5.87) (Table 2).
Table 2.
The morbidity and mortality burden of hepatoblastoma among the 21 GBD regions, percentage change and estimated annual percent change between 1990 and 2021
| Incidence | Deaths | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Number | ASR | Number | ASR | |||||||||
| 1990 | 2021 | PC | 1990 | 2021 | EAPC | 1990 | 2021 | PC | 1990 | 2021 | EAPC | |
| Africa | ||||||||||||
| North and Middle East |
494.49 (363.20, 626.77) |
329.21 (258.26, 418.23) |
−33.43 (−52.17, 8.36) |
0.10 (0.07, 0.12) |
0.05 (0.04, 0.07) |
−1.47 (−1.62, −1.33) |
345.12 (253.95, 439.81) |
207.81 (163.13, 264.61) |
−39.78 (−56.73, −2.33) |
0.07 (0.05, 0.09) |
0.03 (0.03, 0.04) |
−1.82 (−1.94, −1.69) |
| Central Sub-Saharan |
149.69 (80.52, 236.45) |
96.54 (43.07, 177.06) |
−35.50 (−68.31, 67.84) |
0.15 (0.08, 0.23) |
0.05 (0.02, 0.08) |
−3.73 (−3.92, −3.53) |
106.51 (57.59, 169.19) |
67.95 (30.54, 128.14) |
−36.20 (−68.81, 65.85) |
0.10 (0.06, 0.17) |
0.03 (0.01, 0.06) |
−3.77 (−3.97, −3.57) |
| Southern Sub-Saharan |
32.96 (21.31, 44.96) |
39.65 (27.76, 53.36) |
20.32 (−22.38, 97.24) |
0.04 (0.03, 0.06) |
0.05 (0.03, 0.07) |
0.12 (−0.17, 0.41) |
23.09 (14.89, 31.96) |
27.78 (19.73, 37.25) |
20.35 (−22.74, 97.80) |
0.03 (0.02, 0.04) |
0.03 (0.02, 0.05) |
0.11 (−0.19, 0.41) |
| Western Sub-Saharan |
728.20 (528.23, 958.65) |
823.63 (590.15, 1092.90) |
13.11 (−17.72, 54.54) |
0.20 (0.14, 0.26) |
0.10 (0.07, 0.14) |
−2.13 (−2.25, −2.01) |
512.58 (372.73, 672.85) |
570.57 (412.61, 754.29) |
11.31 (−18.83, 51.85) |
0.14 (0.10, 0.18) |
0.07 (0.05, 0.09) |
−2.19 (−2.31, −2.06) |
| Eastern Sub-Saharan |
570.58 (389.58, 750.81) |
509.77 (296.93, 887.71) |
−10.66 (−49.19, 83.09) |
0.16 (0.11, 0.21) |
0.08 (0.05, 0.14) |
−2.08 (−2.19, −1.97) |
403.16 (275.32, 530.64) |
356.09 (208.91, 622.67) |
−11.67 (−49.56, 81.55) |
0.11 (0.08, 0.15) |
0.06 (0.03, 0.10) |
−2.12 (−2.23, −2.01) |
| America | ||||||||||||
| Caribbean |
11.54 (7.37, 16.70) |
7.09 (4.67, 11.03) |
−38.55 (−57.90, −8.87) |
0.03 (0.02, 0.04) |
0.02 (0.01, 0.03) |
−1.23 (−1.45, −1.01) |
8.04 (5.10, 11.68) |
4.79 (3.13, 7.50) |
−40.45 (−59.43, −11.22) |
0.02 (0.01, 0.03) |
0.01 (0.01, 0.02) |
−1.34 (−1.57, −1.11) |
| Southern Latin America |
3.49 (3.00, 4.03) |
3.86 (3.15, 4.63) |
10.57 (−14.73, 42.22) |
0.01 (0.01, 0.01) |
0.01 (0.01, 0.01) |
1.47 (1.20, 1.75) |
2.35 (2.02, 2.72) |
2.14 (1.76, 2.58) |
−8.86 (−29.44, 17.48) |
0.00 (0.00, 0.01) |
0.00 (0.00, 0.01) |
0.69 (0.42, 0.96) |
| Andean Latin America |
39.48 (28.35, 51.85) |
15.54 (10.45, 22.40) |
−60.62 (−76.25, −30.42) |
0.07 (0.05, 0.10) |
0.03 (0.02, 0.04) |
−3.52 (−3.80, −3.23) |
27.72 (19.96, 36.48) |
9.92 (6.85, 14.44) |
−64.22 (−78.28, −38.00) |
0.05 (0.04, 0.07) |
0.02 (0.01, 0.02) |
−3.84 (−4.10, −3.58) |
| Tropical Latin America |
78.10 (67.55, 92.00) |
39.92 (30.90, 48.91) |
−48.88 (−61.65, −34.99) |
0.05 (0.04, 0.05) |
0.02 (0.02, 0.03) |
−1.72 (−2.05, −1.38) |
54.33 (47.04, 64.17) |
25.65 (19.81, 31.37) |
−52.79 (−64.50, −39.98) |
0.03 (0.03, 0.04) |
0.02 (0.01, 0.02) |
−1.94 (−2.29, −1.59) |
| High-income North America |
109.95 (107.09, 112.97) |
179.17 (159.52, 200.12) |
62.95 (44.76, 81.67) |
0.05 (0.05, 0.05) |
0.09 (0.08, 0.10) |
2.10 (1.83, 2.36) |
37.60 (36.71, 38.49) |
44.73 (40.18, 49.66) |
18.95 (6.09, 31.97) |
0.02 (0.02, 0.02) |
0.02 (0.02, 0.02) |
1.04 (0.91, 1.17) |
| Central Latin America |
174.99 (162.17, 191.07) |
86.24 (66.40, 112.87) |
−50.72 (−62.46, −33.64) |
0.08 (0.07, 0.08) |
0.04 (0.03, 0.06) |
−1.54 (−1.69, −1.39) |
122.06 (113.18, 133.02) |
54.97 (42.52, 71.12) |
−54.96 (−65.42, −40.58) |
0.05 (0.05, 0.06) |
0.03 (0.02, 0.04) |
−1.84 (−1.99, −1.70) |
| Asia | ||||||||||||
| East Asia |
2315.21 (1923.65, 2834.26) |
565.79 (401.57, 801.91) |
−75.56 (−83.05, −64.71) |
0.20 (0.17, 0.25) |
0.08 (0.05, 0.11) |
−3.84 (−4.30, −3.38) |
1600.79 (1334.50, 1955.01) |
221.61 (160.34, 309.45) |
−86.16 (−90.39, −79.85) |
0.14 (0.12, 0.17) |
0.03 (0.02, 0.04) |
−5.87 (−6.42, −5.32) |
| Southeast Asia |
649.44 (434.90, 832.71) |
252.42 (185.72, 346.57) |
−61.13 (−71.27, −45.05) |
0.11 (0.07, 0.14) |
0.04 (0.03, 0.06) |
−2.85 (−3.00, −2.70) |
452.62 (303.40, 581.36) |
163.83 (121.81, 226.13) |
−63.81 (−73.08, −48.75) |
0.08 (0.05, 0.10) |
0.03 (0.02, 0.04) |
−3.10 (−3.23, −2.97) |
| Central Asia |
114.69 (93.85, 143.67) |
42.42 (31.03, 56.76) |
−63.01 (−74.19, −48.45) |
0.12 (0.10, 0.15) |
0.04 (0.03, 0.06) |
−3.31 (−3.47, −3.15) |
79.13 (64.84, 99.36) |
28.04 (20.52, 37.26) |
−64.56 (−75.29, −50.80) |
0.08 (0.07, 0.11) |
0.03 (0.02, 0.04) |
−3.49 (−3.63, −3.35) |
| High-income Asia Pacific |
100.06 (83.56, 118.87) |
37.63 (33.08, 44.48) |
−62.39 (−69.91, −52.29) |
0.10 (0.08, 0.11) |
0.06 (0.05 ,0.07) |
−1.82 (−2.56, −1.07) |
47.07 (36.27, 59.14) |
8.55 (7.62, 9.92) |
−81.84 (−86.19, −75.23) |
0.04 (0.03, 0.06) |
0.01 (0.01, 0.02) |
−4.30 (−4.72, −3.88) |
| South Asia |
1177.67 (706.70, 1587.70) |
815.54 (632.69, 1044.53) |
−30.75 (−52.66, 27.01) |
0.08 (0.04, 0.10) |
0.05 (0.04, 0.07) |
−1.04 (−1.15, −0.93) |
833.92 (496.45, 1122.17) |
559.48 (436.13, 716.62) |
−32.91 (−54.23, 22.85) |
0.05 (0.03, 0.07) |
0.04 (0.03, 0.05) |
−1.16 (−1.26, −1.06) |
| Europe | ||||||||||||
| Eastern Europe |
155.17 (144.97, 165.69) |
57.70 (52.12, 63.11) |
−62.81 (−66.19, −59.40) |
0.09 (0.09, 0.10) |
0.06 (0.05, 0.06) |
−2.12 (−2.63, −1.60) |
99.09 (93.00, 105.62) |
25.95 (23.63, 28.27) |
−73.81 (−76.12, −71.46) |
0.06 (0.05, 0.06) |
0.02 (0.02, 0.03) |
−3.50 (−3.86, −3.13) |
| Central Europe |
43.14 (37.20, 50.15) |
8.92 (7.19, 11.04) |
−79.33 (−84.37, −73.01) |
0.05 (0.04, 0.05) |
0.02 (0.01, 0.02) |
−3.56 (−4.00, −3.11) |
28.08 (24.22, 32.74) |
3.52 (2.85, 4.32) |
−87.48 (−90.41, −83.72) |
0.03 (0.03, 0.04) |
0.01 (0.01, 0.01) |
−5.36 (−5.75, −4.98) |
| Western Europe |
105.71 (100.82, 110.75) |
120.09 (104.65, 136.48) |
13.60 (−1.86, 30.48) |
0.05 (0.04, 0.05) |
0.06 (0.05, 0.07) |
0.82(0.64,0.99) |
40.91 (39.01, 42.92) |
26.94 (23.83, 30.28) |
−34.16 (−42.25, −25.28) |
0.02 (0.02, 0.02) |
0.01 (0.01, 0.01) |
−0.81 (−1.02, −0.60) |
| Oceania | ||||||||||||
| Oceania |
2.95 (1.81, 4.87) |
4.03 (2.31, 7.07) |
36.88 (−31.07, 177.07) |
0.03 (0.02, 0.05) |
0.02 (0.01, 0.04) |
−1.26 (−1.60, −0.92) |
2.06 (1.28, 3.56) |
2.78 (1.58, 4.85) |
34.99 (−32.34, 171.80) |
0.02 (0.01, 0.04) |
0.01 (0.01, 0.02) |
−1.30 (−1.64, −0.96) |
| Australasia |
6.22 (5.52, 6.94) |
13.27 (10.41, 16.63) |
113.44 (62.18, 182.36) |
0.04 (0.04, 0.05) |
0.07 (0.06, 0.09) |
2.04 (1.73, 2.35) |
2.05 (1.82, 2.29) |
3.08 (2.46, 3.79) |
49.90 (16.30, 94.17) |
0.01 (0.01, 0.01) |
0.02 (0.01, 0.02) |
1.00 (0.76, 1.23) |
DALYs: disability-adjusted life years, PC: percentage change, ASR: age-standardized rate, EAPC: estimated annual percentage change
Age and sex patterns of hepatoblastoma burden
There were no relevant cases documented for those over 10 years old. The age-standardized incidence rate for patients under 1 year-old group was 1.23 (95% UI: 0.99–1.53), higher than 1–2 years-old group (0.58), 2–4 years-old group (0.29), and 5–9 years-old group (0.08). Except for cases under 1 year-old group, the proportion of male patients in other age groups was slightly higher than that of female patients (Fig. 2A). The age-standardized mortality rate presented a similar trend, the rate has dropped from 0.74 (under 1 year-old group) to 0.06 (5–9 years-old group). The female mortality rate is slightly higher than male for cases under 1 year-old group, while an opposite trend occurred in the 2–4 years-old group (Fig. 2B). The age composition of different GBD regions was also analyzed. Among children under 1 year-old group, the highest incidence rate was in Western Sub-Saharan Africa (74.4%), followed by South Asia (63.5%) and North Africa and Middle East (56.6%). For 1–2 years-old group, Oceania had the highest incidence at 56.3%, followed by North America at 51.6% (Fig. 2C). The age distribution of mortality is similar. The highest mortality rate is in Western Sub-7Saharan Africa (74.2%) for those under 1 year 1–2 years-old group, Oceania (56.1%) for those 1–2 years-old group, Andean Latin America (23.5%) for those 2–4 years-old group, and Southern Latin America (23.5%) for 5–9 years-old group (Fig. 2D). Globally, the age-standardized incidence rate did not differ between male and female. The age-standardized incidence rate in all 21 GBD regions in males was High-income North America (0.11) and Western Sub-Saharan Africa (0.10). As for females, Eastern Sub-Saharan Africa (0.10) and Western Sub-Saharan Africa (0.10) occupies the highest incidence rate (Fig. 3A). The highest age-standardized mortality rates for males were in Western Sub-Saharan Africa (0.07) and Eastern Sub-Saharan Africa (0.04), and for females were Eastern Sub-Saharan Africa (0.07) and Western Sub-Saharan Africa (0.07) (Fig. 3B).
Fig. 2.
The differences in the disease burden of hepatoblastoma among age groups in 2021. (A) The incidence cases and age-standardized incidence rate stratified by gender and different age groups; (B) The number of deaths and age-standardized mortality rate stratified by gender and different age groups; (C) The age group distribution of the age-standardized incidence rate of hepatoblastoma across the 21 GBD regions; (D) The age group distribution of the age-standardized mortality rate across the 21 GBD regions
Fig. 3.
The gender differences in the burden of hepatoblastoma among the 21 GBD regions. (A) age-standardized incidence rate and (B) mortality rate
Temporal trends of hepatoblastoma burden
The APC of age-standardized incidence rate was examined by the Joinpoint regression analysis, and three breakpoints were identified (1997, 2005,2017). Between 1990 and 1997, there was a slight decrease (APC = − 0.52, − 0.76 - −0.29), followed by a significant decrease between 1997 and 2005 (APC = − 3.67, − 3.90 - −3.44). Furthermore, the downward trend is slowing down between 2005 and 2017 (APC = − 1.14, − 1.26 - −1.01), and another significant decrease occurs between 2007 and 2021 (APC = − 3.49, − 4.15 - −2.83) (Fig. 4A). The temporal trend of age-standardized prevalence is similar, with the three breakpoints 1997, 2005, and 2018 (Fig. 4B). The most noticeable decrease in the temporal trend of age-standardized mortality was between 1997 and 2006 (APC = − 4.11, − 4.34 - −3.88), and between 2016 and 2021 (APC = − 3.29, − 3.76 - −2.83) (Fig. 4C). For DALYs, the three breakpoints were 1997, 2006, and 2016 with the highest decrease observed between 1997 and 2006 (APC = − 3.89, − 4.05 - −3.73) (Fig. 4D). Next, the temporal trend of age-standardized morbidity and mortality stratified by SDI and sex was explored. For middle, low-middle, and low SDI regions, a decreasing trend over time was observed. As for high SDI regions, there is a gradual upward trend until reaching a peak of 0.07 (per 100, 000) in 2008, then gradually decreasing to 0.06 (per 100, 000) in 2021. In addition, the proportion of males is significantly higher than that of females. In high-middle SDI, the incidence rate increased gradually from 1990 to 1997, then decreased gradually (Fig. 5A). Consistent with the incidence, the age-standardized mortality in high-middle SDI regions also increased to the peak in 1997, followed by a downward trend until 2021. Both the global and other SDI regions exhibited a substantial decreased tendency in mortality (Fig. 5B).
Fig. 4.
Joinpoint regression analysis of temporal trends of hepatoblastoma from 1990 to 2021. The annual percentage change (APC) of the age-standardized rate of (A) incidence; (B) prevalence; (C)deaths; (D) Disability-adjusted life-years
Fig. 5.
The temporal trends and gender differences of age-standardized (A) incidence rate and (B) mortality rate worldwide and across different sociodemographic index regions from 1990 to 2021
Prediction of age-standardized rate of incidence and mortality
The projection and the changing trends of age-standardized incidence rate and mortality rate were explored with the BAPC model. Globally, the incidence rate will decrease from 0.06 in 2022 to 0.05 (per 100,000 population) in 2035 (Fig. 6A), while the mortality rate gradually decreases to 0.03 in 2035 (Fig. 6B). The predicted age-standardized incidence rates showed a decreasing trend in middle SDI, high-middle SDI, and high SDI regions, while the middle SDI regions had the lowest rate. On the contrary, the incidence rate presents an increasing trend in low SDI and low-middle SDI, and the highest predicted incidence rate occurs in the low SDI regions (0.036) (Fig. 6C). Unlike the incidence rate, the predicted age-standardized mortality rate decreased in all SDI regions except the low SDI regions. The age-standardized mortality rate in low SDI regions will slowly increase to 0.025 over the next decade.
Fig. 6.
The projected trends in age-standardized incidence and mortality rates from 2022 to 2035. The global incidence rate (A) and the mortality rate (B), the incidence rate (C) and the mortality rate (D) among different sociodemographic index regions. The blue region shows the upper and lower limits of the 95% UI
Although with an increasing incidence rate, the mortality rate exhibited a slow decline to 0.01 in low-middle SDI regions (Fig. 6D).
Discussion
The current study provides a comprehensive analysis of the hepatoblastoma burden across regions, countries, time, age, and sex during the period from 1990 to 2021. To our knowledge, this is one of the few studies analyzing the burden of hepatoblastoma based on the GBD study 2021. It has been reported that the majority of hepatoblastoma cases occur between the ages of 6 months and 3 years [15, 16]. Children with cancer have long-term effects on survivors, leading to financial losses and related chronic complications [17–19]. Accurate data on the burden of hepatoblastoma are essential for improving its prevention and treatment strategies and prioritizing health resources.
Few population-based studies have reported the trends in hepatoblastoma incidence over the past few decades. According to the the Surveillance, Epidemiology and End Results (SEER) program, the rate of hepatoblastoma showed a significant annual increase (2.2%) in hepatoblastoma incidence between 2000 and 2015 [20]. Another study also indicated that the incidence of pediatric hepatoblastoma increased from 1975 to 2018 [21]. An asian population-based study analyzing the Taiwan Cancer Registry (TCR) database reported that, the overall incidence of hepatoblastoma in children increased by 7.4% per year and, specifically, by 6.5% among males from 1995 to 2012 [22]. Contrary to these reports, our results indicated that the age-standardized incidence rate of hepatoblastoma decreased significantly globally from 1990 to 2021. The reasons can be attributed to the differences in statistical populations. The varying incidence rates across countries also prompt us to conduct national-level assessments and develop country-specific prevention plans. Early deaths for children with cancer lead to many years lived with disability (YLDs), and years of life lost (YLLs), thus, DALYs provide a useful summary measure of early mortality and treatment-related mortality [23–25]. In the present study, age-standardized mortality and DALYs both tend to decrease over time. With the development of the whole society, advanced screening facilities and improved medical care systems have led to the decreased burden of hepatoblastoma. A recent study also showed a steady decline in the incidence, mortality, and DALYs due to paediatric cancers among children aged zero to nine years worldwide [24].
Unpacking the hepatoblastoma burden varies with sex and geographical regions, and how it has changed from 1990 to 2021 is important to improve the existing public health policies and prevention strategies [2]. In this study, the hepatoblastoma burden differs substantially among regions and nations according to SDI, which is a systematic measure that combines information on the economy, education, and fertility rate of each country or region. Consistent with the reports above [20, 22], our results also indicated that the age-standardized incidence of high SDI regions presented an upward trend with the proportion of males significantly higher than that of females. The increased incidence rate can be attributable to the development of screening tests and early cancer detection in regions with effective healthcare systems [26]. Meanwhile, the easier access to health care also led to a downward trend in deaths and DALYs in high-SDI regions. Low SDI regions bear an overwhelming burden, constituting 35% of incident cases, and 41% of deaths in 2021. The heavier burden can be explained by the unmet need for pediatric healthcare resulting from inadequate health infrastructure, which led to delayed diagnosis, delayed treatment [27, 28]. Therefore, countries with low SDI need to develop an amendment-specific for hepatoblastoma and execute greater investment and research to improve the higher burden.
The increasing proportion of the global birth cohort resides in Sub-Saharan Africa making the burden of hepatoblastoma remains challenging [29]. Across the 21 GBD regions, the highest incidence and deaths both were reported in Western Sub-Saharan. As reported, the large proportion of young people in low-income countries may be associated with an increased risk of childhood cancer [30]. Additionally, caregivers have limited time to care for children due to larger family sizes, which leads to delayed detection of early signs and symptoms of cancer and results in inadequate and poor-quality care for sick children [31]. Thus, the governments in Sub-Saharan Africa regions need to evaluate the current strategies and barriers in order to develop a more robust national action plan for improving the burden of hepatoblastoma.
Due to overall socioeconomic improvements, less-developed countries have made faster progress in terms of SDI over the last twenty years [32]. Besides, substantial improvements to primary healthcare systems have been made in low- and middle-income countries [33, 34]. Recognizing the strong connections between socioeconomic status and health and reducing the hepatoblastoma burden is an important step in prioritizing prevention and treatment policies. In 2035, our prediction model estimates that the morbidity and mortality of middle SDI, high-middle SDI, and high SDI regions will gradually decrease. However, the incidence and mortality rates in the low SDI countries showed an opposite trend. The increasing burden of hepatoblastoma may be related to the development and widespread application of new diagnostic capabilities and early screening throughout the whole society. In addition, the high proportion of children born prematurely, with low birth weight or genetic diseases in developed countries is closely related. Also, the high environmental risks such as pesticide exposure, ionizing radiation, and infections, can help to interpret the elevated risk of hepatoblastoma.
Generally, despite the decreasing burden of hepatoblastoma, it remains a significant public health issue, especially in some African countries. Considering the low SDI regions suffer much more than other SDI regions, the local health departments and policymakers should pay more attention to implementing preventive tactics. The potential strategies include widespread early screening among children under 1 year old, regular medical examination, timely surgical intervention, and management of associated morbidities to improve outcomes [35]. Based on our results, the differences in different age groups and gender across different GBD regions could also be taken into account. Health policies should devote more medical resources to strengthen the welfare of such children. On the other hand, the upward trend in High SDI countries reminds us of the importance of reducing premature and low birth weight children. Monitoring the health of the mother and baby to ensure a healthy pregnancy is extremely important for preventing hepatoblastoma [36].
There were some inevitable limitations in the present study, which mainly exist in all GBD studies [37]. First, the accuracy and robustness of the GBD study depend mainly on the data quality and modeling stability. Due to the high standard of health care, the reported epidemiological data were complete and accurate in developed countries. However, for countries where national systematic surveillance was lacking or insufficient, the data was estimated using prediction models, patterns or trends displayed from nearby countries [11, 38]. The lack of detailed and high-quality data in these countries may lead to some information bias in registration databases, which may affect the accuracy of the result. Future work should focus on expanding data collection efforts in developing regions and populations. Another limitation of this study is the lack of racial differences. Our study estimated the burden of hepatoblastoma cancer by age and sex but not by race. Racial disparities in treatment and outcomes of hepatoblastoma were also recently reported using the National Cancer Database, and showed that black patients experienced inferior overall survival when diagnosed and treated compared to white patients [39]. The apparent regional differences in incidence suggest that ethnicity information differences should be further explored.
Conclusions
In the present study, we comprehensively analyzed the distribution of hepatoblastoma burden by sex, age group, and area and its changing trend over the past 31 years worldwide. The overall burden has been decreasing worldwide. Countries with low SDI still bore the heaviest burden of hepatoblastoma and exhibited an increased tendency until 2035. On the other hand, the incidence of hepatoblastoma in high SDI countries shows a slight increase, but with a decreased mortality rate. The results showed ongoing epidemiologic transitions, demographic shifts, and regional differences in hepatoblastoma burden. Country-specific differentiated intervention and outreach strategies should be considered by policymakers to alleviate the hepatoblastoma burden.
Supplementary information
Below is the link to the electronic supplementary material.
Acknowledgements
This work was supported by the grant from Joint Fund of The Third Affiliated Hospital of Sun Yat-Sen University and Chaozhou Central Hospital (LH202210), Clinical Research Program of The Third Affiliated Hospital of Sun Yat-Sen University (YHJH202206).
Author contributions
QLW and BL: conception and design, revised the manuscript. KS CCX XYZ: data acquisition and analysis, drafted the manuscript. HL XHL data analysis. All authors have read and approved the final manuscript.
Funding
This work was supported by the grant from Joint Fund of The Third Affiliated Hospital of Sun Yat-Sen University and Chaozhou Central Hospital (LH202210), Clinical Research Program of The Third Affiliated Hospital of Sun Yat-Sen University (YHJH202206).
Data availability
The data supporting this study’s findings are openly available in the Global Burden of Diseases Study (GBD) 2021 at https://www.healthdata.org/research-analysis/gbd. These data were derived from the following resources available in the public domain: https://ghdx.healthdata.org/gbd-2021.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Kai Shi, Congcong Xu and Xueyao Zhang contributed equally to this work.
Contributor Information
Bo Liu, Email: hubo96073@126.com.
Qingliang Wang, Email: wangql5@mail.sysu.edu.cn.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data supporting this study’s findings are openly available in the Global Burden of Diseases Study (GBD) 2021 at https://www.healthdata.org/research-analysis/gbd. These data were derived from the following resources available in the public domain: https://ghdx.healthdata.org/gbd-2021.