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Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut atnd Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. +MORE
| Yong Chan Lee |
Professor of Medicine Director, Gastrointestinal Research Laboratory Veterans Affairs Medical Center, Univ. California San Francisco San Francisco, USA |
| Jong Pil Im | Seoul National University College of Medicine, Seoul, Korea |
| Robert S. Bresalier | University of Texas M. D. Anderson Cancer Center, Houston, USA |
| Steven H. Itzkowitz | Mount Sinai Medical Center, NY, USA |
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Hua Zhou1 
, Mengxia Yan2 , Datian Che1 , Bin Wu3
Correspondence to: Datian Che
ORCID https://orcid.org/0000-0002-5574-6411
E-mail cshdoctor@yeah.net
Bin Wu
ORCID https://orcid.org/0000-0002-6696-7471
E-mail scilwsjtu-wb@yahoo.com
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Gut Liver 2024;18(3):539-549. https://doi.org/10.5009/gnl230023
Published online April 19, 2024, Published date May 15, 2024
Copyright © Gut and Liver.
Background/Aims: This study aimed to analyze the trends in mortality attributed to hepatitis B and C around the Western Pacific region from 1990 to 2019.
Methods: We used data from the Global Burden of Disease Study for a systematic analysis. The deaths related to hepatitis B and C were analyzed by age, sex, year, risk factors, geographical location, and Socio-demographic Index (SDI).
Results: From 1990 to 2019, the annual total deaths from hepatitis B decreased from 0.266 to 0.210 million and those from hepatitis C increased from 0.119 to 0.142 million in the Western Pacific region. The age-standardized mortality rate (ASMR) of hepatitis B and C decreased by 63.5% and 48.0%, respectively. The declines in the ASMR related to hepatitis B and C were only detected in 12 and two Western Pacific countries, respectively. As the major risk factors, the contribution of alcohol use to hepatitis B deaths was 52% and drug use to hepatitis C was 80%. In males and females, the ASMR attributed to hepatitis B decreased by 61% and 71%, respectively, and the ASMR attributed to hepatitis C decreased by 43% and 55%, respectively. The association between SDI and ASMRs suggested that hepatitis B and C, respectively, showed an overall decline and stable trends as the SDI improved in the Western Pacific region.
Conclusions: Although the mortality rate from hepatitis B and C decreased from 1990 to 2019, notable variation was observed among 27 Western Pacific countries. Efforts targeting hepatitis B and C prevention and treatment are still required in this region, especially for the pandemic countries.
Keywords: Hepatitis B, Hepatitis C, Mortality, Trend, The Western Pacific Region
Hepatitis infection, including hepatitis B virus (HBV) and hepatitis C virus (HCV), are serious global health problems. In 2019, an estimated 296 million people worldwide were living with chronic HBV infection and 58 million people with chronic HCV infection, representing 4.4% of the world's population.1,2 These viruses are the leading causes of chronic hepatitis, liver cirrhosis, and cancer, which yielded an estimated 1.57 million deaths in 2019, accounting for 2.1% of all deaths worldwide.1 As one of the regions with the highest disease burden, an estimated 126 million people in the Western Pacific region were living with chronic hepatitis, including 116 million with chronic HBV infection (defined hepatitis B surface antigen positive) and 10 million with chronic HCV (positive HCV viremia). These figures accounted for 40% and 17% of the global HBV burden (296 million) and HCV burden (58 million), respectively.3 The World Health Organization committed in 2016 to eliminating HBV and HCV by 2030, through a range of therapeutic interventions.4,5 By 2030, the World Health Organization aims to reduce the incidence of HBV and HCV by 90% and mortality by 65%. Although the recently released 2021 global progress report on viral hepatitis has shown that a “very good trajectory” for the 2020 targets has been met, there are still significant challenges to achieving the goal of eliminating viral hepatitis in the next decade,6,7 especially in those with high disease burden related to HBV and HCV.
HBV and HCV infections are influenced by a variety of factors, including demographic trends, risk behaviors, and socioeconomic development. The past three decades have seen significant changes in sociodemographics, economics, and risk factors. Currently, the reality of increased vaccination coverage, greater access to affordable and effective HBV treatments, and the availability of curative therapies for HCV infection has emerged.8 As a result of these changes, the epidemiology of HBV and HCV infections has changed significantly, with marked geographic variation. Clarifying the components and trends of disease burden may help policy decision makers to determine and identify future targets and interventions. On a Western Pacific region scale, there is a lack of accurate information on the burden of hepatitis B and C. By adopting data from the Global Burden of Disease (GBD) Study 2019,1 this systematic analysis investigated the temporal and geographical trends in mortality from HBV and HCV infections and their associations with risk factors from 1990 to 2019 in this region.
All anonymized data on the disease associated with HBV and HCV infections during 1990–2019 were collected from the Global Health Data Exchange online query tool by sex, age, year, and location (publicly accessed online).9 Based on the World Health Organization data,10 the current analysis included a total of 27 countries in the Western Pacific region: Australia, Brunei Darussalam, Cambodia, China, Cook Islands, Fiji, Japan, Kiribati, Lao People’s Democratic Republic, Malaysia, Marshall Islands, Micronesia (Federated States of), Mongolia, Nauru, New Zealand, Niue, Palau, Papua New Guinea, Philippines, Republic of Korea, Samoa, Singapore, Solomon Islands, Tonga, Tuvalu, Vanuatu, and Vietnam. Because GBD 2019 uses de-identified, aggregated data, a waiver for informed consent was approved by the Renji Hospital Institutional Review Board. This study was conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology reporting guideline.
Cause-specific deaths by sex, age, year, and location were derived from GBD 2019. The GBD study utilized the DisMod-MR meta-regression tool to estimate the seroprevalence of hepatitis B surface antigen and anti-HCV immunoglobulin G in specific age groups, sexes, countries, and years. The DisMod-MR tool utilizes a compartmental offset log-normal non-linear mixed-effects model with hierarchical random effects on geographic factors.11 Its purpose is to generate consistent estimations of disease incidence, prevalence, and mortality. In the present analysis, the causes of death associated with hepatitis B and C were categorized into six distinct groups, including acute hepatitis related to hepatitis B, cirrhosis and other chronic liver diseases related to hepatitis B, liver cancer related to hepatitis B, acute hepatitis related to hepatitis C, cirrhosis and other chronic liver diseases related to hepatitis C, and liver cancer related to hepatitis C. These categories were mutually exclusive. The combined total of hepatitis B-specific causes of death and the combined total of hepatitis C-specific causes of death were referred to as the overall burden attributable to hepatitis B and hepatitis C, respectively.
The GBD 2019 utilized a comparative risk assessment framework to identify risk factors, encompassing environmental and occupational hazards, behavioral risks related to tobacco use, and metabolic risk factors, such as high body mass index. The earlier study provided greater clarity on the hierarchy of these risk factors and their associated definitions of exposure. Based on a previous study,1 attributable deaths were computed by multiplying population attributable fractions by the relevant outcome quantity for each age-sex-location-year. Because alcohol use and drug use are the main risk factors, the current analysis also collected the cause-specific deaths of HBV and HCV related to alcohol use and drug use from GBD 2019.
The Socio-demographic Index (SDI) is a summarized metric that gauges the level of socioeconomic development across GBD locations, ranging from 0 (minimum development) to 1 (maximum development).12 SDI is derived by taking into account the average educational attainment of individuals aged 15 years and older, the total fertility rate among those under 25 years, and income per capita distributed over time. The quintiles for determining SDI were determined based on estimates from countries with populations exceeding 1 million. For further information on the calculation methodology of SDI, please refer to previous GBD publications.13
The number of deaths, the age-standardized mortality rate (ASMR) per 100,000, and percent change with 95% uncertainty intervals (UIs) were used as the endpoints for measuring the burden of disease associated with HBV and HCV, which were depicted by overall and categorized data (age, sex, year, risk factors, and country). UIs were measured from 10,000 sampled estimates, and 95% UIs were set by the 250th and 9,750th values of the ordered 10,000 estimates. In addition, we examined the association between SDI and ASMR related to hepatitis B and C, by year and location. By using the pooling SDI and ASMR data of the countries from 1990 to 2019, the overall changes in the Western Pacific region will be analyzed in the regression analyses. The analytical methods used in this study are described in detail in previous publications,1,14,15 and the related codes are available for download at http://ghdx.healthdata.org/gbd-2019/code. When 95% UIs did not cross zero, statistical significance was achieved.
The design, data collection, analyses, and interpretation of this research were conducted without the involvement of patients or the public.
The trends in hepatitis B and C mortality are shown in Fig. 1. In the Western Pacific region, the number of annual deaths from hepatitis B slightly reduced (from 0.266 to 0.210 million) from 1990 to 2019, while the proportions in the global considerably decreased from 51% in 1990 to 37% in 2019. The ASMR of hepatitis B in the Western Pacific region decreased from 20.98 in 1990 to 7.66 in 2019, a decrease of 63.5%. However, it was still slightly higher than the global ASMR in 2019 (6.74). The annual total deaths from hepatitis C in the Western Pacific region increased from 0.119 million in 1990 to 0.142 million in 2019. Because of the increase in the global death number caused by hepatitis C, the proportion of deaths in the Western Pacific region relative to that in the global considerably decreased, from 35% in 1990 to 28% in 2019. In the Western Pacific region, the ASMR of hepatitis C declined from 10.48 in 1990 to 5.44 (a decrease of 48.0%) in 2019, becoming slightly lower than the global ASMR since 2003.
Figure 1.Death counts and age-standardized mortality rates (ASMRs) caused by hepatitis B and C in the Western Pacific region and global from 1990 to 2019. The percent data are the proportions of the Western Pacific region out of the world.
Variable ASMR trends were shown in 27 Western Pacific countries (Table 1). From 1990 to 2019, the ASMR of hepatitis B significantly decreased in 12 counties, decreasing from 38% in Singapore to 67% in China. The remaining counties showed decreasing trends, but no significant differences were found. When the global ASMR was used as the reference, the 2019 ASMR of hepatitis B was above or below the global level in all 27 Western Pacific counties in comparison with 1990 (Supplementary Fig. 1). However, the gap between the local and global levels narrowed from 1990 to 2019, except in Mongolia, indicating that the ASMR of hepatitis B in the Western Pacific region was decreasing. Supplementary Fig. 2 shows the ranks of the 27 Western Pacific counties in the 204 countries and territories. From 1990 to 2019, the ranking of the ASMR of hepatitis B in the world moved up in 12 countries; e.g., Mongolia moved from rank 3 in 1990 to rank 1 in 2019. The remaining 15 countries moved down; e.g., the Republic of Korea moved from rank 17 in 1990 to rank 27 in 2019. Only two Western Pacific countries achieved a significant decline in the ASMR of hepatitis C from 1990 to 2019 (a decrease of 58% in China, and a decrease of 35% in Japan). The remaining counties maintained a stable trend. The 2019 ASMR of hepatitis C was below or above the global level in all Western Pacific countries in comparison with 1990, except in China (Supplementary Fig. 1), where the reverse result was found (the ASMR fell below the global level). Between 1990 and 2019, the ranking of the ASMR of hepatitis C in the world moved up in 11 countries; e.g., Cambodia moved from rank 5 in 1990 to rank 3 in 2019. The remaining 15 countries moved down; e.g., China moved from rank 65 in 1990 to rank 89 in 2019. Mongolia maintained the second highest ASMR for hepatitis C from 1990 to 2019.
Table 1. ASMR for Both Sexes Combined in 2019 and the Percentage Change from 1990 to 2019
| Countries and regions | 2019 SDI | Hepatitis B | Hepatitis C | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 2019 ASMR per 100,000 people | Decrease in ASMR 1990-2019, % | 2019 ASMR attributable to alcohol use, % | Decrease in ASMR attributable to alcohol use 1990-2019, % | 2019 ASMR per 100,000 people | Decrease in ASMR 1990-2019, % | 2019 ASMR attributable to drug use, % | Decrease in ASMR attributable to drug use 1990-2019, % | |||
| Global | 0.651 | 6.74 (5.92 to 7.63) | 45 (33 to 56)* | 67 (57 to 74) | 35 (–32 to 70) | 6.67 (5.87 to 7.49) | 21 (3 to 36)* | 80 (79 to 80) | 6 (–30 to 31) | |
| Western Pacific region | NA | 7.66 (6.47 to 8.91) | 64 (53 to 72)* | 52 (46 to 56) | 57 (19 to 78)* | 5.44 (4.74 to 6.17) | 48 (36 to 58)* | 80 (78 to 82) | 41 (16 to 59)* | |
| Australia | 0.839 | 1.45 (1.15 to 1.82) | 19 (–20 to 45) | 76 (71 to 80) | 42 (–4 to 67) | 3.91 (3.27 to 4.45) | –7 (–37 to 18) | 93 (92 to 93) | –14 (–48 to 14) | |
| Brunei Darussalam | 0.823 | 8.6 (6.99 to 10.53) | 32 (3 to 52)* | 0 (0 to 0) | 100 (94 to 100)* | 6.55 (5.16 to 8.10) | 4 (–44 to 37) | 89 (82 to 93) | –55 (–228 to 26) | |
| Cambodia | 0.469 | 19.05 (14.02 to 25.10) | 46 (15 to 65)* | 92 (89 to 95) | –708 (–278,128 to –84)* | 24.18 (17.70 to 31.38) | 14 (–36 to 47) | 34 (28 to 39) | –25 (–248 to 56) | |
| China | 0.686 | 8.07 (6.66 to 9.69) | 67 (56 to 76)* | 46 (41 to 49) | 62 (25 to 82)* | 4.04 (3.36 to 4.75) | 58 (46 to 69)* | 91 (91 to 93) | 50 (28 to 65)* | |
| Cook Islands | 0.764 | 7.67 (5.8 to 9.87) | 39 (8 to 59)* | 45 (39 to 50) | –121 (–82,647 to 46) | 4.45 (3.32 to 5.75) | 31 (–10 to 56) | 92 (90 to 93) | 12 (–52 to 49) | |
| Fiji | 0.664 | 6.36 (4.72 to 8.35) | 27 (–13 to 53) | 49 (35 to 58) | 27 (–134 to 79) | 4.25 (3.09 to 5.60) | 9 (–48 to 44) | 95 (95 to 96) | –11 (–94 to 38) | |
| Japan | 0.87 | 2.37 (2.08 to 2.66) | 43 (32 to 53)* | 72 (66 to 77) | 50 (14 to 72)* | 9.80 (8.64 to 10.53) | 35 (27 to 44)* | 59 (49 to 68) | 5 (–87 to 51) | |
| Kiribati | 0.527 | 19.33 (12.59 to 28.13) | 46 (7 to 70)* | 41 (0 to 67) | 53 (–4,481 to 100) | 11.30 (6.97 to 17.12) | 27 (–44 to 64) | 97 (95 to 98) | 15 (–104 to 64) | |
| Lao People’s Democratic Republic | 0.490 | 10.54 (7.38 to 14.47) | 52 (18 to 73)* | 84 (75 to 89) | 24 (–157 to 75) | 9.30 (6.49 to 12.71) | 30 (–23 to 61) | 48 (39 to 55) | –4 (–221 to 64) | |
| Malaysia | 0.737 | 11.15 (8.57 to 14.26) | 13 (–21 to 38) | 52 (15 to 68) | 46 (–165 to 94) | 5.38 (3.85 to 7.23) | –14 (–83 to 30) | 87 (80 to 91) | –59 (–288 to 32) | |
| Marshall Islands | 0.544 | 13.57 (8.97 to 19.27) | 40 (–1 to 66) | 55 (21 to 75) | 35 (–822 to 93) | 8.81 (5.45 to 13.42) | 22 (–48 to 60) | 96 (96 to 98) | 7 (–100 to 57) | |
| Micronesia (Federated States of) | 0.580 | 13.56 (8.2 to 20.83) | 38 (–19 to 70) | 52 (27 to 66) | 60 (–92 to 94) | 8.70 (4.97 to 13.75) | 23 (–63 to 65) | 96 (94 to 97) | 8 (–119 to 64) | |
| Mongolia | 0.606 | 39.65 (28.2 to 54.19) | 8 (–50 to 44) | 27 (16 to 32) | –15 (–431 to 73) | 54.80 (40.83 to 70.85) | –53 (–141 to 3) | 66 (56 to 74) | –56 (–331 to 40) | |
| Nauru | 0.618 | 12.83 (8.12 to 19.24) | 36 (–30 to 68) | 69 (50 to 76) | 33 (–215 to 85) | 8.83 (5.29 to 13.44) | 16 (–85 to 62) | 94 (92 to 94) | –1 (–162 to 59) | |
| New Zealand | 0.840 | 1.25 (1.10 to 1.41) | 11 (–9 to 28) | 68 (64 to 70) | 39 (9 to 60)* | 2.72 (2.45 to 3.02) | –6 (–27 to 11) | 93 (93 to 93) | –17 (–44 to 4) | |
| Niue | 0.711 | 8.75 (6.38 to 11.42) | 40 (1 to 65)* | 59 (6 to 72) | 49 (–267 to 98) | 6.02 (4.20 to 8.20) | 21 (–41 to 57) | 95 (95 to 95) | 3 (–81 to 49) | |
| Palau | 0.738 | 11.84 (8.40 to 16.27) | 25 (–33 to 58) | 42 (2 to 59) | 18 (–11,000 to 99) | 5.94 (3.86 to 8.94) | 13 (–84 to 57) | 96 (94 to 97) | –4 (–143 to 54) | |
| Papua New Guinea | 0.394 | 4.64 (3.27 to 6.50) | 28 (–29 to 60) | 70 (16 to 84) | 60 (–148 to 98) | 3.19 (2.17 to 4.44) | 5 (–69 to 48) | 98 (98 to 99) | –9 (–105 to 42) | |
| Philippines | 0.623 | 7.03 (5.58 to 8.74) | 50 (26 to 66)* | 77 (71 to 79) | 46 (–5 to 74) | 6.35 (5.10 to 7.93) | 21 (–18 to 46) | 18 (15 to 21) | 0 (–162 to 60) | |
| Republic of Korea | 0.878 | 13.09 (11.14 to 15.15) | 58 (46 to 67)* | 49 (36 to 56) | 83 (64 to 93)* | 4.23 (3.23 to 5.31) | 27 (–9 to 51) | 78 (72 to 83) | –8 (–132 to 47) | |
| Samoa | 0.641 | 10.22 (7.66 to 13.39) | 29 (–14 to 57) | 66 (42 to 74) | 26 (–142 to 81) | 5.32 (3.83 to 7.21) | 25 (–29 to 57) | 97 (96 to 97) | 15 (–58 to 53) | |
| Singapore | 0.861 | 6.46 (5.36 to 7.55) | 38 (23 to 52)* | 20 (10 to 26) | 65 (–29 to 92) | 2.99 (2.13 to 3.93) | –2 (–64 to 38) | 88 (85 to 92) | –50 (–209 to 29) | |
| Solomon Islands | 0.407 | 13.89 (10.28 to 18.16) | 39 (–6 to 65) | 52 (11 to 69) | –69 (–4,128 to 90) | 9.16 (6.60 to 12.36) | 14 (–55 to 52) | 99 (98 to 99) | 7 (–80 to 50) | |
| Tonga | 0.636 | 22.29 (16.85 to 29.04) | 28 (–11 to 54) | 13 (1 to 23) | –56 (–12,931 to 97) | 11.29 (8.35 to 14.93) | 10 (–47 to 44) | 96 (95 to 96) | –15 (–101 to 34) | |
| Tuvalu | 0.589 | 12.15 (8.44 to 16.97) | 38 (–7 to 64) | 49 (21 to 65) | 35 (–360 to 91) | 7.24 (4.78 to 10.51) | 25 (–46 to 61) | 97 (96 to 98) | 9 (–92 to 55) | |
| Vanuatu | 0.485 | 14.08 (9.50 to 19.31) | 36 (–16 to 66) | 57 (26 to 74) | 45 (–174 to 91) | 8.44 (5.09 to 12.25) | 16 (–62 to 59) | 97 (96 to 98) | –3 (–121 to 54) | |
| Vietnam | 0.617 | 7.88 (5.72 to 10.76) | 57 (25 to 75)* | 95 (91 to 97) | –5,935 (–4,070,514 to –1,187)* | 7.86 (5.59 to 10.60) | 34 (–20 to 63) | 78 (71 to 81) | 4 (–141 to 59) | |
ASMR, age-standardized mortality rates; SDI, Socio-demographic Index; NA, not applicable.
*Changes that are statistically significant.
In 2019, the leading risk factors for deaths due to hepatitis B and C in the Western Pacific regions were alcohol and drug use, respectively, which accounted for 52% of deaths from hepatitis B and for 80% of deaths from hepatitis C. From 1990 to 2019, the proportions of both hepatitis B deaths attributed to alcohol use and hepatitis C deaths attributed to drug use remained stable (Supplementary Fig. 3). The ASMR of hepatitis B attributed to alcohol use and the ASMR of hepatitis C attributed to drug use significantly declined in the Western Pacific region by 57% and 41%, respectively, from 1990 to 2019 (Table 1). In 27 Western Pacific countries, the ASMR of hepatitis B attributed to alcohol use significantly increased from 1990 to 2019 by 5935% and 708% in Vietnam and Cambodia, respectively (Table 1, Fig. 2), and significantly decreased in five countries (from 39% in New Zealand to 100% in Brunei Darussalam), while other countries had no substantial change related to the ASMR of hepatitis B attributed to alcohol use. The ASMR of hepatitis C attributed to drug use showed no significant change in the whole Western Pacific region, except in China, where it notably decreased (by 50%) from 1990 to 2019.
Figure 2.Age-standardized mortality rates (ASMRs) of hepatitis B and C attributed to alcohol and drug use for both sexes in the 27 Western Pacific countries from 1990 to 2019.
The trends of the ASMR varied by sex in the Western Pacific region. Namely, in men and women, the ASMR attributed to hepatitis B declined from 32.46 to 12.79 (a decrease of 61%) and from 9.97 to 2.85 (a decrease of 71%), respectively. The ASMR associated with hepatitis B showed significant reductions for both men and women (Supplementary Fig. 4). In acute hepatitis, the ASMR reduced by 82% and 88% for men and women, respectively. In cirrhosis and other chronic liver diseases, the ASMR declined by 63% and 72% for men and women, respectively. Additionally, in liver cancer, the ASMR decreased by 58% for men and 68% for women, respectively. As for hepatitis C, the ASMR in the Western Pacific region declined from 13.10 to 7.52 (a decrease of 43%) and from 8.07 to 3.65 (a decrease of 55%) in men and women, respectively. For hepatitis C, the sex-specific ASMR associated with hepatitis C reduced by 89% and 93% in acute hepatitis, by 43% and 55% in cirrhosis and other chronic liver diseases, and by 41% and 54% in liver cancer for men and women, respectively.
The ASMR attributable to hepatitis B and C varied significantly by age and sex (Fig. 3). In 2019, the highest ASMR of hepatitis B in men was about 20,000 in individuals aged 50 to 65 years, while the highest ASMR in women was about 4,000 in those aged 60 years or more. In men, the ASMR of hepatitis C rose steeply from 487 in those aged 25 to 29 years to about 10,000 in those aged 65 years or more; in women, it rose from 267 in those aged 30 to 34 years to about 10,000 in those aged 85 years or more. Compared to 1990, the ASMR of hepatitis B reduced in the younger population in 2019, decreasing from 2% in 65 to 69 years to 95% in 0 to 9 years males, and from 19% in 75- to 79-year-old to 96% in 0- to 9-year-old females. In the older population, the ASMR of hepatitis B in men increased from 8% in 70- to 74-year-old individuals to 196% in those older than 85 years; in women, it increased from 18% in 80- to 84-year-old individuals to 120% in those older than 85 years. The ASMR of hepatitis C in 2019 also reduced in the younger population, declining from 9% in 65- to 69-year-old to 96% in 0- to 9-year-old females, and decreased from 5% in 60- to 64-year-old to 94% in 0- to 9-year-old males, except for the population aged 45 to 54 years. Namely, the ASMR of hepatitis C increased in the older population, from 4% in 45- to 54-year-old individuals to 347% in those aged 85 years or more in males, and from 2% in 70- to 74-year-old individuals to 257% in those aged 85 years or more in females.
Figure 3.(A, B) Age-standardized mortality rates (ASMRs) of hepatitis B and C in the Western Pacific region between 1990 and 2019 stratified by age and sex. The annotation number indicates the decreased level in 2019 compared with that in 1990.
In 12 Western Pacific countries that had a better SDI than the Global SDI level, only five countries had a lower ASMR related to hepatitis B than the global ASMR level. Although the Republic of Korea had the highest SDI in the Western Pacific region, its ASMR related to hepatitis B had a rank of 9 (Table 1). Nearly all of the countries with a worse SDI compared with the global level had a higher ASMR related to hepatitis B compared with the global level, except for Papua New Guinea. The ASMR from 1990 to 2019 across SDI by country were shown in Fig. 4. With the improvement of SDI, a declining trend in the ASMR of hepatitis B was found in the Western Pacific region (the black dashed line in Fig. 4). Based solely on SDI, the ASMR of hepatitis B was much higher than expected in the Republic of Korea and Mongolia.
Figure 4.The age-standardized mortality rates (ASMRs) of hepatitis B and C across 27 Western Pacific countries, whole Western Pacific region, and the world by Socio-demographic Index from 1990 to 2019. For each country, points from left to right depict estimates from each year from 1990 to 2019.
Among the 12 Western Pacific countries with a better SDI compared with the Global SDI level, 11 countries had a lower ASMR related to hepatitis C than the global ASMR level, except for Japan. Although Japan had the second highest SDI in the Western Pacific region, its ASMR related to hepatitis C had the rank of 5 (Table 1). Nearly all countries with a worse SDI compared with the global level had a higher ASMR associated with hepatitis C compared to the global level, except for Papua New Guinea, Philippines, and Samoa. With the improvement of SDI, a stable trend in the ASMR of hepatitis C was found in the Western Pacific region (the black dashed line in Fig. 4). Based solely on SDI, the ASMR of hepatitis B was much higher than expected in Japan and Mongolia.
Our analysis explored the long-term trends in hepatitis B and C mortality in the Western Pacific region from 1990 to 2019. Comparing with the global, the ASMR per 100,000 Western Pacific population more notably decreased from 1990 to 2019. Namely, the ASMR of hepatitis B and C reduced by 64% and 48%, respectively, so the ASMRs of hepatitis B and C in 2019 became not notably different compared with the global level. In an additional analysis (Supplementary Fig. 5), the age-standardized incidence rate of hepatitis B and C per 100,000 Western Pacific population decreased by 47% and 33%, respectively, which was also more favorable compared with the global (35% and 9%). However, it was found that the reduction of the mortality rate was more substantial than the incidence rate. This transition may be attributed to social development and health-care services, including vaccination programs, reducing the risk of exposure, and actively managing patients infected with hepatitis B and C viruses. However, some countries, such as Mongolia, highlight that health transition is not predictably linear with SDI improvement. The underlying reason is that it has not attracted enough attention to the challenge caused by hepatitis B and C. For example, it was in recent years that the Healthy Liver Programme 2017 to 2020 strategy encompassed an ambitious plan to eliminate HCV and control HBV was implemented in Mongolia.3 In the Western Pacific region with the hepatitis B and C epidemic, uniformly efficient health-care services reaching the whole population and effective multisectoral provisions on risk factors (such as alcohol and drug use) still have to be strengthened.16
Despite a significant decrease in mortality rates for both sexes, male ASMRs for hepatitis B and C were four and two times higher than female ASMRs, respectively, from 1990 to 2019. These findings suggest that further efforts are needed to reduce the disease burden of hepatitis B and C in men. The habits of men, such as drinking alcohol, may have caused these sex-specific effects.17 Consumption of alcohol exceeding 50 g per day significantly elevates the risk of cirrhosis in HCV-infected individuals. Those affected by both alcohol-use disorder and HCV infection are prone to developing decompensated liver disease at a younger age, leading to poorer overall survival. Alcohol harm reduction strategies in the Western Pacific region should prioritize evidence-based interventions to change drinking patterns.
The change in the mortality rate is mainly attributed to the dramatically declining mortality rate related to liver cancer and cirrhosis and other chronic liver diseases, especially the complications due to hepatitis B, whose reduction could partly explain the fact that the ASMR of hepatitis B has become comparable with that of hepatitis C. It should also be noted that the ASMR related to cirrhosis and other chronic liver diseases in 2019 has become lower in males than in females regardless of hepatitis B and C, and the ASMR related to liver cancer remained higher in males than in females. Therefore, to further reduce the risk of mortality related to hepatitis B and C, more precise interventions for cirrhosis and liver cancer might be considered by gender.
The peak of the 2019 ASMR related to hepatitis B was in the population aged between 50 and 65 years. By contrast, the mortality rate of hepatitis C steadily increased with age. A relatively lower incidence rate of hepatitis B and a higher incidence rate of hepatitis C in the old population could be partly explained by these divergent age effects.18 The current analysis also showed that the 2019 ASMR in the younger population (below 50 years) was lower than that in 1990 regardless of sex and type of hepatitis. However, the 2019 ASMR in the old population, that is, in individuals over 80 years, was higher than that in 1990. This phenomenon might be explained by the HBV vaccine protection for the young population and the lagged complications in the old population due to the use of antiviral treatment. Cirrhosis and liver cancer may occur 20 to 30 years after antiviral treatment for hepatitis B and C, which may lead to an increase in ASMR with age.19,20
As the main contributors, alcohol and drug use are still related to hepatitis B and C deaths, respectively, from 1990 to 2019 in the Western Pacific region. Although the ASMRs of hepatitis B and C related to alcohol use and drug use significantly declined in the Western Pacific region, the ASMRs of hepatitis B in only five countries and hepatitis C in only one country achieved a significant decline. This finding indicates that combined efforts to reduce alcohol and drug use, such as psychosocial interventions, are necessary for populations with hepatitis B and C.21
Among the 27 Western Pacific countries, there were distinct differences in the mortality rates. The notable improvement in hepatitis B and C mortality in the Western Pacific region was substantially attributed to the Chinese decline, as China was the only country in the whole region that achieved a significant decrease both in hepatitis B and hepatitis C. However, the ASMR of hepatitis B in more than 50% and hepatitis C in more than 90% of countries did not significantly improve. For example, Mongolia was consistently one of the countries with the highest ASMRs related to hepatitis B and C, which were about 31 and 20 times higher than the lowest ASMRs of hepatitis B and C in New Zealand, respectively. National efforts of a comprehensive strategy, such as a vaccination program for hepatitis B and low-cost antiviral drugs for hepatitis B and C, are highlighted by the Chinese experience,22,23 which should be emergently and precisely implemented for countries with high disease burden.24
Several weaknesses should be noted in this analysis. First, this analysis was based on data from the GBD study 2019. Given the recent issues with other reports, the robustness and accuracy of the findings depend on the quality and quantity of the input data. Due to few large-scale population surveys of viral hepatitis seroprevalence in the Western Pacific region, the GBD estimations about hepatitis B and C were based on regional extrapolations and covariates, potentially minimizing spatial heterogeneity and differences in epidemics.11 Therefore, these results depend heavily on covariates and space–time extrapolation, highlighting the need for more longitudinal studies and better ascertainment of disease burden. Second, this study focused on the major risk factors for hepatitis B and C mortality, and did not consider the detailed risk factors. These issues may be addressed in future studies. Finally, due to the lack of relevant data, the effects of prevention and management programs in different countries were not included in this study, and considerable variations might exist among countries.
Although the mortality rate from hepatitis B and C decreased from 1990 to 2019, notable variation was observed in 27 Western Pacific countries. To achieve the global hepatitis elimination targets, Western Pacific countries with high disease burdens caused by hepatitis B and C should urgently adopt the successful experiences of other countries in screening, vaccination, and antiviral treatment.
This project was supported by a grant from the National Natural Science Foundation of China (72074142). The funders were not involved the collection, analysis, or interpretation of data, or in the writing or submitting of this report. The first author and corresponding author had full access to all data and final responsibility for the decision to submit for publication.
We would like to thank the Institute for Health Metrics and Evaluation staff and its collaborators who prepared these publicly available data.
No potential conflict of interest relevant to this article was reported.
Study concept and design: B.W., D.C. Data acquisition: H.Z., M.Y. Data analysis and interpretation: H.Z. Drafting of the manuscript: H.Z., D.C. Critical revision of the manuscript for important intellectual content: B.W. Statistical analysis: M.Y. Obtained funding: B.W. Administrative, technical, or material support; study supervision: B.W. Approval of final manuscript: all authors.
Supplementary materials can be accessed at https://doi.org/10.5009/gnl230023.
Data sources and code used in the Global Burden of Disease Study 2019 are available on the internet (http://ghdx.healthdata.org/gbd-results-tool).
Gut and Liver 2024; 18(3): 539-549
Published online May 15, 2024 https://doi.org/10.5009/gnl230023
Copyright © Gut and Liver.
Hua Zhou1 , Mengxia Yan2 , Datian Che1 , Bin Wu3
1Department of VIP, Shanghai Children's Hospital affiliated with the School of Medicine, Shanghai Jiaotong University, Shanghai, China; 2Department of Pharmacy and 3Clinical Research Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
Correspondence to:Datian Che
ORCID https://orcid.org/0000-0002-5574-6411
E-mail cshdoctor@yeah.net
Bin Wu
ORCID https://orcid.org/0000-0002-6696-7471
E-mail scilwsjtu-wb@yahoo.com
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background/Aims: This study aimed to analyze the trends in mortality attributed to hepatitis B and C around the Western Pacific region from 1990 to 2019.
Methods: We used data from the Global Burden of Disease Study for a systematic analysis. The deaths related to hepatitis B and C were analyzed by age, sex, year, risk factors, geographical location, and Socio-demographic Index (SDI).
Results: From 1990 to 2019, the annual total deaths from hepatitis B decreased from 0.266 to 0.210 million and those from hepatitis C increased from 0.119 to 0.142 million in the Western Pacific region. The age-standardized mortality rate (ASMR) of hepatitis B and C decreased by 63.5% and 48.0%, respectively. The declines in the ASMR related to hepatitis B and C were only detected in 12 and two Western Pacific countries, respectively. As the major risk factors, the contribution of alcohol use to hepatitis B deaths was 52% and drug use to hepatitis C was 80%. In males and females, the ASMR attributed to hepatitis B decreased by 61% and 71%, respectively, and the ASMR attributed to hepatitis C decreased by 43% and 55%, respectively. The association between SDI and ASMRs suggested that hepatitis B and C, respectively, showed an overall decline and stable trends as the SDI improved in the Western Pacific region.
Conclusions: Although the mortality rate from hepatitis B and C decreased from 1990 to 2019, notable variation was observed among 27 Western Pacific countries. Efforts targeting hepatitis B and C prevention and treatment are still required in this region, especially for the pandemic countries.
Keywords: Hepatitis B, Hepatitis C, Mortality, Trend, The Western Pacific Region
Hepatitis infection, including hepatitis B virus (HBV) and hepatitis C virus (HCV), are serious global health problems. In 2019, an estimated 296 million people worldwide were living with chronic HBV infection and 58 million people with chronic HCV infection, representing 4.4% of the world's population.1,2 These viruses are the leading causes of chronic hepatitis, liver cirrhosis, and cancer, which yielded an estimated 1.57 million deaths in 2019, accounting for 2.1% of all deaths worldwide.1 As one of the regions with the highest disease burden, an estimated 126 million people in the Western Pacific region were living with chronic hepatitis, including 116 million with chronic HBV infection (defined hepatitis B surface antigen positive) and 10 million with chronic HCV (positive HCV viremia). These figures accounted for 40% and 17% of the global HBV burden (296 million) and HCV burden (58 million), respectively.3 The World Health Organization committed in 2016 to eliminating HBV and HCV by 2030, through a range of therapeutic interventions.4,5 By 2030, the World Health Organization aims to reduce the incidence of HBV and HCV by 90% and mortality by 65%. Although the recently released 2021 global progress report on viral hepatitis has shown that a “very good trajectory” for the 2020 targets has been met, there are still significant challenges to achieving the goal of eliminating viral hepatitis in the next decade,6,7 especially in those with high disease burden related to HBV and HCV.
HBV and HCV infections are influenced by a variety of factors, including demographic trends, risk behaviors, and socioeconomic development. The past three decades have seen significant changes in sociodemographics, economics, and risk factors. Currently, the reality of increased vaccination coverage, greater access to affordable and effective HBV treatments, and the availability of curative therapies for HCV infection has emerged.8 As a result of these changes, the epidemiology of HBV and HCV infections has changed significantly, with marked geographic variation. Clarifying the components and trends of disease burden may help policy decision makers to determine and identify future targets and interventions. On a Western Pacific region scale, there is a lack of accurate information on the burden of hepatitis B and C. By adopting data from the Global Burden of Disease (GBD) Study 2019,1 this systematic analysis investigated the temporal and geographical trends in mortality from HBV and HCV infections and their associations with risk factors from 1990 to 2019 in this region.
All anonymized data on the disease associated with HBV and HCV infections during 1990–2019 were collected from the Global Health Data Exchange online query tool by sex, age, year, and location (publicly accessed online).9 Based on the World Health Organization data,10 the current analysis included a total of 27 countries in the Western Pacific region: Australia, Brunei Darussalam, Cambodia, China, Cook Islands, Fiji, Japan, Kiribati, Lao People’s Democratic Republic, Malaysia, Marshall Islands, Micronesia (Federated States of), Mongolia, Nauru, New Zealand, Niue, Palau, Papua New Guinea, Philippines, Republic of Korea, Samoa, Singapore, Solomon Islands, Tonga, Tuvalu, Vanuatu, and Vietnam. Because GBD 2019 uses de-identified, aggregated data, a waiver for informed consent was approved by the Renji Hospital Institutional Review Board. This study was conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology reporting guideline.
Cause-specific deaths by sex, age, year, and location were derived from GBD 2019. The GBD study utilized the DisMod-MR meta-regression tool to estimate the seroprevalence of hepatitis B surface antigen and anti-HCV immunoglobulin G in specific age groups, sexes, countries, and years. The DisMod-MR tool utilizes a compartmental offset log-normal non-linear mixed-effects model with hierarchical random effects on geographic factors.11 Its purpose is to generate consistent estimations of disease incidence, prevalence, and mortality. In the present analysis, the causes of death associated with hepatitis B and C were categorized into six distinct groups, including acute hepatitis related to hepatitis B, cirrhosis and other chronic liver diseases related to hepatitis B, liver cancer related to hepatitis B, acute hepatitis related to hepatitis C, cirrhosis and other chronic liver diseases related to hepatitis C, and liver cancer related to hepatitis C. These categories were mutually exclusive. The combined total of hepatitis B-specific causes of death and the combined total of hepatitis C-specific causes of death were referred to as the overall burden attributable to hepatitis B and hepatitis C, respectively.
The GBD 2019 utilized a comparative risk assessment framework to identify risk factors, encompassing environmental and occupational hazards, behavioral risks related to tobacco use, and metabolic risk factors, such as high body mass index. The earlier study provided greater clarity on the hierarchy of these risk factors and their associated definitions of exposure. Based on a previous study,1 attributable deaths were computed by multiplying population attributable fractions by the relevant outcome quantity for each age-sex-location-year. Because alcohol use and drug use are the main risk factors, the current analysis also collected the cause-specific deaths of HBV and HCV related to alcohol use and drug use from GBD 2019.
The Socio-demographic Index (SDI) is a summarized metric that gauges the level of socioeconomic development across GBD locations, ranging from 0 (minimum development) to 1 (maximum development).12 SDI is derived by taking into account the average educational attainment of individuals aged 15 years and older, the total fertility rate among those under 25 years, and income per capita distributed over time. The quintiles for determining SDI were determined based on estimates from countries with populations exceeding 1 million. For further information on the calculation methodology of SDI, please refer to previous GBD publications.13
The number of deaths, the age-standardized mortality rate (ASMR) per 100,000, and percent change with 95% uncertainty intervals (UIs) were used as the endpoints for measuring the burden of disease associated with HBV and HCV, which were depicted by overall and categorized data (age, sex, year, risk factors, and country). UIs were measured from 10,000 sampled estimates, and 95% UIs were set by the 250th and 9,750th values of the ordered 10,000 estimates. In addition, we examined the association between SDI and ASMR related to hepatitis B and C, by year and location. By using the pooling SDI and ASMR data of the countries from 1990 to 2019, the overall changes in the Western Pacific region will be analyzed in the regression analyses. The analytical methods used in this study are described in detail in previous publications,1,14,15 and the related codes are available for download at http://ghdx.healthdata.org/gbd-2019/code. When 95% UIs did not cross zero, statistical significance was achieved.
The design, data collection, analyses, and interpretation of this research were conducted without the involvement of patients or the public.
The trends in hepatitis B and C mortality are shown in Fig. 1. In the Western Pacific region, the number of annual deaths from hepatitis B slightly reduced (from 0.266 to 0.210 million) from 1990 to 2019, while the proportions in the global considerably decreased from 51% in 1990 to 37% in 2019. The ASMR of hepatitis B in the Western Pacific region decreased from 20.98 in 1990 to 7.66 in 2019, a decrease of 63.5%. However, it was still slightly higher than the global ASMR in 2019 (6.74). The annual total deaths from hepatitis C in the Western Pacific region increased from 0.119 million in 1990 to 0.142 million in 2019. Because of the increase in the global death number caused by hepatitis C, the proportion of deaths in the Western Pacific region relative to that in the global considerably decreased, from 35% in 1990 to 28% in 2019. In the Western Pacific region, the ASMR of hepatitis C declined from 10.48 in 1990 to 5.44 (a decrease of 48.0%) in 2019, becoming slightly lower than the global ASMR since 2003.
Figure 1. Death counts and age-standardized mortality rates (ASMRs) caused by hepatitis B and C in the Western Pacific region and global from 1990 to 2019. The percent data are the proportions of the Western Pacific region out of the world.
Variable ASMR trends were shown in 27 Western Pacific countries (Table 1). From 1990 to 2019, the ASMR of hepatitis B significantly decreased in 12 counties, decreasing from 38% in Singapore to 67% in China. The remaining counties showed decreasing trends, but no significant differences were found. When the global ASMR was used as the reference, the 2019 ASMR of hepatitis B was above or below the global level in all 27 Western Pacific counties in comparison with 1990 (Supplementary Fig. 1). However, the gap between the local and global levels narrowed from 1990 to 2019, except in Mongolia, indicating that the ASMR of hepatitis B in the Western Pacific region was decreasing. Supplementary Fig. 2 shows the ranks of the 27 Western Pacific counties in the 204 countries and territories. From 1990 to 2019, the ranking of the ASMR of hepatitis B in the world moved up in 12 countries; e.g., Mongolia moved from rank 3 in 1990 to rank 1 in 2019. The remaining 15 countries moved down; e.g., the Republic of Korea moved from rank 17 in 1990 to rank 27 in 2019. Only two Western Pacific countries achieved a significant decline in the ASMR of hepatitis C from 1990 to 2019 (a decrease of 58% in China, and a decrease of 35% in Japan). The remaining counties maintained a stable trend. The 2019 ASMR of hepatitis C was below or above the global level in all Western Pacific countries in comparison with 1990, except in China (Supplementary Fig. 1), where the reverse result was found (the ASMR fell below the global level). Between 1990 and 2019, the ranking of the ASMR of hepatitis C in the world moved up in 11 countries; e.g., Cambodia moved from rank 5 in 1990 to rank 3 in 2019. The remaining 15 countries moved down; e.g., China moved from rank 65 in 1990 to rank 89 in 2019. Mongolia maintained the second highest ASMR for hepatitis C from 1990 to 2019.
Table 1 . ASMR for Both Sexes Combined in 2019 and the Percentage Change from 1990 to 2019.
| Countries and regions | 2019 SDI | Hepatitis B | Hepatitis C | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 2019 ASMR per 100,000 people | Decrease in ASMR 1990-2019, % | 2019 ASMR attributable to alcohol use, % | Decrease in ASMR attributable to alcohol use 1990-2019, % | 2019 ASMR per 100,000 people | Decrease in ASMR 1990-2019, % | 2019 ASMR attributable to drug use, % | Decrease in ASMR attributable to drug use 1990-2019, % | |||
| Global | 0.651 | 6.74 (5.92 to 7.63) | 45 (33 to 56)* | 67 (57 to 74) | 35 (–32 to 70) | 6.67 (5.87 to 7.49) | 21 (3 to 36)* | 80 (79 to 80) | 6 (–30 to 31) | |
| Western Pacific region | NA | 7.66 (6.47 to 8.91) | 64 (53 to 72)* | 52 (46 to 56) | 57 (19 to 78)* | 5.44 (4.74 to 6.17) | 48 (36 to 58)* | 80 (78 to 82) | 41 (16 to 59)* | |
| Australia | 0.839 | 1.45 (1.15 to 1.82) | 19 (–20 to 45) | 76 (71 to 80) | 42 (–4 to 67) | 3.91 (3.27 to 4.45) | –7 (–37 to 18) | 93 (92 to 93) | –14 (–48 to 14) | |
| Brunei Darussalam | 0.823 | 8.6 (6.99 to 10.53) | 32 (3 to 52)* | 0 (0 to 0) | 100 (94 to 100)* | 6.55 (5.16 to 8.10) | 4 (–44 to 37) | 89 (82 to 93) | –55 (–228 to 26) | |
| Cambodia | 0.469 | 19.05 (14.02 to 25.10) | 46 (15 to 65)* | 92 (89 to 95) | –708 (–278,128 to –84)* | 24.18 (17.70 to 31.38) | 14 (–36 to 47) | 34 (28 to 39) | –25 (–248 to 56) | |
| China | 0.686 | 8.07 (6.66 to 9.69) | 67 (56 to 76)* | 46 (41 to 49) | 62 (25 to 82)* | 4.04 (3.36 to 4.75) | 58 (46 to 69)* | 91 (91 to 93) | 50 (28 to 65)* | |
| Cook Islands | 0.764 | 7.67 (5.8 to 9.87) | 39 (8 to 59)* | 45 (39 to 50) | –121 (–82,647 to 46) | 4.45 (3.32 to 5.75) | 31 (–10 to 56) | 92 (90 to 93) | 12 (–52 to 49) | |
| Fiji | 0.664 | 6.36 (4.72 to 8.35) | 27 (–13 to 53) | 49 (35 to 58) | 27 (–134 to 79) | 4.25 (3.09 to 5.60) | 9 (–48 to 44) | 95 (95 to 96) | –11 (–94 to 38) | |
| Japan | 0.87 | 2.37 (2.08 to 2.66) | 43 (32 to 53)* | 72 (66 to 77) | 50 (14 to 72)* | 9.80 (8.64 to 10.53) | 35 (27 to 44)* | 59 (49 to 68) | 5 (–87 to 51) | |
| Kiribati | 0.527 | 19.33 (12.59 to 28.13) | 46 (7 to 70)* | 41 (0 to 67) | 53 (–4,481 to 100) | 11.30 (6.97 to 17.12) | 27 (–44 to 64) | 97 (95 to 98) | 15 (–104 to 64) | |
| Lao People’s Democratic Republic | 0.490 | 10.54 (7.38 to 14.47) | 52 (18 to 73)* | 84 (75 to 89) | 24 (–157 to 75) | 9.30 (6.49 to 12.71) | 30 (–23 to 61) | 48 (39 to 55) | –4 (–221 to 64) | |
| Malaysia | 0.737 | 11.15 (8.57 to 14.26) | 13 (–21 to 38) | 52 (15 to 68) | 46 (–165 to 94) | 5.38 (3.85 to 7.23) | –14 (–83 to 30) | 87 (80 to 91) | –59 (–288 to 32) | |
| Marshall Islands | 0.544 | 13.57 (8.97 to 19.27) | 40 (–1 to 66) | 55 (21 to 75) | 35 (–822 to 93) | 8.81 (5.45 to 13.42) | 22 (–48 to 60) | 96 (96 to 98) | 7 (–100 to 57) | |
| Micronesia (Federated States of) | 0.580 | 13.56 (8.2 to 20.83) | 38 (–19 to 70) | 52 (27 to 66) | 60 (–92 to 94) | 8.70 (4.97 to 13.75) | 23 (–63 to 65) | 96 (94 to 97) | 8 (–119 to 64) | |
| Mongolia | 0.606 | 39.65 (28.2 to 54.19) | 8 (–50 to 44) | 27 (16 to 32) | –15 (–431 to 73) | 54.80 (40.83 to 70.85) | –53 (–141 to 3) | 66 (56 to 74) | –56 (–331 to 40) | |
| Nauru | 0.618 | 12.83 (8.12 to 19.24) | 36 (–30 to 68) | 69 (50 to 76) | 33 (–215 to 85) | 8.83 (5.29 to 13.44) | 16 (–85 to 62) | 94 (92 to 94) | –1 (–162 to 59) | |
| New Zealand | 0.840 | 1.25 (1.10 to 1.41) | 11 (–9 to 28) | 68 (64 to 70) | 39 (9 to 60)* | 2.72 (2.45 to 3.02) | –6 (–27 to 11) | 93 (93 to 93) | –17 (–44 to 4) | |
| Niue | 0.711 | 8.75 (6.38 to 11.42) | 40 (1 to 65)* | 59 (6 to 72) | 49 (–267 to 98) | 6.02 (4.20 to 8.20) | 21 (–41 to 57) | 95 (95 to 95) | 3 (–81 to 49) | |
| Palau | 0.738 | 11.84 (8.40 to 16.27) | 25 (–33 to 58) | 42 (2 to 59) | 18 (–11,000 to 99) | 5.94 (3.86 to 8.94) | 13 (–84 to 57) | 96 (94 to 97) | –4 (–143 to 54) | |
| Papua New Guinea | 0.394 | 4.64 (3.27 to 6.50) | 28 (–29 to 60) | 70 (16 to 84) | 60 (–148 to 98) | 3.19 (2.17 to 4.44) | 5 (–69 to 48) | 98 (98 to 99) | –9 (–105 to 42) | |
| Philippines | 0.623 | 7.03 (5.58 to 8.74) | 50 (26 to 66)* | 77 (71 to 79) | 46 (–5 to 74) | 6.35 (5.10 to 7.93) | 21 (–18 to 46) | 18 (15 to 21) | 0 (–162 to 60) | |
| Republic of Korea | 0.878 | 13.09 (11.14 to 15.15) | 58 (46 to 67)* | 49 (36 to 56) | 83 (64 to 93)* | 4.23 (3.23 to 5.31) | 27 (–9 to 51) | 78 (72 to 83) | –8 (–132 to 47) | |
| Samoa | 0.641 | 10.22 (7.66 to 13.39) | 29 (–14 to 57) | 66 (42 to 74) | 26 (–142 to 81) | 5.32 (3.83 to 7.21) | 25 (–29 to 57) | 97 (96 to 97) | 15 (–58 to 53) | |
| Singapore | 0.861 | 6.46 (5.36 to 7.55) | 38 (23 to 52)* | 20 (10 to 26) | 65 (–29 to 92) | 2.99 (2.13 to 3.93) | –2 (–64 to 38) | 88 (85 to 92) | –50 (–209 to 29) | |
| Solomon Islands | 0.407 | 13.89 (10.28 to 18.16) | 39 (–6 to 65) | 52 (11 to 69) | –69 (–4,128 to 90) | 9.16 (6.60 to 12.36) | 14 (–55 to 52) | 99 (98 to 99) | 7 (–80 to 50) | |
| Tonga | 0.636 | 22.29 (16.85 to 29.04) | 28 (–11 to 54) | 13 (1 to 23) | –56 (–12,931 to 97) | 11.29 (8.35 to 14.93) | 10 (–47 to 44) | 96 (95 to 96) | –15 (–101 to 34) | |
| Tuvalu | 0.589 | 12.15 (8.44 to 16.97) | 38 (–7 to 64) | 49 (21 to 65) | 35 (–360 to 91) | 7.24 (4.78 to 10.51) | 25 (–46 to 61) | 97 (96 to 98) | 9 (–92 to 55) | |
| Vanuatu | 0.485 | 14.08 (9.50 to 19.31) | 36 (–16 to 66) | 57 (26 to 74) | 45 (–174 to 91) | 8.44 (5.09 to 12.25) | 16 (–62 to 59) | 97 (96 to 98) | –3 (–121 to 54) | |
| Vietnam | 0.617 | 7.88 (5.72 to 10.76) | 57 (25 to 75)* | 95 (91 to 97) | –5,935 (–4,070,514 to –1,187)* | 7.86 (5.59 to 10.60) | 34 (–20 to 63) | 78 (71 to 81) | 4 (–141 to 59) | |
ASMR, age-standardized mortality rates; SDI, Socio-demographic Index; NA, not applicable..
*Changes that are statistically significant..
In 2019, the leading risk factors for deaths due to hepatitis B and C in the Western Pacific regions were alcohol and drug use, respectively, which accounted for 52% of deaths from hepatitis B and for 80% of deaths from hepatitis C. From 1990 to 2019, the proportions of both hepatitis B deaths attributed to alcohol use and hepatitis C deaths attributed to drug use remained stable (Supplementary Fig. 3). The ASMR of hepatitis B attributed to alcohol use and the ASMR of hepatitis C attributed to drug use significantly declined in the Western Pacific region by 57% and 41%, respectively, from 1990 to 2019 (Table 1). In 27 Western Pacific countries, the ASMR of hepatitis B attributed to alcohol use significantly increased from 1990 to 2019 by 5935% and 708% in Vietnam and Cambodia, respectively (Table 1, Fig. 2), and significantly decreased in five countries (from 39% in New Zealand to 100% in Brunei Darussalam), while other countries had no substantial change related to the ASMR of hepatitis B attributed to alcohol use. The ASMR of hepatitis C attributed to drug use showed no significant change in the whole Western Pacific region, except in China, where it notably decreased (by 50%) from 1990 to 2019.
Figure 2. Age-standardized mortality rates (ASMRs) of hepatitis B and C attributed to alcohol and drug use for both sexes in the 27 Western Pacific countries from 1990 to 2019.
The trends of the ASMR varied by sex in the Western Pacific region. Namely, in men and women, the ASMR attributed to hepatitis B declined from 32.46 to 12.79 (a decrease of 61%) and from 9.97 to 2.85 (a decrease of 71%), respectively. The ASMR associated with hepatitis B showed significant reductions for both men and women (Supplementary Fig. 4). In acute hepatitis, the ASMR reduced by 82% and 88% for men and women, respectively. In cirrhosis and other chronic liver diseases, the ASMR declined by 63% and 72% for men and women, respectively. Additionally, in liver cancer, the ASMR decreased by 58% for men and 68% for women, respectively. As for hepatitis C, the ASMR in the Western Pacific region declined from 13.10 to 7.52 (a decrease of 43%) and from 8.07 to 3.65 (a decrease of 55%) in men and women, respectively. For hepatitis C, the sex-specific ASMR associated with hepatitis C reduced by 89% and 93% in acute hepatitis, by 43% and 55% in cirrhosis and other chronic liver diseases, and by 41% and 54% in liver cancer for men and women, respectively.
The ASMR attributable to hepatitis B and C varied significantly by age and sex (Fig. 3). In 2019, the highest ASMR of hepatitis B in men was about 20,000 in individuals aged 50 to 65 years, while the highest ASMR in women was about 4,000 in those aged 60 years or more. In men, the ASMR of hepatitis C rose steeply from 487 in those aged 25 to 29 years to about 10,000 in those aged 65 years or more; in women, it rose from 267 in those aged 30 to 34 years to about 10,000 in those aged 85 years or more. Compared to 1990, the ASMR of hepatitis B reduced in the younger population in 2019, decreasing from 2% in 65 to 69 years to 95% in 0 to 9 years males, and from 19% in 75- to 79-year-old to 96% in 0- to 9-year-old females. In the older population, the ASMR of hepatitis B in men increased from 8% in 70- to 74-year-old individuals to 196% in those older than 85 years; in women, it increased from 18% in 80- to 84-year-old individuals to 120% in those older than 85 years. The ASMR of hepatitis C in 2019 also reduced in the younger population, declining from 9% in 65- to 69-year-old to 96% in 0- to 9-year-old females, and decreased from 5% in 60- to 64-year-old to 94% in 0- to 9-year-old males, except for the population aged 45 to 54 years. Namely, the ASMR of hepatitis C increased in the older population, from 4% in 45- to 54-year-old individuals to 347% in those aged 85 years or more in males, and from 2% in 70- to 74-year-old individuals to 257% in those aged 85 years or more in females.
Figure 3. (A, B) Age-standardized mortality rates (ASMRs) of hepatitis B and C in the Western Pacific region between 1990 and 2019 stratified by age and sex. The annotation number indicates the decreased level in 2019 compared with that in 1990.
In 12 Western Pacific countries that had a better SDI than the Global SDI level, only five countries had a lower ASMR related to hepatitis B than the global ASMR level. Although the Republic of Korea had the highest SDI in the Western Pacific region, its ASMR related to hepatitis B had a rank of 9 (Table 1). Nearly all of the countries with a worse SDI compared with the global level had a higher ASMR related to hepatitis B compared with the global level, except for Papua New Guinea. The ASMR from 1990 to 2019 across SDI by country were shown in Fig. 4. With the improvement of SDI, a declining trend in the ASMR of hepatitis B was found in the Western Pacific region (the black dashed line in Fig. 4). Based solely on SDI, the ASMR of hepatitis B was much higher than expected in the Republic of Korea and Mongolia.
Figure 4. The age-standardized mortality rates (ASMRs) of hepatitis B and C across 27 Western Pacific countries, whole Western Pacific region, and the world by Socio-demographic Index from 1990 to 2019. For each country, points from left to right depict estimates from each year from 1990 to 2019.
Among the 12 Western Pacific countries with a better SDI compared with the Global SDI level, 11 countries had a lower ASMR related to hepatitis C than the global ASMR level, except for Japan. Although Japan had the second highest SDI in the Western Pacific region, its ASMR related to hepatitis C had the rank of 5 (Table 1). Nearly all countries with a worse SDI compared with the global level had a higher ASMR associated with hepatitis C compared to the global level, except for Papua New Guinea, Philippines, and Samoa. With the improvement of SDI, a stable trend in the ASMR of hepatitis C was found in the Western Pacific region (the black dashed line in Fig. 4). Based solely on SDI, the ASMR of hepatitis B was much higher than expected in Japan and Mongolia.
Our analysis explored the long-term trends in hepatitis B and C mortality in the Western Pacific region from 1990 to 2019. Comparing with the global, the ASMR per 100,000 Western Pacific population more notably decreased from 1990 to 2019. Namely, the ASMR of hepatitis B and C reduced by 64% and 48%, respectively, so the ASMRs of hepatitis B and C in 2019 became not notably different compared with the global level. In an additional analysis (Supplementary Fig. 5), the age-standardized incidence rate of hepatitis B and C per 100,000 Western Pacific population decreased by 47% and 33%, respectively, which was also more favorable compared with the global (35% and 9%). However, it was found that the reduction of the mortality rate was more substantial than the incidence rate. This transition may be attributed to social development and health-care services, including vaccination programs, reducing the risk of exposure, and actively managing patients infected with hepatitis B and C viruses. However, some countries, such as Mongolia, highlight that health transition is not predictably linear with SDI improvement. The underlying reason is that it has not attracted enough attention to the challenge caused by hepatitis B and C. For example, it was in recent years that the Healthy Liver Programme 2017 to 2020 strategy encompassed an ambitious plan to eliminate HCV and control HBV was implemented in Mongolia.3 In the Western Pacific region with the hepatitis B and C epidemic, uniformly efficient health-care services reaching the whole population and effective multisectoral provisions on risk factors (such as alcohol and drug use) still have to be strengthened.16
Despite a significant decrease in mortality rates for both sexes, male ASMRs for hepatitis B and C were four and two times higher than female ASMRs, respectively, from 1990 to 2019. These findings suggest that further efforts are needed to reduce the disease burden of hepatitis B and C in men. The habits of men, such as drinking alcohol, may have caused these sex-specific effects.17 Consumption of alcohol exceeding 50 g per day significantly elevates the risk of cirrhosis in HCV-infected individuals. Those affected by both alcohol-use disorder and HCV infection are prone to developing decompensated liver disease at a younger age, leading to poorer overall survival. Alcohol harm reduction strategies in the Western Pacific region should prioritize evidence-based interventions to change drinking patterns.
The change in the mortality rate is mainly attributed to the dramatically declining mortality rate related to liver cancer and cirrhosis and other chronic liver diseases, especially the complications due to hepatitis B, whose reduction could partly explain the fact that the ASMR of hepatitis B has become comparable with that of hepatitis C. It should also be noted that the ASMR related to cirrhosis and other chronic liver diseases in 2019 has become lower in males than in females regardless of hepatitis B and C, and the ASMR related to liver cancer remained higher in males than in females. Therefore, to further reduce the risk of mortality related to hepatitis B and C, more precise interventions for cirrhosis and liver cancer might be considered by gender.
The peak of the 2019 ASMR related to hepatitis B was in the population aged between 50 and 65 years. By contrast, the mortality rate of hepatitis C steadily increased with age. A relatively lower incidence rate of hepatitis B and a higher incidence rate of hepatitis C in the old population could be partly explained by these divergent age effects.18 The current analysis also showed that the 2019 ASMR in the younger population (below 50 years) was lower than that in 1990 regardless of sex and type of hepatitis. However, the 2019 ASMR in the old population, that is, in individuals over 80 years, was higher than that in 1990. This phenomenon might be explained by the HBV vaccine protection for the young population and the lagged complications in the old population due to the use of antiviral treatment. Cirrhosis and liver cancer may occur 20 to 30 years after antiviral treatment for hepatitis B and C, which may lead to an increase in ASMR with age.19,20
As the main contributors, alcohol and drug use are still related to hepatitis B and C deaths, respectively, from 1990 to 2019 in the Western Pacific region. Although the ASMRs of hepatitis B and C related to alcohol use and drug use significantly declined in the Western Pacific region, the ASMRs of hepatitis B in only five countries and hepatitis C in only one country achieved a significant decline. This finding indicates that combined efforts to reduce alcohol and drug use, such as psychosocial interventions, are necessary for populations with hepatitis B and C.21
Among the 27 Western Pacific countries, there were distinct differences in the mortality rates. The notable improvement in hepatitis B and C mortality in the Western Pacific region was substantially attributed to the Chinese decline, as China was the only country in the whole region that achieved a significant decrease both in hepatitis B and hepatitis C. However, the ASMR of hepatitis B in more than 50% and hepatitis C in more than 90% of countries did not significantly improve. For example, Mongolia was consistently one of the countries with the highest ASMRs related to hepatitis B and C, which were about 31 and 20 times higher than the lowest ASMRs of hepatitis B and C in New Zealand, respectively. National efforts of a comprehensive strategy, such as a vaccination program for hepatitis B and low-cost antiviral drugs for hepatitis B and C, are highlighted by the Chinese experience,22,23 which should be emergently and precisely implemented for countries with high disease burden.24
Several weaknesses should be noted in this analysis. First, this analysis was based on data from the GBD study 2019. Given the recent issues with other reports, the robustness and accuracy of the findings depend on the quality and quantity of the input data. Due to few large-scale population surveys of viral hepatitis seroprevalence in the Western Pacific region, the GBD estimations about hepatitis B and C were based on regional extrapolations and covariates, potentially minimizing spatial heterogeneity and differences in epidemics.11 Therefore, these results depend heavily on covariates and space–time extrapolation, highlighting the need for more longitudinal studies and better ascertainment of disease burden. Second, this study focused on the major risk factors for hepatitis B and C mortality, and did not consider the detailed risk factors. These issues may be addressed in future studies. Finally, due to the lack of relevant data, the effects of prevention and management programs in different countries were not included in this study, and considerable variations might exist among countries.
Although the mortality rate from hepatitis B and C decreased from 1990 to 2019, notable variation was observed in 27 Western Pacific countries. To achieve the global hepatitis elimination targets, Western Pacific countries with high disease burdens caused by hepatitis B and C should urgently adopt the successful experiences of other countries in screening, vaccination, and antiviral treatment.
This project was supported by a grant from the National Natural Science Foundation of China (72074142). The funders were not involved the collection, analysis, or interpretation of data, or in the writing or submitting of this report. The first author and corresponding author had full access to all data and final responsibility for the decision to submit for publication.
We would like to thank the Institute for Health Metrics and Evaluation staff and its collaborators who prepared these publicly available data.
No potential conflict of interest relevant to this article was reported.
Study concept and design: B.W., D.C. Data acquisition: H.Z., M.Y. Data analysis and interpretation: H.Z. Drafting of the manuscript: H.Z., D.C. Critical revision of the manuscript for important intellectual content: B.W. Statistical analysis: M.Y. Obtained funding: B.W. Administrative, technical, or material support; study supervision: B.W. Approval of final manuscript: all authors.
Supplementary materials can be accessed at https://doi.org/10.5009/gnl230023.
Data sources and code used in the Global Burden of Disease Study 2019 are available on the internet (http://ghdx.healthdata.org/gbd-results-tool).
Table 1 ASMR for Both Sexes Combined in 2019 and the Percentage Change from 1990 to 2019
| Countries and regions | 2019 SDI | Hepatitis B | Hepatitis C | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 2019 ASMR per 100,000 people | Decrease in ASMR 1990-2019, % | 2019 ASMR attributable to alcohol use, % | Decrease in ASMR attributable to alcohol use 1990-2019, % | 2019 ASMR per 100,000 people | Decrease in ASMR 1990-2019, % | 2019 ASMR attributable to drug use, % | Decrease in ASMR attributable to drug use 1990-2019, % | |||
| Global | 0.651 | 6.74 (5.92 to 7.63) | 45 (33 to 56)* | 67 (57 to 74) | 35 (–32 to 70) | 6.67 (5.87 to 7.49) | 21 (3 to 36)* | 80 (79 to 80) | 6 (–30 to 31) | |
| Western Pacific region | NA | 7.66 (6.47 to 8.91) | 64 (53 to 72)* | 52 (46 to 56) | 57 (19 to 78)* | 5.44 (4.74 to 6.17) | 48 (36 to 58)* | 80 (78 to 82) | 41 (16 to 59)* | |
| Australia | 0.839 | 1.45 (1.15 to 1.82) | 19 (–20 to 45) | 76 (71 to 80) | 42 (–4 to 67) | 3.91 (3.27 to 4.45) | –7 (–37 to 18) | 93 (92 to 93) | –14 (–48 to 14) | |
| Brunei Darussalam | 0.823 | 8.6 (6.99 to 10.53) | 32 (3 to 52)* | 0 (0 to 0) | 100 (94 to 100)* | 6.55 (5.16 to 8.10) | 4 (–44 to 37) | 89 (82 to 93) | –55 (–228 to 26) | |
| Cambodia | 0.469 | 19.05 (14.02 to 25.10) | 46 (15 to 65)* | 92 (89 to 95) | –708 (–278,128 to –84)* | 24.18 (17.70 to 31.38) | 14 (–36 to 47) | 34 (28 to 39) | –25 (–248 to 56) | |
| China | 0.686 | 8.07 (6.66 to 9.69) | 67 (56 to 76)* | 46 (41 to 49) | 62 (25 to 82)* | 4.04 (3.36 to 4.75) | 58 (46 to 69)* | 91 (91 to 93) | 50 (28 to 65)* | |
| Cook Islands | 0.764 | 7.67 (5.8 to 9.87) | 39 (8 to 59)* | 45 (39 to 50) | –121 (–82,647 to 46) | 4.45 (3.32 to 5.75) | 31 (–10 to 56) | 92 (90 to 93) | 12 (–52 to 49) | |
| Fiji | 0.664 | 6.36 (4.72 to 8.35) | 27 (–13 to 53) | 49 (35 to 58) | 27 (–134 to 79) | 4.25 (3.09 to 5.60) | 9 (–48 to 44) | 95 (95 to 96) | –11 (–94 to 38) | |
| Japan | 0.87 | 2.37 (2.08 to 2.66) | 43 (32 to 53)* | 72 (66 to 77) | 50 (14 to 72)* | 9.80 (8.64 to 10.53) | 35 (27 to 44)* | 59 (49 to 68) | 5 (–87 to 51) | |
| Kiribati | 0.527 | 19.33 (12.59 to 28.13) | 46 (7 to 70)* | 41 (0 to 67) | 53 (–4,481 to 100) | 11.30 (6.97 to 17.12) | 27 (–44 to 64) | 97 (95 to 98) | 15 (–104 to 64) | |
| Lao People’s Democratic Republic | 0.490 | 10.54 (7.38 to 14.47) | 52 (18 to 73)* | 84 (75 to 89) | 24 (–157 to 75) | 9.30 (6.49 to 12.71) | 30 (–23 to 61) | 48 (39 to 55) | –4 (–221 to 64) | |
| Malaysia | 0.737 | 11.15 (8.57 to 14.26) | 13 (–21 to 38) | 52 (15 to 68) | 46 (–165 to 94) | 5.38 (3.85 to 7.23) | –14 (–83 to 30) | 87 (80 to 91) | –59 (–288 to 32) | |
| Marshall Islands | 0.544 | 13.57 (8.97 to 19.27) | 40 (–1 to 66) | 55 (21 to 75) | 35 (–822 to 93) | 8.81 (5.45 to 13.42) | 22 (–48 to 60) | 96 (96 to 98) | 7 (–100 to 57) | |
| Micronesia (Federated States of) | 0.580 | 13.56 (8.2 to 20.83) | 38 (–19 to 70) | 52 (27 to 66) | 60 (–92 to 94) | 8.70 (4.97 to 13.75) | 23 (–63 to 65) | 96 (94 to 97) | 8 (–119 to 64) | |
| Mongolia | 0.606 | 39.65 (28.2 to 54.19) | 8 (–50 to 44) | 27 (16 to 32) | –15 (–431 to 73) | 54.80 (40.83 to 70.85) | –53 (–141 to 3) | 66 (56 to 74) | –56 (–331 to 40) | |
| Nauru | 0.618 | 12.83 (8.12 to 19.24) | 36 (–30 to 68) | 69 (50 to 76) | 33 (–215 to 85) | 8.83 (5.29 to 13.44) | 16 (–85 to 62) | 94 (92 to 94) | –1 (–162 to 59) | |
| New Zealand | 0.840 | 1.25 (1.10 to 1.41) | 11 (–9 to 28) | 68 (64 to 70) | 39 (9 to 60)* | 2.72 (2.45 to 3.02) | –6 (–27 to 11) | 93 (93 to 93) | –17 (–44 to 4) | |
| Niue | 0.711 | 8.75 (6.38 to 11.42) | 40 (1 to 65)* | 59 (6 to 72) | 49 (–267 to 98) | 6.02 (4.20 to 8.20) | 21 (–41 to 57) | 95 (95 to 95) | 3 (–81 to 49) | |
| Palau | 0.738 | 11.84 (8.40 to 16.27) | 25 (–33 to 58) | 42 (2 to 59) | 18 (–11,000 to 99) | 5.94 (3.86 to 8.94) | 13 (–84 to 57) | 96 (94 to 97) | –4 (–143 to 54) | |
| Papua New Guinea | 0.394 | 4.64 (3.27 to 6.50) | 28 (–29 to 60) | 70 (16 to 84) | 60 (–148 to 98) | 3.19 (2.17 to 4.44) | 5 (–69 to 48) | 98 (98 to 99) | –9 (–105 to 42) | |
| Philippines | 0.623 | 7.03 (5.58 to 8.74) | 50 (26 to 66)* | 77 (71 to 79) | 46 (–5 to 74) | 6.35 (5.10 to 7.93) | 21 (–18 to 46) | 18 (15 to 21) | 0 (–162 to 60) | |
| Republic of Korea | 0.878 | 13.09 (11.14 to 15.15) | 58 (46 to 67)* | 49 (36 to 56) | 83 (64 to 93)* | 4.23 (3.23 to 5.31) | 27 (–9 to 51) | 78 (72 to 83) | –8 (–132 to 47) | |
| Samoa | 0.641 | 10.22 (7.66 to 13.39) | 29 (–14 to 57) | 66 (42 to 74) | 26 (–142 to 81) | 5.32 (3.83 to 7.21) | 25 (–29 to 57) | 97 (96 to 97) | 15 (–58 to 53) | |
| Singapore | 0.861 | 6.46 (5.36 to 7.55) | 38 (23 to 52)* | 20 (10 to 26) | 65 (–29 to 92) | 2.99 (2.13 to 3.93) | –2 (–64 to 38) | 88 (85 to 92) | –50 (–209 to 29) | |
| Solomon Islands | 0.407 | 13.89 (10.28 to 18.16) | 39 (–6 to 65) | 52 (11 to 69) | –69 (–4,128 to 90) | 9.16 (6.60 to 12.36) | 14 (–55 to 52) | 99 (98 to 99) | 7 (–80 to 50) | |
| Tonga | 0.636 | 22.29 (16.85 to 29.04) | 28 (–11 to 54) | 13 (1 to 23) | –56 (–12,931 to 97) | 11.29 (8.35 to 14.93) | 10 (–47 to 44) | 96 (95 to 96) | –15 (–101 to 34) | |
| Tuvalu | 0.589 | 12.15 (8.44 to 16.97) | 38 (–7 to 64) | 49 (21 to 65) | 35 (–360 to 91) | 7.24 (4.78 to 10.51) | 25 (–46 to 61) | 97 (96 to 98) | 9 (–92 to 55) | |
| Vanuatu | 0.485 | 14.08 (9.50 to 19.31) | 36 (–16 to 66) | 57 (26 to 74) | 45 (–174 to 91) | 8.44 (5.09 to 12.25) | 16 (–62 to 59) | 97 (96 to 98) | –3 (–121 to 54) | |
| Vietnam | 0.617 | 7.88 (5.72 to 10.76) | 57 (25 to 75)* | 95 (91 to 97) | –5,935 (–4,070,514 to –1,187)* | 7.86 (5.59 to 10.60) | 34 (–20 to 63) | 78 (71 to 81) | 4 (–141 to 59) | |
ASMR, age-standardized mortality rates; SDI, Socio-demographic Index; NA, not applicable.
*Changes that are statistically significant.
pISSN 1976-2283
eISSN 2005-1212
Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut atnd Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. +MORE
| Yong Chan Lee |
Professor of Medicine Director, Gastrointestinal Research Laboratory Veterans Affairs Medical Center, Univ. California San Francisco San Francisco, USA |
| Jong Pil Im | Seoul National University College of Medicine, Seoul, Korea |
| Robert S. Bresalier | University of Texas M. D. Anderson Cancer Center, Houston, USA |
| Steven H. Itzkowitz | Mount Sinai Medical Center, NY, USA |
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Supplementary 1
