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About 1.4 million people died from viral hepatitis worldwide in 2016, and most deaths were due to cirrhosis and hepatocellular carcinoma caused by hepatitis B and C (1-2). In China, acute hepatitis caused 9,213 deaths, the number of disability-adjusted life years (DALYs) was 307,720 person years, in which acute hepatitis B accounted for 85.81% of DALYs among acute hepatitis types A, B, C, and E in 2016 (3). However, the nationwide incidence and prevalence of acute hepatitis were not yet reported, and the latest results were not reported. In this report, results were obtained from the latest estimates of the Global Burden of Disease Study 2019 (GBD 2019); the incidence, prevalence, deaths, and indicators of burden of acute hepatitis in 1990, 2000, and 2019 were used; and the standardized rates were calculated using the 2010 National Census as the standard population. In 2019, acute hepatitis caused 3,726 deaths, 4,501,755 cases of acute hepatitis, and 214,165 person years of DALYs; hepatitis B accounted for 66.69% of DALYs among hepatitis A, B, C, and E; percent changes of YLDs in groups aged 50–69 years and 70 years or more for acute hepatitis A, B, and E and in all age groups for acute hepatitis C were increased from 2000 to 2019. Effective vaccines and prompt action on interventions and treatments were major efforts to tackle viral hepatitis to achieve the World Health Organization’s (WHO) goal of reducing new hepatitis infections by 90% and deaths by 65% between 2016 and 2030 (4).
Morbidity and mortality due to acute hepatitis resulting from the acute sequelae of hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis E virus (HEV) infections were estimated by the GBD 2019. With respect to morbidity, anti-HAV IgG, hepatitis B surface antigen (HBsAg), anti-HCV IgG, and anti-HEV IgG seroprevalence data were collected through published literature, grey literature, and surveys, and the meta-regression tool (DisMod-MR) utilizing age group, gender, and year was used to estimate seroprevalence and instantaneous seroconversion rates due to acute infections (5). The instantaneous seroconversion rate was converted to the population incidence rate (the number of infections per person in the total population) using the formula: population incidence rate = (instantaneous seroconversion rate) × (1 – seroprevalence) (6). HBsAg seropositivity typically existed only in chronic carriers, and the association of incidence of HBV infections that resulted in chronic carrying was modelled to estimate the incidence from HBsAg seroprevalence data (6).
The prevalences of acute HAV, HBV, HCV, and HEV infections were calculated as the products of the population incidence rate and estimated durations of acute infections of HAV, HBV, HCV, and HEV, which was four weeks for HAV and HEV, and six weeks for HBV and HCV (6). Hereby, incidence meant the number of new acute infection cases of a given hepatitis virus during a year period in a specified population; prevalence implied the proportion of the number of cases of acute viral infections found in a population.
To calculate mortality, the vital registration, verbal autopsy, cancer registry, and mortality surveillance data were compiled, and the cause-of-death ensemble model (CODEm) was applied to estimate cause-specific mortality by age group, gender, and year for acute HAV, HBV, HCV, and HEV infections (7). Virus specific mortality data for acute hepatitis were too limited to direct use in the CODEm, so a two-step nested-model approach for acute hepatitis virus infections was used to estimate cause-specific mortality. First, the joint mortality from all acute hepatitis using cause-specific mortality data in the CODEm was modelled; second, a separate natural history model for each hepatitis virus infection was developed, in which mortality was estimated as the product of incidence and case fatality (6).
YLDs were estimated as the product of an estimate of prevalence and a disability weight for health states of each mutually exclusive sequela; years of life lost (YLLs) were expressed as the product of mortality estimates and years of life lost due to premature death; and DALYs were calculated as the sum of YLLs and YLDs.
Incidence, prevalence, deaths, and indicators of burden of acute hepatitis in 1990, 2000, and 2019 by gender were obtained, and their standardized rates were calculated using the 2010 National Census as the standard population, expressed as number and rate (1/100,000), respectively. Percent change (%) was calculated as the difference in quantities between 2019 and 2000 divided by the quantity in 2000. All statistical analyses were performed using SAS (version 9.4, SAS Institute Inc., Cary, USA).
InTable 1, standardized rates of DALYs, YLLs, and YLDs due to acute hepatitis declined when quantities in 2019 were compared to those in 2000, and YLLs had the largest percent decrease for males, females, and both genders combined, with the percent decrease for females being greater than that found in males.
Gender Year Incidence Prevalence Deaths DALYs YLLs YLDs N P′ N P′ N P′ N P′ N P′ N P′ Male 1990 38,603,733 5,455.48 3,788,134 555.26 16,651 3.51 887,637 149.59 825,936 139.38 61,700 10.21 2000 37,113,965 5,159.80 3,701,779 523.55 9,191 1.68 456,024 73.17 388,333 63.23 67,691 9.93 2019 27,402,638 3,880.05 2,690,260 379.58 2,661 0.33 143,697 19.11 86,490 11.00 57,207 8.11 2019vs.2000 (%)* −26.17 −24.80 −27.33 −27.50 −71.05 −80.61 −68.49 −73.89 −77.73 −82.61 −15.49 −18.38 Female 1990 28,602,658 4,141.05 2,690,025 403.99 9,511 1.91 521,406 82.99 476,669 75.48 44,737 7.51 2000 26,765,510 3,938.87 2,567,887 383.22 3,952 0.71 216,223 34.91 167,289 27.47 48,934 7.44 2019 19,342,044 2,974.27 1,811,496 275.44 1,065 0.12 70,468 9.91 30,543 3.82 39,925 6.09 2019vs.2000 (%)* −27.74 −24.49 −29.46 −28.12 −73.04 −83.25 −67.41 −71.62 −81.74 −86.09 −18.41 −18.19 Both 1990 67,206,390 4,818.71 6,478,159 481.98 26,162 2.72 1,409,042 117.47 1,302,605 108.56 106,437 8.91 2000 63,879,475 4,565.51 6,269,666 455.24 13,143 1.19 672,247 54.53 555,622 45.81 116,625 8.72 2019 46,744,682 3,433.54 4,501,755 328.24 3,726 0.22 214,165 14.53 117,032 7.42 97,133 7.11 2019vs.2000 (%)* −26.82 −24.79 −28.20 −27.90 −71.65 −81.57 −68.14 −73.35 −78.94 −83.80 −16.71 −18.48 Note:N: Number of cases for incidence, prevalence, and deaths; number of person years for disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs).
$ {P'} $: Standardized rate calculated using the 2010 National Census as the standard population, expressed as 1/100,000.
* Percent change (%) was calculated as difference value between 2019 and 2000 divided by quantity in 2000.Table 1.Overall incidence, prevalence, deaths, and burden indicators of acute hepatitis for the years 1990, 2000, and 2019 in China.
FromTables 2–5, percent changes in the number of person years and standardized rate of DALYs and YLLs in all age groups due to acute hepatitis were decreased when quantities in 2019 were compared to those in 2000. Further comparisons for 2019 and 2000 showed that for acute hepatitis A (Table 2), percent changes in the number of person years and rate of YLDs were increased in groups aged 50–69 years and 70 years or more; for hepatitis B (Table 3), percent changes in the number of person years of YLDs were increased in groups aged 50–69 years and 70 years or more; for acute hepatitis C (Table 4), percent changes in the number of person years of YLDs in groups aged <5 years, 15–49 years, 50–69 years, and 70 years or more were increased, and the standardized rate of YLDs in groups aged <5 years, 5–14 years, and 15–49 years were increased; and for acute hepatitis E (Table 5), percent changes of YLDs in groups aged 50–69 years and 70 years or more were increased.
Age group (years) Year Incidence Prevalence Deaths DALYs YLLs YLDs Number of cases Rate (1/100,000) Number of cases Rate (1/100,000) Number of cases Rate (1/100,000) Number of person-years Rate (1/100,000) Number of person-years Rate (1/100,000) Number of person-years Rate (1/100,000) <5 1990 12,346,148 10,699.23 949,704 823.02 3,527 3.06 312,293 270.63 310,158 268.78 2,134 1.85 2000 7,342,017 8,719.38 564,771 670.72 597 0.71 53,774 63.86 52,465 62.31 1,309 1.55 2019 5,889,462 7,227.14 453,036 555.93 22 0.03 2,982 3.66 1,905 2.34 1,077 1.32 2019vs.2000 (%)* −19.78 −17.11 −19.78 −17.11 −96.37 −96.25 −94.45 −94.27 −96.37 −96.25 −17.74 −15.01 5–14 1990 7,854,676 3,785.08 604,206 291.16 321 0.15 40,464 19.50 25,682 12.38 14,782 7.12 2000 7,595,916 3,390.47 584,301 260.81 128 0.06 25,353 11.32 10,211 4.56 15,142 6.76 2019 4,527,645 3,159.84 348,280 243.06 5 0.00 9,037 6.31 369 0.26 8,668 6.05 2019vs.2000 (%)* −40.39 −6.80 −40.39 −6.80 −96.39 −94.36 −64.36 −44.27 −96.38 −94.35 −42.76 −10.50 15–49 1990 7,576,037 1,133.35 582,772 87.18 3,818 0.57 226,470 33.88 202,265 30.26 24,205 3.62 2000 8,538,864 1,144.40 656,836 88.03 1,533 0.21 107,072 14.35 79,636 10.67 27,435 3.68 2019 8,105,503 1,124.63 623,500 86.51 133 0.02 32,880 4.56 6,753 0.94 26,126 3.63 2019vs.2000 (%)* −5.08 −1.73 −5.08 −1.73 −91.30 −90.99 −69.29 −68.21 −91.52 −91.22 −4.77 −1.41 50–69 1990 111,845 72.60 8,603 5.58 3,398 2.21 103,559 67.22 103,187 66.98 372 0.24 2000 245,064 128.21 18,851 9.86 1,245 0.65 38,519 20.15 37,720 19.73 799 0.42 2019 839,826 227.67 64,602 17.51 223 0.06 9,319 2.53 6,620 1.79 2,699 0.73 2019vs.2000 (%)* 242.70 77.57 242.70 77.57 −82.07 −90.71 −75.81 −87.46 −82.45 −90.91 237.82 75.05 70+ 1990 456 1.19 35 0.09 1,724 4.51 26,969 70.49 26,968 70.49 2 0.00 2000 1,340 2.44 103 0.19 795 1.45 12,027 21.89 12,023 21.89 4 0.01 2019 6,817 6.31 524 0.49 218 0.20 3,127 2.90 3,104 2.88 23 0.02 2019vs.2000 (%)* 408.87 158.91 408.87 158.91 −72.61 −86.07 −74.00 −86.77 −74.18 −86.86 407.09 158.00 Abbreviations: DALYs=disability-adjusted life years; YLLs=years of life lost; YLDs=years lived with disability.
* Percent change (%) was calculated as difference value between 2019 and 2000 divided by quantity in 2000.Table 2.Incidence, prevalence, deaths, and burden indicators of acute hepatitis A for the years 1990, 2000, and 2019 in China.
Age group (years) Year Incidence Prevalence Deaths DALYs YLLs YLDs Number of cases Rate (1/100,000) Number of cases Rate (1/100,000) Number of cases Rate (1/100,000) Number of person-years Rate (1/100,000) Number of person-years Rate (1/100,000) Number of person-years Rate (1/100,000) <5 1990 2,184,080 1,892.73 252,009 218.39 2,369 2.05 210,724 182.61 208,934 181.06 1,790 1.55 2000 1,610,842 1,913.03 185,866 220.73 766 0.91 68,824 81.74 67,503 80.17 1,321 1.57 2019 89,513 109.84 10,328 12.67 95 0.12 8,411 10.32 8,337 10.23 74 0.09 2019vs.2000 (%)* −94.44 −94.26 −94.44 −94.26 −87.65 −87.24 −87.78 −87.37 −87.65 −87.24 −94.40 −94.22 5–14 1990 4,055,400 1,954.25 467,931 225.49 146 0.07 14,950 7.20 11,596 5.59 3,354 1.62 2000 4,296,507 1,917.76 495,751 221.28 101 0.04 11,499 5.13 7,952 3.55 3,547 1.58 2019 185,281 129.31 21,379 14.92 10 0.01 960 0.67 806 0.56 154 0.11 2019vs.2000 (%)* −95.69 −93.26 −95.69 −93.26 −89.90 −84.21 −91.65 −86.95 −89.87 −84.16 −95.65 −93.21 15–49 1990 22,618,450 3,383.66 2,609,821 390.42 3,671 0.55 229,312 34.30 190,162 28.45 39,150 5.86 2000 23,854,779 3,197.08 2,752,475 368.89 2,775 0.37 186,460 24.99 141,158 18.92 45,301 6.07 2019 15,666,424 2,173.70 1,807,664 250.81 658 0.09 64,995 9.02 32,367 4.49 32,628 4.53 2019vs.2000 (%)* −34.33 −32.01 −34.33 −32.01 −76.29 −75.45 −65.14 −63.91 −77.07 −76.26 −27.98 −25.44 50–69 1990 3,654,647 2,372.34 421,690 273.73 3,535 2.29 116,089 75.36 106,488 69.12 9,601 6.23 2000 4,229,083 2,212.55 487,971 255.29 2,537 1.33 87,336 45.69 76,167 39.85 11,169 5.84 2019 5,914,098 1,603.25 682,396 184.99 1,217 0.33 51,939 14.08 36,258 9.83 15,681 4.25 2019vs.2000 (%)* 39.84 −27.54 39.84 −27.54 −52.04 −75.15 −40.53 −69.18 −52.40 −75.33 40.40 −27.25 70+ 1990 642,722 1,679.96 74,160 193.84 1,753 4.58 29,339 76.69 27,729 72.48 1,610 4.21 2000 860,264 1,566.06 99,261 180.70 1,481 2.70 25,095 45.68 22,938 41.76 2,157 3.93 2019 1,239,558 1,148.11 143,026 132.47 908 0.84 16,521 15.30 13,358 12.37 3,163 2.93 2019vs.2000 (%)* 44.09 −26.69 44.09 −26.69 −38.65 −68.79 −34.17 −66.50 −41.76 −70.37 46.61 −25.40 Abbreviations: DALYs=disability-adjusted life years; YLLs=years of life lost; YLDs=years lived with disability.
* Percent change (%) was calculated as difference value between 2019 and 2000 divided by quantity in 2000.Table 3.Incidence, prevalence, deaths, and burden indicators of acute hepatitis B for the years 1990, 2000, and 2019 in China.
Age group (years) Year Incidence Prevalence Deaths DALYs YLLs YLDs Number of cases Rate (1/100,000) Number of cases Rate (1/100,000) Number of cases Rate (1/100,000) Number of person-years Rate (1/100,000) Number of person-years Rate (1/100,000) Number of person-years Rate (1/100,000) <5 1990 511,319 443.11 58,998 51.13 198 0.17 18,198 15.77 17,375 15.06 823 0.71 2000 174,481 207.21 20,132 23.91 55 0.07 5,148 6.11 4,865 5.78 283 0.34 2019 200,678 246.26 23,155 28.41 2 0.00 505 0.62 180 0.22 325 0.40 2019vs.2000 (%)* 15.01 18.84 15.01 18.84 −96.31 −96.18 −90.19 −89.86 −96.31 −96.18 14.90 18.73 5–14 1990 204,102 98.35 23,550 11.35 21 0.01 1,981 0.95 1,650 0.79 331 0.16 2000 82,535 36.84 9,523 4.25 13 0.01 1,152 0.51 1,018 0.45 134 0.06 2019 79,956 55.80 9,226 6.44 0 0.00 165 0.12 35 0.02 130 0.09 2019vs.2000 (%)* −3.12 51.47 −3.12 51.47 −96.54 −94.58 −85.68 −77.61 −96.53 −94.58 −3.21 51.34 15–49 1990 137,739 20.61 15,893 2.38 327 0.05 17,282 2.59 17,059 2.55 223 0.03 2000 88,878 11.91 10,255 1.37 209 0.03 10,844 1.45 10,700 1.43 144 0.02 2019 92,990 12.90 10,730 1.49 22 0.00 1,211 0.17 1,061 0.15 150 0.02 2019vs.2000 (%)* 4.63 8.32 4.63 8.32 −89.71 −89.35 −88.83 −88.44 −90.09 −89.74 4.59 8.28 50–69 1990 25,966 16.86 2,996 1.94 332 0.22 10,023 6.51 9,981 6.48 42 0.03 2000 41,332 21.62 4,769 2.50 189 0.10 5,717 2.99 5,650 2.96 67 0.04 2019 62,256 16.88 7,183 1.95 37 0.01 1,217 0.33 1,116 0.30 101 0.03 2019vs.2000 (%)* 50.62 −21.95 50.62 −21.95 −80.20 −89.74 −78.72 −88.97 −80.26 −89.77 50.58 −21.98 70+ 1990 12,493 32.65 1,441 3.77 169 0.44 2,697 7.05 2,677 7.00 20 0.05 2000 32,793 59.70 3,784 6.89 116 0.21 1,849 3.37 1,796 3.27 53 0.10 2019 42,243 39.13 4,874 4.51 29 0.03 483 0.45 414 0.38 69 0.06 2019vs.2000 (%)* 28.82 −34.46 28.82 −34.46 −75.46 −87.51 −73.91 −86.72 −76.96 −88.28 28.91 −34.41 Abbreviations: DALYs=disability-adjusted life years; YLLs=years of life lost; YLDs=years lived with disability.
* Percent change (%) was calculated as difference value between 2019 and 2000 divided by quantity in 2000.Table 4.Incidence, prevalence, deaths, and burden indicators of acute hepatitis C for the years 1990, 2000, and 2019 in China.
Age group (years) Year Incidence Prevalence Deaths DALYs YLLs YLDs Number of cases Rate (1/100,000) Number of cases Rate (1/100,000) Number of cases Rate (1/100,000) Number of person-years Rate (1/100,000) Number of person-years Rate (1/100,000) Number of person-years Rate (1/100,000) <5 1990 1,049,414 909.43 79,664 69.04 213 0.18 18,910 16.39 18,782 16.28 128 0.11 2000 790,917 939.29 60,104 71.38 72 0.09 6,411 7.61 6,314 7.50 97 0.12 2019 744,117 913.13 56,597 69.45 5 0.01 493 0.61 402 0.49 92 0.11 2019vs.2000 (%)* −5.92 −2.79 −5.84 −2.70 −93.64 −93.42 −92.30 −92.05 −93.64 −93.43 −5.89 −2.76 5–14 1990 1,813,271 873.79 139,482 67.21 7 0.003 2,851 1.37 577 0.28 2,274 1.10 2000 1,901,308 848.66 146,254 65.28 5 0.002 2,927 1.31 429 0.19 2,499 1.12 2019 1,143,697 798.19 87,977 61.40 0 0.000 1,438 1.00 31 0.02 1,407 0.98 2019vs.2000 (%)* −39.85 −5.95 −39.85 −5.95 −92.81 −88.75 −50.89 −23.21 −92.79 −88.72 −43.70 −11.97 15–49 1990 2,246,961 336.14 172,843 25.86 190 0.03 15,084 2.26 9,883 1.48 5,201 0.78 2000 1,984,400 265.95 152,646 20.46 155 0.02 12,499 1.68 7,848 1.05 4,651 0.62 2019 1,499,585 208.07 115,353 16.01 23 0.00 4,706 0.65 1,157 0.16 3,549 0.49 2019vs.2000 (%)* −24.43 −21.77 −24.43 −21.77 −84.96 −84.42 −62.35 −61.02 −85.26 −84.74 −23.68 −20.99 50–69 1990 118,008 76.60 9,078 5.89 302 0.20 9,437 6.13 9,147 5.94 290 0.19 2000 145,119 75.92 11,163 5.84 232 0.12 7,358 3.85 7,001 3.66 357 0.19 2019 281,470 76.30 21,652 5.87 66 0.02 2,647 0.72 1,955 0.53 692 0.19 2019vs.2000 (%)* 93.96 0.50 93.96 0.50 −71.65 −85.31 −64.02 −81.36 −72.08 −85.53 94.06 0.56 70+ 1990 42,656 111.50 3,281 8.58 142 0.37 2,410 6.30 2,306 6.03 104 0.27 2000 63,037 114.76 4,849 8.83 139 0.25 2,382 4.34 2,227 4.06 154 0.28 2019 133,562 123.71 10,274 9.52 54 0.05 1,129 1.05 805 0.75 324 0.30 2019vs.2000 (%)* 111.88 7.80 111.88 7.80 −61.42 −80.37 −52.58 −75.87 −63.86 −81.61 110.54 7.12 Abbreviations: DALYs=disability-adjusted life years; YLLs=years of life lost; YLDs=years lived with disability.
* Percent change (%) was calculated as difference value between 2019 and 2000 divided by quantity in 2000.Table 5.Incidence, prevalence, deaths, and burden indicators of acute hepatitis E for the years 1990, 2000, and 2019 in China.
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In China, the latest results showed that DALY standardized rates of acute hepatitis declined from 1990 to 2019 for males, females, and both genders combined. The decrease of DALYs primarily came from the decline of YLLs, and this was in line with the previous study (8). In 2019, acute hepatitis A, B, C, and E caused 3,726 deaths, 4,501,755 cases, and 214,165 person years of DALYs. Although DALYs decreased over 60% from 2000 to 2019, a high burden of acute hepatitis remains, and viral hepatitis remains a major public health challenge that requires an urgent response.
China implemented the nationwide use of a hepatitis A vaccine beginning in 1992, and the high burden of hepatitis A rapidly declined. The cause of the aforementioned percent changes in YLDs requires further investigation but were likely contributed to by factors such as unsafe water or food, poor sanitation, and poor personal hygiene and high-risk groups such as men who have gender with men, travelers to countries with high levels of infection, and persons who inject drugs (9). People aged 50 years or above in high-risk groups should get vaccinated as this is a safe and effective way available to prevent HAV infection.
Globally, in 2015, an estimated 257 million people were living with chronic HBV infection with 27 million people aware of their infection as of 2016 and 4.5 million of diagnosed people being on treatment (9). This report found that acute hepatitis B caused 2,888 deaths in 2019, accounting for 77.51% (2,888/3,726) of mortality of all acute hepatitis. Of those 2,888 deaths, people aged 50 years or above were responsible for the most deaths at 73.58% (2,125/2,888) of the total. Acute hepatitis B had the highest burden among all types of acute hepatitis, especially in the groups aged 15–49 years and 50–69 years. Prevention and control strategies for HBV infection prioritize vaccinations as the safe and effective vaccine provides over a 98% protection against HBV infection.
The regions with the highest prevalence of hepatitis C were the Eastern Mediterranean Region and the European Region with estimated prevalences in 2015 of 2.3% and 1.5%, respectively (9). China had a relatively low prevalence of HCV infection, and the burden of acute hepatitis C was lower than that of acute hepatitis A or acute hepatitis E from our findings. Though no effective vaccine against HCV infection currently exists, antiviral medicine is effective for curing persons with HCV infection.
Hepatitis E was most common in East and South Asia, and HEV is transmitted by the fecal-oral route, primarily via contaminated water (9). In our report, acute hepatitis E caused 148 deaths, which outnumbered deaths due to acute hepatitis C in 2019 (90 deaths). The number of DALYs was 10,413 person years, which was greater than that of acute hepatitis C (3,581 person years). The hepatitis E vaccine has been developed and is licensed in China (4), and it should be used to control hepatitis E.
This study was subject to some limitations. First, large-scale seroprevalence data used for the estimation of morbidity of acute infections of hepatitis virus was limited, where data were sparse or no data, estimates were based on regional extrapolations and covariates by statistical models, which may lower spatial differences across regions and might deviate from the true value. Second, this report only presented results of incidence, prevalence, deaths, and burden indicators of acute hepatitis by gender for all acute hepatitis, and by age group for acute hepatitis A, B, C, and E at the national level; however, burdens of acute hepatitis A, B, C, and E at the provincial level and municipal level by gender and age group are necessary to make well-directed policy for the prevention and control of viral hepatitis.
Acknowledgement:We would like to thank the team of the GBD 2019 and also thank the Office of Epidemiology, Chinese Center for Disease Control and Prevention, for their support.
Conflict of interest:No conflicts of interest were reported.
Funding:This study is supported by National Key Research and Development Program “Applied Study on the Data-driven Prevention and Control Strategies of the Major Chronic Diseases” (2018YFC1315305).
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