2.1 Time trends and basic information of hepatitis B
From 2004 to 2021, the number of hepatitis B cases in China increased from 916,426 in 2004 to 976,233 in 2021 (AAPC = 0.38%, P = 0.613), and the number of deaths decreased from 783 in 2004 to 413 in 2021 (AAPC=-3.23%, P = 0.076), with local trends showing an up-down-up.The number of cases of hepatitis B incidence in China from 2004 to 2021 decreased from 70.50 per 100,000 in 2004 to 69.25 per 100,000 in 2021 (AAPC=-0.09%, P = 0.901), with local trends showing an upward and then downward trend, increasing at an average annual rate of 9.59% from 2004 to 2007 (AAPC = 9.59%, P = 0.012), and increasing at an average annual rate of 3.5% from 2007 to 2014 and 2014 to 2021 at an average annual rate of 3.64% and 0.44%, respectively (APC=-3.64%, P = 0.003; APC=-0.44%, P = 0.598). Mortality declined from 0.06 per 100,000 in 2004 to 0.03 per 100,000 in 2021 (AAPC=-4.03%, P < 0.001), with an increase at an average annual rate of 0.04% from 2015–2021 (APC = 0.04%, P = 0.981) (Table 1 and Fig. 1).
Table 1
Incidence and mortality trend of hepatitis B in China from 2004 to 2021
Year
|
Incident cases
|
Crude incidence per 100,000
|
Mortal cases
|
Crude mortality per 100,000
|
2004
|
916426
|
70.50
|
783
|
0.06
|
2005
|
982297
|
75.13
|
908
|
0.07
|
2006
|
1109130
|
84.82
|
995
|
0.08
|
2007
|
1169946
|
89.00
|
854
|
0.07
|
2008
|
1169569
|
88.52
|
831
|
0.06
|
2009
|
1179607
|
88.82
|
792
|
0.06
|
2010
|
1060582
|
79.46
|
689
|
0.05
|
2011
|
1093335
|
81.54
|
637
|
0.05
|
2012
|
1087086
|
80.68
|
582
|
0.04
|
2013
|
962974
|
71.12
|
550
|
0.04
|
2014
|
935702
|
69.05
|
360
|
0.03
|
2015
|
934215
|
68.57
|
352
|
0.03
|
2016
|
942268
|
68.74
|
405
|
0.03
|
2017
|
1001952
|
72.61
|
425
|
0.03
|
2018
|
999985
|
71.99
|
413
|
0.03
|
2019
|
1002292
|
71.77
|
447
|
0.03
|
2020
|
902476
|
64.29
|
464
|
0.03
|
2021
|
976233
|
69.25
|
413
|
0.03
|
AAPC (%)
|
0.38
|
-0.09
|
-3.23
|
-4.03
|
P值
|
0.613
|
0.901
|
0.076
|
< 0.001
|
(AAPC:Average Annual Percent Change) |
2.2 The analysis of age differences of hepatitis B
The results showed that the standardized incidence for the 0 ~ 9, 10 ~ 19, 20 ~ 29, 30 ~ 39, 40 ~ 49, 50 ~ 59, 60 ~ 69, 70 ~ 79 and ≥ 80 years age categories were 1: 5.71 :22.75 :20.32 :19.48 :13.66 :8.60 :3.64 :0.91, respectively. The crude incidence of hepatitis B is high among people aged 20 to 60 years in China (Fig. 2). There was an increasing trend of standardized incidence of hepatitis B in the age group over 30 years (P = 0.146 for the 30 ~ 39 group, P = 0.521 for the 40 ~ 49 group, P < 0.001 for the 50 ~ 59 group, P < 0.001 for the 60 ~ 69 group, P < 0.001 for the 70 ~ 79 group and P < 0.001 for the 80 ~ group) (Table 2).
The standardized mortality by age 0 ~ 9, 10 ~ 19, 20 ~ 29, 30 ~ 39, 40 ~ 49, 50 ~ 59, 60 ~ 69, 70 ~ 79 and ≥ 80 years age categories were 1.00 :3.37 :22.63 :49.23 :91.23 :88.68 :63.87 :34.18 :12.51, respectively. The crude mortality of hepatitis B fluctuated with age, and were higher in people over 50 years of age(Fig. 2). With the exception of the 60 ~ 69 years group, the standardized mortality continued to decline at an average annual rate of 10.93%, 13.52%, 12.33%, 9.72%, 10.16%, 7.39%, 6.68% and 3.33% for each age group respectively. Notably, the 60–69 years group of standardized mortality rate have been on the rise in recent years but the difference was not statistically significant (APC = 12.95%, p = 0.098) (Table 2).
Table 2
Changing trends of standardized incidence and standardized mortality of hepatitis B among different age groups in China from 2004 to 2018
Age group (year)
|
Trend 1a
|
|
Trend 2a
|
|
Trend 3a
|
AAPC(95%CI)
|
P
|
Year
|
APC (95%CI)
|
P
|
Year
|
APC (95%CI)
|
P
|
Year
|
APC (95%CI)
|
P
|
ASIR
|
|
|
|
|
|
|
|
|
|
|
|
0~
|
2004–2007
|
-7.09(-12.94~-0.85) b
|
0.032
|
2007–2013
|
-17.32(-20.71~-13.78) b
|
< 0.001
|
2013–2018
|
-4.84(-10.38 ~ 1.04)
|
0.091
|
-10.86(-13.14~-8.53) b
|
< 0.001
|
10~
|
2004–2007
|
0.88(-5.32 ~ 7.48)
|
0.754
|
2007–2013
|
-18.00(-21.05~-14.83) b
|
< 0.001
|
2013–2018
|
-10.41(-15.67~-4.84) b
|
0.004
|
-11.52(-13.71~-9.28) b
|
< 0.001
|
20~
|
2004–2007
|
13.35(5.76 ~ 21.49) b
|
0.002
|
2007–2018
|
-8.01(-8.98~-7.03) b
|
< 0.001
|
|
|
|
-3.80(-5.23~-2.35) b
|
< 0.001
|
30~
|
2004–2007
|
11.95(5.61 ~ 18.68) b
|
0.003
|
2007–2015
|
-3.87(-5.32~-2.40) b
|
< 0.001
|
2015–2018
|
5.01(-0.96 ~ 11.35)
|
0.089
|
1.22(-0.42 ~ 2.89)
|
0.146
|
40~
|
2004–2009
|
7.00(3.95 ~ 10.13) b
|
0.001
|
2009–2014
|
-6.04(-9.76~-2.17) b
|
0.008
|
2014–2018
|
1.39(-2.82 ~ 5.78)
|
0.467
|
0.58(-1.19 ~ 2.39)
|
0.521
|
50~
|
2004–2018
|
2.66(1.88 ~ 3.44) b
|
< 0.001
|
|
|
|
|
|
|
2.66(1.88 ~ 3.44) b
|
< 0.001
|
60~
|
2004–2008
|
13.64(7.87 ~ 19.71) b
|
< 0.001
|
2008–2018
|
2.16(1.11 ~ 3.21) b
|
0.001
|
|
|
|
5.31(3.79 ~ 6.86) b
|
< 0.001
|
70~
|
2004–2009
|
11.79(8.08 ~ 15.62) b
|
< 0.001
|
2009–2018
|
0.13(-1.02 ~ 1.29)
|
0.811
|
|
|
|
4.15(2.86 ~ 5.45) b
|
< 0.001
|
80~
|
2004–2009
|
18.33(13.54 ~ 23.31) b
|
< 0.001
|
2009–2014
|
-5.50(-9.96~-0.82)
|
0.028
|
2014–2018
|
2.54(-2.43 ~ 7.77)
|
0.272
|
4.82(2.52 ~ 7.17) b
|
< 0.001
|
ASDR
|
|
|
|
|
|
|
|
|
|
|
|
0~
|
2004–2018
|
-10.93(-16.22~-5.31) b
|
0.001
|
|
|
|
|
|
|
-10.93(-16.22~-5.31) b
|
0.001
|
10~
|
2004–2018
|
-13.52(-18.19~-8.58) b
|
< 0.001
|
|
|
|
|
|
|
-13.52(-18.19~-8.58) b
|
< 0.001
|
20~
|
2004–2006
|
20.16(-17.74 ~ 75.53)
|
0.306
|
2006–2018
|
-16.82(-19.81~-13.73) b
|
< 0.001
|
|
|
|
-12.33(-17.03~-7.38) b
|
< 0.001
|
30~
|
2004–2018
|
-9.72(-11.89~-7.50) b
|
< 0.001
|
|
|
|
|
|
|
-9.72(-11.89~-7.50) b
|
< 0.001
|
40~
|
2004–2018
|
-10.16(-12.29~-7.98) b
|
< 0.001
|
|
|
|
|
|
|
-10.16(-12.29~-7.98) b
|
< 0.001
|
50~
|
2004–2018
|
-7.39(-8.86~-5.91) b
|
< 0.001
|
|
|
|
|
|
|
-7.39(-8.86~-5.91) b
|
< 0.001
|
60~
|
2004–2009
|
-2.59(-7.16 ~ 2.21)
|
0.238
|
2009–2015
|
-13.22(-18.63~-7.45) b
|
0.001
|
2015–2018
|
12.95(-2.88 ~ 31.37)
|
0.098
|
-4.31(-7.88~-0.60) b
|
0.023
|
70~
|
2004–2018
|
-6.68(-8.95~-4.36) b
|
< 0.001
|
|
|
|
|
|
|
-6.68(-8.95~-4.36) b
|
< 0.001
|
80~
|
2004–2018
|
-3.33(-7.55 ~ 1.09)
|
0.126
|
|
|
|
|
|
|
-3.33(-7.55 ~ 1.09)
|
0.126
|
(ASIR: age-standardized incidence rate by 2010 Chinese 6th population; ASDR: age-standardized mortality rate by 2010 Chinese 6th population;APC:Annual Percent Change;AAPC:Average Annual Percent Change. a:The number of trend columns and time intervals were determined based on the number of linkages and years in the best model, with trends 1, 2 and 3 representing mortality trends over different time intervals respectively; b Indicates that the APC and AAPC is significantly different from zero at the alpha = 0.05. )
2.3 Spatial distribution of hepatitis B
The results of the 2004–2021 hepatitis B incidence rate grading map show that there are large differences in the spatial distribution of hepatitis B incidence rates in various regions of China, and the high incidence of hepatitis B is mainly concentrated in the northwest and southeast coastal regions of China (Fig. 3). The regions with higher incidence rates are Gansu, Ningxia, Qinghai, Shaanxi, Xinjiang, Fujian, Guangdong, Guangxi and Hainan. The regions with lower incidence rates are Tibet, Jiangsu, Heilongjiang, Shandong, Beijing and Tianjin.The results of the 2004–2021 hepatitis B mortality rate grading map show that there were differences in the spatial distribution of hepatitis B mortality rates in various regions of China, and the areas were mainly concentrated in the northwest and eastern regions of China. The regions with higher mortality rates are Qinghai, Beijing and Shanghai. The regions with lower mortality rates are Jiangxi, Jilin and Tianjin.
2.4 Trend surface analysis of hepatitis B
The incidence and mortality rate of hepatitis B was taken as the dependent variable and the geographic position of each province as the independent variable to establish a 2-order trend surface model. A coordinate system was created (one axis for each direction with X for West-East and Y for South-North). The projections of incidence rates (Z axis) reflected the variation trend of West-East with South-North.From 2004 to 2006, the incidence rate of hepatitis B showed an inverted "U" distribution, which means that the incidence was high in the middle and low in the east-west direction. And after 2006, the incidence rate of hepatitis B showed an increasing trend from the east to the west. On the other hand, the north-south direction distribution showed that from 2004 to 2012, the incidence of hepatitis B showed a decreasing trend from the north to the south, and after 2012, the incidence of hepatitis B showed an increasing trend in the north.Overall, except for 2004, the hepatitis B mortality rate was characterized as high in the east and low in the west, and in the north-south direction, the hepatitis B incidence rate was higher in the north than in the south from 2004 to 2021 (Fig. 4).
2.5 Spatial autocorrelation analysis of hepatitis B
Global spatial autocorrelation evaluates the tendency of spatial clustering, dispersing, or random distribution across an entire region. We obtained the Moran’s I value, variance, Z score and P value from 2004 to 2021 using provincial units to carry out the global autocorrelation analysis.The global spatial autocorrelation analysis showed that the annual Moran’s I values of incidence rate of hepatitis B from 2004 to 2021were significantly different, indicating that incidence rate of hepatitis B was nonrandomly distributed, and the distribution of incidence rate of hepatitis B in China was spatially autocorrelated over the 18-year study period. The Moran’s I values of the annual incidence rate of hepatitis B were positive, and the P values were less than 0.05,There was a positive global spatial autocorrelation of hepatitis B incidence in China, with a obvious trend of spatial clustering,indicating that areas with high hepatitis B incidence were adjacent to areas with high hepatitis B incidence, and areas with low hepatitis B incidence were adjacent to areas with low hepatitis B incidence. The global Moran’s I values of incidence rate of hepatitis B is closer to 1 in 2004 and 2005, indicating a more significant clustering feature (Table 3).
The global spatial autocorrelation analysis showed that the statistical results of mortality rate of hepatitis B in 2004, 2013, and 2015–2021 were not significant, the hypothesis of its spatial random distribution could not be rejected, indicating that there was no significant spatial autocorrelation.The statistical results of mortality rate of hepatitis B in 2005–2012 and 2014 were significant, and the global Moran′s I values were less than zero, indicating that of mortality rate of hepatitis B in each region of the country .The statistical results of mortality rate of hepatitis B in 2005–2012, 2014 were significant and the global Moran′s I values were less than zero, with a obvious trend of spatial dispersion, indicating that the spatial distribution of mortality rate of hepatitis B in each region of the country had a negative spatial correlation. The global Moran’s I values of mortality rate of hepatitis B is closer to -1 in 2005 and 2008, indicating a more significant discrete feature.Thus, further spatial clustering analysis of hepatitis B was needed (Table 3).
Table 3
Global autocorrelation of incidence and mortality rate of hepatitis B in China from 2004 to 2021
Incidence rate of hepatitis B
|
Mortality rate of hepatitis B
|
Year
|
Moran′s I
|
Z-value
|
P-value
|
SD
|
E(I)
|
Moran′s I
|
Z-value
|
P-value
|
SD
|
E(I)
|
2004
|
0.338
|
3.4929
|
0.003
|
0.1058
|
-0.0333
|
-0.151
|
-1.3747
|
0.057
|
0.0859
|
-0.0333
|
2005
|
0.311
|
3.1825
|
0.007
|
0.1077
|
-0.0333
|
-0.217
|
-1.8059
|
0.016
|
0.1030
|
-0.0333
|
2006
|
0.280
|
3.0067
|
0.007
|
0.1050
|
-0.0333
|
-0.179
|
-2.1299
|
0.003
|
0.0673
|
-0.0333
|
2007
|
0.268
|
2.7254
|
0.017
|
0.1100
|
-0.0333
|
-0.173
|
-1.9735
|
0.009
|
0.0697
|
-0.0333
|
2008
|
0.259
|
2.7163
|
0.016
|
0.1068
|
-0.0333
|
-0.202
|
-1.8965
|
0.008
|
0.0877
|
-0.0333
|
2009
|
0.200
|
2.3970
|
0.021
|
0.0965
|
-0.0333
|
-0.158
|
-2.2341
|
0.004
|
0.0548
|
-0.0333
|
2010
|
0.217
|
2.3458
|
0.021
|
0.1059
|
-0.0333
|
-0.158
|
-2.2784
|
0.002
|
0.0538
|
-0.0333
|
2011
|
0.267
|
2.7292
|
0.017
|
0.1093
|
-0.0333
|
-0.125
|
-2.4913
|
0.008
|
0.0363
|
-0.0333
|
2012
|
0.202
|
2.1296
|
0.032
|
0.1081
|
-0.0333
|
-0.141
|
-1.4563
|
0.024
|
0.0719
|
-0.0333
|
2013
|
0.103
|
1.2785
|
0.108
|
0.1024
|
-0.0333
|
-0.087
|
-1.3896
|
0.078
|
0.0379
|
-0.0333
|
2014
|
0.181
|
1.9159
|
0.036
|
0.1079
|
-0.0333
|
-0.137
|
-2.3532
|
0.004
|
0.0440
|
-0.0333
|
2015
|
0.193
|
2.0524
|
0.033
|
0.1072
|
-0.0333
|
-0.080
|
-1.1740
|
0.133
|
0.0397
|
-0.0333
|
2016
|
0.149
|
1.8265
|
0.042
|
0.1012
|
-0.0333
|
-0.101
|
-1.0813
|
0.113
|
0.0615
|
-0.0333
|
2017
|
0.174
|
1.8918
|
0.035
|
0.1063
|
-0.0333
|
-0.086
|
-0.9686
|
0.135
|
0.0555
|
-0.0333
|
2018
|
0.193
|
2.0562
|
0.034
|
0.1075
|
-0.0333
|
-0.018
|
0.2432
|
0.348
|
0.0657
|
-0.0333
|
2019
|
0.187
|
2.0289
|
0.036
|
0.1065
|
-0.0333
|
-0.022
|
0.2253
|
0.381
|
0.0572
|
-0.0333
|
2020
|
0.209
|
2.2419
|
0.030
|
0.1062
|
-0.0333
|
-0.101
|
-0.9228
|
0.178
|
0.0720
|
-0.0333
|
2021
|
0.209
|
2.2419
|
0.030
|
0.1062
|
-0.0333
|
-0.101
|
-0.9228
|
0.178
|
0.0720
|
-0.0333
|
2.6 Local spatial autocorrelation analysis of hepatitis B
The local spatial autocorrelation analysis showed different clusters according to the LISA analysis. The High-High cluster areas of incidence rate of hepatitis B in China from 2004 to 2012 were mainly concentrated in the northwest, including Xinjiang, Qinghai, Gansu, and Ningxia, and in the southeast from 2018 to 2021 were concentrated, including Guangdong and Hainan. Low-Low cluster areas were mainly concentrated in Jilin, Liaoning, Shandong, Jiangsu, Shanghai and Heilongjiang.Low-High cluster areas was in Tibet. High-Low cluster areas were concentrated in Shandong and Anhui (Table 4).
There were no High-High, Low-Low and Low-High cluster areas of mortality rate of hepatitis B in China from 2004 to 2012, while the High-Low cluster areas were mainly concentrated in Beijing and Shanghai from 2004 to 2019. From 2015 to 2019, the mortality rate of hepatitis B in China revealed four types of clusters: High-High areas, Low-Low areas,Low-High areas and High-Low areas. The High-High cluster areas was concentrated in Heilongjiang, the Low-Low cluster areas were concentrated in Xinjiang, Qinghai and Jiangxi, the Low-High cluster areas were mainly concentrated in Jilin. There was no cluster area in 2020 and 2021 (Table 4).
2.7 Space-time scan analysis of hepatitis B
The space–time scan statistics identified both the most likely and secondary clusters of location groups for elevated risk of hepatitis B.The results showed that the incidence rate of hepatitis B were spatiotemporally clustered. One probably primary cluster and 2 secondary clusters (P = 0.000, 0.000 and 0.000 respectively) are shown in Table 4 and Fig. 4, the results of space–time cluster analysis for incidence rate of hepatitis B in China from 2004 to 2018 included one primary clustering area and two secondary clustering areas. The primary clustering area was located in the west of China, including Tibet, Qinghai, Xinjiang and Gansu, and the high-risk time frame was from January 2006 to December 2012 (RR = 2.78, LLR = 300786.49, P < 0.001).
Secondary space–time clusters of hepatitis B incidence were identified in Hainan and Guangdong from 2011 to 2017, and also in Sichuan and Chongqing from2004 to 2007 (Table 5) (Fig. 5).
The results showed that the mortality rate of hepatitis B also were spatiotemporally clustered. One probably primary cluster and 2 secondary clusters (P = 0.000, 0.000 and 0.000 respectively) are shown in Table 4 and Fig. 4, the results of space–time cluster analysis for mortality rate of hepatitis B in China from 2004 to 2018 included one primary clustering area and two secondary clustering areas. The primary clustering area was located in Beijing of China, and the high-risk time frame was from January 2007 to December 2013 (RR = 12.14, LLR = 1120.197907, P < 0.001).Secondary space–time clusters of hepatitis B mortality were located in the west of China, including Qinghai, Gansu, Tibet, Sichuan, from 2004 to 2008, and also in Fujian and Jiangxi from 2005 to 2009 (Table 5) (Fig. 5).