Risk factors attributable to LC burden
In 2019, there were 484,577 (95% UI: 444,091 to 525,798) LC deaths and 12,528,422 (11,400,671 to 13,687,675) LC DALYs globally, with nearly half of these being attributed to the five risk factors. Among the 254.7 thousand risk attributed LC deaths, alcohol use accounted for 30.4%, smoking accounted for 27.2%, drug use accounted for 20.6%, high BMI accounted for 20.6%, and high fasting plasma glucose accounted for the remaining 1.3% (Table 1). In 2019, the ASR of the total risk attributed LC deaths and DALYs were 3.1 (2.7 to 3.6) per 100,000 persons and 75.0 (63.0 to 88.2) per 100,000 persons, respectively.
Table 1
Global liver cancer deaths and DALYs attributable to risk factors by specific etiologies for both sexes combined in 2019 and percentage change from 1990 to 2019.
Risk-outcome pairs
|
Deaths
|
DALYs
|
2019 all ages number
(× 103)
|
Change% in all ages number, 1990–2019
|
2019 age-standardized rate per 100,000 people
|
Change% in age-standardized rate, 1990–2019
|
2019 all ages number
(× 106)
|
Change% in all ages number, 1990–2019
|
2019 age-standardized rate per 100,000 people
|
Change% in age-standardized rate, 1990–2019
|
Liver cancer
|
254.7
(218.2 to 297.1)
|
65.1
(42.7 to 92.7)*
|
3.1
(2.7 to 3.6)
|
−18.6
(−29.3 to−5.5)*
|
6.3
(5.3 to 7.4)
|
44.0
(22.4 to 70.2)*
|
75.0
(63.0 to 88.2)
|
−27.3
(−38.0 to−14.3)*
|
Smoking
|
85.9
(50.0 to 123.0)
|
12.9
(−8.6 to 56.2)
|
1.0
(0.9 to 1.4)
|
−36.5
(−47.5 to−23.1)*
|
2.1
(1.2 to 3.1)
|
13.6
(−8.2 to 42.6)
|
25.3
(13.8 to 36.5)
|
−43.1
(−53.7 to−29.5)*
|
Alcohol use
|
96.1
(77.5 to 116.2)
|
77.7
(53.9 to 102.2)*
|
1.2
(0.9 to 1.4)
|
−12.8
(−24.0 to−1.3)*
|
2.4
(1.9 to 2.9)
|
56.0
(31.4 to 82.0)*
|
28.4
(22.9 to 34.5)
|
−21.1
(−32.9 to−8.6)*
|
Drug use
|
71.5
(57.1 to 89.2)
|
85.5
(56.2 to 121.3)*
|
0.9
(0.7 to 1.1)
|
−8.0
(−22.8 to 9.6)
|
1.6
(1.3 to 2.0)
|
55.5
(32.4 to 85.6)*
|
19.4
(15.6 to 23.9)
|
−22.0
(−33.6 to−7.0)*
|
High fasting plasma glucose
|
4.7
(1.2 to 10.4)
|
40.6
(32.0 to 51.1)*
|
0.1
(0.0 to 0.1)
|
13.0
(−1.6 to 32.7)
|
0.1
(0.0 to 0.2)
|
105.5
(76.5 to 276.4)*
|
1.2
(0.3 to 2.6)
|
1.1
(−13.0 to 20.3)
|
High body-mass index
|
60.8
(24.2 to 114.6)
|
162.3
(99.9 to 297.6)*
|
0.7
(0.3 to 1.4)
|
28.9
(−1.1 to 93.4)*
|
1.6
(0.6 to 3.0)
|
137.7
(76.2 to 276.4)*
|
19.2
(7.6 to 36.4)
|
21.0
(−9.9 to 89.8)*
|
Liver cancer due to hepatitis B
|
62.5
(40.3 to 86.1)
|
22.6
(−7.2 to 63.0)
|
0.8
(0.5 to 1.0)
|
−38.3
(−52.9 to−18.0)*
|
1.9
(1.2 to 2.6)
|
12.7
(−15.3 to 52.9)
|
22.1
(14.0 to 30.5)
|
−41.9
(−56.3 to−21.4)*
|
Smoking
|
38.1
(20.9 to 56.4)
|
27.0
(−3.1 to 114.4)
|
0.5
(0.3 to 0.7)
|
−48.6
(−60.1 to−32.7)*
|
1.1
(0.6 to 1.6)
|
−5.9
(−28.1 to 26.8)
|
12.6
(6.7 to 19.2)
|
−52.4
(−63.5 to−36.3)*
|
Alcohol use
|
4.6
(0.2 to 11.7)
|
−17.9
(−49.2 to 82.4)
|
0.1
(0.0 to 0.1)
|
−56.0
(−72.1 to 8.7)
|
0.2
(0.0 to 0.4)
|
−21.8
(−50.6 to 72.7)
|
2.2
(0.1 to 5.2)
|
−56.9
(−72.0 to 6.2)
|
Drug use
|
3.1
(2.1 to 4.6)
|
77.4
(36.9 to 128.3)*
|
0.0
(0.0 to 0.1)
|
−9.8
(−30.0 to 16.0)
|
0.1
(0.0 to 0.1)
|
60.1
(23.5 to 108.0)*
|
1.1
(0.7 to 1.6)
|
−16.8
(−36.0 to 8.1)
|
High body-mass index
|
24.1
(8.7 to 48.3)
|
122.9
(56.9 to 293.8)*
|
0.3
(0.1 to 0.6)
|
13.1
(−20.0 to 98.1)
|
0.7
(0.3 to 1.5)
|
106.0
(42.0 to 271.0)*
|
8.9
(3.2 to 17.5)
|
7.6
(−25.5 to 93.1)
|
Liver cancer due to hepatitis C
|
87.0
(70.7 to 104.8)
|
82.9
(59.1 to 111.5)*
|
1.1
(0.9 to 1.3)
|
−10.8
(−22.3 to 2.9)
|
1.9
(1.5 to 2.3)
|
55.4
(35.3 to 80.8)*
|
22.7
(18.6 to 27.3)
|
−22.8
(−32.7 to−10.5)*
|
Smoking
|
21.9
(12.5 to 31.7)
|
55.7
(36.1 to 80.2)
|
0.5
(0.3 to 0.7)
|
1.7
(−13.7 to 21.9)
|
0.5
(0.2 to 0.7)
|
36.1
(19.5 to 56.5)*
|
5.5
(3.0 to 7.9)
|
−33.6
(−41.5 to−24.0)*
|
Alcohol use
|
0.7
(0.0 to 2.6)
|
16.5
(−34.0 to 135.6)
|
0.0
(0.0 to 0.0)
|
−40.2
(−64.6 to 24.4)
|
0.0
(0.0 to 0.1)
|
−9.9
(−41.5 to 100.0)
|
0.2
(0.0 to 0.7)
|
−53.5
(−69.4 to 10.3)
|
Drug use
|
68.3
(54.6 to 85.4)
|
85.9
(56.2 to 121.8)*
|
0.8
(0.7 to 1.1)
|
−7.9
(−22.8 to 9.8)
|
1.5
(1.2 to 1.9)
|
41.4
(27.9 to 58.0)*
|
18.3
(14.7 to 22.6)
|
−22.3
(−34.1 to−7.1)*
|
High body-mass index
|
19.1
(7.6 to 35.4)
|
189.5
(137.2 to 302.4)*
|
0.2
(0.1 to 0.4)
|
36.4
(12.1 to 89.3)*
|
0.4
(0.2 to 0.8)
|
164.8
(111.8 to 279.4)*
|
5.1
(2.0 to 9.2)
|
29.1
(3.4 to 84.5)*
|
Liver cancer due to alcohol use
|
90.7
(73.3 to 109.4)
|
89.6
(71.7 to 110.5)*
|
1.1
(0.9 to 1.3)
|
−8.0
(−16.5 to 1.8)
|
2.2
(1.8 to 2.7)
|
71.1
(53.9 to 91.5)*
|
26.1
(21.1 to 31.6)
|
−14.8
(−23.1 to−4.8)*
|
Smoking
|
17.7
(9.7 to 26.2)
|
72.8
(53.2 to 95.5)*
|
0.2
(0.1 to 0.3)
|
−16.6
(−25.8 to−6.5)*
|
0.4
(0.2 to 0.6)
|
58.2
(40.4 to 79.7)*
|
4.9
(2.7 to 7.4)
|
−22.3
(−30.9 to 17.0)
|
Alcohol use
|
90.7
(73.3 to 109.4)
|
89.6
(71.7 to 110.5)*
|
1.1
(0.9 to 1.3)
|
−8.0
(−16.5 to 1.8)
|
2.2
(1.8 to 2.7)
|
71.1
(53.9 to 91.5)*
|
26.1
(21.1 to 31.6)
|
−14.8
(−23.1 to−12.4)*
|
High body-mass index
|
14.6
(5.6 to 28.3)
|
221.5
(167.0 to 314.9)*
|
0.2
(0.1 to 0.3)
|
54.9
(29.0 to 99.1)*
|
0.4
(0.2 to 0.7)
|
204.3
(148.6 to 300.4)*
|
4.3
(1.6 to 8.2)
|
50.3
(23.0 to 97.4)*
|
Liver cancer due to NASH
|
7.5
(4.3 to 11.7)
|
118.9
(83.3 to 157.8)*
|
0.1
(0.1 to 0.2)
|
4.3
(−11.7 to 21.6)
|
0.2
(0.1 to 0.2)
|
92.5
(60.1 to 129.4)*
|
1.9
(1.1 to 3.0)
|
−5.7
(−20.6 to 12.0)
|
Smoking
|
5.0
(2.8 to 7.5)
|
92.3
(64.9 to 127.9)*
|
0.1
(0.0 to 0.1)
|
−7.9
(−20.3 to 7.3)
|
0.1
(0.1 to 0.2)
|
70.5
(44.6 to 103.1)*
|
1.3
(0.7 to 2.0)
|
−16.2
(−28.3 to−1.4)*
|
High fasting plasma glucose
|
3.0
(0.7 to 6.9)
|
196.5
(160.7 to 246.0)*
|
0.0
(0.0 to 0.1)
|
38.5
(23.1 to 61.2)*
|
0.1
(0.0 to 0.1)
|
164.3
(130.7 to 212.2)*
|
0.7
(0.2 to 1.7)
|
27.8
(11.8 to 50.6)*
|
Liver cancer due to other causes
|
7.0
(4.5 to 10.3)
|
55.9
(27.4 to 93.6)*
|
0.1
(0.1 to 0.2)
|
−23.1
(−36.9 to−5.6)*
|
0.2
(0.1 to 0.3)
|
39.4
(12.0 to 78.1)*
|
2.2
(1.4 to 3.2)
|
−29.2
(−42.7 to−10.8)*
|
Smoking
|
3.2
(1.2 to 5.7)
|
21.3
(−2.7 to 52.3)
|
0.0
(0.0 to 0.1)
|
−40.2
(−5.8 to 78.0)
|
0.1
(0.0 to 0.1)
|
6.8
(−15.5 to 38.2)
|
1.0
(0.5 to 1.5)
|
−46.2
(−57.0 to 101.8)
|
High fasting plasma glucose
|
1.7
(0.4 to 3.7)
|
74.5
(47.8 to 109.0)*
|
0.0
(0.0 to 0.0)
|
−15.5
(−51.6 to−25.5)*
|
0.0
(0.0 to 0.1)
|
52.9
(27.9 to 84.7)*
|
0.5
(0.1 to 1.0)
|
−23.9
(−36.2 to−31.7)*
|
High body-mass index
|
3.0
(1.2 to 5.7)
|
143.6
(80.2 to 286.2)*
|
0.0
(0.0 to 0.1)
|
21.4
(−9.3 to 89.5)
|
0.1
(0.0 to 0.2)
|
118.8
(57.2 to 261.5)*
|
1.0
(0.4 to 1.9)
|
13.7
(−17.5 to 85.8)
|
*indicates statistically significant change. |
Abbreviations: DALYs = disability-adjusted life years; NASH = non-alcoholic steatohepatitis |
With respect to different etiologies, smoking contributed more than half of LCHB burden, followed by high BMI (35.7%) and alcohol use (8.6%). Drug use accounted for 63.0% of LCHC burden, followed by smoking (18.8%) and high BMI (17.5%). For LCAU, alcohol use had the greatest contribution (73.8%), and other related risks were smoking (14.0%) and high BMI (12.2%). Smoking (64.4%) and high fasting plasma glucose (35.6%) contributed to LCNA burden, whereas for LCOC, the related risks included high BMI (41.0%), smoking (40.1%), and high fasting plasma glucose (18.9%) (Supplementary Figure S1).
Global Exposure Level To The Risk Factors
Exposure to alcohol use was high in Europe, Australasia, and high-income North America, with Estonia (ASR of SEV = 19.9%), Czechia (19.9%), and Germany (19.4%) the highest. For drug use, high-income North America, North Africa, and the Middle East had high exposure levels, with three countries having the highest levels being USA (1.2%), Canada (0.6%), and Australia (0.6%). High levels of high BMI exposure were observed especially in high-income North America, and Australasia, with Qatar (56.5%), United Arab Emirates (53.6%), and Kuwait (53.5%) having the highest levels. Exposure to high fasting plasma glucose was high in Oceania, Sub-Saharan Africa, and Central and Southeast Asia, with Marshall Islands (38.4%), American Samoa (37.2%), and Niue (32.4%) the highest. Exposure to smoking was high in Europe, and Southern Latin America, with the highest rates in Montenegro (24.6%), Greece (23.5%), and Bosnia and Herzegovina (22.9%) (Fig. 1).
Global Lc Burden By Sex And Age Group
The LC burden in males (120.9) was more than three times that in females (32.5) in 2019, in terms of age-standardized DALY rates. From 1990 to 2019, the LC burden in females and males demonstrated a trend of first increasing and then decreasing. The general ranking of LC burden due to risk factors was similar in both sexes. However, drug use attributed LC burden has been increasing in females from 1990, and then decreased in the past decade, and the alcohol use attributed burden has gradually decreased from 1990 to 2019 (Fig. 2).
The LC burden was mainly concentrated in the 45 to 69 years old age group with the heaviest in the 60 to 64 years old for males and the 65 to 69 years old for females (Fig. 3). Overall, LC burden increased with age from 20 to 60 years old and decreased with age after 60 years old. Among patients over 50 years old, LC burden attributable to drug use increased and burden attributable to high BMI decreased in males.
Regional And National Lc Burden
In 1990, the risk attributed LC burden was the highest in East Asia, followed by high-income Asia Pacific, and the lowest in Central Sub-Saharan Africa and Southern Latin America, in terms of DALYs. With respect to specific etiologies, LCHB burden was the highest in East Asia and Oceania; LCHC burden was the highest in high-income Asia Pacific, North Africa and the Middle East; and LCAU burden was the highest in the 17 remaining GBD regions. The highest risk attributed LC burden was observed in Mongolia, Sierra Leone, and Burkina Faso.
By contrast, Central Asia and High-income Asia Pacific had the highest risk attributable LC burden in 2019, and the lowest burden was in Central Sub-Saharan Africa and Eastern Sub-Saharan Africa. LCHB burden was still the highest in East Asia; LCHC burden was the highest in high-income Asia Pacific, North Africa and the Middle East and Oceania; and LCAU burden was the highest in the 17 remaining GBD regions (Fig. 4). The three countries with the heaviest risk-related LC burden were Mongolia, Gambia, and Tonga in 2019.
Trends Of Risk-related Lc Burden
Globally, total risk factors attributed LC burden increased from 1990 to 2000, then decreased from 2001 to 2005, and remained stable. In low SDI regions, LC burden remained stable, while it first increased and then gradually stabilized in high SDI regions, and other regions remained consistent with global trend (Fig. 5).
LC burden due to high BMI, and high fasting plasma glucose continued to grow from 2005 to 2019. Burden due to alcohol use and drug use fell after 2000, and rose slightly from 2005 to 2019, while burden due to smoking continued to reduce from 2005, in terms of ASDR. For alcohol use, drug use, and high BMI, the related LC burden was the highest in the high SDI region, and was the lowest in the low SDI region. For high fasting plasma glucose and smoking, middle SDI region had the highest burden. (Supplementary Figure S2).
Relationship Between Risk-related Lc Burden And Social Development
In general, the SEVs of drug use and high BMI increased with SDI, whereas the alcohol use and smoking exposure levels first increased with increasing SDI and decreased when the SDI became > 0.8. In particular, the high fasting plasma glucose SEV decreased with an increase in the SDI value from 0.5 to 0.8 (Fig. 6).
In terms of the DALY rates, the relationship between the overall LC burden with SDI was roughly similar to that of LC by different causes. The risk-related burden first increased as SDI increased from 0.2 to 0.5, then decreased as SDI ranged from 0.5 to 0.7, and increased again after the SDI value became > 0.7 (Supplementary Figure S3).