Trends in liver cancer mortality in China from 1990 to 2019: a systematic analysis based on the Global Burden of Disease Study 2019

Overall primary liver cancer mortality

Between 1990 and 2019, the age-standardised mortality from liver cancer first increased in China from 28.12 to 31.54 deaths per 100 000 population during 1990–1996 (APC=2.1%, 95% CI: 1.5% to 2.6%). Although these data included both sexes, the increase was driven by that observed in men. Following this period, decreases were observed in 1996–2000 (APC=−3.7%, 95% CI: −5.2% to –2.1%), 2000–2004 (APC=−17.4%, 95% CI: −18.7% to –16.1%), 2004–2007 (APC=−5.4%, 95% CI: −8.3% to –2.3%) and 2007–2012 (APC=−1.4%, 95% CI: −2.3% to –0.4%). However, the rate increased again, beginning in 2012 (APC=1.3%, 95% CI: 0.9% to 1.7%) (figure 1A, online supplemental table S1 and figure S1).

Supplemental material

Figure 1
Figure 1

Age-standardised mortality (per 100 000 population) from liver cancer in China, 1990–2019.

Subgroup analyses according to age and sex revealed similar patterns in mortality changes (figure 1A, B). Mortality rates were consistently higher in men than in women from 1990 to 2019 (mortality ratio: 2.2–3.0). In general, the mortality risk in patients with liver cancer increased with age. Children aged 5–14 years had the lowest liver cancer mortality between 1990 and 2019 (online supplemental table S1 and figures S2, S3).

Primary liver cancer mortality by sex, age group, aetiology, and risk factors

Between 1990 and 2019, hepatitis B virus and hepatitis C virus infections were the two most common aetiological factors of liver cancer in China, accounting for 63% and 18% of the overall age-standardised liver cancer mortality, respectively (figure 2A). The trends in age-standardised liver cancer mortality for all aetiological factors used were close to those for overall mortality from 1990 to 2019. Notably, according to aetiological factors, the spectra of liver cancer mortality differed between men and women. Hepatitis B virus infection accounted for 74% and 37% of liver cancer deaths in men and women, respectively. The percentages of deaths attributed to hepatitis C virus infection were 11% in men and 38% in women (figure 2B, C).

Figure 2
Figure 2

Aetiological factors of age-standardised mortality (per 100 000 population) from liver cancer by sex in China, 1990–2019. NASH, non-alcoholic fatty liver disease.

In men, age-standardised liver cancer mortality attributed to major aetiological factors visibly increased compared with that in women (hepatitis B: 2012–2019, APC=1.3%, 95% CI: 0.9% to 1.8%; hepatitis C: 2011–2015, APC=3.9%, 95% CI: 2.5% to 5.4%; 2015–2019, APC=1%, 95% CI: 0.1% to 1.8%; alcohol use: 2012–2017, APC=4.8%, 95% CI: 4.0% to 5.7%; and NASH: 2012–2015, APC=6.6, 95% CI: 4.2% to 9.1%) (online supplemental table S2 and figures S4–S9).

The aetiological spectra of liver cancer mortality also differed across the five age groups (figure 3A–E). Hepatitis B was most common aetiological factor influencing liver cancer mortality in three age groups (15–49, 50–69 and ≥70 years) and caused 80%, 67% and 48% of total liver cancer mortality, respectively. Hepatitis C was the second leading aetiological factor in liver cancer mortality among adults aged 50–69 and ≥70 years, accounting for 15% and 32% of total liver cancer mortality, respectively. Liver cancer mortality among children younger than 5 years was caused by other aetiological factors. It is crucial to consult primary research studies, medical literature or official reports, such specific aetiological factors including genetic and congenital disorders, liver cirrhosis and exposure to toxins or carcinogens.18 19

Figure 3
Figure 3

Age-specific mortality (per 100 000 population) from liver cancer by aetiological factor in China, 1990–2019. NASH, non-alcoholic fatty liver disease.

During the study period, most subgroups experienced significant increases in liver cancer mortality during the first and most recent decades, with the largest APC of 5.6% for hepatitis C among adults aged 15–49 years from 1990 to 1996. By contrast, in the subgroup analysis, nearly all liver cancer mortality rates significantly decreased in the other periods, with APCs ranging from −0.6% for alcohol use among adults aged ≥70 years in 2005–2012 to −19.9% for hepatitis C among adults aged 15–49 years in 2000–2004 (online supplemental table S3 and figures S10–S15).

In total, 60%–70% of age-standardised liver cancer deaths were attributed to five of the 87 modifiable risk factors considered by the GBD 2019 study group between 1990 and 2019 (figure 4A). Smoking, drug use, alcohol use and a high BMI were the four leading modifiable risk factors for liver cancer mortality in all subgroups (figure 4B, C). The specific criteria for risk factors, including high BMI (overweight: BMI ≥25 kg/m², obesity: BMI ≥30 kg/m²) and fasting plasma glucose levels (impaired fasting glucose: fasting plasma glucose between 100 and 125 mg/dL, diabetes: fasting plasma glucose ≥126 mg/dL), can be found in the GBD risk factors collaborators’ publications and documentation.15–17 However, the spectra of risk factors for liver cancer mortality differed significantly across sex and age groups. For example, smoking was the leading risk factor for liver cancer mortality in men but the fourth leading risk factor in women. The percentage of mortality attributed to drug use rapidly increased with age (figure 4D–F).

Figure 4
Figure 4

Mortality (per 100 000 population) from liver cancer attributed to modifiable risk factors in the China, 1990–2019. Results attributed to modifiable risk factors was omitted for age groups 0–4 years and 5–14 years due to extremely small attributed mortality rates.

The time periods with the greatest increases and decreases in mortality were as follows: smoking in 1990–1996 (APC=4.7%, 95% CI: 3.4% to 5.9%), high fasting plasma glucose level in 1990–1994 (APC=4.6%, 95% CI: 3.7% to 5.6%), smoking in 2000–2005 (APC=−16.6%, 95% CI: −18.5% to –14.7%) and drug use in 2000–2004 (APC=−16.5%, 95% CI: −17.9% to –15.0%) (online supplemental table S4). Sex-specific analyses revealed clear differences in the patterns of mortality changes attributed to specific risk factors between men and women, such as smoking in 2012–2019 for men (APC=1.4%, 95% CI: 1.0% to 1.8%) versus in 2011–2019 for women (APC=−0.7%, 95% CI: −1.1% to –0.3%) and alcohol use in 1990–1996 for men (APC=2.6%, 95% CI: 1.8% to 3.4%) versus for women (APC=0.2%, 95% CI: −0.5% to 0.9%) (online supplemental table S5 and figures S16–S19). In the age-specific analysis, the greatest mortality increases attributed to smoking occurred among adults aged 50–69 years and older (APC=−17.9%, 95% CI: −18.8% to –17.0%), and the most notable mortality increase attributed to the high BMI occurred among young adults aged 15–49 years and older (APC=4.6%, 95% CI: 4.3% to 4.8%) (online supplemental table S6 and figures S20–S24).

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