Time Trends in Primary Liver Cancer Incidence Between China and the United States: Insights From the Global Burden of Disease 2019
Primary liver cancer (PLC) remains a major global health challenge, with significant disparities in incidence patterns between nations. This analysis of data from the Global Burden of Disease (GBD) 2019 study examines the epidemiological shifts in PLC incidence in China and the United States (US) from 1990 to 2019 using age-period-cohort (APC) modeling. The study focuses on four key etiological factors—hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol consumption, and nonalcoholic steatohepatitis (NASH)—to unravel the complex interplay of age, period, and cohort effects driving incidence trends.
Epidemiological Burden of Primary Liver Cancer
In 2020, China and the US ranked first and third globally in new PLC cases, reflecting contrasting risk factor profiles and public health trajectories. By 2019, China reported 211,000 new PLC cases (39.4% of global cases), while the US recorded 28,000 cases (5.2%). Gender disparities were pronounced: males accounted for 75.8% of cases in China and 71.9% in the US. The age-standardized incidence rate (ASIR) in China declined before 2005 but plateaued thereafter, contrasting with consistent increases in the US. These divergent trends highlight the influence of etiological drivers and prevention policies.
Etiological Contributions and Trends
Viral Hepatitis and Immunization Impact
HBV-related liver cancer (LCHB) dominated China’s PLC burden, though its contribution has decreased due to nationwide immunization programs initiated in the late 1980s. Among Chinese women, LCHB incidence fell most rapidly (−6.16% annual decline). Conversely, the US saw a 165% rise in HCV-related liver cancer (LCHC) from 1990 to 2019, linked to delayed diagnosis and limited access to direct-acting antivirals (DAAs). Despite China’s progress, gaps persist—only 19% of chronic HBV cases were diagnosed by 2019, underscoring the need for enhanced screening.
Lifestyle-Related Factors
NASH-related PLC emerged as the fastest-growing etiology in both nations. In the US, male NASH cases surged by 168% over 30 years, driven by rising obesity and metabolic disorders. Alcohol-related liver cancer (LCAL) also escalated, with US males experiencing a 158% increase. China faced similar challenges: alcohol consumption patterns and sedentary lifestyles contributed to upward trends in LCAL and NASH, particularly among men.
Age-Period-Cohort Analysis of Incidence Trends
Net and Local Drifts
Net drift—the overall annual percentage change—revealed declining trends in China (−4.52% for males, −5.95% for females) versus rising trends in the US (+2.44% for males, +2.13% for females). Local drift patterns further stratified age-specific risks:
- China: Sharpest declines occurred at ages 53 (males: −5.2%/year) and 33 (females: −6.6%/year), reflecting HBV vaccination benefits.
- US: Peaks at age 58 highlighted baby boomer cohorts exposed to HCV and lifestyle risks, with males showing a 4.5%/year increase.
Period and Cohort Effects
Period effects (environmental or policy influences affecting all ages) diverged post-2012. China’s progress against LCHB stalled, while LCAL and NASH rose—likely due to lifestyle shifts and delayed HCV management. In the US, slowed LCHC increases after 2012 aligned with DAAs’ introduction, though cost barriers limited broader impact.
Cohort effects (birth-year-specific risks) showed generational contrasts:
- China: Steady risk reductions for cohorts born after 1915, attributable to HBV immunization and dietary improvements.
- US: Post-1975 cohorts faced elevated risks from HCV, alcohol, and metabolic syndromes.
Public Health Implications and Challenges
China’s Dual Burden
China’s PLC landscape reflects transition: HBV control has reduced infections, but lifestyle diseases are rising. Over 20% of adults have hepatic conditions, with NASH prevalence climbing alongside economic development. Persistent gaps in HBV/HCV diagnosis—particularly in rural areas—threaten progress. Strengthening prenatal screening, expanding DAAs coverage, and curbing alcohol marketing are critical steps.
The US Experience
The US confronts entrenched disparities: ethnic minorities and underserved populations bear higher PLC burdens. While DAAs reduced HCV mortality, treatment costs ($66,000–$154,000 per course) limit accessibility. Universal screening for HCV (recommended in 2020) and HBV (initiated for pregnant women in 2009) must expand to high-risk groups. Concurrently, addressing obesity and alcohol abuse requires multisectoral policies, such as sugar taxes and stricter advertising regulations.
Global Lessons and Future Directions
Both nations exemplify the dual challenge of combating viral and lifestyle-related PLC. China’s success with HBV vaccines offers a model for low-resource settings, while the US highlights the need for equitable access to therapies. Emerging threats like NASH demand innovation: no approved drugs currently target NASH-related liver damage, underscoring the urgency of research investment.
Conclusion
The APC analysis elucidates how demographic shifts, policy interventions, and behavioral trends shape PLC trajectories. For China, sustaining declines in viral hepatitis while addressing Westernized lifestyles is paramount. In the US, reducing healthcare inequities and curbing metabolic risks are vital to reversing rising trends. Both nations must prioritize integrated strategies targeting HBV/HCV elimination and lifestyle modifications to mitigate the growing burden of alcohol- and NASH-related PLC.
doi:10.1097/CM9.0000000000001980
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