基于GBD 2023的1990—2023年全球与中国肝癌及肝硬化/慢性肝病疾病负担与病因谱变化分析

Changes in the burden and etiologic profiles of liver cancer and cirrhosis/chronic liver diseases globally and in China from 1990 to 2023: an analysis based on GBD 2023

摘要:

背景与目的 肝癌及肝硬化/慢性肝病是全球重要的肝病负担来源，其疾病负担及病因谱受病毒性肝炎、代谢异常、酒精暴露及人口结构等多重因素影响，并存在明显的地区和人群差异。随着肝病防控措施持续推进及危险因素谱不断变化，全球与中国肝癌及肝硬化/慢性肝病的疾病负担和病因构成亦可能发生改变。本研究基于全球疾病负担研究2023（GBD 2023）数据，系统分析1990—2023年全球与中国肝癌及肝硬化/慢性肝病的疾病负担、变化趋势及病因谱，并比较不同社会人口学指数（SDI）水平以及中国不同年龄和性别人群的疾病负担特征。方法 通过GBD Results Tool提取1990—2023年全球、中国及5个SDI分层肝癌和肝硬化/慢性肝病及其主要病因的发病数、死亡数、年龄标化发病率（ASIR）和年龄标化死亡率（ASMR）。采用估计年变化百分比（EAPC）及其95%置信区间（CI）评价年龄标化率的长期变化趋势，计算主要病因的发病和死亡构成比及死亡/发病比（MIR），并比较不同SDI分层和病因特异性EAPC；进一步分析中国2023年性别和年龄亚组的疾病负担特征。病因构成比以5类纳入病因的点估计之和为分母。结果 1990—2023年，中国肝癌发病数由100 088例增至165 113例，死亡数由92 325例增至143 638例；ASIR由10.68/10万降至7.52/10万（EAPC=-1.386，95% CI=-1.538~-1.233），ASMR由10.13/10万降至6.44/10万（EAPC=-1.645，95% CI=-1.814~-1.474）。同期，中国肝硬化/慢性肝病发病数由11 307 703例增至11 449 246例，死亡数由164 354例降至120 865例，ASIR和ASMR的EAPC分别为-0.789和-4.014。中国两类疾病年龄标化率的下降幅度总体大于全球及相应SDI分层。中国乙型肝炎病毒（HBV）相关肝癌发病构成比由68.18%降至62.94%，2023年HBV相关肝硬化/慢性肝病死亡构成比仍为75.11%；非酒精性脂肪性肝病相关肝硬化/慢性肝病发病构成比由54.77%升至81.80%，其ASIR呈上升趋势（EAPC=0.752，95% CI=0.594~0.910）。全球肝癌酒精相关和非酒精性脂肪性肝炎（NASH）相关ASIR均呈上升趋势，EAPC分别为0.264和0.539；中国各病因肝癌ASIR均下降，但NASH相关和酒精相关ASIR下降较慢。2023年，中国男性肝癌ASIR和ASMR分别为女性的3.20倍和3.04倍，肝硬化/慢性肝病ASMR为女性的2.88倍；≥70岁人群分别占肝癌发病数、肝癌死亡数和肝硬化/慢性肝病死亡数的29.96%、35.39%和38.03%。结论 1990—2023年，全球与中国肝癌及肝硬化/慢性肝病的年龄标化负担总体下降，但绝对疾病负担仍然较重。中国肝病负担呈现HBV相关存量负担仍高、代谢及酒精相关病因贡献逐渐增加，以及男性和老年人群负担较重的特征。未来肝病防控应在持续加强病毒性肝炎防治的基础上，进一步关注代谢危险因素和酒精性肝病，并针对男性及老年人等重点人群实施分层管理。

Abstract:

Background and Aims Liver cancer and cirrhosis/chronic liver diseases are major contributors to the global burden of liver disease. Their burden and etiologic profiles are influenced by multiple factors, including viral hepatitis, metabolic disorders, alcohol exposure, and population aging, with substantial geographic and population-level differences. As liver disease prevention and control measures continue to advance and risk-factor profiles evolve, the burden and etiologic composition of liver cancer and cirrhosis/chronic liver diseases may also change. This study aimed to systematically assess the burden, temporal trends, and etiologic profiles of liver cancer and cirrhosis/chronic liver diseases globally and in China from 1990 to 2023 using data from the Global Burden of Disease Study 2023 (GBD 2023), and to compare disease burden across socio-demographic index (SDI) strata and age- and sex-specific subgroups in China.Methods Data on incident cases, deaths, age-standardized incidence rates (ASIR), and age-standardized mortality rates (ASMR) for liver cancer and cirrhosis/chronic liver diseases and their major etiologies from 1990 to 2023 were obtained from the GBD Results Tool for the global population, China, and five SDI strata. Estimated annual percentage changes (EAPC) and their 95% confidence intervals (CI) were calculated to assess long-term trends in age-standardized rates. Etiologic proportions and mortality-to-incidence ratios (MIR) were calculated, and EAPC were compared across SDI strata and etiologies. Sex- and age-specific disease burden in China was further assessed for 2023. Etiologic proportions were calculated using the sum of the point estimates for the five included etiologies as the denominator.Results From 1990 to 2023, incident cases of liver cancer in China increased from 100 088 to 165 113, and deaths increased from 92 325 to 143 638. The ASIR decreased from 10.68 to 7.52 per 100 000 (EAPC=-1.386, 95% CI=-1.538--1.233), and the ASMR decreased from 10.13 to 6.44 per 100 000 (EAPC=-1.645, 95% CI=-1.814--1.474). During the same period, incident cases of cirrhosis/chronic liver diseases in China increased from 11 307 703 to 11 449 246, whereas deaths decreased from 164 354 to 120 865; the EAPCs for ASIR and ASMR were -0.789 and -4.014, respectively. The declines in age-standardized rates for both conditions in China were generally greater than those globally and in the corresponding SDI strata. The proportion of HBV-related liver cancer incidence in China decreased from 68.18% to 62.94%, while HBV-related disease accounted for 75.11% of cirrhosis/chronic liver disease deaths in 2023. The proportion of NAFLD-related cirrhosis/chronic liver disease incidence increased from 54.77% to 81.80%, accompanied by an increasing ASIR (EAPC=0.752, 95% CI=0.594-0.910). Globally, the ASIRs of alcohol-related and NASH-related liver cancer increased, with EAPCs of 0.264 and 0.539, respectively. In China, ASIRs for all liver cancer etiologies decreased, although the declines for NASH-related and alcohol-related liver cancer were relatively slower. In 2023, the male-to-female ratios of liver cancer ASIR and ASMR were 3.20 and 3.04, respectively, and the ratio of cirrhosis/chronic liver disease ASMR was 2.88. Individuals aged ≥70 years accounted for 29.96% of liver cancer incident cases, 35.39% of liver cancer deaths, and 38.03% of cirrhosis/chronic liver disease deaths.Conclusion From 1990 to 2023, the age-standardized burden of liver cancer and cirrhosis/chronic liver diseases generally declined globally and in China, although the absolute burden remained substantial. China continued to experience a high HBV-related burden, accompanied by increasing contributions from metabolic and alcohol-related etiologies and a disproportionate burden among males and older adults. Future prevention and control strategies should continue to prioritize viral hepatitis while strengthening the management of metabolic risk factors and alcoholic liver disease and implementing targeted interventions for high-risk populations, particularly males and older adults.