中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 41 Issue 9
Sep.  2025
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2025  >  41(9): 1837-1844

Clinical features of hepatitis B virus-related early-onset and late-onset liver cancer： A comparative analysis

DOI: 10.12449/JCH250919

  • Center for Liver Disease，Guangzhou Eighth People’s Hospital，Guangzhou Medical University，Guangzhou 510440，China

Research funding:

Science and Technology Program of Guangzhou Municipality (2024A03J0860);

Science and Technology Program of Guangzhou Municipality (2023A03J0786);

Regional Joint Fund-Youth Fund Project (22201910240001437)

More Information
  • Corresponding author: LI Jianping， gz8hljp@126.com （ORCID： 0009-0007-5335-1938）
  • Received Date: 2025-03-08
  • Accepted Date: 2025-04-07
  • Published Date: 2025-09-25
    Abstract
  •   Objective  To compare the clinical features of patients with hepatitis B virus （HBV）-related early-onset liver cancer and those with late-onset liver cancer， to assess the severity of the disease， and to provide a theoretical basis for the early diagnosis and treatment of liver cancer.  Methods  A retrospective analysis was performed for 695 patients who were diagnosed with HBV-related liver cancer for the first time in Guangzhou Eighth People’s Hospital， Guangzhou Medical University， from January 2019 to August 2023， among whom 93 had early-onset liver cancer （defined as an age of<50 years for female patients and<40 years for male patients） and 602 had late-onset liver cancer （defined as an age of ≥50 years for female patients and ≥40 years for male patients）. Related clinical data were collected， including demographic data， clinical symptoms at initial diagnosis， comorbidities， smoking history， drinking history， family history， routine blood test results， biochemical parameters of liver function， serum alpha-fetoprotein（AFP）， virological indicators， coagulation function， and imaging findings. The pan-inflammatory indices neutrophil-to-lymphocyte ratio （NLR）， platelet-to-lymphocyte ratio （PLR）， and lymphocyte-to-monocyte ratio （LMR） were calculated， as well as FIB-4 index， aspartate aminotransferase-to-platelet ratio index （APRI）， S index， Model for End-Stage Liver Disease （MELD） score， Child-Turcotte-Pugh （CTP） score， albumin-bilirubin （AIBL） grade， and Barcelona Clinic Liver Cancer （BCLC） stage. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or Fisher’s exact test were used for comparison of categorical data between two groups.  Results  There were significant differences between the two groups in the proportion of male patients and the incidence rates of diabetes， hypertension， and fatty liver disease （χ2=6.357， 15.230， 11.467， and 14.204， all P<0.05）， and compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly higher proportion of patients progressing to liver cancer without underlying cirrhosis （χ2=24.657， P<0.001） and a significantly higher proportion of patients with advanced BCLC stage （χ2=6.172， P=0.046）. For the overall population， the most common clinical symptoms included abdominal distension， abdominal pain， poor appetite， weakness， a reduction in body weight， edema of both lower limbs， jaundice， yellow urine， and nausea， and 55 patients （7.9%） had no obvious symptoms at the time of diagnosis and were found to have liver cancer by routine reexamination， physical examination suggesting an increase in AFP， or radiological examination indicating hepatic space-occupying lesion； compared with the late-onset liver cancer group， the patients in the early-onset liver cancer group were more likely to have the symptoms of abdominal distension， abdominal pain， and jaundice （all P<0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly larger tumor diameter （Z=2.845， P=0.034）， with higher prevalence rates of multiple tumors and intrahepatic， perihepatic， or distant metastasis （χ2=5.889 and 4.079， both P<0.05）， and there were significant differences between the two groups in tumor location and size （χ2=3.948 and 11.317， both P<0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had significantly lower FIB-4 index， proportion of patients with HBsAg ≤1 500 IU/mL， and levels of LMR and Cr （all P<0.05）， as well as significantly higher positive rate of HBeAg and levels of log10 HBV DNA， AFP， WBC， Hb， PLT， NLR， PLR， TBil， ALT， Alb， and TC （all P<0.05）.  Conclusion  Compared with late-onset liver cancer， patients with early-onset liver cancer tend to develop liver cancer without liver cirrhosis and have multiple tumors， obvious clinical symptoms， and advanced BCLC stage， which indicates a poor prognosis.

     

    • FullText(HTML)
  • loading
    • References(47)
  • [1]
    ZHENG RS, ZHANG SW, SUN KX, et al. Cancer statistics in China, 2016[J]. Chin J Oncol, 2023, 45( 3): 212- 220. DOI: 10.3760/cma.j.cn112152-20220922-00647.

    郑荣寿, 张思维, 孙可欣, 等. 2016年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2023, 45( 3): 212- 220. DOI: 10.3760/cma.j.cn112152-20220922-00647.
    [2]
    SUNG H, FERLAY J, SIEGEL RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71( 3): 209- 249. DOI: 10.3322/caac.21660.
    [3]
    CHEN WQ, ZHENG RS, BAADE PD, et al. Cancer statistics in China, 2015[J]. CA A Cancer J Clinicians, 2016, 66( 2): 115- 132. DOI: 10.3322/caac.21338.
    [4]
    LLOVET JM, KELLEY RK, VILLANUEVA A, et al. Hepatocellular carcinoma[J]. Nat Rev Dis Primers, 2021, 7: 6. DOI: 10.1038/s41572-020-00240-3.
    [5]
    SINGAL AG, LLOVET JM, YARCHOAN M, et al. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma[J]. Hepatology, 2023, 78( 6): 1922- 1965. DOI: 10.1097/HEP.0000000000000466.
    [6]
    National Health Commission of the People’s Republic of China. Standard for diagnosis and treatment of primary liver cancer(2024 edition)[J]. J Clin Hepatol, 2024, 40( 5): 893- 918. DOI: 10.12449/JCH240508.

    中华人民共和国国家卫生健康委员会. 原发性肝癌诊疗指南(2024年版)[J]. 临床肝胆病杂志, 2024, 40( 5): 893- 918. DOI: 10.12449/JCH240508.
    [7]
    UGAI T, SASAMOTO N, LEE HY, et al. Is early-onset cancer an emerging global epidemic? Current evidence and future implications[J]. Nat Rev Clin Oncol, 2022, 19( 10): 656- 673. DOI: 10.1038/s41571-022-00672-8.
    [8]
    WAN DW, TZIMAS D, SMITH JA, et al. Risk factors for early-onset and late-onset hepatocellular carcinoma in Asian immigrants with hepatitis B in the United States[J]. Am J Gastroenterol, 2011, 106( 11): 1994- 2000. DOI: 10.1038/ajg.2011.302.
    [9]
    CHANG PE, ONG WC, LUI HF, et al. Is the prognosis of young patients with hepatocellular carcinoma poorer than the prognosis of older patients? A comparative analysis of clinical characteristics, prognostic features, and survival outcome[J]. J Gastroenterol, 2008, 43( 11): 881- 888. DOI: 10.1007/s00535-008-2238-x.
    [10]
    LAM CM, CHAN AO, HO P, et al. Different presentation of hepatitis B-related hepatocellular carcinoma in a cohort of 1 863 young and old patients-implications for screening[J]. Aliment Pharmacol Ther, 2004, 19( 7): 771- 777. DOI: 10.1111/j.1365-2036.2004.01912.x.
    [11]
    ZHU HL, ZHAO S, ZHAO TM, et al. Comparison of metastasis and prognosis between early-onset and late-onset hepatocellular carcinoma: A population-based study[J]. Heliyon, 2024, 10( 7): e28497. DOI: 10.1016/j.heliyon.2024.e28497.
    [12]
    CHEN CH, CHANG TT, CHENG KS, et al. Do young hepatocellular carcinoma patients have worse prognosis? The paradox of age as a prognostic factor in the survival of hepatocellular carcinoma patients[J]. Liver Int, 2006, 26( 7): 766- 773. DOI: 10.1111/j.1478-3231.2006.01309.x.
    [13]
    LI L, XU LL, WEN TF, et al. Poor prognoses of young hepatocellular carcinoma patients with microvascular invasion: A propensity score matching cohort study[J]. Gastroenterol Res Pract, 2020, 2020: 4691425. DOI: 10.1155/2020/4691425.
    [14]
    YANG HI, LU SN, LIAW YF, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma[J]. N Engl J Med, 2002, 347( 3): 168- 174. DOI: 10.1056/NEJMoa013215.
    [15]
    MU XM, WANG W, JIANG YY, et al. Patterns of comorbidity in hepatocellular carcinoma: A network perspective[J]. Int J Environ Res Public Health, 2020, 17( 9): 3108. DOI: 10.3390/ijerph17093108.
    [16]
    YIN YL, ZHANG YX, CUI FN, et al. Trends in the burden of liver cancer in China and globally from 1990 to 2021: Analysis, comparison, and projections for the next 15 years[J/CD]. Chin J Front Med Sci Electron Version, 2025, 17( 2): 68- 80. DOI: 10.12037/YXQY.2025.02-10.

    殷雨来, 张银旭, 崔枫宁, 等. 1990—2021年中国和全球肝癌疾病负担趋势分析与比较及未来15年预测[J/CD]. 中国医学前沿杂志(电子版), 2025, 17( 2): 68- 80. DOI: 10.12037/YXQY.2025.02-10.
    [17]
    BRAY F, LAVERSANNE M, SUNG H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74( 3): 229- 263. DOI: 10.3322/caac.21834.
    [18]
    GUO CN, LIU ZQ, LIN CQ, et al. Global epidemiology of early-onset liver cancer attributable to specific aetiologies and risk factors from 2010 to 2019[J]. J Glob Health, 2023, 13: 04167. DOI: 10.7189/jogh.13.04167.
    [19]
    Chinese Society of Hepatology, Chinese Society of Infectious Diseases. Guidelines for the prevention and treatment of chronic hepatitis B(version 2022)[J]. Infect Dis Info, 2023, 36( 1): 1- 17. DOI: 10.3969/j.issn.1007-8134.2023.01.01.

    中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2022年版)[J]. 传染病信息, 2023, 36( 1): 1- 17. DOI: 10.3969/j.issn.1007-8134.2023.01.01.
    [20]
    Chinese Society of Liver Cancer(CSLC); Chinese Society of Clinical Oncology(CSCO); Liver Cancer Group, Chinese Society of Hepatology, et al. Experts consensus on pathological diagnosis of primary liver cancer[J]. J Clin Hepatol, 2011, 27( 4): 343- 345.

    中国抗癌协会肝癌专业委员会, 中国抗癌协会临床肿瘤学协作专业委员会, 中华医学会肝病学会肝癌学组, 等. 原发性肝癌规范化病理诊断方案专家共识[J]. 临床肝胆病杂志, 2011, 27( 4): 343- 345.
    [21]
    LI H, LIU WX. Research progress on the role of androgen receptors on the occurrence and development of hepatocellular carcinoma[J]. Shandong Med J, 2020, 60( 10): 95- 98. DOI: 10.3969/j.issn.1002-266X.2020.10.025.

    李虹, 刘维新. 雄激素受体对肝细胞癌发生发展作用的研究进展[J]. 山东医药, 2020, 60( 10): 95- 98. DOI: 10.3969/j.issn.1002-266X.2020.10.025.
    [22]
    WANG RH, CAI SL, LIU DH, et al. Research progress of androgen/androgen receptor signaling pathway in hepatocellular carcinoma[J]. Cancer Res Prev Treat, 2023, 50( 2): 180- 185. DOI: 10.3971/j.issn.1000-8578.2023.22.0714.

    王瑞华, 蔡仕良, 柳东红, 等. 雄激素/雄激素受体信号通路在肝细胞癌中的研究进展[J]. 肿瘤防治研究, 2023, 50( 2): 180- 185. DOI: 10.3971/j.issn.1000-8578.2023.22.0714.
    [23]
    ZHAO HC, GAO Q. Progress in research, diagnosis, and treatment of hepatocellular carcinoma in 2022[J]. China Oncology, 2023, 33( 4): 315- 326. DOI: 10.19401/j.cnki.1007-3639.2023.04.002.

    赵海潮, 高强. 2022年度肝癌研究及诊疗新进展[J]. 中国癌症杂志, 2023, 33( 4): 315- 326. DOI: 10.19401/j.cnki.1007-3639.2023.04.002.
    [24]
    MAO XH, CHEUNG KS, PENG CZ, et al. Steatosis, HBV-related HCC, cirrhosis, and HBsAg seroclearance: A systematic review and meta-analysis[J]. Hepatology, 2023, 77( 5): 1735- 1745. DOI: 10.1002/hep.32792.
    [25]
    HUANG SC, SU TH, TSENG TC, et al. Distinct effects of hepatic steatosis and metabolic dysfunction on the risk of hepatocellular carcinoma in chronic hepatitis B[J]. Hepatol Int, 2023, 17( 5): 1139- 1149. DOI: 10.1007/s12072-023-10545-6.
    [26]
    LEE YB, HA Y, CHON YE, et al. Association between hepatic steatosis and the development of hepatocellular carcinoma in patients with chronic hepatitis B[J]. Clin Mol Hepatol, 2019, 25( 1): 52- 64. DOI: 10.3350/cmh.2018.0040.
    [27]
    HUANG SC, LIU CJ. Chronic hepatitis B with concurrent metabolic dysfunction-associated fatty liver disease: Challenges and perspectives[J]. Clin Mol Hepatol, 2023, 29( 2): 320- 331. DOI: 10.3350/cmh.2022.0422.
    [28]
    GENG N, NI WJ, RUI FJ, et al. Chronic hepatitis B virus infection and metabolic associated fatty liver disease: The known and unknown aspects[J]. J Clin Hepatol, 2024, 40( 3): 441- 445. DOI: 10.12449/JCH240301.

    耿楠, 倪文婧, 芮法娟, 等. 慢性HBV感染与代谢相关脂肪性肝病: 已知与未知[J]. 临床肝胆病杂志, 2024, 40( 3): 441- 445. DOI: 10.12449/JCH240301.
    [29]
    YIN K, SONG YY, LIU F. Research advances in chronic hepatitis B with metabolic dysfunction-associated steatotic liver disease[J]. J Clin Hepatol, 2024, 40( 12): 2499- 2504. DOI: 10.12449/JCH241221.

    殷珂, 宋玉芸, 刘峰. 慢性乙型肝炎合并代谢相关脂肪性肝病的研究进展[J]. 临床肝胆病杂志, 2024, 40( 12): 2499- 2504. DOI: 10.12449/JCH241-221.
    [30]
    ZHANG SS, MAK LY, YUEN MF, et al. Mechanisms of hepatocellular carcinoma and cirrhosis development in concurrent steatotic liver disease and chronic hepatitis B[J]. Clin Mol Hepatol, 2025, 31( Suppl): S182- S195. DOI: 10.3350/cmh.2024.0837.
    [31]
    WANG XB, ZHANG L, DONG BN. Molecular mechanisms in MASLD/MASH-related HCC[J]. Hepatology, 2024. DOI: 10.1097/HEP.0000000-000000786.[ Epub ahead of print].
    [32]
    TOURKOCHRISTOU E, ASSIMAKOPOULOS SF, THOMOPOULOS K, et al. NAFLD and HBV interplay-related mechanisms underlying liver disease progression[J]. Front Immunol, 2022, 13: 965548. DOI: 10.3389/fimmu.2022.965548.
    [33]
    SCHUSTER S, CABRERA D, ARRESE M, et al. Triggering and resolution of inflammation in NASH[J]. Nat Rev Gastroenterol Hepatol, 2018, 15( 6): 349- 364. DOI: 10.1038/s41575-018-0009-6.
    [34]
    LIU ZQ, LIN CQ, MAO XH, et al. Changing prevalence of chronic hepatitis B virus infection in China between 1973 and 2021: A systematic literature review and meta-analysis of 3740 studies and 231 million people[J]. Gut, 2023, 72( 12): 2354- 2363. DOI: 10.1136/gutjnl-2023-330691.
    [35]
    YANG BH, XIA JL, HUANG LW, et al. Changes of clinical aspect of primary liver cancer in China during the past 30 years: Control study for 3250 cases with primary liver cancer[J]. Natl Med J China, 2003, 83( 12): 1053- 1057.

    杨秉辉, 夏景林, 黄力文, 等. 我国肝癌“临床相”30年的变迁: 原发性肝癌3250例的对比研究[J]. 中华医学杂志, 2003, 83( 12): 1053- 1057.
    [36]
    LIM SJM, HAO Y, GOH GBB, et al. Prognostic impact of presenting symptoms of patients with hepatocellular carcinoma[J]. Singapore Med J, 2024, 65( 8): 444- 448. DOI: 10.4103/singaporemedj.SMJ-2021-283.
    [37]
    LEE YT, KARIM MA, KUM HC, et al. Factors associated with unrecognized cirrhosis in patients with hepatocellular carcinoma[J]. Clin Mol Hepatol, 2023, 29( 2): 453- 464. DOI: 10.3350/cmh.2022.0450.
    [38]
    WANG HY, CHANG DL, LIU WP. Analysis of diagnosis and treatment of young 24 cases with primary liver cancer[J]. J Bengbu Med Coll, 2011, 36( 4): 361- 362, 365. DOI: 10.13898/j.cnki.issn.1000-2200.2011.04.036.

    王恒毅, 常洞镭, 刘伟鹏. 青年人原发性肝癌24例诊疗分析[J]. 蚌埠医学院学报, 2011, 36( 4): 361- 362, 365. DOI: 10.13898/j.cnki.issn.1000-2200.2011.04.036.
    [39]
    REIG M, FORNER A, RIMOLA J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update[J]. J Hepatol, 2022, 76( 3): 681- 693. DOI: 10.1016/j.jhep.2021.11.018.
    [40]
    ZHOU L, WANG J, LYU SC, et al. PD-L1+NEUT, Foxp3+Treg, and NLR as new prognostic marker with low survival benefits value in hepatocellular carcinoma[J]. Technol Cancer Res Treat, 2021, 20: 153303382110‑ 45820. DOI: 10.1177/15330338211045820.
    [41]
    LIU HE, XIN DP, PENG B. Expression of NLR, PLR and SII in patients undergoing radical hepatectomy and their correlation with prognosis[J]. J Chin Physician, 2020( 9): 1352- 1355. DOI: 10.3760/cma.j.cn431274-20190712-00827.

    刘洪恩, 辛大平, 彭彬. NLR、PLR和SII在肝癌根治术患者中的表达及与预后的相关性[J]. 中国医师杂志, 2020( 9): 1352- 1355. DOI: 10.3760/cma.j.cn431274-20190712-00827.
    [42]
    GOH MJ, KANG W, KIM KM, et al. Incidence and risk factors for development of hepatocellular carcinoma at young age in patients with chronic hepatitis B[J]. Scand J Gastroenterol, 2022, 57( 1): 70- 77. DOI: 10.1080/00365521.2021.1988700.
    [43]
    PU JL, CHEN Z, YAO LQ, et al. Long-term oncological prognosis after curative-intent liver resection for hepatocellular carcinoma in the young versus the elderly: Multicentre propensity score-matching study[J]. BJS Open, 2022, 6( 1): zrab145. DOI: 10.1093/bjsopen/zrab145.
    [44]
    YUAN J, ZHOU BP, TANAKA Y, et al. Hepatitis B virus(HBV) genotypes/subgenotypes in China: Mutations in core promoter and precore/core and their clinical implications[J]. J Clin Virol, 2007, 39( 2): 87- 93. DOI: 10.1016/j.jcv.2007.03.005.
    [45]
    YANG JD, ALTEKRUSE SF, NGUYEN MH, et al. Impact of country of birth on age at the time of diagnosis of hepatocellular carcinoma in the United States[J]. Cancer, 2017, 123( 1): 81- 89. DOI: 10.1002/cncr.30246.
    [46]
    YAN HL, YANG Y, ZHANG L, et al. Characterization of the genotype and integration patterns of hepatitis B virus in early- and late-onset hepatocellular carcinoma[J]. Hepatology, 2015, 61( 6): 1821- 1831. DOI: 10.1002/hep.27722.
    [47]
    YANG JL, CHEN C, WANG S, et al. Comprehensive genomic analysis of early and late-onset hepatocellular carcinoma[J]. Genes Dis, 2023, 11( 4): 101031. DOI: 10.1016/j.gendis.2023.06.005.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(1)  / Tables(3)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (108) PDF downloads(19) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return