A cohort study on the association between decline in intrinsic capacity and risk of primary hepatic carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

NI Feitian ¹ , ZHU Yongjia ² , YUAN Qi ³ , YAO Xinmeng ³ ,  MAO Yingying ³

1. The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, P. R. China;
2. The Fifth Clinical Medical School of Zhejiang Chinese Medical University, Hangzhou 310053, P. R. China;
3. Department of Epidemiology, School of Public Health of Zhejiang Chinese Medical University, Hangzhou 310053, P. R. China;

Corresponding?author：

MAO Yingying, Email: myy@zcmu.edu.cn

Keywords：

primary hepatocellular carcinoma; intrinsic capacity; prospective cohort; dose-response; elderly health

DOI：

10.7507/1007-9424.202512097

Video：

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Objective To investigate the association between decline in intrinsic capacity (IC) and the risk of developing primary hepatic carcinoma (PHC), and to provide evidence for early identification and prevention of PHC. Methods This prospective cohort study included 347 874 participants without PHC at baseline from the UK Biobank. Following the World Health Organization framework, a composite IC score was constructed using 7 indicators across 4 domains: psychological, sensory, vitality, and locomotor function. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between IC decline score and incident PHC. Results During the follow-up period from 2006–2010 to 2022, with a median follow-up of 13.6 years, 801 incident PHC cases were identified. IC decline score showed a clear dose-response association [HR=1.18, 95%CI (1.11, 1.26)]. Compared with participants without IC decline, those with IC decline scores of 2, 3, and ≥4 had 35% [HR=1.35, 95%CI (1.10, 1.65)], 72% [HR=1.72, 95%CI (1.34, 2.20)], and 75% [HR=1.75, 95%CI (1.25, 2.45)] higher risks of PHC, respectively. Among individual indicators, slower walking speed [HR=1.33, 95%CI (1.07, 1.66)], lower grip strength [HR=1.38, 95%CI (1.18, 1.62)], and weight loss [HR=1.28, 95%CI (1.08, 1.54)] showed the strongest associations with PHC risk. Conclusions Decline in IC is positively associated with the risk of PHC, demonstrating a clear dose-response relationship. Incorporating IC assessment into routine health management and screening strategies for high-risk populations may improve early risk stratification and inform targeted prevention strategies.

Citation： NI Feitian, ZHU Yongjia, YUAN Qi, YAO Xinmeng, MAO Yingying. A cohort study on the association between decline in intrinsic capacity and risk of primary hepatic carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2026, 33(2): 199-206. doi: 10.7507/1007-9424.202512097 Copy

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2.	Chen X, Shi J, Xue Y, et al. Critical analysis of the liver cancer policies and programs in China: implications for international liver cancer control. Glob Health Res Policy, 2025, 10(1): 50. doi: 10.1186/s41256-025-00450-w.
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18.	Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci, 2001, 56(3): M146-M156.
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26.	van Kleef LA, Hofman A, Voortman T, et al. Objectively measured physical activity is inversely associated with nonalcoholic fatty liver disease: the rotterdam study. Am J Gastroenterol, 2022, 117(2): 311-318.

1. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatocellular carcinoma. J Hepatol, 2018, 69(1): 182-236.
2. Chen X, Shi J, Xue Y, et al. Critical analysis of the liver cancer policies and programs in China: implications for international liver cancer control. Glob Health Res Policy, 2025, 10(1): 50. doi: 10.1186/s41256-025-00450-w.
3. Pinter M, Trauner M, Peck-Radosavljevic M, et al. Cancer and liver cirrhosis: implications on prognosis and management. ESMO Open, 2016, 1(2): e000042. doi: 10.1136/esmoopen-2016-000042.
4. 郝運, 李川, 文天夫, 等. 全球及中國的肝癌流行病學特征: 基于《2022全球癌癥統計報告》解讀. 中國普外基礎與臨床雜志, 2024, 31(7): 781-789.
5. Fujiwara N, Friedman SL, Goossens N, et al. Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine. J Hepatol, 2018, 68(3): 526-549.
6. Beard JR, Officer A, de Carvalho IA, et al. The world report on ageing and health: a policy framework for healthy ageing. Lancet, 2016, 387(10033): 2145-2154.
7. Maheshwari S, Dai C, Giri S, et al. Intrinsic capacity and survival among older adults with gastrointestinal malignancies: the Cancer and Aging Resilience Evaluation registry. Cancer, 2024, 130(20): 3530-3539.
8. Liang Z, Zhang H, Jin H, et al. Intrinsic capacity, genetic susceptibility, and the risks of metabolic dysfunction-associated steatotic liver disease and cirrhosis. Int J Surg, 2026, 112(1): 780-792.
9. Beyene MB, Visvanathan R, Ahmed M, et al. Development and validation of an intrinsic capacity score in the UK Biobank study. Maturitas, 2024, 185: 107976. doi: 10.1016/j.maturitas.2024.107976.
10. Beard JR, Jotheeswaran AT, Cesari M, et al. The structure and predictive value of intrinsic capacity in a longitudinal study of ageing. BMJ Open, 2019, 9(11): e026119. doi: 10.1136/bmjopen-2018-026119.
11. Beard JR, Si Y, Liu Z, et al. Intrinsic capacity: validation of a new WHO concept for healthy aging in a longitudinal Chinese study. J Gerontol A Biol Sci Med Sci, 2022, 77(1): 94-100.
12. Collins R. What makes UK Biobank special?. Lancet, 2012, 379(9822): 1173-1174.
13. Sudlow C, Gallacher J, Allen N, et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med, 2015, 12(3): e1001779. doi: 10.1371/journal.pmed.1001779.
14. Hu W, Tian G, Wang JN, et al. Intrinsic capacity defined using 4 domains, genetic risk, and incident Parkinson disease: a prospective cohort study. Neurology, 2025, 105(8): e214144. doi: 10.1212/WNL.0000000000214144.
15. Ramírez-Vélez R, Iriarte-Fernández M, Santafé G, et al. Association of intrinsic capacity with incidence and mortality of cardiovascular disease: prospective study in UK Biobank. J Cachexia Sarcopenia Muscle, 2023, 14(5): 2054-2063.
16. Ramírez-Vélez R, Iriarte-Fernandez M, Santafé G, et al. Association of intrinsic capacity with respiratory disease mortality. Respir Med, 2023, 212: 107243. doi: 10.1016/j.rmed.2023.107243.
17. Sun M, He Q, Sun N, et al. Intrinsic capacity, polygenic risk score, APOE genotype, and risk of dementia: a prospective cohort study based on the UK Biobank. Neurology, 2024, 102(12): e209452. doi: 10.1212/WNL.0000000000209452.
18. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci, 2001, 56(3): M146-M156.
19. World Health Organization. Integrated care for older people (ICOPE): guidance for person-centred assessment and pathways in primary care. 2025. [2025-01-01]. [2025-12-25]. https://www.who.int/publications/i/item/9789240103726.
20. Yu R, Lai ETC, Leung G, et al. Intrinsic capacity and 10-year mortality: findings from a cohort of older people. Exp Gerontol, 2022, 167: 111926. doi: 10.1016/j.exger.2022.111926.
21. Song J, Fan L, Shi D, et al. Sleep and liver function biomarkers in relation to risk of incident liver cancer: a nationwide prospective cohort study. BMC Med, 2024, 22(1): 261. doi: 10.1186/s12916-024-03440-w.
22. Um YJ, Chang Y, Jung HS, et al. Sleep duration, sleep quality, and the development of nonalcoholic fatty liver disease: a cohort study. Clin Transl Gastroenterol, 2021, 12(10): e00417. doi: 10.14309/ctg.0000000000000417.
23. Petermann-Rocha F, Gray SR, Forrest E, et al. Associations of muscle mass and grip strength with severe NAFLD: a prospective study of 333 295 UK Biobank participants. J Hepatol, 2022, 76(5): 1021-1029.
24. Han L, Fu S, Li J, et al. Association between grip strength and non-alcoholic fatty liver disease: a systematic review and meta-analysis. Front Med (Lausanne), 2022, 9: 988566. doi: 10.3389/fmed.2022.988566.
25. Xia Y, Cao L, Liu Y, et al. Longitudinal associations between hand grip strength and non-alcoholic fatty liver disease in adults: a prospective cohort study. Front Med (Lausanne), 2021, 8: 752999. doi: 10.3389/fmed.2021.752999.
26. van Kleef LA, Hofman A, Voortman T, et al. Objectively measured physical activity is inversely associated with nonalcoholic fatty liver disease: the rotterdam study. Am J Gastroenterol, 2022, 117(2): 311-318.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

A cohort study on the association between decline in intrinsic capacity and risk of primary hepatic carcinoma

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