Weight fluctuation and risk of hepatocellular carcinoma: a nationwide population-based 8-million-subject study



The importance of hepatocellular carcinoma (HCC) caused by obesity has been emphasized. Many studies have shown that weight fluctuations as well as high BMI are associated with various adverse outcomes. In this study, we investigated the relationship between weight fluctuation and HCC in general populations drawn from a nationwide population-based cohort.


A population-based cohort study including 8,001,829 subjects participating in more than three health examinations within 5 years from the index year were followed until the end of 2017. The degree of weight fluctuation and incidence of HCC during the period were evaluated.


When we classified groups according to baseline body mass index (BMI) level, the highest risk for HCC was observed in subjects with BMI of 30 or greater (adjusted hazard ratio [aHR] 1.40, 95% confidence interval [CI] 1.27–1.54). Also, increasing trends for the relationship between weight fluctuation and HCC were observed in multivariable Cox proportional analyses. The risk of HCC increased by 16% (aHR 1.16, 95% CI 1.12–1.20) for the highest quartile of weight fluctuation relative to the lowest quartile. These findings were consistent regardless of the baseline BMI or other metabolic factors. However, these effects of weight fluctuation on HCC were not observed in liver cirrhosis or viral hepatitis subgroups.


Weight fluctuation is an independent predictor of HCC. In the absence of liver cirrhosis or chronic hepatitis, the impact of weight fluctuation on HCC is further emphasized. These results suggest maintaining steady weight is recommended to reduce the risk of HCC.

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Adjusted hazard ratio


Average real variability


Body mass index


Confidence interval


Chronic kidney disease


Coefficient of variation


High density lipoprotein


Hazard ratio


International Classification of Disease, 10th revision




Low density lipoprotein


Nonalcoholic fatty liver disease


National Health Insurance Service


National Health Screening Program




Tumor necrosis factor


Variability independent of the mean


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This work was supported by the Soonchunhyang University Research Fund.



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Corresponding authors

Correspondence to Dong Wook Shin or Su Jong Yu.

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Conflict of interest

All the authors have no conflict of interest.

Ethical approval

The study protocol was approved by the Institutional Review Board of Seoul National University Hospital (E-1909-088-1065) and also conformed to the ethical guidelines of the World Medical Association Declaration of Helsinki. The requirement for informed consent from individual subjects was waived, because we used de-identified secondary data.

Novelty and impact statements

This study demonstrated that weight fluctuation is an independent predictor of hepatocellular carcinoma in the nationwide population cohort. Therefore, maintaining steady weight is recommended to reduce the risk of hepatocellular carcinoma.

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The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Chang, Y., Yoo, JJ., Cho, E.J. et al. Weight fluctuation and risk of hepatocellular carcinoma: a nationwide population-based 8-million-subject study. Hepatol Int (2021). https://doi.org/10.1007/s12072-021-10149-y

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  • Hepatocellular carcinoma
  • Fluctuation
  • Weight
  • Obesity
  • Body mass index
  • Metabolic dysfunction
  • Inflammation
  • Telomere
  • Fatty liver
  • Diabetes