The association between metabolic risk factors, nonalcoholic fatty liver disease, and the incidence of liver cancer: a nationwide population-based cohort study

doi:10.1007/s12072-021-10281-9

. 2022 Aug;16(4):807-816.

doi: 10.1007/s12072-021-10281-9. Epub 2022 Jan 22.

The association between metabolic risk factors, nonalcoholic fatty liver disease, and the incidence of liver cancer: a nationwide population-based cohort study

Yu-Guang Chen^{1

2}, Chih-Wei Yang³, Chi-Hsiang Chung^{4

5}, Ching-Liang Ho¹, Wei-Liang Chen^#⁶, Wu-Chien Chien^#^{7

8}

Affiliations

¹ Division of Hematology/Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
² Cancer Institute, University College London, London, UK.
³ Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
⁴ School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
⁵ Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
⁶ Department of Family Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu District, Taipei City, 11490, Taiwan, Republic of China. weiliang0508@gmail.com.
⁷ School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC. chienwu@ndmctsgh.edu.tw.
⁸ Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC. chienwu@ndmctsgh.edu.tw.

^# Contributed equally.

PMID: 35064545
DOI: 10.1007/s12072-021-10281-9

The association between metabolic risk factors, nonalcoholic fatty liver disease, and the incidence of liver cancer: a nationwide population-based cohort study

Yu-Guang Chen et al. Hepatol Int. 2022 Aug.

. 2022 Aug;16(4):807-816.

doi: 10.1007/s12072-021-10281-9. Epub 2022 Jan 22.

Authors

Yu-Guang Chen^{1

2}, Chih-Wei Yang³, Chi-Hsiang Chung^{4

5}, Ching-Liang Ho¹, Wei-Liang Chen^#⁶, Wu-Chien Chien^#^{7

8}

Affiliations

¹ Division of Hematology/Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
² Cancer Institute, University College London, London, UK.
³ Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
⁴ School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
⁵ Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
⁶ Department of Family Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu District, Taipei City, 11490, Taiwan, Republic of China. weiliang0508@gmail.com.
⁷ School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC. chienwu@ndmctsgh.edu.tw.
⁸ Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC. chienwu@ndmctsgh.edu.tw.

^# Contributed equally.

PMID: 35064545
DOI: 10.1007/s12072-021-10281-9

Erratum in

Correction to: The association between metabolic risk factors, nonalcoholic fatty liver disease, and the incidence of liver cancer: a nationwide population-based cohort study.
Chen YG, Yang CW, Chung CH, Ho CL, Chen WL, Chien WC. Chen YG, et al. Hepatol Int. 2022 Apr;16(2):488. doi: 10.1007/s12072-022-10308-9. Epub 2022 Feb 16. Hepatol Int. 2022. PMID: 35169992 No abstract available.

Abstract

Background and aims: Liver cancer is a detrimental complication in patients with chronic viral hepatitis and alcoholic or nonalcoholic fatty liver disease (NAFLD). However, metabolic risk factors underlying NAFLD usually cause substantial differences in their clinical outcomes. Recently, several studies have used a novel definition of metabolic dysfunction-associated fatty liver disease (MAFLD) to reassess patients with NAFLD and pointed out the importance of metabolic risk factors. Since patients with NAFLD, MAFLD, or metabolic syndrome (MetS) have different burden of metabolic risk factors, it is crucial to decipher the risk of developing hepatic complications in these populations.

Methods: Through a longitudinal nationwide cohort study, the risk of liver cancer was investigated in patients with MetS alone, NAFLD alone, overlap NAFLD/MAFLD, and coexisting MetS and NAFLD. The general characteristics, comorbidities, and incidence of liver cancer were also compared.

Results: Intriguingly, patients diagnosed with MetS alone did not have a significant risk of developing HCC compared to control individuals, while patients with NAFLD alone, NAFLD/MAFLD, and coexisting NAFLD and MetS exhibited 6.08-, 5.81-, and 15.33-fold risks of developing HCC, respectively. Apart from metabolic risk factors, renal function status and liver cirrhosis were the independent risk factors for the development of HCC among these groups.

Conclusion: Our data emphasize that metabolic dysfunction has a significant impact on hepatocarcinogenesis in patients with NAFLD. Moreover, coexisting multiple metabolic risk factors would dampen the risk of developing HCC in patients with NAFLD. Closely tracing HCC formation through laboratory examination or imaging is crucial in these patients.

Keywords: Cirrhosis of liver; Clinical research; Epidemiology; Hepatocellular carcinoma; Metabolic syndrome; National Health Insurance Research Database; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis.

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Comment in

Liver fat and a perturbed metabolic milieu: a consilience of factors driving liver cancer development.
George J, Kawaguchi T. George J, et al. Hepatol Int. 2022 Aug;16(4):733-736. doi: 10.1007/s12072-022-10352-5. Epub 2022 Jun 13. Hepatol Int. 2022. PMID: 35697997 Free PMC article. No abstract available.

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Risk factors and diagnostic biomarkers for nonalcoholic fatty liver disease-associated hepatocellular carcinoma: Current evidence and future perspectives.
Ueno M, Takeda H, Takai A, Seno H. Ueno M, et al. World J Gastroenterol. 2022 Jul 21;28(27):3410-3421. doi: 10.3748/wjg.v28.i27.3410. World J Gastroenterol. 2022. PMID: 36158261 Free PMC article. Review.
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MAFLD: an optimal framework for understanding liver cancer phenotypes.
Crane H, Gofton C, Sharma A, George J. Crane H, et al. J Gastroenterol. 2023 Oct;58(10):947-964. doi: 10.1007/s00535-023-02021-7. Epub 2023 Jul 20. J Gastroenterol. 2023. PMID: 37470858 Free PMC article. Review.
Liver fat and a perturbed metabolic milieu: a consilience of factors driving liver cancer development.
George J, Kawaguchi T. George J, et al. Hepatol Int. 2022 Aug;16(4):733-736. doi: 10.1007/s12072-022-10352-5. Epub 2022 Jun 13. Hepatol Int. 2022. PMID: 35697997 Free PMC article. No abstract available.

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References

1. Yang J, Zhang JX, Wang H, Wang GL, Hu QG, Zheng QC. Hepatocellular carcinoma and macrophage interaction induced tumor immunosuppression via Treg requires TLR4 signaling. World J Gastroenterol. 2012;18(23):2938–2947 - DOI
1. Koulouris A, Tsagkaris C, Spyrou V, Pappa E, Troullinou A, Nikolaou M. Hepatocellular carcinoma: an overview of the changing landscape of treatment options. J Hepatocell Carcinoma. 2021;8:387–401 - DOI
1. Ghouri YA, Mian I, Rowe JH. Review of hepatocellular carcinoma: epidemiology, etiology, and carcinogenesis. J Carcinog. 2017;16:1 - DOI
1. Chen CH, Huang MH, Yang JC, et al. Prevalence and risk factors of nonalcoholic fatty liver disease in an adult population of Taiwan: metabolic significance of nonalcoholic fatty liver disease in nonobese adults. J Clin Gastroenterol. 2006;40(8):745–752 - DOI
1. Hsiao PJ, Kuo KK, Shin SJ, et al. Significant correlations between severe fatty liver and risk factors for metabolic syndrome. J Gastroenterol Hepatol. 2007;22(12):2118–2123 - DOI

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[1] Yang J, Zhang JX, Wang H, Wang GL, Hu QG, Zheng QC. Hepatocellular carcinoma and macrophage interaction induced tumor immunosuppression via Treg requires TLR4 signaling. World J Gastroenterol. 2012;18(23):2938–2947 - DOI

[2] Yang J, Zhang JX, Wang H, Wang GL, Hu QG, Zheng QC. Hepatocellular carcinoma and macrophage interaction induced tumor immunosuppression via Treg requires TLR4 signaling. World J Gastroenterol. 2012;18(23):2938–2947 - DOI

[3] Koulouris A, Tsagkaris C, Spyrou V, Pappa E, Troullinou A, Nikolaou M. Hepatocellular carcinoma: an overview of the changing landscape of treatment options. J Hepatocell Carcinoma. 2021;8:387–401 - DOI

[4] Koulouris A, Tsagkaris C, Spyrou V, Pappa E, Troullinou A, Nikolaou M. Hepatocellular carcinoma: an overview of the changing landscape of treatment options. J Hepatocell Carcinoma. 2021;8:387–401 - DOI

[5] Ghouri YA, Mian I, Rowe JH. Review of hepatocellular carcinoma: epidemiology, etiology, and carcinogenesis. J Carcinog. 2017;16:1 - DOI

[6] Ghouri YA, Mian I, Rowe JH. Review of hepatocellular carcinoma: epidemiology, etiology, and carcinogenesis. J Carcinog. 2017;16:1 - DOI

[7] Chen CH, Huang MH, Yang JC, et al. Prevalence and risk factors of nonalcoholic fatty liver disease in an adult population of Taiwan: metabolic significance of nonalcoholic fatty liver disease in nonobese adults. J Clin Gastroenterol. 2006;40(8):745–752 - DOI

[8] Chen CH, Huang MH, Yang JC, et al. Prevalence and risk factors of nonalcoholic fatty liver disease in an adult population of Taiwan: metabolic significance of nonalcoholic fatty liver disease in nonobese adults. J Clin Gastroenterol. 2006;40(8):745–752 - DOI

[9] Hsiao PJ, Kuo KK, Shin SJ, et al. Significant correlations between severe fatty liver and risk factors for metabolic syndrome. J Gastroenterol Hepatol. 2007;22(12):2118–2123 - DOI

[10] Hsiao PJ, Kuo KK, Shin SJ, et al. Significant correlations between severe fatty liver and risk factors for metabolic syndrome. J Gastroenterol Hepatol. 2007;22(12):2118–2123 - DOI

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The association between metabolic risk factors, nonalcoholic fatty liver disease, and the incidence of liver cancer: a nationwide population-based cohort study

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The association between metabolic risk factors, nonalcoholic fatty liver disease, and the incidence of liver cancer: a nationwide population-based cohort study

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