Highlights
- •NAFLD was associated with HCC development.
- •NAFLD was associated with colorectal cancer development in males.
- •NAFLD was associated with breast cancer development in females.
- •High NFS and high FIB-4 score were associated with developing all cancers and HCC.
Background & Aims
Little is known about the association between non-alcoholic fatty liver disease (NAFLD)
and cancer development. This study investigated the cancer incidence rates in NAFLD
and analysed the association between NAFLD and cancer development.
Methods
This historical cohort study included subjects who were followed up for >1 year after
having a heath checkup at a tertiary hospital in Korea from September 1, 2004 to December
31, 2005. NAFLD was diagnosed by ultrasonographic detection of hepatic steatosis in
the absence of other known liver disease, including alcoholic or viral hepatitis.
Cox proportional hazards regression model was conducted to assess the association
between NAFLD and cancer development.
Results
Of 25,947 subjects, 8,721 (33.6%) had NAFLD. During the total follow-up of 164,671
person-years (median 7.5 years), the cancer incidence rate of the NAFLD group was
higher than that of the non-NAFLD group (782.9 vs. 592.8 per 100,000 person-years; hazard ratio [HR] 1.32; 95% confidence interval [CI]
1.17–1.49; p <0.001). When demographic and metabolic factors were adjusted for, NAFLD showed a
strong association with three cancers: hepatocellular carcinoma ([HCC]; HR 16.73;
95% CI 2.09–133.85; p = 0.008), colorectal cancer in males (HR 2.01; 95% CI 1.10–3.68; p = 0.02), and breast cancer in females (HR 1.92; 95% CI 1.15–3.20; p = 0.01). A high NAFLD fibrosis score (NFS) and a high fibrosis-4 (FIB-4) score were
associated with the development of all cancers and HCC.
Conclusion
NAFLD was associated with the development of HCC, colorectal cancer in males, and
breast cancer in females. A high NFS and a high FIB-4 score showed a strong association
with the development of all cancers and HCC.
Lay summary
Non-alcoholic fatty liver disease (NAFLD) is associated with developing hepatocellular
carcinoma (HCC). There have been limited data on the association between NAFLD and
extrahepatic cancers. This study demonstrated that patients with NAFLD showed a higher
association with the development of HCC, colorectal cancer in males, and breast cancer
in females. A high NAFLD fibrosis score and a high fibrosis-4 score showed a strong
association with the development of all cancers and HCC.
Graphical abstract
Graphical Abstract
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of HepatologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
Author names in bold designate shared co-first authorship
- Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes.Hepatology. 2016; 64: 73-84
- EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease.J Hepatol. 2016; 64: 1388-1402
- KASL clinical practice guidelines: management of nonalcoholic fatty liver disease.Clin Mol Hepatol. 2013; 19: 325-348
- Extrahepatic complications of nonalcoholic fatty liver disease.Hepatology. 2014; 59: 1174-1197
- NAFLD: a multisystem disease.J Hepatol. 2015; 62: S47-S64
- Extrahepatic complications of nonalcoholic fatty liver disease.Clin Liver Dis. 2016; 20: 387-401
- Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States.Hepatology. 2013; 57: 1357-1365
- Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009.Hepatology. 2015; 62: 1723-1730
- High prevalence of colorectal neoplasm in patients with non-alcoholic steatohepatitis.Gut. 2011; 60: 829-836
- Non-alcoholic fatty liver diseases and risk of colorectal neoplasia.Aliment Pharmacol Ther. 2017; 45: 345-353
- Ultrasound scanning in the detection of hepatic fibrosis and steatosis.Br Med J. 1986; 292: 13-15
- The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD.Hepatology. 2007; 45: 846-854
- Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection.Hepatology. 2006; 43: 1317-1325
- A comparison of the cancer incidence rates between the national cancer registry and insurance claims data in Korea.Asian Pac J Cancer Prev. 2012; 13: 6163-6168
- Risk of cancer in patients hospitalized with fatty liver: a Danish cohort study.J Clin Gastroenterol. 2003; 36: 356-359
- Large-scale long-term follow-up study of Japanese patients with non-alcoholic Fatty liver disease for the onset of hepatocellular carcinoma.Am J Gastroenterol. 2012; 107: 253-261
- Hepatocellular carcinoma in the absence of cirrhosis in united states veterans is associated with nonalcoholic fatty liver disease.Clin Gastroenterol Hepatol. 2016; 14 (e121): 124-131
- Nonalcoholic Fatty liver disease, diabetes, obesity, and hepatocellular carcinoma.Clin Liver Dis. 2015; 19: 361-379
- Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study.Hepatology. 2016; 63: 827-838
- Non-alcoholic fatty liver disease and extra-hepatic cancers.Int J Mol Sci. 2016; 17
- Beyond insulin resistance in NASH: TNF-alpha or adiponectin?.Hepatology. 2004; 40: 46-54
- Cytokines, obesity, and cancer: new insights on mechanisms linking obesity to cancer risk and progression.Annu Rev Med. 2013; 64: 45-57
- Prospective study reveals associations between colorectal cancer and type 2 diabetes mellitus or insulin use in men.Gastroenterology. 2010; 139: 1138-1146
- Visceral fat area and markers of insulin resistance in relation to colorectal neoplasia.Diabetes Care. 2010; 33: 184-189
- Association of metabolic syndrome with proximal and synchronous colorectal neoplasm.Clin Gastroenterol Hepatol. 2007; 5 (Quiz 141): 221-229
- Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies.Lancet. 2008; 371: 569-578
- Global burden of cancer attributable to high body-mass index in 2012: a population-based study.Lancet Oncol. 2015; 16: 36-46
- Association of obesity-related metabolic disruptions with cancer risk and outcome.J Clin Oncol. 2016; 34: 4249-4255
- Metabolic syndrome and the risk of breast cancer in postmenopausal women.Ann Oncol. 2011; 22: 2687-2692
- Metabolic syndrome and postmenopausal breast cancer in the ORDET cohort: a nested case-control study.Nutr Metab Cardiovasc Dis. 2010; 20: 41-48
- Hyperinsulinaemia and increased risk of breast cancer: findings from the British Women's Heart and Health Study.Cancer Causes Control. 2004; 15: 267-275
- Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection.Hepatology. 2010; 51: 1820-1832
- Association between screening and the thyroid cancer “epidemic” in South Korea: evidence from a nationwide study.BMJ. 2016; 355: i5745
- Validity of real time ultrasound in the diagnosis of hepatic steatosis: a prospective study.J Hepatol. 2009; 51: 1061-1067
- The relation between non-alcoholic fatty liver disease and the risk of coronary heart disease in Koreans.Am J Gastroenterol. 2009; 104: 1953-1960
Article info
Publication history
Published online: November 14, 2017
Accepted:
September 11,
2017
Received in revised form:
August 11,
2017
Received:
February 15,
2017
See Editorial, pages 10–12Identification
Copyright
© 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
