Non-alcoholic fatty liver disease, NAFLD or NASH is a manifestation of advanced obesity. It can lead to liver inflammation, cirrhosis and even malignancy. This association study suggests it can also increase the risk of colorectal cancer. The bigger the severity of liver disease, the higher the chance of colorectal carcinoma. A group of 26,000 asymptomatic patients were analyzed.
Alimentary Pharmacology & Therapeutics
Background: Non-alcoholic fatty liver disease (NAFLD) is associated with colorectal neoplasia. Yet, NAFLD ranges from simple steatosis to steatohepatitis with advanced fibrosis.
Aim: To investigate the risk of colorectal neoplasia according to the presence and severity of NAFLD.
Methods: A total of 26,540 asymptomatic adults who underwent same day first-time colonoscopy and abdominal ultrasonography as a health check-up programme were analysed. NAFLD was diagnosed by ultrasonography. Advanced colorectal neoplasia was defined as an invasive cancer or adenoma that was at least 10 mm in diameter, had high-grade dysplasia, or had villous histological characteristics or any combination thereof.
Results: NAFLD patients had a higher prevalence of any colorectal neoplasia (38.0% vs. 28.9%) and advanced colorectal neoplasia (2.8% vs. 1.9%) compared to those without NAFLD. In a multivariable model adjusted for age, sex, smoking, alcohol, BMI, first-degree family history of colorectal cancer, aspirin use and metabolic factors, the odd ratios comparing patients with NAFLD to those without were 1.10 [1.03–1.17] for any colorectal neoplasia and 1.21 (0.99–1.47) for advanced colorectal neoplasia.
When NAFLD patients were further stratified according to the non-invasive parameters of liver disease severity, the risk of any colorectal neoplasia or advanced colorectal neoplasia was higher for those with severe liver diseases than those with mild liver diseases.
Conclusions: The presence and severity of NAFLD were closely associated with any colorectal neoplasia and advanced colorectal neoplasia, suggesting that clinicians should be aware of the increased risk of colorectal neoplasia in patients with NAFLD.
Non-alcoholic fatty liver diseases and risk of colorectal neoplasia
J. S. Ahn, D. H. Sinn, Y. W. Min, S. N. Hong, H. S. Kim, S.-H. Jung, S. Gu, P.-L. Rhee, S. W. Paik, H. J. Son, G.-Y. Gwak
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Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth leading cause of cancer deaths worldwide. The recently updated US Preventive Services Task Force concluded that screening for CRC in average risk, asymptomatic adults aged 50–75 years is of substantial net benefit. However, some populations are at increased risk for CRC, and there is a need for a more tailored approach to CRC screening. For example, patients with a family history of CRC are at increased risk for CRC, and recommended to start for CRC screening at a younger age and at a more frequent interval. Identifying the risks of colorectal neoplasia can help inform screening participants and facilitate their screening choice.
Non-alcoholic fatty liver disease (NAFLD), characterised by accumulation of fat in the liver, is a rapidly increasing chronic liver disease. The primary liver pathology in NAFLD affects hepatic structure and function, and causes liver cirrhosis, liver failure and hepatocellular carcinoma, but its clinical burden of NAFLD is not confined to the liver. NAFLD is associated with an increased risk of type 2 diabetes mellitus, cardiovascular disease, and chronic kidney diseases and cardiovascular disease is the leading cause of death in NAFLD patients.
To date, several studies, including two meta-analyses, showed that NAFLD is a risk factor for colorectal neoplasia. However, NAFLD encompasses a wide spectrum of liver diseases ranging from simple steatosis to steatohepatitis with advanced fibrosis. The literature on the association between severity of NAFLD and colorectal neoplasia is limited and inconsistent. The present study was designed to determine the association between NAFLD and colorectal neoplasia according to the severity of NAFLD in a large sample of asymptomatic adults undergoing first-time colonoscopy.
In this large cross-sectional study of asymptomatic men and women undergoing first-time screening colonoscopies, we found a significant association between the NAFLD and colorectal neoplasia. The magnitude of association was stronger for advanced colorectal neoplasia. The association was independent of traditional risk factors for CRC, including metabolic mediators. Furthermore, we found that the risk of any colorectal neoplasia or advanced colorectal neoplasia was higher for those with severe form liver diseases compared to mild form liver diseases. All these findings indicate that NAFLD and its severity are closely associated with the risk of colorectal neoplasia independent of traditional risk factors. Close attention for the increased risk for any colorectal neoplasia and advanced colorectal neoplasia is needed for NAFLD patients.
To our knowledge, there have been only two studies that assessed the association between NAFLD and colorectal neoplasia according to NAFLD severity. Wong et al. recruited subjects aged 40–70 years from community residents (n = 181) and biopsy proven NAFLD patients (n = 199). They found that non-alcoholic steatohepatitis (NASH) is associated with a high prevalence of colorectal adenomas and advanced neoplasm, but not with simple steatosis. Lee et al. studied 44 220 participants for the association between NAFLD severity and colorectal neoplasia by US grading. They found that OR for colorectal neoplasia increases with an increase in NAFLD severity, but the association was not statistically significant in the multivariable model, and there was also no association between NAFLD severity and advanced colorectal neoplasia.
In this study, the association between colorectal neoplasia and NAFLD was independent after adjusting for traditional risk factors including metabolic parameters. When NAFLD patients were stratified according to liver disease severity, the association between any or advanced colorectal neoplasia and NAFLD for patients with severe liver disease was robust after adjustment. However, for those with mild liver disease, the association was not obvious. NAFLD is considered as a hepatic manifestation of metabolic syndrome, and shares common risk factors for colorectal neoplasia including impaired glucose tolerance, dyslipidemia and central obesity. One possible mechanism explaining the increased risk of colorectal neoplasia in NAFLD patients with advanced fibrosis is a pro-inflammatory and insulin resistant condition that elevates serum insulin and insulin-like growth factor, which in turn, may promote growth and anti-apoptosis of colorectal neoplasia. Some studies suggested that tumour necrosis factor-alpha, interleukin-6, adiponectin, leptin and other pro-inflammatory cytokines play a role in the development of colorectal neoplasia, which can be altered in NASH as well. NASH may contribute to the development of colorectal neoplasia independent of traditional risk factors, while individuals with simple steatosis shows a higher risk of colorectal neoplasia by just sharing common risk factors for colorectal neoplasia.
In conclusion, we demonstrated that NAFLD and its severity are closely associated with the risk of any colorectal neoplasia and advanced colorectal neoplasia. The association was independent of traditional risk factors, especially for those with severe liver disease. Thus, clinicians should be aware of the increased risk of colorectal neoplasia in NAFLD patients, especially for those with severe liver disease.
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