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Comorbidities and Nonalcoholic Fatty Liver Disease: The Chicken, the Egg, or Both?

Improvement in NAFLD may lead to improvement of metabolic syndrome, cardiovascular disease, and malignancy and vice versa.
Federal Practitioner. 2019 February;36(2)a:64-71
February 12, 2019|Federal Practitioner
Lisa M. Glass, MD;Christine M. Hunt, MD;Michael Fuchs, MD, PhD;Grace L. Su, MD
Author and Disclosure Information

Lisa Glass is a Staff Physician, and Grace Su is Chief of Gastroenterology and Associate Chief of Medicine, both at VA Ann Arbor Healthcare System. Christine Hunt is a Physician Affiliate and Director of the Cooperative Studies Program Epidemiology Centers at Durham VAMC in North Carolina. Michael Fuchs is Chief of Hepatology and Liver Transplantation at Hunter Holmes McGuire VAMC. Christine Hunt is an Adjunct Associate Professor of Medicine at Duke University Medical Center in Durham. Lisa Glass is an Assistant Professor and Grace Su is a Professor of Medicine, both at the University of Michigan Medical School in Ann Arbor. Michael Fuchs is Professor of Medicine at Virginia Commonwealth University in Richmond. Correspondence: Lisa Glass (lisaglas@med.umich.edu)

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Malignancy

Extrahepatic malignancy (colon, esophagus, stomach, pancreas, kidney, and breast) is the second most common cause of death in patients with NAFLD.21,22 The primary association between NAFLD and malignancy is found in the colon. Most large population-based studies have been performed in East Asia and have found that NAFLD is associated with a 1.5 to 1.7-fold increased risk for colonic adenomas and a 1.9 to 3.1-fold increased risk of colorectal cancer.46-49 Using magnetic resonance spectroscopy and liver biopsy to diagnose NAFLD and NASH, respectively, Wong and colleagues found that NASH, but not simple steatosis, is associated with a higher risk of advanced colorectalneoplasia (OR 5.34; 95% CI, 1.9-14.8), after adjusting for age, gender, BMI, family history, smoking, and T2DM.50

Data showing a definitive causative role of NAFLD in the development of colorectal cancer are lacking, but the presence of increased insulin levels has many potential effects on carcinogenesis in general, including stimulation of cell proliferation and apoptosis. Currently, there are no recommended changes to the standard colorectal cancer screening recommendations specifically for patients with NAFLD.

Conclusion

NAFLD is a multisystem disease that is associated with increased liver-related and all-cause mortality. Data on the close association between NAFLD and several extrahepatic complications, including MetS, T2DM, CVD, CKD, and malignancy are well established. There also is growing evidence of a bidirectional relationship between some of these diagnoses, whereas NAFLD is not only a consequence, but also a cause of MetS, T2DM, and CKD independent of other typical risk factors.

Given the multiple comorbidities associated with NAFLD and its potential to influence the severity of these diagnoses, management of these complex patients requires diligence and a multidisciplinary approach. In order to engage in early recognition and intervention to prevent potential morbidity and mortality, regular screening and surveillance for the development of NAFLD in patients with metabolic risk factors can be considered, and careful screening for metabolic complications in patients with established NAFLD is important.

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