Nonalcoholic fatty liver disease is specifically related to the risk of hepatocellular cancer but not extrahepatic malignancies

Objective We performed a matched cohort study among individuals with and without nonalcoholic fatty liver disease (NAFLD) to determine: 1) the incidence of cancers (extrahepatic and liver) and their spectrum and 2) if NAFLD increases the risk of extrahepatic cancers. Methods The NAFLD and non-NAFLD (control) cohorts were identified from electronic medical records via International Classification of Diseases (ICD) codes from a single center and followed from 2010 to 2019. Cohorts were matched 1:2 for age, sex, race, body mass index (BMI), and type 2 diabetes. Results A total of 1,412 subjects were included in the analyses. There were 477 individuals with NAFLD and 935 controls (median age, 52 years; women, 54%; white vs. black: 59% vs. 38%; median BMI, 30.4 kg/m2; type 2 diabetes, 34%). The cancer incidence (per 100,000 person-years) was 535 vs. 1,513 (NAFLD vs. control). Liver cancer incidence (per 100,000 person-years) was 89 in the NAFLD group vs. 0 in the control group, whereas the incidence of malignancy was higher across other types of cancer in the control group vs. in the NAFLD group. Conclusions The overall extrahepatic cancer risk in NAFLD is not increased above and beyond the risk from background risk factors such as age, race, sex, BMI, and type 2 diabetes.

[1]  H. Tilg,et al.  Global multi-stakeholder endorsement of the MAFLD definition. , 2022, The lancet. Gastroenterology & hepatology.

[2]  A. Venniyoor,et al.  The Troubling Link Between Non-alcoholic Fatty Liver Disease (NAFLD) and Extrahepatic Cancers (EHC) , 2021, Cureus.

[3]  V. Wong,et al.  Non-alcoholic fatty liver disease , 2021, The Lancet.

[4]  Tomohiro Tanikawa,et al.  Fatty Liver, and Not Visceral Fat, Is More Associated with Liver Fibrosis and Diabetes in Non-Obese Japanese Individuals: A Cross-Sectional Study , 2020, Life.

[5]  V. Wong,et al.  A new definition for metabolic associated fatty liver disease: an international expert consensus statement. , 2020, Journal of hepatology.

[6]  L. Cantley,et al.  Insulin–PI3K signalling: an evolutionarily insulated metabolic driver of cancer , 2020, Nature Reviews Endocrinology.

[7]  A. Sanyal,et al.  MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease. , 2020, Gastroenterology.

[8]  Kyungdo Han,et al.  The association between nonalcoholic fatty liver disease and esophageal, stomach, or colorectal cancer: National population-based cohort study , 2020, PloS one.

[9]  T. Therneau,et al.  The Risk of Incident Extrahepatic Cancers is higher in Nonalcoholic Fatty Liver Disease than Obesity - a Longitudinal Cohort Study. , 2019, Journal of hepatology.

[10]  J. Manson,et al.  Intentional Weight Loss and Obesity-Related Cancer Risk , 2019, JNCI cancer spectrum.

[11]  K. Shimada,et al.  Fatty Liver Has Stronger Association With Insulin Resistance Than Visceral Fat Accumulation in Nonobese Japanese Men , 2019, Journal of the Endocrine Society.

[12]  Z. Younossi Non-alcoholic fatty liver disease - A global public health perspective. , 2019, Journal of hepatology.

[13]  M. Cullen,et al.  Socioeconomic Differences in the Epidemiologic Transition From Heart Disease to Cancer as the Leading Cause of Death in the United States, 2003 to 2015 , 2018, Annals of Internal Medicine.

[14]  Youfa Wang,et al.  Use of various obesity measurement and classification methods in occupational safety and health research: a systematic review of the literature , 2018, BMC Obesity.

[15]  T. Therneau,et al.  Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: A 20 year‐community study , 2018, Hepatology.

[16]  M. Fukui,et al.  Metabolically healthy obesity without fatty liver and risk of incident type 2 diabetes: A meta-analysis of prospective cohort studies. , 2018, Obesity research & clinical practice.

[17]  H. Gabra,et al.  Adiposity and cancer at major anatomical sites: umbrella review of the literature , 2017, British Medical Journal.

[18]  H. Lee,et al.  Association between non-alcoholic fatty liver disease and cancer incidence rate. , 2017, Journal of hepatology.

[19]  K. Straif,et al.  Body Fatness and Cancer--Viewpoint of the IARC Working Group. , 2016, The New England journal of medicine.

[20]  L. Henry,et al.  Global epidemiology of nonalcoholic fatty liver disease—Meta‐analytic assessment of prevalence, incidence, and outcomes , 2016, Hepatology.

[21]  Tran Quoc Bao,et al.  Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants , 2016, The Lancet.

[22]  M. Zwahlen,et al.  Adiposity and cancer risk: new mechanistic insights from epidemiology , 2015, Nature Reviews Cancer.

[23]  Cheng-Li Lin,et al.  A population-based cohort study. , 2015 .

[24]  M. Foster,et al.  Adipose tissue, obesity and adipokines: role in cancer promotion , 2015, Hormone molecular biology and clinical investigation.

[25]  Gretchen A. Stevens,et al.  Global burden of cancer attributable to high body-mass index in 2012: a population-based study. , 2015, The Lancet. Oncology.

[26]  D. S̆timac,et al.  Non-alcoholic fatty liver disease and obesity: biochemical, metabolic and clinical presentations. , 2014, World journal of gastroenterology.

[27]  M. Singer,et al.  Metabolic Health Reduces Risk of Obesity-Related Cancer in Framingham Study Adults , 2014, Cancer Epidemiology, Biomarkers & Prevention.

[28]  F. Hu,et al.  Metabolically healthy obesity: epidemiology, mechanisms, and clinical implications. , 2013, The lancet. Diabetes & endocrinology.

[29]  T. Therneau,et al.  Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States , 2013, Hepatology.

[30]  M. Mirza Obesity, Visceral Fat, and NAFLD: Querying the Role of Adipokines in the Progression of Nonalcoholic Fatty Liver Disease , 2011, ISRN gastroenterology.

[31]  K. He,et al.  Meta-analysis of prospective cohort studies , 2011 .

[32]  C. Mathers,et al.  Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 , 2010, International journal of cancer.

[33]  M. Zwahlen,et al.  Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies , 2008, The Lancet.

[34]  Pedagógia,et al.  Cross Sectional Study , 2019 .

[35]  S. Sanderson,et al.  The natural history of nonalcoholic fatty liver disease: a population-based cohort study. , 2005, Gastroenterology.

[36]  E. Calle,et al.  Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms , 2004, Nature Reviews Cancer.

[37]  H. El‐Serag,et al.  Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. , 2004, Gastroenterology.

[38]  K. Flegal,et al.  Epidemiologic trends in overweight and obesity. , 2003, Endocrinology and metabolism clinics of North America.

[39]  S. Gabriel,et al.  Systematic Review of the Literature , 2021, Adherence to Antiretroviral Therapy among Perinatal Women in Guyana.

[40]  S. Leeder,et al.  A population based study , 1993, The Medical journal of Australia.