Onset Age of NAFLD Associated with Cancer Risk


Patients aged less than 45 years at NAFLD onset had a higher risk of cancer compared to older age groups, highlighting an association between younger age at NAFLD onset and cancer risk.

Person wearing gray sweater holding abdomen in pain | Credit: PixaBay

Credit: PixaBay

Developing new-onset nonalcoholic fatty liver disease (NAFLD) at a younger age is associated with an increased risk of cancer, according to a matched cohort study.

Results indicated patients aged less than 45 years at NAFLD onset exhibited a higher risk of cancer, with risk decreasing as the onset age of NAFLD increased.1

“Importantly, the population with NAFLD is becoming younger,” wrote investigators.1 “Among patients with chronic liver disease-related deaths, one-third experienced NAFLD at younger than age 30 years. These outcomes suggest that attention must be paid to the association of new-onset NAFLD at different ages with the risk of developing other diseases, such as cancer.”

About 100 million individuals in the United States are estimated to have NAFLD. People who are overweight, obese, or have diabetes, high cholesterol, or high triglycerides are at risk of developing NAFLD.2 Being considered overweight or obese can also lead to a greater risk of certain kinds of cancer.3

To assess the association between the age of new-onset NAFLD and the risk of cancer, senior investigator Hanping Shi, MD, PhD, of the department of surgery at Beijing Shijitan Hospital in China, and a team of investigators matched patients with and without incident NAFLD using participants from the Kailuan Cohort Study. An ongoing prospective cohort study initiated in June 2006, the Kailuan Cohort Study collected physical examination data, questionnaire interview data, dietary information, and laboratory test results for employees of the Kailuan Group biennially and conducted annual follow-ups.1

To be included in the current study, patients were required to have attended at least 2 physical examinations between 2006 and 2017, with the first examination showing no NAFLD and NAFLD appearing in the subsequent examination. Patients with a preexisting diagnosis or history of NAFLD, cancer, heavy alcohol consumption, hepatitis B virus infection, or other liver diseases were excluded.1

Investigators identified 46,100 incident NAFLD cases. After excluding patients with missing covariate data at the time of diagnosis and matching the remaining patients 1:1 based on age and sex to participants without NAFLD, 31,848 pairs of participants were included in the study. Among the 63,696 participants in the entire cohort, the mean age was 51.37 (standard deviation [SD], 12.43) years and 82.8% (n = 52,764) were male.1

The association between the onset age of NAFLD and the risk of cancer was evaluated using weighted Cox regression models. Investigators used population-attributable fractions to quantify the association of NAFLD with cancer risk at different ages.1

During a median follow up of 10.16 (interquartile range [IQR], 7.89-11.67) years, 2415 patients were diagnosed with cancer. Of those participants, 1134 were in the matched non-NAFLD group and 1281 were in the NAFLD case group.1

Compared with the matched group, patients aged < 45 years at NAFLD onset exhibited a higher risk of cancer (average hazard ratio [AHR], 1.52; 95% confidence interval [CI], 1.09-2.12), and as the onset age of NAFLD increased, cancer risk decreased (P for interaction < .001):

  • Ages 45-54 years: AHR, 1.50; 95% CI, 1.15-1.97
  • Ages 55-64 years: AHR, 1.13; 95% CI, .97-1.33
  • Ages >65 years: AHR, 0.75; 95% CI, .45-1.27

Investigators pointed out the risk of digestive system cancers was higher in patients aged < 45 years (AHR, 2.00; 95% CI, 1.08-3.47) and 45-54 years (AHR, 1.94; 95% CI, 1.46-2.74) at new-onset NAFLD. Younger age of NAFLD onset was also associated with greater risk of liver and lung cancers. Among patients aged < 45 years at new-onset NAFLD, the AHR of liver and lung cancers was 2.66 (95% CI, 1.16-6.11) and 2.14 (95% CI, 1.05-4.36), respectively. Of note, no significant differences were observed in the risk of colorectal cancer among patients who were younger at NAFLD onset.1

Population-attributable fractions of new-onset NAFLD decreased with age, which investigators noted was observed for all cancer types. In patients aged < 45 years at NAFLD onset, 17.83% (95% CI, 4.92%-29.86%) of cancer risk was attributable to NAFLD.‬‬‬‬1

“The increasing incidence of NAFLD among younger populations highlights the underestimation of harmful outcomes associated with this condition. Our findings suggest that early control and intervention against NAFLD progression may be crucial to reduce the occurrence of NAFLD-related cancers and lessen the burden on public health,” investigators concluded.1


  1. Liu C, Liu T, Zhang Q, et al. New-Onset Age of Nonalcoholic Fatty Liver Disease and Cancer Risk. JAMA Netw Open. 2023;6(9):e2335511. doi:10.1001/jamanetworkopen.2023.35511
  2. American Liver Foundation. Nonalcoholic Fatty Liver Disease (NAFLD). Fatty Liver Disease. Accessed October 3, 2023. https://liverfoundation.org/liver-diseases/fatty-liver-disease/nonalcoholic-fatty-liver-disease-nafld/
  3. American Cancer Society. Body Weight and Cancer Risk. Diet and Physical Activity. Accessed October 3, 2023. https://www.cancer.org/cancer/risk-prevention/diet-physical-activity/body-weight-and-cancer-risk.html
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