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Early-onset NAFLD tied to higher cancer risk



New research shows that adults who develop nonalcoholic fatty liver disease (NAFLD) before age 45 are at increased risk of developing cancer, particularly digestive system and lung cancer.


  • Researchers conducted a prospective age- and sex-matched cohort study of 63,696 adults (mean age, 51 years; 83% men) in China. The patients were followed for a median of 10 years; 31,848 had NAFLD, and 31,848 were control participants.
  • Participants were grouped on the basis of age at the time of diagnosis of new-onset NAFLD: younger than 45, 45-54, 55-64, and 65 and older.
  • Multivariable Cox models were used to analyze cancer risk by age at NAFLD onset. Population-attributable fractions were calculated to quantify cancer risk associated with age at NAFLD onset.


  • During follow-up, 2,415 participants were diagnosed with cancer.
  • NAFLD onset before age 45 was associated with highest cancer risk in comparison with the risk among control persons (average hazard ratio [AHR], 1.52). Cancer risk decreased as age at NAFLD onset increased (AHR, 1.50 for the 45-54 cohort, 1.13 for the 55-64 cohort, and 0.75 for the 65-and-older cohort).
  • Among adults younger than 45 at NAFLD onset, cancers were mainly digestive and lung cancers (AHR, 2.00 and 2.14, respectively).
  • Close to 18% of the cancer risk among adults younger than 45 at NAFLD onset was attributed to their fatty liver disease.


“The increasing incidence of NAFLD among younger populations highlights the underestimation of harmful outcomes associated with this condition,” the authors wrote. “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.”


The study, with first author Chenan Liu, MD, PhD, Beijing Shijitan Hospital, Capital Medical University, was published online in JAMA Network Open.


The study population was predominantly male, and NAFLD diagnosis relied on ultrasound rather than liver biopsy, potentially missing mild cases. The study lacked data on liver fibrosis elastography measurement and blood biomarkers. For some cancers, incidence rates were low.


The study was funded by a grant from the National Key Research and Development Program of China. The authors reported no conflicts of interest.

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