NAFLD Associated With Long-Term Risk for Extrahepatic Cancers

Using a systematic review and meta-analysis, researchers investigated the association between NAFLD and the risk for developing extrahepatic cancers.

Nonalcoholic fatty liver disease (NAFLD) is associated with an increased long-term risk for several gastrointestinal cancers, as well as breast and gynecological cancers, according to a study in Gut.

Researchers conducted a systematic review and meta-analysis to determine the association between NAFLD and the risk for certain extrahepatic cancers. They performed a systematic literature search in PubMed, Scopus, and Web of Science for all observational cohort studies on the risk for incident extrahepatic cancers in individuals with and without NAFLD from inception date to December 30, 2020.

A total of 10 unique, observational cohort studies with 182,202 middle-aged individuals (mean age, 51±6 years; mean body mass index, 25±3 kg/m2; 59% men) were included in the meta-analysis. Of the cohort, 45,218 individuals (24.8%) had NAFLD at baseline, and the median follow-up was 5.8 years.

NAFLD was associated with an almost 80% increased risk for incident stomach cancer (pooled random effects hazard ratio [HR], 1.81; 95% CI, 1.19-2.75; I2=80.8%) and an almost 85% increased risk for pancreatic cancer (pooled random effects HR, 1.84; 95% CI, 1.23-2.74; I2=0%). NAFLD was also associated with an almost 60% increased risk for colorectal cancer (pooled random effects HR, 1.64; 95% CI, 1.24-2.19; I2 = 57.9%) and with approximately a 2.5-fold increased risk for thyroid cancer (pooled random effects HR, 2.63; 95% CI, 1.27-5.45; I2=0%).

In addition, NAFLD was associated with a 30% increased risk for lung cancer and urinary system cancers, almost a 40% increased risk for breast cancer, and approximately a 60% increased risk for gynecological cancers.

NAFLD was not significantly associated with an increased risk for prostate cancer or with hematologic cancers.

Study limitations included the retrospective design, which does not allow establishing a causal association between NAFLD and risk for extrahepatic cancers. Also, residual confounding by unmeasured factors is possible. In addition, no detailed information was available for the different cancer histology, and the studies used imaging techniques or International Classification of Diseases-9/10 codes for diagnosing NAFLD instead of liver biopsy. Further, most of the studies originated from Asian countries, where large populations have regular health check-up programs.

“Health care professionals should be aware that the risk [for] developing extrahepatic cancers is increased in people with NAFLD,” the study authors noted. “Further research is required to decipher the complex link between NAFLD and cancer development.”


Mantovani A, Petracca G, Beatrice G, et al. Non-alcoholic fatty liver disease and increased risk of incident extrahepatic cancers: a meta-analysis of observational cohort studies. Gut. 2022;71(4):778-788. doi:10.1136/gutjnl-2021-324191