Non-alcoholic fatty liver disease (NAFLD) is linked to an increased risk of several cancers outside the liver, including those affecting the lungs, gastrointestinal tract and breast, according to findings published in Gut.

Arising from the accumulation of fat in the liver, NAFLD and its more severe form, non-alcoholic steatohepatitis (NASH), are responsible for a growing proportion of advanced liver disease worldwide. As a result of inflammation, NAFLD can lead to the buildup of scar tissue (fibrosis), cirrhosis (advanced scarring) and even liver cancer. With no effective approved medical therapies, disease management is dependent on lifestyle changes, such as weight loss and exercise.

Although it is well known that fatty liver disease can lead to hepatocellular carcinoma, the most common type of liver cancer, its link to other types of cancer has not been clear. Giovanni Targher, MD, of the University of Verona in Italy, and colleagues conducted a meta-analysis to establish the strength of the link between NAFLD and the risk of cancers outside the liver.

The researchers combed through the Scopus, Web of Science and Scopus databases from their inception through December 2020 to find observational studies on NAFLD diagnosis. They identified 10 cohort studies that together included 182,202 people, of whom 25% had NAFLD. There were 8,485 cases of cancer other than hepatocellular carcinoma over an average follow-up period of 5.8 years.

The team found that NAFLD was associated with a 1.5 to 2 times higher risk of developing cancers that affect the gastrointestinal (GI) tract, such as stomach, pancreas, colorectal and esophageal cancers. They also noted that NAFLD was linked to a 1.2 to 1.5 times higher risk of having breast, lung, gynecological or urinary cancers. These risks were independent of confounding factors like age, sex, obesity, diabetes and smoking.

“This large meta-analysis suggests that NAFLD is associated with a moderately increased long-term risk of developing extrahepatic cancers over a median of nearly six years (especially GI cancers, breast cancer and gynecological cancers),” wrote the researchers. Deeper research is needed to better understand this link.

Click here to read the study abstract in Gut.