People with fatty liver disease are at greater risk for multiple cancers

People with non-alcoholic fatty liver disease (NAFLD) were found to have higher rates of cancer, with the greatest increase observed for gastrointestinal cancers, according to findings presented yesterday at the 2018 AASLD Liver Meeting in San Francisco. These findings suggest that NAFLD may be a key driver of the increased risk of cancer associated with obesity.

NAFLD, and its more severe form, non-alcoholic steatohepatitis (NASH), refer to excessive fat accumulation in the liver in the absence of heavy alcohol consumption. Fatty liver disease, which is associated with the metabolic syndrome, is a growing cause of cirrhosis, liver cancer and liver transplantation as obesity rates rise worldwide.

However, the major causes of death for people with NAFLD are cardiovascular disease and non-liver cancers, not advanced liver disease. In the UK, obesity is the second biggest cause of cancer after smoking, according to Cancer Research UK.

Dr Alina Allen of the Mayo Clinic in Rochester and colleagues conducted a study comparing cancer rates among 4791 adults diagnosed with NAFLD in a Minnesota county between 1997 and 2018 and a general population control group of 14,432 people matched by age and sex. Individuals with viral hepatitis and other causes of liver disease were excluded.

In the full study population just over half were women, most were white and the average age was 53 years. People with NAFLD were more likely than those in the control group to be obese (67% vs 35%), to have diabetes (56% vs 26%) and to have hypertension (63% vs 41%). In both groups, 10% were smokers.

Over a median follow-up period of 8 years, a total of 672 cancer cases were recorded in the NAFLD group (about 14%) and 1570 cases in the control group (about 11%).

In both groups, the most common types were breast cancer (182 and 496 cases, respectively) and prostate cancer (138 and 447 cases). Rounding out the top five were colon, lung and uterine cancers. Stomach, oesophageal, pancreatic and ovarian cancers occurred less often. Liver cancer occurred in 34 and 23 people, respectively.

The overall risk of cancer was 91% greater in the NAFLD group compared with the control group (relative risk 1.91). Not surprisingly, liver cancer showed the greatest disparity, with about three times more cases in the NAFLD group (relative risk 3.24). Uterine, stomach, pancreatic and colon cancer were around twice as common (relative risk 2.39, 2.34, 2.09 and 1.76, respectively). Differences in risk were not statistically significant for lung or oesophageal cancer.

Women with NAFLD also had higher rates of breast and ovarian cancer compared with women in the control group, while men with NAFLD had a higher risk of prostate cancer. The increased risk of colon cancer was driven entirely by men, Allen said. Pancreatic cancer occurred at a younger age, on average, among both women and men in the NAFLD group, while colon cancer occurred at a younger age in men only.

The researchers also asked whether fatty liver disease is associated with a greater risk of cancer than obesity in the absence of NAFLD. They found that people with NAFLD had a significantly higher risk compared with obese people in the control group without NAFLD. In fact, obesity was associated with a higher cancer risk only in those with NAFLD, not in those without.

"These data provide an important 'hierarchical' overview of the top most important malignancy risks associated with NAFLD," Allen said. "Liver cancer had the highest increase in relative risk, and this was not a surprising finding. However, the 2.5-fold higher risk of stomach and pancreatic cancer are novel data that the medical community should be aware of. Future studies should further examine this association to determine if screening methods should be implemented in this population."