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.
Glossary
- extrahepatic
Something that has an
effect outside the liver, for example when viral hepatitis affects the kidneys
or causes depression.
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."