Obesity increases the risk of both cardiovascular diseases and type 2 diabetes. These diseases are linked to NAFLD, too. The liver plays an important role in regulating blood sugar and blood lipids, and the accumulation of fat in the liver can disturb these functions. Many risk genes for NAFLD also increase type 2 diabetes and cardiovascular risk.
Whether or not genetic risk manifests itself may depend on epigenetic mechanisms that regulate gene activity. They in turn are affected by environmental factors like diet and lifestyle. For example, the research group recently found that insufficient folate intake was associated with epigenetic changes in diabetes-related genes in the liver. They have also shown that the diabetes drug metformin exerts its action via epigenetic mechanisms in the liver.
“Healthy dietary guidelines also apply in the prevention and treatment of NAFLD. Saturated fats and fructose from soft drinks are specifically known to increase the risk.”
Even moderate alcohol use is not recommended for people with NAFLD. Some drugs can also cause more damage to the liver. However, cholesterol-lowering drugs, or statins, don’t seem to be among them, according to the results from a multi-centre study, including Kuopio. Statins have been underused for patients with NAFLD because their use tends to elevate liver values, but the study showed that statins, in fact, may prevent progression to NASH.
The most common NAFLD risk gene is a PNPLA3 gene variant carried by 40 per cent of the population in Western countries. Homozygous carriers, who have inherited the risk gene from both parents, make up just five per cent of the population, but they have 70 per cent more fat in their liver than non-carriers.
The Physical Activity and Nutrition in Children (PANIC) study at UEF showed that, combined with being overweight, the PNPLA3 gene variant is already linked to altered liver metabolism in children.
An example of the genetic complexity behind NAFLD is a TM6SF2 gene variant. It causes fat accumulation in the liver and may promote progression to NASH while decreasing blood lipid levels. Thus, ideal blood lipid levels may conceal the risk of fatty liver and NASH, which was observed in the PANIC study as well.
“Other gene variants have also been linked to more severe liver disease, but it remains to be seen how genetic information will affect treatment choices in the future.”
“At present, more awareness is needed of NAFLD and the risks it entails. Diagnostics and follow-ups are just as important in NAFLD as in other obesity-related diseases.”