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Lean NAFLD presents similar profile to obesity-related NAFLD
In the first extensive look at lean White patients with nonalcoholic fatty liver disease, researchers found similar genetic profiles, insulin resistance and dysfunctional adipose tissue as their counterparts with obesity.
“The problem of metabolic complications in the absence of overweight or obesity is under-recognized. This population-based study shows that on rigorous criteria, at least 2.5% of the middle-aged population may be affected from NAFLD despite leanness,” Elmar Aigner, MD, of the obesity research unit at the Paracelsus Medical University in Salzburg, Austria, told Healio.com/Hepatology. “One implication of the study is that metabolic complications such as NAFLD and cardiovascular risk need to be actively considered in this patient group.”
Data from 187 White participants taking part in a separate colon cancer prevention study were analyzed. Previous lean NAFLD studies, the researchers noted, were based on Asian participants.
Participants had no known genetic predisposition, no viral likelihood of developing liver disease and did not consume a medically significant amount of alcohol. They underwent a physical examination, provided their medical history and, after fasting overnight, had their blood drawn. Based on this information, participants were then placed in one of three groups:
- lean healthy (BMI ≤ 25 kg/m2 and no steatosis; n = 71);
- lean NAFLD (BMI ≤ 25kg/m2 and steatosis; n = 55); and
- obese NAFLD (BMI ≥ 30kg/m2 and steatosis; n = 61).
Researchers found those with NAFLD, but without obesity, had a higher likelihood of carrying the PNPLA3 allele (P = .007), impaired glucose tolerance and low amounts of adiponectin (P < .001) when compared to their lean counterparts without NAFLD.
“These subjects with lean NAFLD are characterized by a genetic background with a higher … PNPLA3 carrier rate, are insulin resistant and have evidence of severely dysfunctional adipose tissue as indicated by deranged adipokine and cytokine levels,” Aigner said. “This implies a multifactorial pathogenesis similar to the complications in the obese subjects.”
The lean NAFLD group showed higher Fibrosis 4 Score, but lower Nonalcoholic Fatty Liver Disease Fibrosis Score due to its basis in BMI. This difference highlights the challenge of estimating fibrosis in the lean NAFLD group and absence of histologic data provides a window of opportunity for the future, researchers wrote.
“Since lean NAFLD subjects may have distinct metabolic and genetic components contributing to the disease, further study on the lean NAFLD including histology may yield promising results helping to understand obesity-related diseases,” Aigner said. – by Janel Miller
Disclosure: Aigner reports receiving financial support from PMU-FFF (E-13/17/086-AIG and E-15/21/108). The other authors report no relevant financial disclosures.