In a new study, researchers found that inhibition of a key enzyme safely and effectively improved the health of persons with non-alcoholic fatty liver disease (NAFLD), a chronic metabolic disorder that affects hundreds of millions of people worldwide.
The gene silencing approach represents a novel way to reverse NAFLD.
The research was conducted by a team at the University of California San Diego and elsewhere.
NAFLD occurs when fat accumulates in liver cells due to causes other than excessive alcohol intake. The precise cause is not known, but diet and genetics are believed to play substantial roles.
The condition is typically not noticed until the disease is well-advanced and perhaps has transitioned to non-alcoholic steatohepatitis (NASH), a progressive form that can lead to cirrhosis, liver cancer, and liver failure.
There is no cure. Treatment primarily consists of ameliorating contributory factors, such as losing weight, improving diet, exercising more, and controlling for other conditions, such as diabetes and high blood pressure.
No Food and Drug Administration-approved medications exist. In the worst cases, a liver transplant may be required.
In the study, the team tested 44 people at 16 sites in Canada, Poland, and Hungary.
For 13 weeks, participants were injected with either an antisense inhibitor called IONIS-DGAT2 or a placebo.
The inhibitor interferes with Diacylglycerol-O-acyltransferace or DGAT2, one of two enzyme forms required to catalyze or accelerate the production of triglycerides, a type of fat found in the blood.
High levels of triglycerides boost fat storage throughout the body, including the liver.
The researchers found that after 13 weeks of treatment, participants who received the enzyme inhibitor showed reductions in fatty liver levels compared to baseline, without elevated levels of fats, enzymes, or sugars in the blood.
There were six reported serious adverse events, including a cardiac arrest and deep vein thrombosis, but the researchers determined the events were unrelated to the study drug.
These findings showed a robust reduction in liver fat by MRI without corresponding increases in blood lipids.
The team says given a big proportion of patients achieving roughly a 30% reduction in MRI-PDFF, it looks like after just 13 weeks of treatment, the drug was actually slowing the progression of NAFLD to NASH.
One author of the study is Rohit Loomba, MD, a professor of medicine in the Division of Gastroenterology.
The study is published in The Lancet Gastroenterology and Hepatology.
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