Many drug therapy options exist for NAFLD
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Lipid-lowering therapies, diabetes drugs and liver-related therapies are among the medication options for patients with nonalcoholic fatty liver disease, according to a presentation at the National Lipid Association Scientific Sessions.
Weight loss and lifestyle changes are the main ways to improve symptoms of nonalcoholic fatty liver disease (NAFLD), but medications can be used to address conditions associated with NAFLD such as dyslipidemia, insulin resistance, hepatic apoptosis, inflammation and fibrosis, Michael J. Wilkinson, MD, FACC, assistant professor of clinical medicine at the University of California, San Diego, and the Cardiovascular Institute at UC San Diego Health, said during a presentation.
NAFLD is common in patients with diabetes, obesity and/or the metabolic syndrome, and it contributes to elevated risk for CVD, which means treating those conditions is just as important as treating the NAFLD itself, Wilkinson said.
Statins should be first-line therapy in patients with NAFLD, even in most of those for whom it has progressed to nonalcoholic steatohepatitis (NASH), he said, noting there is no evidence that statins cause liver injury. Statins can even be used in patients with NASH cirrhosis, but should not be used in patients with decompensated cirrhosis.
He noted post hoc analyses of statin trials have shown statins of all levels of intensity improve CV outcomes and decrease liver enzymes in patients with elevated baseline alanine aminotransferase.
Nonstatin lipid-lowering therapies such as ezetimibe, bile acid sequestrants, PCSK9 inhibitors and omega-3 fatty acids reduce residual lipid-related risks and may confer liver benefits, he said.
“Lipid-lowering therapy is critically important in patients with NAFLD and NASH, who are often at high risk for cardiovascular disease or have experienced a cardiovascular event already or are at high risk for metabolic syndrome and diabetes,” Wilkinson said. “It’s very important to identify patients who would benefit from statin therapy, and it is clear that statin therapy is safe and effective in patients with NAFLD, reducing cardiovascular risk and transaminase levels. Other lipid-lowering therapies are safe and should be considered in those with residual lipid-related risk.”
Diabetes drugs that have been studied in patients with NAFLD/NASH include pioglitazone, sitagliptin (Januvia, Merck), GLP-1 receptor agonists and SGLT2 inhibitors, Wilkinson said.
He noted that pioglitazone has been associated with reduction in ballooning, lobular inflammation and steatosis and improvement in blood glucose, HbA1c, insulin, HDL, triglycerides and liver function in patients with NASH. However, he said, it was also associated with increases in LDL and weight.
Liraglutide (Saxenda, Novo Nordisk) was associated with more resolution of NASH and less progression of fibrosis compared with placebo, Wilkinson said.
“Antidiabetes medications have benefit in NAFLD and NASH in those with diabetes but also in those without diabetes,” he said. “SGLT2 inhibitors and GLP-1 agonists seem promising with their ability to impact liver-related outcomes, in addition to their benefits in type 2 diabetes.”
Vitamin E is often used as a treatment for NASH because it blocks intrinsic apoptopic pathways and protects against oxidative stress, Wilkinson said. In one trial, vitamin E improved NASH compared with placebo without an increase in adverse events.
Other agents that act on the liver are being investigated for treatment of NASH, including the farnesoid X receptor obeticholic acid (Ocaliva, Intercept Pharmaceuticals), which improved fibrosis but increased LDL and decreased HDL in one study, he said.
References:
- Armstrong MJ, et al. Lancet. 2016;doi:10.1016/S0140-6736(15)00803-X.
- Boettcher E, et al. Aliment Pharmacol Ther. 2012;doi:10.1111/j.1365-2036.2011.04912.x.
- Sanyal AJ, et al. N Engl J Med. 2010;doi:10.1056/NEJMoa0907929.
- Younossi ZM, et al. Lancet. 2019;doi:10.1016/S0140-6736(19)33041-7.
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Wilkinson MJ. Session III: Nonalcoholic fatty liver disease and risk of cardiovascular disease: What clinicians need to know. Presented at: National Lipid Association Scientific Sessions; Dec. 10-12, 2020 (virtual meeting).
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