Noninvasive testing for NAFLD crucial for people with diabetes
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Providers should closely monitor people with diabetes and other high-risk adults for nonalcoholic fatty liver disease and consider multiple noninvasive tests to detect the presence of advanced fibrosis, according to a speaker.
Mazen Noureddin, MD, MHSc, director of the fatty liver program at Cedars-Sinai, said about 73% of people with diabetes also have nonalcoholic fatty liver disease (NAFLD), making it crucial for providers to conduct screening to monitor the development of advanced disease.
“We think this disease should be identified early in the high-risk population using noninvasive testing,” Noureddin said during the presentation. “Once you identify [fibrosis], they need to be referred to a hepatologist or endocrinologist. Those with [advanced fibrosis] need to be monitored for liver cancer.”
Noureddin discussed screening guidelines and treatment options for NAFLD and nonalcoholic steatohepatitis (NASH) at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease.
Screening for fibrosis in diabetes
Globally, NAFLD is present in about 25% of the population, and the prevalence of NASH is between 1.5% and 6.45%. For people with diabetes, the prevalence of NAFLD is much higher at 73%, and advanced fibrosis, defined as a fibrosis stage of F3 or higher, is prevalent in 17.2% of people with diabetes. According to a study published in The New England Journal of Medicine, those with advanced fibrosis had an increased risk for liver-related complications and mortality compared with people with no fibrosis or F1 or F2 stage disease.
Noureddin said all people with type 2 diabetes should be screened using noninvasive testing. Fibrosis-4 (FIB-4) score is used by most providers to predict advanced fibrosis, with a score of less than 1.3 excluding advanced fibrosis and a score of 2.67 or higher predicting advanced fibrosis.
“If the FIB-4 is low, you will want the patient to stay in primary care or a diabetes clinic,” Noureddin said. “If it’s more than 2.67, it’s going to be referred to a specialist. If it falls between 1.3 and 2.67, you can do another test, such as FibroScan.”
FibroScan (Echosens) is a noninvasive test measuring liver stiffness. Liver stiffness of less than 8 kPa indicates low risk for advanced fibrosis, whereas a score above 12 kPa signals a high risk for advance disease. Any liver stiffness between 8 kPa and 12 kPa requires referral to a hepatologist for a liver biopsy or a magnetic resonance elastography.
Fibrosis treatment options
Weight loss is the backbone to treating fibrosis, according to Noureddin. According to a study published in Gastroenterology in 2015, weight loss of 7% or greater was associated with NASH resolution, and weight loss of 10% or more was associated with the reversal of fibrosis.
Other treatments also have benefits in NASH. According to data from the PIVENS trial, people with biopsy-proven NASH who took pioglitazone or vitamin E had improvements in histologic features of NASH, steatosis, fibrosis and other features compared with placebo.
Many agents under development are in phase 2 or phase 3 trials. Among those is obeticholic acid (Ocaliva, Intercept Pharmaceuticals). In the REGENERATE trial, a larger proportion of participants assigned 10 mg or 25 mg of obeticholic acid once daily experienced a 1 stage fibrosis improvement with no worsening of NASH or NASH resolution with no worsening of fibrosis at 18 months compared with placebo. However, Noureddin noted the FDA has not yet approved the agent, asking for more data on its safety and efficacy.
Another promising agent, resmetirom (Madrigal Pharmaceuticals), is a thyroid hormone receptor that targets the liver. In a phase 2 trial, participants receiving 60 mg or 80 mg of remestirom had greater reductions in hepatic fat at 12 and 36 weeks and a higher proportion of participants with NASH resolution compared with placebo.
Noureddin added that two other agents, semaglutide (Wegovy, Novo Nordisk) and lanifibranor (Inventiva), were both associated with improvements in NASH resolution in trial data, with lanifibranor also associated with fibrosis improvement of at least 1 stage.
With NASH resolution and fibrosis improvement involving changes in multiple areas, Noureddin said, multiple drugs will have a role in future treatment of liver disease.
“Fibrosis improvement and NASH resolution are great, but this is a disease that you need reduction in lipotoxic fat, weight loss, atherogenic lipid improvement and glycemic control for a total improvement of clinical liver events and improvement of major adverse cardiac events,” Noureddin said.
References:
- Harrison SA, et al. Lancet. 2019;doi:10.1016/S0140-6736(19)32517-6.
- Sanyal AJ, et al. N Engl J Med. 2021;doi:10.1056/NEJMoa2029349.
- Vilar-Gomez E, et al. Gastroenterology. 2015;doi:10.1053/j.gastro.2015.04.005.
- Younossi ZM, et al. Lancet. 2019;doi:10.1016/S0140-6736(19)33041-7.
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Noureddin M. Diagnosis and treatment of patients with NAFLD/NASH – The future. Presented at: World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease; Dec. 2-4, 2021; Los Angeles (hybrid meeting).
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