The incidence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis continues to rise with obesity and type 2 diabetes, and all clinicians must screen patients at high cardiometabolic risk, according to a speaker.

Approximately 30% to 37% of U.S. adults have nonalcoholic fatty liver disease, known as NAFLD, and about 8-12% have nonalcoholic steatohepatitis (NASH), which leads to fibrosis and liver failure and a leading indication for liver transplant, Christos S. Mantzoros, MD, DSc, PhD, professor of medicine at Harvard Medical School and chief of endocrinology at VA Boston Healthcare System, said during a presentation at the Heart in Diabetes CME Conference. Often such patients are not diagnosed until serious liver or cardiometabolic complications develop, Mantzoros said.

“In our society, as the prevalence of obesity goes up, the prevalence of type 2 diabetes goes up, and the prevalence of NAFLD and steatosis goes up,” Mantzoros said. “The NASH epidemic is part of a cardiometabolic disease group. All of us need to be vigilant to make the diagnosis and to prevent and treat it. All of us need to apply all of the tools we have when we make the diagnosis.”

In the U.S., about 7 in 10 people with diabetes will have NAFLD, Mantzoros said, whereas up to 80% of people with NASH will have metabolic syndrome, leading to type 2 diabetes over time. Additionally, these risk factors lead to cardiovascular morbidity and mortality, he said.

“NAFLD and NASH are common, especially among people with obesity, diabetes and metabolic syndrome, and unfortunately most of the time it remains undiagnosed,” Mantzoros told Healio. “We need to think about it, screen and treat it.”

Strategies to treat NAFLD, prevent NASH

There are currently no FDA-approved therapies specifically for NASH; however, Mantzoros highlighted several strategies that can reduce fat in the liver and inflammation:

• Weight loss is associated with mild to moderate improvement in NASH, though maintaining weight loss is very challenging, Mantzoros said. The Mediterranean diet is inversely associated with liver steatosis and decreases 10-year CV risk in NAFLD, according to evidence from the ATTICA prospective cohort study recently published in Clinical Nutrition. “In a meta-analysis we put together, we do know that if we follow a Mediterranean diet or Dietary Approaches to Stop Hypertension (DASH) diet, lowering total fat or saturated fat — even if high in monounsaturated fat — we decreased risk for NAFLD and CVD,” Mantzoros said. Similar outcomes are expected in response to the DASH diet.
• Bariatric surgery and endoscopic devices have demonstrated improvement in NASH and metabolic syndrome, but evidence for fibrosis improvement is limited, Mantzoros said. “We know from several studies that if we decrease weight by 10% for 1 year, there is NASH resolution in more than 90% of the cases, fibrosis regression in 80% and steatosis improvement in 100% of cases,” Mantzoros said. “Today, we can do this only with bariatric surgery. In the future, we hope we will be able to do this with new anti-obesity drugs.”
• Irrespective of the statin used, data show improvements with statin therapy in lipid levels and inflammation, as well as an improvement in NAFLD and NASH. “In an editorial we recently published in Metabolism, we recommend that patients continue statin therapies, unless one has late stage of the disease,” Mantzoros said. “Statins should not be discontinued.”
• Some diabetes therapies show promise. Pioglitazone improves liver histology in patients with and without type 2 diabetes with biopsy-proven NASH, and may be used to treat those patients, Mantzoros said. Currently, it is premature to consider GLP-1 receptor agonists or SGLT2 inhibitors to specifically treat liver disease in people with NAFLD or NASH, though data shows the agents can lead to weight loss and decrease steatosis. “They do not improve fibrosis to the degree that we want,” Mantzoros said. “We need larger, longer studies with stronger GLP-1 analogues or combination therapies.”

“When adipose tissue storage is exceeded, triglycerides will be stored in muscle and the liver and this leads to insulin resistance, metabolic syndrome, and not only CVD, chronic kidney disease or diabetes, but also NAFLD,” Mantzoros said. “In addition to lifestyle intervention, many of the same medications [used in diabetes] are expected to be used to treat NAFLD.”

A call to action

As Healio previously reported, eight professional societies issued a joint report on the dangers associated with NAFLD and NASH in July, calling on clinicians to work together across specialties and align treatment strategies.

“We need to realize that this is not a disease only for hepatologists,” Mantzoros said. “Cardiometabolic experts, endocrinologists and primary care physicians need to focus on this epidemic along with nutritionists and exercise physiologists. So many patients who come to our offices go unrecognized.”

Mantzoros said patients must be screened for NAFLD and NASH at the primary care level and diagnosed early to avoid serious complications. Similarly, the joint report also notes that most patients with NAFLD — and many with NASH — have a low risk for clinically significant fibrosis and should be managed by primary care providers.

“We must optimize management with the tools that we have at our disposal today,” Mantzoros said. “Industry and academia need to work together on improving new treatments for this metabolic disorder. There is more coming soon from our working group in terms of recommendations, algorithms, and pathways to follow.”