Disclosures: Cusi reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
July 29, 2021
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Experts issue ‘call to action’ to prepare for NASH epidemic

Disclosures: Cusi reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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Eight professional societies issued a joint report on the dangers associated with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, calling on clinicians to work together across specialties and align treatment strategies.

As Healio previously reported, about 25% of U.S. adults have nonalcoholic fatty liver disease, known as NAFLD, which is the most common chronic liver condition in the U.S., according to the American Liver Foundation.

Liver Highlight
Source: Adobe Stock

NAFLD can progress to nonalcoholic steatohepatitis (NASH), which is a leading indication for liver transplant.

Kenneth Cusi

“There is discordance between the level of awareness about dangers from cirrhosis associated with fatty liver related to obesity and diabetes and the lack of action by clinicians seeing patients with these chronic conditions,” Kenneth Cusi, MD, FACP, FACE, an Endocrine Today Editorial Board member and chief of the division of endocrinology, diabetes and metabolism at the University of Florida, told Healio. “We felt it was time for gastroenterologists, endocrinologists, primary care providers and obesity medicine specialists to come together and say that we need to break our patient care silos to work together to increase awareness and start managing this serious condition better, as a team. This is the only way we prevent this from becoming a terrible problem in the future. Already, NASH is the fastest growing cause of liver transplantation. In 10 years, as the epidemics of obesity and diabetes worsen, so will this problem for many patients.”

Incidence of NAFLD, NASH rising

The upward trends in NAFLD/NASH incidence and prevalence underscore the importance and urgency of developing and implementing effective screening, diagnosis and treatment strategies in the U.S and globally, particularly among emerging at-risk cohorts, such as patients with diabetes and obesity, Cusi and colleagues wrote in the report.

Although most patients with NAFLD and NASH have traditionally been diagnosed and managed by hepatologists, the recent availability of noninvasive diagnostic procedures is expanding the role of other health care professionals likely to see patients with these conditions, particularly gastroenterologists, endocrinologists, obesity medicine specialists and primary care providers, the researchers wrote. The American Gastroenterological Association, collaborating with seven other professional associations, convened a “call-to-action” virtual conference, informed by the results of a national NASH needs assessment survey conducted in May 2020, to review the current research and develop a “unified public health response” to NASH and NAFLD in adults. The resulting recommendations were published in Gastroenterlogy.

“The first point is clinicians must put NAFLD and NASH in their minds when seeing patients,” Cusi said.

The conference participants identified several approaches for clinical practice:

  • NAFLD is the one of the most common causes of abnormal liver enzymes; however, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) can be normal in many cases of NAFLD/NASH at all stages, including advanced fibrosis.
    “We must go beyond the reflex of looking at elevated liver enzymes below 40 U/L and think all is good,” Cusi said. “Most patients with fatty liver will have an ALT between 20 U/L and 40 U/L. The ‘real’ normal for women is 19 U/L and for men 30 U/L. We must begin thinking in those terms.”
  • NAFLD and fibrosis are reversible with weight loss.
  • Clinical practice guidelines do not recommend universal screening for NAFLD, but careful case finding for NASH and clinically significant fibrosis is advised for high-risk groups, such as those with moderate to severe obesity, longstanding type 2 diabetes or metabolic syndrome.
    “We are not seeking to identify people with fatty liver ... what we are trying to find is those with clinically significant liver fibrosis, which puts them on the path to cirrhosis,” Cusi said.
  • Rule out advanced fibrosis with the Fibrosis-4 Index, a formula that combines age, platelets, AST and ALT and is available on web browsers, Cusi said. An alternative is the NAFLD fibrosis score that incorporates BMI and plasma glucose, but may overestimate risk in people with diabetes. Patients at intermediate or high risk may require further assessment with a second-line test, such as elastography, or some commercially available serum marker tests with direct measures of fibrogenesis.
  • Accurate fibrosis staging after diagnosis provides information regarding prognosis; need for pharmacotherapy, intensive lifestyle modification and/or bariatric surgery; and screening/surveillance for hepatocellular carcinoma. The most common imaging techniques are vibration-controlled transient elastography and magnetic resonance elastography. Liver biopsy, historically required to diagnosis liver fibrosis and NASH, provides helpful information and should be considered for cases in which there is “diagnostic doubt.”

The 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. “Because NAFLD is not an isolated disease, but a component of cardiometabolic abnormalities typically associated with obesity, the cornerstone of therapy is the same as that for people with obesity and cardiometabolic complications, namely lifestyle-based therapies (altered diet, such as reduced-calorie or Mediterranean diet and regular, moderate physical activity), and replacing obesogenic medications to decrease body weight and improve cardiometabolic health,” the researchers wrote.

‘Identify these people today’

Adults with NASH and fibrosis stage 2 or higher are candidates for liver-directed pharmacotherapy. Some diabetes medications can also treat NASH in adults with or without type 2 diabetes, such as pioglitazone or the injectable GLP-1 receptor agonist semaglutide.

“The daily injectable semaglutide formulation proven to improve steatohepatitis in a recently published phase 2 NASH trial is not available; a phase 3 trial is underway,” Cusi said. “However, injectable semaglutide is approved for the treatment of type 2 diabetes [Ozempic, Novo Nordisk] and at higher doses for obesity [Wegovy, Novo Nordisk].”

Vitamin E (800 IU/d) also improves steatohepatitis in patients with NASH but without type 2 diabetes. No pharmacological agent is currently approved by the FDA for the treatment of NASH.

“In the next 2 or 3 years, we will have FDA-approved drugs for NASH,” Cusi said. “But that should not discourage clinicians from doing something today. We need to identify people at risk for cirrhosis from NASH today, because lifestyle modification leading to weight loss or pharmacological options can halt disease progression. You can prevent cirrhosis. There are things you can do right now.”