AHA: Addressing ‘undiagnosed’ NAFLD could mitigate CVD risk
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Nonalcoholic fatty liver disease remains widely undiagnosed, yet early identification and treatment could mitigate long-term risk for CVD, according to a new American Heart Association scientific statement.
Nonalcoholic fatty liver disease (NAFLD) is believed to affect at least 25% of adults worldwide, according to the AHA. Unless specific testing is done to identify NAFLD, the condition is typically silent until advanced and potentially irreversible liver impairment occurs; hepatic complications include nonalcoholic steatohepatitis (NASH), hepatic cirrhosis and hepatocellular carcinoma. NAFLD is also a risk factor for atherosclerotic CVD, a leading cause of death in patients with the condition.
“Rates of NAFLD are increasing worldwide in association with rising rates of elevated BMI and the metabolic syndrome, but the condition is commonly undiagnosed,” P. Barton Duell, MD, FAHA, chair of the statement writing committee and professor of medicine in the Knight Cardiovascular Institute and division of endocrinology, diabetes and clinical nutrition at Oregon Health & Science University in Portland, told Healio. “This allows patients to experience progression of disease, leading to hepatic and CV complications. Avoidance of NAFLD risk factors in combination with early diagnosis and treatment for NAFLD may have the potential to mitigate long-term complications from NAFLD, including reducing the leading cause of death from NAFLD, which is CVD.”
As Healio previously reported, experts across eight professional specialties issued a joint “call to action” in 2021 on the dangers associated with NAFLD and NASH, calling on clinicians to work together across specialties and align treatment strategies. The new scientific statement, published in Arteriosclerosis, Thrombosis, and Vascular Biology, is the first from the AHA to specifically address NAFLD and highlight associations with ASCVD, diagnostic and screening strategies and potential interventions.
NAFLD and ASCVD risk
The statement notes NAFLD is an “underappreciated and independent risk factor” for ASCVD, even after adjustment for ASCVD risk factors. Subclinical CVD and other CV risk factors are increased among people with NAFLD or NASH and the severity of NAFLD is associated with higher prevalence of ASCVD risk factors such as diabetes and hypertension.
To manage risk, the authors cautioned that many patients with NAFLD have aminotransferase levels in the normal range, although frequently approaching the upper limit of normal.
“Liver biopsy is the gold standard for diagnosis of NAFLD and NASH, but the procedure is expensive and has increased risk of complications,” the researchers wrote. “Noninvasive diagnostic options such as vibration-controlled transient elastography (FibroScan) are available but are underused.”
Duell said the identification of normal liver enzyme levels does not exclude the diagnosis of NAFLD, a key reason many patients remain undiagnosed.
“Early diagnosis and treatment are necessary to improve the health of patients with established NAFLD, as well as preventing the development of NAFLD in patients who are at risk for the condition,” Duell told Healio. “Development of new, inexpensive, readily available screening tools would improve our success in identifying patients with NAFLD. Ongoing development of novel pharmacological agents will expand our options for treatment of NAFLD and NASH.”
Take-home messages for NAFLD
The statement outlines other important messages regarding NAFLD, NASH and CVD risk:
- Most patients with hepatic steatosis do not progress to develop NASH, cirrhosis or hepatocellular carcinoma, but a subgroup will. Imaging studies, in combination with liver biopsy, are essential for monitoring disease severity and progression.
- NAFLD occurs in association with insulin resistance, with or without diabetes, obesity (especially visceral adiposity), metabolic syndrome and dyslipidemia; genetic factors (monogenic or polygenic) modulate the risk for development of NAFLD and progression to NASH.
- NAFLD can be considered a risk enhancer when ASCVD risk is assessed in patients.
- Lifestyle intervention is the key therapeutic intervention for patients with NAFLD. Dietary modification, increased physical activity, weight loss and alcohol avoidance are strongly encouraged.
- GLP-1 receptor agonists may modestly improve NAFLD in association with improved glycemia, weight loss and reduced risk for major adverse CV events. Novel experimental drug therapies are in development, but most have modest efficacy, and toxicity has been a limiting factor for some agents.
“It is hoped that with increased awareness of NAFLD, better access to reliable imaging tools for screening and monitoring for NAFLD and proven tools for the treatment of NAFLD, the rising tide of NASH and more advanced hepatic disease can be reversed and adverse ASCVD outcomes prevented,” the researchers wrote.
Perspective
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Christos S. Mantzoros, MD, DSc, PhD
In this scientific statement, a panel of expert cardiologists introduced NAFLD to the CV community as a novel CV risk in the most emphatic manner — as a formal scientific statement. This initiative aims to not only increase awareness among practitioners but also summarize the evidence and stimulate translational research on the topic. This is not only timely but absolutely necessary. NAFLD is estimated to occur in more than 25% of individuals worldwide, with rates increasing all over the world in parallel with rising rates of obesity and the metabolic syndrome. NAFLD is closely associated with insulin resistance, obesity (especially visceral adiposity) and all the components of the metabolic syndrome. Most important, NAFLD is a strong contributor to and marker for increased CVD risk. Thus, NAFLD needs to be diagnosed and addressed appropriately, especially among persons already afflicted by CVD.
Importantly, the scientific statement presents an overview of helpful interventions, including dietary modification, physical activity, weight loss and the current status of pharmacotherapy and surgical procedures. This report deserves the utmost and undivided attention of the biomedical community since they have the potential to change how we think, diagnose and address NAFLD in CVD, with the ultimate goal of saving lives.
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