By Nathan Painter, PharmD, CDCES, FADCES, FCPhA, FCCP
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of diseases ranging from hepatic steatosis to nonalcoholic steatohepatitis (NASH) to advanced fibrosis and cirrhosis and to liver cancer. Despite the significant morbidity associated with NAFLD, there are no guidelines to screen patients considered high risk, including patients older than 50 years with type 2 diabetes or metabolic syndrome.
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quickly emerging as one of the most common reasons for both liver cirrhosis and
liver transplant in the United States and may soon overtake hepatitis C infection
as the predominant etiology. It is estimated that more than 25% of the world’s
adult population has some degree of NAFLD, the vast majority of which is
undiagnosed and asymptomatic. Currently, there are no FDA-approved
medications to treat these disorders.
pathogenesis of NAFLD and its transition to NASH involves alterations in
nutrient metabolism, hormonal deregulation, onset of inflammation in multiple
organ systems, amount of fat, and degree of insulin resistance. Sound familiar?
It should, because many of these issues are also seen in persons with type 2
diabetes. Risk factors will also look
familiar and include:
- Type 2 diabetes
- Family history of type 2 diabetes
- Metabolic syndrome
- Risk of
NAFLD increases with increasing number of metabolic syndrome components
- Genetic predisposition
- Hispanic ethnicity
NAFLD is the hepatic component of the
metabolic syndrome, with insulin resistance being the common pathophysiological
mechanism. In people with type 2 diabetes:
- Prevalence of NAFLD is more than 2-fold higher
than in the general population
- NAFLD is associated with ~70% higher overall
mortality than in the general population
- The overall prevalence of NAFLD is 55.5%
- Of the people who undergo liver biopsy, 17%
have advanced fibrosis
- Risk of cardiovascular events is increased by
Who should be
screened for NAFLD?
Patients with obesity or metabolic syndrome should be
routinely screened with liver enzymes and/or ultrasound. High-risk patients
(age >50 years, type 2 diabetes, or metabolic syndrome) should be assessed
for more advanced disease. Patients with persistently elevated liver enzymes
should be screened for NAFLD.
Although there are a number of medications in
the research and development pipeline to treat NAFLD and NASH, none are FDA-approved. A
variety of medications and natural products have published data but the
evidence is insufficiently rigorous and sometimes conflicting. There
are a few randomized controlled trials. Vitamin E in daily doses of
800 international units was shown to improve NASH in people without
diabetes. There is growing body of evidence that glucagon-like
peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, and
pioglitazone can improve the cardiometabolic profile and reverse
steatosis. Both liraglutide and semaglutide have been studied for
the treatment of NASH. Although the sample sizes have been
relatively small, results were promising, with improved steatosis and
fibrosis. These improvements appear to correlate with the magnitude
of weight loss.
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