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Understanding Nonalcoholic Fatty Liver Disease (NAFLD)

Sep 28, 2022

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. 

 

Carlessi R, Köhn-Gaone J, Olynyk JK, et al. Mouse Models of Hepatocellular Carcinoma. In: Tirnitz-Parker JEE, editor. Hepatocellular Carcinoma [Internet]. Brisbane (AU): Codon Publications; 2019 Oct 24.

NASH is 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.

The 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:

  • Obesity
  • 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 1.87-fold

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.

 

References:

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  1. Oct 27, 2022

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