Neil Skolnik, MD
I’m Dr Neil Skolnik. Today, we are going to talk about two guidelines: the American Association for the Study of Liver Diseases (AASLD) clinical assessment and management of nonalcoholic fatty liver disease (NAFLD) and the American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings, co-sponsored by AASLD.
Very few things do we see more and notice less than NAFLD.
NAFLD is present in over one quarter of the population in general and in over half of individuals with type 2 diabetes, and it doesn’t exist in isolation. The relation between NAFLD and metabolic syndrome, including obesity and diabetes, is bidirectional: Each makes the other worse.
Let’s clarify terminology. NAFLD refers to all grades of fatty liver disease, defined as more than 5% of hepatocytes having microvesicular steatosis when no other cause is identified. What really concerns us is when fatty infiltration of the liver leads to inflammation of the liver. Then it is called nonalcoholic steatohepatitis (NASH). This occurs in about one out of six people with NAFLD, with a higher proportion in people with type 2 diabetes. When NASH progresses to high-grade fibrosis, defined as stage 2 or higher fibrosis, rate and risk for progression to cirrhosis and liver failure are increased.
The algorithm for the evaluation of NAFLD is essentially constructed to identify those patients who are unlikely to have clinically significant fibrosis so that those people can be confidently given lifestyle interventions and follow-up without a need for further referral. Individuals who are at higher risk can then receive further evaluation.
NAFLD is usually found incidentally on ultrasound that is done for some other reason, as part of the evaluation of abnormal liver function tests, or as a part of targeted screening. Targeted screening can be considered for people at increased risk for NAFLD, such as those with type 2 diabetes or obesity with metabolic complications. Screening is best done using a validated NAFLD risk calculator, such as the FIB-4, which I’ll discuss shortly.
So how should we approach NAFLD? First, other etiologies of liver disease need to be reasonably ruled out. The extent of the evaluation that is needed is a matter of clinical judgement and is not directly addressed in the guidelines. Here’s my opinion. Ask about alcohol use and check hepatitis serologies as well as a ferritin level and a celiac disease panel. Additional testing such as antinuclear antibody, anti–smooth muscle antibody, alpha-1 antitrypsin, ceruloplasmin, microsomal antibody, and protein electrophoresis may or may not be indicated.
Patients who are at high risk for NAFLD based on metabolic risk factors or when fatty infiltration of the liver is incidentally identified by imaging should undergo primary risk assessment with a validated NAFLD risk calculator. The best validated and most frequently used risk calculator is the FIB-4. The FIB-4 score is calculated using a simple algorithm where you input the patient’s age, alanine transaminase and aspartate transaminase levels, and platelet count. Patients with a FIB-4 score < 1.3 are unlikely to have advanced fibrosis. They can receive lifestyle advice and periodic reassessment.
If the FIB-4 score is in an intermediate range, > 1.3 up to 2.67, then secondary risk assessment should be performed. This is most commonly done by ordering vibration-controlled elastography (VCTE), also known as the FibroScan. VCTE measures liver stiffness, and liver stiffness worsens with increasing severity of liver fibrosis. If the VCTE is < 8, then the likelihood of advanced fibrosis is low, and the patient can be periodically reassessed in the primary care office. If the elastography score is > 8, or if the liver function tests are persistently elevated, then the guidelines recommend referral to a gastroenterologist for further evaluation.
Let’s now talk about treatment, which can be divided into three parts: lifestyle, medication, and bariatric surgery. A healthy diet and exercise are important. Though any weight loss is good, 10% or more weight loss is needed to improve inflammation and fibrosis. It’s worth noting, with regard to diet, that high fructose consumption increases the risk for advanced fibrosis independent of calorie intake. Exercise is critically important, as some studies show it can prevent or improve NASH, independent from its effect on weight.
Currently there are no FDA-approved medications for NASH, but there are medications approved for other indications that have evidence of benefit for NASH. These include vitamin E 800 IU daily, pioglitazone, and the glucagon-like peptide 1 (GLP-1) receptor agonists, with the best evidence existing for semaglutide. The dual GLP-1–gastric inhibitory peptide agonist tirzepatide has demonstrated average weight loss of more than 20% and a reduction of liver fat, suggesting that it might benefit NASH, with more trials to come. Finally, bariatric surgery can resolve NASH and improve hepatic fibrosis.
If the patient has type 2 diabetes and NASH, we should preferentially select either pioglitazone or a GLP-1 for their diabetes because there is evidence that this helps NASH as well.
This is a new and confusing area for a lot of us, so here is a SmartPhrase that you can copy, adapt, and use in your EHR:
Nonalcoholic fatty liver disease (NAFLD) occurs when more than 5% of the liver is taken up by fat. A subset of NAFLD, nonalcoholic steatohepatitis (NASH), occurs when there is also inflammation in the liver. Test first with a risk-calculator (FIB-4), and then if needed, vibration-controlled elastography (VCTE) is done to check for advanced fibrosis. A FIB-4 score < 1.3 or a VCTE < 8.0 means that advanced fibrosis is unlikely.
The foundation of treatment is diet and exercise. Weight loss of more than 10% is often needed to improve inflammation and fibrosis. Excessive sugar increases the risk for fatty liver and advanced fibrosis, independent of calorie intake. Although no medicines are FDA-approved for NASH, there is evidence that vitamin E 800 IU daily, pioglitazone, or a glucagon-like peptide 1 (GLP-1) receptor agonist may improve NASH.
I’m interested in your thoughts about the topic and whether sharing SmartPhrases in this column may be useful. Please leave your comments in the comments section.
I’m Neil Skolnik, and this is Medscape.
Resources:
Fib-4 Index for Liver Fibrosis at MD Calc
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