Fatty Liver: Managing a Silent Epidemic in Primary Care

Jay H. Shubrook, DO


September 30, 2021

This transcript has been edited for clarity.

Hi. I'm Jay Shubrook, a professor in the primary care department and a primary care diabetologist at the University of California. I'm really excited to share with Medscape Primary Care a new clinical care pathway for the screening, diagnosis, and treatment of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).

So why are we talking about NAFLD and NASH?

We know that NAFLD is a silent disease and it is incredibly common. It affects 28% of the global population, more than 60% of those with type 2 diabetes. There is a positive and reciprocal relationship between fatty liver disease and diabetes. And most importantly, think of fatty liver disease as a risk factor for cardiovascular disease, because it doubles that risk. Now we have good evidence that fatty liver disease actually doubles a person's risk for cardiovascular disease.

Until recently we lacked comprehensive or consistent guidance on this condition, needed in both specialty and primary care settings. I'm happy to announce that we now have that available.

The American Gastroenterology Association worked with seven organizations comprising 32 experts around the world on Preparing for the NASH Epidemic: A Call to Action.

  • American Academy of Family Physicians

  • American Association of Clinical Endocrinology

  • American Association for the Study of Liver Diseases

  • American College of Osteopathic Family Physicians

  • American Diabetes Association

  • Endocrine Society

  • The Obesity Society

This group worked very hard to come to a consensus on screening, evaluation, and treatment. I'm going to highlight the new Clinical Care Pathway for the Risk Stratification and Management of Patients with Nonalcoholic Fatty Liver Disease which is intended to be a roadmap for busy clinicians to address this very common condition.

Screening for advanced fibrosis.

Who and How to Screen

First, we need to know who to screen. In the wheelhouse of primary care, gastroenterology, endocrinology, obesity clinics, and cardiologists all need to be looking for fatty liver disease. We have some recommendations for who is at high risk.

All patients with type 2 diabetes should be screened, along with anyone who has two or more components of the metabolic syndrome. Other patients might come from the incidental finding of steatosis on an imaging test, or elevated transaminases. All three of these groups should be screened.


One of the first and most important things to do is a history and physical. Make sure there isn't excessive alcohol intake. We can then do a very simple, noninvasive, and inexpensive screening test that helps in determining whether the patient needs further evaluation. With a CBC, patient's age, and transaminase levels, you can calculate a FIB-4 score. It is available on many medical calculators, so it's easily accessed.


If the FIB-4 score is < 1.3, the patient is at low risk for progression to advanced cirrhosis and fibrosis and probably does not need to be referred to another clinical team. Conversely, if the FIB-4 score is > 2.67, that patient is at very high risk for advancing to bridging fibrosis and cirrhosis. These patients should have a direct referral to hepatology. The FIB-4 easily differentiates who needs immediate specialty referral.

Liver Stiffness

Patients with FIB-4 scores between 1.3 and 2.6 are at indeterminate risk. To help sort them out, these patients need further testing with a liver stiffness measurement. We can then see whether there are structural changes in the liver. It used to be that everyone had to have a biopsy, but this allows us to send fewer patients for biopsy. The FibroScan is one of the best ways to test for liver stiffness and it is widely available, although not everywhere. If you don't have access to the FibroScan, work with your gastroenterologist or hepatologist to get that testing done.

If liver stiffness is low, they fall back on the right side in the low-risk category. If high, they fall into indeterminate or high risk and probably need to have an evaluation by a specialist.

It's important to remember that many patients come through with elevated transaminases or with steatosis noted on imaging. Those patients may have fatty liver disease or they might have other conditions. Make sure you take a good history to ensure that they don't have excessive alcohol intake or a risk for or history of hepatitis B or C. If indicated, consider the possibility of autoimmune or metabolic liver disease. If those things are not present and testing is negative, you go back to the original low-risk pathway. If those things are present and testing is positive, then you probably need referral to a specialist.

Role of the Primary Care Clinician

Finally, how do we treat? I want to focus first on the things that apply to all three groups.


Everyone should have lifestyle intervention focused on weight loss. Even small amounts of weight loss can have substantial benefits, not only in the progression of fatty liver disease but also for cardiovascular risk, which is the most common cause of death in people with fatty liver disease. So don't forget lifestyle intervention, including increased physical activity, structured weight loss programs, and if needed, weight loss medications or weight loss surgery.

The left-hand column is patients who are at low risk for progression to advanced fibrosis or cirrhosis. They are typically managed n the primary care setting. No special treatment is needed except for treatment of obesity and to continue to work on cardiovascular risk reduction. If they have diabetes, you will do whatever you normally do for those patients.

If your patient is at indeterminate risk, you may want to engage a structured lifestyle program, cardiovascular risk reduction, and more intensive weight loss methods, including metabolic surgery. Patients with diabetes might have indications for certain medications. I want to highlight that nothing is FDA-approved to date for the treatment of NASH or NADLD. But in studies, among people who don't have diabetes, vitamin E has been shown to be helpful. In patients with diabetes, pioglitazone and the GLP-1 receptor agonists (with most of the data reported on semaglutide) have been shown to help reduce progression in people at risk.

For patients in the high-risk group, you will be working hand in hand with a hepatologist or gastroenterologist. Your role remains the same: focusing on lifestyle intervention. You may be prescribing additional pharmacotherapy for type 2 diabetes. In addition to standard of care for high-risk patients, there are a number of novel agents coming that will be helpful in the treatment of NASH, so getting your patients into hepatology treatment circles will give them access to the newest treatments.

There aren't enough hepatologists to treat everyone, so we hope that this guidance will help determine who you can manage in the primary care setting, who needs further testing, and who should be seen immediately by a hepatologist.

If you want more information, Preparing for the NASH Epidemic: A Call to Action was published simultaneously this year in Gastroenterology, Diabetes Care, Metabolism, and Obesity. Today, the "Primary Care Clinical Pathway for the Risk Stratification and Management of Patients with Fatty Liver Disease" is being published in Gastroenterology. We believe this is going to help the clinicians with boots on the ground managing their patients with fatty liver disease.

We also have assembled numerous resources for you. Visit nash.gastro.org for more information and tools, including the needs assessment that helped us create this work group, the proceedings from the conference with 32 specialists, the Call to Action paper, the clinical pathway, and podcasts. Soon we will also offer an app that will make it simple to work through this clinical pathway.

I hope this was useful for you, and we now have something we can do about a very common and serious — and silent — condition that we see every day.

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