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Melanie Cole, MS (Host): UAB Medcast is an ongoing medical education podcast. The UAB division of continuing education designates that each episode of this enduring material is worth a maximum of .25 AMA PRA Category 1 credit. To collect credit, please visit uabmedicine.org/medcast and complete the episode’s post-test.

Welcome. Today we’re talking about nutrition in non-alcoholic fatty liver disease. My guest is Dr. Meagan Gray. She’s a hepatologist and an assistant professor at UAB Medicine. Dr. Gray, I'm glad to have you joining us today. Tell us about the current state of non-alcoholic fatty liver disease. What’s the prevalence or the burden of this disease?

Meagan Gray, MD (Guest): Well, thank you so much for having me. So non-alcoholic fatty liver disease is very common, much more common than we originally knew. So it’s currently the most common cause of chronic liver disease worldwide, and it effects about 30% of the United States population. We know that it’s also become the most common cause of chronic liver disease in children. So it does vary based on ethnicity. We know that Hispanics are at the highest likelihood of having non-alcoholic fatty liver disease at about 45%, Caucasians about 33%, and African Americans at about 24%. We know that this disease is more common in patients who have diabetes, up to 40 to 70% of patients with diabetes can have this disease. It’s certainly becoming the most common indication for liver transplantation. It’s currently number two. Right behind hepatitis C, but not far behind. Then it’s the third most common cause of hepatocellular carcinoma or liver cancer in the United States.

Host: Wow. Those are some incredible statistics, Dr. Gray. Do we know the etiology? Is there a close association with the epidemic of obesity? Tell us a little bit about the cause.

Dr. Gray: Absolutely. So with the rise of non-alcoholic fatty liver disease parallel with the rise in obesity and type 2 diabetes, high blood pressure, high cholesterol, all of these features of metabolic syndrome that are becoming much more common in the western world, especially the United States. So we know that for the most part, all of these diseases are related to what we eat in our diets. Certainly, there’s a lot of fast foods and processed foods, saturated fats, sugars. All of these things that not only cause these other features of metabolic syndrome but are also now being shown to cause non-alcoholic fatty liver disease as well.

Host: What’s unique about the metabolism with a person with this disease? How do they metabolize cholesterol, for example?

Dr. Gray: So the non-alcoholic fatty liver disease really is a surplus of free fatty acids in the body. So there’s three different ways that the liver gets free fatty acids. So 60% of the free fatty acids come from the systemic circulation. So this is from the adipose tissue. Then 15% come from the portal blood, this is what patients are eating in their diet. Then about 25% are actually made from the liver itself called lipogenesis. So in patients who are overweight, they have extra adipose tissue. So this is the main source of lipids that accumulate in patients who have fatty liver disease. Adipose tissue in these patients makes up about 80% of the free fatty acids. So these patients also often have insulin resistance or diabetes. So that adipose tissue is not able to store fat properly. So that extra adipose tissue, it spills out as these free fatty acids into the circulation, and then that goes to the liver to be processed. Because the liver can only handle so much free fatty acid, it stores as much as it can into triglycerides, and that’s where we see the hepatic fat.

Host: Dr. Gray, let’s talk about diagnosis for a minute. Why do you think it’s largely undiagnosed or unaddressed until it progresses to a more advanced stage? Tell us a little bit about what clinical history findings are characteristic of fatty liver disease. How do you find it?

Dr. Gray: You know, it can be a stealth diagnosis. So that’s why I think it’s often missed. So patients often don’t have any symptoms when they have non-alcoholic fatty liver disease. We know that most patients will have abnormal liver tests, that’s often how it’s picked up on their annual exams with their primary care physician. About 10 to 20% of patients have completely normal liver tests, and so that makes it even harder to diagnose. So in those patients it may be found because potentially they were having some pain and they got an imaging test for a different reason that picked it up incidentally. Or, potentially, their provider—if they had diabetes and had high risk—potentially their doctor was screening them for it. Because patients often don’t have any symptoms, it becomes more challenging to get to the right diagnosis.

Host: Dr. Gray, one of the interesting things that when I'm researching for these shows is because we’re going to be talking about nutrition and the standard therapies that are available right now. Because that’s what’s involved, can it be used as an early marker of coronary heart disease? Is there any correlation there?

Dr. Gray: Yes. Absolutely. That’s a great question. So just like metabolic syndrome, the diabetes, the high blood pressure, the cholesterol increases the risk for cardiovascular disease. Non-alcoholic fatty liver disease is also a similar marker. Actually, in patients who do have non-alcoholic fatty liver disease, the most common cause of death in these patients is actually cardiovascular disease independent of their other metabolic co-morbidities.

Host: What an interesting way that this all goes together. So let’s talk about treatment therapies. What are the standard therapies that you would use once you determine what’s going on?

Dr. Gray: So right now we don’t have any FDA approved medications for non-alcoholic fatty liver disease. Although, there are many in clinical trials. So right now the current mainstay of therapy is weight loss. So we know that if patients can lose more than 10% of their total body weight that they can significantly improve the fat in the liver as well as any fibrosus or scarring that has started to develop. So this is what we focus on most with these patients. Even if they're able to lose about 5% of their body weight, the liver disease can stabilize, and they may even have some improvement in their fibrosus. So that’s really where we start when we’re talking about making lifestyle changes is that the goal is to get them to at least 5 to 10% weight loss.

Host: How do you do that? Tell us about the providers that would be involved because, obviously, losing weight is very difficult for some people. How is that accomplished?

Dr. Gray: Absolutely. So, you know, I think you're exactly right. As providers, we do have a few minutes to spend with patients and get a small assessment of what their diet contains, but you're right. We are limited in our time that we have to counsel them on dietary factors or things that they could improve in their diet. So it’s extremely helpful if you can have a dietician spend time with the patients as well. So at UAB, we have just opened up a new non-alcoholic fatty liver disease clinic. In this clinic, not only do these patients see me, but they also see a registered dietician who can spend a little bit more time going through their diet. And can help them learn how to use tracking programs like MyFitnessPal and also making suggestions and things that they could improve in their diet that would have significant benefit.

Host: What do you see happening in the future, Dr. Gray, with this? As you and I were speaking a little off the air, there’s no FDA approved medicational therapies yet. Correct?

Dr. Gray: That is correct. There are many medications in clinical trials. So I do think over the next several years we will have several different options. But I still think, and what I counsel my patients, is the diet is the most important part. So if they can lose the weight and they can change the way that they're eating, then they can not only get rid of their fatty liver disease, but they may also be able to have significant improvement in their diabetes, their high blood pressure, their high cholesterol, and their risk for cardiovascular disease. So that treatment option is always going to be my favorite because that takes care of the whole picture as opposed to adding on one more medication on their list of 10 to 15 that they're already taking.

Host: Then wrap it up for us. What would you like other providers to know about non-alcoholic fatty liver disease and those standard therapies of weight loss and nutrition, and how important it is that providers refer when they feel that it’s really important?

Dr. Gray: Yeah. So to wrap it up I really wanted to spend a few minutes talking about the nutritional aspects and sort of targeted nutrition advice that I give my patients when I see them in the clinic for non-alcoholic fatty liver disease. So there’s three main components that we go through. So one is fat. So saturated fat is a major cause of fat in the liver. So I specifically talk to them about foods that are high in saturated fat. So these include beef, pork, lamb, processed meats, as well as full-fat dairy products like butter, cream, full-fat milk, cheese. Then some ethnicities use ghee and lard as well.

So we know that when you eat a diet that’s high in saturated fat, it actually increases the adipose tissues lipolysis. So it’s breaking down more of that adipose tissue and releasing free fatty acids into the circulation, which then come into the liver to cause hepatic steatosis. So we know that if you can eliminate that saturated fat from the diet that a lot of that can resolve. So the types of fats that are healthier for these patients to eat are seeds, nuts, avocados, olive oil, unsaturated fats that can be found more in plant products.

Then next I talk to them about sugar. So sugar is, unfortunately, added to so many things that we eat and drink as part of processing. There was actually a recent study showing that about 17% of daily calories in U.S. children and adolescents comes from pure sugar, which is such a huge part of the diet that is unnecessary. So when you eat excess sugar in the diet, this actually increases the de novo lipogenesis, or the liver’s production of fat, and that then increases the lipid content in the liver. So I specifically talk to them about removing sweet tea, full sugar soda, candy, cakes, cookies. Then also refined carbohydrates like white rice, white bread, tortillas. These things are all processed very similarly to sugar in the body.

Then I also talk with them about protein. So we are a little bit protein obsessed in the United States and patients tend to eat much more protein than is actually what is required for their body. There was a study showing that comparing patients with non-alcoholic fatty liver disease to normal healthy controls, that the patients who had the non-alcoholic fatty liver disease actually consumed about 30% more meat than the healthy controls. There’s also been several other studies associating animal product intake with non-alcoholic fatty liver disease.

We know that diets that are high in bread and processed meat significantly increase your mortality, specifically from chronic liver disease as well as cancer and cardiovascular mortality. There’s several reasons that this happens, but some of the theories are that the heme iron that is in the red meat promotes oxidative damage as well as inflammation. Then some of the nitrates and nitrites that are found in processed food can worsen insulin resistance as well as diabetes, cardiovascular disease, and cancer. We actually know that processed meat is classified as carcinogenic by the World Health Organization, meaning that we know it causes cancer. So really it should be reduced or eliminated from the diet.

There’s also some newer studies that are looking into trimethylamine oxide, which is produced when gut bacteria digests choline, lecithin, and carnitine, which are all nutrients that are abundant in animal products, specifically red meat. A recent study out of the Cleveland clinic correlated theorem trimethylamine oxide levels to predict future heart attacks, strokes, as well as death. So we know that the animal products that are high in saturated fats as well as the processed sugars and refined carbohydrates, all of these things have a role to play when it comes to insulin resistance and hepatic steatosis.

So then I specifically talk to them about a couple of different diet options. So one is a plant based diet. So we know that the higher you can adhere to a plant based diet, the less likelihood that you're going to develop fatty liver disease. This came out of a large national health and nutrition examination survey database. So plant based diets are rich in fruits and vegetables, beans, nuts, whole grains, legumes, and are rich in antioxidants and anti-inflammatory phytochemicals, which can reduce oxidative stress and protect against different types of free radicals.

Patients who still do want to consume some animal products, a Mediterranean diet still has significant benefits. So this is very similar to a plant based diet, but also includes lean meats like chicken and fish as well as low fat dairy. So there was a recent study published in 2018 looking at a Mediterranean for non-alcoholic fatty liver disease, and patients did have significant improvement not only in their liver fat, but also in metabolic risk factors after only three months on this diet. So I usually talk with patients about both of those diet options, and then we work together to figure out what’s going to work best for them.

Host: Thank you so much for joining us, Dr. Gray. What an interesting topic. A community physician can refer a patient to UAB Medicine by calling the MIST line at 1-800-UAB-MIST. That’s 1-800-822-6478. You're listening to UAB Medcast. For more information on resources available at UAB Medicine, please visit uabmedicine.org/physician. This is Melanie Cole.