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Practical Clinical Care Pathway for Non-Alcoholic Fatty Liver Disease (NAFLD)
Kenneth Cusi MD, FACP, FACE, discusses the practical clinical care pathway for non-alcoholic fatty liver disease (NAFLD). He helps us understand the magnitude of the epidemic on NAFLD and what it means to primary care physicians and patients. He defines who is at risk, how to screen and when to refer to a liver specialist. Additionally, he examines what treatments are available today and what is coming in the drug development pipeline.
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Learn more about Kenneth Cusi, MD, FACP, FACE
Kenneth Cusi, MD, FACP, FACE
Dr. Kenneth Cusi serves as Chief of the Division of Endocrinology, Diabetes & Metabolism in the Department of Medicine at the University of Florida. He received his medical degree in Argentina from the University of Buenos Aires School of Medicine and is board certified in both Internal Medicine and Endocrinology, Diabetes & Metabolism.Learn more about Kenneth Cusi, MD, FACP, FACE
Transcription:
Announcer: The University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education, ACCME, to provide continuing medical education for physicians. The University of Florida College of Medicine designates this enduring material for a maximum of 0.25 AMA PRA Category 1 credit. Physicians should claim only the credit commensurate with the extent of their participation in this activity.
Melanie: Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole, and I invite you to listen as we discuss the practical clinical care pathway for non-alcoholic fatty liver disease. Joining me is Dr. Kenneth Cusi. He's the Chief of the Division of Endocrinology, Diabetes, and Metabolism in the Department of Medicine at the University of Florida College of Medicine and he practices at UF Health Shands Hospital.
Dr. Cusi, it's a pleasure to have you join us again. We've talked, you and I, before in previous podcasts about non-alcoholic fatty liver disease. Can you help us in this one to understand, as we get into this topic, the magnitude of the epidemic of NAFLD and what it means to primary care physicians and patients? What are we seeing in the trends now?
Dr. Kenneth Cusi: Well, Melanie, thank you for having me again. And as you said, endocrinologists are now facing a new problem, that is an accumulation of fat in the liver that can lead to cirrhosis. So to some extent, this is something that endocrinologists and primary care physicians have somehow overlooked because we didn't have the tools to identify it earlier. But recent studies suggest that this new epidemic related to the epidemics of obesity and type 2 diabetes can lead to a substantial number of adults developing cirrhosis. And it is soon to be the number one cause of liver transplantation. So there's been a lot of activity in the last year and lots of good things are happening that will help us in our clinic -- I'm an endocrinologist -- to identify these people. And it's exciting because there are many new drugs in development, so the clinical care pathway tries to support the work of clinicians in the trenches to do this better.
Melanie: Such an interesting topic and thank you for explaining that to us. So as this epidemic is growing, with the epidemic of obesity and type 2 diabetes, these things are all kind of happening at the same time. How important is early diagnosis and referral to prevent those future cirrhosis in millions of patients, as you just discussed? So help us to understand how fatty liver impacts the care of every patient that also has these co-morbidities of obesity and type 2 diabetes and cardiovascular disease and all the things that are going along with it.
Dr. Kenneth Cusi: Thanks, Melanie. The key thing is early diagnosis, just as you mentioned, and I'm going to tell you in a moment how we get to that early diagnosis. But just to emphasize, because I have many peers in the endocrinology field, sometimes I give talks to my friends in primary care. They are sometimes skeptical. I mean, I have not seen somebody with cirrhosis in my clinic lately. And what happens once they develop cirrhosis, they go just from the liver specialist to the hospital for an admission and back. I work, you know, at UF Health Shands Hospital. I see a lot of people with cirrhosis that have this from NASH. And I wished they would have been diagnosed earlier because there are things you can do.
So what I tell the clinicians is that seven out of 10 people with type 2 diabetes and a close number of those with obesity alone without diabetes have a fatty liver. And about half of them have a chronic inflammation that's going to lead them potentially to cirrhosis. Actually, we published a paper earlier this year in Diabetes Care, which is the official journal of the American Diabetes Association, that showed that about one in every five to six patients with type 2 diabetes have scarring of the liver, what we call fibrosis; and one in ten, it's almost either cirrhosis or pre-cirrhosis.
So answering your question, it's key to identify these people earlier. And that's where this pathway development together with friends in the gastroenterology field, from the American Gastroenterological Association, from primary care, key primary care organizations with the ADA, the Endocrine Society, and the American Association of Clinical Endocrinologists came together to make a simple and practical approach for the early diagnosis of people at risk.
Melanie: So important. So when do you feel it's important to refer to a liver specialist? And tell us a little bit about screening, whether patients that are suspected of being at intermediate or high risk may need liver imaging study. Tell us about that and the role and limitations of current diagnostics and screenings, Dr. Cusi.
Dr. Kenneth Cusi: Yeah. So typically, we've learned in medical school that you only have liver disease if your liver enzymes are elevated and the cutoff used in clinical labs is about 40, but that's a very high cutoff. We know now that if your alanine aminotransferase or ALT is greater than 19 in women or 30 in men, you probably have a problem. So we start by identifying patients at risk. Those with type 2 diabetes are at the highest risk followed by those with obesity and metabolic syndrome or anyone with already elevated liver enzymes. But in our studies and those of others, only a minority of people have elevated liver enzymes.
So we have to take a good history, get some routine labs, and there's a test called the fibrosis-4 index that is calculated based on your age, your liver enzymes, AST and ALT, and your platelet count. This is an equation that you can put on your phone or on your computer. It's on many websites. And that helps you stratify if your risk is high, intermediate or low. And then there's some imaging studies that I'll tell you in a moment that you can do in the clinic, or you can refer to be done in the same way that you order an ultrasound. The test is called elastography, and I'll tell you more in a moment. And that test can tell relatively well if you are near cirrhosis or you're free of that risk. So with those two steps that fit for an elastography, the most common device is called Fibroscan. There are others called shear wave. And I can tell to my friends in endocrinology that are listening or primary care, your hepatologist already has that Fibroscan to do the test and they've done it to their patients for the past 10 or 15 years from the hepatitis C field and now from NASH. They do it in the same way that they take the blood pressure of patients. So that's an easy test to do. And between the FIB-4 and Fibroscan test, you pretty much can tell how close or not to developing cirrhosis your patient is.
Melanie: So then tell us what's exciting in your field right now. What treatments are available? What's coming in the drug development pipeline? Tell us a little bit about what's going on that's really exciting for this condition.
Dr. Kenneth Cusi: Well, great. I was hoping you would ask me that because, in reality, it's a very exciting time. Number one, because we identified this, and again, if about 15% of patients have significant liver disease from NASH, that's four or five million people with type 2 diabetes, so there are things to do.
Number one, diet that reduces caloric intake and induces weight loss is going to improve the liver in proportion to the amount of weight loss. So the more weight loss, the better. Second, we are now learning that for people in whom the obesity is very significant, they might be candidates for bariatric surgery. It works for the liver disease in the same way it has worked to reduce cardiovascular risk and promote weight loss.
Second, that's the weight loss approach alone. There are some diabetes medications that have shown to work very well. Pioglitazone, which was marketed in the past or it's still available as Actos, is now a generic medication, which costs less than $5 a month. That generic medication starting at 15 and building up to 30 milligrams a day improves NASH and the inflammation in about two-thirds of the patients. And we published in March in the New England Journal of Medicine a new approach also based on a diabetes medication, which is a glucagon-like peptide-1 receptor agonist or GLP-1 receptor agonist with a study with semaglutide, that has been very exciting. And there are a number of new drugs too under the belt.
Melanie: Yeah, that's certainly an exciting time to be in your field, Dr. Cusi. And as you and I have talked before, diagnosis is important as many interventions are available, as you've just stated. So many different imaging modalities and tests and screenings, lifestyle modification, weight loss agents, all of these things are working. Can you explain how these modalities are just as important as many of those interventions and a multidisciplinary approach for these patients, why that is so important?
Dr. Kenneth Cusi: Thank you. It's very important to understand that about half of the people with diabetes and obesity could be low risk. So we need to focus on the lifetime intervention, always to promote weight loss but also, more than anything, prevent cardiovascular disease. So a typical mistake is discontinuing the statin. And that's why in the clinical care pathway, we have a very nice table. And again, this clinical care pathway has been published in gastroenterology a few weeks ago. And we want people also, not only to keep them on the statin, to reduce cardiovascular disease, but if they treat the diabetes to use these diabetes medications, pioglitazone and semaglutide, because that is what we see that has really worked very well.
Now, in people with higher risk, we're going to emphasize even more the importance of weight loss, and we're going to emphasize the role of medication. So again, semaglutide showed that about almost 60% of patients responded and what's more important is that the FDA approved in June a weight loss indication for semaglutide. The higher dose of 2.4 milligrams a week promotes weight loss in people without diabetes up to 15%, somewhat less in people with diabetes.
So these are important resources that the primary care and endocrinologists need to know. Treating obesity treats fatty liver. And pioglitazone, by reversing insulin resistance, removes fat out of the liver and has the same effect. So typically now what we're doing is combining both drugs to really help our people. And I have to say there are a lot of new drugs in the pipeline along these lines promoting weight loss. Just last week in the New England Journal of Medicine, lanifibranor, which is a PPAR gamma, alpha and delta, has also shown to improve fatty liver disease. So we're going to see a lot more going on in 2022. And my friends understand that the early diagnosis is something that can be done today in your clinic. And there are things that you can do to prevent progression to cirrhosis in your patients with NASH.
Melanie: What an informative episode and a great educator you are, Dr. Cusi. Thank you so much for joining us. And to refer your patient or to listen to more podcasts from our experts, please visit ufhealth.org/medmatters.
That concludes today's episode of UF Health MedEd Cast with UF Health Shands Hospital. Please always remember to subscribe, rate and review this podcast and all the other UF Health Shands Hospital podcasts. I'm Melanie Cole.
Announcer: The University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education, ACCME, to provide continuing medical education for physicians. The University of Florida College of Medicine designates this enduring material for a maximum of 0.25 AMA PRA Category 1 credit. Physicians should claim only the credit commensurate with the extent of their participation in this activity.
Melanie: Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole, and I invite you to listen as we discuss the practical clinical care pathway for non-alcoholic fatty liver disease. Joining me is Dr. Kenneth Cusi. He's the Chief of the Division of Endocrinology, Diabetes, and Metabolism in the Department of Medicine at the University of Florida College of Medicine and he practices at UF Health Shands Hospital.
Dr. Cusi, it's a pleasure to have you join us again. We've talked, you and I, before in previous podcasts about non-alcoholic fatty liver disease. Can you help us in this one to understand, as we get into this topic, the magnitude of the epidemic of NAFLD and what it means to primary care physicians and patients? What are we seeing in the trends now?
Dr. Kenneth Cusi: Well, Melanie, thank you for having me again. And as you said, endocrinologists are now facing a new problem, that is an accumulation of fat in the liver that can lead to cirrhosis. So to some extent, this is something that endocrinologists and primary care physicians have somehow overlooked because we didn't have the tools to identify it earlier. But recent studies suggest that this new epidemic related to the epidemics of obesity and type 2 diabetes can lead to a substantial number of adults developing cirrhosis. And it is soon to be the number one cause of liver transplantation. So there's been a lot of activity in the last year and lots of good things are happening that will help us in our clinic -- I'm an endocrinologist -- to identify these people. And it's exciting because there are many new drugs in development, so the clinical care pathway tries to support the work of clinicians in the trenches to do this better.
Melanie: Such an interesting topic and thank you for explaining that to us. So as this epidemic is growing, with the epidemic of obesity and type 2 diabetes, these things are all kind of happening at the same time. How important is early diagnosis and referral to prevent those future cirrhosis in millions of patients, as you just discussed? So help us to understand how fatty liver impacts the care of every patient that also has these co-morbidities of obesity and type 2 diabetes and cardiovascular disease and all the things that are going along with it.
Dr. Kenneth Cusi: Thanks, Melanie. The key thing is early diagnosis, just as you mentioned, and I'm going to tell you in a moment how we get to that early diagnosis. But just to emphasize, because I have many peers in the endocrinology field, sometimes I give talks to my friends in primary care. They are sometimes skeptical. I mean, I have not seen somebody with cirrhosis in my clinic lately. And what happens once they develop cirrhosis, they go just from the liver specialist to the hospital for an admission and back. I work, you know, at UF Health Shands Hospital. I see a lot of people with cirrhosis that have this from NASH. And I wished they would have been diagnosed earlier because there are things you can do.
So what I tell the clinicians is that seven out of 10 people with type 2 diabetes and a close number of those with obesity alone without diabetes have a fatty liver. And about half of them have a chronic inflammation that's going to lead them potentially to cirrhosis. Actually, we published a paper earlier this year in Diabetes Care, which is the official journal of the American Diabetes Association, that showed that about one in every five to six patients with type 2 diabetes have scarring of the liver, what we call fibrosis; and one in ten, it's almost either cirrhosis or pre-cirrhosis.
So answering your question, it's key to identify these people earlier. And that's where this pathway development together with friends in the gastroenterology field, from the American Gastroenterological Association, from primary care, key primary care organizations with the ADA, the Endocrine Society, and the American Association of Clinical Endocrinologists came together to make a simple and practical approach for the early diagnosis of people at risk.
Melanie: So important. So when do you feel it's important to refer to a liver specialist? And tell us a little bit about screening, whether patients that are suspected of being at intermediate or high risk may need liver imaging study. Tell us about that and the role and limitations of current diagnostics and screenings, Dr. Cusi.
Dr. Kenneth Cusi: Yeah. So typically, we've learned in medical school that you only have liver disease if your liver enzymes are elevated and the cutoff used in clinical labs is about 40, but that's a very high cutoff. We know now that if your alanine aminotransferase or ALT is greater than 19 in women or 30 in men, you probably have a problem. So we start by identifying patients at risk. Those with type 2 diabetes are at the highest risk followed by those with obesity and metabolic syndrome or anyone with already elevated liver enzymes. But in our studies and those of others, only a minority of people have elevated liver enzymes.
So we have to take a good history, get some routine labs, and there's a test called the fibrosis-4 index that is calculated based on your age, your liver enzymes, AST and ALT, and your platelet count. This is an equation that you can put on your phone or on your computer. It's on many websites. And that helps you stratify if your risk is high, intermediate or low. And then there's some imaging studies that I'll tell you in a moment that you can do in the clinic, or you can refer to be done in the same way that you order an ultrasound. The test is called elastography, and I'll tell you more in a moment. And that test can tell relatively well if you are near cirrhosis or you're free of that risk. So with those two steps that fit for an elastography, the most common device is called Fibroscan. There are others called shear wave. And I can tell to my friends in endocrinology that are listening or primary care, your hepatologist already has that Fibroscan to do the test and they've done it to their patients for the past 10 or 15 years from the hepatitis C field and now from NASH. They do it in the same way that they take the blood pressure of patients. So that's an easy test to do. And between the FIB-4 and Fibroscan test, you pretty much can tell how close or not to developing cirrhosis your patient is.
Melanie: So then tell us what's exciting in your field right now. What treatments are available? What's coming in the drug development pipeline? Tell us a little bit about what's going on that's really exciting for this condition.
Dr. Kenneth Cusi: Well, great. I was hoping you would ask me that because, in reality, it's a very exciting time. Number one, because we identified this, and again, if about 15% of patients have significant liver disease from NASH, that's four or five million people with type 2 diabetes, so there are things to do.
Number one, diet that reduces caloric intake and induces weight loss is going to improve the liver in proportion to the amount of weight loss. So the more weight loss, the better. Second, we are now learning that for people in whom the obesity is very significant, they might be candidates for bariatric surgery. It works for the liver disease in the same way it has worked to reduce cardiovascular risk and promote weight loss.
Second, that's the weight loss approach alone. There are some diabetes medications that have shown to work very well. Pioglitazone, which was marketed in the past or it's still available as Actos, is now a generic medication, which costs less than $5 a month. That generic medication starting at 15 and building up to 30 milligrams a day improves NASH and the inflammation in about two-thirds of the patients. And we published in March in the New England Journal of Medicine a new approach also based on a diabetes medication, which is a glucagon-like peptide-1 receptor agonist or GLP-1 receptor agonist with a study with semaglutide, that has been very exciting. And there are a number of new drugs too under the belt.
Melanie: Yeah, that's certainly an exciting time to be in your field, Dr. Cusi. And as you and I have talked before, diagnosis is important as many interventions are available, as you've just stated. So many different imaging modalities and tests and screenings, lifestyle modification, weight loss agents, all of these things are working. Can you explain how these modalities are just as important as many of those interventions and a multidisciplinary approach for these patients, why that is so important?
Dr. Kenneth Cusi: Thank you. It's very important to understand that about half of the people with diabetes and obesity could be low risk. So we need to focus on the lifetime intervention, always to promote weight loss but also, more than anything, prevent cardiovascular disease. So a typical mistake is discontinuing the statin. And that's why in the clinical care pathway, we have a very nice table. And again, this clinical care pathway has been published in gastroenterology a few weeks ago. And we want people also, not only to keep them on the statin, to reduce cardiovascular disease, but if they treat the diabetes to use these diabetes medications, pioglitazone and semaglutide, because that is what we see that has really worked very well.
Now, in people with higher risk, we're going to emphasize even more the importance of weight loss, and we're going to emphasize the role of medication. So again, semaglutide showed that about almost 60% of patients responded and what's more important is that the FDA approved in June a weight loss indication for semaglutide. The higher dose of 2.4 milligrams a week promotes weight loss in people without diabetes up to 15%, somewhat less in people with diabetes.
So these are important resources that the primary care and endocrinologists need to know. Treating obesity treats fatty liver. And pioglitazone, by reversing insulin resistance, removes fat out of the liver and has the same effect. So typically now what we're doing is combining both drugs to really help our people. And I have to say there are a lot of new drugs in the pipeline along these lines promoting weight loss. Just last week in the New England Journal of Medicine, lanifibranor, which is a PPAR gamma, alpha and delta, has also shown to improve fatty liver disease. So we're going to see a lot more going on in 2022. And my friends understand that the early diagnosis is something that can be done today in your clinic. And there are things that you can do to prevent progression to cirrhosis in your patients with NASH.
Melanie: What an informative episode and a great educator you are, Dr. Cusi. Thank you so much for joining us. And to refer your patient or to listen to more podcasts from our experts, please visit ufhealth.org/medmatters.
That concludes today's episode of UF Health MedEd Cast with UF Health Shands Hospital. Please always remember to subscribe, rate and review this podcast and all the other UF Health Shands Hospital podcasts. I'm Melanie Cole.