Recognizing the Clues: Keys to Identifying Fatty Liver Disease In Primary Care

[00:00:07] Neeraj Mistry, MD: Hello everyone. And welcome to episode three of Unlocking the Fatty Liver Mistry. I'm Dr. Neeraj Mistry and I'm the Chief Medical Officer of the Fatty Liver Foundation. for episode three, we will be covering a clinical approach to a patient with a steatotic liver disease. And this is primarily aimed at the primary care level, where patients would come into a doctor's office. Based on our survey that we did at the Fatty Liver Foundation, we found that most people got their diagnosis of fatty liver disease at the primary care level, where there was a suspicion of the disease. So today, we're actually delighted to have Dr. Rinella, who is an expert in the field. You know, very often when we talk about experts in the field, we say this person wrote the book about a particular issue, and this is true in this case where Dr. Rinella actually wrote the practice guidance for steatotic liver disease and nonalcoholic fatty liver disease. In terms of background, Dr. Rinella is the professor of medicine at the University of Chicago. Pritzker School of Medicine, and she's also the director of the Metabolic and Fatty Liver Disease Program, at the university. So, we're delighted to have her. Dr. Rinella, thank you so much for joining us.

[00:01:26] Mary E. Rinella, MD: Thank you, Neeraj. Thanks for the invitation. I'm delighted to be here.

[00:01:30] Neeraj Mistry, MD: Excellent. So, let's just dive straight into it. So, given that MASLD and MASH are what we call a silent disease, when and what should raise the suspicion among primary care providers that a patient could have this disease?

[00:01:45] Mary E. Rinella, MD: Yeah. So, I think the most difficult part about it is that the most effective way to identify people at risk is to be aware of their cardiometabolic comorbidities and, and these are of course very common. So, in a patient who has obesity, who has type two diabetes or hypertension, those patients are at particularly elevated risk and, and that would require that a primary care doctor, just consider the liver among the multiple downstream negative effects of having those comorbidities so there's nothing specific at the outset without blood tests and imaging. It's just the suspicion needs to start with that.

[00:02:24] Neeraj Mistry, MD: Okay, so it's the collection of comorbidities, which we've talked about a lot on this episode series. and that's sort of metabolic syndrome, high cholesterol, Type 2 diabetes, obesity. Would you include autoimmune disease in this?

Mary E. Rinella, MD: I would not, I would include autoimmune disease as something that should be on the differential diagnosis if liver enzymes are elevated. But it is not an autoimmune condition. That being said, one of the most common autoimmune antibodies, the anti-nuclear antibody happens to be elevated in about 30 percent of people with metabolic or fatty liver disease. And so, it's something that should come to top of mind, especially if liver enzymes are elevated in those patients.

[00:03:10] Neeraj Mistry, MD: Okay, so we have a patient that's been coming to the PCP for the management of their diabetes. The doctor's been helping them to try and lose weight, etc. and what happens next? There's a collection of comorbidities. What, what's the next step the primary care physician should take?

[00:03:30] Mary E. Rinella, MD: So, I think it's actually quite simple in the sense that if you just think about the liver being a possible, player in this constellation of metabolic risk factors, then instead of ordering just a basic metabolic panel, you would order a comprehensive metabolic panel or a hepatic panel. To go along with the basic metabolic panel that in conjunction with, a CBC with which most of the time will be part of the annual labs, will allow you to calculate something called a FIB-4. And that is a very good way in a primary care setting to exclude the presence of severe fibrosis or scarring in the liver that will lead to cirrhosis and other adverse, liver-related outcomes.

[00:04:11] Neeraj Mistry, MD: and so, the FIB-4 is not a special test that the doctor would order on his blood screen, right?

[00:04:17] Mary E. Rinella, MD: No. No, it's a calculation that is based on the patient's age, the ALT, AST, and the platelet count. And so, it can be derived directly from routine blood tests. So, by that metric, it doesn't have a cost associated with it other than what you would already be doing with blood work. it's a test that can be incorporated into electronic medical records quite easily. and that can auto calculate, or you can request it to auto calculate some laboratories across at least the U. S. are providing an output. So, for example, if you order those tests, you will get a FIB-4 calculated for you with the sort of implications. below it, but that's fairly uncommon. You can use an app to calculate that very easily. It’s available, you know, on your phone or on your computer, or again, you can incorporate into the electronic medical record too.

[00:05:13] Neeraj Mistry, MD: Okay, so the FIB-4 result comes back. How should that be interpreted?

[00:05:18] Mary E. Rinella, MD: So, the number to remember is 1.3. So, if the number is less than 1.3, then the likelihood of that patient having severe fibrosis or scarring in the liver is extremely low, and that is just, is a general statement. In a primary care setting, where the prevalence of a lot of scarring is low. And so, just like when you interpret any test, you need to understand, you know what the performance characteristics are of that test. And so, the FIB-4, is unfortunately not as accurate, in excluding disease when you apply it to a high-risk population. So, for example, if you have somebody with multiple cardiometabolic risk factors, particularly diabetes, where the liver enzymes tend to be lower, then a low FIB-4, should be I think it's still valuable, but it needs to be repeated, in the future, and then ideally, if possible, a secondary test should be performed in people who have very high metabolic burden, and I would say people with diabetes, those are really the, the target population to do secondary testing in, depending on what's available to, to the provider.

[00:06:28] Neeraj Mistry, MD: Okay, and so the frequency of testing, if there's a normal test, that would be part of the annual blood work for the patient.

[00:06:35] Mary E. Rinella, MD: Yes, exactly

[00:06:37] Neeraj Mistry, MD: So, if it's greater than 1.3, what would the next steps be?

[00:06:42] Mary E. Rinella, MD: So, we provide two basic choices. If it's so high is greater than 2.67, then that really increases the likelihood that this is a patient who has scarring in the liver and really should probably be referred, depending on your resources. Depending on your availability of specialist care around you, you can either refer directly to a specialist at that threshold, or you can then engage in secondary testing. And by that, I mean, some measure of liver stiffness. And liver stiffness, most commonly is done with something called transient elastography or fibroscan. In a hepatology office, it's almost like a vital sign for us. We check it in most of our patients in this context. and so that's a possibility if you're in a center that has that, that technology, but importantly, if you don't have that, there are multiple other modalities using ultrasound, and of course, using MRI that can give you very nice liver stiffness measurements. And I, what I found is that many providers are not even aware. that these technologies exist in their healthcare system.

So, I would suspect that most people will have access to one of those tests, if you really don't have those, then something called an ELF test, which is a proprietary test. that does have a cost associated with it. So, depending on the insurance, that would be something to consider also that can help you nudge you towards, yes, this person is high risk or no, I think we're pretty safe keeping this patient in primary care for follow up.

[00:08:15] Neeraj Mistry, MD: the initial referral to then do secondary testing. Would that be to a hepatologist or gastroenterologist?

[00:08:23] Mary E. Rinella, MD: It depends on the resources. I would say if you have access to a hepatologist, that's probably better because they're more likely to have a fibroscan in their office. They're more likely to have. sort of higher expertise in how to identify people with advanced fibrosis, or even just moderate fibrosis, because now we have a drug that we can use to treat patients in addition to various other interventions. So again, I would say by preference hepatology, if that exists in your area, and if not, gastroenterology is a great place to start. And then general gastroenterology can refer if the patient really is more advanced than they are comfortable dealing with.

[00:09:01] Neeraj Mistry, MD: There was another really telling piece of information that came from the survey that we did of patients and their care on, on fatty liver disease. One of which was, in most situations, the doctors just told them to go home and lose weight or not to worry about this. And so, at this particular point where there's a high suspicion that there might be a fatty liver disease or some form of fibrosis based on the FIB-4, what advice should the primary care physician give to the patient?

[00:09:33] Mary E. Rinella, MD: Yeah. So, you're absolutely right. I mean, telling somebody to go home and lose weight is just not effective, right? And if it were effective, then we wouldn't have a problem in this country or across the world with obesity and metabolic disease. So that is ineffective. And so just like when you provide advice on a medication or treatment, you really do need to be specific about it. And if you're going to request weight loss, you really need to provide support for that patient, to achieve that and be successful because that is critical. If you don't do that, the success rates are very low.

I think, and this is a little bit digressing, but one of the reasons why I think, we pressed forward with the nomenclature change. is that this concept of you just have fatty liver, and it's a benign phenomenon is what got us to, you know, having patients presenting very late in their disease stage, either with cirrhosis already or pre cirrhosis. And it being the number one reason for liver transplantation, in those over 65 and in women. Late diagnosis and referral is a big problem. And I think a lot of that was perpetuated by disease minimization, which was, I think it's just part of the way people thought about fatty liver. Part of it is because it's difficult to modify lifestyle. Now we have drugs that are very effective in weight loss, like the GLP one agonist, for example. We understand better about how to modify disease. So that's really important. And then now we have a drug. So, I think that this sort of lackadaisical approach of, oh, it's just fatty liver. It really needs to be stopped because it's not appropriate. Okay. If you look at a population level, yes, the majority of people with fatty liver or steatotic liver disease will not die a liver related death. The majority, if you look at 100 patients, you know, only 25 percent will develop chronic liver disease. Okay. But that doesn't mean that they don't have increased rates of cardiovascular disease, cancer, and other things, right? So, I think it's critical for us to change our perspective on that and to also understand that liver enzymes are not an indicator of liver health a lot of the time.

You can have cirrhosis with normal enzymes. In fact, the sicker your liver is, the lower the liver enzymes get in this disease. And so, this concept of your liver enzymes are only a bit abnormal, so you don't have to worry about it yet is a complete fallacy. And so, we really have to re-educate our workforce to understand that and to serve our patients better.

[00:12:07] Neeraj Mistry, MD: and I, I really appreciate that point that, with liver disease, particularly, patients are going to possibly succumb to their morbidities through cardiovascular disease. cerebrovascular disease. But I do think the important thing about picking up fatty liver disease is that it's your early warning sign. And we found also from the patient perspective is that adding another pathology tends to reinvigorate their health seeking behavior and effort towards their own health. So, it has a huge sociological impact. So that's quite important.

I do want to ask, from your clinical experience, have you seen an increase in the number of multidisciplinary practices? And might that be a one stop shop for people with these comorbidities that's quite a matrix of, of different issues affecting different organ systems in the body?

[00:13:08] Mary E. Rinella, MD: Yeah, so I think there is more, there's more of a focus on multidisciplinary care, certainly, than there was, you know, 5, 10 and 20 years ago. I know that for a fact. But I think that also it can be a little bit overwhelming to think, well, yes, you do need to approach this in a holistic multidisciplinary fashion with the patient at the, at the center and participatory in the, in the process, but many health systems cannot really do that in a physical sense.

So, I think that yeah. We shouldn't be discouraged if you can't have, you know, a metabolic clinic where you have a dietitian that's resident in there, like we do or, or an endocrinologist, for example, because I think what, what needs to be holistic really is the approach. And I think that the communication with the primary care doctor or the endocrinologist or the obesity medicine specialist or the cardiologist, depending on the patient's, sort of predominant comorbidities is, is critical.

So, I think. We need to do more than have physical multidisciplinary clinics. I just don't think that's possible in many places, but having a multidisciplinary approach to care is really important. And this is a lot for a primary care physician to deal with, but I do think that creating these relationships with different subspecialists can help you.

You know, better care for the patient and depending on how much time you have, as in, if they have other things that are not distracting you from being able to focus on the liver. There are certainly approaches to diabetes that are going to be more helpful in this context or for the treatment of hypertension in this context.

So, there's a lot you can do. It's just a question of how much you have time to do personally, I suppose. But if not, you can always refer and create relationships with others that can.

[00:14:52] Neeraj Mistry, MD: That's excellent. And I think that sums it up really nicely to maintain. holistic view of your patient, with the comorbidities that they have, but also to think about it in a very incremental way. One step at a time. What do you do next? What do you do next? Who do you consult with next? Et cetera. And I think that would be really, really helpful for primary care physicians.

And I think as we get better in the management of multidisciplinary approaches, to these complex diseases, sure we'll get more protocols, and management pathways,

[00:15:25] Mary E. Rinella, MD: it doesn't just have to fall completely on the, on the primary care. So, one example, again, that came out of the nomenclature was this concept of the combination of alcohol intake and metabolic disease, right? And so, what I really think that's done is it has increased the awareness of people who live in the metabolic space, like myself, to really, really hone in and think about and ask about alcohol and manage alcohol use disorder, which I think we strangely didn't really do very well. But then also it, I think it puts the onus on people who are more focused on alcohol to think about diabetes, to think about, you know, drugs or recommendations that could also maybe curb alcohol intake.

[00:16:06] Neeraj Mistry, MD: And so, I think that on a subspecialist side, it also is important for us to think in a multidisciplinary holistic way. The way we've been doing it in the metabolic space, but I think that needs to apply to all of hepatology, gastroenterology as well. We just need to be better doctors, that was beautifully put. Thank you so much, Dr. Rinella. I think our primary care physician community will definitely benefit from this and we appreciate your time and please keep up the good work.

[00:16:34] Mary E. Rinella, MD: It's my pleasure. Thank you.

[00:16:35] Neeraj Mistry, MD: Wasn't that a great conversation with Dr. Rinella? I know that this will help you in managing your patients better. And join us for the next episode of Unlocking the Fatty Liver Mistry.

This transcript has been lightly edited for clarity.