Comprehensive Liver Disease Risk Assessment in Primary Care: Identifying MASLD and Viral Hepatitis

QUEST WEBINAR

Title: Comprehensive liver disease risk assessment in primary care: Identifying MASLD and viral hepatitis 

Presenter: Kenneth French, Sr. Clinical Consultant, Quest Diagnostics

French, Kenneth W  [0:24] When I travel the United States and I interact with primary care providers all across the US and the different parts of the United States, oftentimes I ask them what are the things that they're most concerned about in their practice? Commonly, I get answers like hypertension. They're concerned about, you know, diabetes, chronic kidney disease, they're concerned about cardiovascular risk, but rarely do I hear that there's a concern or an emphasis on liver disease. But when you think about liver disease, it's likely, if not the fastest growing organ system disease we see in the United States.

My name is Kenneth French. I'm the Director of Clinical Consulting at Quest Diagnostics.

And the time that I want to spend today is understanding comprehensive liver disease risk assessment in particular within primary care. And we're going to focus on MASLD or metabolic associated steatotic liver disease and viral hepatitis in particular.
So before we kind of jump into liver disease by itself, it's important to understand the cardiometabolic continuum and how that necessarily increases the risk for any patient as they journey through life. So what you see on your screen is an example of a patient in the middle.

This is the patient within the four walls of a clinic in a doctor's office. That interaction with the patient and the doctor is very important because lots of things and lots of pieces of information can be gleaned. Of course, of course, we know the patient's age. We can get their weight, we can get their blood pressure, we can listen to their heart. We can start asking them questions about their lifestyle to see if they're sedentary, if they're active, how well do they sleep? What type of stress are they involved in? What is their job? Do they smoke? Do they not smoke? We can get a lot of information out of that interaction as well as reproductive history. Did this particular individual experience preeclampsia or did or did they have gestational diabetes?

We can look into their family history, but immediately from that interaction we're getting a lot of information. The primary care providers beginning to see certain patterns that brings concern to their mind and as a result that individual provider may want to order some testing to see why a patient may experience some recent weight gain, or why a patient may be feeling fatigue, or why they may have changes in bowel habits or their heart beginning to act funny and show signs of some strange anomalies or effect. The point in this is though if a provider orders a particular testing in any one of these categories outside of that patient interaction and that test comes back positive. What that means is of the other circles are at risk and they must be assessed and ruled out. And I'll give you an easy example of a patient type that clicks all of these circles. Take a patient with type 2 diabetes. That's clearly an endocrine disorder. Or where there's a loss of glycemic control, many of those patients suffer from and have chronic kidney disease. A majority of them, almost half or more of them have metabolic associated steatotic liver disease and the leading cause of mortality is cardiovascular related disease.

Diabetes is one example of a patient type that touches all of these circles. There's many other different disease states that do that. In particular, the one we're going to be talking about today are diseases of the liver, particularly metabolic associated steatotic liver disease and viral hepatitis.

So let's look at liver disease. What do we see and what are we learning from this particular disease state? Well, let's look at some example patients. This is where a lot of times primary care providers get tripped up on the results that they see in these three examples, all of these individual males are between the ages of 47 and 57. Two of them are overweight, one of them is in the category of obesity and they all have diabetes. And of course their lipid profiles are very similar and as well as the ALT AST values, the liver values that we see, they're very similar. Some are slightly elevated.

Or the upper limits of normal on the scale. But we can't assume they all are suffering from exactly the same thing. So when we take it, ask the question, well, wonder why you have elevated liver enzyme values. Why do we see these values up in these individuals? Is it because of your diet? Is it because of your weight? Is it because of something that you're taking? Could it be a viral infection? There's a lot of questions there that we don't know the answers to. But if we do some testing, for example, and we assess their risk, we can see a clinically very different picture.

So for example, patient one upon screening for a viral hepatitis, we find out they have HCV. Well, that's bad news in one sense, but the good news is we can use direct-acting antivirals to eliminate that HCV infection. But the point here is, is that infection is potentially the reason why we see elevations in this person's liver enzymes.

Now let's look at patient #2. We screen for hepatitis. The good news is they don’t have hepatitis B or hepatitis C infection, but unfortunately it uncovers this patient has metabolic associated steatotic liver disease. Well, what can we do about that? Well, the good news is it's been shown that certain lifestyle changes particularly weight loss and control of glycemic parameters can have a very favorable effect on MASLD and in some patients you can actually resolve that MASLD risk initially completely. Now patient three unfortunately is positive for MASLD as well. But unfortunately is also positive for HBV. So what do we do for this individual? Knowing that HBV can't be cured, what can we do to help preserve the function of this individual's liver?

Well, certainly we can target the MASLD. We can help with the weight loss. We can get better glycemic control. We can increase muscle mass. Decrease, you know, body fat mass and we can also use certain, you know, medications to help control the inflammation that's being caused by the HBV virus to preserve liver function. But the overarching picture of all three of these patients are they're very different clinical pathways that are followed as a result of screening these individuals appropriately, finding out exactly what they have and then the steps that needed be taken to resolve or help resolve their issues.

Now when we look at liver disease, what's interesting is MASLD and hepatitis.
While the entry point or how they start is different, the progression of that disease to, you know, early inflammation to late inflammation to cirrhosis, fibrosis and ultimately in many cases hepatic cellular carcinoma, that progression is very similar.
So we can't look at all liver enzyme values and assume that the patients are all suffering from the same condition. We need to be assessing using the appropriate testing to find out exactly what are the causal reasons and then where we can take action to reverse or address those reasons we do it. And at the same time, we help the patient with their condition in such a way that we preserve the function of the liver for the long haul.

Now, when we think about MASLD, one of the scariest statistics, and you heard me in the beginning, a lot of providers don't see liver disease at the top of the list as leading concerns. It needs to be. Why? Right now in the United States, one in three U.S. citizens are affected by this condition. And you think, well, how can it be so prevalent? How come so many individuals have this particular condition given where we are in the United States? Well, the leading cause for this is obesity. Second to it is glycemic disorders like diabetes, like prediabetes, metabolic syndrome, insulin resistance.

And if you think about the impact of obesity and diabetes and the risk of diabetes in this country, now you can appreciate why one in three citizens are affected by this condition. The real concern is, is less than 1% of these patients have been diagnosed with this condition. And then when you look at just diabetes in particular as a patient population, those individuals with diabetes, 52% of them, so half or more of them have MASLD. And of course right now up to 19,000,000 patients have clinically significant liver fibrosis.

And many times and oftentimes, they don't even know it. Now, when we look at viral hepatitis, we see 14K new cases of hepatitis B infections each year. And in 2023, there were 70,000 cases of hepatitis C. So both of these conditions, these are large numbers, these are disturbing numbers and there's a lot of information that's being.
Yes, because we're not appropriately testing these individuals to find out what are the causal reasons for why we're seeing abnormal values in the CMP or hepatic panels that we're performing. Now, why is it important to look at both of these? We can't assume that just because you're overweight and have diabetes that all you have is MASLD.

Or maybe you’re normal risk, but you have a high risk lifestyle where you're exposed to certain hepatitis issues like hepatitis B or hepatitis C and we just assume you have a viral infection. No, each one of these conditions carries a risk for advanced fibrosis. So in the case of MASLD, you see a 2.2 odds ratio for developing advanced fibrosis. When you see viral hepatitis, you carry a risk of 3.2 and you may be thinking, well together if a patient has both of these, it's around 5.4. No, it's actually an order of magnitude higher. It reaches up to 6.8 odds ratio for developing advanced fibrosis.
Than just the two by themselves. So it's important to understand what does my patient have because it helps us understand the degree or the risk of advanced fibrosis overtime.

Now, not only is MASLD important to know and important to treat, but it also it dilutes the effectiveness of any retroviral or any viral therapy in patient with HCV. So for example, if a patient has MASLD and they contract HCV. Well, the bad news is, is having MASLD and HCV together at that time and neither one of them being treated. That means we're speeding up the fibrosis risk. We're speeding up the risk for cirrhosis and in the risk for hepatic cellular carcinoma.

Not only does it speed up progression, but it also impedes the ability for the direct antiviral medications to have their impact. So patients may need to be on these medications longer and then once the virus is cleared, the presence of MASLD if it's not appropriately addressed with weight loss, glycemic control and trying to control these things, they're still progressing to advanced fibrosis, they're still progressing to cirrhosis, and they're still progressing to increased risk for hepatic cellular carcinoma. So it's important to know and understand does my patient have either or these conditions and address them simultaneously so you get the best outcome.

So how do we do this? What's the best way to do this? What's the consensus documents? What are the guidelines saying regarding, you know, liver disease and how should we best assess it? The easiest tool we have is the tool called the Fibrosis 4 index or Fib 4 index. This tool uses the commonly ordered ALT, the commonly ordered AST, the platelet count, and then the addition of the patient's age. By using those four parameters, we can calculate the Fib 4 or the fibrosis 4 index. This is the screening tool we use to throw the widest net possible over the largest population of people so that we can get some idea of who do we need to be concerned.

And then we can start pulling those patients with abnormal values to the side and we can look at them more closely. And you say, well, how do we look at those individuals more closely when they have these abnormal Fib 4 results? That's where the enhanced liver fibrosis score or ELF score comes into play.

This test actually is looking for who's at risk for the progression to advanced fibrosis. So in other words, are they at risk for progressing to cirrhosis or a liver related event, ie, transplant or death. So when we look at the various guidelines and we compile them all together, what you see on the screen is the recommendation.

You take your at-risk population on the left hand side. Those are people with insulin resistance, prediabetes, type 2 diabetes. They're overweight. They have elevated triglycerides. They have abnormal liver, you know, findings. But maybe they did an ultrasound for something and they saw some imaging anomalies that were suggestive of a fatty liver. Well, we'll take that population and we do the fibrosis 4 index and you have one of three possibilities. If the score comes back below 1.3, that means you're at the lowest risk for advanced fibrosis. So that individual certainly can stay within primary care and we would continue to manage the reasons why this person is under the PCP's care, whether it's insulin, manage the diabetes better. Help with the weight.

Let's find out why the liver enzymes are elevated. Are you taking too much of a medication that could be damaging the liver or drinking too much alcohol? What are the reasons? Can we help you with the weight? If the Fib 4 results come back between 1.3 and 2.67 or greater than 2.67, these people are at high risk for advanced fibrosis. Now the question becomes, are they progressing or not? This is where the enhanced liver fibrosis test is the tiebreaker. If the provider performs the enhanced liver fibrosis test and these individuals come back low risk, those individuals really can stay within primary care and we can continue to manage the comorbidities and the things that brought them to have a an initial concern for liver disease. We can manage those. However, if the ELF score, the enhanced liver fibrosis scores comes back elevated, indeterminate or high risk, these people need to be shuttled quickly to subspecialties that deal with hepatic care. Why?

Oftentimes liver diseases, in particular MASLD and even viral hepatitis to a certain extent, they progress rapidly and they progress silently. And so by shuttling these individuals to get the subspecialty care that they need, we can put the current therapies in place and manage their risk to preserve as much liver function as possible so that we can actually prolong and improve that patient's outcome.

So at Quest, we've made it easy to order these tests either in a panel, or if a provider would prefer to order these individual tests uniquely by themselves, they can do that. But the point is, whether it's a panel approach or individual test, you have that option. Now, what about viral hepatitis, HBV and HCV? What are the current screening guidelines? What do we see that's being recommended at large across the United States? Well, clearly the CDC has helped us in understanding the different patient types that would best qualify clearly at least once all adults in their lifetime.

But certainly people who are pregnant, we want to certainly test them in within the first trimester. And of course the infants that were born from people who have an HPV or HCV infection, we want to make sure that they're tested as well. But there's  another population of people who, based on their lifestyle, they're at high risk for coming in contact with HBV or HCV, whether it's certain, you know, illicit use of certain drugs or certain multiple partners or you know, working in a healthcare setting, these individuals should be screened more periodically just to make sure that there's not an infection on board and if there is one, the intervention, the earlier the intervention, the greater the benefit we can provide. So for HBV, the CDC recommends a triple panel test.

We have that available at Quest. I'll show you more information on that. And then currently for the HCV, the guidance recommends a two-step testing sequence. Well, Quest offers the two-step screening and confirmation as well as reflex options, and I'll show you that information as well.

Now, why HBV triple panel screening? This is interesting because I look at, you know, millions of different blood draws and I get to look at the testing patterns of different providers and what I oftentimes see is providers ordering one or two, but they're not ordering the complete picture by ordering the triple screen panel. This provides the opportunity for providers to see and understand which patients have an active HBV infection versus a chronic HBV infection, and it allows the opportunity to assess the immunity after an HBV vaccination or infection. So the triple panel will assess all of this for you in one blood draw and of course.

Some of the features is that all of the components needed are clearly laid out in one single test code, and these results come back that are with enhanced reporting and certain interpretive results to help the provider understand next steps.

So if you're interested in ordering or if a provider wants to order this testing from Quest, we have again the panel codes where the reflexes are at play. Or if you want to order the individual testing by themselves, you can certainly do that. It's your choice as a provider.

So the point here is not all elevated liver enzymes are the same and it's important to recognize given the prevalence of MASLD and the prevalence of these viral infections, we need to understand which patients have what so that we can better give them the care that they need.

If you want to find out more information about viral hepatitis and MASLD, you can certainly go to QuestDiagnostics.com, forward slash MASLD or forward slash hepatitis. We have a very rich Education Center with cornucopia of different documents and illustrations and papers to help us understand this and of course.

We have clinical experts on our team at Quest Diagnostics, so if you need help with test selection and interpretation, we'll be more than happy to provide that information to you. Thank you for this opportunity to share this information with you and we look forward to seeing you in future events.