Transcript: Slightly Elevated Liver Enzymes: Lab Interpretation for New Grad NPs

​Liz Rohr:

Hey there. It's Liz Rohr from Real World NP and you're watching NP Practice Made Simple, the weekly videos to help save you time, frustration, and help you learn faster so you can take the best care of your patients. So today I'm going to be talking about liver enzymes, liver function tests, hepatic panel, LFTs, whatever you call them. There's many names. Lab interpretation using a case study of a really common presentation that I see in primary care. I'm going to be talking about when to worry, the common causes, the evaluation, and when to send them to GI. And again, this is super, super common, so if you're in primary care I'm sure you're going to see this set of labs in this case scenario, so definitely check it out. If you're interested in hearing more, LFTs are a really big topic. They're going to be included in the Lab Interpretation Course for New Nurse Practitioners. So again, if you are interested in hearing more about it, sign up at realworldnp.com/labs. Otherwise, without further ado, I'm going to share my screen with you.

So let's hop into the case study. So this is Jeanine. She's 42. She is a new patient establishing care. This again is not her real name or her photo. So she's establishing care with a new PCP from another clinic. She doesn't have any concerns today, she just needs med refills. Past medical history of diabetes, type two diabetes I should say, hypertension and obesity. She's a nonsmoker. She doesn't drink alcohol or use drugs. She has one male sexual partner and she has a ParaGard IUD. So no past surgical history or family history. She's taking Metformin 1000 milligrams twice a day, and Lisinopril 10 milligrams daily. Her blood pressure at this visit was 138/78. Heart rate of 77. Her oxygen and respiratory rate were normal, and her BMI is 30.

So, plan. So I'm going to be checking some labs today. So CBC, a CMP, her A1C for diabetes, and then a urine microalbumin. And again, I'm going to focus today on liver function tests, the LFTs, liver enzyme test, there's many names for them. But I'll touch on the other components of her holistic care at the end. So, here are the results. So her CBC, her BMP, basic metabolic panel portion is normal. Her A1C is 6.7%, so that's controlled. And her microalbumin is also normal.

And so here's her liver function test. So when you order a CMP, it's usually a basic metabolic panel spliced with a liver function test, hepatic panel, with some nuances. The hepatic panel specifically has a little bit more information, and it usually breaks down bilirubin, which is kind of important. But anyway, so here are her results. Her albumin is normal, her alkaline phosphatase is 74 which is normal. Her ALT is 74 which is high. Her AST is also high at 62. Her total bilirubin is normal and her protein is normal as well.

So some key points I'm going to go over for LFTs, liver function tests again. So how many times the upper limit of normal is a really common phrase when we talk about liver function tests of any kind, whether it's AST, ALT, alk phos, bilirubin. Bilirubin I guess not as much I don't see, but people usually talk about how many times upper limit of normal. Is it twice, 10 times, 20 times? Et cetera, et cetera. And really important to look at is, in your kind of holistic perspective, is it just one element that's high, or is it... so for example, is it just the alkaline phosphatase that's high, or is it the ALT, AST, and alk phos and bilirubin are high? That's going to really guide your differential diagnosis going forward in terms of how to work them up and what further testing to do. And then again, keeping in mind if they have any comorbidities. So do they have CHF? Do they have other medical problems that may influence their liver health, right?

So one overarching thing to think about when you're looking at interpreting the LFTs is, is this hepatocellular or cholestatic? And so before you roll your eyes or skip over, this is really important, and it's pretty basic once I explain it, right? It's just the fancy way of referring to it, right? So this is talking about whether there's damage to the cells, to the hepatocytes, to the liver cells themselves. So the primary problem is from the liver cell injury. And what that means is mainly the ALT and the AST are the highest elements compared to everything else, whether it's by themselves or you also have alk phos elevated, then those are going to be the predominant ones, right? And so it's going to fall into that category. And so bilirubin may or may not be elevated in those cases.

And then cholestatic or cholestasis refers to the primary problem comes from the biliary tree, the bile duct, the gallbladder, et cetera, et cetera. But functionally what that means is that the alk phos is the highest element, whether it's by itself or whether it's in conjunction with AST and ALT, but in terms of the highest upper limit of normal, alk phos wins out, right? And again, bilirubin may or may not be elevated in those cases. So that's one kind of framing thing to keep in mind in terms of you branching your differential diagnoses. Looking at how high it is above the upper limit of normal, and then what kind we're kind of talking about.

There's actually a couple of other things, like isolated alk phos by itself or isolated bilirubin by itself, which I'm not going to be talking about in this case today. But those are kind of the two main ones to think about is, is it coming from the liver or is it coming from the bile duct, determined by the different type of lab you're looking at. And that is not concrete 100% exactly, that's just kind of like a broad brush approach, right?

So four steps if you have a high AST and ALT. So number one is do they have symptoms. So this is always the question when it comes to lab interpretation. Did you order it because they had abdominal pain or another symptom, or did you order it with another thing and you accidentally, kind of incidentally found it, right? And then once you incidentally find it, questioning further do you need to call the patient back and see if they have these symptoms? Things like that. So number two, what's the pattern? Again, the pattern that I'm talking about in terms of liver function tests, liver labs, you're looking at is it predominantly liver specific or is it predominantly alk phos? Which one is higher, right? And then is it mild, moderate, or severe? And that's really important in terms of the categorization of the result, because that's going to lead you down a different differential diagnoses path.

And number four, this is kind of key for any lab interpretation that we're talking about. Is it new, stable, worsening, improving? So looking at, if you have the luxury of looking at their last labs from a previous PCP or they've been in that clinic before, what were their last labs? When were they done, and what did they show, right? Is this consistent, is this worsening, or is it improving? Or is this the first time you've ever seen it, right?

So step one, do they have any symptoms. So were they symptomatic or was this incidental, correct? So worst case scenario is acute liver failure, so this kind of really breaks it down. Whatever liver lab you are looking at, the worst case scenario is liver failure. So it's kind of one key, regardless of what number we're talking about, it's the same signs and symptoms. Altered mental status, jaundice. Fun fact, it kind of has an affinity for the tissue type in the sclera, so you can kind of see it in the sclera maybe first. You can also notice it under the tongue, and then skin, it's a whole body diffuse yellow/orange undertone, depending on the baseline skin tone of the patient you're talking about. There are other conditions where you can have orange parts of your skin, but it's not like a diffuse whole body one, right? So right upper quadrant pain, nausea, vomiting, and malaise. Those are all kind of signs of liver failure. And then if you have a patient that comes into you and seems like they have liver disease right, and you're checking their liver tests, you want to think about ordering an INR as well, because that's assessing the function of the liver, even if it's not on the hepatic panel necessarily. But that's the criteria that fits for acute liver failure, includes an INR of 1.5 or more.

So step number two, is it mild, moderate, or is it severe? So the normal AST and ALT, it really depends on the lab that we're talking about, but the kind of universally adopted accepted number is about 10 to 40 units per liter. And then some say 20 for women and 30 for men in terms of the upper limit of normal, but for all intents and purposes I'm going to keep it at 10 to 40. Your lab may be different, but just something to think about. This is kind of all approximate, right? It's not hard and fast, "Oh, it's two and whatever." So mild is considered to be up to two times the upper limit of normal. So if it's around there, a little bit more, a little bit less, around there is something to think about right? So up to 80 approximately.

Moderate is up to 15 times the upper limit of normal, right? So if you're worrying about a couple points being off, don't worry a whole lot, because you can see up to 600 being concerning obviously. Everything, it's really concerning. But in terms of the worst, which is severe, that's greater than 600. So those are the people where it's 700, 1000, things like that. And those are very different differential diagnoses and very different treatment, right? So you want to think about, so do they have symptoms number one. Number two, do they have mild elevations, moderate or severe?

And then, so mild, I'm just going to break this down. So it's up to two times the upper limit of normal. So common causes that we're talking about, and this is the vast majority of people in primary care right? Medications, herbs that they're taking, some over the counter supplements. There's recreational drugs. You want to get a really good social history for these people. Fatty liver disease, huge, huge, huge. Hepatitis B or C, and it tends to be chronic. Acute hepatitis tends to be more of the acute reaction with more severe elevation liver enzymes, but these ones will tend to be low level chronic. And I've actually found a couple of chronic hep Bs and hep Cs this way. Hemochromatosis is another one. It's an iron overload kind of in your liver. Not very common, but it is considered to be one of the more common causes. And then alcohol. So the ones that are in bold, medications, fatty liver, hepatitis and alcohol, those are kind of the main ones that we're talking about.

And then another fun fact is that most of the time, you'll see AST and ALT will be in a one to one ratio. And if it's a two to one ratio with the AST higher than ALT, because ALT is the one that's more specific for the liver and AST can be from a couple of other different kinds of tissues. But if you see that in a two to one ratio, that kind of points you to the direction of differentials of like, is this more likely to be alcohol related? Is it more likely to be cirrhosis from hep C? Or something called Wilson's disease or Wilson disease, it has to do with copper metabolism.

So in terms of the evaluation, it's really going to center on the most common causes. There's a whole laundry list of reasons why we can have elevated liver enzymes, but for all intents and purposes in primary care, you're going to be focusing on the common causes and evaluating those, and that's your first passive workup. And then once you've kind of that criteria and you've figured out or you haven't figured it out, that's when you're going to consider sending them to GI. I'd recommend sending to GI actually.

So evaluation, I have history starred with two stars, because the history is really key in terms of uncovering what's behind the liver enzyme tests, right? You're going to test for hep B and C serologies, and then on the next slide I'm going to show you the kind of algorithm workup. But just as a brief introduction, here are the evaluation things you're going to do. Getting a history, asking about medications, hep B and C serologies. You're looking for more chronic hep B, so that's like the surface antigens, surface antibody for hep B and hep C antibody. If you're interested in hearing about the hepatitis serologies, I'd definitely be happy to make a video about that.

Iron studies is one to think about, because again, you're tying it to the differential diagnosis right? So hemachromatosis, you're going to be looking at iron and signs of iron overload, right? And then liver ultrasound. That is going to be pretty important in terms of ruling out... it's going to tell you that, it has a very consistent finding in terms of fatty liver. It'll say, I believe it's echogenicity consistent with fatty liver. Typically what the results will say. But then also you can kind of put your mind at ease that there's nothing else that's kind of causing those liver enzymes to be abnormal like a mass or something like that.

So here's the algorithm here. So if you have an elevated AST and ALT, so again this is the predominant elevation. Even if you have alk phos and bilirubin, this is kind of the first pass that we're looking at, and we're also looking at mild, right? So these people, if they are symptomatic even if it's super low level and they have jaundice, abdominal pain, nausea, vomiting, malaise, they're confused, send those people right to the ER. There's no need to keep those people on outpatient right, especially confusion because that's a sign of hepatic encephalopathy, right? So if we're talking it's less than two times the upper limit of normal, which is the vast majority of people in primary care, you're going to look at their history. So is it alcohol? Do they have signs of metabolic syndrome like obesity or diabetes or things like that? Do they have other medical problems like a CHF? Because fluid overload can cause liver congestion and some abnormal liver enzymes as well.

What drugs do they take? And kind of a quick note about drugs is that there's dose dependent ones, so Tylenol is one of those main ones that you think about right, in terms of liver injury. There's a huge laundry list, right? But there are idiosyncratic reactions, which means that it's like you've had Cipro once before and you were fine, and then the next time you had it you just had full blown hepatitis from Cipro the antibiotic, right? So that's like an idiosyncratic reaction, where it's not just dependent, it's not duration, it's not the first exposure. It just kind of happens, which is really frustrating. But that's something I think about if you've got really weird labs, right?

And then what are their risk factors for hep B and C? So for these, if you've listened to some of the other lectures that I've posted here, a lot of labs that we look at, you have to be mindful of how accurate the lab is in terms of testing. For example, potassium, platelets, those are not super accurate from the lab. There's a high risk of error so you definitely want to recheck those. There's nothing really about that for liver function tests. However, you want to consider repeating those in two to four weeks depending on... and this is experiential knowledge. There's nothing in a textbook that tells you you need to do that, which is so frustrating about lab interpretation right? But typically this is my personal practice, of if this person seems like they're getting worse and I don't really have a good picture of what's going on, you could consider repeating it to see if it was... was it just a fluke? Just kind of seeing from there.

But if they have a lot of alcohol use, there are certain drugs that could be causing it, you do whatever intervention that is. Whether it's cutting down on the amount of Tylenol they're having, cutting down on their drinking, try to do that as the intervention and then rechecking them in about three to six months, reviewing those alarm signs and symptoms along the way. So this is a very kind of conservative, cautious approach, right?

So I made this in conjunction with a hepatologist, a GI doctor, and he was kind of saying if you find abnormal liver enzymes, you can recheck it in six months, and then if it's still there then that's considered a chronic hepatitis, and then you can go to your next step of workup. In terms of my personal practice as a primary care primary care physician, I feel a little bit uneasy waiting a full six months if I'm not really sure what's going on. Even if it's like, oh okay, most likely that it's this, fatty liver or whatever, whatever. He was kind of saying that you could assume it's fatty liver, do those interventions or the alcohol interventions right, and then recheck.

And if you go back to normal then fine, and then if they don't then you can go to the next step. So again, these are just side notes of your own personal practice, right? So you can either recheck in two to four weeks, or you can check in three months or six months. I would probably check not longer than three months myself personally. And then depending on how it goes, if there's an obvious source, you can kind of do that intervention. But if there's not really an obvious source, it's not alcohol related, it's not drug use, they don't have metabolic syndrome, I would go right to secondary testing, which is again, that first passive evaluation of, is it chronic hep B or C? Is there any risk for hemochromatosis? And then doing a liver ultrasound.

And this is not comprehensive. I didn't list all of the possible reasons you could have those mild elevations. However, in terms of the primary care guidance, this is the first pass of the most common causes. And once you get to the second, kind of second tier other causes, I really recommend that you send those people to GI to do those workups, because those are things like autoimmune disease and Wilson's disease. You're going to be ordering ceruloplasmin and smooth muscle antibody... you don't want to be ordering that stuff. I don't know, you can choose to do that yourself if you'd like to, but I would recommend as a new grad that you send those people to GI for further assistance with the workup. Or you can do it in collaboration with a GI, and just call them and say, "What labs do you recommend that I do? Do you want to see them or do you just want me to do those labs?" Like I kind of spoke about in the CBC lecture about cold calling specialists. So really up to your personal discretion.

So yeah, that's the mild workup, and this is the really common one, right? So if it's still high, you're going to kind of order those labs. And that's up to your determination if you want to check those right away or if you want to wait and see if you can fix them first. So let's just recap with Jeanine. So she's 42, new patient. Most likely she has fatty liver, right? So she has risk factors of obesity and diabetes. So the plan is, going forward, is to discuss this with the patient, just give her a call and say... or have her come back in for a visit and say, "Listen, here are the options," right? So we can try to improve the diabetes, work on weight loss, see if this goes away.

Or we can kind of do some further tests to make sure that it's not the hepatitis, hemachromatosis. Do an ultrasound, things like that. I'm going to request records from the previous PCP to get some more kind of information to kind of compare with previous labs that she had had before. I'm going to have her come back for a physical and talk a little bit more about diabetes. And then yeah, just following up every three to six months is the kind of plan going forward, because that's just kind of how I work with patients who have diabetes. Every three months until they're controlled, and then every six months after that, and depending on their health literacy and how comfortable they feel.

So that's it. Did you like this video? If so, hit like and subscribe, and share with your NP friends so together we can reach as many new grads as possible to help make their first years a little bit easier. You sharing really does make a really big impact in terms of helping more people, so I really do appreciate it when you do. And definitely leave a comment below. I'd love to hear your thoughts about what you see in primary care, if you see this kind of case a lot or if there are other questions you have about LFTs, other frustrations that you have. And definitely if you're interested in learning more about the full range of LFT interpretation in primary care, definitely sign up for the interest list at realworldnp.com/labs for that Lab Interpretation Course for New Nurse Practitioners. It'll be talking all about LFTs, CBC, BMP, all of that stuff.

And don't forget to head on over to realworldnp.com for the Ultimate Resource Guide for the New NP. You'll get these videos sent straight to your inbox every week with notes from me, more patient stories, helpful insights, and other bonus content that I just don't share anywhere else. Thank you so much again for watching. Hang in there, and I'll see you next time.