Liver function testing occurs often in the primary care setting. Amanda J. Chaney, APRN, D.N.P., a liver transplant nurse practitioner at Mayo Clinic in Florida, discusses what testing is done when determining liver injury and liver function, including liver injury related to COVID-19, and how to appropriately triage and manage the patient with these abnormalities.
This education is supported in part by an independent medical education grant from Pfizer Inc. and is in accordance with ACCME guidelines.
here to claim credit and view faculty disclosures. Select Register to begin the credit claim process. Welcome to Mayo Clinic Cove in 19 expert insights and strategies. The following activity is supported in part by an independent medical education grant from Pfizer Inc and is in accordance with a C CMI Guidelines. High. Thanks for joining me today. I'm Amanda Cheney. I'm a nurse practitioner at Mayo Clinic in Jacksonville, Florida, and transplant department hepatology. I'm going to bring you another lecture on the Cove in 19 Expert Lecture Siri's. This one is regarding abnormal liver profiles and liver function testing. And how do we approach that? Here are some disclosures that I have. So we're going to talk a little bit about some reasons why there could be abnormal LFTs and patients we're gonna talk about despite ing the why and what's that process look like? And then when to refer. First, we want to talk a little bit about the liver's function, and what does it dio, I gotta admit? When I first started in hepatology and liver transplant, I was pretty clueless about what the liver did, which is a lot. We wanted to talk a little bit about the synthesis of what it produces so it produces proteins like albumin, produces clotting factors. Fibrinogen, Proton, drin There's metabolism of nutrients so you know, acids, cholesterol, fat and glucose. And then there's detoxification of substances. So whatever medications you consume, it's gonna be detoxified within the liver. And ammonia is converted from its toxic form of NH three over to your area in the liver and then excreted out through the urine. And if the liver is impaired and that's not happening, then that can cross. The ammonia can cross the blood brain barrier and lead to confusion and more more problems and so definitely very important functions that the liver does. It also aids and immune response, so the cup for cells are activated within the liver and then digestion. It helps with digestion. It creates about a leader of vile a day, which seems like an enormous amount. Um, bile salts are critical for fat soluble vitamin absorption, and so if the patient has a biliary disease or if they have longstanding malnutrition or cirrhosis, very typical that these patients will have impairment of those facts. Label vitamin approach. So vitamins A B, vitamin K. All of those are impaired and then fat. Cholesterol absorption occurs in the liver as well when we think about liver function tests, liver biochemical test is really the more appropriate term. Um, these were the ones that we think about. So Al Fossil Ta ste. Billy Rubens Total and direct both time or I N r g t f five nuclear taste as well as a B. A trouble. For the purposes of this lecture, we're going to really focus in on the's five studies when we think about testing and figuring out what's going on the liver we can break it up into have had a cellular testing and cola static test. The cola static testing is really looking mawr at the biliary sort of process. And so alkaline phosphate taste would be one of those in the grouping of cola static. Um, normal is anywhere from 30 to 1 15 if there's an isolated elevation and the outflow. Austin, you can't get a G t to see. Is it more from the liver? Is it more from bone on that guide? Some of your def off a fractionated alp could be Dunas well, which also can do the same and guide you into which direction Um, it's happening Well, we think about Billy Rubin. Billy Rubin is the direct breakdown from him. Eso If there is an isolated Billy Rubin elevation, you wanna think about biliary disease as well as a problem going on with the breakdown of him and breakdown of the hemoglobin. And so definitely, if this is isolated and there's more of a direct hyper bill bilirubin AMIA um, you could do a hemolytic screen to further look into that album. It is as protein that is synthesized in the liver, and so it's very common to be low in patients who have longstanding cirrhosis and or malnutrition or cancer. And so definitely we can look at that as a part of the whole picture When thinking about liver disease. One of the best liver function tests is truly an i n r. So when we know that the I N. R. Is high, that is really a good indicative sign of or function on the livers part. It could be a sign of vitamin K deficiency, which again can happen in a patient who has Billy Rubin problems or has malnutrition or prolonged cancer prolonged Yanda's um, and you can figure out whether or not that's going on or not if you give them a Bullis dose of vitamin K, so 10 mg of Q for three doses. And if the Einar gets better following that Boulis, then it's probably a relation to vitamin K deficiency. If it doesn't get better than it's indicative of more core liver fund, so it can be really confusing. So normal level metal levels don't always mean that the patient's liver is good. Some patients with liver injuries, particularly long standing chronic hepatitis um, will have normal labs and then some patients with normal APS may have liver injury, and it may make you feel really frustrated and like you're studying for an exam and you're never going to get it right, eso um, What you have to do is look at the patient and look at the different. So there are some abnormal liver testing, and when that happens, and it frequently happens for patients in the outpatient and in the inpatient setting could be a mixed picture. A lot of times, the patient's gonna be completely asymptomatic and walking and talking and doing just fine, so you want to know if the patient, if this is an acute thing going on so in between a month and six months. Or is this more of a chronic issue? And so you can divide it into that categorization if the PETA Seiler Cola static disease, if that's the picture that's going on. So if it's a viral hepatitis, if it's an alcohol hepatitis, only those patients are gonna have. Elevations are not more than 10 times the normal range her patient, who has primary about a cellular disease. So this is talking about patients who have seen a minimum toxicity, acute liver failure for unknown ideology, or patients who have a trauma where they all of a sudden don't have any blood flow to the liver. Those liver cells are actually dying, and the enzymes within those liver cells are released and very high abouts. And so those lead to elevations that air 25 times the normal range. And so we're talking about the Trans Am in Aces Ale TVs here and the thousands. And so that's how you can kind of differentiate a little bit between Mawr of the You're cute abnormalities that are super super high versus those who may be in the more 100 ranges. We're going to talk a little bit about a case study. So this is an actual patient to super sweet. Um, Ms asked. She's pleasant 55 year old lady. She went to the emergency room for one week. History of change, yellowing of skin. It gone toe work the day before, and a friend of hers at work said, Oh my gosh, you are so yellow And not on Lee. What it kind of give her a bit of a complex, but she thought that she should go to the ER and have that evaluated. She's been diagnosed by your PCP with some chronic bronchitis about two weeks before, and she was started on Bathroom DS for twice a day for 14 days, and so far she's completed seven days of that treatment reports, really feeling fatigued, nauseous, And they actually did in the e. R. A. Right overconfident, um, ultrasound, because of nominal came that she was happening. Denies any history of liver disease. She denies any alcohol consumption. She does have medical history significant for obesity for diabetes. On Matt Foreman, she's on Synthroid for hypothyroidism, and she has the known chronic bronchitis. This is her physical exam, so blood pressure is pretty good. Um, her heart rate's 90 respiration rate is 24 she has a little bit of a temp. It's 38.2. She is very yellow. She appears very Jonah's and Swiss Claire electricity, and she collected severe itching and so badly where she has, like, scrapes on her arm from just excoriating her skin because she's scratching so much because she's itching so bad. She also has a mild macular popular rash to the chest and the back, and it started the day that she came to the emergency room. This is what her labs looks like. So number total. Billy Rubin is anywhere from 0 to 1, right, and so on. Her labs. It's 12. Her office is 250. Her lt is 75 STS 40. To her, I N r is 1.2. CBC is normal and her renal profile is normal. So no evidence of any homicide. Api mia. No evidence of anemia specifically looking at the kidney function, no electrolyte imbalances and created and is normal. Her ultrasound showed fatty infiltrate of the liver consistent with fatty liver disease. Peyton Vasculature. So all the vessels in the liver portal vein competitors artery All that's flowing well and there is some presence of gall stones. So what do you dio do you A and get her to the hospital? Do you be repeated? Liver panel. Do you see? Send her for blood cultures and a lactic acid you d center for viral hepatitis studies. Do you e stop the antibiotic or do you f do all the above and what we did? Waas do f all of the above. We're gonna go back to her in a few minutes, but we're going to talk through some of this abnormal liver testing. So when I was for starting and hepatology, one of my wise precept er physician mentors said, It's really not that hard. You can break it up into four disease infection. Drugs are pregnancy. And so I have taken that to heart, and I like to categorize things and keep things very organized in my brain. And so this helped me a lot to think about this very organized and strategically, this is a really good table that I have found very useful when talking about abnormal liver testing. And it's adapted from the American Association for the study of liver disease who actually have some great resource, is on that website to help with some of these understanding liver disease specific things. So if we're looking at liver injury tests, those are going to be the out fost a swell as the Trans Am in Aces, which is a L T A S T. And like I mentioned before, those get really, really high and had a cellular injury, though the Al Fosse's more of a cola static picture and so thinking about something wrong with the bile ducts or something going on biliary system wise, that would be really, really elevated in cola static problems. And then we break it into the function of the liver. So the true function of the liver is, um, using the N R. That's one of the best ones. And so if it's long and does not correct with vitamin K, then that's more liver cell. Have had a cellular injury. If it corrects with vitamin K, that's probably because of the deficiency, because it's not, um, it's not working with the fat soluble vitamins. And so, um, that will correct with vitamin K total and direct. Billy Rubens can be really, really high in either disease, whether it's just kind of cellular or with cola Stasis. And then Alva human is gonna be low, very low in patients who have malnutrition with chronic liver disease. So again, take this table and make it your own. But it really helped me to kind of put it all into very structured pieces. So we mentioned that the patient with moderate elevation of those train Seminis and so we're talking about in the high, you know, 50 60 seventies up to the mid hundreds. Maybe those were gonna be more your viral hepatitis patients, fatty liver, alcohol, disease, but really, really high elevations. Looking at the and the 1000 ranges those air patients who have a toxic hepatitis. So I've seen this once better patient who had an acute hepatitis B. I've seen it once for a patient who had an acute hepatitis A sometimes those most of the time. Those acute phase is air more self limiting and symptomatic treatment versus um needing to come into the hospital for a transplant evaluation. But it can happen. And then patients who have a scheme makers chock liver so thinking about a trauma, Um, specifically, you know, like a car accident or some sort of trauma that had, ah, shock Thio the liver, where there wasn't any blood flow for a period of time. Patients who have elevated Billy Rubin. So that's that more cola static picture they Billy Rubin gets into the skin into the premise, and it cause a severe um, and there are some ways to treat that. Some patients with severe head Peru bilirubin AMIA like thinking in the fifties or 60 ranges. It's sometimes really, really difficult to control their pure itis. Um, there's some school of thought out there that plasmapheresis or, um, those sorts of measures drastic but can be done toe help with some of the symptoms of that. And so that can happen with medication. It can happen with alcohol disease. I've seen a few cases where a patient was on a herbal medication and they had an acute elevation of their Billy Rubin levels. And viral hepatitis could have sometimes an elevation in the billy ribbons as well, particularly for biliary disease. We're talking about primary sclerosing cholangitis or primary biliary cirrhosis. Those are very commonly known, um, reasons why a patient could have a very, very high Billy Rubin level. I crossed out abnormal LFTs because we really wanna think about this more as abnormal liver testing vs LFTs. Because not all of these are true. Yeah, this is another depiction of the school of thought that I was bringing to you earlier. Looking at the more in the 100 range is gonna be chronic hepatitis alcohol, and then we get to auto immune. That can be into the 1000 range, but not really much higher than that Acute viral hepatitis command, 1000 rains, ischemic or toxic liver entry like acetaminophen toxicity. Those could be very, very high. One of your steps to your evaluation. So, as always, you want to get a really good history and a base for differential diagnosis on what you find on your labs. What you find on your imaging studies, we definitely need to know whether this is a huge process versus a chronic process. And then if it does have chronic liver disease and they have cirrhosis, we need to know if they are compensated or if there d compensated, and then we'll go into a little bit of complications of so as far as history. You want to know alcohol consumption if they have any risk for viral hepatitis travel outside of the country or any blood transfusions prior to 1992? Um, there's a lot in the history that can be gained to kind of guide you on your differential where you're going to go medication. So I mentioned before. Herbal medications are not, um, benign. And so I think it's really important to get a full history of all the medications that patients could be taking looking at physical exam findings, So does the patient have a societies where they have muscle wasted? Do they have temporal wasting? Were they yellow? Do they have any squirrel interests? Do they have any Venus, um, for two appearances on their belly because of the societies or catapult produce? A. There is some Palmer era thema that could happen in the patient with chronic disease and then risk factors. You want to know, um, or do they have any risk risk factors for cardiovascular disease? Do they have any co morbidity, ease of diabetes or any sort of inflammatory bowel disease that could lead you to more of an auto immune picture. And so all of these pieces, um, are really important to talk to the patient about talk to their caregivers, see if there's anything that guides you into the direction of where, um, where this abnormal testing could have come from. So I'm gonna ask you why do you think Miss s had hyper bilirubin? EMEA? Do you think it was a because of viral hepatitis? Do you think it was B? Because, ah, drug reaction from her antibiotic? Do you think it was CIA from fatty liver disease, or do you think it was d from from a cola static disease? And the answer is actually be She actually had hyper bilirubin anemia because of a drug reaction because of that antibiotic. So what is your next step in reading this? Do you a stop the Bactrim? Do you be a nerd? Urgent referral to an expert for transplant evaluation. Do you see consult infectious disease, or do you d starter on her style. So your immediate next step is going to be to stop the antibiotic? Um, she actually was seen at an outside emergency room. And because her her liver enzymes were so high and her Billy rooms were so high. Do ascent Thio are er for transfer. And so we accept her. And we did a nerve agent evaluation a hospital. Just a case of the ruins have responded and improve. But thankfully they did. We're going to talk just a minute about drug induced liver injuries. So when we think about liver and three have seen it ah, lot in in antibiotics, especially sulfa medications that the patient was on to contribute to hyper bilirubin. EMEA can be because of seeing medicine. Can be because incense And then I've had another patient who was on some weight loss supplements with his wife and, um, he wanted to support her and help her with her weight loss journey. And he ended up having, um, an acute elevation and his liver enzymes as well as the Billy Rubens and needed transfer to our center for an urgent transplant evaluation. And that was the only thing that we confined. We did viral hepatitis studies. We did all the other studies in the book and, um, did not find anything that could that cause. But we took away that piece of the equation and eventually his, um, lab's got better and his wife was fine. She didn't have any problem with the weight loss supplement. But those supplements and, um, you know, just anything a patient puts in their body is definitely, um, important to review in the in the history toe get a very well rounded, clear picture of what's going on. So this talk is in the lecture series of Koven. 19. So what about patients with Koven? 19. So there are in this paper. There are some medications that are being tested for patients who have moderate to severe co vid symptoms and thes medications. Antibiotics and antivirals do cause some elevated liver enzymes and abnormal liver labs. And so it's really important, Thio know that and Thio take the whole picture into consideration Anything. Any new medication could be blamed for this sort sort of reaction. And so this paper I'll guide you back to this paper. But it was a really good one that was put out by the International Association for the Study of Liver Disease, um, and had a great table, and it that shows which medication specifically can be related thio, normal liver profiles and labs. So in the evaluation piece. You want to stop anything that could be possibly about a toxic. Consider drug drug interactions definitely for patients who are older and who are on a lot of medications, or even though both transplant sending patients from a ton of medications consider drug drug interactions. Like I said, antibiotics are to be blamed, frequently thinking about additional lab tests that you want to get. So we want to rule out other causes of liver disease. So get those viral hepatitis studies. Iron studies rule out hemochromatosis, alcohol screen, toxic screen, any sort of steroids or any anything else that could be a cause for that, as well as autoimmune markers to rule out any auto immune disease. And then your first step for imaging is always going to be an ultrasound. So the usual patient is gonna be completely asymptomatic. They're gonna have Mobley elevated contaminates. Is there blood test work up? All the other labs that you've gotten are completely normal and negative. So you're deferential is pretty standard thinking about Is it medications? Is it from disease, or is it from, um, pregnancy usually can rule out especially and, uh, area, who is a no older population and who are men. That's not gonna You can rule that out pretty easily. Um, and so in your differential, a lot of times, this is from alcohol, hepatitis, alcohol related disease, fatty liver disease or from medication from the drug interaction for patients with alcohol injury. The typical board question is that there s a L T. Ratio is 2 to 1, and there's an elevation in the G T A S T is usually less than 300 so it's high, but it's less than that 300 number. So what are our recommendations? So typically we like to trend it. We like to see what happens. So if there's no kind of compensation um, no significant lab findings you did the work up and nothing else coming back positive. So there's nothing to treat lifestyle modifications. Tell the patient, not toe drink alcohol. You don't wanna add any more insult to injury. So if the liver is already irritated, you don't wanna make it more irritated with more, thanks to detoxify weight loss. If the patient does have a need for that, then definitely that is one of the mainstay of treatment for fatty liver disease. And so we want Thio. Advise them on that. Maybe consult with a nutritionist and see what their recommendations are for some guidance on, um, some good food choices and then controlling the diabetes. So again, you don't wanna ADM or insult to injury and you want to control um, if there is any insulin resistance or any sort of issue with that, and you wanna have that under good control so that the liver doesn't have to work harder, there is repeat testing that's recommended in six months or so, And if they're still elevated, then you can go ahead and get a consult with a specialist to see what else could be done or what other image and you should consider for patients who have viral hepatitis, hepatitis A and B typically clear on its own. Um, if it doesn't and um, hepatitis B, particularly than antivirals, could be recommended depending on the case. The iron studies or abnormal that you got then patient could be, um, have a history genetic profile consistent with human comatose isso. Consider that testing stopping all iron supplements because again, I want to add more problems to that and stop alcohol consumption and then liver biopsy. If there are ongoing abnormalities for a patient with an abnormal out false Onley, then we could get G d testing. Could do a fractionated LP, um, and then his history. Physical exam. If the GT testing is that normal, then that could point you in the direction of getting more studies. So in a m A and an ultrasound specifically looking at an auto immune piece, um, and then liver biopsy if there's on going abnormalities. We have seen this a nice, elated A S T elevation, particularly in, like marathon runners or really strenuous exercisers. And it's related to muscle injury, So that is a possibility. Each other. So what do you do if there is, um, biliary duct deputation. So this is the coolest static picture there's on ultrasound and picked up something that was concerning for ductile delegation and the bile duct. We would recommend a May testing. So looking for PSE PBC, um sort of picture as well as ercp. That's one of the best things to dio to visualize what's going on in the bile ducts if their structures, If there's, um specific, um, tightness that's going on in those Val ducks. They can place a stent and that and open it up. Um, possibly sometimes patients need external drainage. Um, if the internal drainage does not work, um, we want to keep those ducks open. If they do get structured and tight and block from drainage, those patients can become septic very fast. And so we definitely want Thio. Identify that soon and quick and get them the proper treatment. If there's abnormal Billy Rubin levels again. We talked about this a little bit earlier, getting hemolytic testing to see if the Billy Rubin is being broken down appropriately and again. If the conjugated Billy Rubin has elevated along with other abnormalities on the liver profile, then further imaging and testing could be done. So again, When we think about this, we think about it in a kind of cellular in the liver injury piece and then in the cola static piece of looking for the pilot empty So it za cute that could lead us down the differential for how to cellular injury of viral hepatitis or drug or toxin. It is called static injury, then could be drug induced or could be from a bile duct obstruction And so the questions to ask yourself in that acute phase is number one. If it's more, have had a cellular, is there evidence failure? And if your answer is yes and the patient probably needs to be hospitalized specialist, if your answer is yes for the coolest static picture, then again admission and further work up with a specialist toe. See if they have cholangitis. If they dio get it corrected sooner rather than later. Because if you don't, then this which is to get very sick and have subsystem subject shot on the chronic side again. Pettitte Cellular Injury Mawr for alcohol, fatty liver disease, viral hepatitis and pull a static. Is there evidence of primary biliary cirrhosis? Is there evidence of drug induced injury? So the question to ask yourself in the chronic phases roses for the yes, is it compensated or is a decomp and and we're going to talk about when to phone a friend. So when you get that expert consultation, you really are asking, why is this patient? I've I've done the initial work up. I've gotten a really great history, but six months later they still have persistent LFTs. This is a time when you go ahead and get that evaluation and the liver biopsy can be done, but it should only be done by a trained expert. It does come with its risks leading bowel preparation, infection and so definitely want to do it in a place where they do a lot of them. They do them well and by clinician who knows what they're doing. We talked a little bit about cirrhosis. Um, this is this is kind of my world in transplant where I live And there's about five million people in the United States living with liver disease and cirrhosis is the eighth. Because of that, the United States complications result in significant morbidity and our morbidity and mortality. And so I talked briefly about the Compensated versus D compensated. If the patient has compensated cirrhosis, they could be walk and talk and doing just fine until they moved to that be compensated state. And so what? What does that mean? Complications of cirrhosis include SBP, so spontaneous bacterial peritonitis at a renal syndrome sides. Daffodil embarrasses with leading portal hypertension thes air, just to name a few. But if a patient develops any one of those, they have successfully or unsuccessfully moved from compensated to a D compensated psoriatic. And that's when we need toe do a transplant evaluation. So how sick are these patients with patients with cirrhosis? So we evaluated that two ways. The first was back in the sixties that felt you score was created, and it was used to estimate the severity of illness it took into consideration. The total Billy Rubin, the N R the alp human and then the presence of societies and supple apathy. Patients with a child's pew a score. They had a pretty good survival in 1 to 2 years. As we get to more of the sea scores, it's these air, the more D compensated cirrhosis station. Um, at two years, they have a 35% survival in the two thousands. Doctor Wiesner sought Thio do the 2.0 version of the calculation for ceramics and see how bad the cirrhosis was. And if they could figure out a way. Thio put patients on a priority on the wait list for transplants, for the sickest person gets the train, not just by their wait time of how long they're waiting on the list. So he took into consideration. The total bilirubin, the I N R. And the creatine inputs in on a calculation, and you pop out a number on it ranges from 9 to 40 so nine is too early for transplant. 40. It's patient who's an urgent need for transplants. So those were the patients who are there listed for transplant those air higher on the list, and it is used by the United Network for Organ Sharing to prioritize the wait list. A little bit later, the sodium was added to the calculation, and it's now called the Meld Sodium score. And what was found in the evidence and literature was that the patients who have had cirrhosis and who had d compensated liver disease who also had high pony tree mia. Those patients were had, ah, higher risk of death, and we're definitely sicker. And so that's the reason why they added the sodium into the calculations. For those who are high, bony tree Mick, um, are are sicker, and they need to be prioritized at a higher level for transplant. This is another slide of that table that we mentioned earlier and again. Just take take indictment, consideration these agents and so liver injury in a covert world. So what? What exactly does that mean? And this is adapted from that, um, article that I lead you to earlier so patient could have a lt and a s T elevation with some of the antiviral medications. This was seen to happen more often in patients who are older, who were male, gender and who had diabetes mellitus and hypertension. So fan thinking about patients who have valvular disease who have, um, metabolic syndrome. Patients typically are sicker with cove in 19. And then the medication that you're giving them can cause isolated trade Seminis elevation as well. It's important to note that patients with Kobe 19 who have tested positive about 2 to 11% of them have underlying chronic liver disease and that many patients with over 19 have developed some sort of degree of hepatic dysfunction. And so, again, something really important for us to to be mindful of mortality was about 0 to 2%. And in our latest current literature for patients with chronic liver disease, with that, I want to thank you for joining me and for listening to this lecture. I hope it was helpful for you. This is my contact information. If you have any questions or anything that I can answer research for you that you were wondering about and with that I thank you very much.