Amanda J. Chaney, APRN, D.N.P., a liver transplant nurse practitioner at Mayo Clinic in Florida, provides a brief overview of fatty liver disease and its complications. Topics include diagnosis, treatment options, as well as additional challenges facing a patient with fatty liver disease and COVID-19.
This education is supported in part by an independent medical education grant from Pfizer Inc. and is in accordance with ACCME guidelines.
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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. Hello, my name is Amanda Cheney, and I am bringing you today a lecture assed part of the cova 19 expert lecture. Siri's. We're going to talk today about naff Aled and Nash and what the differences between those diagnoses are as well as a little bit about Cove in 19 and how to approach the patient who has fatty liver disease with Koven Night. Here are my disclosures. We have a few objectives to talk about today. With this talk, we're going to differentiate between nah filled and Nash. We're going to stay two reasons why a liver biopsy would be needed for the patient with fatty liver disease. We're going to discuss three non pharmacological treatments in the treatment of fatty liver disease, as well as's and current investigational pharmacologic pharmacology regiments. But first of all, we need to talk a little bit about the background of match and baffled, and we know for sure that it is definitely underestimated. We believe that many more patients have fatty liver disease than what is discussed in the literature. We estimate that there is a global prevalence of about 25%. Patients with metabolic syndrome has tend to have a higher prevalence of fatty liver disease, and we know that there is an increased mortality risk in the patient with fatty liver disease, specifically with coronary artery, an event or cardiovascular disease. It's the third most common com common cause of Peninsular carcinoma, And Nash currently is the second most common cause for a liver transplant for an indication for liver trains. Currently, our numbers reflect a viral hepatitis being the number one cause hepatitis C. But soon we believe that because of fatty liver disease becoming more common and hepatitis C having such great treatment regimens that Nash related cirrhosis is quickly gonna be coming. Taking over for that number one spot. We know that obesity is a predictor of national related cirrhosis as well. When we think of natural when we say that term, it means non alcoholic fatty liver disease, and really all that means is that there is evidence of a paddocks tho sis or fat in the liver cells. There's a lack of secondary causes of why there would be fat in the cells, and there's no significant alcohol consumption or coexisting liver disease as a cause for this to happen. We know there's several co morbid conditions and association with fatty liver disease, and those include just academia, diabetes mellitus, obesity, polycystic ovarian disease. Metabolic syndrome is common as well. And when we think of Mass aled, we need to think of it as a spectrum of disease. So we have non alcoholic fatty liver, so that's just like the big umbrella of disease. Then we can break that down into the hip paddocks ketosis, where there's fat in the liver cells gradually. If that goes on for a prolonged amount of time, inflammation occurs. And that, and so that inflammation is called non alcoholic STI attitude. Hepatitis. That's the inflammation piece and then eventually cellular changes occur and can cause fibrosis and then cirrhosis. And sometimes that cellular carcinoma, the path of physiology is not well understood. It is complex, but there is not thio to be believed that there is an insulin resistance problems, so insulin respect er's become less responsive to insulin in the cell and blood sugars in the cells and, as a result, the liver response by increasing fat into those cells. In addition, fat going out of the cells becomes impaired, and there's decreased fatty accid Austin oxidation, and as a result, these fat globular its form in the cells and they just large and enlarge. Later on. There's a second hit and side of canes are released and inflammation occurs, which leads more to oxidative stress and cellular death, which then causes of cellular and structural changes leading to fibrosis and cirrhosis. This is a really good depiction of the fat globules in the cells, the state Acis, as I mentioned, and thes fat droplets form and grow in the within the parasites. The liver becomes enlarged, its soft. It's greasy, it's yellow, the cells become fragile and unstable, and as a result, the side of kinds are released free. Radicals are released, and this reaction occurs, leading to mitochondrial death and leading to cellular death. This inflammation occurs, and so this inflammation plus fat in the liver cells equals D attitude hepatitis, and it can be with or without alcohol. So if it's because of alcohol, that is alcohol beatitude hepatitis. If alcohol can't be blamed, then it would be non alcoholic. Ski attitude. Hepatitis chronic, natch, leads to fibroid tissue and leads to structural design. Um, impairment. And so then fibrosis develops as well. A cirrhosis. We believe that there is a dietary component to this, with high consumption of cholesterol and or sugar. It causes more fat to be deposited into the liver. This can cause more inflammation and injury. And then we know that there's influence resistance problems with patient who has diabetes and so that can cause further injury as well as if a patient has hyper triglyceride anemia or Hyperloop anemia, that cholesterol is high and elevated within the plasma and the blood cells bloodstream. And so, with more of that occurring, there could be more of the fat being available for consumption and the liver. All of this cause it's more injury and inflammation. It's good to point out, though, and we should point out it several times, and this that can be reversed with my exercising but blood glucose control. So what do you do at first? So with your initial evaluation, you're gonna exclude other causes, so you're going to get some laboratory testing, ruling out any auto immune components ruling out any other biliary issues or viral hepatitis that could have caused liver injury. And you want to understand if there are any other presence of other co morbidity. So any other issues of hypertension, metabolic disease, auto immune disease anywhere else in the body. Liver biopsy is the gold standard for diagnosis, but it does come at a cost, and it does have its risks with the procedures such as bleeding and infection, bowel perforation. And so definitely this should be done at a center where they do a lot of them. And there is an expert who does it some non invasive ways to figure out if a patient possibly could have fatty liver disease for a few calculations, one is the best. One is the Fed, for there's additional imaging. And then there's a fairly new school of thought about sido keratin, 18 fragments, um, again being studied, not anything that's readily available in our current state in 2020. So the first stop point assed faras what image ing studies to get you would want to get an ultrasound at first. You just like this happening with your patients and any of these images. Studies can pick up fat in the liver cells, so ultrasound CT scan. Anne Marie all can see fatty and fill treats in the liver. You also want to know if there's a degree of fibrosis, so the degree of fibrosis should be evaluated. And how do we do that? Well, there's a few laboratory testing, um, scores that you can look into such as enough old fibrosis. Score the fib before the STM platelet ratio, but then fiber scanner last. Geography is another great way to do that. We'll look at what's really important for us to know is that higher degree of fibrosis equates to poorer outcome. So we definitely want to know earlier if we can and know how to reverse the issues going on with the insulin resistance and the fat deposit ation in the liver, let's talk a little about the last geography, so fiber scan is becoming more and more popular. It's fear wave through the Livermore stiff equals more fibrosis. So if it is really good in determining the degree of fibrosis, that's an F three of four, which is advanced fibrosis before cirrhosis and so the score on that would be 8 to 12 K p A. Or greater magnetic. Residents can let us know fibrosis scores, but it is expensive and not easily as available as the fiber scan would be. So there are some complications of fatty liver disease and the most important and independent risk factor with for cardiovascular disease. So if a patient has fatty liver disease, they should also be evaluated for cardiovascular disease. Eso number one Looking at Combe abilities such as hypertension, hyper trifles for anemia, hypercholesterolemia looking for any reason for cardiac disease. And so stress testing may be necessary if a patient has chest pain or symptoms of cardiovascular disease. And if, um, organization is indicated based on stress test findings, then definitely that should be done and should go ahead and proceed with that. Just nobody me A. You would treat disobeyed EMEA, just as you would anybody in the general population. Um, I do get frequent consults about patients who have liver disease for one reason or another, and should they continue on their standing and the answer is yes, please. On there. Vibrates are important and good for patients with hypertrophic lister anemia, hypertension goals as the per the general population. And we can use things like ACE inhibitors or ARBs. Um, those are good for For this patient population, the things we need to think about is obstructive sleep apnea. So if a patient is, um, has co morbidity a significant for obesity thing, we would want to have them go for a sleep study to understand if they are having any sort of sleep apnea, as well as getting them a CPAP machine that is needed. We also want to think about chronic kidney disease, especially in a patient who has had long standing diabetes. They could have kidney injury, and we would definitely want to make sure that they have that identified and treated approach. So what about fatty liver and Cove in? So this was a paper that was published earlier this year in 2020 that talks quite a bit about patient with liver disease during the cove in 19 p. M. Gemma. One thing that we really have to think about is there has been noted significantly noted in the literature that patients who have metabolic syndrome, who have obesity, who have hypertension, metabolic syndrome, thes patients when they do have Kobe, 19, are more at risk for a severe infection. And so we have to be aware of that. And we have to make sure that, um, if it is identified, then we promptly get those patients treatment as soon as possible. So what are some non pharmacologic treatments for fatty liver disease? Weight loss and lifestyle modifications are the mainstay of treatment. We want toe aim for a patient to reduce calories about 500 to 1000 per day. Incorporate moderate intensity of exercise. And there have been some research studies that have shown and proven that with a 3 to 5% weight loss, their liver pathology changes and improves. And so just with the 3 to 5% weight loss there's shown toe have improvement. Instituto Sis. With a greater than 7% weight loss, Nash, it's improved, and with a greater 10% weight loss, then we know that fibrosis is improved in those patients, and so to me, this is a very powerful piece of data, and I think it's important to share this with our patients that we know that weight loss and diet and exercise and lifestyle changes can work If you do that, if you do the hard work, we want to tell them to avoid alcohol consumption. So don't add any more insult to injury. Yet the diabetes under control um make sure that there's no additional contribution thio causing more fat be in those cells and aggressive modification of the cardiovascular disease risk factors. So definitely controlling the diabetes controlling the DISIP anemia ordering the staten, um, if indicated, and they need that and then making sure that they have a sleep study, Um, if sleep apnea is a concern as well as a CPAP machine. So what do we do when we talk about lifestyle changes? So it's It's not a diet, it's not. It's something that they need to go out for the rest of their lives. And so making sure that there's protein with every meal. Ah, healthy portion of Cuba, Big portion of vegetables and fruits focus on carbohydrates and ensure that they're not exceeding a certain number. They can partner with a nutrition to actually guide them on what those numbers to be set a reasonable goals using the smart goals, so making it sustainable, making measurable, um, making it accessible, realistic. So I was thinking about very specific ways and small, tiny goals at first. And then, as they see that that's working and that that's a positive change and that they feel better than it will encourage them a little bit more. I always like to keep a positive focus and make sure that patients are not being in themselves up. Too bad about not losing weight quick enough it za lifestyle changing. It's a marathon. It's a journey. It's not anything that's gonna happen quick with a snap of our fingers. So one important question that I think we've need to be mindful of what the patient who has obesity is can patient with obesity, have malnutrition, and the answer is yes. But they can't have both diagnosis at the same time. Obesity is a measurement, Um, usually by definition of b m i. Onda malnutrition is looking more at muscle mass, um, looking Maura about quality nutrition. And so I have had many patients who have had who are both who have Onda notes, documented a well nourished person. But then they have malnutrition because the quality of their nutrition is not good and they're having significant muscle wasting, especially in the patient with liver. Marco Pina is common, and it is actually related to more poor outcomes and the post transplant setting. So that's really something that we should be mindful of in this, like the National Patient is most likely to be. Circle Penick and partnership with physical therapy. Nutrition is really important. Thio optimize nutrition choices as well as talked about strategic exercise to improve muscle mass conditioning. There are some options for surgery for patient who is obese and has Nash and I would consider it on a case by case basis. Um, there are some studies out there that are doing bariatric surgery at the time of a liver transplant. For a patient with Nash related cirrhosis, Um, and more details will be coming forth in the coming years. I think about that. We definitely know that very interest surgery is effective in weight loss and decreases a patient's cardiovascular events and mortality as well as improves their diabetes. And so, um, just know that this option is out there, and that it is should be different, determined on a case by case basis, and a patient really needs to be ready for such a drastic lifestyle changes well. There's several different kinds. Ruin. Why is one of the earlier versions and most common? And then there's an adjustable band where the band is around a portion of the stomach and just limits the amount of food and liquids that a patient can take. And they do it, you know, switch with another one ruined. Why a duodenal switch to have their risks of jumping Centrum and more malabsorption issues. But again, close collaboration with surgical team and a multi disciplinary approach is definitely important if this is the route that you wish to go. So there have been a lot of buzz in the literature and at meetings about when are we gonna have a medication to treat Nash? And currently we're not there. There is no FDA approved medication for the treatment of cash that Foreman has been studied, but it's not. It recommended as a treatment for Nash. There are some thighs sides that improve histology or Nash proven cirrhosis and then plus or minus whether or not they have diabetes or not. But there's no for sure recommendation our practice guideline that supports that more studies are needed on these other medications, but again, they've been studied, but they just haven't been approved yet for this purpose yet. So again, the mainstay of treatment is lifestyle changes, and there is no medication right now to treat mash other things in the literature. Vitamin E, um, is prescribed sometimes for patients who do not have diabetes, but have Nash proven cirrhosis or fibrosis. It's not recommended in other groups, so it's not recommended in patients who are diabetic. Then, er so is not recommended. It's been studied, but again, not recommended. It didn't have a really proven exceptional outcome for those patients, and then omega three fatty acids are not recommended for National baffled, but you can consider it in a patient who has high triglycerides along with value later. So the patient with Nash related cirrhosis, we do have to be mindful that the risk of cardiovascular disease and cardiovascular events is higher, so knowing that um is helpful when determining your next steps and managing this patient long term, the patient has cirrhosis. They should be screened per practice guidelines for esophageal various sees as well as for penance cellular carcinoma. The routine screening for competitive cellular carcinomas every six months by either C T. With contrast or Emery, and then a stop until very issue screening with G D. Um is recommended every 6 12 months. If there's banding, then possibly more often. If if that those were found, various Cesaire found and they needed to be treated routine. Repeat. Liver biopsy is not really recommended. They have cirrhosis. There's not really a point and getting another biopsy to show that they have cirrhosis again. So, um, and then we need to determine. At this stage, we know the patient has cirrhosis. So are they compensated, and they have no evidence of societies or any other complications of cirrhosis or if they moved into a D compensated state. And if that's true, then they need an evaluation for a libertarian stance at a trade etcetera. If they also have developed a notable HCC or a Peninsular carcinoma, then they would need to go to a transplant center for evaluation. The post transplant setting Um, we know that it does worsen Metabolic syndrome, especially for patients already have that initially made of suppressants such as, um, Checker Lima's as well a steroids can worsen triglycerides it can worsen cholesterol, it can worsen hypertension eso as well as glucose levels. And so we need to be aware of that in the post transplant setting and treat those promptly and other complications and challenges with Nash patients who have already because of their complications of cirrhosis, say the pattern renal syndrome. This possibly could be worsened in a patient with fatty liver disease because of coexisting renal damage, maybe because of diabetes. For a patient who already has about a pulmonary syndrome, if they have on top of that obstructive sleep apnea or cardiovascular disease, that could contribute more to their risk for hypoxia and make that worse. For the patient who has societies, there could be some challenges with getting a good sample, Um, for a piercing thesis due to the deposit e of the truck tal obesity that could that could lead to some challenges, and then patient with portal hypertension. Um, that is a little bit worse, and the patient with obesity and so having all of these notations in your mind and considerations is important when caring for the patient with fatty liver disease, patient with obesity and diabetes, their risk of cancer increases even in the absence of cirrhosis. Just because of those two coexisting diagnoses, Um, that risk for cancer does go up. So again, that image ing every six months is really important to make sure that they do not have and HTC or, if they do, we identify it quickly and treated accordingly. And then the patient who has ongoing use of alcohol, whether it's social or even just a drink every now and then that does increase their risk for HTC as well. So another key component to be aware of we mentioned earlier Thio treat hypertension treats, um, hyper live anemia and high cholesterol Justus, if you would the general population. So please make sure that you tell your colleagues, um, Thio treat that accordingly. And then the patient with, um, fatty liver disease and who is a pediatric patients? Um, definitely. The same is the same. Treatment. Evaluation is the same as with adults, so test for other causes. There's not enough evidence to support routine screening, so just because a mom or dad has fatty liver disease or metabolic syndrome, it doesn't necessarily mean that we need to screen their Children for that. Um, there just isn't enough literature out that out there to back that up. Liver biopsy would be indicated in the area and the if the diagnosis is unclear prior to start of any of PETA toxic medication. Specifically like I'm thinking for acne or anything like that on Ben. Potential Promotable Causes of Liver Disease Biopsy There's many characteristics seen on pathology with this patient population. And, um, having that biopsy done at a pediatric transplant center would probably be your best idea again. The mainstay of treatment is lifestyle modifications. Again, there's no medication to treat fatty liver at this time. So what's on the horizon? So the goal of the new Nash treatments, or what we hope that we can accomplish in the next the next few years, is that these treatments provide histological improvements. They improve fibrosis, and the new medications are like once a day, one pill, once a day with minimal side of. And so that would be, you know, a dream that would be fantastic to be able to set it up out. There are some medications that are inveighs three trials, but again, nothing is approved as of yet, So in conclusion, I just want to remind you that there batty liver disease is a broad spectrum of disease. Other causes of liver disease should be ruled out. Many patients are asymptomatic and are walking around just doing fine. Sometimes we don't even know a patient has fatty liver disease, and so they have an ultrasound for another abdominal imaging. For another reason, and incidentally, we find fatty liver. There is a strong association between fatty liver disease and cardiovascular disease, so please be aware of that and treat other risk factors for cardiovascular disease. Appropriately, Lifestyle changes are the mainstay of treatment. If there are any signs of D compensated cirrhosis, the patient should be referred to in transplant center refer transfer, liver transplant evaluation. And we know that the risk factor for PETA cellular carcinoma is increased with alcohol consumption, no matter how little bit of it is, and with fatty liver disease. That concludes this presentation. And here's my contact information. If you have any questions, feel free to contact me any time. Um, email is usually the best way to get a hold of me, and I hope this was really helpful for you. Thank you so much
