Welcome to the Clinical Practice Special Interest Group session. This year, we will be discussing common problems in clinical hepatology. I'm Chris Cowdley, Director, Liver Institute Northwest, and the Chair of the Clinical Practice Special Interest Group, and I'm delighted to host this session with Dr. Paul Thilovath, who is the incoming Chair for the Clinical Practice SIG. We have several state-of-the-art lectures by experts scheduled for this session, and hopefully there will be some time for interaction. The talks include discussion of interpretation and evaluation of elevated iron studies in the patient with liver disease, management of acute kidney injury in the hospitalized patient with cirrhosis, surveillance for hepatocellular carcinoma and cholangiocarcinoma in patients with liver disease, and current management of non-alcoholic fatty liver disease, describing both pharmacologic and non-pharmacologic approaches. So I think we're due for a special and invigorating session, and I want to thank the speakers and the audience for participating with us here in the Clinical Practice Special Interest Group. Thank you. Thank you to the AASLD Clinical Practice Special Interest Group for allowing me to present this talk regarding the interpretation and evaluation of elevated iron studies in the patient with liver disease. This is my biography, and these are my disclosures. What I'd like to provide first is an overview of the definitions of commonly used terms when discussing iron overload. Hepcidin is a hormone synthesized by the liver, which reduces intestinal iron absorption through the binding and degradation of ferroportin-1. And what is ferroportin-1? It's a transmembrane protein found in a variety of cells, including the intestinal enterocytes, hepatocytes, and macrophages, which facilitates extracellular iron export. Transferrin is a glycoprotein synthesized in the liver, which carries iron into the systemic circulation. It's important to know the definition of transferrin, as there are several commonly used terms regarding hereditary hemochromatosis which are associated with transferrin. These include the following. Unsaturated iron binding capacity, or UIBC, is the portion of iron binding sites on transferrin which are not occupied by iron. Therefore, a low UIBC is consistent with hereditary hemochromatosis, since this suggests that the majority of iron binding sites on the transferrin protein are in fact occupied by iron. The total iron binding capacity, or TIBC, is calculated as the sum of the serum iron and UIBC. The transferrin iron saturation, also known as transferrin saturation, is a mathematical calculation of serum iron divided by TIBC. Oftentimes when you order an iron panel, the transferrin saturation and TIBC will be provided for you. A transferrin saturation of above 45% may be indicative of hereditary hemochromatosis. Finally, there is the serum ferritin. Ferritin is an intracellular protein that stores and releases iron. Keep in mind that it has both dietary and diurnal variation, and therefore should ideally be drawn in the morning and in a fasted state. A ferritin level greater than 300 ng per mL in men or greater than 200 ng per mL in women is considered elevated. The most common form of iron overload, hereditary hemochromatosis, is a genetic disorder, which is usually autosomally recessive in inheritance and which leads to increased iron deposition in human tissue. Iron is regulated predominantly through intestinal absorption with some contribution of menses in premenopausal women. However, aside from menses, the body has no way to remove iron intrinsically, and therefore the only mechanism to regulate it is by reducing intestinal absorption through a negative feedback loop. And it is the dysregulation in this negative feedback loop because of defects in the hormone hepsidin which ultimately lead to an increase in iron absorption. This figure displays the physiology of iron absorption. Pay attention to the right side. In the upper right corner is displayed hepsidin, which is the hormone which regulates iron absorption by binding to and degrading ferroportin-1 when there is sensation of elevated iron in the systemic circulation. Hereditary hemochromatosis can be grouped into four categories designated as types one through four depending on the mutation which leads to the disease. In type one hereditary hemochromatosis, also known as HFE-related hemochromatosis, the primary genetic mutations are the C282Y and H63D mutations. Patients who are homozygotes have two C282Y mutations, which accounts for more than 90% of cases of hereditary hemochromatosis. Subsequently, these patients have higher hepatic iron concentration relative to compound heterozygotes. Patients who have a single C282Y and H63D mutation are known as compound heterozygotes and they comprise anywhere from 2% to 7% of cases. Typically, they have a lower hepatic iron concentration than homozygotes. Finally, when genetic testing is ordered, additional mutations may be reported which are not clinically relevant. This includes the S65C mutation and the H63D mutation in isolation, meaning without a concomitant C282Y mutation. In both cases, there is no risk of iron overload unless there is another iron loading condition present. This includes patients who have two H63D mutations and are thus H63D homozygotes, which comprises less than 1% of hereditary hemochromatosis cases. Type two hemochromatosis, also known as juvenile hemochromatosis, is associated with greatly increased iron stores relative to type one hemochromatosis, along with the possible earlier onset of disease. The primary mutations are in either hemojuvalin, which is classified as type 2A, or in hepcidin, classified as type 2B, though with significantly less activity as compared to type one hemochromatosis, which is also noted to have hepcidin deficiency. Clinical symptoms are overall similar to that of hemochromatosis, though along with the earlier onset of disease, the transfer and saturation is often greatly elevated above 70%, and the ferritin is also often elevated to above 1,000. In addition, non-hepatic manifestations such as hypogonadism and cardiac disease with risk of sudden cardiac death are more prevalent in type two hemochromatosis. Type three hemochromatosis, also known as transfer and receptor two associated hemochromatosis, is due to a mutation in the transfer and receptor two gene. Overall, the presentation is similar to type one hemochromatosis with regards to the degree of iron overloading, pattern of hepatic iron deposition, and response to phlebotomy, although there may be an earlier age of onset. Type four hemochromatosis is a slightly different disease, as the mutation which occurs in the SLC40A1 gene is associated with the ferroportin transporter itself, rather than with hepcidin. In particular, the genetic mutation leads to a gain of function in the ferroportin transporter, ultimately leading to hepcidin resistance. The pattern of inheritance is autosomal dominant, though there is incomplete penetrance, and the clinical presentation is overall similar to that of type one hemochromatosis. And finally, there is ferroportin disease. This condition also occurs due to a mutation in the SLC40A1 gene. However, this leads to a loss of function in ferroportin transport, rather than a gain of function as seen in type four hemochromatosis. The inheritance pattern is also autosomal dominant, and what is occurring physiologically is due to the defect in the ferroportin protein, it leads to iron deposition, but this preferentially occurs in the macrophages and the reticuloendothelial cells. In fact, the hallmark of ferroportin disease on liver biopsy is iron deposition in the cup for cells. With regards to clinical presentation, oftentimes the presentation is a combination of hyperferritinemia with a normal or even low transferrin saturation as compared to a high transferrin saturation as seen in types one through four hemochromatosis. I'd also like to discuss secondary iron overload, which is the occurrence of excess iron absorption or elevated iron studies in the absence of a genetic mutation. The clinical presentation is often mild to severe hyperferritinemia with a normal or low transferrin saturation, and if iron deposition does occur, it typically involves the reticuloendothelial cells. Secondary iron overload can be divided into hematologic and non-hematologic causes. The hematologic causes, such as iron-loading anemias, chronic blood transfusions, or parenteral iron overload, often yield a low transferrin saturation, a highly elevated ferritin, and of course, the presence of anemia. The non-hematologic causes, which include other forms of liver disease, such as non-alcoholic fatty liver disease, as well as systemic inflammatory states, such as malignancy or rheumatoid arthritis, lead to a normal or possibly low transferrin saturation, but with or without anemia, and a mild to moderately elevated ferritin level. It is possible to get a high ferritin level of above 1,000 nanograms per milliliter in a non-hematologic cause of secondary iron overload, but this is not typical. At this point, let's try to put this information into the context of a clinical case. This is a patient who was referred for elevated liver enzymes. He's a 54-year-old male with a past medical history of diabetes and class 1 obesity. He drinks socially and has no family history of liver disease. His liver enzymes demonstrate an elevated ALT and AST to 64 and 58, respectively, and the remainder of his hepatic panel was within normal limits. His complete blood count and creatinine were also within normal limits. His iron studies demonstrated an elevated ferritin to 1,012 nanograms per milliliter with a transferrin saturation of 38%. His gene testing was negative for the C282Y or H63D mutations. Viral and autoimmune hepatitis panels were negative, and an ultrasound demonstrated diffuse fatty infiltration with a normal liver contour. There are several considerations for this patient. First, could the ferritin level be falsely elevated? For instance, was it drawn in the morning and when fasting? Could his elevated aminotransferases and elevated ferritin be from non-alcoholic fatty liver disease, or could the patient have a non-HFE-related iron overload condition? Ultimately, after discussing the available options for evaluation, the patient underwent a liver biopsy, which demonstrated steatosis without steatohepatitis, diffuse iron deposition in the cup for cells and stage 1 fibrosis, and the diagnosis of ferritin disease was made. In general, a liver biopsy is not often used as a modality to determine a diagnosis of type 1 hemochromatosis due to the availability of genetic testing. The primary purpose is for fibrosis staging in someone with established hemochromatosis, particularly if the serum ferritin level approaches or is above 1,000 nanograms per milliliter. In addition, a liver biopsy can help to differentiate between the different types of hemochromatosis, as well as ferritin disease and secondary iron overload, depending on the pattern of iron deposition seen in the biopsy. In this next slide, I want to illustrate the importance of the serum ferritin level as a marker of end-organ damage and an indicator to consider fibrosis staging in the setting of hemochromatosis. In this study published in 2003, 182 patients with biopsy-proven hemochromatosis were studied. None of the patients consumed high amounts of alcohol or had risk factors for non-alcoholic fatty liver disease. In the graph, there are three columns. On the left side, we see that 22% of the patients in the total study cohort had cirrhosis. Now in the next two columns, patients are grouped according to the serum ferritin level at the time of biopsy. Less than 1% of patients with a serum ferritin level less than 1,000 had cirrhosis, compared to nearly 45% of patients with a ferritin level above 1,000. Therefore, this study underscores the importance of fibrosis staging among patients with type I hemochromatosis, particularly C282Y homozygotes, with a ferritin level above 1,000. This slide displays two biopsy samples from a patient with type I hemochromatosis. The stain for iron is called a Prussian blue stain, and in type I hemochromatosis, iron typically stains in the hepatocytes, particularly in the periportal regions. This slide shows biopsy samples from patients with type II and III hemochromatosis, along with variportin disease. In the upper left corner, designated as picture A, is a patient with type III hemochromatosis. There is periportal iron staining within the hepatocytes, similar to that of type I hemochromatosis. Picture B in the upper right corner illustrates type II or juvenile hemochromatosis, which is designated by a significant increase in iron deposition and iron staining. Finally, in picture C and D, biopsies from early and late variportin disease are shown. The main point to illustrate is that iron uptake occurs not in the hepatocytes themselves, but in the cup for cells which surround the hepatocytes. MRI has recently become a very useful tool in the evaluation of patients with elevated iron studies. It can quantify hepatic iron deposition in the liver, and in combination with MR elastography can also stage for fibrosis. It's important to note that the MRI scan must be performed with specific software, such as FerriScan or T2SpinEcho, to accurately quantify the degree of iron deposition. On the right side of this slide, there are two MRI pictures of patients with hepatic iron overload. The one on top is a patient with type I hemochromatosis, while the one on the bottom is a patient with variportin disease. As you look at the top picture, you can see the liver is black, consistent with iron deposition, whereas the spleen is bright. However, in the bottom picture, both the liver and the spleen are dark, indicating both hepatic and splenic iron uptake. This is a simple way to differentiate type I hemochromatosis from variportin disease, since genetic testing for variportin disease is not commercially available. Finally, to bring this talk back to our patient case, I'd like to highlight the differences between type I hemochromatosis and variportin disease. Clinically, type I hemochromatosis presents with an elevated ferritin level and transfer and saturation, whereas variportin disease presents with an elevated ferritin level but normal or low transfer and saturation. Histologically, iron deposition occurs in the hepatocytes in type I hemochromatosis versus the cup for cells in variportin disease. With regards to management, serial phlebotomy is the treatment for both conditions. However, in variportin disease, there is a higher risk of anemia. And finally, with regards to dietary and supplement restrictions, in both conditions, there are no food restrictions for patients undergoing serial phlebotomy. However, in type I hemochromatosis, even for a patient undergoing phlebotomy, there is a recommendation to avoid iron and vitamin C supplements. However, no such restriction exists with regards to variportin disease. Although the primary focus of this talk was regarding the interpretation and evaluation of elevated iron studies, I'd like to finish up by discussing the treatment of iron overload. In general, when counseling a patient who is about to undergo phlebotomy, I tell them that phlebotomy would occur weekly. And on average, 500 milliliters of blood would be removed each session. The goal would be for the patient to have a serum ferritin level of between 50 to 100 milligrams per milliliter. After this is attained, the frequency of phlebotomy can be reduced to as little as three to four times per year. While undergoing phlebotomy, there are no dietary restrictions, but I advise avoidance of iron supplements as well as vitamin C supplements. Finally, it's important to counsel the patient that conditions such as cirrhosis, arthralgias, hypogonadism, and diabetes may not improve with serial phlebotomy. Certain patients may not be ideal candidates for phlebotomy, including those with baseline anemia or with phobia of needles. In such cases, chelating agents may be used, but keep in mind they are not considered to be first-line therapy. Currently, there are three agents approved by the FDA. Defaroxamine is given as a subcutaneous injection or IV infusion and has side effects including retinopathy and ototoxicity. Differiprone is an oral agent which can cause cytopenia. And the newest approved agent, Defesorox, is an oral chelator which can cause renal toxicity, rash, and GI upset. Beyond phlebotomy and chelation, additional treatments are available, though their indications are overall limited. Erythrocytophoresis is the selective removal of red cells with return of platelets and clotting factors. So it can be beneficial among those patients with cirrhosis who have severe thrombocytopenia. It can also lead to a reduction in ferritin level using fewer treatments than phlebotomy. Proton pump inhibitors are not considered a primary treatment modality, but can be used as an adjunct to phlebotomy. The reason for their efficacy is because gastric acid inhibition reduces the release of iron from food. In a randomized control trial comparing phlebotomy to phlebotomy plus pantoprazole 40 mg daily, it was found that the use of pantoprazole led to a significant reduction in the number of phlebotomy treatments required to achieve a goal ferritin level. However, due to their own associated adverse side effects, the routine use of proton pump inhibitors in the setting of iron overload treatment is not recommended. With regards to secondary iron overload, the majority of cases are due either to frequent blood transfusions, IV iron administration, or from an iron loading anemia. Therefore, chelation as opposed to phlebotomy is often the first line treatment. A ferritin level of above 1,000 is considered a reasonable threshold to initiate treatment, though for certain anemic states a lower threshold of 800 is recommended. Finally, for patients who have elevated iron studies from a separate liver disease such as non-alcoholic steatohepatitis, there is no indication that concurrent iron removal leads to improved outcomes. For my final takeaway slide, I'd like to review this algorithm from the most recent American College of Gastroenterology guidelines with regards to when to initiate treatment. If there is a patient with suspected hemochromatosis based on appropriate symptoms, elevated liver enzymes or genetic predisposition, first check an iron panel to determine the transfer and iron saturation along with the serum ferritin level. If the percent saturation is less than 45% and the serum ferritin is within normal limits, then no further evaluation is needed. If the transfer and saturation is above 45%, then HFE genotyping should be performed. It is also reasonable to perform genotyping if the ferritin level is elevated to above 300 nanograms per milliliter in men or greater than 200 nanograms per milliliter in women. Once genotyping is performed, if the patient is a C282Y homozygote, then phlebotomy should be initiated unless the baseline serum ferritin level is less than 100 nanograms per milliliter. For patients with a baseline ferritin level above 1,000 nanograms per milliliter, fibrosis staging should be done either with a liver biopsy or MR elastography. Finally, for patients who are either compound heterozygotes or who do not have any of the typical genetic mutations associated with HFE-related hemochromatosis, they should be evaluated for other etiologies of liver disease or for hematologic causes of elevated iron studies. In this setting, a liver biopsy may be indicated. An MRI can also be done to quantify hepatic iron content. In this situation, if other liver diseases have been ruled out which could cause elevated iron studies, and if there is an elevated hepatic iron concentration as demonstrated on biopsy or MRI, and particularly if the ferritin level approaches or is above 1,000, phlebotomy can be considered. For patients who are at risk of developing anemia, chelation is an alternative treatment and is the preferred treatment. And I thank you for your attention. Hello, my name is Josh Levitsky. I'm a professor of medicine, surgery, and medical education at Northwestern University Feinberg School of Medicine. The title of my talk is Management of Acute Kidney Injury in the Hospitalized Patient with Cirrhosis. These are my disclosures. So I wanted to start with an outline for this lecture. We're going to start off with a case presentation that's going to be a good representative example of acute kidney injury in a patient with cirrhosis who's hospitalized. We'll then move into the evaluation and diagnosis of acute kidney injury in this patient population, then discuss management and outcomes, and with prevention of acute kidney injury and some biomarkers that are, I think, very exciting for detection, early detection of acute kidney injury and outcomes. So let's start with a case presentation. This patient is a 62-year-old male with hepatitis C and alcoholic cirrhosis, complicated by hepatic encephalopathy, diuretic-resistant ascites, who presents with an elevated creatinine to 2.9 mg per deciliter and a sodium of 125. Three weeks ago, the patient had a serum creatinine of 1.2, so this is a significant increase from the baseline. The most recent LVP was one week ago in which 10 liters of ascites fluid were drained. There was no evidence of SBP. In addition, diuretic doses were increased. Patient presents to the emergency room after being called because of his elevated creatinine. Patient has a temperature of 101.2. Blood pressure is low at 92 over 66. He has moderate muscle wasting ascites with a tender abdomen, 2 plus peripheral edema and mild asterixis. Patient is admitted to work up the renal dysfunction and possibility of infection. And so the question is, what is the approach to this patient who presents with a significant deterioration in renal function acutely? And so let's talk about the evaluation and diagnosis of acute kidney injury for which this patient is presenting with. It's really important to know about evaluating renal function in the general population and this can be applicable to the patients with cirrhosis. So what's really important is that serum creatinine only gives you a value and really what needs to be done is to correlate that serum creatinine with the glomerular filtration rate based on patient's age and other comorbidities. And so we have three different people with a serum creatinine of 1.2 can mean a different GFR in someone who's young and healthy versus an older person and a significantly older person where the GFR is about half that of the younger person. So serum creatinine is not a good measure independently of itself of renal function. Really have to correlate this with GFR equations either estimated or measured and we'll get into that in a few slides. How is this different in cirrhosis? The principles are quite similar to the previous slide with a few caveats. So in cirrhosis, elevated bilirubin can interfere with creatinine assay. So if bilirubin is above 5 or 10, this may give you an inaccurate value for creatinine where you base your estimated GFR on. Also because of muscle loss and there's elevated creatinine can be very significant in patients who have decreased muscle mass or it's more significant if the muscle mass is low. There's also decreased hepatic production of creatinine and creatine in cirrhosis because the liver is not functioning as well and there's increased volume of distribution of creatinine with anisarca. So this really kind of drives down the serum creatinine in patients with cirrhosis. Really overestimates the GFR. As such, a creatinine in a patient with muscle wasting, high bilirubin, and refractory ascites, when creatinine is 1.0, that is quite significant deterioration in GFR. The second point is, which goes along with this concept that renal function in patients with cirrhosis is important to evaluate at all different stages, really drives home the point on the right, which is that a large change in GFR can occur with just a little change in creatinine. So creatinine going from 0.5 to 0.9 is a significant change compared to a creatinine going from 3 to 6. And so that is a concept that not everybody is familiar with and we get less concerned about lower changes or changes in creatinine at the lower levels when we really should be more concerned because it results in a significant difference in GFR even when the creatinine is at a low level. Let's talk next about evaluating renal function. So estimated GFR is really how it's done in the clinic. You have your serum creatinine, which we know is not as accurate in patients with cirrhosis, but you put it into an equation that accounts for these other factors and can better estimate the true GFR, particularly if you use cis-statin-C when combined with creatinine, it appears to be a more accurate estimate of true GFR. Well, the real estimate or the real GFR is done by measuring GFR and these are complicated tests and expensive, but they're the most accurate measure. So what you're measuring is clearance of a substance from the blood, such as inulin, iothalamate, iohexol, or doing a nuclear GFR using DTPA, sometimes creatinine clearance, but there are issues with 24-hour collection, especially in patients who do not have significant urine output. But again, these are not useful for serial monitoring and can be difficult logistically. So we tend to go back to estimated equations and to estimate the true GFR. Looking at the spectrum of AKI and cirrhosis, really there's a lot of overlap. Chronic renal failure due to structural renal disease or renal obstruction can overlap with functional renal failure, which is classically type 1 and type 2 HRS. And so it sometimes can be difficult to distinguish these etiologies. Let's talk about hospitalized patients with cirrhosis and they're presenting with AKI. What is the likelihood that they're going to have these different diagnoses, pre-renal, intra-renal, or post-renal dysfunction? And so about 20% of the hospitalized patients with cirrhosis have acute kidney injury. Of that percentage, two-thirds of them are pre-renal in nature. So only a third of them will be intra-renal, like ATN, glomerulonephritis, pretty rare, obstruction pretty rare, so more often ATN. That's only a third. Two-thirds of them will be pre-renal and two-thirds of pre-renal will be volume responsive. So the patient is dehydrated, on too many diuretics, you give volume back and they improve. And then one-third are non-volume responsive and these are HRS type 1 and type 2. So the answer for the question of hospitalized patient with cirrhosis with AKI, a lot of people think, well, that's got to be HRS when in fact, it's only a small percentage that actually have HRS who are hospitalized with AKI. There are new criteria that have been developed to better define acute kidney injury in patients with cirrhosis. And I'm not going to go through every one of these definitions, but really what we're looking at is there's acute kidney injury, there's chronic kidney disease, and then there's acute on chronic kidney disease, where there's a rise in serum creatinine above the baseline on top of patients who have chronic kidney disease. And then there are different stages of AKI, stage 1, 2, and 3, and this is important because it relates to in-hospital mortality. So stage 1 would be an increase in serum creatinine of greater than or equal to 0.3 or an increase in serum creatinine by greater than 50 to 100% from baseline. And this increases as the stage progresses to where there's worsening renal dysfunction, more increases from the baseline, or need for renal replacement therapy. We'll get to prognosis and outcomes a little bit later. So how do we evaluate and manage AKI and cirrhosis? The first thing to do is to look at the patient's volume status and give them back volume, usually by intravenous albumin, and discontinue their diuretic regimen so that you can adequately replete their intravascular volume. We certainly, as we know, a third of the patients have some intrinsic renal dysfunction that's acute. And so an abdominal ultrasound can evaluate for any obstruction, which is uncommon but worthy of evaluating. And doing a urinalysis and microscopy to look for casts is important to rule out glomerulonephritis, interstitial nephritis, or acute tubular necrosis. Early in infection, workup is mandatory. Treating infection early can help with the renal function. And then evaluating for post-renal obstruction with the ultrasound or residual urine volume. So what comes of this is basically excluding intrinsic and post-renal, and then you've got pre-renal dysfunction. And if they are non-responsive to fluid repletion, then the diagnosis should be hepato-renal syndrome, either type 1 or type 2, depending on the acuity. The issue with type 1 HRS, which is the most severe, which is a significant change in serum creatinine or diminishment in GFR in a short period of time, two to three weeks, is that sometimes the diagnostic criteria are not always easy to adhere to. So diuretics are not always stopped, or they have a long half-life, and so they sort of need to wash out before you really make this diagnosis. There can be ongoing fluid losses. An example would be with fever or with diarrhea from lactulose. That needs to be corrected. The volume expands with saline rather than albumin, which can just leak into the interstitium. Oliguria can prevent the exclusion of urinary cast and sediment. Ultrasound showing small kidneys, which means that this patient likely has acute onchronic kidney injury. And to really make the diagnosis, you sort of need recent serum creatinine values, and so if that's not available, you have to make the assumption of the increase is really acute. So let's discuss management and outcomes. So this is a big table of HRS treatment data on the use of albumin and vasoconstrictors for the treatment of HRS type 1. You'll note that the data on regimen of octreotide and midodrine is about half or less as effective as turlopressin or norepinephrine, and it's very apparent that turlopressin and norepinephrine are likely the best therapies to provide systemic and splanchnic vasoconstriction and increase the perfusion to the kidney. There are more recent studies for turlopressin and norepinephrine, and we hope to get drug approval in the United States soon for turlopressin to be able to use it in a hospitalized patient who's not in the intensive care unit. Hyponatremia is also very important. These patients often present with hyponatremia alongside HRS. Certainly assessment of volume status is critical. The vast majority of these patients follow along the pathway of hypervolemic hyponatremia and have low urine sodium, which goes along with either pre-renal or pre-renal with hepatorenal syndrome. And we know that hyponatremia, along with AKI, is an independent risk factor for mortality in patients with liver failure. It's very important to recognize this mortality increase from hyponatremia. This is why hyponatremia boosts up patients' MELD scores who have low MELD scores, and so it helps patients get liver transplanted earlier. The general treatment principles for hyponatremia are that there's really no need to correct it rapidly if it's mild and asymptomatic, but if it's symptomatic, it needs to be corrected more abruptly. And if it's chronic but symptomatic, meaning the patient has fluid overload, then you have to be a little bit more conservative in your fluid replacement. Certainly things like VAPTANs, which were of significant interest in this patient population, don't work well in this setting of cirrhosis. They increase mortality and the risk of liver injury. And along with hyponatremia, patients with cirrhosis admitted to the hospital with AKI have a significant diminishment in survival. And this is really, as I mentioned before, based on AKI stage. So as you progress from AKI stage 1 to 2 to 3, the probability of survival in 90 days significantly declines. And these are for patients who are hospitalized, so this goes back to the initial case that I presented. Let's talk a little bit about prevention, because prevention itself will help reduce the risk of AKI and reduce the mortality associated with it. It's a great quote from Benjamin Franklin that an ounce of prevention is worth a pound of cure. That's really true here. So just to present two slides on proven data and statements that help prevent AKI in patients with cirrhosis. So antibiotic prophylaxis and variceal bleeding prevents AKI. Giving albumin with large volume paracenteses over 5 liters. Close monitoring of diuretic therapy. Monitoring patient's electrolytes, urine output, and weight. Making sure that lactulose is not given in too high of quantities to create significant volume loss from diarrhea. SBP, clearly giving albumin at the time of SBP and on day 1 and day 3 can help prevent acute kidney injury, and also giving antibiotic prophylaxis for a patient with a history of SVP or who are at risk, meaning the protein in the fluid is low and the setting of hyponatremia and AKI. That should read low protein. Also goes without saying, although this sometimes happens, that patients accidentally and or inadvertently get aminoglycosides. That is the absolute wrong thing to give these patients. Of IV contrast also, even in early stages of AKI, you have to really consider the benefit versus the risk. It can really cause significant kidney injury. Of course, avoiding NSAIDs, and in some cases of refractory ascites, tips can help prevent acute kidney injury from happening, or if there's resolution of acute kidney injury, tips performed can maybe prevent the next acute kidney injury event. I'm gonna finish off with biomarkers because I think these are exciting in terms of prognosticating and helping manage patients with acute kidney injury. This is a study published in Hepatology that looked at a number of biomarkers, particularly NGAL and some of the others to statin C, generally showed that the more biomarkers that patients had in the urine, the worse prognosis, and so, or the more likelihood that they had acute tubular necrosis. You can see on the right here, that green bar is acute tubular necrosis, and this is in patients with four biomarkers above the cutoff, where if you don't have any biomarkers above the cutoff, it's more often pre-renal azotemia. These biomarkers, proteins are coming from intrinsic kidney injury. We published a study, two studies actually, one of discovery and one of validation that looked at acute kidney injury occurring before a liver transplant to see if there were markers in the blood that could help us determine if there was reversible kidney injury after a liver transplant or could predict that. And this whole interest was to determine who could get a liver transplant alone versus a simultaneous liver kidney transplant if the biomarkers were showing a high likelihood or a low likelihood of reversibility. And so this model that incorporates age, diabetes, osteopontin, and TMP1, which are two markers, can, with good certainty, predict reversible AKI in patients undergoing liver transplantation, such that if you are above on this model, if you're predicted to have reversibility, then perhaps a liver kidney may not be necessary. And we're looking at further studies to test this in real time. So back to the case very briefly. I'm not gonna go through the whole case again, but our management strategy was to give 5% albumin. We performed a paracentesis, which showed actually SBP, not surprising. Antibiotics, octreotide and mitadrine, the creatinine improved to 1.8. The patient was listed and got transplanted 30 days later. So in summary, kidney injury and hyponatremia are common, difficult to prevent, and detrimental to survival in hospitalized patients with end-stage liver disease. Early prevention, recognition, and management strategies are really critical to optimize outcomes. And we are working on biomarkers that could help risk stratify patients for response to therapy, response to liver transplant, who have kidney injury, which would allow for more proactive management. Thank you. Hi, today I will be talking about surveillance for hepatocellular carcinoma and cholangiocarcinoma in patients with liver disease. Here you can see my disclosures. To start, liver cancer is the fourth leading cause of cancer-related death worldwide, with the highest burden in East Asia and Africa, driven by a high prevalence of chronic hepatitis B in those areas. Although it has an intermediate incidence in Europe and in the United States, it has garnered a lot of attention, given that it's one of the fastest increasing mortality rates among all solid tumors. The most common types of primary liver cancer include hepatocellular carcinoma, accounting for over 75%. And the second most type is cholangiocarcinoma, which accounts for about 10 to 20% of all liver cancers. Today, once again, we will be talking about the evidence base and best practices for surveillance for both of these cancers. Starting with HCC. One of the unique things about HCC is that we have an identifiable patient population with over 80 to 90% of cases in the Western world occurring in the setting of cirrhosis from any etiology. Once a patient develops cirrhosis, the annual risk of HCC is typically between 2% to 4%, with a higher risk from patients with viral hepatitis-related cirrhosis than those who have alcohol or NASH-related cirrhosis. One of the questions that continues to arise in clinical practice is the risk of HCC in patients with advanced fibrosis, but without cirrhosis. This was particularly concerning for NASH in light of several case series showing that 10 to 15% of HCC can occur in the absence of cirrhosis. Fortunately, there have been a couple informative publications over the past couple years that have addressed this controversy. The first was a cost-effectiveness analysis by Feld and colleagues, suggesting that HCC surveillance is not cost-effective in patients with F3 fibrosis. The second was a retrospective cohort study using data from the National VA by Conwell and colleagues, showing that the risk of HCC in patients with NASH exceeded 1% if patients had cirrhosis, but was exceedingly low in those without cirrhosis. These data suggested that HCC surveillance should really be performed in those with cirrhosis alone and not performed in those without cirrhosis. Now, one of the other important premises that is needed for screening programs is the availability of treatment options if patients are found at an early stage. For HCC, patients detected at an early stage are eligible for curative treatments, including surgical resection, liver transplantation, and local ablative therapies. The median survival with any of these three therapies exceeds five years and is somewhere between seven to 10 years, in contrast to a median survival of two to three years if you're found beyond an early stage. Now, the highest level of evidence for HCC surveillance comes from a large randomized control trial on patients with chronic hepatitis B infection. There were over 18,000 patients in this trial that were randomized to receive surveillance or not receive surveillance. And those randomized to surveillance were significantly more likely to be detected at an early stage and undergo curative treatment. Most importantly, surveillance resulted in a 37% reduction in HCC-related mortality. Unfortunately, there is not a similar randomized control trial supporting HCC surveillance in patients with cirrhosis. When one was attempted in Australia years ago, it failed to accrue patients and it had to be closed prematurely. Therefore, we are forced to depend on cohort studies. Now, when one examines these cohort studies, you find that there was a consistent association between HCC surveillance and improved outcomes, including early detection, curative treatment receipt, and improved survival, with the odds ratios you can see here. Of course, it's noteworthy that cohort studies are prone to several biases, including lead time bias, length time bias, and the risk of residual confounding. However, studies that have attempted to adjust for these biases, including lead time bias, statistically, have continued to find an association between surveillance and improved outcomes. Now, guidelines have differed in their recommendation for the best choice of surveillance modality. Not only is there disagreement between guideline societies, for example, the AASLD compared to EASL, but even within the AASLD, there's been changes over time. For example, comparing the 2010 guidelines versus the more recent 2018 guidelines. Now, the most recent recommendation from the AASLD recommends abdominal ultrasound with or without AFP to be done every six months in at-risk patients. Over the next couple slides, I will discuss data that suggest, at least in my opinion, that ultrasound with AFP is currently the best strategy. We conducted a systematic review of the literature, examining the sensitivity of ultrasound for early tumor detection. Now, the first thing that you can note here is that there is vast differences between studies when you take a look at the sensitivity of ultrasound to find HEC at an early stage, ranging all the way down from 21% all the way up to 89%. And this really highlights the operator-dependent nature of ultrasound. Now, second, when you look at the pooled sensitivity for finding HEC at an early stage, you see that the ultrasound's pooled sensitivity was only 47%. Missing over half of HEC at an early stage. In this retrospective cohort study with nearly 1,000 patients, we found that ultrasound visualization was suboptimal in up to one-fifth of patients undergoing surveillance. 14% of patients who had definitely inadequate visualization and another 6% that had likely inadequate visualization. Now, we recently validated these findings using a contemporary cohort after release of the LIHRAT's visualization score and similarly found that one-fifth of patients had moderately or severely limited visualization. Now, particularly of concern is that suboptimal visualization is associated with obesity, alcohol-related liver disease, and NASH cirrhosis, all populations we're seeing more and more commonly in our clinical practice. And these data suggest that ultrasound poor visualization and poor sensitivity and specificity is only gonna become more problematic over time. Now, as I mentioned before, there has been significant controversy about the role of AFP in surveillance. And I by no stretch think that AFP is a perfect biomarker. But available data do suggest that it is helpful when you use it in combination with ultrasound. Now, first, starting on the left-hand side of the slide, this is a continuation of the prior meta-analysis that I showed before. And these studies here compared ultrasound alone versus ultrasound with AFP for early HEC detection. And you can see here that studies show a consistent improvement in sensitivity when using the two tests in combination. And overall, when you look at the pooled sensitivity, the sensitivity of ultrasound alone, 45%, increasing up to 63% when it's used in combination with ultrasound. Now, of course, this was offset by a small decrease in specificity, but this was thought to be clinically insignificant. And the diagnostic odds ratio using the two in combination was higher for ultrasound with AFP than ultrasound alone. And when these updated data were included in a cost-effectiveness analysis, as you can see on the right-hand side of the slide, ultrasound and AFP were found to be the most cost-effective strategy in the vast majority of simulations, suggesting once again that this is the preferred strategy at this current time. Now, while ultrasound and AFP is currently the best strategy, I don't think it's the best we can do. I'm cognizant that the sensitivity of the two in combination is still only 63%, missing over one-third of HEC at an early stage. Fortunately, there are novel blood and imaging-based biomarkers that are in investigation. Now, one such blood-based panel is the GALAD score, and this incorporates gender, age, and three biomarkers, AFP, AFPL-3, and DCP. GALAD has been evaluated in a large multinational case control study as shown here, achieving sensitivities of 60% to 80% across population. These data are promising, although this panel still requires validation in cohort studies, prior to us routinely using this in clinical practice. Now, fortunately, we've had maturation of large cohort studies through the Early Detection Research Network, as well as the Texas HEC Consortium, and we anticipate data evaluating some of these blood-based biomarkers to become available early in 2021. GALAD is only one such blood-based biomarker panel. There are other biomarker panels that are also coming out from other companies looking at things like methylated DNA markers, which also look highly promising. Now, in terms of alternative imaging, a prospective cohort study from South Korea with 407 patients showed that MRI-based surveillance can achieve higher sensitivity for early HEC detection than ultrasound-based surveillance. Sensitivity of MRI for early HEC detection in this cohort study was 86%, compared to only 28% for ultrasound. It's worth noting that most patients in this study were found and treated at a very early stage, so this study likely underestimated the performance of ultrasound. And you can see that by ultrasound sensitivity in this study being substantially lower than the prior meta-analysis that I showed you. Further, these results need to be validated in a Western non-hepatitis B patient population. Of course, now, cost-effectiveness continues to be a concern if MRI-based surveillance was implemented widely. So there are studies that are evaluating abbreviated versions of an MRI-based surveillance strategy, where you take in-scanner time and you decrease it from a typical 45-minute exam all the way down to a 15-minute exam. Now, while this is also interesting and I think intriguing, prospective studies evaluating abbreviated MRI protocols as well as alternative reimbursement structures are still needed for this to move forward. Now, in terms of surveillance intervals, semi-annual surveillance was initially recommended based on tumor doubling time. Data, including a large cohort study from Italy shown on the left-hand side of the slide, showed better survival when you did semi-annual surveillance than annual surveillance. And this really highlighted why guidelines changed from every six to 12-month recommendations to semi-annual surveillance between the 2005 and the 2010 guidelines. Subsequently, a large randomized control trial from France on the right-hand side of the slide subsequently showed that quarterly surveillance did not improve early detection compared to semi-annual surveillance. And so overall, these two studies really suggest a Goldilocks effect where semi-annual surveillance isn't too short and isn't too long, and so it may be a very nice interval for us to implement HTC surveillance. Now, of course, there haven't been comparative studies looking at other intermediate intervals, and so the optimal surveillance interval is somewhere likely between five and eight months. Finally, I've spent a lot of time discussing best practices, but one of the biggest take-home points is simply to perform surveillance. Despite some improvement over time, we find that only one-fourth of patients with cirrhosis undergo surveillance at this time, with even lower proportions when examining semi-annual surveillance over longer periods of time. One of the strongest correlates of surveillance receipt is subspecialty care by either gastroenterology or hepatology. However, even patients followed by GI or hepatology, one-fourth of these patients fail to undergo surveillance, suggesting that, once again, we need to continue doing better. Now, for the last five minutes, I'd like to move on to cholangiocarcinoma and surveillance for this other type of liver cancer. Recent guidance from the AGA highlights best practices for cholangiocarcinoma surveillance, with three take-home points, as you can see here. First, surveillance should be performed in patients with PSC, given that this is truly a high-risk state. Second, surveillance should include imaging with or without CA99 every six to 12 months. And finally, ERCP is considered a diagnostic modality and should not be used for surveillance. The AASLD is currently updating their guidelines on PSC and cholangiocarcinoma management, and so we should expect similar guidance recommendations from AASLD coming out in 2021 regarding the benefits of surveillance in this patient population. Now, it's clear that patients with PSC are a high-risk state for cholangiocarcinoma, as highlighted by this study from the International PSC Study Group. Of over 7,000 patients included in the study, 721 developed hepatobiliary malignancy during the follow-up of 14.5 years, including 594 who developed cholangiocarcinoma. Now, the incidence of cholangiocarcinoma in patients with PSC was high, at 1.4 per 100 patient years. And you can see that the highest incidence was actually in the first year after PSC diagnosis, at 2.8 cases per 100% years. These cancers that were detected in the first year were likely prevalent cancers at the time of PSC diagnosis, but really highlights the importance of surveillance, particularly in this first year after PSC diagnosis. Now when you look at subgroups, the risk of cholangiocarcinoma was significantly higher in older patients, males, and those with IBD, either Crohn's or ulcerative colitis. Similar to our discussion with HCC, we next need to consider if treatment options exist if patients are found in an early stage. Now patients who are found with early stage cholangiocarcinoma can undergo curative treatments, whether this is surgical resection or liver transplantation. Notably, patients with PSC, once again the at-risk population in whom surveillance is currently recommended, who have hylocholangiocarcinoma should preferentially undergo transplant, given a field defect and a higher risk of recurrence if these patients simply undergo resection. Now historically, cholangiocarcinoma transplants did not have good outcomes, but more recent protocols have suggested that these patients can do well. And on the right hand side, you can see data from the Mayo Clinic that have shown that liver transplant can be associated with good long-term survival, with five-year survival exceeding 60%. Since these data have become available, many other transplant centers have set up similar protocols and have shown good long-term outcomes, once again paralleling these from the Mayo Clinic. However, all of these protocols really do highlight careful patient selection to achieve those good long-term outcomes. Now this study from the Mayo Clinic is one of the first to show that cholangiocarcinoma surveillance is associated with improved outcomes in patients with PSC. This study included 830 patients with PSC, followed over 20 years, over which time 79 developed hepatobiliary carcinoma. Approximately half of those patients with cancer were surveillance detected and half were not. Those patients detected by surveillance had earlier stages of disease, higher transplant eligibility, and higher five-year survival at 68% versus 20%. So the studies we've reviewed so far have highlighted that PSC patients are a high-risk cohort and there appears to be benefit of surveillance in this high-risk cohort. This study, also out of Mayo, compared different surveillance modalities including ultrasound, CT, and MRI in 266 patients with PSC. I'm really focusing on the MRI and the ultrasound data here on this slide and all of the patients that I show you had both modalities, both ultrasound and MRI performed within three months of each other. Whether considering all patients included in the study or the subgroup who are asymptomatic, MRI showed higher sensitivity and similar specificity compared to ultrasound-based surveillance. MRI-based surveillance was also associated with reduced mortality compared to ultrasound among asymptomatic patients, suggesting that this really should be the preferred surveillance strategy for a clandio in patients with PSC. Finally, we're left with a similar debate about the clinical utility of biomarkers, with the most common in cholangiocarcinoma being CA99. This older study suggests that using CA99 in combination with MRI may improve sensitivity, although with a notable decrease in specificity. Overall, this is likely an area where we will continue to need more studies to see if MRI is sufficient or if biomarkers can help improve early detection. In summary, HTC surveillance is associated with improved outcomes, including survival in both hepatitis B patients and those with cirrhosis. Current data suggests surveillance should be performed using semi-annual ultrasound with AFP while we await novel imaging and blood-based strategy. As we've discussed, HTC surveillance is underused in clinical practice and we must do better. Similarly, routine cholangiocarcinoma surveillance is now recommended in patients with PSC and has been shown to improve survival in light of improved treatment options. Surveillance should be performed using imaging, likely MRI based on most recent data, with or without CA99 every 6 to 12 months. Thank you. Good morning, everyone. I'm Elisabetta Buttanesi from the University of Turin in Italy. These are my disclosures. Lifestyle modifications are certainly very important for the therapy of patients with NAFLD and NASH because weight loss and exercise are able to reverse all the histological features of NASH. But the degree of improvement is proportional to the degree of weight loss. So for a weight loss between 3 and 5 percent, you can have an improvement of steatosis. For a weight loss up to 7 percent, you can have NASH resolution. If you are able to lose more than 10 percent of your initial body weight, you can have a significant improvement also in fibrosis. The main problem of lifestyle modification that we all know is that less than 10 percent of those who start can sustain weight loss at one year. Now, weight loss can also be achieved by bariatric surgery. This is a French study that was enrolled in 187 obese patients with biopsy proven NASH. They underwent bariatric surgery and were followed for five years with liver biopsy at one and five years. The primary endpoint was the resolution of NASH without worsening of fibrosis at five years, and it was met by 84 percent of patients. And if you look at the percentage of patients with fibrosis stage equal or greater than one before and after bariatric surgery, you see that this percentage decreases from 72 percent at baseline at 66 percent after one year and at 36.5 percent after five years. So, the reduction of fibrosis is progressive and is continuing through five years. Now, the benefit of weight loss is also well known for the high response rate in the placebo arm of the randomized control trial. Here, you can see the prevalence of NASH resolution in blue and the prevalence of fibrosis improvement higher or equal to one stage in orange. This is probably due to the so-called Olson effect, that is, the compliance to diet and lifestyle is increasing if the follow-up by your physician is more tight. Now, this is also going to be a bias in randomized control trial because you see there is a large variability in the response rate. So, the Liver Forum has recently published recommendations for standardization of diet and exercise in all the trials. Both the European and American guidelines besides lifestyle intervention advise on the use of pioglitazone in diabetic NASH patients and vitamin E in non-diabetic NASH patients. All these recommendations come from the PIVENS trial. However, we have no long-term data on this intervention. In the end, there is no FDA or IMA-approved therapy. But the landscape of therapy is changing very rapidly, and here you can see this constellation is the number of compounds that are currently being tested from phase one to phase three. All these compounds can be grouped into three categories, drugs with a metabolic action, drugs with an anti-inflammatory, and with an anti-fibrotic action. These are the studies currently in phase three. So, we have two anti-inflammatory, anti-fibrotic drugs, beta-colic acid, an FXR agonist, and senicribiroc, a dual CCR2-CCR5 antagonist. Then we have metabolist modulator, resmetirum, and romcol, because alafibranol, a dual PPR alpha and delta agonist, has been stopped due to inefficacy at the interim analysis. Now, FXR is central to a multitude of pathways from bile acid homeostasis to inflammation to fibrosis, so there is a good rationale for the use of obeticolic acid for the treatment of NASH. And recently, the interim analysis at 18 months of the REGENERATE phase three study has been published involving almost 2,000 participants that were randomized one-to-one-to-one to receive obeticolic acid 10 mg versus 25 mg versus placebo. Obeticolic acid 25 mg met the primary endpoint of improvement in liver fibrosis with no worsening of NASH, and here you can see on your left that there is a stepwise increase by increasing dosage of obeticolic acid. And on your right, if you look at the proportion of patients who worsened fibrosis compared to those who improved fibrosis, the balance is definitely in favor of obeticolic acid, particularly 25 mg. Pruritus is the most common effect, and obeticolic acid also increased by 17% LDL cholesterol, but this increase was really responsive to statin therapy. Now, thyroid hormone receptor beta can be found in liver membrane and regulates lipid metabolism and inflammation, and the selective antagonist rosmetirone has been used in a 36-week phase two trial where patients were randomized two-to-one to receive 8 mg of rosmetirone versus placebo. The primary outcome was change in the fatty fat fraction at week 12 and 36, and on your right, you can see that the proportion of patients who achieved a fat reduction greater than 30% was definitely higher in the active arm, in the rosmetirone arm, which is in green, both at 12 and 36 weeks compared to placebo. This was associated with a significant resolution of NASH and a significant reduction in LDL cholesterol and triglycerides. Aramcol is a novel liver-targeted steroid coadesaturase-1 inhibitor with a dual mode of action on liver fibrosis, downregulation of steatosis, and a direct effect of hepatic stellate cell, and this compound has been tested in a phase two B trials where participants were randomized two-to-one to receive Aramcol 400 mg versus 600 mg versus placebo. The primary endpoint was change in liver fat at week 52, and it was met by Aramcol 600 mg with 47% achieving this endpoint versus 24% in the placebo group, and this was also associated with a higher degree of NASH resolution without worsening of fibrosis in the Aramcol 600 mg arm as well. Now, GLP-1 agonists, GLP-1 receptor agonists are drugs that can be effective in a variety of tissue and organs that can promote weight loss by increasing society-delayed gastric amputee, they can improve glycemic control, and also have cardiovascular benefits. We already know about the benefits of lauraglutide that was given at a dosage of 1.8 mg versus placebo in the lean trial, and the primary outcome, that is, resolution of NASH with no worsening of fibrosis was met by 39% of patients in the lauraglutide arm compared to 9% in the placebo arm. The effect is probably most remediated by weight loss, and I must say that pharmacological weight loss is definitely improving. Here on your left, you see the comparison between lauraglutide, which is in yellow, to increasing dosage of semaglutide from 0.1 to 0.4, and you see that semaglutide can be twice as much effective compared to lauraglutide. The same is also true for the novel dual-GIP-GLP-1 receptor agonist terzapatide, and compared to dulaglutide, which is the yellow line, increasing dosage of terzapatide can improve the weight loss up to 11 kilograms, less 11 kilograms in 24 weeks. Semaglutide is currently being tested in NASH patients. Patients were randomized to receive semaglutide 0.1, 0.2, or 0.4 mg subcutaneous daily, and the primary outcome was resolution of NASH and no worsening of liver fibrosis. The primary endpoint was met for all doses of semaglutide. Here you can see 40 percent compared to 17 percent in the placebo group for the low dosage and 59 percent for the high dosage of semaglutide. The safety profile of this drug is well known, and the side effects are mainly gastrointestinal. Now, PPR. We know that pioglitazone, which is a PPR gamma, is effective. Elafibranol, which is a dual PPR alpha and delta, is not effective. And now there is lanifibranol, a PAM PPR that has been used in a 24-week phase 2b study, where patients were randomized to receive lanifibranol 800 mg a day or 1200 mg a day versus placebo. Lanifibranol was able to meet both endpoints, so improvement of the self-activity score, meaning improvement of steatosis, 49 percent in the high dosage compared to 27 percent in the placebo, but also an improvement of fibrosis by at least one stage with no worsening of fibrosis, 42 percent in the high dosage compared to 24 percent in the placebo. And in the end, the future landscape of NAFLD therapy, of course, the standard of care still requires an effective weight loss strategies, careful management of comorbidities, and we should get rid of liver biopsy, also randomized controlled trials, because we need parameters of biomarkers that could be available to judge the effectiveness of the drug also in clinical practice. An ideal drug candidate should correct the metabolic defect, insulin resistance, anti-fibrotic effect in the liver, and improve both liver-related and cardiovascular survival. So, to this extent, a combination therapy may be ideal. Anti-metabolic therapy, particularly those proposed at the first line for cardiovascular benefit together with modulator of inflammation and fibrogenesis, and in the end, precision therapy is the future. And I thank you so much for your attention. Good morning. I hope you all enjoyed this session. I'm Paul Toluor. I'm the incoming chair of the ASLD Clinical Practice SIG. On behalf of ASLD Clinical Practice SIG committee, I want to thank all four speakers for their excellent talk. The goal of the Clinical Practice SIG is to discuss and debate common clinical issues, especially the areas where there are controversies. And I believe that our speakers have done an excellent job in this session. I know you have many questions. I would encourage you to send your questions through our chat box. More importantly, I want you to send your feedback and topics for future meetings to me by email. This is also an opportunity for you to invite your colleagues and trainees to join the Clinical Practice SIG. Last month, we started a case-based discussion series. So, like a webinar, it was organized by doctors Jennifer Guy and Karen Kropp. The first topic was on hepatic adenoma it was a multidisciplinary meeting and it was done very well. And I hope to continue this throughout the year and doctors Guy and Kropp will take a leadership role in this. This may be an opportunity for your trainees to participate in the Clinical Practice SIG. They could bring some interesting cases. They could send it to either Dr. Guy or Dr. Kropp. And we can get an expert panel around it and do it as a part of the webinar. This will also give them an opportunity to participate in the ASLD activities and this may be an excellent platform for them to be part of the Clinical Practice SIG. So, please encourage your colleagues and trainees to join the Clinical Practice SIG group. Finally, I want to thank the ASLD staff. Throughout this pandemic, it has been difficult times. They did an excellent job. Without them, we could not have done this. Until we meet again in 2021 in person, thank you once again and stay safe. Thank you.

Clinical Practice Special Interest Group

common issues in clinical hepatology

elevated iron studies

acute kidney injury

cirrhosis patients

surveillance for liver cancer

non-alcoholic fatty liver disease

iron metabolism

hereditary hemochromatosis

hepato-renal syndrome

hyponatremia