I'll kick us off with a talk on cirrhosis and portal hypertension. This is very important, I think. It's an important entity within our practice that APPs can really make a significant intervention in caring for our patients, both in the inpatient setting and with continuity in the outpatient setting. So I think this is a very important topic. I have no disclosures today. We're going to touch on the functions and definition all the way through briefly touching on several complications of cirrhosis and portal hypertension. You could really spend a whole week going through liver disease and portal hypertension to understand all of these, but we'll touch on a lot of different topics during this morning's talk. So just starting with a brief overview of the various functions of the liver. It's important to understand that there's a multitude of functions that the liver performs in terms of regulating our metabolism and nutrient storage and detoxification for their body. It plays an important role in the immune system and protein synthesis. So when we start to develop liver disease and cirrhosis, all of these functions can be dysregulated during that process and as further disease progresses as patients go from acute liver failure or acute liver disease through the progression to chronic liver disease and cirrhosis more and more of these functions become affected. So cirrhosis is defined as the fibrotic replacement of liver tissue from any form of chronic liver disease. It's characterized by the development of regenerative nodules surrounded by areas of dense fibrosis and it leads to advanced and irreversible scarring. As a result of this, it affects the blood flow through the portal system as it traverses the liver and interferes with perfusion of the liver cells themselves, the hepatocytes and then thereby disrupts hepatic synthetic function. So the features of liver disease and chronic liver disease both reflect portal hypertension from that impediment to the blood flow as well as synthetic dysfunction of the liver. This slide shows on the top low power views of pathology slides from a normal liver on the left hand side and then a liver with cirrhosis on the right hand side and on the bottom a more high power view to understand the architecture. On the left hand side we see the normal liver and the bottom labeled there for you is the portal triad and that constitutes the portal vein, the bile duct and the hepatic artery and in the bottom left of that slide you see the central vein. As compared to the right hand side where you really lose that normal architecture of the hepatic parenchyma and what you have are nodules separated by these bands of fibrosis. The next slide shows cirrhosis of cirrhotic liver in gross section and then on the right hand side again in red those nodules regenerative nodules that have developed and then in the darker purple color is more the bands of fibrosis that separate those nodules and that's the irreversible scarring. So there's a multitude of etiologies of chronic liver disease that we need to be aware of and paying attention to particularly when we're working patients up. We'll touch on the most common ones but as we start to think about our patients we also have to consider less common entities including autoimmune diseases and hereditary disorders and disorders of metabolism. This is a nice diagram that kind of summarizes a lot of the various functions and thereby dysfunction that can occur as a result of cirrhosis and portal hypertension. I won't go through this in detail but that's a nice reference for you. So why is this important for us? Cirrhosis affects over 2 million adults in the United States. The majority of those are male but slight male predominance and mean age of diagnosis is in the 60s but we have noticed that there's an increasing incidence in diagnosis in young people particularly those people born in 1980 or after and we believe a lot of that is attributable to alcoholic liver disease. In terms of mortality this affects almost 22 per 100,000 people in the U.S. and that's an increase from just under 15 per 100,000 people in 2010 and that rate has actually tripled over the course of one decade from 2010 to 2020 for those young people ages 25 to 34. Again, mostly attributed to alcohol related liver disease. When we talk about the prevalence of cirrhosis the majority of the patients with cirrhosis that we see are due to these three etiologies. Approximately 45% from alcohol related liver disease, 41% from hepatitis C and 26% from what was formerly known as non-alcoholic fatty liver disease now known as metabolic dysfunction associated steatotic liver disease or MASLD. There are of course overlap syndromes to pay attention to so historically patients may have both components of alcoholic liver disease and hepatitis C or more commonly now MASLD in combination with alcoholic liver disease and you'll see this abbreviation METALD. In terms of incidence, the rising incidence is mostly attributable to increasing diagnosis and increasing recognition of MASLD with alcohol taking the second most common incidence for chronic liver disease and cirrhosis. Again, that incidence is increasing in young people whereas hepatitis C we're seeing less and less of probably because of better screening protocols by our primary care providers and use of antivirals by those primary care doctors as well. Some basic clinical features that patients may complain of who may not know their cirrhosis or early on in the course of their cirrhosis. Muscle cramping is common insomnia or other poor quality sleep, pruritus and sexual dysfunction. Early early labs or labs that you may notice that are changing or indication of chronic liver disease and cirrhosis would be thrombocytopenia, coagulopathy, so an elevated INR or PT, hypoalbuminemia. These are reflective of poor synthetic dysfunction or poor synthetic function rather. And then on imaging you may notice features related to cirrhosis itself. Radiologists may describe a nodular liver cirrhosis. Sometimes we've seen this on CT scans and then other features that are secondary to that. So features that would suggest portal hypertension, the presence of ascites, splenomegaly and varices. This is an old old image that was from one of, I remember seeing this when I was in medical school, one of our old textbooks. You see a diagram of the various different physical exam manifestations that a patient can develop from cirrhosis. Our updated version is this. I think it's taken from up to date. You can see both, they've tried to write this down in terms of the effects of portal hypertension on the left hand side and the effects of hepatocyte dysfunction on the right side. So the portal hypertension will lead to the development of esophageal varices and subsequent symptoms of GI bleeding, the development of ascites, varices in other parts of the body not just the esophagus, but caput medusa is basically varices in the peri-umbilical region and then anorectal varices as well. There's the results of hepatocyte dysfunction. Again, remembering all those various different functions of the liver as those are affected. Patients can develop hepatic encephalopathy, jaundice, and icterus. There is a change in the hormone balance. So due to increased estrogen levels patients can develop gynecomastia and testicular atrophy and the development of asterixis and bleeding tendencies through those coagulopathies and thrombocytopenia that develop. So a whole host of physical exam findings that are important to recognize as secondary to cirrhosis. What are some of the complications that can develop? The more common ones we see are ascites, variceal bleeding, hepatic encephalopathy, but cirrhosis does put you at risk of various other complications on the inpatient setting. Many times we get consulted for spontaneous bacterial peritonitis. Anybody, a cirrhosis patient with kidney dysfunction, you get concerned about the possibility of hepatorenal syndrome. Because of the clotting disorders that develop, there's risks of portal venous thrombosis. And then less common, but still important to recognize would be some of the cardiopulmonary manifestations. So cirrhotic cardiomyopathy, hepatopulmonary syndrome and portal pulmonary hypertension and hepatic hydrothorax, which is basically pleural effusion that develops similar pathophysiology to ascites but instead of presenting with ascites in the abdomen they present with fluid in the pleural space to account for that. So we won't touch on all of these today, but it's important to recognize that there are a whole host of complications that can develop from cirrhosis. Highlighting those most common ones, the, sorry, so hepatic encephalopathy, ascites and variceal bleeding some highlights there I've outlined in red. So hepatic encephalopathy carries a 40% 5-year overall mortality risk for patients, oh sorry, 5-year development incidence risk within 5 years of diagnosis of cirrhosis. Median survival after the onset of hepatic encephalopathy is as low as 1-2.5 years. And hepatic encephalopathy accounts for 10% of all hospitalizations for patients with cirrhosis. Ascites, there's anybody with cirrhosis has a 40% lifetime risk of developing ascites and then once ascites develops the median survival can be as low as 1 year. And again, ascites accounts for, is present in at least nearly 50% of cirrhosis hospitalizations. Variceal bleeding has a very high mortality rate, mortality risk can be as high as 17% at 6 weeks from the initial presentation with variceal hemorrhage and that occurs in nearly 10% of cirrhosis hospitalizations. Hepatocellular carcinoma, once this develops the 5 year survival is less than 20%. There are techniques to try to treat hepatocellular carcinoma whether that's transplant or other techniques but unfortunately the survival is still poor. SBP as I mentioned is a complication for those patients with ascites and has again a very poor median survival of just 11 weeks after the diagnosis of SBP and this accounts for approximately 3% of cirrhosis hospitalizations. And then finally hepatorenal syndrome also a very high mortality rate, median survival of only 2 weeks after initial diagnosis. So it's important to recognize the severity of some of those complications and the significance of those for our patients. How do we diagnose cirrhosis? The traditional way of diagnosing cirrhosis is through a liver biopsy. This can be obtained either percutaneously through a transjugular approach particularly in those patients with ascites, those who have significant thrombocytopenia, coagulopathy or are on anticoagulants or antiplatelet agents. Those are both most commonly done by our interventional radiology colleagues and we do still find some gastroenterologists in the community that are doing percutaneous liver biopsies but as a trend over the last decade or so those have mostly shifted to our interventional radiologists at least in our practice here. Endoscopic ultrasound guided liver biopsy is a little bit newer. The endoscopic ultrasound just as when you're using ultrasound guidance for your percutaneous guidance, endoscopic ultrasound does allow you the opportunity to in real time evaluate the liver, use Doppler flow and obtain samples from both the right lobe and the left lobe of the liver so it can optimize some sampling, can improve sampling. It is done during EUS so it is a little bit more of an invasive approach in the sense of the patient is going to go for anesthesia or sedation to perform the procedure but it does offer us a nice alternative to the traditional approaches for liver biopsy. There are also non-invasive forms to assess fibrosis. There's several laboratory tests that can be ordered. These use various equations and algorithms to try to estimate the amount of fibrosis that's developed in the liver. Fib4, Fibrosher, Fibrometer are just three examples of those more commonly used laboratory based assessments. Then there's also imaging based assessments for fibrosis. The most common one that we see is vibration controlled transient elastography. This is ultrasound based technology as you see in the picture on the right hand side. Then MRE elastography is through MRI. Both of these are alternative imaging based methodologies to understand the degree of liver fibrosis and help understand if patients have advanced fibrosis or cirrhosis. Here's an example on the left hand side of the results from the transient elastography, the FibroScan as opposed to the right hand side, the MRE elastography imaging. When we talk about cirrhosis and portal hypertension I like to break it down into understanding is the disease compensated or decompensated. When we talk about decompensated that basically means that they have a manifestation of their portal hypertension. That can include any of those presentations that we discussed, ascites, encephalopathy, variceal bleeding. The incidence of decompensational liver disease is anywhere from 5-10% per year. The definition for portal hypertension you see there is an increase in the portal pressure gradient between the hepatic vein and the portal vein of greater than 10 millimeters of mercury, where normal is less than 5. This can be measured predominantly and traditionally with our interventional radiology colleagues. If they're doing a transjugular liver biopsy, they can also obtain the portal pressure measurements to give us an assessment of how severe the portal hypertension is. There's newer techniques that allow us to also do that by endoscopic ultrasound. So this diagram basically outlines the various factors that lead to the development of portal hypertension, how that also affects the presentation. So there's increased hepatic resistance on the left-hand side. You see that in the top. As a result of the fibrosis that's developed within the liver, leading to increased resistance to portal blood flow. And that then basically leads to several different hormones that lead to splenic vasodilation and affect the distribution of the blood flow through the body. So patients will have increased portal venous inflow, but reduction in... Sorry, I'm blanking on the word. But this basically outlines the development of varices as a result of portal hypertension through increased splenic blood flow and vasodilation. And sorry, sodium water retention. So this is another diagram basically outlining how cirrhosis can lead to the various different presentations for ascites. Again, through portal hypertension, sodium retention, plasma volume expansion leading to ascites, and down the road to the manifestations of hyponatremia, hepatorenal syndrome, and SPP. It's important to remember also hepatorenal syndrome, you need, by definition, needs to have ascites. So patients with cirrhosis without ascites, if they're presenting with renal dysfunction, you have to think about the more common presentations for renal dysfunction, such as pre-renal etiologies. So management for liver disease, any form of cirrhosis with liver disease, you want to discuss with your patients the importance of complete alcohol abstinence. If they are not immune to hepatitis A or B, consider them for vaccination. Again, any form of cirrhosis, we also have to be thinking about screening for those complications. So even in patients who are asymptomatic, well compensated, they are still at an elevated risk of developing hepatocellular carcinoma. So we routinely do a screening alpha-fetoprotein and right upper quadrant ultrasound looking for dominant nodules. We do that every six months. Endoscopy to screen for esophageal varices. In patients who are well compensated, we may be doing these once every two to three years. But in patients who have started to develop varices, even in the absence of bleeding, you may want to do that more frequently. We recommend avoidance of NSAIDs and limiting acetaminophen to less than 2,000 milligrams per 24 hours. Most patients understand the importance of avoiding acetaminophen but don't actually recognize the dangers of NSAIDs as well. And that has to do with the bleeding diatheses that develop. And then controlling comorbidities. This is particularly important for those patients who have metabolic associated liver disease. So understanding the other complications, cardiovascular disease, diabetes, obesity. Many of these patients will actually suffer from more complications related to their cardiovascular disease as opposed to their cirrhosis. So diagnosis of ascites. Many times we can do this just by our physical exam and obviously using imaging to our advantage. Looking for features such as flank dullness, shifting dullness, and presence of a fluid wave. A diagnostic paracentesis is important to help us evaluate a patient with new diagnosis of ascites. We're looking for a serum ascites albumin gradient and total protein levels. And when we're concerned about the possibility of SBP, we also send off Gram stain cell count and differential and cultures to allow us to assess for that. When you're, if you're working with a patient with ascites and you're not certain that they have underlying liver disease and you're thinking about other potential etiologies, there are other tests that you may want to send. For instance, somebody with pancreatitis or chronic pancreatitis, you may want to consider sending an amylase. Patients who you're concerned about biliary etiologies, you might want to actually send a bilirubin, but there's other other forms as well. Triglycerides are helpful to look for. Chylus ascites and such. But if we have somebody with cirrhosis and where we believe that their ascites is related to the cirrhosis and portal hypertension, the SAG and total protein are helpful for that diagnosis. Oh, there are the other ones. Glucose, LDH, I mentioned amylase, bilirubin, triglycerides are all helpful. The total protein that I mentioned previously helps to differentiate portal hypertension from liver disease from alternative etiologies such as cardiac reasons for portal hypertension. Cytology is important when you're considering a malignant etiology as well. This is another diagram showing the various factors that lead to the development of ascites. The pathophysiology there. And it's important to understand the pathophysiology as to why we make some of our interventions too. One of the most important interventions is a low sodium diet and that's because there's a significant component of salt and water retention that leads to the development of ascites. So this is essentially third spacing where intravascular volume depletion, but overall the patient is fluid overloaded. So that's where the importance of a low sodium diet plays in and that's why we use diuretics to help manage the ascites. It's usually a combination of spironolactone and furosemide. And usually the ratio is 100 milligrams of spironolactone to 40 milligrams of furosemide. And that combination helps to manage the ascites and also balance the electrolyte abnormalities that may develop. Therapeutic paracentesis can be used particularly for those patients who either are presenting with exacerbations of ascites, whether that's due to non-compliance with their medications or poor sodium compliance, low sodium diet compliance, or even just refractory ascites, difficult to control ascites. And therapeutic paracentesis will relieve them of many of the symptoms. We'll see patients that have 10 liters or more sometimes taken off in a single setting. It's important to remember that because of that third spacing, the fluid shifts that result as a consequence of therapeutic paracentesis, it's important to consider the intravascular volume replacement. And we typically do that with IV albumin, 25%, doing so at this ratio of 6 to 8 grams per liter removed. That helps to reduce the risk of complications from the paracentesis, including hepatorenal syndrome. And then for those patients who have significant refractory ascites where they're on diuretics or they can't tolerate the diuretics due to renal insufficiency, they're undergoing frequent therapeutic paracentesis, it's important to consider long-term or frequent paracentesis. Those patients may benefit from the placement of a TIPS. TIPS is a transjugular intrahepatic portosystemic shunt. This is also typically performed by our interventional radiology colleagues and allows basically a bypass shunt from the portal system into the hepatic system to reduce the portal hypertension and thereby treat the ascites. TIPS can be helpful for other management of other disease processes as well from cirrhosis that we'll touch on in a minute, but this is helpful for these patients with ascites. SBP develops as a result of immune dysfunction and an important piece of that is bacterial translocation from the gut. It can present without symptoms in up to a third of patients. We typically think of the symptoms being generalized abdominal pain and fever. In these patients, we're looking for an ascites fluid neutrophil concentration greater than 250 microliters. So this is where using that cell count and differential is helpful or is important to understand that. It's also the majority of patients with SBP actually they present with culture negative nutraceutical ascites. So it's only by the neutrophil count that we actually can make that diagnosis. The fluid doesn't actually grow anything in culture. There are forms of SBP that do grow in culture, but the majority are presenting with this culture negative ascites. We typically treat this with a third generation cephalosporin, most commonly ceftriaxone for a five-day course. And albumin is important in the management of SBP as well, again, to reduce the risk of complications including hepatorenal syndrome and mortality. The recommended doses are there at 1.5 grams per kilogram of patient weight on day one and then 1.0 gram per kilogram of patient weight on day three. And then once the patient has been diagnosed with SBP, we do recommend secondary prophylaxis with suppressive antibiotics. So this is typically done in the form of Bactrim or ciprofloxacin once a day after that initial diagnosis. Moving on to esophageal varices. So we're starting with screening for esophageal varices. These patients we want to consider, even in compensated patients who've never had a presentation, we want to consider for screening. And that would be every two to three years. We favor every two years, particularly in those patients where the underlying disease is not controlled. So those patients who continue to drink alcohol after a diagnosis of cirrhosis are those patients who have cardiovascular comorbidities and metabolic associated dysfunction, diabetes that's inadequately controlled. We would do a screening in DOSP approximately every two years. If they have decompensated liver disease but not a history of bleeding, that would be on an annual basis. And those patients who have developed varices, again without a history of bleeding, would repeat the endoscopy on an annual basis. And it's when we start to see those medium or large size varices, grade two or three varices, that we need to start to think about prophylactic treatment. And we have two forms, two options available for us, the use of a non-selective beta blocker such as carvatalol, propranolol, natalol, or variceal band ligation. So this is an endoscopic images of the various grades of esophageal varices starting on the left-hand side. Panel A essentially shows grade one esophageal varices. These are varices that flatten out during endoscopy and they separate nicely when you insufflate air into the esophagus. Panel B is grade two esophageal varices, so these separate but they don't completely flatten with air insufflation. And then panel C is grade three esophageal varices, but they really don't separate. They're still touching despite insufflation during endoscopy. On panel three, you can also see these red markings on the surface of the varices. These are what we call red whale signs. Those are considered high-risk stigmata for risk of bleeding. So in our management, we talked about non-selective beta blockers. These help to reduce the splenic blood flow and the most common examples used are carvatalol, propranolol, and natalol. The goal is to achieve a heart rate of about 55 beats per minute. That's how we use titration. Obviously, that may be limited by blood pressure or other symptomatic side effects from beta blockers. And then the other option is variceal band ligation, and this is an endoscopic image of a band performed. So you see the cap on the outside of the scope. You see the blue rubber band, which has been placed to basically, as Dr. Cole showed in his images yesterday, create a pseudopolyp. But this is not being done for endoscopic mucosal resection. This is being done to ligate that varice. So once that band is in place, it will basically strangulate the origin of the varice. It'll lead to inflammation, fibrosis, and scarring, and the band will typically fall off approximately one to two weeks after placement, resulting in scarring and reduction in blood flow and filling into the esophagus. When a patient presents with variceal bleeding, the most important thing, first and foremost, of course, is resuscitation. Resuscitate, resuscitate, resuscitate, make sure that the patient has adequate perfusion. We start these patients on IV octreotide, a 50-microgram bolus, followed by a continuous infusion and antibiotics. Antibiotics are important because they've been shown to reduce the risk of complications, including infections and mortality from variceal hemorrhage. Turlopressin is not widely available. I think maybe some academic centers, it's not available where we are currently, but that is an alternative to octreotide for these patients in the acute presentation. And then urgent endoscopy, typically within 24 hours of initial presentation. Many times we'll do dual therapy for these patients using a beta blocker and band ligation. And then, again, emergency TIPS. This is where TIPS is helpful, another area where TIPS is helpful, particularly if there's refractory bleeding that we're not able to control endoscopically. TIPS offers a way to kind of bail out to allow us to control that bleeding by emergently reducing the portal hypertension. In those patients that we are able to control endoscopically, it's important to consider early TIPS for those patients for secondary prophylaxis against future bleeding presentations. This is advocated to be considered at that initial hospitalization and within 72 hours of management of the variceal bleeding. Again, this depends on the availability of TIPS by your IR colleagues nearby. Gastric varices, gastric varices, this is the sarin classification. So, there's four different classifications for gastric varices. GOV1s are basically a continuation of the esophageal varices along the lesser curvature of the stomach, whereas GOV2 are a continuation of the esophageal varices into the greater curvature into the fundus of the stomach. And that stands for gastroesophageal varices, whereas IGV1 stands for isolated gastric varices. And IGV1s are typically in the fundus where there's not a direct connection to esophageal varices. Sometimes we'll see these even in the presence of patients with pancreatic disease as opposed to liver disease. And then, finally, IGV2, which basically could be elsewhere in the stomach, could even be what we call ectopic varices elsewhere in the GI tract. And you see a red mark down in the duodenum there. So, gastric varices and ectopic varices, again, typically managed by nonselective beta blockers. You can consider variceal band ligation primarily for those gastroesophageal varices that extend along into the lesser curvature into the stomach. Alternatives for management would be endoscopic injection of cyanacrylate or glue. Coil placement, typically done through EUS guidance or a combination of both where we'll use endoscopic ultrasound. Place a coil which serves as a threshold for the glue to subsequent, so, combination management. And then, again, whether you consider TIPS and another technique by our interventional radiologist called balloon-occluded retrograde venous obliteration. This is a diagram of what TIPS looks like. So, they've created this shunt from a branch of the portal vein directly into a branch of the main branch of the hepatic vein to allow for bypass of the increased resistance in the liver. This is a diagram of what a BRTO looks like. And this requires a gastrosplenic collateral to have developed. So, our IR colleagues will typically examine or need a CT scan. To determine if this is even feasible, but they'll do a vascular intervention. They'll occlude the gastric varices through this procedure and manage bleeding that way. So, a lot of that will depend on your local expertise. Moving on to hepatic encephalopathy. Hepatic encephalopathy can have a various range in presentations all the way from very mild presentation with basically changes in patient symptoms of sleep or gait disturbance, maybe even just in those high-functioning individuals, changes in their executive function. So, minor disturbances all the way up to somnolence and coma. And those with more overt presentations, they will typically manifest disorientation, lethargy, coma, and they'll show signs of asterixis on examination. So, it's important to identify and treat the causes for hepatic encephalopathy. When we have a patient presenting to the hospital with acute onset hepatic encephalopathy, it's important to identify why that might have occurred, rule out infection, look for GI bleeding, changes in medications, dehydration, other illnesses. In the outpatient setting on the chronic basis too, it's important to review those medications, see if there are potential contributing factors for those, for hepatic encephalopathy. Treatment, we start with lactulose, usually start with a 10-gram dose, a couple, two, three times a day. Your goal is to achieve approximately three soft to loose bowel movements daily. Rifaximin as an antibiotic is a nice adjunct to that. That's given as a dosing of 550 milligrams twice a day. It remains expensive, so it can be a barrier, that can be a barrier for some patients on the outpatient setting to continue that medication. And then in those patients that you identify zinc deficiency, replace that as well. And then nutrition, this is something that I think we commonly forget or commonly overlook for our patients. Our patients are lacking in good guidance in terms of nutritional needs. Nutrition plays a very important role in the management of hepatic encephalopathy. You want to make sure that they have an appropriate protein intake, including sometimes encouraging nighttime snacks to keep their calorie intake up. The use of ammonia levels, this is a bit controversial. There are, there is older data to suggest the use of ammonia levels and correlations with hepatic encephalopathy. Although the more recent literature would suggest that these levels do not always correlate. There's inconsistency among the levels and the severity of the hepatic encephalopathy and it's also not specific to hepatic encephalopathy. So an elevated ammonia level is not required to make the diagnosis of hepatic encephalopathy and it's not recommended for screening for hepatic encephalopathy. It's not recommended for long-term follow-up to follow patients with encephalopathy when you're managing them either. So we try to shy away from the use of ammonia levels and are making decisions based off of. These ammonia levels, you make your decisions more based off of the clinical presentation. Hyponatremia can, some patients can present with hyponatremia as a complication of portal hypertension and cirrhosis. It's important to assess whether these patients are presenting that way because of pre-renal presentation. So are they intravascularly deplete? Do they need volume replacement? Is it an effect of their diuretics? And those patients who seem to be adequately intravascular, intravascularly replaced, is it more a need for fluid restriction in addition to their 2-gram sodium diet? So a lot of times we'll have patients that are on a 2-gram sodium diet and fluid restricted. Hypoalbuminemia, I was going to skip over this. This is, I had this in an older slide. There is some older data or some data that suggested using albumin to replace those patients with hypoalbuminemia to a target of 3 grams per deciliter. But more recent data suggests that there's, that has actually shown no improvement in significant side effects such as infection, kidney dysfunction, or death. So we don't actually advocate for the use of IV albumin specifically to treat low albumin. Coagulopathy, it's important to recognize these patients. And because they present with coagulopathies, they have elevated INRs and they have thrombocytopenia, a major bleeding occurs in a very, very small portion of patients who are undergoing paracentesis. This is actually advocated now that the, through the ASLD and the Society for Interventional Radiology, that we do not actually need to provide prophylactic plasma, platelet transfusions, or vitamin K prior to paracentesis for coagulopathy or thrombocytopenia related specifically to cirrhosis. And then hepatorenal syndrome I touched on earlier. This is presenting basically kidney injury, kidney dysfunction in the setting of decompensated cirrhosis, has, by the definition, there needs to be ascites present. It's defined as a 50% increase in the serum creatinine within seven days or a 0.3 milligram per deciliter increase. That does not respond to two days of IV fluids to try to make sure and to establish normal intravascular volume. So we'll start with this. If patients do respond, then that does not meet the criteria or meet the definition for hepatorenal syndrome. The urinalysis is typically very bland, benign, but urine sodium level will be less than 10, similar to what we see with pre-renal patients. We replace volume with IV albumin. So once we've established the diagnosis, we'll treat that initially with IV albumin to improve that intravascular volume at a rate of one gram per patient weight of kilogram per day. We can add mitadrine and octreotide to improve the renal perfusion. And again, turlopressin, where available, can be useful for management of hepatorenal syndrome in those patients in the ICU. You may choose to use norepinephrine as well. And that's particularly helpful for those patients who are also hypotensive with their hepatorenal syndrome. And then finally, do we need to consider these patients for a combination liver-kidney transplant if they're already being considered for a liver transplant, but they've developed hepatorenal syndrome because of the significant mortality and early mortality related to hepatorenal syndrome. If you're in a transplant center, consideration for adding kidney transplant to that, for that patient, is important. This is basically another diagram showing, again, the same pathophysiology effects on ascites and increased risks of infection, SBP, and bleeding related to advanced portal hypertension. I wanted to touch on hepatocellular carcinoma. So this is the development of liver cancer and occurs with a high mortality rate. But as I mentioned earlier, there are several treatment options available. We screen for this with right upper quadrant ultrasound and AFP every six months. The importance of screening is to detect these early on when we can intervene and provide curative therapies, not just transplants, but also interventional radiology guided treatments, chemoembolization, and radiofrequency therapy can be used to treat HCC without a transplant. The criteria for which we consider this, so if imaging identifies a mass that's greater than one centimeter in size, or if on your screening alpha-fetoprotein, you have a rising or elevated AFP, you want to use cross-sectional imaging, so CT scan or MRI with multi-phase contrast, which allows you to assess for the various phases, arterial phase, portal venous phase, and then the washout phase afterwards, and you're looking for characteristic features of HCC. HCC is one of those cancers where two out of three criteria, if you have an elevated AFP and characteristic imaging findings, you may not actually, you would not actually need a diagnosis, need a biopsy to make the diagnosis. Finally, evaluation for liver transplant. I think I'm closing up soon. So when do we consider patients, or what are some important considerations for liver transplant? So any patient with end-stage liver disease, we use two scoring factors. There's the Child-Turkot-Fuse score, and then the MELD score, which is the most commonly, and actually the nationally used score for liver transplant listings. So there are various disease processes for which patients can receive exception points on the transplant list. HCC is the most well-known one. And liver transplant can be performed in combination not just with kidney transplant, but also others such as a heart transplant. Patients after transplant will need lifelong immune suppression. So this diagram basically shows the increasing incidence recently over the last 20 years or so for liver disease and cirrhosis related to NASH and alcoholic liver disease as compared with chronic hepatitis C, which is the top line that's downtrending. Most of the other etiologies for chronic liver disease all constitute a very low proportion of listings for transplant. And again, same idea here, the increasing incidence and recognition of metabolic-associated steatotic liver disease as compared with other forms of liver disease. So the Child's-Puse score was developed to understand long-term prognosis for patients with liver disease. It was designed to predict mortality associated with major surgery. It uses the bilirubin, albumin, and INR in the calculation, as well as the clinical manifestations of ascites and hepatic encephalopathy. So patients with low Child's-Puse score have a high 75% five-year survival, whereas those with 12 to 15 have a low five-year survival. And that's used to guide those decisions around surgery, but also kind of guide our understanding of what the long-term risk is for those patients. So low Child's-Puse score of five or six, that's Child's-Puse score A. Those are five or six. Those are Child's-Puse score A. Those are well-compensated patients, low risk of surgery, low overall one-year mortality. As that score goes higher, you have a higher risk associated with surgery and a higher one-year mortality in those D-compensated patients. MELD is what we most commonly use now, and this is what's used for those patients for transplant listing. This is a better shorter-term prognostic understanding for D-compensated cirrhosis. It uses the bilirubin, INR, creatinine, sodium, albumin levels, as well as the patient sex. This has developed, has actually gone from a MELD score to a MELD sodium score to now the most recent development is the MELD 3.0 score. It's evolved over time to allow for better allocation of organs based on sex now. That's the most recent factor added. The range in terms of the value, anywhere from six all the way up to 40, and at the low end, well-compensated, low MELD score, 90-day mortality is very low, but those patients that have very high, or at the upper end of that range, have a very high 90-day mortality. The higher the number, the higher they would be considered on that wait list for transplant. The mortality benefit, so for our outpatients that we're evaluating, considering when do we refer them to a transplant center for transplant evaluation, really that mortality benefit is once they reach a MELD about 15 or higher. That's the end of my talk. Thank you, everybody.

cirrhosis

portal hypertension

Advanced Practice Providers

liver disease

hepatic encephalopathy

transjugular intrahepatic portosystemic shunt

liver transplantation

Child-Pugh and MELD scoring