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and thought, Maybe just give people a bit more background context around chronic liver disease and portal hypertension and some of the issues around treatment and management. And then come a couple of interactive pieces in the middle and then and some more overview of hepatitis A The end because again, probably quite helpful in this context. So it's already generalists internal physicians need to know about never disease liver disease. As we said, yes, they kind of coordinate huge number of metabolic functions is related to wound healing. Impaired clotting with deficiency and factors and reduce platelets, usually secondary to hyperspace is, um, the risk of blood borne viruses and the consequences that that has, and everything from family tracing and risk of an onward infection and as well as increased risks of hepatoma need for surveillance. Um, and then, overall, you know that the prevalence of chronic liver disease is increasing along with increased morbidity and mortality. So the liver functions principal issues around protein metabolism, carbohydrate. A double is, um, lipid processing, Bella acid production and storage, Billy Ruben metabolism hormone and xenobiotic metabolism and immunological defense. So one of the issues that will come back onto the principle around. The conjugation off bilirubin have processed across the powder statement curricular him and the processing that takes place. And then again, we'll look at some of the clinical manifestations of this. This is just the kind of seen that we touched on yesterday. Iran conjugation bean bilirubin being banned passage across a parasites and eventually conjugation being past for the, um, polar and into the form of you know, you're a pill in a gyn or stay a couple energon, depending on how it's processed. So one of the main questions against medical students all the time has heard you know if a patient has liver disease, so usually it's a combination of clues which may be past history. And I can include family history of liver disease, which increases the risk. The presence of John this on usually people have some suspicion based on the stick matter of chronic liver disease was important to note that actually proportion patients will have new signs or symptoms at all. And remember that books patients have to present is an index case most common presentation to return with and G I bleeding or presentation with John this so there's two most common index presentations of patients with liver disease. So I think that causes of cirrhosis most common in the Western world no, well, a scribe. Alcohol is the principal cause. What would you have increasing and preponderance off metabolic associated fatty liver disease and not filled as previously iterated and smaller print things? Then, in terms of the third, most common would be the infection supported these hepatitis B and C, but it's very tiny smattering of hepatitis delta we didn't look at. Some of the autoimmune are co existent closes. That's just the things like clumped a bell disease primary biliary cholangitis, sclerosing cholangitis. Um, as we mentioned best, they've got hemochromatosis, very common and Irish from Scottish populations to do with the underlying genetic mutation, which is a and single point amputation, which is acquired from one coffee from each parent on about 63 d mutation. The there's very rare cases of Wilson's in your case will only see two or three per 500 per five million in Scotland of Wilson's disease in again as a strong hereditary base based on and chromosome six off. One of the trips in is a mixture and can be co existent rather than a primary cause. Yesterday was varying levels, depending on the genotype that their patients have acquired. And usually they need a second hits to develop florid chronic liver disease. But a certain well recognized contributor would. Chiari is rare, but this is essentially occlusion of veins, and we see it most commonly in protime about Extavia a factor. Five Leiden disease azelas thie jack to mutated associative changes such as polycythemia rubra vera on essential thrombocytosis and then thinking that toxins and other causes of methotrexate is very strongly associated with advanced fibrosis. And that's usually given for things like psoriatic arthropathy year and four just for psoriasis and skin conditions with an Amitiza tablet. And and And it has very potent fibrosis and dosing inducing factors. And added to that, a lot of these patients will have also had other immunosuppressants considerably considering main use of court with steroids so again, often they have a coat factor of obesity. 30 diabetes and with methotrexate is quite potent. Multiple hit which well prominent in cirrhosis on and other factors which are cc or four, which is actually a toxin that we don't see very much anymore, but we actually use it in our mice models and to actually give us and models off fibrosis that we continue use in our experiments. So they're thinking about signs of services that you might see in your patients. The most common ones are spider nearby, which generally existed in the distribution of the S P. C. Become be normal in pregnancy. So again, and they follow that distribution and the thing about off the drainage into that right side of the heart so you can exist in the face, neck and upper or torso, and after after pregnancy, they should resolve. And so is it more than six. But any Viagra wise is relatively pathognomonic off cirrhosis. Palmer erythema is secondary one, but again, tomorrow theme is is more common in females because it's generally under control, um, of estrogen. So again, hyper estrogen effects can actually induce Palmer erythema and clubbing zoo Well recognized wonder and under diagnosed cause. In terms of cirrhosis, we see it more commonly, and and obstructive airways disease, lung malignancy there a toxic OSIs, but it can occur and cirrhosis depending on meteorology. Gynecomastia again relatively common because we know that It's principally when once we develop cirrhosis, there's a change in the metabolism of testosterone and so on. Man gynecomastia becomes quite prominent because you get changes in aromatase. I'm on the production off female hormones approximately may or may not be present and is generally we think about cirrhosis. People have small, shrunken numbers, but in in presentations like alcoholic hepatitis them and, incidentally, having a powder megaly during the acute phase. And then that resolves. And then the secondary small, shrunken appearances predominate. Them splenomegaly again common feature and would suggest you the presence off the portal hypertension or the main factor. No, no signs that all, particularly in metabolic, it's excluded fatty liver disease. Then the first time I probably introduced this concept is the idea of between compensate and decompensated. When patient presented decompensated cirrhosis suggest that they now have evidence of evolving extra. It's presence of a safety's presence of evolving or worsening and careful up the and easy bruising or bleeding cities of the hallmarks of the of it, very like optimized shift from very compensated Well, patients very own well patients with a very high risk of mortality on presentation. So there's this new theory A as existed around acute on chronic liver failure. And this is the hallmark is is the shift and decompensation and why is this important? While patients who have compensated cirrhosis of the median survival of about 12 years, patients who presented cirrhosis and a decompensation event of a medium life expectancy of about two years? So it's important that he said before, to try and find the patients on do modify what we can to improve there. It comes in terms of risk of decompensation. So overall and mortality of these admissions in all cause decompensation if you like, You said, these are the main causes and 10 to 20% for any patient who presents to hospital. Common causes of the compensation include anything and everything, really, from acute portal vein thrombosis, which is very common, you said. These patients are relatively pro from about IQ and true G I bleeding, which could be virus it on on variceal. Patients presented with bleeding actually even with cirrhosis, have about a 30% chance of having non variceal bleeding. And so again, it's important to consider that we were thinking about had a treatments may differ. Patients present infection. Sepsis come anything from just upsets. Urinary. True, too spontaneous bacterial peritonitis to cellulitis so it could be relatively innocuous or can be very widespread. Systemic sepsis. As we said, it's came a liver injury so they can have secondary hits for whatever reason. What about it is because they get the range circulatory from dysfunction because of their sepsis. What do they have? No developed a new patterson or carcinoma and just again relatively common in terms of becoming an incidental decompensation events or patients presented with decompensation. You always looked update our imaging studies and drugs air credibly common for those who have alcohol related disease, more alcohol is more likely to decompensate, um, true to opiates, causing constipation and get a locker. The insides, which increase the risk of bleeding. Right. True Teo Consequence opiates, which cause constipation, causing death, allopathy or dehydration. And he's kind of precipitate, Um, and the compensation episode alcoholic hepatitis is in here is well because actually probably most common cause of decompensation, and it's obviously linked back. Um, today they're incidental, alcohol least. So if we think about what is gone, this and John, this is a clinically apparent Hyperbilirubin a Me and Billy Rivers. Normal range is less than 17, but would usually say clinically, we could be able to detect it about a greater than 40 micromoles per liter in terms of clinical signs that you like to see. So we tend to look at the sclera or then because of the common common places to see them. And these are probably very common in patients where it's relatively subtle. We usually get them to look in the unilateral direction, and you can just expose this clearer. And and again you can see that even you develop some He's got depict arrests. You begin to develop florid skin changes as well. So what types of liver disease tend to cause, John This essentially all commerce. So acute liver disease acute on chronic liver disease, longstanding chronic liver disease, and John the secondary to biliary obstruction of the main ones that I want you to know. Okay, this is just a wee schematic off some of the aspects, Rand, um, increased John, this on day of the consequences are chronic liver disease. So one of the things that do you want to highlight is shunting and come back to that. But essentially shunting is incredibly important because this is the change in being a circulation and the ability for the liver, too. Assimilate these toxins. If you think about most of you, your intestinal blood flow will come back by the portal system through the liver, to which there's no direct connection to their product systems or has to go through with sinusoids and be absorbed through the various cuniculus eye on eventually work its way up through the liver. So if we create shunts, we run the risk of increasing certain dynamic blood flows, which increases risk of bleeding on. Been careful up the as well, so the portal hypertension aspect will come back to you. So the commonest clinical features that would expect to see from somebody presents or actress, maybe dark urine, just a conjugated Billy Ruben. Pill stools with these might not always be president if they've got a and, um, conjugated and hyperbilirubinemia patients often complain of itching, and I tend to be very deeply jaundiced when they get to that stage. Most work most common at nighttime, and you'll often see a lot of excoriations on the extensive surfaces and and this is a really problem for patients and actually a significant morbidity in terms of quality of life and and morbidity. Patients often have lethargy, malaise, and then they often have this profound anorexia where they have no interest in eating or drinking. And some patients may or may not have features of underlying disease, so they may be profoundly anorexic, the hectic secondary to a malignancy. And they may have developed secondaries, features such a type two diabetes from their pancreas cancer and then have peripheral neuropathy and other things. We always look for these clues when you're assessing patients that go on this for the first time. So looking at the biliary system, think with the natural drainage, so we think of it, or the congregation that happens within the liver. Parenchyma you can get most absorption is via the small ducts, which then makes the way into the larger doctor of the biliary system of the main right and left the paddock ducts. He's then form coalesce into the common bile duct where it meets the system, which come off the gold bladder. You think about the gold Better is responsible for a storage of the bile acids which are necessary for a multiplication of fat and released under the influence of CCK. And once you actually sends fatty meal one in the stomach CCK is released and you get release of digestive enzymes from the pancreas, as well as a contraction of the gold better and secretion of the bile acids for and a multiplication of the facts within To be the fat may seals that you might remember from being sick biochemistry to allow an absorption in the in the Judean um, proximal judgment. This is an ercp image which you may or may not know about it. So this is endoscopic retrograde pancreatitis fee and planned your pancreatitis. Really, Really. And what we do is we pass a side view scoped and the mace through the esophagus stomach passed to the pylorus into the first part of the Judean, um, around the bend into the second part, where you can then see if the very tip of the scoop very fine wire that's passed the and and you can see See that one of the gold better the rectal doctor appear me See that? And then you can see this off structure off here is this the pancreatic duct as it makes its way down. So you have both of these offices kind of coalesce within the ampulla Vater, which is relatively muscular, a sphincter at this thing for a body. And Andi, you can pass wires up into the biliary system or indeed, into the pancreatic cyst in depending on what you're looking to achieve. And we can take brushings if we think there's cholangiocarcinoma. Zorro got classic and tumors were in the common bile duct, and we can actually put stents in dilate. The common bile doctor would balloon trolls. We have to make an incision along here on delays. Improved drainage, but may need. The addition of some stents is well to keep things open after is external compression and or big stones that we can't quite poor lately sometimes leave a temporary pigtail stent to just a lot of drainage past the stones. We can give drugs like our so doxy call it acid that hopefully help re absorption. And then we have a slightly newer machine that we can add onto the your CP scope, which is called Spyglass, which allows direct visualization, and we can also use things like Electra wave lithotripsy to break up stones and the doctor in pancreas is the light in structure. It's over here yet, so it's very hard in, and in this to make out and physical circle is it's not completely visible. No, no, no. And your CP. It is very properly appreciated. So it's much better identifying ducts because we're just putting contrast up into the doctor system. Only content to see is that line of the small bail, actually, so you can see when the Judean, um but beyond that actually is very hard to make it structures and because of the levels off in izing radiation that we use, and it's just they're not very good and technique, but it is very helpful because stones are generally radio opaque, so they showed very, very well, so you can even get very, very small pancreatic ductal stones. You can sometimes seek pancreatic calcification, and that's usually a sign of chronic pancreatitis. Charlotte. Yeah, I am. So what happens when under normal circumstances, what happens when you on this are normal? Processing of Billy Ruben goes wrong, and we kind of touched on this yesterday in relation to increase production failure of the expression, um, so you need to have defective conjugation within the parasite. Effective delivery to connect lists within the apartment. Off taking two you're parasite or get complete blockage of bile doxy. Other with in the in in the liver itself, intrahepatic or within the extra padding biliary tree that we just saw so again kind of restricted what we mentioned yesterday but increased production. Oh, Billy Ruben is usually related to kind of sequestration when they're going to feel your system breakdown of hemoglobin of the separation it was relative for get processing off the Hemed albumin is transported to deliver and then undergoes and normal conjugation to form the bile acid conjugate. It's but in homologous again overwhelming effect of this with premature breakdown of the red blood cells and and you often then just get release of Billy Ruben into the air circulation. Um, in terms of the ones that we mentioned. Yes, there's well in terms of congenital effects. I get on conjugated forms, so she'll bears and crawl in a jar. There inherited conditions with lots of enzyme functions. Gilbert's is really common. It's probably 2 to 5% of the population and it's a failure of the This glucagon is still transfers enzyme, and it's not pathological. Very common for patients with job is often times of stress or co existent illness, often kind of a very low level hyperbilirubinemia that resolves and patients getting better. And it's not of any significant consequence. Kremlinology era can again be relatively benign, but type one can be a bit more and life threatening, and patients often undergo what we call piggybacking. Are small grafts transplantation when they're relatively young, But it can also use certain drugs and to try and improve the congregation off the liver even now, as well as things like UV lights and lamps that patients can go home with but tends to be less well accepted to patients usually and look of transplantation at some point. And then the conjugated ones that we think about or Diovan Johnson and Roaches Syndrome. And these are incredibly rare, be pediatric population. Step down. That's discomforting. Yes, you know the Gilberts one is that can that occur any time, or is it usually in early life? Or most people have jobs and never know better. To be honest, it is inherited, and people have it as a a baseline the first time people notice it tends to be when they first become unwell. So Children with a fever and and often that it was just incidental, picked up, but usually so low level, and that we pick it up in clinic when people get blood tests for something else. And they have a very low level, slightly higher within slightly above the normal reference range but relatively benign. So usually patients will have a bilirubin of 30 which isn't particularly consequential on. If you did a split of conjugated on conjugated, you then be able to say that actually is a known conjugated. I bilirubinaemia we send it Teo Scotland, Mr Dundee, actually for genetic screening. No one really knows why we do it, but it's nice to know expose, and we can then reassure ourselves. It's not another cause of unconscious, gated hyperbilirubinemia, and but it's usually completely benign. Patients never know they have it, even though it's relatively common. I think Mohammed had raised his hand. What is the difference between Gilberts on Johnson crap in a jar syndrome? There Mawr pathogenic, if you like, so they're much less able to handle so that they're functioning level is much lower than Gilbert's, where your grades is a his appointment a shinin the enzyme, but you still have relative functionality required, and Jared tends to be more prominent because it they have less functioning ability to conjugating job Ear's I'm Again. Most most type two's, uh, again have very intermediate levels of John this. But again, it's not pathological, and but the type ones are more pathological, and they sometimes do undergo transplant. But with a lot of these, it's it's a spectrum. And so, even if you have a type one so people can have a relatively benign course, what are people in their first year of life? Develop a bilirubin of to 300 me transplanting quite quickly. So it's not having one or the other is not instantly predictive off of a come and obviously any patients presenting with significant John this we, usually particularly Children, would usually do a split a splitting of the bilirubin to tell if it's conjugated on conjugated and and then we can we send for genetic studies. If we thought it was one of these particular ones. Okay, um, but one of the things and Children in particular is elevated. John. This can cross the blood brain barrier. I'm sort of is a condition called connector ist. So that's why it is quite important in Children to maintain it below a certain level. And it's because connector is controls, profound learning disabilities and brain damage. And so again, it's it's mainly based on the severity off their jaundice level, depending determines what we need to do. So then, if you think it's just another nice ercp picture and off this is an MRI CPU sorry, and which is a magnetic version of the Ercp, which can just give us really nice pictures of the biliary tree. And what we can do is you can actually create treaty reconstructions on what we can see. Them here is a very dramatic tailing off, and as it comes down on also in here, we've got what we call kind of beating or development of what we call moderate see syndromes that is usually it's still stuck in the neck of the cystic duct and which can cause a secondary fistula to occur, and that can be quite challenging. So the MCP is just really a nice way to visualize the tree is not invasive, but I didn't mention it. Terry is the risk of pancreatitis is about 2% to Ercp in Syria's dangerous and particularly the young women man who have a higher risk of severe outcomes from that. So in terms of the secondary causes, we call a static jaundice and so we can get it is an intrapelvic on extra product. Intrahepatic is within the parenchyma itself. We spoke about most of these estate, but viral hepatitis, drugs, alcoholic hepatitis scerosis of any form will effect the ability to process bilirubin pregnancy. So we go and cholestasis of pregnancy, which is again a benign condition, is often exaggerated in people with your bears. And but that can be problematic and again can cause problems for fetal groups. And sometimes and very rare circumstances would necessitate delivery of the baby early. And we monitor that, looking at by Lasses and and again we tend to manage the complications off there. John this because that tends to manifest as it and which is the most problematic thing. But again, monitoring baby on getting baby out, even if it's premature, is the mainstay of treatment And then it's a whole lot of miscellaneous Uh oh comers in here, including drug X, liver interest, extra pad it causes. If you think about these just a structural issues Goldstone's in the CBD or any other form of CVD disruptions of biliary strictures, whether that's due to sclerosing cholangitis, secondary biliary cirrhosis am or whether it's pancreatitis and extrinsic compression or cholangiocarcinoma very typical hepatocyte alert carcinoma. It's just blocking the doctor, not allowing the normal passage of conjugated bilirubin after what other example of drugs that cause problems. So the classic ones that would say, or things like refund person and reform person methotrexate in itself, spoke with earlier, is of bruising causing issue, but can cause cholestatic. John this alkylating steroids particularly bad and then anti epileptics. And and there was, ah, again, I don't want to give you too much smoke print stuff that is important to nobody. Now there is a condition called dress syndrome, which is a drug reaction is in a failure of systemic symptoms of patients often present relatively John list Ranger lefties. They may have a swinging pyrexia on bacon have developed Great Florida exam tomorrow and renal dysfunction on and they often have a very pronounced serum is in a failure, and there's a scoring system you can use to determine the likelihood. So some of these patients will need byopsying. But the common culprits are anti epileptics, particularly some of the older ones see it less with the newer drugs like leaves to rise the time. And but we do see it with some of the older ones or sodium valproate and on D leave, or dopa is the other one that's very common. So then it's just being aware of these. And if you're ever on, sure, there is a website called Never Talks, which gives a very comprehensive You just keep in your drug. And it tells you every two case case report that's been published a swell, a likelihood of being the cause, it of agent. And that's really helpful resource for you guys to use as well. And we still use it commonly. This what healthy never looks like. This is what we're all striving for. This is micronodular. Cirrhosis you can see is very pronounced difference. And it's this nobly appearances what the sonographer often sees on the ultrasounds of the regular outline and what features of Mackinaw jeweler seriousness. And as I said, yes, the cirrhosis is really this final pathway between value evolving fibrosis and the constant regeneration of the liver, which causes this piecemeal regeneration but per re establishment of the parenchyma on the normal liver architecture that causes this stiffening on lots of layering of collagen and see here so initially really nice small spaces and around the blood vessels. But they're really jump packed. Full of inflammatory infiltrate is NFL's on a whole lot of and extra cellular proteins that shouldn't be there. Liver function tests. As we said yesterday, important to think of eight and common ones we touched on a low T e S t a l peon comedy tea about really are well, you know, understand is your tree liver test is a bilirubin, albumin and protein from been time. It's one of the things that we did say yesterday that, um, again would be nice to kind of touch on with this idea that patients have elevated prothrombin times a renovated iron or but that that doesn't translate to increase risk of bleeding. And and again, this is just a really nice diagram of of this very gentle seesaw, if you like. Between thrombin generation, um, fibrin generation on fibrinolysin is and it's this constant equitably, um, that we have was with normal function livers and normal human static potential and and cirrhosis. You get huge changes in that from changes in activated. Lately, it's on their surface marker expression too low production off the coagulation factors to 579, 10 being the common ones that we think about it and also on this other side. So that's on the bleeding component. But if you think about, uh, thrombosis side, they also get low levels of protein. CNs antithrombin three on heparin cofactor three. And these are a natural, intrinsic anticoagulants if you look so these patients exist in this very delicate equilibrium. And but if anything, we know from studies that patients probably exist slightly more on this profound about Exide and but there are certain events that can knock patients off. So if you think about it, this is This is, uh, Sinemet a little having normal hemostasis and you get most of these potential prothrombin stick events. Um, but particularly hepatoma development. So patients will incredibly profound about IQ. Get what we call malignant thrombosis with hepatitis, and but they might present with bacterial peritonitis. And they actually do have uninterested of bleeding. So it's about kind of clinically, really re evaluating constantly. There is a lot of evolving evidence around whether or not we should anticoagulated these patients and and some centers in mainland Europe. Do you actually do this routinely, even in the absence of any from boxes? So I thought at this point to be nice if people want to shake it, some answers. I'm any takers for what this is. Want these air straight to live Jesus about an IV? I yeah, it's a really, really prominent in this one Ondas you see on the on the face that become very unsightly, and patients often convict frustrated with, um so we can get and camouflage and I'll ask. People t use makeup on them. Have had some patients who try to cut them off a razors, and they bleed horrific Lee and often actually grow on their related to these new on Joe Cardiogenic growth factors. And but otherwise there's no real treatment for them, And but we encourage patients try not to pick them or encourage bleeding. So if we think of eight, anyone who wants to tell me what is demonstrated on this person stuff and what does it represent? Hello. It's a scientist, Doctor. Say that again today. Sites and clubbing. Okay, so it's hard to tell clubbing from the angle, but you would do is probably in any suggestion. What about playing weight? Now, what does that suggest? Clinically, if you're to do a yes. So I think people suggested kind of low a low albumin. So that's really common leukonychia. And that's that's low albumin state. That's good. This one here should be relatively straightforward. Come with me. My, uh, primary theme. Asas A really nice broad definition of it. These are some of our local patients. Previously, um, again the expired an IV, I and you see just what? Using clean, um, microscope slide. You can see how it coalesce. Coalesces when pressed. So you empty contempt of the vessel, and then it feels on removing the pressure. And what about this shop here? What's this? Here Sites? Eighties. What's this here. This here, you know? Yeah. So someone mentioned her knees. Yeah, I think hernia. He probably has to put my do say, which would see from the front and on if you look at this job. What? What was the most prominent? Finally the list. Chuck, do you think Joe's John this? Yes. Citing pill. Nose A. C Uh, you're perfect yet. What do you think that is? He's got ascites. Hey, present with the eyes under erection, it's like under X ray says maybe so. Circle, circle, Penick Uncredible we wasted isn't a so you can see his arms. He's got lots of loose skin, lots of bruising on. He's got an injury to which is usually about fine. Uh, what's What's the market? Isn't it very a central line? Central line? Anything else it might have been in bio. See? Liver biopsy? Yes, a transrectal. A liver biopsy. Anything else you might have done? Transgender comes to school. We'll come back. It's hips. Proceed. So you might have had a tips? Yeah. Yeah, like March of not who knows. So this one here, this is hopefully just a normal feeding tube, but we'll come back home to sing Stack and Blakemore's. And but he might have had a tips, so we'll come back onto that first two pictures on the top, left and corner. Decent. Yeah. So this is a big spot, an IV. I just here on this is what happens when you just press it with that's clear microscope slide so you can completely coalesce. So you just empty it the vessel, and then when you remove it, it fills from the periphery. And I'm not. So you can. It's kind of the classical diagnostic sign, and it's really just for information with anything. Okay, Thank you. So this is the other chart from the front of you. You probably just have to put my juices Now It's a very old picture there, and he's got a huge volume of safety is big hernia. And again, you can see the natural muscle wasted. He's he's got some chest here, but we do see loss of just there and males and and kind of overall feminization again. That comes back to the aromatase on the shift from testosterone to estrogen. Um, in these patients street here that you see, you know what's the reality was the actual name of the street. So you can get just street distancing is kind of like you see, in Cushing's, and it's really just descriptor that he stretched. And then when we drained that goes away and gets big shifts and street a distance, see is probably the the old Latin term that we use. And there is there is a bunch about discovering the drainage area like drainage. So what? What do you think he's had here? Synthesis? Synthesis? Yeah, somebody has been someone's been brave and put a needle in a having May and they're not in a large volume person teases. I think it's unlikely because he would, and we usually leave the patch on for 24 48 hours to re accumulate. That much would be unheard of, so he's probably had a diagnostic aspirate to exclude SPP. But this strap is needing a drain never missed. An MRI hasn't had and and again, this is him from the side. So you can imagine that the volume and these is absolutely enormous. So it's very easy for patients that have a third of their body weight. Imagine if you remove this. There's not much left, so this is what we call also 75. This is a rare complication, and you can see longstanding hernia development, chronic areas, and they often just have weak points. And so this is the ascites coming straight out, and so we tend to just left that this happened naturally. These patients, often to, um well to undergo reparation of these to attend to the NASCAR tissue viability nurses to try and improve and try to optimize the diuretics and management of the ascites because this tends to be quite a difficult complication to manage. Actually, this is just notice and finding of what we see, so you see a lot of black fluid. You see the small, shrunken liver here that's almost a bit like a nutmeg, and and it's it's just surrounded by lots of fluid and see some small, small bell floating around, so we often just use this for safe marking site. And in realty I'm. But when patients have huge volume ascites, we don't tend to realistically even know to send them before we drain them. So how else can you manage? The more we can use a diuretic? So, he said, So this is a very old slide because we don't really tend to use these drugs very much anymore. You do you still use for eczema, and we think it. You think about it acting on the ascending loop of the name of Henry, and we use spironolactone or any of the eldest ear on antagonists. We do use a meteorite. So on these work on the distal collecting ducts, so spironolactone would be first line but again can worsen painful gynecomastia and men. And if that was a problem, we would usually you moved to and really right or a player unknown and for is, um, I'd on spironolactone. And these two drugs tend to work quite synergistically because they work on different, different aspects of collecting ju bills and nephron, and we tend to steer away from anything that works on the proximal Giulio Am just because it they tend to be very overtly and sodium specific. And these patients are very delicate food. Balance is really except that frusemide and spinal actor and can effect that as well, and they tend to be gentler. So if you think about large volume person T sis. So if you think about that shot before was probably about 15 to 20 liters of fluid that provides rapid relief, and there is a risk of infection, but is actually works both ways. So by leaving the fluid in there, you know there's lots of translocation of bacteria across the colon and which can induce spontaneous back to your peritonitis. So we know that they've often very leaky and membranes between the colon and into the peritoneal space on deed from the biliary system as well. So again, it's not. It's not benign thing having what's usually steroids we were there. There is really risk of that becoming a true SPP. But there is a very small risk of what's putting a drain into the fluid to drain as well, in terms of introducing infection. So we tend to do a sterile issue can, and we tend to leave the drain in for less time than previously, So some centers will you for six hours for 12 and some for 24 hours. But generally we would never leave it in longer than that, and most we would don't tend to even use long term indwelling drains, even for patients who are on the palate. If it is because you know the risk of infection is so large, but that's generally assessed on a case by case basis. But most patients will have about 70% of their fluid removed within about 12 to 24 hours, so that tends to be long enough for most patients. And then we can optimize in between drains on. Some patients may only need it once every 4 to 6 weeks. Some patients will still need it every week, but we can think about what else we could do for them. And if you think about that, A said 15 to 20 liters may, because it's huge, fluid shifts. And again, any of these big fluid shifts and consequent changes in circulation can knock patients off significantly and induce and careful apathy. And but more worrying is usually this idea of the fluid shift between intravascular and peritoneal space is as remove it from the peritoneal space. There is a consequence change in the renal circulation, so we know that there's a risk of what we call paracentesis induced circulator dysfunction, and that can induce this new idea. You might have read about about a renal syndrome, but we know it May was about a renal syndrome, a chiari, so that's very sudden. Acute kidney injury related to changes within the splanchnic circulation, and to minimize that effect, we tend to give quite large volumes of albumin for every 2 to 3 liters of fluid that we removed. We give a large volume of albumin and a small concentration of fluid, so it's usually about 100 miles of fluid. 20% human albumin solution has for every 2 to 3 liters of fluid drained off, so we usually will then give patients maybe 121 140 g of albumin. So if you think it's 2020 g about of arguing with 100 mils of 20 g and 20% project so so that we tend to give them a big book off this albumin, which acts to induce more oncotic pressure within the vascular spaces. So feeling patients who have recurrent ascites, which have failed to respond to your usual measures who are not candidates for transplantation. We do have this idea of the tips that some people have mentioned, and this is the creation. As we said earlier, there's this. There's no natural bridge between the portal venous system in the paddock system. In the paddock, veins lead up to the IV see SPC and into the right heart. And so what we're looking to do is the bridge between the portal vein and the product system, so we can do that by a transgender. Read it, and this is what the stent itself looks like. And But if you think we tend to pass a catheter, then and then the internal jugular vein manages to find a way down into right paddock vein. The radiologist then looks to induce attract puncturing, so they they puncture relatively blindly, actually, until they managed to hit and a part of the portal vein. Following that, we pass a catheter across and to create this false Lumen, and then they pass the actual stent itself over that and look to create this essentially new passage, which induces a shunt essentially between the parent portal and a bad existence. So, she said earlier, So this is what it looks like fluoroscopically. So they managed to pass the wire over. The stent is in place, and they can measure the pressure change. So there's a pressure Grady and talk because the product vein wedge pressures and and that's how we know a test ablest of portal. Venous pressures are in terms of their portal hypertension, and that has not gone effects for their varicies. So tips is not just use is a treatment for ascites. It can be used for acute bleeding patients who have refractory on the esophageal variceal bleeding. So I thought it might just be very helpful. Very quickly. Touch on some of the viral hepatities won't cover GI necessarily, and but we'll hopefully try and cover it. Theaters could be practicing on a leave it and so hepatitis A as relatively common, very common in developing world and fecal oral spread. It tends to occur a relative to per hygiene. Access to sanitation, overcrowding, food and water. Most common can be vectored by animals as well, and some cases are important on it tends to be a relatively straightforward acute hepatitis and with an obvious exposure, is very infectious. So we usually isolate. Patients tend to have a relatively profound John. This does get better. Very, very rarely can cause acute liver failure, and it has a higher mortality in older women. Older men on did in pregnancy, and but generally it's a relatively straightforward conditioner on. There's no such thing as a chronic hepatitis A, and it tends to want to pass on to develop antibodies. You shouldn't get reinfection again. And for people traveling the reserve, there is a vaccine. The laboratory confirmation is serology. Usually a gold top tube on we look to do for acute infection will be the classical I GM is the first and incident antibody, and that will be followed in time. But a a rise in your I G as your IgM begins to fade away. As we said, we generally try and manage patients and isolation. Encourage good hygiene practices. On there is a vaccine on demeanor, globulin for pre exposure prophylaxis and high risk groups. Very cute onus, Very small numbers diagnosed in the UK, and there is more in Eastern Europe on D in India on day. So the seizure is normally very self limiting, really progressive forms failure. But we did have a small and group of held early patients who did progress the product failure, and it's generally just conservative management. For most patients, hepatitis B is a bit more, um, interesting transmission is generally blood cell. Most common in the U. K. We see is a needle user, but there is vertical transmission as well, and between from mother to child say him. There is possibility of transmission by sex and sex workers and is rare mother. The child is most common and and non, uh, drug users. And the rates of chronic carriage very between ethnic groups of some groups, spontaneously care of the virus better than others and chronic carriages more likely to result if their first exposure is in childhood rather than an adult hood. So actually that will. Do you get when you first acquire it, the more likely you are to spontaneously clear it. In terms of how we go about investigating, we tend to look for the hepatitis B surface antigen on that is present and all of lectures individuals. There's a very straightforward infectious screen for you to organize and for the city or bit more interested multiple different phases of hepatitis B infection. But if you're looking to determine how infectious someone is, you tend to also request hepatitis B antigen and and you can also do happens. Be DNA to ascertain a viral load a bit like an HIV on these patients who remain HB antigen positive have rapidly replicating virus until had incredibly high viral load on remain very highly infectious. So we do warn about ongoing transmission with sexual partners or even use off hygiene equipments are using two pressures razors or anything else that might be possible to carry the virus onwards. And anti HBs is present in immunity. So those people who have been vaccinated well actually have this antibody and which you contest for a swell. So how do we manage it? So we tend to encourage safe look practices. And it didn't not be able to donate blood safe sex, needle exchange, prevention of needle stick injuries, vaccination of all Children, sexual partners or risk people that patients may be in contact on Decem particular vaccination of Children is very straightforward. On is a rapid and, uh, Chloe inoculation program, because the usual program is is initial index injection and second one that one month on the third one at six months is your nose is the kind of usual process for most people, which you have had for a medical skill. And but there was a slightly more rapid and path it up. You can give to patients who are deemed at risk. Yeah, um, and then this post exposure prophylaxis, sir, For patients who have been exposed potentially to hepatitis B, there is administration for a referred a vaccine dose on the use of each big, which is the hyper immune. Have be immunoglobulin just very quickly that they're kind of natural lifespan or natural history. Off HPV. So often you get a huge hepatitis B and with resolution, and most people small amount will convert to formulate a pad. Evaluated failure is probably less than that nowadays, but that's the traditional one. And we know you are a bit more aggressive in the use off on dirty eyes, just tenofovir at the early stage of infection. If it looks like patients developing significant liver injury, they also then have conversion to chronic hepatitis B, when people present them with and these various chronic states, which again this is relatively postgraduate, but and patients who remain surface antigen positive on very infectious. There is a very high carriage rate and have a higher rate of hepatoma because they've got much more ongoing immunopathogenesis process and lots of high viral load in a minute. Genesis he and then you get patients who become surface antigen positive and and the H B antigen, which is this conversion. So they become Hve antibody negative. So they have this kind of active hepatitis and cirrhosis, and major talks from There's Already and the treatment for some of these are relatively old out interferon and peg a horrible one year program of treatment with very low conversion rates of only about 30% have patients achieving clearance. At that point, we tend to use older drugs like the movie Dean of have Gone eight, Um, and there is combination therapies they're developing with. Anything more commonly would use a devil here at enough of year, um, and then take a veer on. There's also transplantation because you think your hepatitis B the reservoir is the liver. So if we can remove deliver than essentially, patients become disease free, or they often need ongoing treatment to minimize any risk or external carriage. Hepatitis C. Now this is but look at landmark change in the hepatitis realm and infection results in chronicity In the majority of cases confirmation and the laboratories antibodies hepatitis C, and so patients will retain this antibody so it uses a screening mechanism but you dont HCV antibody. If they're positive, we can then go on and ask for a PC or they do and Aurtenetxe traction an amplification, then get a discernible hepatitis C viral load. That again Comten fluency how we manage these patients. But in actuality, most of these patients and they have access to really profound direct like the anti virals, have incredible curettage rates. So, unfortunately, virus. There's no vaccine hepatitis C, and that's treated in the number of point mutations that can happen. So the bit like her own a virus. It's very hard to develop an antibody and as a test, a lot of variable changes once it becomes established. And it was very hard to to have a cover pan genotype pick one, if you like to the realm the maximal managed to. We have his immunization of exposure and then we've got really incredible treatments. So much lower rates of spontaneous resolution. My patients was only 20 to 30% of the majority, becoming kind of chronic active, low grade hepatitis where small amount of patients will transfer to cirrhosis and it depends on a number of factors. And and again, patients haven't not and significant risk of a part of senator carcinoma again, some, even in the absence of cirrhosis so they can move from this chronic hepatitis with fibrosis. Teo had a set of the carcinoma, so again they tend to undergo surveillance for that. So you know it's 170 people world, million people worldwide, um, in taste and Scotland of 100 for 100,000 of the population. We know about 4% of male patients and and the classical hospital. And the majority of those were undiagnosed for we increase their surveillance and a very small amount, but not significant again. Number of pregnant women who can were actively the inventively low risk over on unknown toe have and when looked at contact tracing. So the recent one is the French fibrosis. It's very important to try and identify the date of infection. We are a bit more, um, aggressive with biopsying these patients. But actually, again, that landscape is changing. We're using a lot more of a lost Agassi and non invasive methods. The time to cirrhosis is probably the rounds of 20 to 30 years, and for these patients, in the absence of any other cofactors I'm whenever there is a precaution that will be cirrhotic in 20 years. And and here you can see that, as we mentioned yesterday, effect on alcohol in males that significantly reduces their time scale to developing cirrhosis and where females almost exclusively removed and simply influenced by age similar patients get it in their older age. I am are more likely to develop more rapidly accelerated fibrosis, and so exists Just skip over that, but obviously be able to go back and have a look at those slides. And these are just the kind of developmental stages of the new treatments and how they came a bait. And these are the targets that the effect. So we've got a mixture of NS three and four protease inhibitor of tennis five A and NS five people. Emery's inhibitors, and we tend to use a combination of these drugs and depending on genotypes but actually have no developed Pantene a typical treatments, and we're going and readily giving them to most patients. This is just a relatively old trial at this point, and but you can see that actually SP or 12 that's the spontaneous fire. A resolution at 12 weeks, and this is the percentage that we're looking is almost for 12 weeks of treatment we can manage to in 100 65 patients, including those of cirrhosis. We're achieving cure rate in the 97 to almost 100% range. And there are patients who are non treatment, naive are experiencing there, bit more difficult to tend to treat him a bit longer. But even then, we're only looking at 16 to 24 weeks of a one today seem so it really has been a complete paradigm shift and the other thing to know about the viral hepatitis it eases. They have significant extra product manifestations, and they include the vascularity. So have polio traitors. Introducer mix the central cryoglobulinemia on purpose. So looks a bit like, and then i g a day and a front of the type A picture. I'm often something with a rash on. Coalescing into more widespread purpura on often then can involve on immune complex. Deposition on DPA found American the frankness, sir, and then, lastly, hepatitis C E and his worldwide, and it's very common in lower middle income countries, and it's only really come more obvious and are horizon the last 10 years or so, it's incredibly a powder true pick. The least four different zero virus takes 123 and 41 into our exclusive. The infective in humans three and four concertedly amongst while stock and lifestyle, including pigs, world boards and dear were parent any significant disease PathoGenesis and very very case report level infection of humans. And again, it tends to be fecal oral spread. Most common way that it presents. Transmitted Scotland his pork products so usually sausages meet that has been tightly packed and may not be cooked to a core temperature. Um, and again in Detrol is feeders. We stirs, and shellfish is the urine, usually from Syria. Drain off from animal livestock. Yeah, and typical signs of of the condition is usually mild fever and our exit nose and vomiting. Real, nondescript viral prodrome can then present abdominal discomfort. That tends to be a hepatic phase, where they get swelling of the head of the liver, parenchyma and stretching of the liver capsule, and they often get relative puritis and sometimes get there widespread rash. And they often get arthralgia and they're often relatively John Wrist, and we often get mild cardiomegaly and treatment is just supportive. And except in those patients with cirrhosis. So again, investigation is just a hepatitis C G. M. And we can do PCR to look for levels you can do it and blood in stool and the only one step monitoring in our post transplant and are those with cirrhosis, cause mortality can be a size 30%. I am from a study, read it in Scotland and published in A P and T. Yeah, so? So it was a bit of a whirlwind, but I just wanted to give you a bit more contextual bit because our was afraid you maybe didn't have enough name theory and rather than too much case based stuff, so I'm happy to do some more. Case makes things in the future. And but just thought, least if you have access to the slides and and at least you have a bit more of a theoretical basis if you need it but really have to take any questions. I noticed for quite a few things in charge and and I lost the overrun usual. Excuse me, Doctor, you said that we we will go back to one off those slides to see that picture off. The we did that the commits that you There's things that I know of. I was just wondering I I haven't seen it in my slides. I don't know why it didn't project you ck. I have it in another one. Let me find it. Um but yes. The second Blakemore tube is and I'm Have you ever seen them before? No. No secret. Got another presentations for me. Sit too many. Yeah. Seek from here. Ah, all right. Can we see? Can you see this? Oh, yes. Excellent. Sorry. So So these are what the virus is look like. And on end endoscopy. So and these are the grading is that we use is 12 and three and this kind of bluish blue issue that you can see. And so if you look at the picture be there's three, maybe four columns of Aris's and and the idea of what we're trying to do a first is to put these rubber bands and a PSA first line so ago. Disbanding system goes over the scope and and they just took them up and they like a tamale die and drop off if we can't manage hemostasis using that, what we can do is the second line of the other things that can tube. So basically, the TV was this'll picture of a straight since passing through the nose, but actually tend to pass it orally. Patients are usually introverted on have a really protection, but sometimes if it's life or death, you just have to put it down. It's generally quite a floppy tube, a number of ports that you can see here on the on the manic in. And what happens is we passed the balloon down past the DOJ. We insufflated and then we pull it, and it's really quite a robbery latex tube. And when you pull it, what you're doing is you're actually company out in the feeding vessels. So the vessels actually fill from you. See where the portal vein and the left gastric er left district veins there so they feel from the bottom on, give up the way and towards the esophagus. So what we do is if we tamponade from underneath on, we pull the balloon really, really taught, and we actually interrupt those feeding vessels, and that's how we stop the bleeding, so it's only a temporizing measure, and you can only leave it in for 24 hours because it can actually cause the stomach than to become a schematic. This this, um, it's incredibly vascular, so it tends to be less less common. But the problem is, people used to blow up the esophageal balloon and the esophagus can develop what we call Uh huh, Suffolk AST desiccant is We're basically they get in the chronic esophagus. So nowadays, even though most billions haven't suffered, you balloon, we don't blow them up at all, because if you can get your balloon tight enough, that's usually enough to Tampa Nad. And so there is a move away from using the sense that can Blakemore achieved to using a slight variation for the Minnesota tube, and and then you can also see then, if that fails, we can use a tips, which is this shunt that we create across the liver. Um, one thing I haven't shown is there is a new stent called down a stent that goes at the bottom on just tampon ad eight completely blocks off the feeding vessels again, and we can leave that in a temporizing measure to see evil. The varicies he looked and stop bleeding themselves. Or what? A patient needs to go in and have the tips. But there are relative contraindications to the tips of sometimes These are just temporizing. Measure is to buy us, buy some time. Thank you, Doctor. No, it's okay, but yeah, that you won't You won't see them use very often. And but they are incredibly life saving. If you have nothing else and but usually with trying it and then with any PSA test president, sometimes you just after you put it down as best you can. Yeah, I have a question. Yeah, uh, he said, like in kids, some of them. If there is there any I put a little big state, they might end up getting connectors right, and the might have learning disabilities. And what about in adults that have bone? Does that have this type of a little bit state after you cured them on, They also like developed some problems. So we do notice that a lot of them developed a kind of a low grade and careful apathy, and on day, so obviously patients can have very profound than careful a pretty, and that's easy to diagnose because people are floppy or obtunded and sleepy. But actually, if you do an e e g on most patients will never disease. You have a shunt. Quite a lot of them will have low grades slowing of the delta waves. And and so we try and prove that as best we can. But there are some people who do develop permanent changes, and and it's probably to do with the plasticity of the brain being careful. Apathy is mediated by changes in the neurotransmitters between glutamate in glutamine and the changes in the astrocyte and very subtle fluid changes. So they get very my new demands of persistent cerebral edema. And so most people do get better after transplantation. But often they have a very difficult phase of getting over the hangover and careful opposite and can last quite a few months. Oh, okay. Thank you. Thank you, Doctor, for today's session. Really helpful. Um, there was a couple of questions in the tact, as welts were going through. There was one about How do you deal with it? Prison is a lethal yet so expresses. Sorry. Is the fancy name for John List that I can to use more. And so, uh, Hyperbilirubin on its own, we usually say when it gets to about 400 microgram olds for a liter once, once that persists for 4 to 6 weeks, people tend to get very obtunded. They have to get quite a lot of changes of cerebral edema. I'm They also get very constituent changes, and they're me in a logical ability. So they often succumb to, um, opportunistic infections. So again, because the liver is so involved in processing of inflammatory site of kinds and flammatory mediators, um, it seems that they become relatively immune, immune it efficient. So again, this was The important thing is to come back and think about what? What is the underlying cause? Is it because they've got an obstructive biliary tree? There's extrinsic compression from the pancreas can be coming on, come extended or decompress the biliary system? Or is it a parenchymal thing within the liver that patients need a liver transplant? Is it a tumor that we could potentially cut out? Is there a shunt that we could block off? He's an interventional radiology just really, really just about finding the etiology on managing that. So, yeah, I suppose it really Detective work is finding it. What's the cause for the jaundice? And because that again, that's going to help you to develop your prognosis and your management plan. Thank you dot Uh, we do have another question. Um, how to be the ultrasound or liver Cirrhosis. So I seem that thing. How do you diagnose or identify with cirrhosis on another song? Yeah. So again, we'll quick bad at, um, establishing all of the criteria, but usually and the sinografin is should report the radiologist a regular rate line is probably the strongest future. Um, they'll often say infiltrated or parenchymal changes consistent with liver disease, but that in itself is not diagnostic. Um so irregular outline. Shrunken appearance are very strong features. Even then, unless there's splenomegaly and presence of peri Hyler viruses, it's ascites than ultrasound on its own is usually not enough, and so we usually have to take it in context of clinical features, blood markers, ultrasound or cross section imaging. Did you need an MRI or a CT scan? Because there is causes off noncirrhotic portal hypertension so people can have splenomegaly and ascites but a normal liver. And so again, it's good to think about those because again changes your management. So I think if if annulled just and suggest a regular outline and parenchymal changes in keeping with cirrhosis, that's very strong indicator. But it's no 100%. So we usually like to have more than one piece of evidence to determine someone has cirrhosis. And again it's It's even difficult to get consensus along hepatologist for that, Um, so it's really about the whole clinical picture. To be honest on, sometimes you will still need to refer to biopsy, but we're using a lot of fiber scanning transient, the last Agassi to try and move away from that. And again, you're trying to put many pieces off evidence together to support the diagnosis. Thank you so much, Doctor. I think that concludes a lot of the questions that that there is one more. Yeah, I have a question like for the for the patients that start showing these D competition doesn't take, um, with eating, is it? Condition can only be treated to have, like, a normal life? Oh, it's just a don't want smoke from the downward spiral, so it's a really good question. And I suppose, um, it depends on the etiology. And so we usually say to alcohol induced liver disease if they can stop drinking, their risk of the compensation is greatly improved. They still have a risk, but it's massively reduced, and patients with nonalcoholic fatty liver disease are more difficult, and they tend to have worse. Prognosis. The viral hepatitis again If if they've still got active hepatitis, can we treat? They're very good evidence of hepatitis C. If we can treat, then go on treatment, program that again. That reduces the risk of decompensation I have. So it is usually worked looking for all these factors if they have a paracellular carcinoma, is a small one that we can just do a limited resection or what we call tastes. And again, those things might reduce the risk. If they have a portal. Vein thrombosis should be anticoagulated, um, and again improve their flow and reduce the shunt. Formacion, onda all those things. So it's very etiology dependent on dispose. That's the so that's the carrots that we try to use the patients that well they can get better. And what if they continue to not be able to modify the disease risk. Then their mortality becomes incredibly high. And again, it should also act as a trigger to us to think, should we refer them for transplantation assessment? Because that is a very viable treatment option for some patients. So again, it works both ways that tree physicians have a duty of care as well as the patients on trying to optimize their outcomes. But yeah, as a really good point. All right, Thank you. I think you are, uh, is just past about acute to chronic conversion. And I suppose if you manage to find the right, you'll get yourself a Nobel Prize. No one really knows. Some of it's probably driven by genetics and way. Know that. And hepatitis B that's carried from mother to child. It seems that Children very, really have acute hepatitis from hepatitis B, attempted almost immediately go into a carrier state, and then it becomes a Sierra convert when they're older, and that has picked up on the 18 19, and they never knew they carried it to begin with. Um, parents may not have known and they tend to be the ones that get this chronic active hepatitis. And if you develop, if you acquire hepatitis B, is your older through whatever means, most patients tend to clear it spontaneously, whether that's just because you have a more mature immune system that would better viral recognition and pathways toe overcome it or because the viral load never get tying off the trigger. UM, a certain conversion and the ability for the virus to hide the virus hides in the parasites, and so we're not quite sure to be honest. And it's almost a complete inverse for hepatitis C. Very few people seroconverter on clear the virus, as we said, 25 30%. But as we mentioned yesterday, patients who get a very pronounced Billy Rubin rise seemed to clear the virus more readily and again, whether that's because they have um, or efficacious immune system that manages to suppress the virus on develop antibodies quicker, we don't really know, but they're they're kind of sneak in sites that we have into the pathology under it. Thank you, Doctor. I think that definitely concludes that Thank you so much extra playing with the question. No, probably tell us. That's what I get for talking forever on for everyone that's still in the chart. It would be really appreciate it if you could complete the feet but form. It's beneficial for yourself on the lecturers. I think we can call that the end. Thank you so much again, Doctor. Paul. Thank you so much. Enjoyed it, you know. Thank you, Doctor. Thank you so much. I'll and today's six. PM session is counseled, by the way, if someone hasn't actually got the message still Thank you, doctor.