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Yeah, so I think we'll just uh we can make a start now. Um So hi, everyone. I'm Nejad Istvan Day. I'm one of the committee members on the Bima academic team. Um I'm on the, I'm on the clinical team. Um And today will be delivering a talk on gastroenterology and hepatology conditions by Doctor Debashish Das who is a consultant at capturing general hospital. Um and hoping that it will be a very informative and interesting session for everyone. So can we move to the next slide? So just before we start a brief introduction to Bima. So, um the British Indian Medical Association is a national nonprofit organization founded on developing a supportive network among students and doctors. Um And we provide tutorial series uh conference events, networking careers talks. Um And we also hold socials. So just give us a follow on our Instagram or Facebook page. Um And you can sign up to our mailing lists to, to get the latest updates about our talks and I'll just post um the links to these mailing lists in the chat. So next slide, please. Just an introduction to our speaker. Um Dr Devesh Estas is an associate professor at the University of Leicester Medical School. Um and he is an honorary consultant, hepatologist at Kettering General Hospital. Um and he will be talking over um the most common conditions and presentations to gastroenterology and hepatology. Um And uh it's meant to be if we can leave most questions till the end, but it's meant to be an engaging session as well. So, um feel free to engage as much as you like. Uh You can just, you can just raise your hand and speak or just pop any questions in the chat. Uh I'll just pass it on to you. Doctor Death. Thanks, Mia. Um Good evening everybody. Um Obviously, I've got one screen and I can't see any, a few while I'm present ng. Um So maybe if you have questions, you may put it on the chat and NIA if you're lucky to ask the questions in between. Um There is a sort of two sections to it. Um The second section is more of an interactive case discussion's and you're more than welcome to join in and contribute. Okay. Um So as you said, I'm a consultant, Capitalia Gist and I'll talk through interpretation of liver function test in the clinical context. Hopefully, that will be useful for many of you. Okay. Let's see. So quite often starting off when you're seeing abnormal LFTs that can be quite frightening, but going by a previously known um E C G interpretation book, Interpreting LFTs see is really easy if you know the basics and follow the basic principles. What we'll discuss today is a bit of concept of the liver function test various components of the panel that is generally used, we'll discuss on each of the components and then more importantly, the other components and the importance. And in the second half, we'll do some interpretation of laboratory reports in the clinical context. So the concept of liver function test, um the liver has mighty had functions and we usually assess a very few of them in clinical practice. Um What we actually sort of mean by liver function tests, uh generally looks at a combination of inflammatory markers and some functional markers to tell us how well the liver is working is the liver inflamed. And is there features of liver failure? Um rather than assessing too many of the many functions of the liver and that is there. So in most hospital settings, you will see the typical components of the panel include Billy Ruben, alanine amino transfers or A L T album in and alkaline phosphate is now I've given some values of the normal range in in here, but this can differ from one lab to another. So when you're working in a hospital setting or wherever you're working, just try and get to know what the normal range is. Also. Um There would be variation in the normal range is depending on the age of the patient. And other conditions. For example, um alkaline phosphatase is will be normally quite high in the new bones and in the growing phase and the values that I've given for normal adult range in most um lab settings. Now, A S T or aspart at um a new transfers and gamma gluten will transfer is G T are also quite often included. But because A S T almost parallels LT for most re purposes and GT parallels alkaline phosphate is in uh many uh settings. Um They are not always included. Um I'm really sorry for the type where there is alkaline phosphate is will be A L P rather than the second day L T. Now, these tests are not specific to the liver and these tests are also not sensitive to the functional changes of the liver. So we need to interpret them in the context. Now, LT and alkaline phosphate ease can come from other organs and other systems and does not always relate to the liver. So I'll go through a few of the components. Um So bilirubin, one of the communist features that we get asked about. Oh, this patient has got isolated, raised bilirubin. Um what would be causing this now, for most practical purposes, uh This will be Gilbert Syndrome where there is a high fasting level and that goes down postprandially is a very common condition. About 5% of the population in some countries are prone to having Gilbert syndrome. It's mainly a symptomatic but some may report abdominal pain, the cause of which is not very clear. Uh but Gilbert Syndrome generally is of no real consequences. The bilirubin would be raised but the rest of the liver function test parameters are normal. The other differential diagnosis would be Hemel icis which can also cause isolated rising bilirubin from among the components of the LFTs. Now look for low hemoglobin with macro cytosis or microcytosis which may point toward presence of hemolytic conditions, check haptoglobin level, which would generally be low and ridiculous site count, which will be generally high with him Elasis. Now, there is a condition called parcel anemia, which is seen in advanced liver disease, patient's and this is associated with him Elasis because of the change in the cell membrane components of the red cell, which make them less plastic. And therefore, when they passes through the fine capillary network rather than bend and pass through the network, they snap when they have to pass through very narrow networks. This leads to him Elice iss as part of the spectrum of advanced liver disease. If total bilirubin is disproportionately high in your patient. Check for the direct and indirect bilirubin and this might give clues to differentiate between Gilbert syndrome and him Elasis in many conditions. Uh especially if there is a presence of sparse L anemia. Uh You will see there is a significantly raised proportion of indirect bilirubin in patients with liver disease. The other thing that we quite commonly get asked is about situations where there is a raised alkaline phosphate is in isolations. Um The first thing to do, the situation is to check for Gamma GT. And if the Gamma GT is normal, think that uh this is coming from uh not from the liver but from something else. The communist being born origin. So common conditions that can cause this includes patches disease in the older generation. Uh recent fractures, generally, the alkaline force for these can be raised in teenage years, especially around the time when the um bones are remodeling and joining up at the appetite changes in calcium homeostasis, especially vitamin D deficiencies and parathormone problems can also cause raised alkaline phosphate is in isolation with normal GT in the first trimester of pregnancy, placenta can be a source of alkaline phosphate is um as uh the gamma GT will in that situation be normal. Um In the correct clinical context, you can ask for isoenzyme asses of alkaline phosphatases which can differentiate between bone and no liver alkaline phosphate ease. Now, if the G G T is raised, then there is coalesced Asus. But this does not necessarily mean there is a biliary obstruction. What I mean by that is that you can have, it can have a hostess. Sorry. Um If you can just uh mute yourself if you're not talking case. Oh dear. Um sorry. Um So going on, hopefully you can hear me. Uh if, if there is biliary obstruction, that can be at two levels. One is where it is within the hepatocytes, that the bilirubin is not being excreted. Or it could be at the level of the biliary ducts that can be intrahepatic or extrahepatic Nicola STIs is generally means that there is a blockage to the excretion of bilirubin in the hip it aside level, whereas biliary obstruction refers to the bile duct problems. If the bilirubin is also raised and the ultrasound scan does not show any biliary dilatation in, then it's most likely that there is intrahepatic cholestasis I E at the level of the hepatocytes coming to raise A L T N A S T. Uh they're generally markers of hepatice I'd damage, but A L T N E S T both can come from streit and, and cardiac muscles. And therefore you need to be careful that when you're seeing raised A L T, uh it, it can come from heart damage or muscle damage and you need to be putting those things in the clinical context. Now, generally, there are basically three causes of the A L T being more than 1000. So if you see somebody's LFTs with A L T, more than 1000 think about acute viral hepatitis, ischemic hepatitis or drug induced hepatitis. Other than this, it's very unusual for other causes to cause um A L T of more than 1000. The other thing to be careful about is in alcoholic liver disease or alcoholic hepatitis. The LT is hardly ever going to be above 2 50 almost never above 300. So if you have got somebody who, you know, during significant amount of alcohol and you're interpreting their LFTs and they're a lot is more than 300. Think about other causes in addition to alcohol as a problem causing the abnormal changes. Now, relatively raised LT, compared to the G T R A L P can be seen in acute biliary obstruction to uh especially in young females where there is no dilated bile duct. And a sudden stone pass is from the cold blood er, into an Annville ATED CBD. They can present with sudden abdominal pain, especially in the right up accordion going through to the back with nausea and abnormal LFTs. And quite often they're present to any get the LFTs done as part of their uh initial blood test. And quite often the ELT being predominantly higher in the 1st 24 48 hours. Uh the patient is often referred to the medics rather than to the surgeons. Now, that's fine. But when you're interpreting these results be be cognizant of the fact that if they're presented with right up a quarter in severe pain with nausea in formatting, uh the L T value being higher than GT does not rule out biliary obstruction or stone in the bile duct. A ST more than A LT is generally seen in alcoholic liver disease or is suggestive of advanced fibrosis or cirrhosis. Um A L T N S T maybe near normal and significantly advanced chronic liver disease, especially in many cirrhotics where the cause of the liver inflammation that led to the cirrhosis of liver has been addressed. For example, uh they may have had significant alcohol use in the past or hepatitis C in the past has been treated for hepatitis C has been abstinent of alcohol. Yet they have developed cirrhosis, which is obviously the scarring of the liver. Yet there is no ongoing inflammation in the liver. They can have basically normal aced knelt. Also one of the common causes of presentation to live. A clinic is with so called cryptogenic cirrhosis in slightly older patient's. And if you go back on their history, they're generally slightly obeys you've got hypertension or diabetes. And if you look back over the years, they have had a grumbling abnormal LFTs for quite some time. And this is a typical presentation of nonalcoholic fatty liver disease. Patient's present ing with advanced fibrosis or even cirrhosis at a later stage uh with essentially almost normal A L T R E S T. And as I said, remember, muscles release A L T N A S T and consider connective tissue diseases or even cardiac problems in the correct setting if you check their creating in kindness. Um that might be useful in differentiating connective tissue disorder release um related A L T rice compared to hepatic diseases. Now raise G G T is a very nonspecific taste. Um usually perils, the rise of alkaline phosphate is and in the correct context, cereal assessment, maybe a quite a sensitive marker of active alcohol use. Now, a lot of patient's with alcohol use may be able to abstinent for a bit of time, but then it's quite a significant urge to go back to alcohol in the future. And if you're monitoring this type of patient's, uh G G T may become a surrogate marker to assess their abstinence. G G T is also raised by various drugs that are extensively metabolized by the cytochrome P 4 15 times, especially a lot of the anti epileptic medications cause gamma GT to go up. This is a spurious sort of marker, chemical marker. It doesn't have really any significance in in clinical practice but being cognizant of what medications they're using might be useful to interpret raised gamma GT in isolations. Now, if alcohol and drugs and primary biliary cholangitis are excluded, yet there is significantly raised G T and alkaline phosphate is even if the initial ultrasound is essentially normal suspect billy retract pathology. And that is best assessed by doing uh M R C P examination, which is much more sensitive to strictures and irregularities of the bile ducts compared to ultrasound. Um often they will speak up ductal stones and sometimes stricture. Now, perhaps the most useful test in the standard LFT panels in assessing the function of the liver is the albumin level. It is a synthetic functional marker and, and low albumin level or falling albumin level would be a good indicator of the loss or the progressive loss of the synthetic function of the liver. Now again, uh low album in may reflect renal loss or sometimes uh nutritional problems like protein losing enteropathy. He's uh so you have to just be careful that you are interpreting the albumen level in the correct setting. And there are no other obvious causes of low albumin level in the patient. Now, the serum albumin is also useful in assessing the serum a psychic album in gradient, which helps to differentiate portal hypertension related societies from other causes. So you measure the serum albumin level and on the same day, get a sample of a psychic fluid and measure the albumen level and you just simply subtract one from the other. The difference when it's more than 1.1 g per liter is consistent with ascites related to portal hypertension. Whereas if the difference is uh more um sorry, if the difference is less than 1.1 g per liter, then it will suggest a different cause of example, malignancy or tuberculosis. Now coming to some of the other components and their importance. Now the most helpful other marker is the coagulation studies. It's a good marker of synthetic liver function and it helps to progressively monitor um the worsening of liver status as a patient progresses with liver disease. Now, obviously, vitamin K deficiency is also pretty common in alcoholics and elderly population, especially from care homes or if they are having uh heat and eat type of meals on a regular basis, uh they're very quickly develop vitamin K deficiency and this may have an impact on interpreting the coagulation studies. So, if the proton been time is raised, um it is worth giving vitamin K 10 mg IV to see the response. Now, if the liver is able to use the vitamin K, then only there will be an improvement in the prothrombin time, which is different from using fresh frozen plasma to correct abnormal clotting in liver disease where you actually, you're giving the clotting factors and you're not assessing whether they deliver can use the vitamin K to improve the prothrombin time. This is important in dealing with patient's with acute liver failure, especially if you look at the King's College criteria for whom to refer for transplant consideration in say paracetamol overdose related acute liver failure. Um The other things that we quite often check is ferritin, it's an acute phase reactant and will be raised significantly in any acute hepatitis or alcohol abuse itself. So, checking ferritin in acute liver injury situation is not very helpful in setting of the chronic abnormal LFTs restoration should be supplemented with testing for fasting transfer in saturation to get a diagnosis of hemochromotosis. The ferritin has to be raised and also the transfer in situation has to be raised. Now, absence of the two common mutations that we test for that is the C 282 Y mutation and the 8 63 D mutation does not rule out hemochromotosis. There are several other mutations that also can lead to hemochromotosis. But these are the two that is most commonly tested and available for routine news. Similarly, normal ferritin level does not exclude predisposition to hemochromotosis in later life, especially in females while they are having their periods, they almost veni sect and lose blood on a monthly basis. And therefore, it takes much longer for the ferritin level to rise in patient's uh especially female patient's with genetic mutation for hemochromotosis to manifest abnormal ferritin levels in their blood. So when you have got uh somebody who's saying, oh my sort of say sister has been diagnosed with hemochromotosis just doing the ferritin level would not be enough to either include or exclude, you know, hemochromotosis and your patient, you need to do the genetic testing along with the ferritin and transfer in saturation. Another test that we quite often do is alpha one antitrypsin levels. It's one of the commonest genetic defects in Caucasian population. It's got complex phenotypic variations and includes P I M M M S M Z or M dash genotypes. These are generally associated with enough levels of the antitrypsin in the blood to not cause any really uh lung damage nor any liver damage. It's the P I S S and P I Z Zeno types that are involved with lung changes in early life. And because um the alpha one antitrypsin that has been produced in the liver cannot leave the hepatitis side, they keep on accumulating in the hepatitis side. And that leads to squashing out of the other organelles in the hepatitis side that leads to malfunction of the liver. Now, generally, there is a second hit that results in significant liver disease uh rather than alpha one antitrypsin deficiency on its own. So for example, if somebody has alpha one antitrypsin deficiency and also has um say a significant alcohol use, they will progress to liver disease much more faster and at an earlier age than if they did not have the alpha one enter trips in problem coming to several A plas been and copper tests. The implication is that a Wilson's disease and it can be quite difficult to diagnose unless you have a significant uh sort of look out for it. Ceruloplasmin is again an acute phase reactant and maybe falsely elevated in Hackett hepatitis and is not helpful to measure in that setting. So, low ceruloplasmin level when tested in chronic liver disease patient, especially if they're presenting below the age of 45 can be a good marker, but this is supplemented by looking for serum copper levels which should be low and 24 hour urinary copper excretion, which should be raised. Now, if you then challenge these patient's with penicil Ammen, the urinary copper expression increases significantly and it's almost one of the confirmatory changes that you can do um relatively easily. But to do absolute confirmation, you would generally need um other uh serum um sorry, liver copper estimation from a liver biopsy or the genetic changes. It really presents as fast presentation after the age of 45. Um But in in younger age group, if not clearly picked up at an early stage, they can progress quite quickly. And most of the patient's are scerotic or presenting with decompensation in their late twenties. Um or even some in their early twenties, sleet lurk, um examination for the cornea may be helpful to find the cave ring uh but can be very difficult to um clinically assess in in in the clinic without a sleet lamp coming to some of the viral serologies that we use. Um. So acute hepatitis C is generally subclinical and anti HCV positive testes just means that at some point this patient had been had the infection. It does not say that the patient has got active infection. So to show that the patient has an active infection with hepatitis C, we test there are any quantification and two to do the genotyping to guide treatment planning. There are generally about six big genotypes of hepatitis C with some having further sub classification. And in the last 8 to 10 years. There's been a significant improvement in availability of medications for Hepatitis C that has got a very high chance of clearing the virus with very little side effects. We clear about 99% of patient's when we treat the hepatitis C nowadays. Whereas a few years back when we're using ribavirin and pegylated interferon, the treatment used to be very, significantly um challenging for patient's due to side effects and the clearance rate was down well below 50% for most patient. Um and this has been a big revolution in hepatitis C treatment and hepatology in the last eight years. Now, on the contrary, the screening test for hepatitis B is to test for hepatitis B surface antigen or hepatitis B S A G. Now, if that is positive, it means that there is active infection, whether it's uh in, in um controlled by the immune system of the patient or whether it's rampaging with high vitamins A, that's a different thing. But being hepatitis B surface antigen positive means there is active infection. Other tests are done in assessing the status or hepatitis B infection, which includes the hepatitis B E antigen status, hepatitis B E antibody status and HBV DNA quantification. These help in deciding whom and went to treat for hepatitis B. If there is a question with acute hepatitis, the other viral serologies that we should test is hepatitis A, hepatitis E C M V and E B V serology. But specifically asking for I G M antibodies rather than I G G coming to some of the auto antibodies that are relevant. Um antimitochondrial antibody is seen to be positive in primary biliary cholangitis, especially if there is an M to subtype positive. That's, that's what's got significantly high specificity. Anti smooth muscle antibody is relevant to autoimmune hepatitis type one. Similarly anti nuclear factor or anti nuclear antibody is positive in many patient's with type one, autoimmune hepatitis anti L came antibodies positive especially in type two or drug induced liver injury with autoimmune phenomenon. Okay. But low titer, anti smooth muscle antibodies and anti nuclear antibodies are quite often reported. They're very nonspecific and you need to be careful that you don't badge any and everybody with a low titer positive anti smooth muscle antibody or any uh as autoimmune hepatitis. Uh we need to take further things into consideration. A good thing to look at. In conjunction with the auto antibodies would be the serum immunoglobulin levels. At the same time with primary biliary cholangitis, you will often get an I G M fragment raised. Whereas with autoimmune hepatitis I G levels, especially if they are monoclonal raised I G, it's a good supportive indicator of activity of autoimmune hepatitis polyclonal rise in immunoglobulins are very nonspecific. And we quite often see that with patient with advanced liver disease and especially if they're starting to have liver failure, starting the albumen level going down. You quite often get a polyclonal rise in immunoglobulins. The other thing that you quite often get to see is testing for ammonia. Now, this is a surrogate marker to assess for detoxification function of the liver. Um It's not specific, no sensitive test for um for hepatic encephalopathy, but it's probably one of the easiest one that we can get done in the clinical context. It needs a fresh sample of EDTA, uh sent an EDTA bottle taken to the lab, not sort of ported down through the um pneumatic channels. Uh like you would do for your A B G tests. However, use this with caution, low levels does not exclude hepatic encephalopathy and high levels does not always exclude other pathologies for low G C S in a patient with liver disease. Uh The other thing that we want to know is how much deliver has got fibrosis in it. There are several markers that has been in issues previously pro college in three um highly Renault kiss. It used to be used. Uh an easy one is the A S T L T ratio and ace TLT bottom um platelet ratio are also in use, but these are not very good and there are pitfalls. Um If you look at the nice guidelines, uh elf test or or FibroTest can be used. But more commonly, most hospitals will now use fibro scan or A RFI machines to use um to gather information about the degree of fibrosis. Now these are non invasive, easily repeatable tests. So you can follow up a patient over time. Whereas a liver biopsy still remains a gold standard. It is an invasive test. It's painful and it's got significant chances of complete, you know, complications and most patient's will resist you trying to biopsy them twice, let alone repeatedly. Um So fibro scan has become almost the standard of assessment for liver fibrosis. So hopefully that was useful overview of the liver function tests the components, what they mean. And some of the other ones that are not part of the liver function test but helps in assessing the liver. Uh I'll present a few cases to put this into the clinical context and I'm more than happy for you to contribute with suggestions on what's going on. Okay. All right. So the first case, um it's an 80 year old male. He's known to have prostate cancer. He's been on Zoladex which is Gosselin uh LHRH agonist for about 18 months. He's been feeling extremely tired for about 3 to 4 weeks. He noted itching for five days and noted his urine to be very dark. And his wife also commended that he looked a funny color for about a week when he was tested, his bilirubin was raised at 83 A L T at 556 alkaline phosphate is 580 albumin of 37. And rest of the results are also there. Um any ideas as to what's going on? What suggestions do we have from, from the group then? Okay. Um I don't hear anything. So obviously, yeah, go on. Sorry. Someone's just commented um that it could be pancreatic cancer. Um but their abdominal examination is normal. Um Someone else has commented posthepatic jaundice and someone else has commented that PT is raised. So um it might be coagulation problems or liver cirrhosis. Okay. Good, good point. Um So I agree that is the prothrombin time race well marked. Um But with the bilirubin raised and the album in on the lower side of the normal range does suggest that there is a bit of um liver dysfunction going on. So this is not just acute hepatitis or acute liver inflammation, but also rightly picked up that there is a bit of dysfunction also going on. Yeah. Um In terms of the pancreatic cancer, I agree. Um at age of 80 has already got a cancer. It's not uncommon and a lot of these features can present with um pancreatic cancer causing biliary obstruction. Uh The only thing that is slightly unusual about it is that the E L T is disproportionately raised, which you would normally not get with alcohol. You know, abnormal LFTs from pancreatic cancer causing biliary obstruction. The alkaline phosphate is would be raised. The gamma GT if tested would be raised. Bilirubin can be raised if there is reasonable amount of obstruction. But the A L T S here A bit disproportionately high. Okay. Um But, but good points. Um So one of the things to notice here is the extreme tiredness and um that in this clinical context, especially with the raised L T is um somewhat of a clue. But I agree for most um medical students, if that is the population we're looking at this would be um a slightly difficult one to start with. But let's see what goes on. So because he's jaundiced alkaline phosphatases raised, he's itching as, as somebody did mention about possible obstruction from bility, obstruction, secondary to pancreatic cancer. The first test to do would be ultrasound of the abdominal which was done and was normal. So it generally, by the time there is a raised bilirubin of more than 50 if there is ability obstruction in the true sense, he would pick it up on an ultrasound. Um test for viral serology was sent given that the E L T was significantly raised. Uh They came back as negative too. There was no reported alcohol use but as I said with uh L T of more than 2 53 100. This was not alcohol anyway to start with. But his E any came back as positive. One in 1 60 his I G was significantly raised at 23.6. Uh normal range is about up to 16 or 18 depending on which lab you're working at. Um his antimitochondrial antibody was negative. Does that change anything in terms of suggestion, what's going on? You have a few suggestions for autoimmune, liver cirrhosis and autoimmune hepatitis. Okay. That's, you have one for liver mets. Okay. That's good. So, autoimmune hepatitis is a good point. Obviously, it's a reasonably strongly positive. Anyone in 1 60 immunoglobulin G is raised. So that's good that you've been sort of picking things up there. Um, in terms of the other one, what was the other one? He said the last one, uh liver metastasis. So with liver metastatic is very, very rare to get uh a raised billy Ruben unless the liver is riddled with metastasis. And there is very little functioning liver tissue left. Uh Also the ultrasound of the domine was normal, that would have probably picked up uh significant metastatic disease in the liver. Okay. So we can, we can park the uh metastatic disease but good on the alcohol uh autoimmune thing coming up here. Now, that's the importance of taking and probing more of the history. Now, interestingly, this guy has been having several bouts of cystitis and the last time around about three weeks ago, has been given a course of trimethoprim for proteus species that grew. This was resistant to nitrofurantoin that he has been having long term for the last 12 months. So that's more prodding in, in the consultant ward round and this came up. Does that make any change? Is it drug in hepatitis? Yes, we're coming there, isn't it? So, which drug do you think is, is the culprit here? Nitrofuran Toyne. Yes, it's the nitrofurantoin. That was the problem. Now, this is obviously the trimethoprim is the one that was given about three weeks ago. So most people will think is the trimethoprim that has possibly caused the problem because the symptoms sort of dates from similar time. But trimethoprim generally does not cause this type of a problem. It's nitrofurantoin is a particular culprit which even if it has been there for uh you know, several months, they have been using it, it can cause a late onset, typically immune mediated drug induced liver injury. So, this was one of the typical presentations of nitro foreign Toyne induced drug induced liver injury with an autoimmune input or a mechanism causing the any to be positive, the A L T to be significantly raised I D G to be raised. Uh And that is uh typical presentation. Now, this is, this is um can present many months after the culprit drug was started. Um, biopsy shows almost classical autoimmune like features. The extreme tiredness is a very prominent feature and that is something to look out for in this group of patient's uh as a clue to the diagnosis. However, these will most of the time completely resolve over several weeks after you stop the culprit drug and may show improvement with prednisoLONE also because they are immune mediated hepatitis. There's a great resource um that is easily available uh to look for liver toxicity, it's called Liver Talks website. Um And um this is almost like um I don't know whether you've heard of Talks Base. Um that is quite often used in any setting when people present with um drug overdoses or, or clinical suggestion of drug toxicity. Liver talks is a specific one for liver toxicity from almost all known drugs that have been reported. So you can search by the drug name, um start with A B C D, whichever the drug name starts with. And it will get quite a good information based on whether uh the particular drug that you are requiring has been reported with any liver toxicity and what type of toxicity and what the outcomes have been. So this is, this is a very nice resource to to be aware of. Okay. So the take home message from that is drug induced liver injury is very common, actually is one of the communist cause of abnormal librettist in um in the community where a lot of medications as prescribed. And if you do LFTs, um quite often, it might be one of the drugs that the patient is taking that is causing uh the changes it can present with acute or chronic presentation and not only new drugs that has been given immediately by through the presentation, but also look at long term drugs. There is increasing use of herbal and traditional medications. A lot of which have got whiter estrogen's and these can be a cause of cholestatic liver injury. Um, and you need to be sort of probing quite well about, um, over the counter horrible and traditional medications when you're looking for a drug history, uh, common things that you would see being used, um, from day to day antibiotics, especially flu clocks, insulin or co amoxiclav are two particular ones that quite often um implicated in drug induced liver injuries. Uh, Many of the antifungals, uh Statins is a type print. Um many of the older antiretrovirals and Ison is I'd and revamp acing as anti TB dogs are common culprits to be aware of. Uh and they can present with fulminant hepatic failure. Uh and and getting a good history is quite useful um to try and get to the bottom of them. Okay. Um So looking at the second case, uh this is a 44 year old male. He drinks about two liters cider a day regularly for many years. His first presentation with jaundice and a situs, he had an ultrasound down which showed him small irregular liver, slightly enlarged spleen with the site is so clearly there is cirrhosis. There is high portal hypertension with splenomegaly enos itis. So no doubt he's got advanced liver disease. By the same time, his bilirubin was 186, his ale, he was 376, raised alkaline phosphate is significantly raised gamma gt low albumen level. Um Prothrombin time is an increased, low platelet count again another feature of portal hypertension uh because the platelet gets um sort of add sobbed and and uh sequestration in this in large spleen. Obviously a ferritin was done, it was raised at 1800 but the transfer in saturation was 32%. So, thoughts on this case, let's uh hear from the group then what's what's the issues going on here? What to think about any suggestions you have a suggestion for I E sorry, we have a suggestion for alcoholic liver disease. Okay. So alcoholic liver disease is is probably is there, isn't it? You know, it's significant alcohol um use over the long time. But remember we talked about the A L T being quite high here. 376, it's very, very unusual for alcohol to cause that um the gamma GT raised would certainly go with significant alcohol use. Raised ferritin will go with raised alcohol use. Whereas the transfer in saturation being normal range goes against hemochromotosis. So, normal transfer in saturation is about 50% in females and 55% in males. Uh Here, the transfer in saturation is within normal limits. So even though the ferritin is raised with the transfer in saturation, normal, this is not hemochromotosis. Um going against this being purely alcoholic hepatitis with cirrhosis on the background with portal hypertension is the fact that the L T is significantly raised. So, further testing showed that he was Hepatitis B surface antigen positive hepatitis B E antigen negative and hepatitis B E antibody positive I E. This patient has an active hepatitis B infection. His viral load was significantly raised at 10 to the power of eight International Unit Parimal and his Hepatitis D antigen test was negative. So on a background of significant alcoholic Hughes, he also had hepatitis B infection. But interestingly, this patient also tested positive for hepatitis C antibody positive status and he had active hepatitis infection with hepatitis C RNA levels also significantly high. His HIV test was negative. So this person um stays in a longboat, has had a bit of a hippie culture uh many years ago and has had shared needles um used in the past. Um So he had unfortunately contracted happy and HEP C both were active infection and with the significant continues use of alcohol, he was truly well advanced liver disease with cirrhosis portal hypertension. And on top of that, he had an acute alcoholic hepatitis along with hepatitis secondary to HEP B and HEP C. So you got that sort of really mixed picture. Okay. So the take home message from this is quite often there'll be more than one reason for abnormal LFTs or progressive liver disease, especially if they're progressing faster. I earlier age advanced liver disease. Think about possibly more than one cause of liver disease. Lt more than 2 50. Even if it is uh you know, in a patient with significant alcohol use, think that there is something else going on ferritin. In this case, was an acute phase reactant, but also it reflected his significant alcohol use. So start keeping in mind that you need to sometimes think outside the box ferritin raised always does not mean hemochromotosis checking the transfer in saturation was useful. Uh that being within normal levels sort of took out the the hemochromotosis story here. Okay. So let's go to case three. Um This is a 25 year old female presenting with two days of right up abdominal discomfort with nausea and anorexia. And you can see the abnormal LFTs. Um Here, the prothrombin time is within normal level, platelet count is normal. Um Bilirubin is raised to an extent but significantly raised. A L T alkaline phosphatase and gamma GT are raised. Also the albumin is normal. So with the clinical context and the lefties, um what do we need to think about here? Then any suggestions coming through? Yeah. In the chat, we have uh drug induced liver injury, potentially paracetamol overdose. Uh And we have any autoimmune diseases or PBC. Okay. So the first three were great. Uh PBC is unlikely here. Um because of various reason PBC is very uncommon to start at that early generally. They, they are in there sort of forties to sixties. Um in terms of age. Um also in PBC. LT is very, very, very, very, very rarely uh more than sort of uh 50 60. It's never generally above 1000. Um ba Roomba we talked about um A L T over 1000 is caused generally by three conditions. Um One is autoimmune hepatitis. As somebody has said the other one is viral hepatitis. Uh drug induced can be and paracetamol overdose is a good point. Uh Here, young female. Um Unfortunately, there's the biggest sort of demographic group that we do get with paracetamol overdose. Um So keeping that in mind is very good. Um And the other one was at this age without any severe illness. Ischemic hepatitis is very unlikely, isn't it? So get point on autumn in hepatitis, drug induced hepatitis, including possibility of uh paracetamol overdose. Um So we started working this patient up a bit further. Um There's a bit more of information there. Uh 11 normal's clean, slightly enlarged G B wall ID emitters but no calculi seen and no doubt validation. Does that help in any way? Could there be an element of portal hypertension because of the spleen? Okay. Um So yes, that's a good point. Um The point against that is the platelet count is normal. Albumin is normal, prothrombin time is normal. And at the same time, this is a relatively acute presentation in a youngish patient. Um So portal hypertension, yes, it does cause a spleen to enlarge. Uh But at the same time, the liver was normal, which makes portal hypertension in the context. Uh slightly uncommon, but uh in in certain condition that can So that's a good thought. But think about um what other causes of splenomegaly can be there that also is associated with abnormal LFTs. Um Some prodromal symptoms of nausea and erection to uh upper abdominal discomfort uh in a relatively young uh patient E B V. Very good, very good. Uh So EBV is, is one of the biggest considerations. So we're see MV, uh especially if you uh no dived a bit deeper into the history. Um She had a three year old son, started going to Playschool recently and had a recent febrile illness and bang on if you look at, look at the serology, uh hepatitis B test and see test were negative but the E B V I G M was positive. So this is a presentation of E B V induced hepatitis um in a young female who probably contracted it from her young son who contracted it from uh the police school. Um or we mentioned about the abdominal discomfort is quite common in patient's with acute hepatitis, whether is hepatosis, I'ts swelling that stretches the liver capsule. And quite often the pain is described as a dragging sensation in the right of the quadrant. Um It's quite often associated with the nausea and vomiting again due to the irritation of the diaphragm uh and the nauseating feeling secondary to the stretching of the capsule. The other thing that we quite often see in ultrasound reports of acute hepatitis is that the gallbladder wall becomes edematous. Now, this is similar to what happens with prola fusion in many patient's with pneumonia. So there is a sin pneumonic infusion or a sympathetic effusion that happens along the inflamed lie. Similarly, the goal blood is sitting at the bed of the gold blood are just underneath the liver is quite often is irritated by the inflammation in the liver and often they get a pedometers, cold blooded wall. Now, the other thing that this could have easily be um uh caused by is um gallstones shooting through the CBD. So this arema, the A L T could be quite raised in acute presentation. But by the time the bilirubin was 85 you'd have expected the bile ducts to have already started dilating by the stage. So, um uh that is a real life case that uh we had again with the upper abdominal discomfort, nausea, anorexia. This patient was initially passed on to the surgeons. Uh But after further assessment was diagnosed with EBV induced um acute viral hepatitis. Okay. So take home message from this one was all abnormal LFTs with right up according discomfort and not colecystitis or choledocholithiasis. If L D is more than 1000 strongly consider viral hepatitis, drug induced hepatitis or ischemic injury. Collateral history is very important, not only of the patient, but also, um you know, close contacts is quite important here right up. According discomfort is common in any acute hepatitis due to the stretching of the capsules, often ultrasounds who's thick wall, cold blooded in acute hepatitis does not necessarily mean that they've got acute colecystitis. Ok. Moving onto case four, uh this is a 56 year old meal known to have decompensated cirrhosis due to alcohol abuse. He's been abstaining, he's being assessed for possible liver transplantation. Now, his wife, after returning from the corner shop, found him, collapsed at home. He was trouser E three M four V two on the Glasgow coma scale. There was no history of seizures in the past. He has been drowsy when he developed uti in the past. Uh but that resolved quite quickly once the UTI was sorted out. Uh this is a past history. There was no obvious societies, no Molina on P R, but there was dried blood around the mouth when brought to A and E okay. So while this is not directly an implication of abnormal LFTs, but obviously, uh this is uh advanced liver disease, especially in presenting with a sudden collapse, what would be going on in your mind in the situation? Any suggestions, let's hear them. Would it be a G I bleed? So maybe from a variceal bleeds? Yeah. So there was a possibility there were dried mouth, dried blood around the mouth when brought to a any has found collapsed at home, could have been hemodynamically compromised by a GI bleed. It hasn't passed through the gi tract fully as yet. Therefore, there is no Molina as yet. So yes, it could have been a gi bleed uh that led to the collapse. Anything else? So obviously, with the drowsiness drop in G C S, with that history, one has to think about the possibility of developing hepatic encephalopathy. Uh Also it could be the first episode of Caesar's in a patient who previously never had cesars. Okay. So for the blood tests, um so hemoglobin was 10.2, which was not very different from his previous records. Uh His platelet count was low at 44 P time. Raised at 19.9 A P T T was also raised at 43. Obviously, we knew he was quite deeply jaundice, part of his uh advanced liver disease. His albumen was low and then we've got a few others going on there. The sodium's 125 petition 3.1. Uh both of which are quite low. Um urea and creating in a low magnesium is reasonably low phosph. It is just borderline law ammonia. 28 is actually normal. So less than 50 is normal ammonia level. Bedside urine test did not show any overt changes. Sample came back by 24 hours. There was no white cells and then there was a bit of red cells, no cast. Um culture was spending but nothing grew in the 1st 24 hours. As expected, there was a small liver on ultrasound spleen was enlarged. Uh There was no Doppler webs in the portal vein, um suggesting portal vein, thrombosis mild ascites around the liver was noted and deep in the pelvis, there was no focal revelations. So any suggestion on what this test results may imply in terms of his collapse episode, adding any clues to to the cause of the collapse. Mhm Okay. So with, with the sodium level of 1 to 5, um especially if this has developed relatively quickly, especially if they have been prescribed diuretics or over direst, then that can cause significant risk of uh collapsed due to dyselectrolytemia. Similarly, with low magnesium and low potassium, you need to be careful that they have not had a cardiac dysrhythmia episode that has led to the collapse. So these abnormal um electrolytes are quite common in advanced liver disease. Patient's especially those that are still actively using alcohol or are on diuretics. Um So, looking at the trend in their electrolytes is quite important, but this patient sodium has been slowly dropping over time as part of advanced liver disease. Um and was not an acute change. The potassium and magnesium again are not new for him. Um So without possibly these are not contributing in this situation. But something um you need to be sort of careful about when dealing with uh collapsing a patient with advanced liver disease with sudden abnormal uh changes in their electrolytes with the low ammonia. Um We felt that most likely this is not hepatic encephalopathy, but it did not rule out hepatic encephalopathy all together, um delirium or infection leading to hepatic encephalopathy being precipitated was also considered uh the quickest one that we got back was the urine, which did not show any infections. Obviously, he had very minimal dose itis which was tapped later on. And that did not show any suggestion of uh SBP. Now, obviously, um pending results coming back, we started treating him as if he had a bleed, A gi bleed. A very she'll bleed along with covering for other infections. So, Terazosin as a broad spectrum antibiotic was started. Turley present was started as part of feeding vary, she'll bleed and lactulose were started to try and flush off any gi bleed that might have still not gone on to pass out through the gi tract which will, if not cleared off will increase the risk of developing hepatic encephalopathy. And he was for an urgent upper gi endoscopy to look for venetian bleeding, given that there was blood uh around the mouth or dried up blood at the mouth when he was picked up by the ambulance crew in about two. Any which sounds very, very um straightforward but awaking very trousers overnight with billions vomiting and with the significant drop in his uh worsening in his drowsiness and drop in his G C S. We arranged for an urgent ct head. Remember he had platelets which were below 50 and his p time was quite raised. APTT was quite raised So they were actually quite significant risk factors for uh bleeding. And he did turn out to have a large brainstem hemorrhage with intraventricular hemorrhage, with fourth ventricle and lateral and third ventricle validation. The obstructive hydrocephalus was developing in this patient. So this was the pictures. So you can see, I don't know how clear it is, but you can see there's around the third ventricle, there is increased intensity of acute bleed and similarly in, in the back of the brain here. So this guy actually had a brain hemorrhage which probably led to his collapse and his little G C S which was decreasing. The blood around the mouth turned out to be from a lung bite which we, you know, sort of looked for later on. Um It was not picked up on the initial assessment. Um and unfortunately, um he was just palliative care given his significant advanced liver disease. Um No neurosurgical intervention was thought appropriate. So, take a message from this is not all drowsy patient's with chronic liver disease is hepatic encephalopathy. Not all blood in and around the mouth is hepatic masses. In the true sense, raised ammonia level can be helpful to corroborate hepatic encephalopathy, but it's non specific and quite often not sensitive enough. This patient's are coagulopathic and prone to intracranial bleeds like any other bleeds. And you need to be careful about patient's suddenly dropping the G C S. Think about possibility of intracranial bleeds paradoxically, they're also prothom bra tick because rumba protein C and proteins and antithrombin three, which are the natural anti quagga Linz uh in our body, they are produced by the liver. So when the liver starts failing, the level of protein C and proteins and anti trump in three production can also go down and this leads to an imbalance of the thrombotic and prothom batic factors. Uh sorry, antithrombotic and prothrombotic factors in the blood. And quite often they develop portal vein. Thrombosis is one of the complications of advanced liver disease. Okay. Uh So the last case now, um it's a 52 year old female presents with six days of cough and worsening breathlessness. Since returning from a business conference, uh presented with tachycardia, bit of hypertension for otherwise fit 52 year old female um is Perec Shal chest X ray showed confident consolidation in the left lower lobe, raised white cell count. CRP was significantly raised. She had low sodium, um slightly raised Durian creating with a bit of dehydration and had abnormal LFTs. So L T L P both a razor of a mixed picture here. Uh neither truly hepatitic, not truly cholestatic or purely cholestatic. It's a mixed picture. Ultrasound of the domine was normal. So we do see this type of non specific abnormalities in FTS in in quite commonly in systemic illness. However, it's important to ensure that are no concurrent primary liver problems. Also mostly the abnormalities in the liver test settled quickly after resolution of the systemic illness. However, review of this particular patient's previous blood test showed that she had gamma GT and alkaline phosphatase has been raised for over four years. Alfred and Albert only marginally and actually has not been picked up in primary care till she presented with these episodes. In this particular case, her antimitochondrial antibody test came back as positive, including the mitochondrial m to fragment antibody positive and thus pointed to the diagnosis of underlying primary biliary cholangitis, which is um not been so far diagnosed before. So take a message from this case was delivery is often stressed as other parts of the body in systemic illness. We are more aware of acute kidney injury as part of acute illness. But a similar situation can happen in the liver. It's important to look at trends in LFTs rather than as a snapshot. And looking back at previous LFTs in this patient helped to get to a diagnosis of a conquering liver disease that was unmasked by other conditions. For example, the systemic illness with uh a typical pneumonia in this patient. So it's time to look at the bigger picture. If you look at the picture superficially, you'll think it's probably Charles Darwin or a tiger. Once you look bigger, they appear very different. I'll bet there is a tiger in in the second picture. Um Now people remember things in very different ways and I will suggest you look at what works for you. I found this one, uh, in one of my searches. Um, I just wonder how that particular person, remember things written this way if it worked for him or her. That's great. Uh, I would suggest, uh, you will all find your own ways of remembering things. Thank you. Um That's the QR code for your feedback. I will unshared now if that's okay. Thank you, Doctor dot uh, um, I have, uh I have just posted a link to the feedback form as well in the chat. Um I think we just had one question that we missed out in the chat. Um I think someone asked earlier which herbal medications in particular cause liver disease or liver damage. So it depends upon where you're working in Africa. One of the communist causes is practice of chewing leaf called cut or Chat ch 80 or kh 80. It's quite prevalent in um Northern European, northern African countries. Um and is quite well associated with even accurate liver failure. Um The other ones are some of the bush tease that quite often used in many parts of Africa. Uh, a lot of mushrooms can cause abnormal liver tests. Um A lot of Chinese herbal preparations. So there and quite often these are mixed with, with various herbs going together. Sometimes it's very difficult to isolate which particular one it is there is a plant called Black Cohosh. Now, Black Cohosh as a plant with a lot of fitter estrogens and there's been significantly reported incidents of acute liver failure from use of Black Cohosh. Now, these were being used as um sort of symptom relief medications for many post menopausal women. Because of the fight or estrogen. They had, they were helping with a lot of their post menopausal symptoms. Unfortunately, several patient, especially in Australia. Uh there was a series of patient's who developed actually to liver failure from use of Black Cohosh. Okay. Thank you. Thanks a lot. Do we have any more questions at all? I'll just be on the, on the, on the meeting for a little while longer if anyone has any, anything else to ask. But thank you very much for a very interesting talk. Doctor Das. I'm sure many of us would have found us very useful for our vision. Yeah, I mean, obviously, um it was a bit of an open um clean slate that you presented. Uh I'm more than happy to sort of do for the session if that helps and useful on. I mean, generally have not been doing Luminal gastroenterology for some time. So I'll prefer probably if, if we need any further liver related things, I'm more than happy to come back if you give me a brief on what would be useful and what is needed. Yes. Well, something like this would, I'm sure would be very useful because I think we had a good turn out of students as well. Yes, we'll be in touch. Uh I think uh Sri Vidia has asked about, will it get access to the slides? Uh I think this is recorded uh video. So I guess he'll be able to access to slides from there. Yes. So, um if you can, so just to the students, if uh you can, if you complete the feedback form on metal, uh you just need to create a metal account. Um It just, just takes a minute and then you're, you'd be able to complete the feedback form afterwards. You'll have access to the slides and the recording. And, um, you also get a certificate of attendance. So I've just posted the link in the chat and, um, thank you. Yeah, and we'll also be sending you a speaker certificate. It's all done by a but all, actually, it's just a very, it's an automated platform, I think. So it just makes it very easy to and people certificates, kid. If there's any other questions, shoot. Okay. In that case, I have a nice rest of the evening and best wishes for your careers. Bye bye. Thank you. Bye. Thanks.