John Martin here again. It's my privilege to join our course director Caitlin Cookson to present case number two to you. Caitlin? All right, so we'll be looking at a case study here to highlight biliary stricture workup and management. I'll slide forward here. We have no disclosures. So I'll read the case to get us started. You have a 25-year-old male that comes to your clinic. He was referred by his primary care provider for new liver enzyme elevations. Blood work was drawn routinely when he was applying for a private disability insurance policy. He has generalized pruritus for the past five months, recently more progressive. He does have a past medical history notable for ulcerative pancolitis diagnosed nine years ago, treated with steroids and then 5-ASA, no other medications. And he was lost to follow-up during a move two years after diagnosis, and he has not had any subsequent flares or symptoms. He is on no medications. He has no allergies. He reports drinking zero to two alcoholic beverages a month, and otherwise his review of systems is negative. On exam, vital signs are normal. He's 5'9", weighs 150 pounds. The exam is largely normal. His labs are normal for a normal CBC. His CHEM 7 is normal, but he does have those elevated LFTs still. AST is 50, ALT 62, ALKFOS 187, and a T-BILI of 1.5. So looking at those labs, John, does anything stick out to you? I'll slide back there. What sticks out to you when you look at those labs? Well, sure. Thanks, Caitlin. I mean, we've got a young man, and he has a history of inflammatory bowel disease, which apparently is quiescent, or at least not symptomatic right now, right? But he's had some mild itching that's recently progressive. So itching, pruritus in a patient who at least has a personal history of IBD of the colon, at least diagnosed as ulcerative colitis. And I'm noticing that these liver enzymes, however mildly elevated, are elevated, right? They're not normal. And so that starts making me wonder, okay, what causes itching with elevated liver enzymes? And does that have anything to do with the person's IBD, at least historically? Yeah. That's what I'm thinking. I like those thoughts. I think we can keep moving forward and working our way a little bit closer there. Sounds good to me. So yeah, I think we're all pointing one way, but let's talk about what some other studies we may proceed with in order to try to tease out what might be going on for our young friend here. Options for ordering viral hepatitis serologies. I don't think that this is necessarily a wrong answer, but I don't know if this gentleman has a lot of high, if we have a high level of suspicion for him to be having a viral hepatitis. Yeah, I totally agree with that. I mean, I didn't hear any risk factors for viral hepatitis really in his history anyway, did you? No, I didn't appreciate any of those at all. And then what about the autoimmune markers though? Because we did hear about the ulcerative colitis. What do you think about those? Yeah. I don't know. I don't think they're cheap. And people sometimes, providers when doing a workup for liver enzyme elevations will just order everything as a battery. Just get the viral hepatitis serologies anyway, and the autoimmune markers. And a lot of times they're non-diagnostic and can sometimes be sort of trivially elevated and then take you on sort of a non-specific workup path. So I don't know, I might pass on that right now. Yeah. I think that's reasonable. Liver biopsy, that may provide us with some additional information, but it's certainly a expensive test, definitely more invasive test with a lot more risks. So that might not be our next best step. Yeah. And doesn't necessarily give you a diagnosis in spite of the fact that it's invasive and has real risks like bleeding associated with it, I think. Don't you? Yeah. Right upper quadrant ultrasound, that is certainly safe and cheap, easy to get done for patients, or I should say relatively cheap, but it's not overly sensitive either. So might not give us our exact answer that we want. Yeah. I don't think you'd be wrong to get it right because it's risk-free. There is some inconvenience because you're probably not going to be able to get it the same day that you're seeing the patient. So they're going to have to come back and if they live 300 miles away, that's an inconvenience. But I think it's okay, but 50-50 on that one, at least that's my vote. What do you think? I completely agree. It's fairly benign, but it's not going to be as sensitive as we hope. And then we have ERCP, which I think poses the same problem as the liver biopsy, isn't going to absolutely give us our answer here. It is invasive. It is expensive. It's a procedure. And as we spoke about earlier today, certainly has some pretty significant risks associated with it. Mm-hmm. Totally agree. And then MRCP is, I think, a great option here. It is a highly sensitive test to evaluate the liver as well as the biliary tree. It is a little bit more expensive, maybe more difficult to schedule, but I do think it could be a good option here. What do you think? Yeah, it's non-invasive. There's some minuscule risk with the contrast administration if you do it with contrast, which if you're going to get the full tilt MR with MRCP, then you will. Although the MRCP itself doesn't in and of itself require contrast, but you'll usually get an MR to evaluate the liver as well. It is substantially more expensive than an ultrasound. An ultrasound is a few hundred bucks and MR is a few thousand, so it's about an order of magnitude more expensive. I've had an MRI, if any of you have had one, and actually seen your bill, it's always a four-digit number, whereas an ultrasound might be a three-digit number. But yeah, those are both non-invasive. I think it really depends on what you're looking for and what the turnaround time is. MR can take a lot longer to get scheduled at my institution than an ultrasound. Yeah, same here. Yeah, right. So those MR scanners are used for a lot of things, and at most institutions they run them 24 hours a day because they cost several million dollars apiece. And then another form of evaluation we could pursue is a percutaneous trans-hepatic cholangiogram, or PTC. This is a procedure with interventional radiology where they advance a wire essentially through the skin into the bile ducts and then inject dye for a cholangiogram. Also a very invasive and risky procedure, probably a little bit too aggressive to jump to just yet for this gentleman. I agree. The main serious complication of a diagnostic ERCP is post-ERCP pancreatitis, and depending on the risk factors, that's anywhere from about five to twenty percent, which isn't nothing. It requires a hospital admission. And with a percolangiogram, it's bleeding, and that's not an insubstantial risk. So those along with a liver biopsy are the ones that are invasive and can cause their own adverse events associated with those diagnostic procedures. I think which one to pick also depends on what your differential diagnosis is, sort of climbing back up to the top of your slide, right, Caitlin? Yeah, absolutely. What do you think about when you know that somebody has IBD, or at least a history of it, you think, and they have elevated liver enzymes and they have new itching? I'm worried about PSE. Yeah, which is what? Primary sclerosing cholangitis. Right, primary sclerosing cholangitis, not a terribly common thing to be seen like in a primary care office, but most of us that see liver and biliary patients see it with some frequency. And why is that at the top of your differential? We know that a couple reasons. His age, his lack of other risk factors. We don't see heavy alcohol use. There's not a lot of, like we talked about, viral risk factors here. He's not over-raped. I'm not worried about metabolic issues playing into liver disease here. And we know that PSE is heavily diagnosed concurrently with IBD ulcerative colitis. Right. The majority of patients who have PSE actually have concomitant inflammatory bowel disease, which we're going to discuss in a few minutes. And so that's absolutely number one. I agree on the differential. There's another disease with a similar abbreviation, which is PBC, which is primary biliary cirrhosis. That's a different disease, right? Yes. Not PBC. Not PBC because what? Is there a particular known association between PBC and IBD? I don't believe there is. Agreed, there's not. But the association is very strong with PSE. Other things, you know, autoimmune hepatitis, the aminotransferases are kind of low for that, right? They tend to be higher and more relatively elevated than like the ALKFOS would be, right? Right. Yes. He had a very cholestatic, you know, elevation in his LFTs with that ALKFOS and T-Billy, you know, a little bit more pronounced than the AST, ALT. Yeah. A cholestatic pattern of elevation. And you said really no risk factors for viral hepatitis and some of the constitutional symptoms that people tend to get with acute viral hepatitis. He didn't really complain about any of them, right? Right. Right. Yeah. Sounds good. What do you think? Should we move on? I think so. I think that we want to order an MRCP, right? I definitely would join you on that. Fabulous. So here we ordered our MRCP. Yeah. What if you put on your radiologist hat? What do you see there? So looking at this, so with the MRCPs, we get a really nice highlight of the biliary tree. I am seeing a pretty notable structure at the hyler bifurcation. And then further out into those ducts, you can see an almost beaded-like appearance. That's kind of like the keyword you see on your radiology reports, where these ducts start getting kind of thick and thin, thick and thin, go out through the biliary tree. Hey, Caitlin, do you have access to the laser pointer? Oh, you know what? Sam, can you get the laser? Awesome. Yeah. Yeah, so you see, if you think of the small ducts, like the branch ducts as being creeks, and the bigger and bigger ducts as being rivers, the creeks should be narrower than the rivers. If you see any point, oh, like right there where you're pointing at in the right anterior branches, you can see there's an area where the duct downstream is narrower than the duct upstream. And that's the sort of beading-type stricturing change that we see, which is stenosis with pre-stenotic dilatation. It's like a dam with not just a river upstream, but a lake starting to form, right? Yeah, and then what about the, you were talking about the top of the common hepatic duct down south of the bifurcation. Actually bring that down there, yes. Right? So this is a really very diagnostic MRCP. And as you were suggesting, MRCP will show not only the bile ducts, but what else here? Looks like fluid in the stomach, in the renal collecting system, and the CSF. Why is that? So it's the way that the image is weighted. It is weighted to visualize slow-moving aqueous solutions. Yeah, so this is T2 imaging, right? Yeah, T2 weighted. Yeah, awesome. All right, that's a great image. Anything more to extract out of that? No, I don't think so. I think we got most of it. Yeah, I think we're good. OK, great. So as we discussed, that would be a diagnostic image for PSC. We don't necessarily need to continue with ERCP or liver biopsy. That image there is going to give us our diagnosis. So what is PSC? It's an autoimmune disorder causing inflammation and fibrosis of the bile ducts. It is progressive, and it often results in obstructive complications, including jaundice, acute cholangitis episodes, which sometimes can be pretty severe and lead to bacteremia, lead to hospitalizations requiring IV antibiotics, and then furnace, which can be mild to really very severe and something that heavily inhibits these patients' abilities to live their lives. And our patient has that, right? Yes, he does. It's his is mild so far, but that was one of his main presenting symptoms. Yeah, and pruritus, it certainly can be a symptom associated with biliary obstruction, right? Mm-hmm, yeah. I don't think we know why, but it is. PSC, but yep. Yeah, and PBC as well, right? Any cholestatic disorders, yeah, itching can be a big problem. Yep. Cirrhosis, it can lead to cirrhosis eventually, and that's due to this longstanding unmediated biliary stasis. And that cirrhosis can be complicated by portal hypertension as well as synthetic dysfunction. You may see coagulation factors, albumin, impaired glucose metabolism, as well as impaired immunoproteins synthesis. And they also have an elevated risk of malignancy, including cholangiocarcinoma and gallbladder carcinoma, but they also have a higher risk of colon cancer outside of what they would be at a higher risk of with just ulcerative colitis alone. That is so important, isn't it? And that changes the interval for surveillance, right? Mm-hmm. Yeah. It does. I think we go into that in a minute. Yeah, we'll talk about that for sure. OK, John, what other workup might we get for this gentleman? Yeah, that's a good question. I think now that we have that diagnosis, as for further blood work, when I look at that MR, and granted, we don't get to see the rest of the MRI. We just put the MRCP up there for case simplicity. But with the MRI being normal, and I'm assuming that the rest of the blood work was normal as opposed to the liver enzymes. Liver enzymes don't tell us about synthetic function of the liver, but an INR certainly will. And I think an albumin is reasonable to give us additional insight into synthetic function, because I do think we want to know to what degree this patient's liver has been affected by the bile duct disease, because if you have chronic obstruction of the bile ducts for any reason, including PSC, you can develop secondary biliary cirrhosis, right? And so we would get some clues just from blood work. I think the imaging suggests to us that no cirrhosis is evident. So I don't think I would bother doing something like a fibroscan, when I think the likelihood of cirrhosis is low. And certainly, the patient isn't demonstrated already to have cirrhosis. So we've done the right diagnostic imaging modality. As for invasive procedures, honestly, I'm a little bit concerned about that stricture that's below the confluence of the intrahepatics, that common hepatic duct stricture. Does that bother you at all? Yeah, especially with that elevated bilirubin. It seems like something that might be targetable. Yeah, and so we might do the patient some good by doing an ERCP to perform a balloon dilation of that stricture. And maybe even short term, leave a stent behind to increase the hope that that dilation that we perform might stay open longer. Obviously, while we're up there, we'll brush the duct, at least send it for cytology, and maybe for chromosomal studies like FISH, which is fluorescence in situ hybridization, which can increase the sensitivity of our brushing by 10% or 20%, because we're worried about that stricture being representative of not just inflammation, but what else? Answer of cholangiocarcinoma. Yeah, right, because the risk of cholangiocarcinoma over a lifetime in these patients is higher, right? Yeah, we have to keep a close eye on that. Yep. And then other investigations, Sarah talked a little bit about that CA-19-9. Yeah, she did. I think this is very practice dependent, because like she said, it's kind of a dirty marker, because it can be elevated just from biliary obstruction or inflammatory cholangitis alone. And if it's low, then it doesn't mean they don't have cancer. So I'm 50-50 or less on that. How about you? Yeah, I think that's very reasonable. And I think it is a little location and practice dependent as well. Choloscopy every year to every other year, is that reasonable for these patients? Yeah, that's the guideline actually in these patients who have existing history of UC or colonic Crohn's disease in the setting of once you've diagnosed PSC on top of that. You're right. It's every year or two. If they don't already have a diagnosis of inflammatory bowel disease, and they only have a PSC diagnosis, they still need to be screened every five years, right? And then for gallbladder imaging, since we know that they're at a higher risk for gallbladder, adenocarcinoma as well, ultrasound is the preferred modality. Is that correct? That sure is. Great. And then we're looking for polyps. And if we see any polyps greater than 8 millimeters within that ultrasound, we would recommend cholecystectomy for those patients. Absolutely. That is exactly what the guidelines say. All right. We're on it. Here we are. So as we mentioned, he had that dominant structure, worried about possible cholangiocarcinoma, and also possibly hoping to provide some therapeutic relief. He went to ERCP. Do you want to talk a little bit about this cholangiogram? Sure. And if you remember the MRCP, this is almost identical. Obviously, it's a better defined image because it's a contrast cholangiogram. But you see that structure just below the bifurcation there in the top of the common hepatic duct. And it's even more apparent on the CRCP than it was on the MR. And some of those beating changes that you showed, Caitlin, in the MRCP show up here very, very well also. They're really clear here. Sure is. All right. What's next? Yeah, it's what to do, right? It's always about what to do. Right. Unfortunately, for these patients, it's not that we don't have a lot. We don't have any curative treatment. We don't have any treatments that are going to reverse this existing disease. And we don't really have any treatments to reduce the progression either. Yeah, so no, no, and no to each of those questions, right? Yeah. I hate talking to people about this diagnosis, but it's brand new. It's rough, isn't it? Yeah, it's a tough one. Yep. So what's the upside, then? What can you do? So we can try to manage our symptoms. Pharmacotherapy really is focused on trying to reduce. The big symptom is probably going to be pruritus, and that's using cholecystermine or bile acid sequestrant. And then endoscopy to utilize any type of dilation on dominant strictures to help with risk of recurrent cholangitis, as well as with LFTs. Sure. Yep, sounds good. So there are things we can do to make them feel better. And we also let them know, hey, just because there's no solution in terms of cure, reversing existing disease, or reducing progression today, that doesn't mean there won't be tomorrow. So let's get you comfortable. Make sure we survey you for cancer properly, like we talked about. Manage your IBD like we're supposed to, especially in the setting of cholangiocarcinoma, where the risk of colon cancer is even higher than IBD alone. While we wait and hope for disease management that can actually help with the underlying condition. And then as a last resort, we could also talk liver transplantation with these patients. Sure, absolutely. And it doesn't necessarily, my understanding is that these patients don't necessarily have to progress to severe disease like you may see for more traditional liver transplant patients. They get a lot of points added on for PSC, and they can be transplanted for even intractable pruritus. Or two episodes of cholangitis that have led to hospitalization may also qualify them. That is true. And even severe pruritus that is intractable can be a special consideration for these patients. What you don't want to do when there's concern for cholangiocarcinoma, though, is to not perform that percutaneous cholangiogram, that PTC. Because if they do end up having cholangiocarcinoma and you went through the skin and the liver and went through there and potentially have seeded the tract, that patient will not qualify for transplantation as a solution for the cholangiocarcinoma. Yeah, that's a really good point. We have to be careful with sampling anything concerning for cancer with them. Absolutely. I think we already talked about the screening colonoscopy intervals, right? I think we did. All right, any other thoughts? I think we covered it. Great, that was fun, Caitlin. Thank you for letting me team up with you on this one. Thank you, John.

primary sclerosing cholangitis

ulcerative colitis

pruritus

MRCP

bile acid sequestrants

liver transplantation