During this 20-25 minute pre-recorded lecture, Dr. Nancy Bach discusses the topic of cholestatic liver disease. This in-depth review will provide an update on this topic for your clinical practice as well as supplement your learning for the ABIM Gastroenterology and Hepatology boards. CME pre-requiste of live Q & A webinar, 8th Annual Mount Sinai Intensive Board Review in Gastroenterology & Hepatology on Oct 13.
Hi my name is nancy box and I've been tasked with talking to you about cole aesthetic liver diseases. Unfortunately I don't have anything to disclose. So um co static liver disease can involve the bile ducts within the liver and those without on the outside of the liver. And this is not exhausted but um slide. It does show many of the different liver diseases that can cause cola stasis. So anything shown on this slide is fair game for question. However. Um in my experience the majority of the questions are um are based on questions involving PBC and PSC. So this slide comparison contrast the two diseases PBC and PSC. So PBC is a disease that has a predominance in middle aged or perimenopausal women. Um So the majority of patients between the ages of 35 55 years of age upon presentation although there are case reports of teenagers with the disease and patients may record may present as old as their nineties PSC has a slightly increased male predominance. Um And there are two peaks of onset. There are those patients that present in childhood and then the majority who present somewhere between the ages of 20 and 45 years of age in PBC. The target of the attack of the immune system are the interim paddock biliary ducts. While PSC can involve any part of the biliary system, the majority of patients with PB PSC have large or extra paddock biliary duct involvement. Both of these are cole stated cola static liver diseases. So you would expect to see an elevation of the album possibilities and G. T. P. In both of these diseases. Though you can see many auto antibodies and PBC. The hallmark of the disease is the finding of a positive AM A. Which is found in somewhere between 95 98% of patients PSC um can be associated with a variety of positive autoantibodies. But none of these autoantibodies is specific for the diagnosis of PSC. The diagnosis of PBC rests upon the liver biopsy. Um and one should have a normal kel angiogram and PSC. You typically need a kel angiogram which will show the classic features of PSC. Although 15% of patients with PSC have involvement of the interim paddock biliary duct system. Only any auto immune disease can be associated with PBC. Although the majority of patients will complain of sickle syndrome, about 10 to 15% of patients with PVC have thyroid disease as well. The common association of PSC is with inflammatory bowel disease and somewhere between 75 to 80% of patients who have PSC will either have or develop inflammatory bowel disease. The converse isn't true however, because only somewhere between 2.5 to 7.5% of patients who have inflammatory bowel disease will have PSC. The classic symptoms of PBC or fatigue and poor itis. Although um in fact the majority of patients with the disease are asymptomatic although their conversation always involves fatigue and poor itis. Um PSC. Again, most patients are asymptomatic though they can present with pariah itis and if they have features of cholangitis they can have joined us fever and chills. The prevalence of the disease is 40.2 cases per 100,000 in PBC and 6.3 cases per 100,000 in PB PSC. So because it's a board review course the format of my talk is going to be a question and answer um um format. So the first question involves a 68 year old woman who's referred to you for evaluation of elevated liver chemistry's and as you can see the predominant elevation of the alphas and GTP her billy Rubin slightly above the normal range. It's 1.3 she and she has a positive AM a platelet count is 125,000 so it's slightly decreased and she has an elevated I. G. M. Level. What would which of the following recommendation would be the most reasonable to make for this woman A initiate therapy with pregnant alone. Be initiate therapy with her. So dial C. Start her on therapy with a beta colic acid or caliber D. Started on therapy with her. So dial and obey to colic acid or e refer her to a transplant center. So the most reasonable recommendation would be to start her on therapy with ursa dial. And that's because basically when we looked at this lady the diagnosis of PBC has been established with reasonable sensitivity and specificity as such. The S. A. S. L. D. Guidelines suggest that if you have two of the three following criteria you can make a diagnosis of PBC. So if you have biochemical evidence of cola synthesis and the presence of an A. M. A. This should be enough to make the diagnosis of PBC. If you don't have that either of those then you need histological evidence of non supportive destructive cola gingivitis and destruction of interlocutor bile ducts. Um So again the diagnosis of PBC has been established and your saddle is the main story of therapy and PBC. Uh though a bit of colic acid has been FDA approved as a treatment for PBC, it's not recommended as first line therapy. It can be considered as an add on therapy to her. So for patients who have not had a biochemical response with her. So after a year of treatment or for patients deemed to be intolerant diversity, oxy coke acid. Um Though the patient can be referred to a transplant center um If you're not comfortable dealing with the patient, this patient is clearly too early for transplant evaluation. So as you probably recognize, we have the same patients. Um So which of the following variables is not a risk factor for her disease progression in this patient, her age. Remember she's 68 years of age or B. E. You find out that the patients actually a male not female. See that the patient has a liver stiffness greater than 9.6 killer paschal's which is the equivalent of having increased fibrosis D. The patient has a markedly elevated billy Rubin. Or e. The patient has a positive anti glycoprotein to 10 antibody. So the variable that would not be a risk factor for disease progression would be her age. So the risk factors for disease progression and PBC are it tends to be a little bit more aggressive when patients present at a younger age. Male patients tend to have more or more likely to have disease progression as well as patients of hispanic ethnicity. An elevated billy Rubin is considered a negative prognostic marker or um yeah negative prognostic marker as is the presence of G. P. To 10 antibodies and having evidence of advanced fibrosis on a fiber skin is also um suggestive of disease progression. Um Though a little bit controversial most studies seem to suggest that if you have an alkaline foster case greater than 1.5 to 1.67 times the upper limited normal after being treated with one university oxy kulik acid. Um Your prognosis is not quite as good as if you have normalization of your ankle and hospitals. So the same patient which is not recommended by A. S. L. D. Guidelines that should be screened for various is that should be screened for patty cellular carcinoma that you monitor. TSH periodically for direct disease that you give her a statin because this is a pretty wicked looking um lipid panel or e all of the above are recommended for this patient. So the one that the A. S. L. D. D. Guidelines does not necessarily recommend is that statin use must be used in this patient. And that's because although status can be used in patients with PBC and hypercholesterolemia an increased risk of cardiovascular disease has not been firmly established for patients even with this horrible looking lipid profile. Uh While statins are safe and effective in patients with PBC, their use actually needs to be individualized. Taking into consideration other risk factors, screening for viruses is recommended for patients with suspected evidence of cirrhosis. And there were two different studies looking at platelet levels but a reduction in platelet level and or in the last photography score on a fiber scan of greater than 17. Kill A paschal's which is consistent with cirrhosis is also an indication for screening patients for various is patients with suspected cirrhosis should also have regular screening for Battistelli carcinoma. And because thyroid disease can be reported in up to 15% of patients with PBC. It's been recommended that TSH levels also be checked periodically. So we finally have a new patient. So this is a 23 year old male who has undergone a massive for section of the small bowel for Crohn's disease. He's now two months post op and he's been requiring TPN which of the following statement is not true. A is an in that having increased episodes of catheter sepsis increases the likelihood of cola synthesis and liver disease. Be the use of ventral um feedings will increases risk of cola synthesis. See remaining bowel segment less than 50 centimeters increases the risk of cola synthesis. D in the increased duration of TPN use increases the risk of coLA synthesis and liver disease or e life threatening liver disease is rare with TPN induced cola synthesis. So the statement that's not true is that the use of ventral feedings will increase his risk of coal synthesis because in fact it's the opposite it's lack of ventral feedings that can contribute to cola stasis by leading to reduction of gut hormone secretion, reduce bile flow and biliary stasis. So another patient, 52 year old males been diagnosed with ulcerative colitis three years ago and he's really done well and treatment with Miss salome. However, during a recent exam he complains of poor itis and you know that he's yellow. His alphas and GTP are elevated and his billy Rubin. This five he sent viral serology is negative. His a and as positive at 1 to 1 60 a C. A. 19 9 is markedly elevated at 1245. He sent him for a sonogram and that's reported as normal. However you're smart enough to send him for an M. R. C. P. As well. And this shows a stricture you then um schedule him for an ERCP with brushing and a diagnosis of colon carcinoma is made which of the following statements is true about this patient. His lifetime risk of Kalinda carcinoma is 7-15%. Be pancreatic cancer is 14 times greater than the general population. See the risk of colon cancer is 10 times greater than the general population. D screening for colon adenocarcinoma is recommended but it's not terrific. Or e all of the following statements are true. So all of these statements are true. So the important take on message here is that PSC should kind of be viewed as a pre malignant conditions. And although the cost effectiveness of surveillance has not been established it's still recommended. Um There's no sure shot way to screen for colon carcinoma using on the scans or tumor markers. Um And it's important to note that the C. A. 19 9 is not sensitive enough to really rely upon as well as the fact that there are more than 30% of patients who have an elevated C. 19 9 don't have Kalinda carcinoma. It's important to always remember clinically that an ultrasound is operated dependent and it has various limitations. One of which is because it occurs with PSC. Because the PSC can have a sclerotic appearance, ductal dilatation may not always be appreciated on an ultrasound. So this like um slide shows a study that was published about two years ago looking at um the benefits of surveillance. So if you look at the surveillance group they had a significantly higher five year overall survival. And in fact 68% of patients who did have some sort of surveillance had um had a five year survival compared to only 20% who had not had any sort of surveillance. So uh um surveillance significantly lowers the five year old year probability of experiencing a pata biliary cancer related adverse effect events. And again is recommended are, so our next patient is a 48 year old male who's had multiple bouts of pancreatitis. And again he presents with coal, aesthetic liver chemistry's and ability Reuben that's slightly elevated. He has this M. R. C. P. So which additional blood tests might prompt you to recommend treating this patient with predniSONE or toxin Map A. He has a smooth muscle and body. That's 1 to 1 60 B. He has an elevated immunoglobulin G. Four level. See his cereal plasmas low D. He has an elevated I. G. M. Level or e. He has an elevated angiotensin converting enzyme level. So um this question actually has a lot of clues. Probably the most important is that he's had multiple bouts of pancreatitis. But the other thing is that you're thinking of treating him with predniSONE and or toxin map. So this is A. M. R. C. P. That's consistent with some sort of sclerosing cholangitis. So the test you would want to order would be an elevated I. G. G. G. G. G. Four level. So um if you had an elevated serum I. G. Four level this would help make the diagnosis of an I. G. Four sclerosing cholangitis. An elevated serum I. G. Four level is found in somewhere between 66 80% of I. G. Four related disease. The diagnosis of this rare disease can be very difficult to make because the I. G. Four level is neither sensitive nor specific for the disease um In the air cp biopsy is really going to be done. That's gonna be deep enough to be able to stay in for I. G. Four. So it's a difficult way to make the diagnosis. Uh Most patients um have um pancreatic pancreatic involvement. Um and the absence of pancreatitis is rare and i. g44 related cholangitis and in fact 60 to 90% of I. G. Four related sees um present with multi organ involvement is again it's very important to make this diagnosis because it is highly steroid andorra toxin. Retook some apps. Responsive. The next patient is a 19 year old male who is an Ashkenazi jew who's been noted to have significant impact of splenda mentally during a routine exam on careful questioning. He also tells you that he is back pain. His labs show that he is cold static liver chemistry's and he's slightly anemic with a low platelet count. An ultrasound confirms that he is a really large liver and spleen. So you perform a liver biopsy based on this biopsy shown here, the most likely diagnosis would be benign, recurrent interior padded. Coolest Asus or brick Sarcoidosis, Corollas disease, Gaucher's disease or tuberculosis. So the right answer is gosh, she's disease. And this slide shows these Goucher cells which are characterized by like a crinkle tissue paper appearance which has been caused by accumulation of glue grocery, riverside days and cook for cells and macrophages. Um these um these cells can infiltrate the liver spleen and bone marrow. Um about 94% of patients with gashes will also have bone marrow involvement. And again, there are several clues to making the diagnosis of Galaxies disease, including the fact that this patient is an Ashkenazi jew, he's got back pain and he may have some bone marrow involvement. So um the um the key points here that attaches disease is the most common license almost storage disease and is caused by deficiency of glucose, cerebral side is this is a picture of tuberculosis where we see Casey and granulomas. Um and one would expect could possibly see a positive afb stain. The next one um slide shows non Casey and granulomas. And one would expect to see that in sarcoidosis. Brick is characterized by recurrent episodes of cola static joined us. Um The histology can show central lobby like cola stasis. However, typically you don't see evidence of progressive liver disease and or other features of obstruction and lost of all this is corollas disease, which is a rare inherited disease characterized by dilatation of the interim Paddick bile ducts. So the next patient is a 26 year old male who has a history of ulcerative colitis. And he's undergone a living donor liver transplant about three months ago for PSC. He now presents to the emergency room with politis and low grade temps. His donors C. M. V. Positive and he C. M. V. Positive. So the CMB matches his laboratory tests showed. Um That is billy Rubin is now 4.8 and he's cola static liver chemistry's his attacker lima's um three months out as eight nanograms per mil leader. And he has an ultrasound which shows no ductal dilatation. Um And although his he has a Peyton hepatic artery, there is some high resistance. Um Doppler wave forms reported, which are the following would be the most likely diagnosis based on what we have here, would it be the patient has recurrent PSC. You suspect in a systematic biliary stricture. See acute cellular rejection. D. The patient has C. M. V. Hepatitis or E. Um He's having a flare of all sort of colitis. So this question is loaded with clues. Again, his patient, it's a living donor liver transplant. The timing is three months after the transplant. His tackle LIMAs is actually good for um someone three months after transplant. And the big clue or hint here is that he's got these high resistance. Doppler wave forms. So the right answer would be that you suspect that he has an N. S. Thematic biliary stricture. So although C. M. V. Infections are more common in the first months after transplant, patients with C. M. V. Hepatitis typically are sicker and it's usually seen when you have a C. M. V. Donor um with the C. M. V. Negative recipient. And if you recall both of these, the donor and the recipient with CMB positive, acute cellular rejection always remains a possibility. Um And a liver biopsy may in fact be indicated. However the patient does have good tackler lima's trough levels. Um The current PSC occurs in 20% of PSC transplant so it's important to always look for occurrence. However the median occurrences usually 4 to 5 years and so this would probably be a little bit early for disease recurrence. Living donor transplants are known to have a higher rate of biliary complications than disease donor transplants. Making you think maybe there's a biliary complication and based on the Doppler studies which show increased resistance in the paddock artery um You may have a paddock artery stenosis that can predispose to biliary complications due to ischemic injury. Um You have to remember that the paddock arteries, the primary supply of the bile ducts. So the next study in this patient would be a clan a clan diagram to exclude a biliary stricture. Uh So our next patient is a 43 year old male who has altered a colitis and he presents with new onset of Jaundice. Kalla static liver chemistry's and he's got a billy Rubin of 6.8. He has an M. R. C. P. And it shows a dominant structure. Which of the following statement is not true or false. Which which is false. A. A dominant stricture occurs in 45 to 58% of patients. Um With this presentation 80% of patients with PSC. Have I. B. D. C. 30% of patients with IBD have PSC. Um D this patient should have an ERCP with brushing or e. There's no medical therapy that's been approved of this particular disease. So the statements that that is not true is that 30% of patients with I. B. D. Do not have PSC. And if you were awake at the beginning of the talk you would have noted that. Um Because while 80% of PSP PSC patients have IBD, it's only somewhere between two and 8% of patients with IBD who have PSC. A colonoscopy with biopsy should be performed in all newly diagnosed with PSC. Even if they're asymptomatic because of this highest high likelihood of association with inflammatory bowel disease. Um If the dominant structures seen it should be brushed um and biopsied. And if Qala ange itis occurs in a patient with dominant structure. They should have a correction of the bio duct obstruction along with antimicrobial therapy. The risk of colorectal cancer increases in patients with us cm PSC. And surveillance column colonoscopies are usually recommended at 1 to 2 year intervals and patients that are the U. S. C. And P. S. C. And it's also been recommended that ultrasound surveillance for gold bladder polyps um be performed because of the increased um risk of gold bladder cancer. This is a histology question. So which liver biopsy would match the following patient, A 52 year old woman who's got cola static liver chemistry's Zampa Lehman examples machine here and the positive AM A. A. B. C. D. Or E. And the right answer would be that this is a patient with PBC. So you need to recognize that this is a bile duct and put in a portal track. There's mixed inflammatory infiltrates which are attacking or disrupting the basal membrane of this sick looking bile duct. And this is a classic stage one PBC lesion. So this picture was interest had a kalandia carcinoma. And you see um glands lined by cells and there's an increased nuclear um nuclear solar um cytoplasmic ratio with prominent new clio lie this is a picture of PSC which if you're lucky enough to see on a biopsy is very helpful in making diagnosis of PSC. Where you see this onion. Skin fibrosis. Um The fact that this patient had a positive AM A. Is not consistent with PSC. So again this is not the right answer. Um The next picture is a patient comes from a patient automatic amyloidosis and you'd use a congo red stain to confirm that diagnosis. A pearl that's been thrown around for years is that you should be very cautious when you buy if you intend on bypassing someone who has suspected amyloidosis because of the risk of aesthetic rupture and bleeding. And the last picture comes from a patient, a biliary atresia, which is the most common cause of neonatal cola synthesis um where you can have partial of complete obstruction of the common bile duct. So this is my last question and I'm gonna do it as a jeopardy question. So I'm going to give you the answer and pretend I'm Alex Trebek. And you're gonna give me the question. So the answer is a genetic disease caused by a mutation and the A. B. C. B. 11 gene that leads to a deficiency of the BCF protein and has an increased risk of patty cellular carcinoma in some individuals. So the question is what is benign recurrent inter paddock? Cold synthesis one of brick one. Brick to progressive familial inter paddock. Coolest Asus one or P 51. Um What is perfect to e what is P. 53? And the question is what is progressive familial interim paddock um cold synthesis to so um that completes my talk. Good luck. Bye bye