During this 20-25 minute pre-recorded lecture, Dr. Jennifer Leong discusses the topic of liver transplant 1. 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. So I won't be giving my talk and liver transplant one and this talk will really focus on the pre transplant phase of the transplant process. So let's just start with some statistics. Um there are about 12,000 people on the waiting list this year. Um What you can see on this table is that over the years the number of transplants has steadily gone up, which is great. Um The weightless mortal mortality historically has very geographically ranging anywhere from 6.5 to 37.4 deaths per 100 weightless years. And that's a pretty significant range depending on where you live. Um For those who actually do get transplanted, the national survival rate is pretty good. Uh One year, it's at 93% five years. It's 75-80 And at 10 years it's 60%. This line just shows you the indications for liver transplant by ideology. So here on this green line um you'll see is Hepatitis C. And historically Hepatitis C is the leading indication for transplants in our country. However, you can see it's starting to dip down and this is due to all the new effective therapies that we have for Hepatitis C now um leading to high cure rates and um a decrease in the number of patients who have progression of disease and need a liver transplant here in this pink line. You see a rise in the patients who are getting transplanted for alcoholic liver disease. And this is partly due to the fact that many centers are now considering patients with acute alcoholic Hepatitis as potential transplant candidates. It's whereas before this was a contradiction in this blue line here, which is at the very top. And it's starting, it's going up on the rise. This is actually this is considered unknown but this is felt too likely include many patients with non alcoholic fatty liver disease. And as we all know, um obese obesity is a major issue in this country and fatty liver is expected to shortly become the number one leading indication for liver transplant in this country. So up until recently, Organs were allocated according to arbitrarily drawn geographic boundaries that divided our country into 11 regions. And as you can imagine, this led to significant disparities in organ allocation and distribution and led to the highly variable mortality um on the waiting list by regions. So fortunately that old system has since been eliminated and a new Orleans organ allocation system was implemented this past february. This new system eliminates those map based boundaries and corrects the inequities that, but unfair advantages and disadvantages based on where liver transplant recipients lived. So before where you lived, where you chose to got to get listed for transplant made a huge difference and how sick you needed to be before you got a liver transplant. This new system changes that and it prioritizes the medical urgency of liver transplant candidates in relation to the distance between the donor hospital and transplant hospitals. So the patients who are both most in need and closest to the donor now gets the organ. First organ offer first. So I don't want to go into this too much detail because it does get a little bit complicated. But if you have your donor offer here from this hospital And you're gonna look at first the status one patients typically your full minutes within a 500 nautical mile radius of that donor hospital. If there are no status one patients within 500 nautical miles, then they look at they divide the meld score up into categories and they look at the 1st 150 nautical mile radius Who has the highest meld in that range. And if nobody meets that score set then it goes into 250 then 500 and so on. And then and then it keeps continuing in a sequence of progressive offers from local to more distance for candidates with a range of certain smells. Um They also established a national liver review board to consider exception scores for liver candidates whose calculated melt or pell score does not reflect their medical emergency. So question one which of these patients should be referred for a liver transplant. A a 36 year old male with chronic hepatitis C cirrhosis. No asides or encephalopathy and meld score of 10. He should be listed to receive a heP C. Positive donor liver be a 42 year old male with nash cirrhosis complicated by asides requiring weekly L. B. P. S. With the multiple of 10. See a 50 year old female with hepatitis cirrhosis, newly diagnosed one centimeter. HTC well compensated with the meld score of eight who should lister to appeal for HCC exception points. D. A 68 year old male with a history of alcoholic liver disease and stage renal disease on dialysis for six months Has been sober for a year but has not completed a rehab program. His melt scores 30. He needs a dual liver kidney transplant, E. B. And E. Or F. All of the above. So before I answer this question, let's talk about some of the factors that get take into account when assessing a patient's need for a liver transplant. So let's talk about some of the indications for liver transplant. Of course acute liver failure and complications of cirrhosis. So well compensated psoriatic doesn't necessarily need a liver transplant. But if they have, the cities have had a hydro thorax, spontaneous bacterial peritonitis, chronic gi blood loss due to portal hypertensive retinopathy, encephalopathy, liver cancer or factory very still hemorrhage or synthetic dysfunction. Um liver based metabolic conditions with systemic manifestations such as Apple. one. Anti trips and disease. Familial amyloidosis, glycogen storage disease, hemochromatosis. Primary axillary area wilson's disease or other systemic complications of chronic liver disease such as a paddle pulmonary syndrome portal pulmonary hypertension or her paddle Renault syndrome. Mm. So question to which of the following is a contra indication to liver transplantation. A five months of sobriety from alcohol be portal vein thrombosis? See well controlled HIV. D. End stage renal disease and the need for dialysis or e an ejection fraction of 30 2%. So the answer here is a an ejection fraction of 30%. So let's talk about absolute contraindications to transplant. So anybody with significant cardiac and pulmonary dysfunction obviously would not be transplant candidate, they wouldn't be able to survive the surgery. Um patients with severe hypoxia, severe pulmonary hypertension. A study published back in 2008 showed that patients with even mild pulmonary hypertension had mortality at 50% and those with Severe pulmonary hypertension had 100% mortality. So that's why these patients would not be candidates. Um I paddle cellular carcinoma with metastatic spread. Obviously a liberal transplant is meant to cure HTC but once it's metastatic and spread you're not able to remove that and you're not going to cure this disease uncontrolled sepsis or an occult infection. Our patients get immuno suppressed significantly after liver transplants to go into a transplant with an infection, they're just going to get even sicker and it's gonna be more difficult to control that infection and they will die with that infection. Active drug abuse and ability to comply with post transplant treatment? Those kind of fall in the same line of really, how well is the patient going to be able to comply with doing what they need to do to take care of this new graft patients with AIDS. The caveat being that well controlled HIV is allowed uh in patients with fulminate hepatic failure with a sustained intracranial pressure over 50 or a cerebral profusion pressure greater than 40. What are some relative contraindications? So um extensive portal vein thrombosis or S. And v thrombosis. This is where getting your surgeons involved is so important. So they can tell you realistically whether or not they can transplant a patient with extensive thrombosis, advanced age, how old is too old? And I can tell you that this is going to vary by transplant centers, patients with HTC or Colangelo carcinoma. If certain if the guidelines are exceeded certain extra paddock malignancies. On a case by case basis these can be considered and patients with alcoholic hepatitis. Again this once used to be a contraindications to liver transplant. But now on a case by case basis some patients can actually qualified and be transplanted. So let's talk about the transplant evaluation process which is pretty extensive. Patients undergo financial screening and counselling transplant is obviously very expensive. Patients have to take a lot of medications after transplant. So you want to make sure that they have the appropriate insurance coverage to cover these medications. They undergo a hepatology evaluation to assess the disease severity and prognosis and confirm diagnosis and optimized management. Um They get a surgical evaluation to confirm the need for transplant, identify any technical challenges cardiac evaluation to make sure their heart is strong enough to withstand major surgery. A general health assessment, psych psych evaluation. Social workers evaluation for support um a nutrition evaluation to assess the nutritional status and provide patient education and an infectious disease. Consult to identify any infectious processes that require intervention prior to transplant. Um Such as whether or not certain vaccinations required if patients have latent TB. And things like that. So moving on to question three A 58 year old female with hepatitis C cirrhosis presents for initial transplant evaluation. She has a history of aerosol bleeding for which she underwent banding and had required transfusion in the past. She also has societies which is being managed with directs history is also significant for diabetes and hypertension. She's an ex I. V. Drug user, a smoker, she doesn't drink and she is married with three Children. Her medications include blacks, yellows, furosemide, Aldactone, insulin, My my center pro and a multivitamin. Her exam is significant for a soft abdomen. She's got a city some low trim edema but no extras. Asterix is. She's a no times three. Her labs show an alderman of 2.3 billy Rubin of 4.1 minor of 1.8 cramping of 0.9. A sodium of 1 30 potassium five hemoglobin of 10.8 and a platelet count of 54,000. It's a priority on the wait list for liver transplantation depends upon a history of aerosol bleeding. And asides be it's contraindicated to her to her history of I. V. Drug use and active smoking. See it's based upon her child Pugh score. D. It's based upon laboratory data only or E. All of the above. So the answer is D. It's based upon laboratory data only. So let's talk about the child puked arco score a little bit. This is an old allocation system adopted by units for listing and prioritizing patients for liver transplant. Um As you can see the table the score consists of five variables encephalopathy. Besides billy Rubin, albumin and pro thrombin time. The pros of the score is that it takes into account of cities and emphatic encephalopathy which can be a reflection of how psycho patient is on the flip side. Taking into account the cities and emphatic encephalopathy. These can be very subjective measurements. Um the score is also limited in its discriminatory capacity due to both a ceiling and floor effect. So for example a patient with Billy Rubin of four would receive the same number of points as a patient with Billy Rubin of 15. And since there were only three categories each category contained numerous patients and waiting time would actually play a big role in the allocation process rather than how sick a patient would be within the same category as compared to others. So moving on to question for which of the following are components of the meld score. A sodium bi billy Rubin. See creating D. Besides E. A. B. N. C. Or F. All of the above. So this is a little bit of a trick question. Um The original meld score did not include sodium but the newest meld score actually does. So the answer is E. A. B. And C. sodium billy Rubin and creating are all components of the meld score. So let's talk about the meld score a little bit. This scoring system replaced the child pooped to co score for assessing prognosis and organ allocation. In 2000 and two, it was initially devised to evaluate the three month prognosis in patients with cirrhosis undergoing tips procedure and it's a continuous scale from 6 to 40. We kept it at 40 that corresponds to a three month survival of 90% to 7% respectively. And when this score was adopted, the impact was pretty immediately evident and that there was a reduction in the waiting list registration, waiting list mortality and median waiting times within an increase in the number of patients being transplanted within 30 days of listing in the first year of the post-Meld era. So as you can see, the meld score incorporates serum creatinine billy Rubin and I and our um that was the original score. The sodium does get incorporated. We'll talk about that in a little bit. The crowning caps at four. This value is also automatically assigned to patients who have received dialysis at least twice or cvV. H. for 24 hours in the preceding week, the iron ore holds the most weight. And as you can see in this table on the right um as the melt score goes higher through three month mortality rate in the hospital patients goes up significantly and a prior study had found that the risk of deceased of a deceased donor liver transplant. In patients with the meld score of less than 15 outweighs its benefits in most circumstances. The downside of the meld score is that it does not reflect the impact of complications such as refractory of cities and recurrent encephalopathy. And I'm sure we've all seen our patients with low melt scores who keep getting hospitalized for encephalopathy or whoever for factory site is requiring weekly taps but they're melting or just does not reflect how sick they are. So let's talk about the mouth sodium score. The original meld score was updated in 2016 to include the serum sodium and the goal of this was to increase priority for organ allocation to candidates with hyponatremia. The serum sodium is a reflection of the vessel dilatory state in cirrhosis and studies have shown that the development of hyponatremia predicts increased weightless mortality independent of the meld score. There is a linear increase in mortality by 5% for each. Each minimal decrease in serum sodium between 125 140. The table on the right here shows you the number of points that are added to each meld score depending on the sodium level. As you can see the lower the sodium and lower the meld score, the more points are added. But as a meld score increases, the sodium holds less weight. As the risk of death. It calibrates due to the high risk of death from just having a high melt score. This new change has been shown to increase the transplant priority for about 12% of listed patients. One of the limitations of the score is that serum sodium levels may be vulnerable to alterations by diuretic use and intravenous fluid administration um correction of the hyponatremia. All will lead to a better looking meld score but it doesn't correct the underlying disease state that led to the hyponatremia. So question five. The 62 year old male with hepatitis cirrhosis and control decides undergoes MRI that shows to hyper vascular lesions compatible with HTC measuring 2.5 centimeters at 1.8 centimeters in the right lobe. He's on parole. Simeon vary it and not along on exam he has by temporal wasting smaller cities trace lower extremity gmail. He has no asterix is. He's a no times three. Yeah. His album is 2.5 billion urban is 1.8 sts 25 lt of 32 iron are is 1.7. His platelets are 35,000. His A. F. P. Is 250. So which of the following is true. A. He's not a transplant candidate because he has cancer be he's not a candidate due to having more than one lesion consistent with HTC. See he meets priority for liver transplantation for HTC under milan criteria or D. He is outside milan criteria. So the answer is C. He meets priority for liver transplantation for HTC under milan criteria. What is the next best step in management? A surgical resection list for a liver transplant. See radio frequency ablation of the lesions or D. Give him straffan, airborne Ebola, mob or E. C. And D. So the answer here is B. List for a liver transplant. So let's talk about a parasailing carcinoma a little bit. Um Since HTC is a very important indication for liver transplant, all psoriatic patients should be screened with bi annual imaging and a serum A. F. P. This is an increasing problem in patients with nash and Pepsi. It accounts for about 30 to 40% of all transplants importantly a biopsy is not needed. You can make the diagnosis for HTC purely based on radiologic characteristics meaning you see contrast enhancement on late arterial phase with washout on portal venous phase on CT or MRI with one of the following a late capsule um pseudo capsule enhancement or growth on serial studies. Or you can get a tissue biopsy confirming the diagnosis of HSC. If not a tissue diagnosis, the tumor must be confirmed by M. R. I. Or C. T Interpreted by radiologist at an O. P. T. N. Approved center. So let's talk about my long criteria. So Milan criteria consists of one lesion less than or equal to five centimeters or no more than three lesions each less than or equal to three centimeters each. And this was a study that was published by mozza pharaoh in 1996 that showed that patients who were transplanted with HTC within this criteria had a four year survival after transplant of 75%. Recurrence free survival was 83% provided tumor burden was met milan criteria and and was without metastatic spread at the time of transplant importantly a single lesion should be at least two cm to meet appeal requirements. So patients who are listed for HTC for transplant with HTC exception points. You have to get a Ct or MRI every three months to exclude extra paddock spread and portal vein thrombosis. And to ensure that the patient is still within Milan criteria. Um Have there been other criteria that have been looked at to see if we can expand our transplant HTC criteria. So UCSF criteria has been looked at and this has been shown to extend size limits beyond my long criteria without sacrificing survival outcome. So this is basically one lesion less than 6.5 centimeters Or three or no more than three lesions of what the largest being less than or equal to 4.5 cm or a total tumor diameter less than 8.5 cm and all without vascular invasion. So even though the study had been shown that these patients still did well these this has not been accepted by O. P. T. N. And these patients are not given the priority. But importantly even if patients are outside of milan criteria initially they can be downstage to meet milan criteria and you can submit an appeal to request exception points for listing these patients. So let's talk a little bit about hepatitis C therapy and psoriatic patients. So now with all these new D. A. S. We have over 90 95% curates um and well compensated strikes and 12 to 24 weeks of therapy you get equal success in HIV co infected patients. Um It has been recommended that you should be using these medications with caution and child tube be patients and that is not advised at all in child puke see patients. Um There was controversy in the past about whether or not treatment of Pepsi with D. A. S led to an increased risk of developing HTC and studies are now showing that there really is no impact on de novo HTC or its progression. Um One of the things that always comes up in patients who are referred for transplant who have active hepatitis C. Should they be treated while on the waiting list Further Hepatitis C. And I would say that this needs to be on a case by case basis if you can avoid treating a patient with hepatitis C while actively awaiting a liver transplant? The recommendation is that you should because if you treat them you can get them a little bit better but not better enough that they no longer need a transplant, but they actually have a drop in their mouth score. And this is something known as meld purgatory. So you have to really choose your patients carefully because cirrhosis is not always going to be reversible even if you treat anchor the hepatitis C. In addition, patients who have hepatitis C who are waiting for a liver transplant can also be offered a hepatitis C positive donor. And this would expand their donor pool and you can just treat the Hepatitis C after the transplant. Mhm. If you have a patient who is well compensated and they don't they're not on the transplant list, they don't need a transplant, then yes, you should absolutely try to treat their hepatitis C because you can avoid potentially them needing a liver transplant in the future. So hepatitis C positive donors is now widely used um for hep C positive recipients. But we've now also expanded this to hep C negative recipients because this has been found to be an effective way of decreasing the waiting time expanding the donor pool for these patients. And we have very effective treatment options for patients for Hepatitis C with very minimal side effects. So what about the use of HIV positive organs for donation? Um The HIV Oregon Policy Equity Act, also known as Hope. This was a legislation legislation that was proposed to end the federal ban on use of organs from HIV positive deceased donors and HIV positive recipients. This was introduced in february of 2013 and it was passed in june and of 2013 and also passed by the house in november of 2013. Currently, there's an NIH sponsored research program underway to examine the safety and outcomes of organ transplantation from HIV positive deceased donors. Um patients with HIV are now prioritize on the list and this can ultimately increase their access to transplantation. We here at Mount Sinai are part of this research program where we are transplanting patients who have HIV with HIV positive donor organs with their consent. And our patients have been doing very well thankfully. So finally going back to question one which of these patients should be referred for a liver transplant? A a 36 year old male of chronic hep C. Cirrhosis, no cities or encephalopathy. His melt is only 10. He should be listed to receive a HEP C positive donor liver. This patient is well compensated has no complications of cirrhosis. His melt is only 10. As we discussed earlier. Meld score of 15 is where you start to see the benefits of a transplant outweigh the risks. He's not quite there. So he doesn't need a transplant at this point. Be a 42 year old male with natural Asus complicated by cities requiring weekly L. V. P. His meld scores 10. Yes. His meld scores low, he's 10. But he's a D compensated psoriatic. He has a complication of cirrhosis. His refractory cities he should be referred for transplant. See a 50 year old female with the cirrhosis newly diagnosed one centimeter. HTC. She's well compensated. Her meld scores eight. Let's to appeal for HTC exception points. So as we discussed earlier, this patient, despite having HTC, she would not meet criteria because She has a single tumor that is not yet two cm and you need to have at least a tumor that is at least two centimeters before you can apply for exception points. She can potentially be treated with other options, such as surgical resection or R. F. A. And those could be potentially curative for her and she could avoid a liver transplant or and finally, D a 68 year old male with history of alcoholic liver disease and stage renal disease on dialysis for six months, Has been sober for one year but has not completed a rehab program. The Mount scores 30 needs to do a liver kidney transplant. Absolutely yes. This patient should be referred for a liver transplant. He has a high meld. He's clearly very sick and he's been sober for a year. So the answer is E. B. And D. So after all of that, why refer stable psychotic patient for liver transplantation? So acute on chronic liver failure has a very high mortality. As some patients who um may have to leave for medications, infections can lead to decompensation. Stone disease, adequate renal function can be grossly underestimated antibiotics, especially in females. Repeated episodes of encephalopathy have acute and chronic sick. Well, a although this really isn't such a stable patient, then the safety net of being on the list chronicle aesthetic disease is not are not prioritized adequately by the melt scoring system. And there's a risk of liberty compensation with HCC treatment and that ends my talk.