Good morning, everybody. Excuse me. And thank you to the organizers for allowing me to participate in this session. I'm going to get some water, if that's OK. So here's my disclosures. So this talk is really focusing on liver transplant outcomes. And as we all know, the outcomes after liver transplant have continued to improve. When I first started working with liver transplant recipients, it was about 30 years ago. And the focus was very different than what we have today. In 2018, the last year for which we have any complete data, over 8,200 liver transplants were performed. It is now the treatment of choice for chronic liver failure, acute liver failure, and hepatocellular carcinoma. And as you can see, we have good survival data approaching 90% at one year, 80% at three years, and 72% at five years, meaning that we have more and more long-term liver transplant patients that we are seeing. So this talk will look at the management of complex chronic illnesses, cancer screening, and chronic immunosuppression, which are the things that are contributing to some of the complications long-term after transplant. I have to add to my disclosures here that I know Angela mentioned I might be talking about MELD score and the child PUS score, but I wasn't really going to, because this was post-transplant. But just briefly, MELD score is used to identify those who are sicker and approaching the need for transplant, and looks at four variables, including sodium, creatinine, bilirubin, and INR. The child's PUS score is a way of differentiating between compensated and decompensated cirrhosis, and looks at five variables. Child's A is compensated, B, moderately decompensated, C is severely decompensated, and there's, I have no relationship to this app, but I love my little liver calc app, where I can calculate my MELD sodium score, and my child PUS score, and a variety of other things. So that may be helpful for some. So who provides this long-term care post-transplant? It may be the primary care provider, it may be transplant hepatology providers, it could be the transplant surgeons, it may be a combination of all. The things that I'm gonna highlight in this talk are cardiovascular disease, hypertension, diabetes, dyslipidemia, chronic kidney disease, and malignancies. In terms of cardiovascular disease, this is a real risk, and is the leading cause of non-liver-related post-transplant death and complications. Up to 30% of post-transplant deaths are related to cardiovascular or cerebrovascular complications. And when you look at the incidence after transplant, you can see in the graph over here to the right, that at one year, it's about 10%, five years, 20%, and by eight years, about 30% of patients have some type of cardiovascular complication. Contributing factors include their underlying liver disease. It's a higher risk for those that have fatty liver disease or alcoholic liver disease at time of transplant. Other factors are similar to the general population, obesity, age, male sex, diabetes, metabolic syndrome, renal dysfunction, and of course, immunosuppression in this population. Those who develop post-transplant fatty liver disease, whether or not it was present at time of transplant, are also at higher risk. How do you manage this? Well, good control of metabolic syndrome. And any associated factors with a focus on lifestyle modification, immunosuppression, try and minimize whenever possible, screening for vascular and cardiac issues. Hypertension is a very common post-transplant complication. Up to 85% of patients may develop hypertension post-transplant. The goal would be a blood pressure less than 130 over 80, and I don't know about most of you, but I rarely see that in clinic. Most patients, I'm happy if it's 140 over 90. In many patients, they come in much higher, and they tell me it's okay, that they have white coat hypertension, and it's better at home, but I don't necessarily believe them. So management of this is, according to guidelines, in terms of monitoring blood pressure at least every six months. Treat the blood pressure when it's elevated. Calcium channel blockers in post-transplant patients are typically my first line of choice. Imlodipine or nifedipine. Imlodipine, you may see a little bit more lower extremity edema. If that happens, you can switch them to nifedipine. It's a little bit less likely to occur. Some of the calcium channel blockers, as you already know, such as dultiazem, verapamil, nicardipine, may also affect immunosuppression levels. So if those are being used, you need to monitor the immunosuppression levels a little bit more closely. You can add on diuretics, such as furosemide, chlorothalidone, hydrochlorothiazide. The use of ACEs and ARBs, in many settings, that's not my go-to, and it's currently recommended to avoid in the early post-transplant period because of the complication of hyperkalemia. You can use them in the transplant population, but I would really look at their potassium prior to starting it. If they're borderline high, they're likely gonna develop hyperkalemia, and you may be able to get them on a minimal dose, but long-term, this may not be the class of drugs of choice. And alpha blockers and beta blockers are also used. Sometimes patients need more than one, similar to the general population. Carvedilol may increase immunosuppression, and so immunosuppression needs to be monitored as well. Diabetes. There's a really wide variation in reported incidents of diabetes after liver transplant, anywhere from 10 to 33% in the first year post-transplant. Now, those numbers may decrease with time as corticosteroids are reduced or removed, but there is still a higher incidence of diabetes in this population. It's higher in some than in others. Those with hepatitis C at time of transplant are a particular risk for developing diabetes post-transplant. Early on, this is just a total aside, early on when, this was probably 20 years ago, when hepatitis C was coming out as a bigger issue, there was a discussion about this relationship between hepatitis C and diabetes, and it was something that I did as part of my doctoral research. And at the time, in the hepatology literature, they talked about that viral hepatitis C caused diabetes. In the endocrinology literature, they talked about diabetes causing hepatitis C. We all know which one is the actual, well, just pathophysiologic occurrence. So contributing factors to diabetes are your classic risk factors in the general population. Viruses, as mentioned, CMV, as well as HCV. The pre-transplant diagnosis of fatty liver disease, immunosuppression, and then, of course, donor factors, which are not something that we have any control over. It does contribute to a higher mortality at five years post-transplant, 36.5% versus almost 14%. That's a very significant difference. There's a higher incidence of renal insufficiency in patients with diabetes, and management would include early strict glucose control to minimize long-term risks. Good long-term control is beneficial. Follow the ADA guidelines. Target hemoglobin A1C would be less than 7%, with a focus on lifestyle modification and medications. This is where having a multidisciplinary approach can be very helpful. It's not uncommon for patients to come in and not particularly see a primary care provider on a regular basis. You may not be sure of what's been done in terms of screening tests, and if they don't know, or if I don't have those data available to me, I will include a hemoglobin A1C in their annual testing. Another common complication is dyslipidemia, with an incidence approaching two out of three patients. Risk factors include obesity, diabetes, cholestatic liver disease, and immunosuppressant medications, especially sirolimus. So the recommended management is to do a lipid panel screening annually after the first year. If the LDL is greater than 100, treatment is recommended. And lifestyle modifications, including exercise and weight loss, are also discussed. Now based on the last three slides, you may be thinking you came to a primary care conversation, a primary care presentation, but these are all really common post-transplant complications that as the transplant providers, we need to help the patient understand and make sure that they get treated appropriately. So in terms of medications, statins are okay to use post-transplant. The pravastatin and fluvastatin, which are considered moderate intensity statins, are not metabolized by the CYP3A4. So are less likely to have any interaction with their immunosuppression. The torvastatin and rosuvastatin, which are high intensity, are metabolized by that pathway. It doesn't mean we don't use them. And if they need those medications, you use those medications, you monitor their immunosuppression. Part of the conversation may be in also informing the primary care provider that it's okay to use these medications post-transplant, that the liver is actually working okay, and they need these medications more than they need the complications related to dyslipidemia. If you need to add on something, ezetimib would be one option. If they have isolated hypertriglyceridemia, fish oil up to four grams a day, if they tolerate that. And then you can add on gemfibrozil or fenofibrate, but you wanna watch for side effects, which includes rhabdomyolysis and myopathy. Another complication is chronic kidney disease. Liver transplant recipients have the second highest rate of post-transplant chronic kidney disease. At one year it's about 8%, but by 10 year it's about 26%. It may be even higher than that if you were to incorporate renal insufficiency. Some studies in the past have suggested by five years, 85% of patients have some degree of renal insufficiency. Much of that decline occurs in the first year. It's associated with anemia, renal osteodystrophy, and electrolyte abnormalities. Contributing factors include pre-transplant renal function, immunosuppression, hypertension, and diabetes, which is why the good control of these other metabolic comorbidities is important to, as Renee said, protect the kidneys. You wanna protect them before transplant, and you really need to protect them post-transplant. Management would be monitoring creatinine clearance using an estimating equation, such as a GFR calculator. The creatinine by itself may not be adequate to really tell you the degree of renal dysfunction. Minimize immunosuppression as tolerated. Do an annual spot urine protein creatinine ratio. Control or reduce other contributing factors and avoid NSAIDs and nephrotoxic medications. I still have the conversation with patients that acetaminophen is preferred over NSAIDs. Malignancy is one of the more serious complications post-transplant. There's a higher risk of de novo malignancy after liver transplant. About three to 5% at one to three years post-transplant, 11 to 20% at 10 years. That's pretty high. But the relative risk can vary based on the type of cancer. Skin cancer is the most common. And it can be up to 70%, between 20 and 70% of squamous and basal cell, and three to 5% for melanoma. It's encouraged for patients to get a good skin check at least once a year, starting at five years. Sooner if they have other risk factors, if they're pale skinned and have had sunburns like me. During their childhood. But having these numbers is sometimes helpful to have the conversation with the patient because they don't really understand why they need to see a PCP for a good skin check or see a dermatologist. These cancers can be much more aggressive depending on the degree of immunosuppression. And we've had some patients who, they're having skin cancers removed three, four, five times in a six month period of time. Which is where minimizing immunosuppression as you can, can be helpful. Colorectal cancer, it's similar to the general population if they do not have IBD and PSC. However, it's up to 30% if they have ulcerative colitis associated with their PSC. So getting regular colonoscopies is very important. Lymphoma, 10 to 30%. Oropharyngeal, three to 14%. Kidney, five to 30%. And then lung is 1.7 to 2.5%. Interestingly, breast cancer risk is similar to the general population. But having routine screening for any type of cancer is recommended. So for skin, as I said, an annual skin check with a dermatologist five years or more after transplant. More frequent if they have other risk factors or history of skin cancer or a suspicious lesion. I pick out a lot just looking at them and like, what's this thing on your ear? Oh, that's been there forever, but it's getting bigger. Go see a dermatologist. Colorectal cancer, annual screening colonoscopies with biopsies for patients who have IBD and PSC. Otherwise, follow the American Cancer Society guidelines for other screening. Same for breast cancer. Follow the American Cancer Screening Guidelines for the general population. And if graft cirrhosis were to develop, abdominal imaging every six to 12 months, similar to management of any cirrhotic patient prior to transplant is recommended. Obesity is a common complication post-transplant. Weight gain is very common. Approximately 20% of non-obese patients become obese. All patients require ongoing dietary counseling, recommendation for regular exercise. Consider referring for behavioral weight loss programs. Discussing the different types of options in terms of diets that are available, whatever diet they can follow is the one that will work best. And I usually lay out several options for them and then have the conversation again and again and again. But we've had some really good successes and some patients have followed Weight Watchers and some patients have just done calorie reduction with their little Fitbit app on their phone. And some people have followed a keto diet under supervision. Where I was at VCU, we had a medically supervised weight loss program. But sometimes they need more and a bariatric surgery referral may be an option for them. Other preventive care, looking at bone health, similar to what was discussed earlier prior to transplant, there's a risk of bone loss after transplant, there is a risk of bone loss. Testing should be done annually for the first five years if osteopenic, which the majority of transplant candidates are at baseline. Every two to three years if normal bone density at time of transplant. And after five years use screen based on results of your DEXA scans. Calcium and vitamin D supplementation is recommended, weight bearing exercise is helpful. And at this point bisphosphonates have indicated the risk in terms of the esophageal varices are typically gone with the reduction in portal hypertension. Other preventive care vaccines. This is one thing that is really important to me. I think it's really important to have the conversation with the patients. They should have no live vaccines, which means they need the flu shot, not the flu mist. And annual flu shot is recommended, as well as both Pneumovax 23 and Prevnar 13. Tetanus, hepatitis A and hepatitis B. Hopefully many of the hepatitis A and B and other things are up to date at time of transplant. But if not then you pick up the ball afterwards and go from there. Smoking cessation, it's not good for anybody. It's really not good for transplant patients. There's a higher risk of all sorts of complications including thrombi that can affect the graft. And everybody knows the lung is bad. It's not good for the lung. But I usually come up with a couple of other organs and tell them why they shouldn't be smoking. Alcohol, abstain if alcohol is the etiology of liver disease. And enter therapy or counseling if there's a return to drinking, which can happen. Sun exposure, avoid excess sun exposure. Wear sunscreen and protective clothing. Other health promotion important points are frequency of monitoring labs and liver tests. This can really be individualized over time based on their transplant complications and stability of labs. Every center has their own protocol that they follow. Immunosuppression regimen should be reviewed every six months. So if there's an opportunity to reduce then you can do that. You want to minimize the risk of tick, mosquito, and sun exposure. Frequent hand washing for the patients. Avoid consumption of water from rivers or lakes. Avoid unpasteurized food products, raw undercooked eggs, seafood, meat, chicken, pork. And then weight management as well. So the key takeaway points from this presentation which really was a very Reader's Digest overview of the many things that you have to monitor in your post liver transplant patients. Our liver transplant recipients are living longer and they develop many medical comorbidities. They have a higher risk for many cancers and cancer surveillance is really important. Metabolic comorbidities are common and these require treatment. You may initiate the treatment and then work in conjunction with a specialist or the primary care for ongoing treatment and monitoring. So you want to monitor and provide guidance for medical comorbidities. And as I said, it may require collaboration with multiple providers. You want to encourage prevention strategies including vaccination and lifestyle modification which is part of the conversation that happens at every visit. Sometimes it's hard to take everything up at once but if you work on it one visit at a time then hopefully they'll be able to make those changes as well. Thank you very much.

liver transplant outcomes

survival rates

long-term complications

cardiovascular disease

management strategies

preventive care