Hello and welcome to the Women's Health and Liver Disease Program. I'm Monica Sarkar, a transplant hepatologist at the University of California, San Francisco. My co-moderator today is Dr. Susan Orloff, a transplant surgeon from Oregon Health Sciences. We're excited to feature reproductive health at this year's liver meeting and have some fantastic speakers and topics for our discussion. We'll start off with Dr. Vandana Kumar from Yale University who will discuss fertility and contraceptive options in women with liver disease. This will be followed by Dr. Michael Hennigan from King's College on cirrhosis and pregnancy, including risk stratification, management, and counseling. Dr. Laura Kulik from Northwestern University will then address management of liver lesions in pregnancy. Our final speaker will be Dr. Jamie Locke, a transplant surgeon from the University of Alabama, Birmingham, to address sex disparities in liver transplant. To end our session, Dr. Orloff and I have prepared a couple of cases, and our panelists will share their approach to these challenging clinical questions. Throughout the session, you'll have the opportunity to submit questions for our speakers in the chat box to your right. Presenters will be available real-time to answer questions using the online chat feature. Please enjoy the program. I would like to thank the program chairs, Drs. Orloff and Sarkar, and the ASLD for the opportunity to speak at this important session on women's health. Fertility and contraception are issues germane to the quality of life for a large majority of our patients, whether women, men, or gender non-conforming individuals. This is not a niche topic and it's wonderful to see it receiving the attention that it deserves. I'm an associate professor of medicine at Yale University School of Medicine. I have interests in quality improvement and digital health with a focus on underserved populations and women's health. I do not have any financial disclosures. When speaking of fertility, it's important to treat the whole patient and not just the liver. We know that's an immense source of stress for patients and families, even those without liver disease. There's often reticence on the part of both patient and provider to bring up such a delicate topic. We should always think about fertility for women, men, gender non-conforming, and transgender patients, as well as anybody with the capacity for pregnancy. Hepatologists and surgeons can sometimes single-mindedly be focused on the liver, so we have to expand our horizons to treat the whole patient. Contraceptive education is essential, both for patients and providers. We should ask every reproductive age person about contraception as well as plans for conception. Discuss options with them and collaborate with OB-GYNs in their care. Going into particular modes of contraception, as well as concerns specific to cirrhosis, we know that those with decompensated cirrhosis generally have decreased fertility, but that pregnancy is still possible. Irregular or intermittent ovulation can make fertility difficult to assess and one can falsely assume a patient is not fertile and then have to contend with an unintended pregnancy. Patients with compensated cirrhosis or non-cirrhotic liver disease can also be at risk for complications from a pregnancy. It is not only the decompensated population. Those with compensated cirrhosis or non-cirrhotic liver disease can also be on teratogenic medication, so they should be watched closely. We should be asking every reproductive age person about their current habits and sexual history. Hepatologists and surgeons feel very out of their realm in the domain of contraceptive selection. While we won't be prescribing the contraceptive, knowledge of safety is essential. We do not need to memorize particular contraceptive options as there are several excellent resources. The recently published ASLD, Reproductive Health and Liver Disease Practice Guidance, has important modifications to the national and international guidelines, including the World Health Organization, medical eligibility or MEC criteria, as well as the US CDC MEC for contraceptive use. Many more options are available for patients with less caution with hormonal contraception than before, and this is largely because the newer formulations do not contain the very high doses of hormones that previous formulations did. We should always balance the risks and side effects of medications versus a risk of pregnancy in our patients. This figure from the CDC shows the effectiveness of contraceptive methods, and as you can see, the most effective are implants, whether copper or hormonal, sorry, IUDs, whether copper or hormonal implants, as well as permanent sterilization. Secondarily, are injectables, pills, patches, rings or diaphragms, and finally, barrier methods. Many of us likely remember carrying this wheel around as med students so that we could readily calculate gestational age and determine appropriate timing for testing during pregnancy. If you're anything like I am, you firmly believe that this wheel was going to leave your pocket after your rotation was over and you would never think about it again. Of course, now we realize how interconnected our reproductive health is to all specialties, including the care of the patient with liver disease. Borrowing from the gestational age wheel, the CDC created the US MEC eligibility criteria wheel, which allows one to line up medical conditions and contraceptive options for a given patient. Fortunately, this has now been converted to an app for, on the left, the World Health Organization contraception tool, and on the right, the US MEC. Both are free to download and very useful to have on hand when discussing options with patients or with colleagues in OB, particularly because these are the resources that the OBs will be using. Our guidance document from the ASLD has slightly differing recommendations. We want to make sure that we work collaboratively with the patients and their other providers to appropriately treat their liver disease and their contraceptive needs. Focusing on the US MEC because that's more germane to our population here, if you look at the left panel, it is recommending contraception for compensated cirrhosis and the right panel for decompensated cirrhosis. It's important to note that all modes of contraception are deemed appropriate for compensated cirrhosis. Whereas on the right panel, in decompensated cirrhosis, the US MEC states that only the copper IUD is an appropriate choice with combined hormonal contraceptives being contraindicated. This differs from our guidance document in which we know that the copper IUD remains a great choice, but it does have the risk of increased bleeding in patients who may already be thrombocytopenic and anemic. In that case, we can consider progesterone-only pills or even implants as acceptable. Again, with the US MEC, if you look at the left panel, it's for benign tumors including FNH. The middle panel is for hepacellular adenomas and the right panel is for malignant hepatomas. Again, the US MEC is more conservative than we will be in our guidance document. This guidance document came out in 2021 and we'll go through what we say that differs from the national and international OB guidelines. Anywhere that I have boxed in red is where we differ from the World Health Organization and the CDC MEC. Essentially, progestin-only contraception, including IUDs and decompensated cirrhosis used to have historical concerns and those stem from higher dose progestins, which may have a small amount of conversion to estrogens. But due to the fact that these higher doses are no longer used in contemporary formulations, this should no longer be a concern. We can inform our OB colleagues that we do not have an objection to the use of the progestin IUD in our patients. For hepatocellular adenomas, we know that estrogens have a very direct effect on adenomas, but there have been case reports of regression of adenomas after cessation of agents containing progestin. These higher dose formulations, again, are no longer used, so it should not be a concern. IUDs in post-transplant patients with graft failure, there have been case reports of unplanned pregnancy, but those were older, less effective IUDs. Really, the risk of unplanned pregnancy, pelvic inflammatory disease in our immunocompromised patients has not been substantiated, and these should not be contraindications to use an IUD in a post-transplant patient. LARCs are long-acting reversible contraceptives, particularly effective and durable modes of contraception, particularly in patients such as adolescents or those who do not want to become pregnant for a long period of time. Patients with normal liver functions, including post-OLT, can use a LARC without restriction. It's important to note that their package inserts for the hormone-containing IUDs list acute liver disease or tumor as contraindications, but that evidence is severely lacking. Hormonal IUDs or implants do reduce menstrual volume, but we avoid them in Bug Chiari syndrome, hepatic adenomas, if estrogen-containing are the two hard contraindications. The copper IUD, as we all know, has no hormones, so it can be confidently used in decompensated cirrhosis and patients with hepatic adenomas. But you should exercise caution because it increases menstrual volume and can be dangerous in a patient with thrombocytopenia or heavy bleeding. Also, it cannot be used in any patient with Wilson disease. Preconception counseling and pregnancy planning is extraordinarily important in any patient, but particularly in those with a coexisting liver disease. We want to ensure that we inform patients about the risks of the liver disease during pregnancy or postpartum, obstetric complications, and potential medication toxicities for pregnancy or breastfeeding. We know patients have impaired fertility and we should be appropriately looking at timing of their desire to have a child and helping them to plan. We should be transitioning them from teratogenic medications and performing liver-related evaluations that might be more difficult to do during pregnancy such as HCC screening or variceal banding and ensure that our patients are equal partners in their care in deciding these life-changing decisions. Adolescents are unique and that many of them struggle with managing their own disease. We like to arrange for scaffolding support with financial and housing support, health services if they don't have family or friends. We know that 75 percent of pregnancies and adolescents are unplanned, so LARCs are particularly useful here. We should collaborate with pediatric and adult hepatology as well as maternal fetal medicine. Men are a unique population in that teratogenic drugs still can affect the fetus and their potential for birth defects, particularly with mycophenolate. Whether the patient is a man or a woman, they should always use two forms of contraception and have no plan for conception within six weeks of a dose of mycophenolate. Cystic fibrosis patients who are men have generally 97-98 percent of cystic fibrosis male patients are infertile due to congenital bilateral absence of the vas deferens. We should ask all of our male patients with CF-related liver disease if they plan on having a family and plan for sperm banking or IVF. Assisted reproduction is the new frontier in liver disease and reproduction. It's an eye-opening paper presented here by Professor Hennegan and his colleagues in the June issue of the Journal of Hepatology. This is the first paper to report on the safety and efficacy of IVF in the chronic liver disease population and those who have received a transplant, and it's the first major series of such outcomes. A very insightful and company editorial was published in the same issue. The first pregnancy was in the 1980s, so really it has not been around that long and it has had rising popularity. We also know that prevalence of pregnancies in liver disease has increased, so safety of IVF and assisted reproductive methods is still unclear. We know there are delays to timing and ability of women to conceive, and we know that we have to take account for their fecundity and their fertility to ensure that they are successful. Liver-related subfertility is any decreased fertility due to liver disease. We know this can be due to chronic liver disease or liver transplantation and subfertility is common with amenorrhea, and 30-50 percent of our patients with chronic liver disease. But luckily, it does improve in 70-95 percent of patients, but we should be careful to avoid unintended pregnancies in the post-transplant period as fertility returns as soon as three months post-transplant. Immunosuppressive meds, etiology of the liver disease, adhesions can all affect fertility, and of course, age, psychosocial factors, depression, and primary reproductive issues. The pathophysiology of liver-related subfertility is thought to be due to the hypothalamic pituitary axis as well as portosystemic shunting of weak androgens and impaired metabolism of sex hormones with peripheral aromatization of androgens. Etiology as well as malnutrition are also important factors. The process of IVF is not entirely clear in liver disease. The actual process itself is the same, but the potential impact on liver disease is not fully understood and their hypothetical mechanisms postulated in this figure as to what might cause something to go wrong in a liver disease patient. This is so new to our field that it wasn't even mentioned in the 2005 consensus conference on reproductive issues and transplantation. It's something that we will continue to learn about together. There are potential complications of IVF, including ovarian hyperstimulation syndrome, liver test abnormalities, which are usually mild and hepatocellular. Development of abnormal liver tests can be associated with lower rates of pregnancy and hypertensive disorders, as well as help can occur. But there are case reports of successful IVF in liver transplant and autoimmune patients. In the series by Dr. Hennigan, this retrospective analysis of data from King's College and the easel registry showed that over a 30-year period, only 42 women and 57 cycles of IVF occurred. It's important to note that the data were obtained from liver disease registries and not from IVF registries, so some metrics related to IVF safety are unavailable. Over the 30-year period, of course, techniques have evolved significantly. There are unfortunately no comparator groups for women without liver disease receiving IVF, or groups of pregnant women with liver disease or post-liver transplant, who conceived with spontaneous conception. It's unclear if the adverse events in this population are due to IVF or the inherent risk with the pregnancy itself. A future direction would be to link IVF databases with liver disease databases. In the same study, we see that the safety, the etiology of liver disease in these patients was quite disparate, but interestingly did not include much alcohol or fatty liver related disease, which are now our predominant etiologies. In this population shows success rates in cirrhosis as well as post-liver transplant, we see that the MELD score was generally quite low in this population. There were patients with portal hypertension, but generally overall good outcomes. In post-liver transplant, there were no graft failures or deaths in the pregnancy period. We did see erratic tachylimus levels in five out of nine cycles, but despite this, there were no confirmed cases of rejection and no graft losses. Really, we see that IVF is feasible and successful in select patients with decreased fertility from liver disease. There is an increased likelihood of OHSS, deranged liver enzymes, OC, and erratic tachylimus levels. This is in keeping with previous case reports, but it's very nice to have such a large case series over time. It was interesting to note that some women did not have monitoring of their liver enzymes during IVF therapy, which really underscores the need for collaboration. Fertility preservation is an absolutely untouched field in liver disease and really we can borrow from our colleagues in oncology to advance the field. Key points really are that we have some interesting new developments in this field, but there's still a paucity of data. We know that fatty liver is associated with PCOS and infertility, and the number of patients with liver disease seeking ART is likely to grow. Alcohol-related liver disease is also growing. We should exercise an abundance of caution, but not be too cautious because if we go too far in one direction, we can cause lasting psychological harm or overstep our bounds. Patients have different value systems. We should avoid paternalism and ensure full informed consent with multiple discussions if necessary. Approach these discussions with humility and compassion, and inform patients that there's more than one way to become a parent. Fertility and contraception in liver disease are areas ripe for future investigation. Thank you. Well, I'd like to really thank the organizers for inviting me to participate in this session, and I'm really thrilled to again participate in the Women's Health program. These are my disclosures. So I've been tasked with discussing pregnancy in cirrhosis, and what is very clear that even in our own institution, there is no doubt that the prevalence and the rates of pregnancy in chronic liver disease, both non-cirrhotic patients and cirrhotic patients, is actually increasing over time. And this is something that we are increasingly finding as a challenge in our clinical practice as hepatologists. Women want to become pregnant with chronic liver disease. This study is a population-based study from Canada, and really this also reflects the data that I have just shown at a single center level. And this is probably the most important paper in the field. And what you can see is that over almost a 20-year period, there has been a really significant increase in the rates of pregnancy in women with cirrhosis. But not all cases of cirrhosis have equal rates of pregnancy. Some etiologies are much more favorable in terms of childbirth rates. The overwhelming number of patients that we will be seeing in our clinical practices, however, are those patients with naphrodi or fatty liver causing cirrhosis. And what you can see from these data quite elegantly is that women with fatty liver and hepatitis B, their outcomes in terms of childbirth rates are really very favorable. And in contrast, women with alcohol-related liver disease, as you would expect, their childbirth rates are reduced. And again, this slide really summarizes these data. And this is such an elegant study. As I have said, a seven-fold increase in the rates of childbirth in women with cirrhosis, predominantly naphrodi-related cirrhosis. But actually what this data elegantly demonstrates is that when you identify women with cirrhosis, that their pregnancy outcomes are modified. They have increased rates of cholestasis or pregnancy, higher rates of preterm delivery, induction of labor, increased rates of puerperal infections, larger babies, and a greater rate of neonatal distress. What is also important to iterate is the fact that death and liver-related events up until one year postpartum are actually rare. And the group of patients that we really need to focus on are those patients who have had decompensation at some point in the past, because this is the group that are more likely to have poorer outcomes. So what we can tell are compensated patients with cirrhosis, that the likelihood of them coming to harm is very low, less than 2%, closer to 1% in contrast to this decompensated group. Now, what we know from other population-based studies in the United States, actually, is that the impact of the disease outcome is also very, very important. I have shown you that there are, there is a lower birth rate in alcohol, but that also translates into greater complications or greater rates of complications for the mother during the pregnancy. And what this translates to, compared to the general population, is both maternal death, fetal death, as we have said, preterm delivery in the Canadian cohort, growth restriction, but also look at the differential in terms of cost between these two groups. As I have also outlined, and this is data from Dr. Sarkar and colleagues, the predominant disease entity in cirrhosis that we will see in the United States and worldwide is likely cirrhosis related to fatty liver disease. And this study, again from the National Inpatient Survey, demonstrated that the characteristics of these women with NAFLD, they had a lot of diabetes, high rates of obesity, as you would expect, around 40%, dyslipidemia, and although there were not many women with cirrhosis, the important take-home message is that these characteristics actually predispose towards hypertension-related complications in pregnancy. And of course, for obstetricians and obstetric physicians, they're well aware of the preeclampsia risk factors, hypertension, chronic kidney disease, autoimmune diseases, so our autoimmune liver disease patients, we need to be mindful of as having a high risk factor for hypertension in pregnancy, type 1 or type 2 diabetes, and preexisting hypertension. And the reason that this is important is that you increase the rates of hypertension-related complications with one risk factor or more than one moderate risk factor. So when we are seeing our patients with cirrhosis, we need to be considering, do they need to have aspirin as prophylaxis to potentially protect them against hypertension-related disease and the complications associated with that in these high-risk pregnancies? So aspirin, what we know from a pivotal trial, the ASPRAY trial, that actually 150 milligrams of aspirin daily from 11 to 37 weeks actually is associated with better outcomes, including primary outcomes and secondary outcomes for the neonates, admission to the neonatal intensive care, reduced length of stay, and potentially cost savings if this is applied across the population. Now, I will focus the next proportion of this talk on understanding cirrhosis at an individual patient level and what we can use to stratify patients. Early work from my group suggested and looked at the common tools for stratifying patients like MELD score or UKELD score, which is a modification of MELD sodium. And what we could find is that a standard MELD score of 10, which is not a particularly high score, was associated with poorer outcomes. These women were at increased risk of either a liver-related adverse event. So UKELD score, this modified sodium MELD score, and MELD score very important in looking at stratifying patients. In a much bigger group of patients, we have also looked at some other parameters for stratification, ALBI scores, APRI scores. And what you actually find is that ALBI, this association between albumin levels and bilirubin levels is very sensitive in predicting live birth in pregnancy. So when we look at these tools for stratification, arguably ALBI is the one that is most important in predicting a live birth. If you stratify patients according to the severity or the depth of their ALBI score, what you can do is actually stratify patients and quantify their likelihood of having a term birth. As your ALBI grade increases, the likelihood of getting to term decreases significantly. And this is very important in counseling women in relation to their outcomes. And this can be done looking at albumin and bilirubin at conception. The other tool that we have investigated is APRI, the AST to platelet ratio. And again, it is possible to look at these parameters in terms of gestational length. If you have patients who you have cirrhosis, how should you be screening them in relation to portal hypertension? These are algorithms from the ASLD clinical practice guidelines. And certainly pragmatically, if you have variceal screening within one year of conception and you have got varices, then you should be thinking about primary prophylaxis. If you have larger varices, you should be getting on with trying to obliterate these varices or proactively using non-selective beta blockers. In women who have not had an endoscopy, then the recommendation is to go ahead and organize an endoscopy in the second trimester and then deal with varices accordingly. These are data from King's College Hospital, where we have a long-standing cohort of patients. Patients will potentially bleed in their pregnancies, 13% of our pregnancies in women with cirrhosis who had varices bled. These were treated with standard treatment paradigms. But what is important is that women who had undergone planning, pre-pregnancy counseling, were more likely to undergo endoscopy. But even then, it was not perfect, with only roughly 60% of women having undergone an endoscopy. If you have a bleed in pregnancy, the data is extrapolated from the non-pregnant state. Beta blockers are generally considered safe and recommended, although they can be associated with intrauterine growth restriction and around the delivery can be associated with neonatal bradycardia, hyperglycemia, and some respiratory depression. If you have an acute bleed, octreotide is considered safe. Use antibiotics as you would in the non-pregnant state. Terlepressin, although it has traditionally been considered a class D drug, it boils down to risk and benefit, so that if you have somebody who is torrentially bleeding, there may be a risk-benefit ratio in favor of terlepressin. And occasionally, salvage tips has been performed in pregnancy. Women are also increasingly inquiring with regard to the safety of IVF or assisted conception in chronic liver disease and in the context of cirrhosis. And this data from our group just published this year demonstrates really some of the only data in the field. But what I would bring to your attention is that if you have chronic liver disease without cirrhosis, the live birth rate is roughly 62%, miscarriage rate 11.8%, and stillbirth rate 2.9%, with a prematurity rate of approximately 33%. If you have cirrhosis, established cirrhosis, albeit a small sample, the likelihood of an unsuccessful implantation is a bit higher, although in truth, not much different between the groups, but the live birth rate is reduced, the miscarriage rate is reduced, and prematurity is almost universal. So what do women want and what are the optimal management paradigms in pregnancy? This is a study performed in our own center. What our patients are interested in is knowing whether their health will deteriorate, whether they will die in pregnancy, whether or not they will lose the pregnancy, safety of medication for genetic disease, the risk of passing on the disorder, and the need for breastfeeding. So the ideal paradigm in looking after our women is pre-pregnancy counseling, assessing the risk of portal hypertension and medication effect, calculation of risk scores and stratifying at an individual patient level, ensuring that if an endoscopy hasn't been performed, that it's done in the second trimester, getting a delivery plan, breastfeeding and contraception, and finally, using pregnancy as an opportunity to actually focus on risk and positive health messages for both the mother and their families going forward. Thank you for allowing me to participate, and this is my team. Hello, my name is Laura Kulik, and I will be discussing liver lesions in pregnancies, surveillance and interventions. I am a professor of medicine and a transplant hepatologist at Northwestern. My area of focus has really been in HCC and treatments to get patients to transplant. In my free time, I enjoy hanging out with my Frenchie Miles. These are my disclosures. So liver lesions in pregnancy causes a lot of anxiety. It is not a routine recommendation that patients who become pregnant should undergo any kind of imaging to look for any masses. Hepatic masses, however, can cause symptoms due to suction of the capsule, which can lead to pain. There can be compression of adjacent organs in the setting of a gravid abdomen and difficulty with eating, and bleeding can occur, which is the most feared complication. So liver lesions in general can cause panic in people, but people really need to take a deep breath and really use the radiologist as best as they can by making sure they have the correct information, review the films with radiologists, taking that time is essential, and attempting to find old films can really help in determining what a lesion truly is. So let's start with the most common, which is hepatic hemangiomas. These are basically a tangle of blood vessels. It is reported in autopsy reports to be up to 20% of the population. It is predominantly seen in middle-aged women with a ratio of men to women of three to one. It is supplied by the hepatic artery, and these lesions can be quite large, up to 20 centimeters has been reported and caused symptoms. They have a very classic appearance of filling in in the periphery first, and then gradual fill-in in a centripetal motion. They are bright on T2, and this can really help with the diagnosis of hemangioma. However, they can mimic HCC, and you should be aware, especially in people who have risk, particularly underlying chronic liver disease, and larger lesions may show an area where there is no, what is called a vascular zone, so no blood in there, and therefore it is important to distinguish from malignancy. But in a group of women who are becoming pregnant, this is less likely due to their age. So pregnancy and the use of OCPs is not a contraindication when these hemangiomas are stable and not causing any kind of symptoms. They can rarely rupture, and this has been reported in pregnancy, and a risk factor is if it's greater than 10 centimeters. There's also this consumptive coagulopathy, the Casablanca syndrome, and this is more common in patients who have lesions greater than 5 centimeters. There is a low-grade DIC that occurs, and in women with a hemangioma, if they are starting to show a picture of decrease in platelets and coagulopathy and have a hemangioma, this should be considered. By the ESL guidelines, however, pregnancy and oral contraceptives are not contraindicated, and patients should not be dissuaded from becoming pregnant. Now let's go on to the second most common lesion that we see, which is a focal nodular hyperplasia. And this results due to a vascular anomaly. These contain Kupfer cells, so this is how you distinguish this from an adenoma, which is void of Kupfer cells. One of its pathognomonic features is that you have this central scar that is bright on T2. It is more commonly seen in females. It's more commonly located in the right lobe of the liver. Most of the time, it tends to be solitary, but you can see growth with these over time. So if it has a very classic appearance, then the fact that it's growing should not cause alarm if it looks very much like an FNH. An MRI is 100% specific, however, there are concerns about using any gadolinium in a woman who is pregnant. Contrast and ultrasound can be very helpful in lesions that are less than 3 centimeters. And these lesions are also associated with cardiac issues and things such as osteorebrurandia. So there is no evidence that this is a premalignant lesion. We hear that this can be confused with a malignancy called fibrolamellar, however, this is a very rare, rare cancer. The difference is that this tends to have a calcified scar in over 50% of the time. The management of these is conservative regardless of the size, and there is a very poor correlation of the size leading to symptoms. Pregnancy as well as birth control do not seem to have any effect on these. However, in talking with radiologists, they hear that it was read as an FNH and it grew in pregnancy and then decreased after pregnancy. That may have been a mistaken adenoma. There had been an adenoma, a new classification of adenomas that I'll talk about that used to be called a telogen tagia FNH, which is truly an adenoma. And we start to get concerned and refer when patients are having symptoms. This can be embolized or resected, particularly if these lesions are hanging from the liver in an exophytic manner. So hepatic adenomas are the ones that we really get concerned about in pregnancy. Its true incidence is really not clear, but it had been associated with birth control pills, but now the amount of estrogen has become very low. What we are seeing is a rise in these as it relates to fatty liver disease. It's most common in females in the age of 35 to 40. It tends to be solitary and it also tends to be in the right low, but near the subcapsular area, which can be problematic in terms of risk of bleeding. Its size can be up to 30 centimeters, but the average is reported to be about eight centimeters and it is known that this increases with stimulation from estrogen. So pregnancy as well as birth control pills. A big concern is too hemorrhage, particularly when these lesions are greater than five centimeters or exophytic. These patients can have symptoms of epigastric pain and tenderness. And when that's present, there's over a 60% chance that there has been hemorrhage. Risk factors include recent pregnancy, if it's an inflammatory type of adenoma, if you've been on birth control pills within the six months, and if there has been an increase in the size over time. The treatment for this is embolization, not immediate resection. If patients are embolized first, there has been shown that there is less bleeding and less complications and then doing a delayed resection. The other concern is development of HCC. So as I told you, these are estrogen dose dependent. There is an increased rise of this as we have seen an increased rise in obesity across the United States. Also anabolic steroids, there can be seen with PCOS and some genetic factors here, as well as some abnormalities in the hepatic vasculature. So there is a subclassification. This has actually been redone again, but for simplicity, I used this one. The two that I will concentrate on are the inflammatory adenoma. This was previously called the telogen tatic FNH, and these are associated with obesity and alcohol consumption. These are the ones that have the highest risk of hemorrhage, which is about 30%. When they're biopsied, they tend to have sinusoidal dilatation. There is immunohistochemistry that can be done to tell you what type of FNH this is. The other concern is a beta ketatin. These are the ones that are higher risk of patients developing cancer, particularly in males and androgens. And I know we're talking about a female population, but I do want to point out that if a male has an adenoma, regardless of size, this should be removed. These are different in terms of when you're dealing with a female. The most benign adenoma, I would say, is the one that you see in a very diffuse fatty liver. These are the ones that are here with the mutation of HNF1. So this can be very helpful. The radiologist can distinguish these based on the way that they are seen on MRIs without the need for a biopsy. So again, talking with your radiologist will be very important and helpful. So what about pregnancy, specifically in adenomas? In the past, it had been recommended that women avoid pregnancy if they had adenomas. This is no longer taught. It is no longer discouraged that patients who have an adenoma less than five centimeters should avoid pregnancy. If it's greater than five centimeters, or there has been a complication such as a bleed in the past and it's not been resected, one should consider doing resection before trying to become pregnant and being seen in a specialized center. Currently, there has been a lack or a paucity of algorithm-based data to guide us in the management of patients when they have adenomas and they're pregnant. It causes women to be very anxious about this and delay potential attempts to become pregnant. In pregnancy, it's generally recommended that they be followed every six to 12 months with ultrasound. There's no data to suggest that how the baby is delivered via C-section or a vaginal delivery in terms of risk of causing any issues with the adenoma. If there's growth, one would consider embolizing. Prior to 24 weeks, surgery may be preferred, especially if it is in the periphery. Again, we want to avoid radiation and IV for the sake of the baby. The highest risk of rupture is in the third trimester, particularly when the lesion is over 10 centimeters. Importantly, the number of adenomas does not increase the risk of rupture. This was a study out of the Netherlands looking at women who had an adenoma less than five centimeters comparing to healthy women. Their purpose of the study was really to come up with what should be done based on the incidence of adenoma growth, how we should follow patients. They had various time points that they were doing ultrasounds on patients during their pregnancy. This is some of the results. They had a total of 48 patients with 51 pregnancies with an adenoma that was confirmed by a contrast enhanced ultrasound prior to pregnancy in 78% of these patients. The median age was 30. BMI was considered obese at 31 was the median. The median size at the time of diagnosis was 3.3 centimeters, and the median size right before pregnancy was 2.2 centimeters. Interestingly, they showed that 25% showed growth, 51% were stable, and 22% actually had regression. The median increase during pregnancy was 1.4 centimeters. There was one patient who it grew greater than seven centimeters that led to being treated with embolization. Basically, this was very reassuring that patients with a lesion less than five centimeters that there was no harm to the fetus and there was no evidence of bleeding or rupture. The observations that they made with that one particular patient who required embolization for growth was that patient did have regression of their adenoma after stopping birth control pills. They surmise that adenomas that regress after cessation of OCPs may be more sensitive to hormones and therefore may be the ones that are more prone to grow. The mechanism of regression is currently unclear. Further studies are needed to determine if there's an impact on the type of adenoma in terms of management in pregnancy. And 18% of these patients were found to have an FNH post-delivery. So it's really important to get imaging prior to decrease undue stress. We are concerned about acute rupture. This can be disastrous in pregnancy. This can be due in adenoma. It can be due to HCC. It can be seen with help, which is the picture that I'm showing here. And it's important to know that once a patient has bled and there's a subcapsular hematoma, it can be very unreliable in determining if there is an underlying lesion. This is a patient who had preeclampsia and health and during her third trimester had an infarction, and you can see that there is necrosis, which is pretty extensive in this right lobe. So just another thing to consider, things that are very specific to pregnancy as opposed to going into pregnancy with a known lesion. This is something that I think is important as we are seeing patients at younger ages developing cancers, particularly colon cancer. We're seeing increase in survivorship and increased strategies to preserve fertility in patients who are undergoing chemotherapy. And this has been noted with oxaliplatin, which is used in colon cancer. This was a series of 14 patients, and they found that these lesions occurred and showed up after the completion of their chemotherapy at 47 months, so long after their chemotherapy had been completed. And there was growth in 42%, increase in size of 16%, and another 16% had both growth and increase in size. So this can be extremely alarming if you are seeing a liver lesion grow in somebody or showing more lesions in someone who previously had malignancy. But they showed that all these lesions were FNH. This was based on imaging. Its pathogenesis is not known. Imaging can be highly specific to show that this is an FNH. And it's very important to realize that the detection of these post-chemotherapy was much longer than what you would expect for someone to develop new onset metastatic disease. There were no reports of metastatic disease detected 3.5 years after resection of the primary. So women may be becoming pregnant after they have had completion of chemotherapy, and this is important to keep in mind. Now, lastly, HTC is very uncommon. Fortunately, this is primarily amongst women who have chronic hepatitis B. In 2020, I found many reports that stated there were only 60 to 64 case reports in the literature. I suspect that there are more. I, unfortunately, have had to deal with this myself and have not reported it. It is very sad in trying to make decisions regarding the mom and the fetus in terms of treatment. The prognosis is quite poor. Overall survival is approximately 18 months. 20% have metastatic disease at the time of their presentation. Another 10% may present with rupture. And it's thought that this is due to estrogen leading to increase in the growth of HTC as well as the immunotolerant state that we see in pregnancy that may lead to further growth of the cancer. So my takeaway points are that most liver lesions of pregnancy are benign and can be managed conservatively with reassurance to the patient. It's important to get imaging prior to planned pregnancy so that there is not this state of constant confusion during pregnancy. A multidisciplinary approach with the OB-GYN, a hepatologist, surgeon, and radiology are important in dealing with lesions, especially in pregnancy. And hepatic adenomas less than 5 centimeters appear to impact minimal risk in patients who are planning pregnancy. With that, I'd like to thank you for your attention and I hope you enjoy the rest of the meeting. Great. Well, thank you so much for the opportunity to present today. It's really an honor and looking forward to discussing how we might go about reducing sex-based disparities in liver transplantation. I do have several disclosures, but I will not be discussing any off-label or investigative use of a commercial product or device. So we obviously have a conundrum between the supply of organs and the demand. You can see in the figure that there are far more people waiting for a liver transplant than there are liver transplants performed every year. And I think many of us in transplant feel a lot like the deck chair rearrangement officers on the Titanic. And how do we actually make sure that we ensure equity in the context of a limited supply? Well, that's part of the reason the Organ Procurement and Transplant Network issued the final rule. And basically, what they said is that given substantial difference in supply and demand, that allocation rules are needed. And the final rule mandates that there can really be no disparities in transplantation based upon race, gender, or geography. But it also mandates that allocation be based on medical urgency. And all of this is to say that what they're really getting at is that there has to be equity, not necessarily equality in allocation. So how do we define medical urgency in liver transplantation? And I think this audience is obviously very familiar with the model for end-stage liver disease. We know what it's comprised of, and it ranges from six to 40. And you can see that with increasing MELD score, if you look at the top line, and we'll just take hospitalized patients, for example, and you look at the three-month mortality, you can see when your MELD score is less than nine, it's about 4%. When it gets to 10 to 19, 27%, 20 to 29, 76%, and so on, such that when your MELD is 40 or greater, you have almost 100% mortality within 90 days if you don't actually receive a liver transplant. And so that's how we define medical urgency, and that's how we go about allocating livers. And so again, as I mentioned, liver allocation algorithms rely on MELD to assign priority. But we have really, of late, focused more on geographic disparities and how differences in MELD might impact that. So on the left-hand side of the screen, we looked at geographic disparities, and we decided that, well, they're geographic disparities based on median allocation MELD scores, and allocation is different than laboratory MELD, right? So allocation MELD scores include exception points that are granted that have nothing to do with the actual calculated MELD score. And you can see that if you look at allocation MELD scores, there appear to be disparities such that in the West, they have very high median allocation scores as well as in the Northeast compared to the rest of the country, and that would suggest that perhaps that's where livers need to go. But when you look at age-adjusted death rates for liver disease in the United States, some of that overlaps with these median MELD scores, and some of it doesn't. So you can see in the West, they have very high age-adjusted death rates, but in the Northwest, the Northeast, excuse me, they don't compared to some other areas in the country that actually have lower allocation MELD scores. And importantly, we see differences by gender. So this is looking at the same figure, but now you're seeing age-adjusted death rates for females. And again, you can see that this doesn't exactly match up with where we say our highest allocation MELD scores are. So what we do know is that MELD-based allocation has introduced gender disparities in the U.S. And here's some great work done and published in JAMA in 2008. And to cut to the chase, we know that on the waiting list that women are 1.3 times more likely to die than their male counterparts. And if they have hepatocellular carcinoma, they're almost four times more likely to die. And why is that? Well, if you look at the right-hand side of the screen, the data will tell you that women are 1.4 times less likely to achieve transplant. And if they have hepatocellular carcinoma, that also holds true with a 1.4 times less likely to achieve transplant. And this is really problematic. So clearly gender disparities exist, and we need to understand why that might be, because we've known about these gender disparities since MELD was introduced in 2002. That's more than 20 years ago. So what are the critical assumptions related to MELD-based allocation? Well, the first assumption is that MELD accurately captures disease severity. And as we showed earlier in the presentation, one of the components of the MELD score is serum creatinine. So in this graphic on the left-hand side of the screen, you see a white female, age 60, with a serum creatinine of 1.3. For that woman, that gives her an estimated glomerular filtration rate of 44. If you take a male who's also white, also age 60, and also has a serum creatinine of 1.3, that person actually has a glomerular filtration of almost 60, suggesting that their kidney function is actually better for a given creatinine than a woman with the same creatinine measure. And why does that matter? Well, let's take that female patient, for example, and let's calculate her MELD score. She's got a bilirubin of 4, a sodium of 140, an INR of 2, and that creatinine of 1.3. Well, that gives her a MELD score of 22. So what about the male on the other side? Well, if we were going to have a man that had the same GFR as the woman with a creatinine of 1.3, he'd have to have a creatinine of 1.7. You can see that gives him a GFR of about the same. And with that creatinine of 1.7 holding the bilirubin, sodium, and INR constant, you can see that the MELD score increases to 25. So what does a difference in MELD scores between 22 and 25 translate to? Well, if you look at my center and you take a patient with a MELD score between 15 and 24, you can see that the number of patients that are still waiting at 30 days is about 91% of the patients. What happens when that MELD score increases to the 25 to 29 range? Well, only 63% of those patients are still waiting at 30 days. So that small difference in MELD score greatly impacts the likelihood of that individual candidate achieving transplant. And because MELD utilizes serum creatinine, which is a poor measure of glomerular filtration, it introduced gender-based disparities. And the potential solution that has been put forth a number of years ago is to replace creatinine with EGFR. And you can see if you look on the left-hand side of the screen at MELD category by serum creatinine, you can see it keeps men and women roughly the same. Whereas if you look at EGFR-based, you can see that it helps push women into higher MELD categories. And so I think having EGFR as part of MELD probably makes a lot more sense than serum creatinine-based. The second assumption is that the patient at the top of the list actually receives the liver for transplant. Yet we know that donor-recipient size mismatch was reported as a reason for declining in organ four times more commonly than any other reason. And this is particularly true for women and in particular, small women. So if you look at small women compared to small men, on adjusted analyses, 1.2 times less likely or more likely to have an organ declined, excuse me, for size compared to their small male counterparts. But what's really interesting and really disturbing is that if you compare small women to small men, you can see that small women compared to an average size man are 1.4 times more likely to have an organ declined for size. Whereas if you compare small men to an average size male, they're only 1.17 times more likely. And again, that suggests that there are gender biases and that women are much more likely to have an organ turned down for them because of size differences compared to men. And that's even true when men and women are relatively the same size. And I think that really begs the question, do we have implicit biases? When we look at women, do we think that they look smaller than a similar size male? Do we have some sort of implicit bias driving this? And I think it's a subject that needs further study. And I would argue that size absolutely matters. So what's the potential solution to problem number two? Well, I would say that a potential solution is exception points. So let's look at that because there is precedent for this. On the right-hand side of the screen in figure B, this is looking at median calculated male score at transplant. And you can see that there really aren't major geographic disparities in that other than in the sort of West Coast that includes California. Yet despite this, we decided to suggest that there are geographic disparities because instead of using calculated male, we looked at allocation male, which of course is a biased measure because that involves giving exception points, right? So why then if we decided to give exception points for hepatocellular carcinoma, for example, which is a largely male-driven disease, why can't we give exception points for women when they are of smaller stature and smaller size, such that their male increases and it gives them more swings at the bat, something that I think we need to consider. So liver allocation, are the assumptions true? And I would say no, they're not. And we've looked at this further, and this is looking at weightless mortality and looking at what disparity actually attributes the most gender-based disparities in liver allocation. And if you look at the figure, geography contributes very little to weightless mortality. Lab meld or that serum creatinine measure contributes more, and size is the biggest contributor of disparity in weightless mortality between men and women. And if you look at the same study, but you look at transplant rate, again, size here is the biggest contributor of the disparity between men and women. So liver allocation disparities, are there other things that we need to think about? And I'll end by sort of circling us back to pregnancy related issues. And I would argue that pregnancy related sensitization may exacerbate the problem. So let's take a few lessons learned from kidney transplantation. So what is sensitization? Well, it's a recipient state in which HLA antibodies are circulating in the blood and create a potential for a rapid production of HLA antibodies after transplantation through an immune memory response. We measure it through something called panel reactive antibody. And in kidney transplantation, the likelihood of finding a compatible match is roughly 100 minus the PRA. So the higher your PRA, the less likely you are to find a compatible match. And you're sensitized through exposure to foreign antigen, through blood transfusions, prior transplants, and pregnancy, which is a state that is unique to the female gender. We know pregnancy related sensitization occurs. 50 to 75% of women have detectable HLA antibody at the time of delivery. Many women develop these antibodies in the first trimester. And we know that HLA antibody formation increases over the course of gestation. As I mentioned, it increases between the first and second pregnancies. Antibodies increase within 90 days of delivery. And anti-HLA antibody has been demonstrated to disappear in some cases. But importantly, even when it disappears, there is a primed memory arm that is ready to create problems in the setting of foreign antigen exposure, again, i.e. in the form of a transplant. We know that this sensitization impacts access to transplant. Women are more likely than men to be listed with a high CPRA. They represent more than 60% of kidney transplant recipients, the CPRA greater than 98%. And the difference in CPRA between men and women likely contributes to longer waitlist times. And this is some great work done by Dr. Port that basically shows that in a single center study that women are more likely to be listed with high CPRA and that this is in large part driven by pregnancy. She went on to show that women are more likely to be incompatible with more than one living kidney donor. And again, this is related to pregnancy related sensitization. We know that if we introduce things like incompatible kidney transplant programs, and we really go after how we might get these individuals transplanted, that we see a more than 100% increase in the likelihood of living donor kidney transplantation. And this is particularly true among sensitized minority women who are much more likely to be multi-paris. They see a fourfold increase in the likelihood of transplant. So how does this path result as a potential solution in the setting of sex-based disparities in liver transplant? Well, perhaps there should be priority points in kidney transplantation. We give priority points based on CPRA, such that patients with CPRAs of 100% have access to a national pool of organs. Should we be doing that in the setting of liver transplantation and particularly SLA, or excuse me, SLK transplantation. And you can see when we instituted this in kidney, the number of transplants for high CPRA patients went up exponentially. And I would argue that we need to really consider the role of preformed antibodies and liver transplantation and how avoiding these could improve outcomes in liver alone, as well as increasing access to SLK for our sensitized women. So in conclusion, disparities do exist in liver allocation, but we can overcome them. I think there are solutions. I think they're obvious. Number one, we need to update MELD to account for sex-based disparities in serum creatinine. We should consider exception points for size to create equity and access for small women. And we should consider exception points for sensitization related to pregnancy so that we can increase access for our patients with regard to SLK and potentially improve outcomes after liver alone. So at the end of the day, I'm with her. So thank you very much for your attention and I look forward to answering questions. Well, thank you everyone for joining our women's health and liver disease case discussion. Dr. Orloff and I have prepared a couple of cases for our panelists, Dr. Coongar, Michael Hennigan, Laura Kulik, and Jamie Locke. So we'll jump into our first case of a 36-year-old woman with primary sclerosing cholangitis. She has recurrent cholangitis and has now progressed on to have cirrhosis with portal hypertension. On lab, she has a sodium level of 140, creatinine of 0.6, her bilirubin 7, and INR is 1.5 for calculated MELD sodium of 18. She's thrombocytopenic with a platelet count of 70,000 and her albumin level is 3.5. She has no complications of volume overload or encephalopathy. She has had non-bleeding varices that have required banding. Her paritis is well managed on cholestyramine. She has a four-year-old son and she's also interested in having a second pregnancy. Her first pregnancy was complicated by intrapartic cholestasis of pregnancy, but otherwise no liver-related issues or adverse outcomes for her son. She does have a potential live donor and she wants to discuss with you whether to pursue pregnancy now in the setting of having portal hypertension versus waiting until after her living donor liver transplant. So I'll turn it over to our panelists to ask how you counsel her thinking about the pros and cons of pregnancy across time periods. So one of the things that I would take into account is her age. If she clearly has portal hypertension, so there is some risk to her in terms of her esophageal varices and she would need to be seen by high-risk OB-GYN and be at a place where she could be seen quickly if there was an emergency. So her age would be important because if she undergoes a living donor, we know that that could take some time to identify the donor. And then once she has had the transplant, you know, depending on each center's preference, there's going to be a time period where they would want to wait a period of time, generally up to two years before telling her to try to get pregnant. So depending on what her age is and how easy it was for her to get pregnant the first time, I think that that would be something that would be important in terms of my discussion with her. I agree completely. I think this is really kind of a collaborative decision. So I would reach out to the patient's OB-GYN and I would say, what is this patient's general fertility profile at this point? Are there any considerations that I need to be aware of as her treating hepatologist? And then I would ask the patient what their general family plan was, as Laura said. But I think also we need to have more crosstalk because often we operate in these silos and we think that the patient, we're doing what's right for the patient, but it may either not be in line with their wishes or in keeping with standard of care for their OB practice. I'm sure it was not by chance that this woman also had ICP with her first pregnancy, which obviously is going to make it a little bit more difficult to discern what is going on if she does become pregnant, especially during that timeframe. Is this her PSC that's worsening? Using any kind of contrast dye, specifically gadolinium during pregnancy can be of concern. We can do an MRCP without gadolinium, but it just makes the whole situation a little bit more complicated in terms of symptoms that she may have if she undergoes her pregnancy prior to getting out her liver that is disease. And maybe I'll ask Dr. Hennigan. So what if she also wants to seek some infertility treatment, like thinking about IVF? Do we know about how outcomes look for women who chronic liver disease or she's having complications or difficulty getting pregnant after transplant, thinking about IVF in that context? For the situation of IVF, what we absolutely know is that for patients with established cirrhosis, their outcomes, based on very, very small numbers, is not fantastic. With, from our data, really just a live birth rate of about 44% for women with cirrhosis. So if you contrast that with the safety of IVF in post-transplant patients, which was a bigger cohort in our study, actually, while the outcomes aren't as good as in women who have chronic liver disease without cirrhosis, actually, the outcomes are better, around 50%. I think that the challenge is not so much deciding on whether or not IVF is warranted in this sort of situation. I think in clinical practice, many women will just fall pregnant with established cirrhosis. And actually, that becomes the bigger challenge because you're always on the back foot. And I think that is probably where we have evolved our experience in clinical practice. And I'm sure many of you will have that experience. You have somebody who may have subfertility, but actually is menstruating, is ovulating, and they're presenting with a pregnancy at eight or 10 weeks. And that is the bigger challenge for us as hepatologists. So I'd be interested in the other speakers in their views in relation to that and how we manage that. I think, of course, like you said, we've all run into this problem. And so it really depends on whether the patient is decompensated or compensated and to what degree, and then to what degree do they want to keep this pregnancy. And it's a very personal decision and we tend to be paternalistic in medicine. So we try to give some agency to the patient while making sure that they're obtaining full informed consent of what their risks are. So I think that banding at appropriate times of varices, of portal hypertension's present like with this patient, and just much more close monitoring and even co-visits with OB are recommended. And people are so stressed for time. And then especially if this isn't something that you think about, the idea of reproductive health, how do you incorporate that into your visit to be asking these questions or making sure you, you're going through the laundry list of other things that are more imminently dangerous regarding adjusting their medications and making sure you're doing all of the treatments that you can to keep portal hypertensive complications under control. So when are you addressing this with patients? How much time are you spending doing it? And how do you remember? So I would say, fortunately, we have not had, have not seen many women of childbearing age with cirrhosis, but that is changing now that alcohol induced liver disease is becoming more prominent. And we are seeing people in their twenties who have cirrhosis from alcohol. And the way that I usually address it is when they come in the first time, I will ask them what are their plans for pregnancy? A lot of times they say, I have no plans right now, but I would like to become pregnant at some point. And that's when I will kind of discuss with them, you know, what the chances of pregnancy may be lower because of their underlying cirrhosis. They may need to take that into account that it may be more difficult to become pregnant. I then tell them very clearly that if they do become pregnant, that they do need to see again and establish a high risk OB-GYN. And then go about talking about what could happen if pregnant. Doing the banding, controlling ascites, talking about not using L-dactone if it's a male fetus, all those types of things. And then I even go so far as to talk about if there were to be something catastrophic, talking about tips and what we would do and having these things kind of planned. But not everyone lives around the corner from a transplant center. So it becomes really important, I think, for patients to understand what is involved in some of these patients who have cirrhosis and really want to have a child. And as a non-hepatologist on the panel, just I don't usually see these patients who are actually referred for transplant as when I'm evaluating them as the transplant surgeon. And so certainly all of our female patients of childbearing age, this is something that we try to address at the outset. And I think Dr. Hennigan really hit on it. I think the idea is that if we do this, ideally it's planned. It's something that we're having a conversation about and know it's really hard when it's not planned and sort of having those conversations upfront and really, I think, educating them and making sure they're aware of the risks so that they can sort of make that a part of their care plan as it relates to their sort of journey along the journey of transplant. And I think that's important because I think there's a misconception that once you have a transplant amongst patients that you can't have a child, that they feel like something happens where they're not able to have children. As Dr. Hennigan said, it's not as robust in terms of their ability to conceive, but it's certainly not zero. So educating them that this is a possibility and then also talking to them about the immunosuppression and cell cell, et cetera, medications that would be worrisome at the time of conception and knowing and needing to get a good enough lead time as to when they're gonna plan to start trying so that medications can be adjusted. Yeah, and I would just echo, I think, what Dr. Kulik said, which is you have to say it at every meeting or every visit with a patient who has reproductive potential, whether that's a woman, a transgender patient, somebody who's gender nonconforming, and sometimes we'll forget about that in certain visits. And I've actually incorporated it in my template after we wrote the reproductive health guidance document because before I was forgetting to mention that at every visit. So I think it is important to remind ourselves because it's not one of the standard decompensations that we worry about. And then like Dr. Locke said, after transplant, often patients, I've actually seen several patients become pregnant with unintentionally post-transplant because their axis finally reverted to normal. And although they were not menstruating, they were ovulating. So I think we have to be hypervigilant in the post-transplant period. I think it's also worth stating that actually, even though the recommendations and the guidelines suggest a year of stability, good graft function, a graft that's embedded, actually there are reasonable outcomes even within that first year after transplant if there is an inadvertent pregnancy. And indeed, although there are some concerns with regard to rejection post-transplant, the data in itself, as limited as it is, the acute cellular rejection rates are less than 10%. The graft loss as a consequence of an unintended pregnancy within even one to two years is actually really quite low. So I think we're better at adjusting and being prepared post-transplant. Where we're less good is for women who may fall pregnant while they're still taking microphenolate based immunosuppression. And that's the bigger risk in that post-transplant phase. You have good graft function, but actually you have an immunosuppression burden that is very problematic. And that can be a really difficult discussion when you have patients who fall pregnant on microphenolate and you're saying there's a really significant high risk of a significant malformation. Yeah, I think it's really important to have those conversations about what is your birth control plan. I think that's absolutely critical for that reason specifically. And having sort of had to help patients through that sort of not intending to get pregnant end up coming in sort of in that 10 to 12 week mark and they've been on microphenolate the whole time. It's really tragic. And so making sure that that's part of the decision that that's part of the transplant evaluation discussion, it's part of that initial hospitalization. Hey, when you leave, like what's your plan? When are we starting this? In the same way that you think through all the sort of opportunistic prophylaxis, I think birth control plans need to be a part of the discussions with our patients. I think it's really critical. And I think Dr. Kumgar had some discussions about this in her talk, really trying to dispel some of the myths about what had previously thought to be harmful hormonal exposures in our patients. And so I think for a lot of practitioners, it's historically been thought that they can't be, if they have cirrhosis, maybe estrogen containing agents might be harmful, older data about concerns regarding intrauterine devices and patients who've had transplants. And so I think it seems like we're trying to catch up with really understanding what those true risks are and trying to dispel some of these myths so that we're having more of an engaging conversation with patients and connecting them with effective contraception that works for their lifestyle, but throughout the course and making sure that they are having those conversations with their obstetricians. Yeah, I really appreciate everybody's discussion points and your input. It's fascinating to think about this topic, which we didn't even think about 20 years ago. I have a little bit of elephant in the room question. And that is, if this particular patient that we're discussing is open to adoption amongst the panelists, would you persuade her to go that route given that she's had intrapanic coastal pregnancy? If she were up for that, or would you say we'll take the risks and go for it? What would you advise if she were totally open to adoption, but still wanted to go the natural route if possible? I'm just curious as to what each of the panelists think. I think that's a great and very difficult question. And I like the way that OBs phrase it when they speak to their patients, which is to say, what is your ideal vision for having a child? And then what other visions would you be okay with? And so I think I would ask it in that way. And if the patient says, I would be fine with adoption, I would ask them to elaborate more and say, do you mean fine as in it's a distant second to having your own biological child and then go through with them what the risks are? Especially if it's a patient who can understand and make those calculations, I would let them make the decision at the end of it. I don't think I would sway them one way or the other, but that is wild to hear that 20 years ago we weren't having this discussion. So I'm glad we're here. No, it is a good point. I've had to sign papers for a patient who wanted to get a child via adoption and not go through the risk of pregnancy with cirrhosis. And it can be a little bit more challenging for patients who have any chronic underlying condition because they're worried about what is the life expectancy of that parent. So having to say that cirrhosis can be a little bit, you don't really know what's going to happen and if someone's going to require a transplant in a way that is not putting that patient at complete risk of being turned down as being an adoptive parent while being honest at the same time. It's a good point. And there seems to be such complexity around the psychosocial resources that you have available when you're thinking about what you need, the whole process of going through adoption. And then on the other hand, still thinking about what it's like to have a child in the pre-transplant time period versus post where we require people to have really dedicated social support for being a recipient of transplants. And then you need somebody who's going to be able to be that support for the children as well. And then as well as support for the donor. So I think there's some added complexity especially if the donor is a partner, is a spouse. So there's a lot that goes into it that we have to think about beyond the medical management that's directly in front of our eyes. It's so intricately involved and relevant to the outcomes of our patients. I think we also have a lot to learn from the oncology community because they've been doing this successfully for much longer than we have. And it is a regular component of their visits. So I think really we should borrow from how they approach their patients realizing that certain chemotherapies create risk for pregnancies. Granted the pre-op or the pre-treatment stage in cancer is different than being a pre-transplant liver patient. But I think we can borrow from their tactics because we as a field are definitely behind in discussing reproductive health with our patients. Fantastic. Well, thank you all. We're going to move on to the second case. We'll turn this over to Dr. Orla. Okay. This is sort of an extension of the first case. So the patient from case one has a close friend approved for live donation. She too, meaning the friend wants to start a family down the road. And so does live liver donation influence future fertility or pregnancy risks? And also what about kidney donation? Would you consider if this live donor were 30 versus 40, would there be a change in your counseling and your advice how to proceed? Because, you know, given age is a factor especially age on top of wanting to get pregnant and fertility issues. So let's throw that out there. First of all, you know, what would you do with a 30 year old best friend that wants to become pregnant at some time versus the 40 year old best friend that also wants to be a live donor but wants to have a family soon and a biologic child if possible. So we'll throw that one out there. So these are not easy scenarios. And obviously, this is not something that is that pertinent in Europe, particularly for a live donation has really not been as prominent as a source of organs. I think in approaching any woman who is potentially donating, I have to say that, and I've assessed many donors over a 20, 25 year career. This is not a discussion that I have, I believe ever had and shame on me for not even thinking about it. It hasn't actually come up. And I guess what you want to do is you want to choose your program very carefully because obviously you want a relatively straightforward operation. You do not want any complications. And of course, this is where the experience of the total program becomes really important in how you advise any patient. But shame on me for not even thinking about that. I don't think it's actually shame on you. I think that a lot of our patients as female physicians will be much more open with us about their pregnancy desires. So that may be a big part of it because we actually just turned down a donor for this reason. She's in her late thirties. It's an absolute desire of hers to have a biological child. So we moved down the list to the next donor because we knew if we delayed her too long, that may not be a possibility for her. So I think if the 40-year-old said it to me, I might try to look for other donors for this patient. Yeah, I agree with everything that's been said. I worry a little bit less about the younger donor in terms of living liver donation and a little bit more in terms of living kidney donation just because there is a slightly higher risk for preeclampsia in previous living kidney donors. I do worry a little bit about that. And I think with the 40-year-old individual in both cases, I would sort of try to move on to the next donor for fear that it would hang them up in the system and they'd kind of miss their window and that age puts them at high risk anyway. So I sort of wouldn't want to complicate that for them and prefer them to have the pregnancy, recover from that if they were still interested, we could reconsider at a later time. Is there a timeframe for the surgeons after a pregnancy taking out all the, you know, the psychosocial, the stress of being a new mom, taking care of the child, et cetera, if that was, you know, something that could magically be wiped away. But from a liver standpoint, I remember our surgeons always saying that a woman who is pregnant, that the liver becomes almost like butter in terms of the consistency that you would advise not doing a live donor transplant for that donor because they were just pregnant. Is there a timeframe that you would want to see their liver kind of go back to its pre-pregnancy state? Yeah, we always sort of hang our hat around a year is what we like. It doesn't take a year for the liver to get back to that state, but I think there's just a lot of physiologic changes that occur with pregnancy. I think making sure that the mom is completely recovered, the thought of trying to be a living donor when you're still breastfeeding is not, I think it's very challenging. And so there's a lot of things that go into that. And so we sort of just tell folks that ideally a year after the pregnancy is when we would consider having a conversation about proceeding with living donation. I want to thank all of our panelists for contributing to another successful reproductive health session and for this engaging conversation. And we will see you again next year. Thanks all, appreciate it. Appreciate your expertise and your opinion and your openness as well as your brains. Thank you so much. Well, thank you so much for such a fabulous session covering so many topics that are pertinent and really impactful to pregnancy and liver disease, as well as looking at sex disparities in allocation, which is really an up and coming topic. I want to thank my co-moderator, Monica Sarkar for accompanying me on this wonderful journey, listening to these experts. And I want to thank them and their lively discussion, not only in their presentations, but also in the case discussions. And so I thank all of you. I think this has been a really great session and I think we should continue to support this for the ever ending future. And I also want to put a pitch in for, in half an hour at six o'clock, there is a program that's being put on by the Women's Initiative Committee for the ASLD and that is a networking reception for women where Katrina Lake, the daughter of the famous, of course, Jack Lake, who was the actually founder and CEO of Stitch Fix. And she will talk about her journey. And then Dr. Jen Fleming will introduce to you something that we're really excited about. And that is a longitudinal program for female junior hepatologists in leadership development. And this is through mentoring and also the mentees perspective and applications will be open soon. You'll hear more about that. So please stay tuned and come to the women's reception and networking in half an hour. Thanks again to everybody and have a great afternoon. Bye-bye.

Women's Health and Liver Disease Program

reproductive health

liver disease

fertility

contraceptive options

cirrhosis and pregnancy

holistic patient care

contraceptive education

assisted reproduction

comprehensive care

reproductive goals

hepatology