Liver Complications After Transplant

Note: In the following discussion, the term “bone marrow transplants” also refers to “stem cell transplants.” 

Transcript of Presentation:  

(00:00): Susan Stewart: Introduction. Welcome to the workshop Liver Complications After Transplant. My name is Sue Stewart and I will be your moderator for this workshop.

(00:09): It's now my pleasure to introduce to you today's speaker, Dr. Manhal Izzy. Dr. Izzy. is an Associate Professor of Medicine and Director of Hepatology Research in the Division of Gastroenterology, Hepatology, and Nutrition at Vanderbilt University Medical Center. He specializes in the clinical management of patients with liver disorders and also serves on the editorial board for Liver Transplantation and serves as an ad hoc reviewer for multiple gastroenterology and hepatology journals. Please join me in welcoming Dr. Izzy.

(00:51): Dr. Izzy: Overview of Talk. Hello everyone. Thank you very much for the kind introduction and I appreciate the invitation. It is my pleasure to talk today about liver complications after bone marrow transplant. This presentation aims to help patients and their caregivers understand potential liver complications and the risk factors for them after bone marrow transplant.

(01:22): Over the next hour or so, we'll discuss information that's sufficient to identify types and symptoms of liver complications that can occur post-transplant as well as identifying the risk factors for those complications. Toward the end of the presentation, we should have a good understanding of the outcomes and treatment of post-bone marrow transplant liver-related complications.

(01:54): The liver is a vital organ performing several important functions. The liver is an organ located here in the right upper quadrant of the belly, where the red arrow is. The liver is important not because it's my specialty, but because it's very important for filtering toxins and waste from the blood.

(02:11): It helps digest food because the liver produces bile, which is a yellow to golden pigment, and that bile goes to the intestine where it helps digest the fat component of the food that is going through the intestine.

(02:35): The liver also acts as a storage pool for energy in the form of glycogen, a type of sugar, so when the body needs it, it can be consumed. Think of it as an energy bank for the body.

(02:52): Moreover, the liver produces proteins. Those proteins can help manage our clotting abilities, and they can help fight infections. It produces what we call globulins, which are proteins that have the capacity to combat bacterial and viral infections.

(03:18): When discussing liver disease after a bone marrow transplant, we are referring to four categories. Number one is medication-induced liver disease or medication-induced liver injury. This goes into two types of injury, where the medication directly impacts either a) the liver cells or the liver, or b) the blood flow inside the liver, which will then affect the liver cells. Either way, it's a problem that's directly related to the medication consumed by the patient.

(03:58): The second type of liver disease is graft-versus-host disease (GVHD), which occurs when the cells from the donor attack the cells of the recipient.

(04:12): The third type is liver disease that could be pre-existing, pre-dating the bone marrow transplant. If a patient has fatty liver disease or iron accumulation in the liver from before the bone marrow transplant, it can continue to evolve and eventually cause manifestations of liver disease after bone marrow transplant. It's not directly related to bone marrow transplants, but it's the natural evolution of liver disease that pre-existed the bone marrow transplant, and the bone marrow transplant happens at some point during the course of this liver disease.

(04:49): Last is viral infection. Viral liver disease after bone marrow transplant can be due to immunosuppression or due to acquiring a virus from the environment. These are the four main categories of liver disease: medication induced, GVHD, pre-existing, and viral.

(05:08): Whenever we talk about liver disease, we must understand that the liver is like any other organ. If you have an injury like a cut to your hand, it will have a scar later. Likewise, if we injure the liver with fat in the liver, iron in the liver, chronic medication use, or viruses that exist there and affect the liver for a long time, then the liver will end up with a scar. That scarring evolves inside the liver into four stages. Stage four is what we call cirrhosis.

(05:46): Stage four scarring is a synonym for cirrhosis. When the patient has cirrhosis, the scar tissue has the potential to evolve into liver cancer, which happens in about 3-5% of the patients with cirrhosis every year. Every year, out of every 100 people with cirrhosis, three to five of them may have liver cancer. That's why we do ultrasounds for our patients with cirrhosis every six months – to try to catch that cancer early, because that is a curable cancer, it can be cured if it's detected very early.

(06:33): Symptoms of liver disease don’t appear until the disease is very advanced. What are the symptoms of liver disease? When we talk about liver disease, it is typically a silent troublemaker, so we won't see symptoms until things are very advanced. We can appreciate signs of liver disease, such as elevated liver enzymes and things like that, early in the course of the disease, but the symptoms develop later in the course, toward the advanced stage, such as cirrhosis or advanced liver disease.

(07:08): There are mainly four symptoms of liver disease. There's ascites, which means fluid buildup in the belly – suddenly the belly is significantly distended, and the patient is very uncomfortable. The belly doubles in size within a few days, which is different than the bloating that we get sometimes from gases after eating and things like that. This is a much more remarkable increase in the belly size.

(07:41): Ascites is usually confirmed with an ultrasound that shows fluid in the belly. It will need to be drained and analyzed because, while liver disease is the reason for ascites in 90% of cases, 10% of cases are from other reasons. Therefore, we need to analyze the fluid and check its chemical characteristics to determine if it's truly indicative of liver disease or if it's from another source.

(08:09): Yellowness in the eyes and skin can be another symptom of liver disease. We also can see yellowness in the eyes and in the skin because, when bilirubin (which is a yellow to gold pigment) goes into the blood, it will manifest as yellow color in the white part of the eyes or as yellowing of the skin.

(08:34): The other manifestation of liver disease is confusion. The fancy name for this is hepatic encephalopathy. One of the functions of the liver is to clear the toxins from the body. When the liver cannot do that because it's very sick, those toxins can go to the brain and cause confusion. That's why confusion is one of the signs of very advanced liver disease.

(09:04): The last symptom is bleeding from the gut. When there is bleeding from the gut, it manifests either as throwing up blood or defecating blood, i.e., it comes out either from the mouth or from the bottom. That usually reflects that the veins in the gut of the patient with cirrhosis have opened up because of the high pressure inside of them and are bleeding. That's an indication of advanced liver disease, an indication to rush to the emergency room.

(09:40): What test can be utilized to diagnose liver disease? Liver disease is typically a silent troublemaker because it doesn't cause symptoms until it's very late. So how can we catch it early on?

(09:57): There are three ways to diagnose liver disease; blood tests, imaging studies, and biopsy. We have three tools to catch it. First, we have blood tests that can show elevated liver enzymes like bilirubin.  Second, we have imaging studies such as ultrasound, CAT scan or MRI, or elastography to assess the liver's stiffness from scarring.  Liver scar tissue is stiff tissue, just as a scar on the skin is stiffer than normal skin. Scarring means there's something going on that is not normal.

(10:31): Last is liver biopsy. The radiologist will insert a needle through the belly or through the neck veins and take a tiny specimen from the liver. These are our three tools to assess liver disease and to assess its type: blood tests, imaging, and biopsy.

(10:55): Medication-induced liver injury can arise from transplant medications or supplements. Let's talk about medication-induced liver injury. The other name is drug-induced liver injury and it's abbreviated as DILI. In DILI the liver cells are injured either by medications used during the bone marrow transplant patient or by a supplement.

(11:18): It's very common now to take supplements – everyone wants to be healthier. The problem is that the liver is very sensitive to these supplements. In fact, one of the most common causes of liver injury in the United States is supplements, also called alternative medicine.

(11:39): An example of this is green tea extract. While green tea as a drink is believed to be beneficial and an antioxidant, the concentrated form has been proven to be very injurious and, in fact, devastating to the liver.

(12:02): How do we diagnose this type of injury? We look at the liver enzymes called aspartic transaminase (AST), alanine aminotransferase (ALT), and total bilirubin. We look at these and, if they're elevated, that is a sign of drug-induced liver injury.

(12:19): Sometimes the liver enzymes can tell you that the liver is irritated, and even though you do blood work to find out what is bothering the liver, you can't find the reason, so you do a liver biopsy. Sometimes you stop the medication before you consider the biopsy to see if the liver enzymes improve upon discontinuation of the medication. In most cases of drug-induced, medication-induced, or supplement-induced liver injury, the liver labs would show you improvement within a week or two. But if blood tests and waiting provide no clue on why this is not improving, then the key is through a liver biopsy.

(13:17): The other type of medication-induced injury is medication-induced blood flow impairment – the blood that's flowing through the liver gets impaired by the medication. How is that possible?

(13:34): There are tiny blood vessels in the liver that supply the liver cells with blood. Sometimes, certain types of chemotherapy, such as high-dose chemotherapy, can cause those tiny vessels to be blocked. When they're blocked, it's harder for the liver to function because it's not getting the blood that it needs. The patient turns yellow, they may develop fluid in the belly (ascites), and the liver will be very congested and become enlarged.

(14:18): Not all three of these symptoms need to happen. Sometimes one of them, sometimes two of them. The symptom would be the trigger to make us check the blood work, and then the blood will show elevation in liver enzymes, AST, ALT, alkaline phosphatase, or in the total bilirubin, the same marker that can cause DILI that we talked about.

(14:47): Only a liver biopsy can provide a definitive diagnosis of liver disease. When we see this, the only way to make sure this is the diagnosis is to do a liver biopsy. We do liver biopsy for these patients to confirm the diagnosis when the blood testing does not reveal any other cause, for example, no viral infection, nothing else that can explain the elevation in liver enzymes.

(15:08): What do you do then? It's really supportive care. If the patient's having ascites or fluid buildup in the belly, you give them diuretics and cut down on their salt intake to try to get them to pee out the fluid that's building up. You stop the medications or the high-dose chemotherapy that could have caused this.

(15:30): There's a medication called defibrotide (Defitelio) that may help but more studies are needed to figure out the exact benefit of it. But as of today, this is largely supportive treatment, treating the symptoms and stopping the drug. That works for many patients with this problem.

(15:54): The second category of the four types of liver disease is graft versus host disease (GVHD). That means the donor cells are attacking the host, i.e., the bone marrow transplant recipient, and specifically they're attacking the host’s liver cells.

(16:16): There are certain factors that increase the risk for this, such as older aged donors, older aged recipients, history of viral infection, or mismatch between the donor and the recipient.

(16:31): The diagnosis of GVHD can be challenging because the symptoms are not very specific. They could be as simple as a skin rash, or it could be just an upset stomach. But if we see liver enzyme elevation in a bone marrow transplant recipient combined with a skin rash, then GVHD, or graft versus host disease, comes to mind. This is another disease that really needs tissue specimens to prove it.

(17:03): What do you do when you diagnose GVHD? Immunosuppression is the key because this is an attack from the donor cells on the recipient's cells, so we need to calm down those donor cells, lower their immune potential. Immunosuppression is the key for that. When we use immunosuppression, the patient will be at risk of infection, so, along with immunosuppression, we work with our partners in the bone marrow transplant team on giving medications to prevent fungal, bacterial and viral infection.

(17:47): This entity of graft versus host can happen either early on following transplant, within the first 100 days or three months (known as acute), or beyond that, which we call chronic or late. It's not exclusive to early on; it can happen at any point post-transplant.

(18:07): Signs that would raise concern for GVHD are skin rash and GI upset. Those would trigger further investigation to see if it affects the liver or not. Not all graft versus host disease affects the liver, but sometimes it can, so GVHD is one of the liver diseases after bone marrow transplant.

(18:32): The third type of liver disease is pre-existing liver disease, which involves something that happened prior to bone marrow transplant and has nothing to do with bone marrow transplant. The most common example of this is fatty liver disease, which is fat accumulation in the liver. That happens because of what we call metabolic dysfunction, i.e., there is a problem in the patient’s metabolism. The most common feature that we see in patients with fatty liver disease is being overweight. The other source for fat accumulation in the liver is alcohol.

(19:12): Pre-existing liver disease can arise from fat in the liver, alcohol, or iron deposits. When we see fat in the liver, there are two processes that can lead to it, number one being overweight. When that is the case, some of the fat that's in the belly, that we call visceral adiposity, transmits through blood circulation to the liver and sits there and deposits there, which can cause liver scarring and cirrhosis.

(19:46): The other source or cause is alcohol. When we drink alcohol, it converts in the body to fat, and that fat also gets stored or deposited in the liver, which then causes injury to the liver, including elevation of liver enzymes, scarring, cirrhosis, and then cancer.

(20:09): The other material that can deposit in the liver is iron, especially in patients with bone marrow transplant and prior blood disorders, which often require prior blood transfusion. The fancy name for that condition is hemochromatosis.

(20:26): How do we deal with these conditions? Metabolic dysfunction associated with steatotic liver disease (i.e., fatty liver disease) is very common. The estimate is that up to 40% of the United States have fatty liver disease and it is estimated that, by 2030, half of the country will have fatty liver disease because being overweight is very common. Metabolic derangements such as diabetes, being overweight, or having high blood pressure or high cholesterol, are very common, and all of these things increase the risk for developing fat deposits in the liver.

(21:15): How do we diagnose it? We may see elevated liver enzymes in patients with fatty liver disease, but that's not always the case. Over 20% of patients with fatty liver disease have perfectly normal liver enzymes, so that's not enough of a sign. The other way is through imaging.  Patients receiving a bone marrow transplant get imaging assessments beforehand, and fat in the liver is something you see on CT ultrasound or MRI.

(21:54): The treatment will depend on the stage of liver scarring, which is assessed by special blood testing or more commonly by special imaging called elastography, which assesses how stiff the liver is.  How scarred the liver is determines the stage of scarring. In patients with no scarring at all, to resolve the fat deposits in the liver, they need to lose at least 5-7% of their current body weight.

(22:45): However, once scarring occurs, even if it's stage one, very early, the patient needs to lose at least 10% of their body weight to eliminate the scarring and fat in the liver. Now, that doesn't mean that people should starve themselves and start dieting extensively and lose 10% in two weeks. No, this could be over three to six months, a slow but sustainable process.

(23:03): Stage two or three liver scarring is treated with weight loss and a medication called resmetirom (Rezdiffra). If there is stage two or three scarring in the liver, in addition to the minimum of 10% of the current body weight that needs to be lost, there is a medication that was approved by the FDA last year, called resmetirom (Rezdiffra). It works on the liver specifically to help reverse the scarring and the fat in these patients. The success rate for the medication to reverse either the fat or the scarring in the liver is about 50%. That's along with weight loss, which gives the patient a much higher likelihood of resolving scarring.

(23:52): Cirrhosis, which is stage four scarring, is not reversible in most patients. It could be reversible if it's caught very, very early before developing any complication of it, before causing increased pressure in the veins around the liver, which we call portal hypertension. If cirrhosis is caught just after it has developed, it may reverse. That's unlikely but possible.

(24:22): Weight loss is helpful, whether the cirrhosis is reversible early or not, because when you optimize the weight, the fat in the liver will be gone and that helps slow the progression of cirrhosis to end stage liver disease. In general, weight loss is helpful throughout the spectrum of fatty liver disease. If there is stage two or three scarring in addition to weight loss, there is an FDA-approved medication available to help with that.

(25:01): Iron buildup is a common cause of liver disease in transplant patients due to blood transfusions. Hemochromatosis is literally iron buildup in the liver and liver cells. It causes injury, it causes scarring. Its most common cause, in patients who are bone marrow transplant recipients, is repetitive blood transfusions. There are patients who have hereditary hemochromatosis, but that's a much less common scenario with bone marrow transplant than with secondary hemochromatosis, which comes from repetitive blood transfusion.

(25:36): We identify hemochromatosis through blood tests showing elevated liver enzymes, and that pushes us to assess the appearance of the liver on imaging where we can see the iron on the liver MRI.

(25:49): How do you treat it? You need to address the root cause, which is blood transfusions. We need to minimize blood transfusions, and sometimes our hematology experts may recommend deferoxamine (Desferal), which is a medication to remove the excess iron from the body.

(26:09): The last of the four general categories of liver disease is viral hepatitis, and we have four categories of viral hepatitis: hepatitis A and E, which we get from food, and hepatitis B and C, which we get through blood contamination or sexual intercourse.

(26:43): For hepatitis A, the common sources are undercooked food, contaminated water, close contact with infected individuals (such as sharing a spoon), and poor sanitation. Sometimes we see it in individuals who deal with plumbing and other jobs that entail contact with dirty water.

(27:21): The good thing about hepatitis A is that it is generally an acute infection; it's not chronic. And the better news is that it is a virus that you can vaccinate against and that's what we recommend for all of our liver transplant patients, and we recommend it also for bone marrow transplant patients. There is no treatment needed, and it goes away on its own, so it's a self-limited infection, and it is rarely a life-threatening infection. It can happen in patients with cirrhosis which can be life-threatening, but for patients with an intact liver, it's rarely a problem.

(28:06): Hepatitis E comes from handling raw pork or raw deer meat. These are the two most common types of meat that can lead to this infection. It can happen by handling it, like working in a meat factory, or eating these types of meats raw or semi-raw. It's rarely chronic, but in patients with immunosuppressed status, such as liver transplant patients, bone marrow transplant recipients, and patients with AIDS, it can be chronic.

(28:47): There is no available vaccine for hepatitis E. The way to manage it in patients with, for example, bone marrow or liver transplant, is to minimize immunosuppression. That cures the viral infection in 30% of the patients. But if that doesn't work, then we give a medication called ribavirin (Rebetol, Ribasphere, RibaPak, Copegus, Virazole, Moderiba). It's an antiviral medication. The outcome of this infection is typically self-limited, but again, if the patient is immunocompromised, it may not be self-limited, it may be chronic.

(29:23): Hepatitis B and C are the most common chronic hepatitis viruses. Risk factors include injecting drugs, snorting drugs, sharing nail clippers, razors, personal belongings like toothbrushes, tattoos by unlicensed parlors, or sexual intercourse with infected individuals. Hepatitis B is chronic: once somebody has had hepatitis B infection, they will always have it. It may not be active, it may be dormant in the liver, but it is there. There is a vaccination for it, and it's very effective, so we recommend it.

(30:12): If somebody has an active infection, they need to be treated. If the infection is inactive and the patient gets high-dose immunosuppression, like rituximab, then prophylactic treatment should be started. Sometimes the patient who is immunocompromised gets infection reactivation, which also requires treatment.

(30:40): Hepatitis B remains in the liver forever. Although it may disappear from the blood, it remains in the liver forever, and that's why, when we get immunocompromised in the setting of bone marrow transplant or getting a rituximab, the infection can flare and may go from the liver back into the blood again. In that case we find the virus in the blood.

(31:14): For hepatitis C, about 80% of the cases are chronic. In 20%, the body can fight it and clear the virus. Some studies say 80/20, some studies say 75/25, some studies say 66% versus 33%. The point is that the majority of patients who get hepatitis C infection end up with a chronic infection. A minority can get their body to beat it.

(31:44): Hepatitis C can be treated with antiviral medications. 15 years ago, I would have said that hepatitis C is not a treatable or curable infection in most patients. But now the treatment for hepatitis C has evolved remarkably, and direct-acting antivirals can clear the infection in the vast majority – over 99% – of our patients. Those are the four hepatitis viruses.

(32:12): Another virus that happens in our patients with bone marrow transplant or liver transplant is cytomegalovirus, CMV. It transmits through body fluids. The most common risk factor is immunosuppression. It can be diagnosed through elevated liver enzymes and a high viral load in the blood, as detected by PCR testing. The medication for it is valganciclovir (Valcyte) and it's very effective.

(32:43): In conclusion, we need to think about how to keep the liver healthy in view of the risk factors and the liver diseases that we discussed. It is very important to maintain a healthy diet and regular exercise to avoid being overweight, because fatty liver disease is becoming extremely common and it's a common cause of cirrhosis, so we need to be careful.

(33:11): We must stay up to date with immunizations for hepatitis A and B. These are the two liver viruses with effective immunization against them. We must practice good hygiene and avoid undercooked or uncooked meat. We must maintain our scheduled checkups with our providers, who routinely check liver enzymes. And we need to avoid alternative medicine or supplements such as green tea extract, ashwagandha, or turmeric because these are common causes of liver injury.  

Question and Answer Session

(33:57): Susan Stewart: Does turmeric as a spice create problems for the liver?

(34:15): Dr. Izzy: Absolutely not. Spice is totally fine, but the pills that include high concentrations of it can cause liver injury. Not every person who takes ashwagandha or turmeric will have liver injury. It's a minority, or subset, of patients who'll get that.

(34:42): We as liver doctors, we see only those who get the problem, we don't see the many others who don't get the problem. Unfortunately, there is no way to foresee who will get liver injury and who will not get it. When we are dealing with bone marrow transplants, we want to avoid any other problem.

(35:09): Susan Stewart: Is green tea okay to drink regularly in small amounts?

(35:40): Dr. Izzy: That's a great question and it's a frequent question. Green tea extract is very toxic to the liver. We've seen liver failure from it; we've done liver transplants for it.

(35:54): However, green tea as a drink has not been reported to cause catastrophic liver injury, but it can cause fluctuation in liver enzymes, which indicates mild liver injury. It is not going to cause any life-threatening issue, but it may cause mild fluctuation in liver enzymes.

(36:24): Susan Stewart: On the last slide of your presentation you said avoid supplements, alternative medicine. Does that include probiotic supplements?

(36:39): Dr. Izzy: Probiotics have not been reported – or there is no good quality evidence to suggest – that they can cause liver injury. So that statement about avoiding supplements in relation to the liver doesn't cover probiotics.

(36:54): Susan Stewart: How long would you watch a liver function test before starting steroids for liver GVHD for a patient? This patient is six weeks post donor lymphocyte infusion; for the past two weeks ALT has been four to five times as normal; AST three to four times as normal; ALP near two times normal; and total bilirubin has been normal. Can we afford to monitor it a bit longer?

(37:29): Dr. Izzy: That would depend on the dose of steroids. If the patient is not maximized with these liver enzymes, I would maximize the dose of steroids and see how things go. If the steroids are maximized, and with these labs in magnitudes of four or five times the upper limit of normal, I may be inclined to liver biopsy in that patient.

(37:54): Susan Stewart: Does gallbladder inflammation or blockage mimic the symptoms of liver issues?

(38:05): Dr. Izzy: Gallbladder inflammation would not mimic liver disease manifestations, but gallbladder stones can move and block the bile duct, causing jaundice and mimicking diseases that originate from the liver itself.  

(38:50): Susan Stewart: After having increased liver function tests with GVHD, do you normally see that the liver tests remain slightly elevated?

(39:05): Dr. Izzy: In the vast majority of patients with liver GVHD who get treated for it, eventually the liver enzymes go back to normal. In a minority, the alkaline phosphatase may remain slightly elevated.

(39:22): Susan Stewart: This is a person with multiple myeloma who is on maintenance therapy consisting of Revlimid, Darzalex (Faspro) and Velcade. Her liver AST and ALT have been elevated for several weeks, and last week, the bilirubin doubled and is now in the high range. What is done to determine which of these drugs may be contributing to the escalating liver enzymes, and can stopping a drug cause my disease to relapse?  

(39:56): Dr. Izzy: The last question about the possibility of disease relapse upon stopping the medication, that's outside of the scope of my practice. I'm a liver doctor, I don't have oncology practice, so I will only be able to answer the other questions.

(40:16): When we see this elevation, first we need to assess for other types of liver injury before blaming it on the drug. Especially with significantly elevated bilirubin, we need to make sure there is no blockage in the liver pipes or the bile ducts. We typically use ultrasound, MRI, or magnetic resonance cholangiopancreatography (MRCP), for that purpose.

(40:39): We need to make sure that none of the viral hepatitis types are there. We need to do blood testing for rare liver diseases. If all these things are ruled out, then the next step is thinking about these medications as the possible culprit or cause of the injury.

(41:05): The way to see the likelihood of a medication causing or not causing liver injury is through a database that's available for everybody online, it's called LiverTox. It's an NIH (National Institutes of Health) database that has pretty much every drug under the sun in relation to liver injury. And that would tell you, or tell the provider, what the likelihood is that this or other drugs are causing it.

(41:38): The way that we and most of our partners in the oncology clinic approach this is to start with drugs that have the highest likelihood to cause liver injury, stop the drug and see how liver enzymes behave, then the next drug, then the next drug. That's usually the approach.  

(42:03): Susan Stewart: Does that LiverTox database also list supplements that can increase liver toxicity, or is it strictly drugs?

(42:17): Dr. Izzy: Yes, it lists supplements too. Not all supplements, but probably most supplements are listed there, too.

(42:24): Susan Stewart: What about matcha tea? Is that a problem?

(42:48) Dr. Izzy: I don't know matcha, but I can say that black tea is perfectly fine.

(42:52): In the context of chronic GVHD, do you have concerns about long-standing mild abnormalities in transaminase levels? Should additional evaluation for fibrosis be pursued at some point?

(43:08): Dr. Izzy: I assume that question is coming from a clinician. A mild but chronic elevation of liver enzymes warrants assessment of fibrosis through elastography, which assesses liver stiffness and should be done every one to two years. I personally do it every year, but some of my colleagues do it every two years. There is no solid evidence to suggest one year versus two years, but that's our current practice.

(43:48): Susan Stewart: Can swelling on the left abdomen around the spleen be a result of out-of-range liver function tests?

(44:07): Dr. Izzy: Spleen enlargement typically does not reflect liver inflammation. It can reflect cirrhosis and increased pressure on the veins around the liver, which then divert the blood to the spleen and make it larger, but spleen enlargement is not a sign of acute inflammation of the liver.

(44:32): Susan Stewart: What do you define as a healthy diet? Are things like keto diets or some of the other popular diets good or bad for the liver?

(44:49): Dr. Izzy: When we talk about a healthy diet, it's a low-carb, high-protein diet that we refer to. There are studies about different types of diet in relation to liver disease. The best evidence that we have is for the Mediterranean diet in relation to liver disease and fatty liver disease. I believe that the favorable outcomes with the Mediterranean diet can be attributed to the fact that it contains significantly fewer carbs and less harmful fat than the American diet. The short answer is: high-protein, low-carbs.

(45:41): Susan Stewart: You talked about not eating raw meat. What about raw fish like sushi?

(45:49): Dr. Izzy: There are reports of raw fish associated with hepatitis E, but those reports are mostly from outside America in areas where hepatitis is more common, such as South America or Eastern Europe. Conceptually it can happen, but in the US that's extremely uncommon.

(46:29): Susan Stewart: Is drinking coffee effective for treating liver disease?

(46:38): Dr. Izzy: That's an excellent question. Coffee is beneficial for the liver. Studies have shown that drinking three cups of coffee a day, equivalent to 24 ounces, may slow the progression of scarring in the liver, for example, in patients with fatty liver disease. Coffee wouldn't cure liver disease, but it may – that’s may, it's not for sure – it may slow the progression of liver disease.

(47:17): Susan Stewart: What are your thoughts about menopausal hormone therapy used in patients with GVHD of the liver with elevated transaminases but no advanced liver disease?

(47:36): Dr. Izzy: It depends on the supplement or the hormonal replacement being used and which enzyme is elevated, such as AST, ALT, alkaline phosphatase. There's no straight answer to this. This is a nuanced question and I would suggest discussing it with a liver provider so they can go through which enzyme is elevated and what type of hormonal replacement is being considered and take it from there.

(48:15): Susan Stewart: What side of the body is the liver on?

(48:20): Dr. Izzy: It's the right upper corner of the belly.

(48:24): Susan Stewart: Closing. On behalf of BMT InfoNet and our partners, I'd like to thank you, Dr. Izzy, for a very informative presentation. I certainly learned a lot. And thank you, the audience for those interesting questions that you submitted. Please contact BMT InfoNet if there's anything we can do to help you.