Liver Tumors and Transplantation: Liver Tumors and Transplantation: Transplant Care

0:00Welcome to Board Pearls. This is episode four of four of the Liver Tumors and Transplantation chapter, in the Liver Disease module. This episode follows liver transplant from referral to the long-term recipient. A woman whose hepatologist wants to wait shows when to refer, how the Model for End-Stage Liver Disease, MELD, three point zero score works, what the evaluation looks for, which vaccines have to come first, and why her muscle matters as much as her score. A man with liver cancer and a low MELD shows why exception points exist, why a cancer patient waits six months, which lung syndromes earn points and which rule a patient out, what the review board decides, and what each donor type means for the recipient. A woman whose enzymes rise five weeks after her transplant shows how complications follow the calendar, how rejection is diagnosed and treated, how cytomegalovirus, CMV, is prevented, and what each drug does to her. A man with a rising creatinine and new skin cancers shows the late toxicities. And a man whose creatinine jumps on fluconazole shows which diseases come back and the tacrolimus interactions every clinician has to know.

1:06Here's the first patient. A fifty-four-year-old woman has cirrhosis from metabolic dysfunction-associated steatohepatitis, MASH, with type two diabetes. Three months ago she developed ascites, her first decompensation. Her MELD three point zero is seventeen. She's lost weight from her arms and legs, though her abdomen is larger, and she gets tired walking a block. Her hepatologist wants to wait until her MELD is higher before referring her.

1:33She has decompensated MASH cirrhosis, and she should be referred for transplant now. Referral is triggered by a decompensation, meaning variceal hemorrhage, ascites, hepatic encephalopathy, liver cancer, or hepatorenal dysfunction, or by a MELD of fifteen or higher. Fifteen is the threshold because below it, the perioperative mortality of transplant exceeds the short-term mortality of medical care, and above it, transplant offers a survival benefit. She meets both triggers.

2:02The threshold works in the other direction too. A fifty-nine-year-old man with compensated cirrhosis from treated hepatitis C and a MELD of eleven isn't referred yet. He continues surveillance, and he's referred if he decompensates, reaches a MELD of fifteen, or develops liver cancer. A two-centimeter LR-5 lesion within the Milan criteria would make him a candidate, and he'd need exception points, because his MELD would never reflect that urgency.

2:27Her place on the list is set by MELD three point zero, which replaced MELD-Na for allocation in twenty twenty-three. It includes creatinine, now capped at three point zero rather than four, bilirubin, the international normalized ratio, INR, sodium, female sex, which adds points, and albumin in the range of one and a half to three and a half grams per deciliter. Sex and albumin were added because women faced higher waitlist mortality. A woman has a lower creatinine than a man with the same kidney dysfunction, so creatinine-based scores undervalued how sick women were, and her older MELD values may have understated her illness.

3:08Her evaluation starts with the organs that have to survive the operation. Her heart gets stress imaging or coronary angiography, depending on her age and risk factors, because end-stage liver disease brings cirrhotic cardiomyopathy and accelerated coronary disease. Her MASH and diabetes add to that risk, since cardiovascular disease is the main cause of death in metabolic dysfunction-associated steatotic liver disease, MASLD. Her lungs get an arterial blood gas and contrast echocardiography to look for hepatopulmonary syndrome and portopulmonary hypertension. Her kidneys get a creatinine, urine studies, and imaging, to identify a candidate for simultaneous liver-kidney transplant and kidneys that may not tolerate years of calcineurin inhibitors. Her age-appropriate cancer screening is brought up to date, with chest imaging, before lifelong immunosuppression begins.

4:01The next part of her evaluation is infection, because immunosuppression will unmask anything she carries. She's tested for the hepatitis viruses, human immunodeficiency virus, HIV, CMV, and Epstein-Barr virus, EBV, whose results decide prophylaxis after transplant. She's screened for latent tuberculosis and syphilis, and for Strongyloides if she's had endemic exposure. She needs dental clearance, because an oral infection becomes dangerous on immunosuppression.

4:33Her vaccines are completed before she's listed: hepatitis A and B, pneumococcal, influenza, varicella if she's seronegative, and measles, mumps, and rubella, MMR, if she's seronegative and the timing allows. The order matters because the live vaccines, varicella and MMR, are contraindicated after transplant.

4:53The psychosocial evaluation covers social support, finances, adherence, and substance use, and alcohol shows how it's applied. A forty-seven-year-old man with alcohol-related cirrhosis, ascites, and a MELD of twenty-two stopped drinking two months ago. Alcohol-related liver disease is judged by a structured psychosocial assessment, the Stanford Integrated Psychosocial Assessment for Transplantation, SIPAT, or the High Risk Alcoholism Relapse score, not by a rigid six-month rule. Early transplant is even supported for highly selected patients with severe alcoholic hepatitis who don't respond to steroids. He's referred now, and the transplant team assesses his alcohol history.

5:39Her wasted limbs show what her MELD misses, which is her muscle. Sarcopenia and frailty independently predict death on the waitlist. The most consistent measure is the skeletal muscle index at the third lumbar vertebra on computed tomography, CT, and sarcopenia is an index under fifty square centimeters per square meter in men or under thirty-nine in women. Hand-grip strength, the six-minute walk, and the Liver Frailty Index add information about function that the laboratory score can't capture, and they predict both decompensation before transplant and outcomes after it. Her index is thirty-four, so she's sarcopenic and at higher risk than her MELD suggests. Her nutrition becomes part of her preparation, with one point two to one point five grams of protein per kilogram a day and a bedtime snack to preserve muscle.

6:29She also needs an upper endoscopy. Variceal screening is done in everyone awaiting transplant with portal hypertension, including portal vein thrombosis, because a thrombosis can produce new varices that an earlier screening didn't show.

6:42The second patient shows what MELD can't measure. A sixty-four-year-old man with compensated cirrhosis from treated hepatitis C has two LR-5 cancers, two and a half and two centimeters, without vascular invasion or spread. His MELD three point zero is nine. He's listed, and he wants to know why his place doesn't move.

7:02He has hepatocellular carcinoma within the Milan criteria and a MELD that doesn't reflect his urgency, which is why exception points exist. MELD predicts death from liver failure, but some conditions threaten life or transplant candidacy without raising it, and standard exceptions correct for that. His urgency is the cancer, which could grow beyond the criteria while he waits. Cancer within Milan receives the regional median MELD after a six-month waiting period, with periodic upgrades after that. The wait is deliberate. It selects out aggressive biology, because a cancer that would progress beyond Milan within six months would likely recur after transplant.

7:40While he waits, he gets ablation or chemoembolization to keep him within the criteria, with ongoing imaging, because growth beyond Milan costs him his eligibility unless locoregional therapy brings him back within it. The same logic allows downstaging. A cancer brought within Milan by locoregional therapy and then stable on imaging for three to six months can be listed, because biology that responds and stays stable is unlikely to recur after transplant.

8:07His wait also raises living donation. A living donor graft is available at select centers for patients with a heavy symptom burden but a low MELD, who would otherwise wait too long for a deceased donor, and for time-sensitive situations such as a cancer at risk of progressing beyond the criteria. He's that patient, so it's raised with him, along with the higher rate of biliary complications that comes with a partial graft.

8:32The lungs earn exceptions too, and they work in both directions. Hepatopulmonary syndrome earns a standard exception with a room-air arterial oxygen pressure, PaO2, under sixty, a right-to-left intrapulmonary shunt documented on bubble echocardiography, and no significant primary lung disease. It earns points because the hypoxemia can reverse after transplant, once the splanchnic vasodilation that dilates the lung vessels resolves. Portopulmonary hypertension earns an exception when, after vasodilator therapy, the mean pulmonary artery pressure is under thirty-five, the pulmonary vascular resistance is under four hundred dyne, and the transpulmonary gradient is under twelve, with all three required. A mean pressure over fifty is an absolute contraindication, because the right ventricle fails during the operation.

9:21Conditions outside the standard exceptions go to the National Liver Review Board. Its list includes cholangiocarcinoma under the Mayo protocol, primary hyperoxaluria, often with a combined liver-kidney transplant, familial amyloid polyneuropathy with a transthyretin, TTR, mutation, and cystic fibrosis with a forced expiratory volume in one second, FEV1, under forty percent. It includes recurrent cholangitis that hasn't responded to medical, radiologic, or surgical treatment, and Budd-Chiari syndrome not eligible for a transjugular intrahepatic portosystemic shunt, TIPS. It includes an unresectable hepatic adenoma or adenomatosis, neuroendocrine metastases confined to the liver, polycystic liver disease, hereditary hemorrhagic telangiectasia with high-output heart failure, and hepatic epithelioid hemangioendothelioma.

10:14The board also covers ischemic cholangiopathy after a graft donated after circulatory death, DCD, and recurrent hepatic hydrothorax not eligible for TIPS. The hydrothorax has strict criteria: weekly thoracentesis of more than a liter for four weeks, a transudate, and no heart failure. In each of these conditions, the liver may still be working while the disease disables or endangers the patient.

10:39When an organ is offered, the donor type tells the team what to watch for afterward. Donation after brain death, DBD, gives the standard whole organ, with the shortest warm ischemic time. A DCD graft has a longer warm ischemic time, which raises the rate of primary non-function and of biliary complications, especially ischemic cholangiopathy from microvascular injury to the bile duct epithelium during prolonged hypoperfusion. DCD use has expanded with normothermic machine perfusion, which reduces ischemia-reperfusion injury. A living donor gives a partial graft, usually the right lobe in an adult, with a biliary complication rate of about ten to thirty percent, higher than with a whole graft from a brain-dead donor.

11:24The third patient brings the period after transplant. A fifty-year-old woman had a transplant for primary biliary cholangitis five weeks ago, from a brain-death donor. The donor was CMV-positive and she was CMV-negative. She's on prednisone, mycophenolate, and tacrolimus, with valganciclovir. She feels well, but her aspartate aminotransferase, AST, alanine aminotransferase, ALT, and alkaline phosphatase have risen over the past week.

11:55What her rising enzymes mean depends on how long it's been since her transplant, because complications follow the course of immunosuppression. Induction is high-dose intravenous methylprednisolone at the time of transplant, sometimes with anti-thymocyte globulin or basiliximab. The first months use triple therapy, a steroid taper, mycophenolate, and a calcineurin inhibitor at higher targets. After about a year, maintenance is a calcineurin inhibitor alone at lower targets, with or without low-dose steroid or mycophenolate.

12:27The complications follow the same calendar. In the first month they're technical and surgical. Hepatic artery thrombosis presents with biliary ischemia and severe graft dysfunction, and when it's early it qualifies for relisting at Status one. Bile leak, primary non-function, which also qualifies for Status one, and gram-negative or fungal surgical infections belong to this month too. From one to twelve months, opportunistic infections peak, CMV most commonly, along with Pneumocystis jirovecii and Aspergillus, and this is also the time of acute cellular rejection, biliary strictures, and early recurrence. Beyond a year come kidney failure from tacrolimus, new cancers, metabolic syndrome, late strictures, late recurrence, notably of sclerosing cholangitis, and community infections. At five weeks, her rising enzymes point first to acute cellular rejection. The same rise in the first week, with severe graft dysfunction, would point to hepatic artery thrombosis.

13:28Her suspected rejection needs a biopsy. Acute cellular rejection occurs in about a third of liver transplants, typically within six weeks, and it's often found on surveillance labs as a rise in AST, ALT, and alkaline phosphatase in a patient who feels well. Histology is required because strictures, infection, and recurrence share the same window. The Banff triad is portal inflammation, bile duct injury, and inflammation of the venous endothelium, and the Rejection Activity Index scores each from zero to three, for a total of zero to nine. Her biopsy shows all three, with an index of six, which is moderate rejection.

14:08First-line treatment is intravenous methylprednisolone, five hundred to one thousand milligrams daily for three days, then a taper, plus a higher calcineurin inhibitor target. It works in about ninety percent, and her enzymes fall. Rejection that resists steroids is treated with thymoglobulin, at the price of severe immunosuppression and a high risk of CMV and other opportunistic infections. Early acute cellular rejection doesn't affect patient or graft survival, except in untreated hepatitis C, where treating the rejection accelerates the recurrence of the virus.

14:41Her biopsy also excludes the two rarer forms of rejection. Antibody-mediated rejection is less common in the liver than in other organs, because the liver resists humoral injury. It's diagnosed by donor-specific antibodies and C4d staining of the sinusoidal endothelium, and it's treated with plasmapheresis, intravenous immunoglobulin, IVIG, rituximab, and intensified maintenance. Chronic ductopenic rejection, a vanishing bile duct syndrome, presents months to years after transplant with cholestasis and loss of bile ducts in more than half of the portal tracts. It's treated with intensified immunosuppression and conversion strategies, and with re-transplantation when it's refractory.

15:24Her valganciclovir is there for CMV, the most common opportunistic infection after transplant. Her risk is the highest there is, because a CMV-positive donor and a CMV-negative recipient, a D-plus R-minus mismatch, means she has no immunity of her own. Risk also peaks with intense immunosuppression, at induction and after treatment of rejection, which is exactly where she is now. Prevention is valganciclovir nine hundred milligrams daily for three to six months in D-plus R-minus and selected R-plus recipients, or preemptive weekly CMV polymerase chain reaction, PCR, testing with treatment once viremia crosses a threshold.

16:05If prevention fails, CMV disease ranges from viremia alone, to CMV syndrome with fever, leukopenia, thrombocytopenia, and malaise, to tissue invasion as hepatitis, gastritis, colitis, retinitis, or pneumonitis. Treatment is intravenous ganciclovir, five milligrams per kilogram every twelve hours, switching to oral valganciclovir, usually for about three weeks or until the viremia clears. Resistant virus, with UL97 kinase or UL54 polymerase mutations, is treated with maribavir, foscarnet, or cidofovir. Letermovir is for prophylaxis, not for treating active or resistant disease. Chapter thirty-three covers CMV colitis.

16:52Each of her drugs has toxicities that follow from how it works. Corticosteroids cause hyperglycemia, weight gain, osteoporosis, cataracts, and at high doses mood swings, mania, or psychosis. Mycophenolate inhibits inosine monophosphate dehydrogenase and so blocks purine synthesis in lymphocytes, and it causes dose-dependent leukopenia and gastrointestinal effects, especially diarrhea. Tacrolimus causes nephrotoxicity, acutely by constricting the afferent arteriole and chronically by interstitial fibrosis and tubular atrophy. It also causes neurotoxicity, with tremor, headache, and seizures at high levels, along with hypertension, hyperlipidemia, diabetes, alopecia, and hyperkalemia. Cyclosporine shares that profile and adds hirsutism and gingival hyperplasia.

17:44The mechanistic target of rapamycin, mTOR, inhibitors, sirolimus and everolimus, cause hypertriglyceridemia, fluid retention, mouth ulcers, anemia, proteinuria, bronchiolitis obliterans, and impaired wound healing, but they're less nephrotoxic, which makes them the preferred conversion when kidney function declines on tacrolimus. For her, the prednisone means attention to her bones and glucose, and the tacrolimus means her metabolic care starts now.

18:17The fourth patient shows what accumulates after the first year. A sixty-one-year-old man transplanted for alcohol-related cirrhosis four years ago is on tacrolimus alone. His creatinine has risen from one point one to two point one over two years, and he has two new squamous cell skin cancers. His creatinine is chronic tacrolimus nephrotoxicity, so he's converted to an mTOR inhibitor. New cancer is a major late complication: squamous cell skin cancer more often than basal cell, cancers driven by human papillomavirus, post-transplant lymphoproliferative disease, often driven by EBV, and Kaposi sarcoma from human herpesvirus eight. Oropharyngeal cancer is a risk in recipients transplanted for alcohol-related disease who have also used tobacco, and colon cancer is a risk in recipients with sclerosing cholangitis and ulcerative colitis, who need annual colonoscopy. He's referred to dermatology, and if he has smoked, his mouth and throat are examined too.

19:16The last patient brings recurrence and drug interactions together. A forty-nine-year-old man was transplanted for primary sclerosing cholangitis four years ago, from a DCD donor. His ulcerative colitis has been active over the past year. His alkaline phosphatase has risen over six months, and magnetic resonance cholangiopancreatography, MRCP, shows intrahepatic biliary strictures. He's on tacrolimus. Last week he started fluconazole for esophageal candidiasis, and today his creatinine has jumped.

19:47His new strictures raise recurrence of his original disease. The process that destroyed his first liver, whether metabolic, viral, autoimmune, or biliary, can re-establish itself in the graft, so disease-specific surveillance continues indefinitely. Sclerosing cholangitis recurs in about twenty-five percent by ten years, most often with active inflammatory bowel disease, and it's identified by intrahepatic strictures on MRCP with a rising alkaline phosphatase. It has to be distinguished from an anastomotic stricture at the surgical join, from ischemic cholangiopathy, especially in a DCD graft, and from chronic ductopenic rejection, because each is managed differently. His strictures are intrahepatic and his colitis is active, which favor recurrence, but his DCD graft makes ischemic cholangiopathy possible, so the whole picture, with a biopsy if needed, decides. Ischemic cholangiopathy would qualify him for a review board exception. His annual colonoscopy continues either way.

20:43His creatinine jumped because of an interaction. Tacrolimus is metabolized by CYP3A4, and inhibitors of that enzyme raise its level, causing nephrotoxicity, neurotoxicity, hyperkalemia, and hyperglycemia. The inhibitors are the azoles, fluconazole, voriconazole, posaconazole, and ketoconazole; the macrolides, erythromycin and clarithromycin; diltiazem and verapamil; the hepatitis C protease inhibitors; and amiodarone, metoclopramide, cimetidine, imipenem, and ceftazidime. Inducers lower the level and risk rejection: rifampin, phenytoin, carbamazepine, nafcillin, and St John's wort. His fluconazole raised his level, so his tacrolimus level is checked, his dose adjusted, and his creatinine followed.

21:33The rule for every recipient is to check the tacrolimus level whenever a drug is added. Diltiazem for atrial fibrillation, clarithromycin for a chest infection, or metoclopramide for nausea will raise it. St John's wort, carbamazepine, or phenytoin will lower it and invite rejection, which is why recipients are asked about supplements. A rifampin-isoniazid regimen for tuberculosis is a trap, because isoniazid inhibits CYP3A4 rather than inducing it, so the rejection risk comes from the rifampin.

22:05Viral disease recurs unless it's prevented. A fifty-seven-year-old woman transplanted for hepatitis B cirrhosis with liver cancer had detectable hepatitis B virus DNA before her transplant. Recurrence is prevented with hepatitis B immune globulin, HBIG, plus entecavir or tenofovir, with the passive antibody neutralizing virus while the antiviral suppresses any breakthrough replication. Reduced-intensity HBIG, or stopping HBIG and relying on a high-barrier antiviral alone, is used in selected low-risk recipients, but indefinite combination therapy remains the default with detectable DNA before transplant or with liver cancer. She has both, so she stays on HBIG and entecavir indefinitely, with imaging for recurrence of her cancer.

22:53Hepatitis C is now far simpler. A sixty-two-year-old woman transplanted for hepatitis C cirrhosis was viremic at transplant. Recurrence was once universal and a major cause of late graft loss, but sofosbuvir-velpatasvir or glecaprevir-pibrentasvir now achieve sustained virologic response in more than ninety-five percent. Her treatment starts early after transplant, once her kidney function is stable. Glecaprevir is a protease inhibitor that interacts with tacrolimus, while sofosbuvir-velpatasvir contains none and avoids that interaction, and either can be used with her tacrolimus level followed closely. Hepatitis C is cured with a short course, while hepatitis B is controlled for life.

23:33Autoimmune and metabolic disease recur too. Autoimmune hepatitis recurs in twenty to thirty percent and is treated like rejection, with steroids plus a higher baseline regimen. On biopsy it can be hard to separate from acute cellular rejection, because both cause portal inflammation, so timing, serology, and immunoglobulin G help, and the treatments overlap. MASH recurs commonly, because the metabolic problem persists and is worsened by weight gain after transplant, diabetes, and the metabolic syndrome that immunosuppression drives, so weight, glucose, lipids, and blood pressure are part of long-term care. HFE hemochromatosis doesn't recur, because the donor liver makes hepcidin normally. A disease recurs when its cause lives outside the liver.

24:19Here are the traps the boards set in these patients. A first decompensation means referral now, without waiting for a higher MELD, while a compensated patient with a MELD under fifteen isn't referred yet. Allocation uses MELD three point zero, not MELD-Na. A patient with MASH and diabetes needs a full cardiac workup, and every candidate needs lung screening. Live vaccines are given before transplant, never after. Alcohol-related disease is judged by structured assessment, not six months of sobriety. And sarcopenia raises the risk even when the MELD looks moderate.

24:53The waitlist traps follow the same logic. MELD doesn't capture the urgency of a cancer, which is why exception points exist, and they come after a six-month wait. Downstaging into Milan is accepted, and living donation is an option for a time-sensitive cancer. A hepatopulmonary exception needs all three criteria. A mean pulmonary pressure over fifty rules a patient out. Conditions outside the standard exceptions go to the review board. And DCD grafts bring ischemic cholangiopathy, while living donor grafts bring more biliary complications.

25:24The traps after transplant start with the calendar. Rising enzymes are read by time since transplant, and rejection is diagnosed by biopsy, not by enzymes alone. CMV risk peaks after rejection treatment, a D-plus R-minus recipient needs prophylaxis, and letermovir doesn't treat active CMV. A climbing creatinine on tacrolimus calls for conversion to an mTOR inhibitor. Skin cancer, lymphoproliferative disease, and colon cancer need surveillance.

25:52The traps about recurrence and drugs close the list. Not every stricture is recurrent sclerosing cholangitis. A high-risk hepatitis B recipient stays on HBIG and an antiviral, and hepatitis C is treated early. An azole, macrolide, or diltiazem added without checking the tacrolimus level causes toxicity, and rifampin causes rejection. And a recipient transplanted for MASH needs cardiometabolic care for life.

26:21So, start to finish. Refer at the first decompensation or a MELD of fifteen. MELD three point zero adds female sex and albumin and caps creatinine at three. Evaluate the heart, lungs, kidneys, cancer screening, and infection, vaccinate before transplant, judge alcohol-related disease by structured assessment, and measure sarcopenia.

26:43Exception points cover what MELD underrates. Cancer within Milan earns the regional median after six months, and downstaging is accepted. Hepatopulmonary syndrome with a PaO2 under sixty qualifies, and portopulmonary hypertension controlled under thirty-five qualifies, while a mean pressure over fifty contraindicates transplant. Other syndromes go to the review board. DCD grafts carry ischemic cholangiopathy and living donor grafts biliary complications.

27:13Read complications by time: technical failure in the first month, CMV and acute cellular rejection from one to twelve months, and nephrotoxicity, cancer, and metabolic disease after a year. Rejection is diagnosed by biopsy and treated with pulse methylprednisolone, and declining kidneys on tacrolimus mean conversion to an mTOR inhibitor. Prevent CMV in D-plus R-minus recipients with valganciclovir or preemptive PCR.

27:42Expect sclerosing cholangitis, autoimmune hepatitis, and MASH to recur. Cure hepatitis C early, and control hepatitis B with an antiviral, plus HBIG in high-risk recipients. And check the tacrolimus level whenever a drug is added.

27:59That completes the Liver Tumors and Transplantation chapter, and the Liver Disease module. The next chapter is acute pancreatitis.

28:07For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode four of four of chapter twenty-four, and I'll see you in the next one.