Managing the most complex liver transplant cases: when to consider a second opinion 

Determining whether—and when—a patient is a candidate for liver transplant can be challenging. That’s especially true when treatment considerations are complicated by comorbidities such as concurrent heart disease, autoimmune diseases, or cancer, or by behavioral health concerns such as alcohol use.

Liver transplantation has been the leading option for end-stage liver disease since the 1980s, but has often proved a challenging option for both patients and their caregivers, who must contend with the complexities of the waiting list and the evolving qualifications for advancement to transplantation. To ease the experience of transplantation and advance the success of liver transplantation, the specialists at the Penn Transplant Institute (PTI) draw on expertise across specialties to evaluate and treat patients, and to expand transplant options for those with complex medical needs.

“There are a lot of nuances in terms of when to send patients with rare liver diseases and complex conditions for transplant,” says Stacey Prenner, MD, associate professor of clinical medicine (gastroenterology) at the Perelman School of Medicine at Penn Medicine. “Because of our experience managing complex conditions and comorbidities, we often take patients for transplant who might be turned away by other centers.”

Liver transplant in high-risk patients with comorbidities

Medical comorbidities can increase the risk of major surgery and are an increasingly important consideration when evaluating patients for liver transplant. The prevalence of metabolic dysfunction-associated steatohepatitis (MASH), an advanced form of fatty liver disease, is increasing worldwide. MASH causes scarring of the liver and often occurs concurrently with type 2 diabetes, obesity, and heart disease. Outside of its role as a serious comorbidity, MASH presents postsurgical issues that can complicate liver transplantation.

Penn Medicine works across disciplines to help manage comorbidities and optimize patients for surgery. “We have access to some of the best subspecialists in medicine who can help us treat these patients and get them to transplant,” Dr. Prenner says.

Patients with a very high BMI, for example, may be deemed too high-risk for surgery. In such cases, PTI’s liver transplant team has collaborated with bariatric experts to help patients achieve a healthier weight ahead of transplantation. Similarly, the team collaborates with specialists in cardiology to manage conditions such as heart failure or valve disease through medical management and surgical intervention.

Recently, the team performed a combined heart-liver transplant for a patient with MASH cirrhosis and heart failure with a low ejection fraction. “Traditionally, a patient with heart failure would not be eligible for liver transplant, but that’s not necessarily a barrier for us,” Dr. Prenner says. Among the benefits the PTI can offer to these patients are dedicated cardiac anesthesiologists, an asset that enables surgeons to operate on higher-risk patients that might not be considered surgical candidates at other centers.

The team is also adept at managing surgical risks, such as portal vascular issues that can be common in patients with liver disease, she adds. “As a high-volume center, we have extensive experience with a variety of patients, including those with comorbidities that increase risks during major surgery,” she says. “Our surgeons are open to these challenging cases.”

Alcohol-related liver disease

Like medical complexities, social and behavioral complexities can also make liver transplants challenging, Dr. Prenner says. In the past, patients with alcohol-related liver disease were ineligible for transplant unless they had been abstinent from alcohol for at least six months. Today, that recommendation has evolved. Rather than establishing strict criteria about the amount of time abstinent, the Penn Transplant Institute offers a comprehensive team of specialists to assess patients with alcohol use disorder who may be good candidates for transplant and provide them with dedicated resources to support their sobriety as they move forward with transplant.

PTI’s Integrated Liver Transplant Engagement and Recovery Network, or ILEARN clinic, includes hepatologists, psychiatrists, and social workers to support transplant patients struggling with addiction. “Our multidisciplinary alcohol clinic really sets Penn Medicine apart from other programs,” Dr. Prenner says. “We have a comprehensive program and resources that set patients up to succeed.”

Autoimmune diseases and other rare liver diagnoses

Penn Medicine’s hepatologists also have wide-ranging experience in managing autoimmune conditions that affect the liver, such as primary sclerosing cholangitis (PSC), primary biliary cholangitis, and autoimmune hepatitis. “These are rare diseases that can be challenging for community gastroenterologists. Some patients with autoimmune hepatitis, for example, require advanced immunosuppression—often using the same medications we use in transplant,” Dr. Prenner says.

Patients with PSC are also at high risk of developing bile duct cancer. But traditional endoscopic retrograde cholangiopancreatography procedures often miss those early malignancies. Penn Medicine’s team uses advanced endoscopy and next-generation sequencing to identify strictures with pre-malignant potential. In many cases, these patients may not yet have Model for End-Stage Liver Disease (MELD) scores that qualify them for the transplant waiting list, Dr. Prenner says. Yet they may benefit from moving forward with a transplant from a live donor before the premalignant cells progress to cancer. “With living donation, we can send some of these patients to transplant earlier, before they develop cancer,” she says.

Living donation can also provide an option for patients with autoimmune liver diseases who have begun experiencing significant symptoms without high MELD scores. Dr. Prenner recently provided a second opinion for a patient with PSC who was being monitored at another center. Although his MELD score was not very high, he had developed hepatic encephalopathy. With several family members eager to take part in living donorship, the patient moved forward with a transplant evaluation at PTI.

Cancer, sickle cell disease, HIV, and other disorders

As transplant medicine evolves, patients with conditions once considered too risky or complex for transplantation may now have new treatment options. Penn Medicine has multidisciplinary care teams that provide specialized care for conditions that affect the liver, such as cystic fibrosis, sarcoidosis, and sickle cell disease. “We have the disease-state experts and protocols in place to help more patients with complex cases,” Dr. Prenner says.

Recent advances are making liver transplants an option for some patients with these disorders, including sickle cell disease. “Traditionally, patients with sickle cell weren’t offered transplant—it was considered too high-risk because there was concern that the sickled cells could clot off a graft,” she explains. “We developed a protocol to provide transplants to these patients, and we are one of only a few centers in the country to do so.”

Similarly, transplant specialists have collaborated with Penn Medicine’s infectious disease doctors to perform liver transplants in HIV-positive patients, even those with lower CD4 counts. Transplants may also be an option for patients with cancer—not only cancer in the liver, but also the bile ducts and, more recently, in cases of colorectal cancer that has metastasized to the liver. While in the past, transplantation was contraindicated in the presence of these cancers, Dr. Prenner notes, today, in certain cases, transplantation is curative for some patients.

Liver transplants may also be an option for some patients with liver disease who have cancer in other parts of the body, such as the prostate, she adds.

About liver transplantation at the Penn Transplant Institute

The Penn Transplant Institute has performed more than 4,000 liver transplants. The program also performs twice as many living donor liver transplants as its closest competitors, expanding lifesaving options to more patients with liver disease.

The transplant team also treats pediatric patients through its affiliation with Children’s Hospital of Pennsylvania and offers access to new hepatology treatments through its robust clinical trial program. “Our hepatologists are involved in national committees and collaborate with experts nationwide, keeping us up to date on the latest advances in hepatology,” Dr. Prenner says. “Diagnoses that are rare in the general population are familiar or even common to us.”

Referrals and consultations

Early referral is a critical element of patient outcomes in liver transplantation. Unfortunately, Dr. Prenner says, many patients—especially those with autoimmune liver diseases—are not always referred early enough to take full advantage of living donation and clinical trials.

The transplant team at the Penn Transplant Institute welcomes referrals and informal inquiries from physicians considering whether their patients are eligible for transplant, even for patients not yet sick enough to be added to the organ waiting list.

“Patients with complex cases can sometimes be sicker than their liver numbers would suggest,” she says. “An earlier referral allows us to co-manage a patient’s care and start the evaluation process to prepare them for an eventual transplant. We also have clinical trials for many of these conditions that may be an option.”

With satellite locations across the region, the PTI team partners with local providers in a variety of ways, from answering questions to spearheading the transplant evaluation process. “We are happy to take on as much or as little of a patient’s care as the patient and their referring provider would like,” Dr. Prenner says.

Learn more about liver transplant at Penn Medicine. To refer a patient or consult with a transplant specialist, please call 877-937-7366, or submit a referral through our secure online referral form.