Liver transplantation (LT) is a definitive surgical treatment primarily offered to patients with end-stage liver disease. While cancer generally represents a strong contraindication for organ transplantation, the liver is a unique exception. Specific primary cancers originating within the liver are recognized as conditions for which LT can be curative. The procedure removes the tumor and replaces the severely diseased liver, which is often the underlying cause of both the cancer and liver failure. This selective approach ensures that the limited supply of donor organs is directed toward candidates with the greatest likelihood of long-term survival.
Cancer Types That Qualify for Liver Transplant
The vast majority of liver transplants performed for cancer involve hepatocellular carcinoma (HCC), the most common form of primary liver cancer. HCC frequently develops in a liver already compromised by chronic diseases like cirrhosis from viral hepatitis or alcohol-related liver disease. For these patients, transplantation offers the advantage of eliminating the tumor while simultaneously curing the underlying liver failure.
Beyond HCC, a few other cancer types confined to the liver are considered for transplantation under extremely strict protocols. Intrahepatic cholangiocarcinoma (iCCA), a cancer of the bile ducts within the liver, was historically excluded due to poor post-transplant outcomes. However, highly selected patients with very early-stage iCCA, typically a single tumor less than two centimeters, or those who respond well to pre-transplant therapy are now being considered in specialized centers.
Neuroendocrine tumor (NET) metastases that have spread exclusively to the liver are another rare exception. This is only considered when the primary tumor outside the liver has been successfully removed and the liver metastases are extensive but cannot be treated by other means. The selection process for NETs is rigorous, requiring the disease to be confined entirely to the liver with no sign of spread to lymph nodes or other organs. Long-term outcomes for these NET patients are comparable to those receiving transplants for HCC.
Strict Eligibility Criteria for Transplant Candidates
To ensure the best possible use of donor organs and to maximize patient survival, stringent criteria have been established for HCC transplant candidates. The most widely adopted benchmark is the Milan Criteria, which dictates eligibility based on tumor burden. To qualify, a patient must have either a single tumor no larger than five centimeters, or up to three separate tumors, with none exceeding three centimeters in diameter.
These size and number limits were developed to identify tumors that are least likely to have spread undetected outside the liver. Meeting the Milan Criteria predicts a five-year post-transplant survival rate of over 70%, which is comparable to survival rates for patients transplanted for non-cancerous liver disease. Some transplant centers utilize slightly expanded guidelines, such as the UCSF Criteria, which allow for a single tumor up to 6.5 centimeters or a total tumor diameter of up to eight centimeters across a maximum of three lesions.
The goal of using these specific size-based criteria is to predict tumor biology and aggressiveness before the transplant is performed. Tumors within the established limits are considered to have favorable biology and a low risk of recurrence after the procedure. Patients who fall outside these criteria face a significantly higher risk of the cancer returning in other parts of the body following transplantation.
When Cancer Makes a Patient Ineligible
While transplantation is an option for specific confined liver cancers, the presence of widespread or advanced cancer remains an absolute contraindication. The most common reason for ineligibility is extrahepatic metastatic disease, where the cancer has spread beyond the liver to other organs or distant lymph nodes. A transplant cannot remove cancer that has already spread throughout the body, making the procedure futile.
Another immediate disqualifier is the presence of macro-vascular invasion, which occurs when the tumor has visibly grown into the main blood vessels of the liver, such as the portal or hepatic veins. This invasion signifies a highly aggressive tumor and a very high risk of immediate cancer recurrence after the transplant. High levels of the tumor marker alpha-fetoprotein (AFP), often exceeding 1,000 ng/mL, can also signal aggressive tumor biology that makes a successful outcome unlikely, leading to ineligibility.
Serious co-existing health conditions, such as severe heart or lung disease, can also deem a patient ineligible if they make the major surgery too risky. Similarly, the presence of any other active, non-curable malignancy outside of the liver is typically an exclusion criterion.
The Transplant Evaluation and Listing Process
Once a patient meets the initial tumor criteria, they undergo a comprehensive, multidisciplinary evaluation involving transplant surgeons, oncologists, and hepatologists. Imaging studies, including specialized CT and MRI scans, are performed to precisely map the tumor burden and definitively rule out any spread outside the liver. The patient’s overall health and the status of their underlying liver disease are also thoroughly assessed to confirm they can tolerate the surgery and lifelong immunosuppression.
A crucial part of the process for HCC patients is “downstaging,” which involves using treatments like localized radiation or chemotherapy to shrink tumors that initially exceed the size criteria. If these treatments successfully reduce the tumor to fall within acceptable limits, the patient becomes eligible for transplantation. This process serves as a biological test, showing that the tumor responds to treatment and is less aggressive.
Eligible HCC candidates are listed on the national organ registry and receive priority through the Model for End-Stage Liver Disease (MELD) exception system. Because patients with small HCC tumors often have good liver function, their calculated MELD score would otherwise be low. The MELD exception assigns an artificial, higher score, ensuring priority access to a donor liver that reflects the urgency of their cancer diagnosis.