Denied Candidates for MELD Score Exception Requests for Hepatocellular Carcinoma: Higher AFP Levels and More, Larger Tumors

Patients who were denied Model for End-Stage Liver Disease (MELD) score exceptions for hepatocellular carcinoma had more aggressive cancer characteristics than approved candidates, a recent analysis of Organ Procurement and Transplantation Network (OPTN) data found. The multicenter coauthors include Scott W. Biggins, MD, FAASLD, chief, hepatology, medical director, UPMC Liver Transplant Program, and current chair, OPTN Liver and Intestine Committee.

A MELD score may not reflect the severity of a candidate’s liver disease. When a liver transplant candidate’s initial MELD score does not accurately reflect their medical urgency, their transplant program can request a score exception. “For many years, all MELD exception requests were manually assessed,” Dr. Biggins explains. “In the last 10 years or so, MELD exception request reviews have become more automated through the analysis of discrete data.”

Under OPTN policy (effective 12/10/2025), candidates are eligible for automatically approved MELD score exceptions if they meet specific clinical criteria for any of these nine diagnoses:

• Cystic fibrosis
• Familial amyloid polyneuropathy
• Hepatic artery thrombosis
• Hepatocellular carcinoma
• Hepatopulmonary syndrome
• Hilar cholangiocarcinoma
• Metabolic disease
• Portopulmonary hypertension
• Primary hyperoxaluria

If an exception request is not automatically approved, the National Liver Review Board (NLRB) will review and approve or deny the request.

The research team focused on hepatocellular carcinoma (HCC) in their review of the efficiency of the MELD exception request review process due to its variability in presentation and frequency as an exception request.

“Hepatocellular carcinoma comes in a lot of different presentations. It’s also the most common MELD exception,” Dr. Biggins says. “Thoughtfully automating part of the request process for the most frequent MELD exception can save efficiency in the system, which is very important for patients, transplant centers, and the national system.”

Researchers reviewed HCC initial exception requests that were not auto-approved and were referred to the NLRB for review. They did not include requests that were withdrawn before an NLRB decision was made. They also did not include requests that were approved due to a lack of reviewer response within the 21-day review window.

Researchers reviewed 4,179 request forms submitted from 07/01/2022 through 07/01/2024. These 4,179 requests were submitted for 3,124 liver transplant candidates.

84% of non-standard exception requests were approved. 15% of non-standard requests were denied, and 1% of requests were withdrawn after the NLRB approved the exception request.

Researchers compared cancer characteristics, specifically tumor size, number of tumors, and alpha-fetoprotein (AFP) levels, for approved and denied requests. Tumor size and AFP levels were measured both at the time of original evaluation and at time of initial exception request submission.

Denied requests, on average, had more aggressive cancer characteristics than approved requests, both when they were originally evaluated and when their exception request was submitted.

At time of exception request submission, denied requests’ AFP levels were almost three times higher than approved requests’ AFP levels (44.9 v. 15.5 nanograms per milliliter).

Denied requests, compared to accepted requests, also averaged more tumors (1.1 v. 1.0) and larger tumors (0.8 v. 0.6 centimeter) at time of exception request submission.

“The finding that the more aggressive or more complex cases were more likely to be declined is important because it’s evidence that the more complicated cases that needed to be evaluated by a human reviewer were still being treated in an appropriate manner,” Dr. Biggins says. “The automation didn’t go too far, and the professional assessment by the human reviewers was still there. The more complex, aggressive cases that are not appropriate for deceased-donor liver transplant are not being approved.”

The efficiency of the MELD score request process is important for both transplant patients and transplant centers. “With more automation, it allows the message of, ‘If you think someone is eligible for a MELD exception, go ahead and submit it on behalf of the patient’,” Dr. Biggins says. “If it were a very inefficient system, it might not be able to accommodate all of the requests. But a more efficient system can allow centers, on behalf of their patients, to more freely advocate for MELD exceptions and additional priority for liver transplant from a deceased donor.”

UPMC’s Transplant Oncology Expertise

Patients with aggressive cancer characteristics still have access to transplant through the living-donor liver transplant pathway. “At UPMC, we are at the leading edge of what we call transplant oncology,” Dr. Biggins says. “We do offer living-donor liver transplants to some of those patients who are declined for their MELD exceptions for a deceased-donor liver transplant.”

A living-donor liver transplant offers several potential benefits for patients, including flexible scheduling. “With a living donor, we can time the transplant patient’s chemotherapy and their immunotherapy, such that we can control the cancer and then do the transplant when those treatments have been stopped at an appropriate time.”

As national leaders in the field of living-donor liver transplant, experts at UPMC have expanded options for patients with novel indications, including those with complex primary and metastatic liver cancers.

Our experts have developed innovative living-donor liver transplant protocols for the following cancers:

• Hepatocellular carcinoma
• Hilar cholangiocarcinoma
• Intrahepatic cholangiocarcinoma or mixed cholangio/hepatocellular carcinoma
• Unresectable metastatic colorectal cancer
• Unresectable neuroendocrine tumor

Contact the UPMC Liver Transplant Program

To refer a patient for a liver transplant evaluation, or for more information, call 412-647-5800 or email transplant@upmc.edu.

Read the full abstract.