By: Jason Ifeanyi, PharmD Candidate c/o 2022

              The liver is one of the most commonly transplanted solid organs in the United States (US) today. The United Network for Organ Sharing (UNOS) is a mission-driven non-profit that leads the network of transplant hospitals, organ procurement organizations, and thousands of volunteers who are dedicated to saving lives through organ transplants.¹ According to UNOS, 8,494 livers were transplanted in 2021. These numbers are similar to data provided from 2020 which showed that a total of 8,906 liver transplants occurred.² Despite these impressive numbers, there are a significantly larger number of patients still in need of a liver transplant who are currently on a waiting list. One of the many factors that gets taken into consideration when determining which patients are in more urgent need of a liver transplant is the MELD score. ^1,3,4

The MELD score stands for “Model for End-Stage Liver Disease”. This is a prognostic scoring system based on specific laboratory measurements, used to predict 3-month mortality due to liver disease in patients 12 years of age and older.³ The MELD score, as previously mentioned, helps clinicians determine how urgently a patient needs a liver transplant. Scores can range anywhere from 6-40, and are based on results of several lab tests. The higher the number, the more severe the liver impairment, and the more likely that the patient will receive a liver transplant from a deceased donor when an organ becomes available.^3,4

In order to calculate the MELD score, clinicians must have access to the patients most recent INR (international normalized ratio), Scr (serum creatinine), bilirubin, and serum sodium levels. INR levels are indicative of how well the liver makes proteins necessary for blood to clot, while bilirubin levels are indicative of how well the liver clears bile. Serum creatinine is indicative of how well the kidneys are functioning, while serum sodium is indicative of well the body regulates fluid balance. A logical question one may ask is how often the MELD score needs to be calculated. Typically, this is variable, and will depend on the patients current MELD score at the time. For instance, a patient with a MELD score >25 will typically get their MELD score recalculated every week. A patient with a MELD score of 19-24 will have their MELD score recalculated every 30 days. Patients with a MELD score of 11-18 will have their score recalculated every 30 days, patients with a MELD score <10 will have their score recalculated ever year.⁴

The PELD (Pediatric End-Stage Liver Disease) score is similar to the MELD score, with a few key differences. Firstly, the PELD score is meant for patients who are less than 12 years of age. Secondly, the criteria used in calculating a PELD score differs from that of the MELD score. In particular, to calculate a PELD score clinicians will need access to a patients albumin, which measures the liver’s ability to maintain nutrition. Additionally, clinicians need to determine if the patient has growth failure, which is based on the patients height, weight, and gender. Age at listing is also recorded.⁵ Shared lab values recorded both for PELD and MELD score are bilirubin and INR. As is the case with the MELD score, a patients PELD score may fluctuate depending on the status of their disease state. Most patients will have their scores assessed numerous times while they are on a waiting list.⁶

It is important to note that the MELD score does not accurately predict survival in all patients with liver impairment. There are certain forms of liver disease that are associated with higher mortality than a MELD score would be able to predict.³ Consequently, there exists a MELD exception scoring system. This system of exception points gives patients who have certain liver conditions a standard score on the UNOS transplant waitlist. The patients transplant hospital makes customized exception score requests to a national review board of independent medical experts comprised of liver transplant physicians and surgeons. Requests should not contain any patient or hospital identifiers so that the review remains completely unbiased, and the decision based solely on medical information presented.⁷

Penn Medicine is an example of one transplant institution with a MELD score exception system. Patients who qualify for a MELD exception at Penn Medicine include patients with hepatocellular carcinoma, cholangiocarcinoma, cystic fibrosis, hepatopulmonary syndrome, familial amyloid hypertension, portopulmonary hypertension, and primary hyperoxaluria.⁸ At Penn Medicine, in order to qualify for an exception, each of the conditions mentioned above has specific guidelines or protocols, which require diagnostic testing, blood work, and/or genetic markers, among other materials. Additionally, each exception must be re-certified, or re-reported to UNOS, every 3 months, with updated information that is diagnosis- specific. For example, as outlined on their website, hepatocellular carcinoma requires an updated MRI or CT abdomen along with an alpha-fetoprotein (AFP) tumor marker test, every three months. For reference, AFP is a protein made in the liver during fetal development. AFP greatly reduces by 1 year of age, and should only be found at low levels in adults (10-20 ng/ml). Higher than normal levels (> 400 ng/ml) of AFP could be suggestive of liver cancer, among other health conditions.⁹ Cystic Fibrosis (CF), however, requires no new additional information once the first exception has been submitted. Penn Medicine simply needs to re-verify with UNOS every three months that the patient remains listed with a diagnosis of CF.⁸

Patients who are listed with a MELD exception are listed with what is known as a Median MELD at transplant (MMaT). The MMaT varies for each transplant program, and is calculated using the median of the MELD scores at the time of transplant of all recipients at least 12 years old, who were transplanted at hospitals within 250 nautical miles (NM) of the candidate’s listing hospital, in a 365-day period.¹⁰ The MMaT scores were updated on September 29th  of 2021, with scores being updated twice yearly. MPaT refers to the Median PELD at Transplant, and applies to patients less than 12 years of age. The MPaT is a national calculation and, unlike the MMaT score, is the same for all transplant programs with PELD exception candidates. It will remain at 35.¹¹

In conclusion, liver transplant is a procedure that for many patients can be the difference between life and death. The MELD and PELD score are both prognostic scoring systems based on laboratory parameters used to predict three-month mortality due to liver disease, and aid clinicians in determining which patients are at the greatest need of a liver transplant. Despite the clear utility of both scores, it is important to note that there are some patients with certain liver conditions for which the MELD or PELD score cannot accurately characterize long-term risk. Consequentially, there are MELD and PELD exception scores, which aid in providing patients with the best chance possible for getting a liver transplant based on their health condition. As aspiring healthcare clinicians, it is important to understand that our role involves much than knowing the medications used in managing a disease state. Having a solid understanding of common prognostic tools used in assessing the overall status of disease severity will ultimately enable us to achieve optimized patient outcomes. While it is impossible to know all the prognostic tools, one should take advantage of every opportunity to become more familiar with those encountered during clinical practice.

References:

1. About UNOS. UNOS. https://unos.org/about/. Accessed November 13, 2021
2. Organ transplant trends | More transplants that Ever. UNOS https://unos.org/data/transplant-trends/. Accessed November 26, 2021.
3. What Is the MELD Score and When Do We Use It? U.S. Department of Veterans Affairs. https://www.hepatitis.va.gov/cirrhosis/background/cirrhosis-meld-score.asp.  Accessed November 26
4. Understanding Meld Scores for Liver Transplantation | UPMC. https://www.upmc.com/services/transplant/liver/process/waiting-list/meld-score. Accessed November 26, 2021
5. About MELD and PELD – OPTN https://optn.transplant.hrsa.gov/data/allocation-calculators/about-meld-and-peld/. Accessed November 26, 2021
6. Questions & Answers for Transplant Candidates about MELD and PELD. United Network of Organ Sharing. https://unos.org/wp-content/uploads/MELD_PELD.pdf. Accessed November 23, 2021.
7. The National Liver Review Board Policy Process. UNOS. https://unos.org/policy/nlrb-overview/. Accessed November 26, 2021
8. Understanding Model for End-Stage Liver Disease (MELD) Exception Criteria – Penn Medicine. https://www.pennmedicine.org/updates/blogs/transplant-update/2020/july/understanding-meld-exception-criteria. Accessed November 10, 2021.
9. Alpha-Fetoprotein Tumor Marker (Blood) – Health Encyclopedia – University of Rochester Medical Center. https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=alpha_fetoprotein_tumor_marker. Accessed November 28, 2021.
10. Calculate Median MELD at Transplant around the Donor Hospital and Upstate Sorting within Liver Allocation – OPTN. https://optn.transplant.hrsa.gov/policies-bylaws/public-comment/calculate-median-meld-at-transplant-around-the-donor-hospital-and-update-sorting-within-liver-allocation/. Accessed November 26, 2021
11. Updated Median MELD at Transplant scores take effect September 29 – OPTN. https://optn.transplant.hrsa.gov/news/updated-median-meld-at-transplant-scores-take-effect-september-29/. Accessed November 27, 2021.

Published by Rho Chi Post