Update on Liver Transplantation: The Jefferson Experience

Educational Objectives

The goal of this program is to improve allocation of resources for liver transplantation. After hearing and assimilating this program, the clinician will be better able to:

1. Review recent updates to the regulatory structure and framework for organ transplantation.
2. Determine patient eligibility for liver transplantation.
3. Develop strategies to expand the donor pool of organs.

Summary

Background: the development and approval of cyclosporine in 1983 was a major breakthrough in the field of liver transplantation (LT); in the same year, the National Institutes of Health (NIH) approved LT as a valid therapy at a consensus development conference; the National Organ Transplant Act was passed in 1984 and established the National Organ Procurement and Transplant Network (OPTN), which established the Scientific Registry for Transplant Recipients (SRTR)

Regulations: United Network for Organ Sharing (UNOS) is the umbrella, nonprofit organization involved in transplantation in the United States (US); the OPTN is a unique public-private partnership that links all professionals involved in organ transplantation; Organ Procurement Organizations (OPOs) are under the umbrella of the OPTN; the Philadelphia OPO is the Gift of Life Program; SRTR maintains the database of all donor and recipient data, which are accessible to the public; there are 11 UNOS regions, which are further subdivided into 58 federally approved donor service areas (DSAs); each DSA is served by an OPO

Indications for Organ Transplantation

Acute liver failure (ALF): also known as fulminant hepatic failure and is characterized by development of coagulopathy, any degree of hepatic encephalopathy (HE) without a pre-existing liver disease, and an illness of <26 wk duration; it accounts for ≈5% of LTs in the US; acetaminophen toxicity is the leading etiology (≈50% of cases); patients who require LT are listed as the highest priority

Decompensated cirrhosis: comprises the largest group of patients presenting for LT; the complications of cirrhosis can be due to portal hypertension (PH) or liver insufficiency; complications of PH include hepatopulmonary syndrome, portopulmonary hypertension, variceal bleeding, ascites, hydrothorax, spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (HRS); complications of liver insufficiency include jaundice, coagulopathy, and hypoalbuminemia; HE and sarcopenia are observed with both PH and liver insufficiency; according to the most recent OPTN 2020 Annual Data Report, nonalcoholic fatty liver disease-related cirrhosis and alcoholic liver disease are the leading indications for LT; hepatitis C virus (HCV) was the leading indication for LT 10 yr ago

Clinical considerations: patients with any form of chronic liver disease (nonalcoholic steatohepatitis, HCV, or alcoholic liver disease) can remain well compensated for many years; patients with Child Pugh Score (CPS) stage A cirrhosis may have a median survival of >12 yr; development of clinically significant PH reclassifies them to CPS stage B (or decompensated cirrhosis) and the median survival is ≈2 yr; these patients should be referred for LT evaluation; clinically significant PH is the main driver of decompensation and starts with increased intrahepatic resistance to blood flow due to scarring of liver tissue; this progresses to secondary increase of flow through the portal vein due to splanchnic vessel dilation with cirrhosis, causing complications (eg, varices, HE, splenomegaly, ascites)

Outcomes of cirrhosis complications: patients with nonrefractory ascites have a 1-yr survival of 90%; patients with refractory ascites have a 1-yr survival of 40%; median survival is ≈9 mo in patients with a single episode of SBP; the median survival is 6 mo for the slow progressing form (type 2) of HRS and ≈2 wk without LT for type 1

Hepatocellular carcinoma (HCC): diagnosis may be an indication for LT even if the patient has well compensated cirrhosis; patients with a single lesion diagnostic of HCC that is <2 cm, a lesion ≤5 cm, or 3 lesions, each of which are <3 cm without macrovascular invasion or extrahepatic spread, should be worked up for LT; they can be listed based on standard protocols for work up and get Model for End-stage Liver Disease (MELD) exception points (score equal to median MELD at transplant [MMat] minus 3) 6 mo after listing; as per Barcelona approach, patients belonging to stage 0 or A are eligible for transplantation; while waiting on the transplant list, bridging therapy (locoregional treatments through interventional radiology) is given to prevent progression

Evolution of the scoring system: CPS was used in the 1990s to list patients for transplantation; it had limited discriminating ability, used subjective parameters, had laboratory variability, was never validated to predict death, and was of no advantage for a patient who developed HRS because it did not include creatinine; the MELD score, introduced in 2002, was initially validated for patients undergoing transjugular intrahepatic portosystemic shunt procedure in the Mayo Clinic and was later validated for patients undergoing LT; it is calculated using the bilirubin, creatinine, and the international normalized ratio; it de-emphasized the wait time, focused on disease severity, and was objective, transparent, continuous, and very effective; patients with a MELD score <10 have a 3-mo survival rate of 95%, whereas those with a MELD score >35 have a 3-mo survival rate of <40%

MELD exception criteria: similar to HCC, patients who have portopulmonary hypertension, mean pulmonary artery pressure <35 mm Hg, or hepatopulmonary syndrome with a room air pulse oximetry <60 mm Hg can qualify for MELD exception points; other metabolic conditions in which LT is indicated include familial amyloidotic polyneuropathy, hyperoxaluria, and cystic fibrosis

Strategies to increase the donor pool of organs: to meet the large gap in the supply and demand of organs for transplantation, expanded criteria donors are being used; these include donors who may not be optimal but can be used safely; risk factors for impaired graft function include older donor age, evidence of donor obesity or steatosis, donation after circulatory death (DCD), and disease transmission; split liver transplant and live donor transplant are examples of reduced graft sizes; HCV-positive to -negative transplantations are being performed to meet demands; a guidance document (includes informed consent process and assurance of access to HCV treatment) is in place to facilitate the process

Evolution of the MELD system: since its introduction in 2002, the MELD score underwent various iterations until the current system, the Acuity Circles (AC) policy; due to challenges with liver organ allocation, organ disparity, limitations of the MELD and MELD-Na scores, and wide variations in center-specific practices, multiple different but unsuccessful district models were proposed by UNOS (8- and 4-district); the current AC system has allowed for a broader distribution of organs; distribution zones of various sizes are now available around the donor hospital; data indicate that candidates with MELD scores of 15 to 28 and HCC exception received a larger proportion of DCD offers, but those with higher MELD scores and no exceptions had better access to transplants with same donor quality

Jefferson LT program: the first liver transplantation at Jefferson was performed in 1984; >1500 transplants have been performed to date; this is 1 of 2 programs in the Delaware Valley that performs live donor transplantation; over the last 5 yr, ≈80 transplants per yr have been performed; the 3 main elements attributable to these high numbers are wide satellite presence, full outpatient LT evaluation in 4 days, and telehealth; during the COVID-19 pandemic, the program created a closed transplant unit where patients were directly admitted

Readings

Brown RS Jr, Higgins R, Pruett TL. The evolution and direction of OPTN oversight of live organ donation and transplantation in the United States. Am J Transplant. 2009 Jan;9(1):31-4. doi: 10.1111/j.1600-6143.2008.02433.x. Epub 2008 Oct 6; Del Valle K, DuBrock HM. Hepatopulmonary syndrome and portopulmonary hypertension: Pulmonary vascular complications of liver disease. Compr Physiol. 2021 Oct 12;11(4):3281-3302. doi: 10.1002/cphy.c210009. PMID: 34636408; Hughes CB, Humar A. Liver transplantation: current and future. Abdom Radiol (NY). 2021 Jan;46(1):2-8. doi: 10.1007/s00261-019-02357-w; Krowka MJ, Fallon MB, Kawut SM, et al. International liver transplant society practice guidelines: Diagnosis and management of hepatopulmonary syndrome and portopulmonary hypertension. Transplantation. 2016 Jul;100(7):1440-52. doi: 10.1097/TP.0000000000001229; Liu C, Cao Z, Yan H, et al. A Novel SAVE score to stratify decompensation risk in compensated advanced chronic liver disease (CHESS2102): An international multicenter cohort study. Am J Gastroenterol. 2022 Oct 1;117(10):1605-1613. doi: 10.14309/ajg.0000000000001873. Epub 2022 Jun 15; Philip G, Hookey L, Richardson H, et al. Alcohol-associated liver disease is now the most common indication for liver transplant waitlisting among young American adults. Transplantation. 2022 Oct 1;106(10):2000-2005. doi: 10.1097/TP.0000000000004202. Epub 2022 Sep 29; Trifan A, Minea H, Rotaru A, et al. Predictive factors for the prognosis of alcoholic liver cirrhosis. Medicina (Kaunas). 2022;58(12):1859. Published 2022 Dec 16. doi:10.3390/medicina58121859; Wald C, Russo MW, Heimbach JK, et al. New OPTN/UNOS policy for liver transplant allocation: standardization of liver imaging, diagnosis, classification, and reporting of hepatocellular carcinoma. Radiology. 2013 Feb;266(2):376-82. doi: 10.1148/radiol.12121698; Yoshiji H, Nagoshi S, Akahane T, et al. Evidence-based clinical practice guidelines for liver cirrhosis 2020. J Gastroenterol. 2021 Jul;56(7):593-619. doi: 10.1007/s00535-021-01788-x. Epub 2021 Jul 7.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Sass was recorded at the 40th Advances in Gastroenterology Conference, held on June 18, 2022, in Atlantic City, NJ, and presented by the Sidney Kimmel Medical College at Thomas Jefferson University. For information on upcoming CME activities from this presenter, please visit jefferson.edu. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.75 CE contact hours.

Lecture ID:

GE370301

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.