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Living Donor Liver Transplantation for Hepatocellular Carcinoma Within and Outside Traditional Selection Criteria: A Multicentric North American Experience

Ivanics, Tommy; Claasen, Marco P A W; Samstein, Benjamin; Emond, Jean C; Fox, Alyson N; Pomfret, Elizabeth; Pomposelli, James; Tabrizian, Parissa; Florman, Sander S; Mehta, Neil; Roberts, John P; Emamaullee, Juliet A; Genyk, Yuri; Hernandez-Alejandro, Roberto; Tomiyama, Koji; Sasaki, Kazunari; Hashimoto, Koji; Nagai, Shunji; Abouljoud, Marwan; Olthoff, Kim M; Hoteit, Maarouf A; Heimbach, Julie; Taner, Timucin; Liapakis, AnnMarie H; Mulligan, David C; Sapisochin, Gonzalo; Halazun, Karim J; ,
OBJECTIVE:To evaluate long-term oncologic outcomes of patients post-living donor liver transplantation (LDLT) within and outside standard transplantation selection criteria and the added value of the incorporation of the New York-California (NYCA) score. BACKGROUND:LDLT offers an opportunity to decrease the liver transplantation waitlist, reduce waitlist mortality, and expand selection criteria for patients with hepatocellular carcinoma (HCC). METHODS:Primary adult LDLT recipients between October 1999 and August 2019 were identified from a multicenter cohort of 12 North American centers. Posttransplantation and recurrence-free survival were evaluated using the Kaplan-Meier method. RESULTS:Three hundred sixty LDLTs were identified. Patients within Milan criteria (MC) at transplantation had a 1, 5, and 10-year posttransplantation survival of 90.9%, 78.5%, and 64.1% versus outside MC 90.4%, 68.6%, and 57.7% ( P = 0.20), respectively. For patients within the University of California San Francisco (UCSF) criteria, respective posttransplantation survival was 90.6%, 77.8%, and 65.0%, versus outside UCSF 92.1%, 63.8%, and 45.8% ( P = 0.08). Fifty-three (83%) patients classified as outside MC at transplantation would have been classified as either low or acceptable risk with the NYCA score. These patients had a 5-year overall survival of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplantation would have been classified as a low or acceptable risk with a 5-year overall survival of 65.3%. CONCLUSIONS:Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-year rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria.
PMID: 37522174
ISSN: 1528-1140
CID: 5613372

Living donor liver transplant candidate and donor selection and engagement: Meeting report from the living donor liver transplant consensus conference

Jesse, Michelle T; Jackson, Whitney E; Liapakis, AnnMarie; Ganesh, Swaytha; Humar, Abhinav; Goldaracena, Nicolas; Levitsky, Josh; Mulligan, David; Pomfret, Elizabeth A; Ladner, Daniela P; Roberts, John P; Mavis, Alisha; Thiessen, Carrie; Trotter, James; Winder, Gerald Scott; Griesemer, Adam D; Pillai, Anjana; Kumar, Vineeta; Verna, Elizabeth C; LaPointe Rudow, Dianne; Han, Hyosun H
INTRODUCTION/BACKGROUND:Living donor liver transplantation (LDLT) is a promising option for mitigating the deceased donor organ shortage and reducing waitlist mortality. Despite excellent outcomes and data supporting expanding candidate indications for LDLT, broader uptake throughout the United States has yet to occur. METHODS:In response to this, the American Society of Transplantation hosted a virtual consensus conference (October 18-19, 2021), bringing together relevant experts with the aim of identifying barriers to broader implementation and making recommendations regarding strategies to address these barriers. In this report, we summarize the findings relevant to the selection and engagement of both the LDLT candidate and living donor. Utilizing a modified Delphi approach, barrier and strategy statements were developed, refined, and voted on for overall barrier importance and potential impact and feasibility of the strategy to address said barrier. RESULTS:Barriers identified fell into three general categories: 1) awareness, acceptance, and engagement across patients (potential candidates and donors), providers, and institutions, 2) data gaps and lack of standardization in candidate and donor selection, and 3) data gaps regarding post-living liver donation outcomes and resource needs. CONCLUSIONS:Strategies to address barriers included efforts toward education and engagement across populations, rigorous and collaborative research, and institutional commitment and resources.
PMID: 36892182
ISSN: 1399-0012
CID: 5457392

Practice patterns of the medical evaluation of living liver donors in the United States

Jackson, Whitney E; Kaplan, Alyson; Saben, Jessica L; Kriss, Michael S; Cisek, Jaime; Samstein, Benjamin; Liapakis, AnnMarie; Pillai, Anjana A; Brown, Robert S; Pomfret, Elizabeth A
Living donor liver transplantation (LDLT) can help address the growing organ shortage in the United States, yet little is known about the current practice patterns in the medical evaluation of living liver donors. We conducted a 131-question survey of all 53 active LDLT transplant programs in the United States to assess current LDLT practices. The response rate was 100%. Donor acceptance rate was 0.33 with an interquartile range of 0.33-0.54 across all centers. Areas of high intercenter agreement included minimum age cutoff of 18 years (73.6%) and the exclusion of those with greater than Class 1 obesity (body mass index, 30.0-34.9 m/kg2 ) (88.4%). Diabetes mellitus was not an absolute exclusion at most centers (61.5%). Selective liver biopsies were performed for steatosis or iron overload on imaging (67.9% and 62.3%, respectively) or for elevated liver enzymes (60.4%). Steatohepatitis is considered an exclusion at most centers (84.9%). The most common hypercoagulable tests performed were factor V Leiden (FVL) (88.5%), protein C (73.1%), protein S (71.2%), antithrombin III (71.2%) and prothrombin gene mutation (65.4%). At 41.5% of centers, donors were allowed to proceed with donation with FVL heterozygote status. Most programs discontinue oral contraceptive pills at least 28 days prior to surgery. At most centers, the need for cardiovascular ischemic risk testing is based on age (73.6%) and the presence of one or more cardiac risk factors (68.0%). Defining areas of practice consensus and variation underscores the need for data generation to develop evidence-based guidance for the evaluation and risk assessment of living liver donors.
PMID: 36111606
ISSN: 1527-6473
CID: 5362442

The use of nondirected donor organs in living donor liver transplantation: Perspectives and guidance

Fox, Alyson N; Liapakis, AnnMarie; Batra, Ramesh; Bittermann, Therese; Emamaullee, Juliet; Emre, Sukru; Genyk, Yuri; Han, Hyosun; Jackson, Whitney; Pomfret, Elizabeth; Raza, Muhammad; Rodriguez-Davalos, Manuel; Rubman Gold, Susan; Samstein, Benjamin; Shenoy, Akhil; Taner, Timucin; Roberts, John P
Interest in anonymous nondirected living organ donation is increasing in the United States and a small number of transplantation centers are accumulating an experience regarding nondirected donation in living donor liver transplantation. Herein, we review current transplant policy, discuss emerging data, draw parallels from nondirected kidney donation, and examine relevant considerations in nondirected living liver donation. We aim to provide a consensus guidance to ensure safe evaluation and selection of nondirected living liver donors and a schema for just allocation of nondirected grafts.
PMID: 34859474
ISSN: 1527-3350
CID: 5362412

The ALT upper reference interval debate: Blame it on the alcohol

Vera, Michael A; Koch, Christopher D; Liapakis, AnnMarie; Lim, Joseph K; El-Khoury, Joe M
BACKGROUND:In 2017, the American College of Gastroenterology (ACG) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition published clinical guidelines recommending the use of alanine aminotransferase (ALT) upper reference limits (URL) of 33, 25, 26, and 22 U/l for men, women, boys, and girls, respectively. This was opposed by laboratory experts who advocated for the use of higher URL of 59, 41, 33, and 24 U/l instead. We suspected that the variable inclusion of individuals who consumed alcohol to be a major contributing source of URL variability and debate. METHODS:Outpatient ALT data (n = 7379) were collected from unique individuals ≥13 y with BMIs of ≥19 and ≤25. A total of 222 (3%) were excluded due to suspected liver disease. Patients were split into a pediatric group (age 13-17 y), an alcohol-restricted adult group (age 18-20 y), and adults with access to alcohol by decade (i.e., age 21-29, 30-39, 40-49, 50-59, 60-69, 70-79, and ≥ 80 y). All ALT values were measured on Roche Cobas 8000 with pyridoxal phosphate and traceable to the IFCC-reference measurement procedure. RESULTS:We derived URL similar to CALIPER for our pediatric population, but closer to ACG-proposed URL in our alcohol-restricted adult group. The URL increased significantly in men and women for all other age groups. CONCLUSIONS:The discrepancy in ALT URL in clinical laboratories may be attributable in part due to the variable inclusion of individuals who recently consumed alcohol in local population derivation studies.
PMID: 34973184
ISSN: 1873-3492
CID: 5362422

Creating a Workflow for the Electronic Medical Record Allows Living Donor Liver Transplantation Programs to Track Candidates and Identify Areas for Optimization. [Meeting Abstract]

Liapakis, A.; Batra, R.; Cohen, E.; Haakinson, D.; Schilsky, M.; Ventura, K.; Mulligan, D.
ISI:000842606302138
ISSN: 1600-6135
CID: 5362642

Variation in Adult Living Donor Liver Transplantation in the United States: Identifying Opportunities for Increased Utilization. [Meeting Abstract]

Lentine, K.; Axelrod, D.; Schnitzler, M.; Li, R.; Dew, M.; Bitterman, T.; Olthoff, K.; Locke, J.; Emre, S.; Hunt, H.; Tanaka, T.; Liapakis, A.
ISI:000842606302135
ISSN: 1600-6135
CID: 5362632

Equitable Access to Liver Transplant: Bridging the Gaps in the Social Determinants of Health

Rosenblatt, Russell; Lee, Hannah; Liapakis, AnnMarie; Lunsford, Keri E; Scott, Andrew; Sharma, Pratima; Wilder, Julius
The COVID-19 pandemic and social justice movement have highlighted the impact of social determinants of health (SDOH) and structural racism in the United States on both access to care and patient outcomes. With the evaluation for liver transplantation being a highly subjective process, there are multiple ways for SDOH to place vulnerable patients at a disadvantage. This policy corner focuses on three different methods to reverse the deleterious effects of SDOH-identify and reduce implicit bias, expand and optimize telemedicine, and improve community outreach.
PMID: 34060678
ISSN: 1527-3350
CID: 5362402

Pregnancy Outcomes After Living Liver Donation: A Multi-Institutional Study

Sonnenberg, Elizabeth M; Lee-Riddle, Grace S; Walls, David O; Caicedo, Juan C; Jackson, Whitney E; Hughes, Lisa; Ladner, Daniela P; Liapakis, AnnMarie; Pomfret, Elizabeth A; Sarkar, Monika; Selzner, Nazia; Torres, Ana Marie; Abt, Peter L; Olthoff, Kim M
Nearly half of living liver donors in North America are women of child-bearing age. Fetal and maternal outcomes after donation are unknown. We conducted a retrospective cohort study of female living liver donors (aged 18-50 years at donation) from 6 transplant centers. Participants were surveyed about their pregnancies and fertility. Outcomes were compared between predonation and postdonation pregnancies. Generalized estimating equations were clustered on donor and adjusted for age at pregnancy, parity, and pregnancy year. Among the 276 donors surveyed, 151 donors responded (54.7% response rate) and reported 313 pregnancies; 168/199 (68.8%) of the predonation pregnancies and 82/114 (71.9%) of the postdonation pregnancies resulted in live births, whereas 16.6% and 24.6% resulted in miscarriage, respectively. Women with postdonation pregnancies were older (32.0 versus 26.7 years; P < 0.001) and more frequently reported abnormal liver enzymes during pregnancy (3.5% versus 0.0%; P = 0.02) and delivery via cesarean delivery (35.4% versus 19.7%; P = 0.01). On adjusted analysis, there was no difference in cesarean delivery (odds ratio [OR], 2.44; 95% confidence interval [95% CI], 0.98-6.08), miscarriage (OR, 1.59; 95% CI, 0.78-3.24), combined endpoints of pregnancy-induced hypertension and preeclampsia (OR, 1.27; 95% CI, 0.36-4.49), or intrauterine growth restriction and preterm birth (OR, 0.91; 95% CI, 0.19-4.3). Of the 49 women who attempted pregnancy after donation, 11 (22.5%) self-reported infertility; however, 8/11 (72.7%) eventually had live births. Aside from increased reporting of abnormal liver enzymes and cesarean deliveries, there was no significant difference in pregnancy outcomes before and after living liver donation. One-fifth of women who attempt pregnancy after liver donation reported infertility, and although the majority went on to successful live births, further exploration is needed to understand the contributing factors. Future research should continue to monitor this patient-centered outcome across a large cohort of donors.
PMID: 33993632
ISSN: 1527-6473
CID: 5362392

Transversus Abdominis Plane Block with Liposomal Bupivacaine Reduces Post-Operative Opioid Requirements in Living Liver Donors

Girone, Gianna; Do, Vincent; Cohen, Elizabeth; Liapakis, Ann Marie; Mulligan, David; Deshpande, Ranjit; Batra, Ramesh
ORIGINAL:0016705
ISSN: 2471-982x
CID: 5457442