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Multicenter Study
. 2024 Jun 19;8(7):e0462.
doi: 10.1097/HC9.0000000000000462. eCollection 2024 Jul 1.

Liver disease and transplantation in telomere biology disorders: An international multicenter cohort

YunZu Michele Wang  1   2 , Batul Kaj-Carbaidwala  3 , Adam Lane  1   2 , Suneet Agarwal  4 , Fabian Beier  5 , Alison Bertuch  6 , Kristin A Borovsky  7 , Steven K Brennan  8 , Rodrigo T Calado  9 , Luiz Fernando B Catto  9 , Carlo Dufour  10 , Christen L Ebens  11 , Francesca Fioredda  12 , Neelam Giri  13 , Nicholas Gloude  14 , Frederick Goldman  15 , Paula M Hertel  7 , Ryan Himes  16 , Sioban B Keel  17 , Divya T Koura  18 , Christian P Kratz  19 , Sakil Kulkarni  20 , Iris Liou  21 , Taizo A Nakano  22 , Silvia Nastasio  23 , Marena R Niewisch  12   18 , Daniel D Penrice  24 , Ghadir S Sasa  25 , Sharon A Savage  12 , Douglas A Simonetto  24 , David S Ziegler  26   27 , Alexander G Miethke  2   28 , Kasiani C Myers  1   2 ; Clinical Care Consortium for Telomere-associated Ailments (CCCTAA)
Affiliations
Multicenter Study

Liver disease and transplantation in telomere biology disorders: An international multicenter cohort

YunZu Michele Wang et al. Hepatol Commun. .

Abstract

Background: Patients with telomere biology disorders (TBD) develop hepatic disease, including hepatitis, cirrhosis, and hepatopulmonary syndrome. No specific treatment exists for TBD-related liver disease, and the role of liver transplantation (LT) remains controversial. Our study objectives were to describe the clinical characteristics, management, and outcomes in patients with TBD-related liver disease, and their LT outcomes.

Methods: Data from 83 patients with TBD-associated liver disease were obtained from 17 participating centers in the Clinical Care Consortium of Telomere-Associated Ailments and by self-report for our retrospective, multicenter, international cohort study.

Results: Group A ("Advanced") included 40 patients with advanced liver disease. Of these, 20 underwent LT (Group AT). Group M ("Mild") included 43 patients not warranting LT evaluation, none of whom were felt to be medically unfit for liver transplantation. Supplemental oxygen requirement, pulmonary arteriovenous malformation, hepatopulmonary syndrome, and higher bilirubin and international normalized ratio values were associated with Group A. Other demographics, clinical manifestations, and laboratory findings were similar between groups. Six group A patients were declined for LT; 3 died on the waitlist. Median follow-up post-LT was 2.9 years (range 0.6-13.2 y). One-year survival post-LT was 73%. Median survival post-LT has not been reached. Group AT patients had improved survival by age compared to all nontransplant patients (log-rank test p = 0.02). Of 14 patients with pretransplant hypoxemia, 8 (57%) had improved oxygenation after transplant.

Conclusions: LT recipients with TBD do not exhibit excessive posttransplant mortality, and LT improved respiratory status in 57%. A TBD diagnosis should not exclude LT consideration.

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Conflict of interest statement

Suneet Agarwal consults, received grants, and owns stock in Rejuveron Telomere Therapeutics and advises Cimeio Therapeutics. Steven Brennan owns stock in Merck. Christen Ebens consults for Elixirgen Therapeutics. Nicholas Gloude consults for Rocket Pharmaceuticals. Sioban Keel consults for Disc Medicine. Douglas Simonetto consults for Mallinckrodt, BioVie, Resolution Therapeutics, and Evive. David Ziegler consults and received grants from Accendatech and consults for Bayer, AstraZeneca, Novartis, Day One, FivePhusion, Amgen, Alexion, Norgine, and Roche. Alexander Miethke consults, advises, and received grants from Mirum. Kasiana Myers received grants Elixirgen Therapeutics and Incyte. The remaining authors have no conflicts to report.

Figures

None
Graphical abstract
FIGURE 1
FIGURE 1
Group A clinical course and outcomes. Abbreviation: LT, liver transplant.
FIGURE 2
FIGURE 2
Post-liver transplantation clinical course of 14 liver transplant recipients. Positive (blue boxes) and negative (red boxes) changes post-liver transplantation in individual patients. Each row represents 1 patient unless otherwise indicated by n = 2 (2 patients) or n = 4 (4 patients). Abbreviations: GI, Gastrointestinal; hgb, hemoglobin; SAA, severe aplastic anemia.
FIGURE 3
FIGURE 3
Kaplan-Meier survival curve by (A) group assignment in entire cohort, (B) HPS status in entire cohort, and (C) LT status in cohort with HPS. Abbreviations: HPS, hepatopulmonary syndrome; LT, liver transplant.
See this image and copyright information in PMC

References

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