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. 2021 Oct 1;274(4):613-620.
doi: 10.1097/SLA.0000000000005070.

Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation

Michael K Turgeon  1 , Shimul A Shah  2 , Aaron M Delman  2 , Benjamin V Tran  3 , Vatche G Agopian  3 , Joel P Wedd  1 , Joseph F Magliocca  1 , Ahyoung Kim  4 , Andrew Cameron  4 , Ali Olyaei  5 , Susan L Orloff  5 , Matthew P Anderson  6 , Chandrashekhar A Kubal  6 , Robert M Cannon  7 , Jayme E Locke  7 , Mary A Simpson  8 , Mohamed E Akoad  8 , Chelsey P Wongjirad  9 , Juliet Emamaullee  9 , Amika Moro  10 , Federico Aucejo  10 , Cyrus A Feizpour  11 , Parsia A Vagefi  11 , Mindie H Nguyen  12 , Carlos O Esquivel  12 , Kiran Dhanireddy  13 , Vijay Subramanian  13 , Alejandro Chavarriaga  14 , Marwan M Kazimi  14 , Maia S Anderson  15 , Christopher J Sonnenday  15 , Steven C Kim  16 , David P Foley  16 , Marwan Abdouljoud  17 , Reena J Salgia  17 , Dimitrios Moris  18 , Debra L Sudan  18 , Swaytha R Ganesh  19 , Abhinav Humar  19 , Majella Doyle  20 , William C Chapman  20 , Shishir K Maithel  1
Affiliations

Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation

Michael K Turgeon et al. Ann Surg. .

Abstract

Objective: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT).

Summary of background data: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate.

Methods: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS).

Results: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01).

Conclusions: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

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Conflict of interest statement

S. A. Shah, Veloxis Pharmaceuticals Role(s): Membership on advisory committee or review panels. Organ Recovery Systems Role(s): Other activities (please specify), Research funding. J. Emamaullee, iSPY COVID trial Role(s): Other activities (please specify), Data Monitoring Committee. Gilead Role(s): Other activities (please specify), Research funding. American Society of Transplant Surgeons Role(s): Other activities (please specify), Research funding. American Association for the Study of Liver Diseases Role(s): Other activities (please specify), Research Funding. National Cancer Institute Role(s): Other activities (please specify), Research funding. M. H. Nguyen, Gilead Role(s): Other activities (please specify), Research support. Glycotest Role(s): Other activities (please specify), Research support. National Cancer Institute Role(s): Other activities (please specify), Research support. Bayer Role(s): Consulting. Esai Role(s): Consulting. Novartis Role(s): Consulting. Gilead Role(s): Consulting. Exact Sciences Role(s): Consulting. Laboratory of Advanced Medicine Role(s): Consulting. W. C. Chapman, Novartis Role(s): Membership on advisory committee or review panels. Pathfinder Role(s): Other activities (please specify), IP royalties.; S. K. Maithel, Celgene (Bristol Meyers Squibbs). All the other authors report no conflicts of interest.

Figures

FIGURE 1.
FIGURE 1.
HCC recurrence-free survival by SVR for interferon-naïve patients with HCV-associated HCC within Milan criteria who underwent liver transplantation.
FIGURE 2.
FIGURE 2.
HCC recurrence-free survival by timing of DAA therapy initiation for interferon-naïve patients with HCV-associated HCC within Milan criteria who underwent liver transplantation.
See this image and copyright information in PMC

References

    1. Kim HS, El-Serag HB. The epidemiology of hepatocellular carcinoma in the USA. Curr Gastroenterol Rep. 2019;21:17. - PubMed
    1. White DL, Thrift AP, Kanwal F, et al. Incidence of hepatocellular carcinoma in all 50 United States, from 2000 through 2012. Gastroenterology. 2017;152:812–820e5. - PMC - PubMed
    1. Ghouri YA, Mian I, Rowe JH. Review of hepatocellular carcinoma: epidemiology, etiology, and carcinogenesis. J Carcinog. 2017;16:1. - PMC - PubMed
    1. González-Grande R, Jiménez-Pérez M, González Arjona C, et al. New approaches in the treatment of hepatitis C. World J Gastroenterol. 2016;22:1421–1432. - PMC - PubMed
    1. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142:1264–1273e1. - PMC - PubMed

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