Direct-Acting Antiviral Therapy Immune-Mediated Graft Dysfunction in Liver Transplant Recipients with Hepatitis C

C. Chan,¹ E. Agudelo,² J. Haydek,³ M. Hoteit,⁴ M. Laurito,⁵ J. Norvell,³ T. Schiano,⁶ N. Terrault,² E. Verna,⁵ A. Yang,¹ J. Levitsky.¹

¹Northwestern University, Chicago, IL
²UCSF, San Francisco, CA
³Emory University, Atl, GA
⁴University of Pennsylvania, Philadelphia, PA
⁵Columbia University, NY, NY
⁶Mount Sinai, NY, NY.

Meeting: 2018 American Transplant Congress

Abstract number: 250

Keywords: Graft function, Liver transplantation, Multicenter studies, Viral therapy

Session Information

Session Name: Concurrent Session: Liver: Viral Hepatitis

Session Type: Concurrent Session

Date: Monday, June 4, 2018

Session Time: 2:30pm-4:00pm

Presentation Time: 3:18pm-3:30pm

Location: Room 602/603/604

Background and Aims:

Interferon (IFN) treatment of hepatitis C virus (HCV) infection after liver transplantation (LT) can result in severe immune-mediated graft dysfunction (IGD). The occurrence of and risk factors for IGD during or after direct-acting antiviral (DAA) therapy have not been reported.

Methods:

We conducted a multicenter study of LT recipients with recurrent HCV who did or did not develop DAA-IGD (1 case: 2 controls; total of 33 cases vs 66 controls, matched by transplant year). We performed a multivariate analysis of factors during and after treatment predictive of DAA-IGD and reported relevant outcomes.

Results:

The incidence of DAA-IGD in patients treated between 2014 and 2016 was 3.4% (33/978). IGD occurred only after treatment (113 ± 84 days post-therapy). IGD was diagnosed by liver biopsy: 48% of cases had plasma cell hepatitis, 36% acute cellular rejection, 9% chronic rejection, and 6% had a combination of findings. Mean time to liver test resolution was 103 ± 121 days; 25% had persistent abnormalities. Complications: 33% hospitalized, 20% steroid-induced hyperglycemia, 9% infection, one death; no retransplantation. A multivariate regression analysis found significant associations between abnormal liver tests during and soon after DAA therapy and the later diagnosis of IGD. No other risk factors were identified, including type or degree of immunosuppression.

		Odds ratio	p	AUC
During treatment	ALT TB AP	1.004 1.061 1.001	0.009 0.087 0.134	0.727
Post-treatment	ALT TB AP	1.002 1.026 1.001	0.001 0.218 0.001	0.937
[Delta] baseline to during treatment	ALT TB AP	1.002 1.028 1.001	0.08 0.391 0.119	0.641
[Delta] baseline to post-treatment	ALT TB AP	1.001 1.012 1.001	0.002 0.557 0.03	0.822

Odds ratio p AUC

During treatment ALT

TB

AP
1.004

1.061

1.001
0.009

0.087

0.134

0.727

Post-treatment ALT

TB

AP
1.002

1.026

1.001
0.001

0.218

0.001
0.937

[Delta] baseline to during treatment ALT

TB

AP
1.002

1.028

1.001
0.08

0.391

0.119
0.641

[Delta] baseline to post-treatment ALT

TB

AP
1.001

1.012

1.001
0.002

0.557

0.03
0.822

Conclusions:

Liver tests not significantly improving on DAA therapy and/or worsening soon after completion may be a sign of impending IGD. These indicators should guide clinicians to consider augmentation of immunosuppression and/or liver biopsy to diagnose and treat IGD early on before the more deleterious later clinical presentation.

CITATION INFORMATION: Chan C., Agudelo E., Haydek J., Hoteit M., Laurito M., Norvell J., Schiano T., Terrault N., Verna E., Yang A., Levitsky J. Direct-Acting Antiviral Therapy Immune-Mediated Graft Dysfunction in Liver Transplant Recipients with Hepatitis C Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Chan C, Agudelo E, Haydek J, Hoteit M, Laurito M, Norvell J, Schiano T, Terrault N, Verna E, Yang A, Levitsky J. Direct-Acting Antiviral Therapy Immune-Mediated Graft Dysfunction in Liver Transplant Recipients with Hepatitis C [abstract]. https://atcmeetingabstracts.com/abstract/direct-acting-antiviral-therapy-immune-mediated-graft-dysfunction-in-liver-transplant-recipients-with-hepatitis-c/. Accessed May 11, 2025.

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