Survival and Risk of Severe Hepatitis C Virus (HCV) Recurrence in Liver Transplant

Survival and Risk of Severe Hepatitis C Virus (HCV) Recurrence in Liver Transplant (LT) Recipients Coinfected with Human Immunodeficiency Virus (HIV) and HCV

N. Terrault1; B. Barin2; T. D. Schiano3; F. Poordad4; M. Wong5; M. E. de Vera6; D. Simon7; L. Rosenthal8; D. Jayaweera9; L. B. Johnson10; K. M. Olthoff11; V. Stosor12; K. E. Sherman13; B. Eghtesad14; R. Harland15; F. Regenstein16; J. P. Hamilton17; T. L. Pruett18; M. Roland1; P. Stock1
1. UCSF, San Francisco, CA, USA.
2. The EMMES Corporation, Rockville, MD, USA.
3. Mt. Sinai School of Medecine, New York, NY, USA.
4. Cedars Sinai Medical Center, Los Angeles, CA, USA.
5. Beth Israel Deaconess Medical Center, Boston, MA, USA.
6. University of Pittsburgh, Pittsburgh, PA, USA.
7. Rush University, Chicago, IL, USA.
8. Columbia University, New York, NY, USA.
9. University of Miami, Miami, FL, USA.
10. Georgetown Medical Center, San Diego , CA, USA.
11. University of Pennsylvania, Philadelphia, PA, USA.
12. Northwestern University, Chicago, IL, USA.
13. University of Cincinnati, Cincinnati, OH, USA.
14. Cleveland Clinic, Cleveland, OH, USA.
15. University of Chicago, Chicago, IL, USA.
16. Tulane University, New Orleans, LA, USA.
17. Johns Hopkins University, Baltimore, MD, USA.
18. University of Virginia, Charlottesville, VA, USA.


Background: HCV is the most common indication for LT in patients with HIV. Prior studies suggest higher rates of wait-list mortality and worse post-LT survival but U.S. data are limited.

Aims: To compare 1 and 3 year survival and rates of severe HCV disease in HCV-HIV coinfected vs HCV monoinfected LT recipients and identify predictors of these outcomes. Methods: All coinfected LT recipients in the multicenter HIVTR cohort were included. For each case, 1-3 consecutive HCV monoinfected controls matched on single/dual organ transplant, HCC and study site were selected. Study endpoints were patient and graft survival, and severe HCV disease (cholestatic hepatitis, bridging fibrosis or cirrhosis on biopsy, or graft loss due to HCV).

Results: 81 HCV-HIV coinfected cases and 213 HCV controls were followed for median (IQR) 1.5 (0.5-2.5) and 1.4 (0.7-2.3) yrs. HCV-HIV and HCV patients had similar % male, median MELD at LT, % HCC, % dual kidney-LT and % HCV+ donor.

HCV-HIV had lower median recipient age (50 vs 54; p<.0001), donor age (37 vs 42; p=0.05), lower BMI at enrollment (25 vs 28; p<.0001), higher % treated acute rejection (AR) (35% vs 18%; p=0.001) and higher rates of HCV therapy (38% vs 16%; p<.0001) than HCV. One and 3 year graft survival rates (95% CI) were 71% (59-80%) and 59% (45-70%) in HCV-HIV, and 86% (80-90%) and 67% (58-75%), p=0.01. In multivariate analysis, treated AR, dual kidney-LT, HCV+ donor and BMI<21 were significant predictors of graft survival, with history of splenectomy and tacrolimus as initial IMS of borderline significance (Table). One-year cumulative incidence (95% CI) of severe HCV disease was 18% (10-30%) in HCV-HIV and 8% (5-13%) in HCV (p=0.19). The only significant predictor of severe recurrence was treated AR, with HIV status positively but not significantly associated (HR: 1.7, CI 0.8-3.4, p=0.16).

from Jules: in the presentation by Terrault she said I recall that coinfected patients had higher rates of dual kidney/liver transplant, more acute rejection. It appears that coinfected patients need better management & decision-making including better management of drug-drug interactions between HIV meds and transplant meds, coinfected patients should not wait so long to arrange for transplants: they are sicker than monoinfected and so by going on the transplant wait-list they are subject to the same wait as monoinfected and so this places them at an automatic disadvantage so a way to deal with this is to try to get a donor liver and bring that person to the transplant doctor.

Conclusions: Patient and graft survival were lower in HCV-HIV coinfected LT patients than HCV monoinfected patients, but the key predictor of graft loss and severe HCV disease was treated AR. These results support LT in coinfected patients, but highlight the need for better markers of immune activation-suppression in this population, and suggest that dual kidney-LT, low BMI and use of HCV+ donors may confer a higher risk of poor outcome.

Multivariate Predictors Graft Survival in Coinfected Patients Hazard Ratio (HR, 95% CI) P Value
Treated acute rejection (AR)* 3.4 (1.4, 8.4) 0.01
Dual Kidney-LT 4.4 (1.4, 14.1) 0.01
HCV+ Donor 3.4 (1.3, 9.1) 0.01
BMI at Enrollment <21 3.3 (1.2, 9.0) 0.02
Hx of Splenectomy 4.4 (0.9, 21.7) 0.07
Tacrolimus Initial IMS (vs Cyclosporine) 2.5 (0.8, 7.6) 0.10
* As a time-dependent covariate