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Direct-Acting Antiviral Therapy and Improvement in Graft Survival of Hepatitis C Liver Transplant Recipients

Cholankeril, George MD1; Li, Andrew A. MD1; Yoo, Eric R. MD1; Ahmed, Aijaz MD1

doi: 10.1097/TP.0000000000001926
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1 Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA.

Received 1 July 2017. Revision received 2 August 2017.

Accepted 10 August 2017.

The authors declare no funding or conflicts of interest.

G.C. participated in the study concept and design, acquisition of data, analysis and interpretation of data, drafting and critical revision of the article, and study supervision. A.A.L. and E.R.Y. participated in the study concept and design, interpretation of data, drafting of the article, and critical revision of the article. A.A. participated in the study concept and design, interpretation of data, drafting and critical revision of the article, and study supervision.

Correspondence: Aijaz Ahmed, MD, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 750 Welch Road 210, Palo Alto, CA 94304. (aijazahmed@stanford.edu).

Liver transplantation of patients with untreated hepatitis C virus (HCV) infection leads to universal reinfection of the graft. Up to 10% of liver transplant (LT) recipients with recurrent HCV infection can develop fibrosing cholestatic hepatitis (FCH) followed by acute graft failure (AGF). LT recipients with severe and rapid recurrence of HCV infection, including FCH and cirrhosis-related hepatic decompensation with a life expectancy of 1 year or less were offered treatment under the sofosbuvir compassionate use program in 2013 (prior to regulatory approval of sofosbuvir).1 Due to the lack of direct corroborating evidence, it has been presumed that direct-acting antiviral (DAA) agents, such as sofosbuvir, may have impacted and potentially improved the short-term graft survival in HCV LT recipients.

Using the United Network for Organ Sharing (UNOS) registry, annual rates for AGF were analyzed among HCV and non-HCV LT recipients. AGF was defined as graft failure diagnosed within 1-year of LT surgery and documented in the UNOS registry.

From 2011 to 2016, there was a significant decline in the annual rate of AGF in HCV compared with non-HCV LT recipients (Figure 1). Notably, AGF rate in HCV group declined sharply in 2013 to 2014 by 26.3%. From 2014 to 2016 (DAA era), annual rates for AGF in HCV and non-HCV LT recipients were comparable and statistically insignificant (HCV 3.6% vs non-HCV 3.5; P = 0.85). For the first time in 2016, AGF rate in HCV LT recipients was observed to be lower than that in non-HCV (HCV 2.8% vs non-HCV 3.0%, P = 0.15) counterparts.

FIGURE 1

FIGURE 1

HCV LT recipients with AGF had a higher mortality rate (HCV 58.7% vs non-HCV 35.1%; P <0.001) and a lower retransplantation rate (HCV 39.7% vs non-HCV 54.4%; P < 0.001) during 2011 to 2016. In addition, HCV recipients also had a lower median donor age (HCV 40 years vs non-HCV 43 years; P <0.001). Temporal trends in mortality, retransplantation, or donor age were not observed during this study period.

Specific data regarding the use of DAA agents in the pretransplant and posttransplant setting were not available within the UNOS registry. Nevertheless, clinical guidelines have recommended the use of DAA therapy in this subpopulation.2,3 Widespread use of DAA agents for recurrent HCV infection including FCH can be contributing to the rapid decline in AGF among HCV LT recipients.

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REFERENCES

1. Forns X, Charlton M, Denning J, et al. Sofosbuvir compassionate use program for patients with severe recurrent hepatitis C after liver transplantation. Hepatology. 2015;61:1485–1494.
2. Terrault NA, McCaughan GW, Curry MP, et al. International Liver Transplantation Society consensus statement on hepatitis C management in liver transplant candidates. Transplantation. 2017;101:945–955.
3. Terrault NA, Berenguer M, Strasser SI, et al. International Liver Transplantation Society Consensus Statement on hepatitis C management in liver transplant recipients. Transplantation. 2017;101:956–967.
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