Hepatitis C genotype influences post-liver transplant outcomes

Isabel Campos-Varela, Jennifer C. Lai, Elizabeth C. Verna, Jacqueline G. O'Leary, R. Todd Stravitz, Lisa M. Forman, James F. Trotter, Robert S. Brown, Norah A. Terrault

Research output: Contribution to journalArticle

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Abstract

In nontransplant patients with chronic hepatitis C virus (HCV), HCV genotype has been linked with a differential response to antiviral therapy, risk of steatosis and fibrosis, as well as all-cause mortality, but the role of HCV genotypes in posttransplant disease progression is less clear. Methods. Using the multicenter CRUSH-C cohort, genotype-specific rates of advanced fibrosis, HCV-specific graft loss and response of antiviral therapy were examined. Results. Among 745 recipients (605 [81%] genotype 1, 53 [7%] genotype 2, and 87 [12%] genotype 3), followed for a median of 3.1 years (range, 2.0-8.0), the unadjusted cumulative rate of advanced fibrosis at 3 years was 31%, 19%, and 19% for genotypes 1, 2, and 3 (P = 0.008). After multivariable adjustment, genotype remained a significant predictor, with genotype 2 having a 66% lower risk (P = 0.02) and genotype 3 having a 41% lower risk (P = 0.07) of advanced fibrosis compared to genotype 1 patients. The cumulative 5-year rates of HCV-specific graft survival were 84%, 90%, and 94% for genotypes 1, 2, and 3 (P = 0.10). A total of 37% received antiviral therapy, with higher rates of sustained virologic response in patients with genotype 2 (hazard ratios, 5.10; P = 0.003) and genotype 3 (hazard ratios, 3.27; P = 0.006) compared to patients with genotype 1. Conclusion. Risk of advanced fibrosis and response to therapy are strongly influenced by genotype. Liver transplantation recipients with HCV genotype 1 have the highest risk of advanced fibrosis and lowest sustained virologic response rate. These findings highlight the need for genotype-specific management strategies.

Original languageEnglish (US)
Pages (from-to)835-840
Number of pages6
JournalTransplantation
Volume99
Issue number4
DOIs
StatePublished - Jan 1 2015

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Hepatitis C
Genotype
Transplants
Liver
Hepacivirus
Fibrosis
Antiviral Agents
Graft Survival
Chronic Hepatitis C
Therapeutics
Liver Transplantation

ASJC Scopus subject areas

  • Transplantation

Cite this

Campos-Varela, I., Lai, J. C., Verna, E. C., O'Leary, J. G., Todd Stravitz, R., Forman, L. M., ... Terrault, N. A. (2015). Hepatitis C genotype influences post-liver transplant outcomes. Transplantation, 99(4), 835-840. https://doi.org/10.1097/TP.0000000000000413

Hepatitis C genotype influences post-liver transplant outcomes. / Campos-Varela, Isabel; Lai, Jennifer C.; Verna, Elizabeth C.; O'Leary, Jacqueline G.; Todd Stravitz, R.; Forman, Lisa M.; Trotter, James F.; Brown, Robert S.; Terrault, Norah A.

In: Transplantation, Vol. 99, No. 4, 01.01.2015, p. 835-840.

Research output: Contribution to journalArticle

Campos-Varela, I, Lai, JC, Verna, EC, O'Leary, JG, Todd Stravitz, R, Forman, LM, Trotter, JF, Brown, RS & Terrault, NA 2015, 'Hepatitis C genotype influences post-liver transplant outcomes', Transplantation, vol. 99, no. 4, pp. 835-840. https://doi.org/10.1097/TP.0000000000000413
Campos-Varela I, Lai JC, Verna EC, O'Leary JG, Todd Stravitz R, Forman LM et al. Hepatitis C genotype influences post-liver transplant outcomes. Transplantation. 2015 Jan 1;99(4):835-840. https://doi.org/10.1097/TP.0000000000000413
Campos-Varela, Isabel ; Lai, Jennifer C. ; Verna, Elizabeth C. ; O'Leary, Jacqueline G. ; Todd Stravitz, R. ; Forman, Lisa M. ; Trotter, James F. ; Brown, Robert S. ; Terrault, Norah A. / Hepatitis C genotype influences post-liver transplant outcomes. In: Transplantation. 2015 ; Vol. 99, No. 4. pp. 835-840.
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title = "Hepatitis C genotype influences post-liver transplant outcomes",
abstract = "In nontransplant patients with chronic hepatitis C virus (HCV), HCV genotype has been linked with a differential response to antiviral therapy, risk of steatosis and fibrosis, as well as all-cause mortality, but the role of HCV genotypes in posttransplant disease progression is less clear. Methods. Using the multicenter CRUSH-C cohort, genotype-specific rates of advanced fibrosis, HCV-specific graft loss and response of antiviral therapy were examined. Results. Among 745 recipients (605 [81{\%}] genotype 1, 53 [7{\%}] genotype 2, and 87 [12{\%}] genotype 3), followed for a median of 3.1 years (range, 2.0-8.0), the unadjusted cumulative rate of advanced fibrosis at 3 years was 31{\%}, 19{\%}, and 19{\%} for genotypes 1, 2, and 3 (P = 0.008). After multivariable adjustment, genotype remained a significant predictor, with genotype 2 having a 66{\%} lower risk (P = 0.02) and genotype 3 having a 41{\%} lower risk (P = 0.07) of advanced fibrosis compared to genotype 1 patients. The cumulative 5-year rates of HCV-specific graft survival were 84{\%}, 90{\%}, and 94{\%} for genotypes 1, 2, and 3 (P = 0.10). A total of 37{\%} received antiviral therapy, with higher rates of sustained virologic response in patients with genotype 2 (hazard ratios, 5.10; P = 0.003) and genotype 3 (hazard ratios, 3.27; P = 0.006) compared to patients with genotype 1. Conclusion. Risk of advanced fibrosis and response to therapy are strongly influenced by genotype. Liver transplantation recipients with HCV genotype 1 have the highest risk of advanced fibrosis and lowest sustained virologic response rate. These findings highlight the need for genotype-specific management strategies.",
author = "Isabel Campos-Varela and Lai, {Jennifer C.} and Verna, {Elizabeth C.} and O'Leary, {Jacqueline G.} and {Todd Stravitz}, R. and Forman, {Lisa M.} and Trotter, {James F.} and Brown, {Robert S.} and Terrault, {Norah A.}",
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AU - Campos-Varela, Isabel

AU - Lai, Jennifer C.

AU - Verna, Elizabeth C.

AU - O'Leary, Jacqueline G.

AU - Todd Stravitz, R.

AU - Forman, Lisa M.

AU - Trotter, James F.

AU - Brown, Robert S.

AU - Terrault, Norah A.

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N2 - In nontransplant patients with chronic hepatitis C virus (HCV), HCV genotype has been linked with a differential response to antiviral therapy, risk of steatosis and fibrosis, as well as all-cause mortality, but the role of HCV genotypes in posttransplant disease progression is less clear. Methods. Using the multicenter CRUSH-C cohort, genotype-specific rates of advanced fibrosis, HCV-specific graft loss and response of antiviral therapy were examined. Results. Among 745 recipients (605 [81%] genotype 1, 53 [7%] genotype 2, and 87 [12%] genotype 3), followed for a median of 3.1 years (range, 2.0-8.0), the unadjusted cumulative rate of advanced fibrosis at 3 years was 31%, 19%, and 19% for genotypes 1, 2, and 3 (P = 0.008). After multivariable adjustment, genotype remained a significant predictor, with genotype 2 having a 66% lower risk (P = 0.02) and genotype 3 having a 41% lower risk (P = 0.07) of advanced fibrosis compared to genotype 1 patients. The cumulative 5-year rates of HCV-specific graft survival were 84%, 90%, and 94% for genotypes 1, 2, and 3 (P = 0.10). A total of 37% received antiviral therapy, with higher rates of sustained virologic response in patients with genotype 2 (hazard ratios, 5.10; P = 0.003) and genotype 3 (hazard ratios, 3.27; P = 0.006) compared to patients with genotype 1. Conclusion. Risk of advanced fibrosis and response to therapy are strongly influenced by genotype. Liver transplantation recipients with HCV genotype 1 have the highest risk of advanced fibrosis and lowest sustained virologic response rate. These findings highlight the need for genotype-specific management strategies.

AB - In nontransplant patients with chronic hepatitis C virus (HCV), HCV genotype has been linked with a differential response to antiviral therapy, risk of steatosis and fibrosis, as well as all-cause mortality, but the role of HCV genotypes in posttransplant disease progression is less clear. Methods. Using the multicenter CRUSH-C cohort, genotype-specific rates of advanced fibrosis, HCV-specific graft loss and response of antiviral therapy were examined. Results. Among 745 recipients (605 [81%] genotype 1, 53 [7%] genotype 2, and 87 [12%] genotype 3), followed for a median of 3.1 years (range, 2.0-8.0), the unadjusted cumulative rate of advanced fibrosis at 3 years was 31%, 19%, and 19% for genotypes 1, 2, and 3 (P = 0.008). After multivariable adjustment, genotype remained a significant predictor, with genotype 2 having a 66% lower risk (P = 0.02) and genotype 3 having a 41% lower risk (P = 0.07) of advanced fibrosis compared to genotype 1 patients. The cumulative 5-year rates of HCV-specific graft survival were 84%, 90%, and 94% for genotypes 1, 2, and 3 (P = 0.10). A total of 37% received antiviral therapy, with higher rates of sustained virologic response in patients with genotype 2 (hazard ratios, 5.10; P = 0.003) and genotype 3 (hazard ratios, 3.27; P = 0.006) compared to patients with genotype 1. Conclusion. Risk of advanced fibrosis and response to therapy are strongly influenced by genotype. Liver transplantation recipients with HCV genotype 1 have the highest risk of advanced fibrosis and lowest sustained virologic response rate. These findings highlight the need for genotype-specific management strategies.

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