The course of posttransplant hepatitis c infection: Comparative impact of donor and recipient source of the favorable IL28B genotype and other variables

Andres Duarte-Rojo, Bart J. Veldt, David D. Goldstein, Hans L. Tillman, Kymberly D. Watt, Julie K. Heimbach, John G. McHutchison, John J. Poterucha, Florencia Vargas-Vorackova, Michael R. Charlton

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

BACKGROUND AND AIMS: The IL28B genotype has been linked to sustained virological response (SVR) in hepatitis C virus (HCV). Its role on disease biology and progression is less clear. We characterized the effects of IL28B genotype on HCV recurrence, allograft histology, rate of SVR, and survival after liver transplantation (LT) in HCV. METHODS: Consecutive patients who underwent LT with HCV were studied. The rs12979860 genotype from both the donor was and recipient was determined. Measured endpoints included histologic HCV recurrence (inflammatory grade and fibrosis stage), acute cellular rejection, SVR, retransplantation, and death. RESULTS: The study cohort comprised 272 consecutive LT in 255 patients. C-allele frequency was 56% in recipients and 70% in donors (P<0.001). Recipient IL28B CC genotype was associated with lower alanine aminotransferase levels and viral load at recurrence and a lower frequency of F2 on liver biopsy at 1 year after LT, when compared with the non-CC genotype (P=0.012). The opposite was observed in LT with donor CC genotype (P=0.003). Both recipient and donor CC genotype favored SVR, and when the two of them occurred together, the SVR rate reached 90%. Survival analysis after 5.5 years of follow-up showed a higher rate of progression to cirrhosis (hazard ratio, 5.96; 95% confidence interval, 1.29-27.6), liver-related death, or retransplantation among liver transplant recipients with a CC genotype donor. CONCLUSIONS: The IL28B genotype is predictive not only of SVR but also of the histologic diagnosis of posttransplant hepatitis C, with donor CC genotype favoring inflammation and fibrosis, and adverse outcomes during long-term follow-up. A favorable effect of donor CC genotype is manifest only after antiviral therapy.

Original languageEnglish (US)
Pages (from-to)197-203
Number of pages7
JournalTransplantation
Volume94
Issue number2
DOIs
StatePublished - Jul 27 2012

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Hepatitis
Genotype
Tissue Donors
Infection
Hepacivirus
Liver Transplantation
Fibrosis
Recurrence
Liver
Survival Analysis
Hepatitis C
Viral Load
Alanine Transaminase
Gene Frequency
Antiviral Agents
Allografts
Disease Progression
Histology
Cohort Studies
Confidence Intervals

Keywords

  • Acute cellular rejection
  • Fibrosis
  • Histologic grade
  • Interferon L
  • Survival
  • Sustained virological response

ASJC Scopus subject areas

  • Transplantation

Cite this

Duarte-Rojo, A., Veldt, B. J., Goldstein, D. D., Tillman, H. L., Watt, K. D., Heimbach, J. K., ... Charlton, M. R. (2012). The course of posttransplant hepatitis c infection: Comparative impact of donor and recipient source of the favorable IL28B genotype and other variables. Transplantation, 94(2), 197-203. https://doi.org/10.1097/TP.0b013e3182547551

The course of posttransplant hepatitis c infection : Comparative impact of donor and recipient source of the favorable IL28B genotype and other variables. / Duarte-Rojo, Andres; Veldt, Bart J.; Goldstein, David D.; Tillman, Hans L.; Watt, Kymberly D.; Heimbach, Julie K.; McHutchison, John G.; Poterucha, John J.; Vargas-Vorackova, Florencia; Charlton, Michael R.

In: Transplantation, Vol. 94, No. 2, 27.07.2012, p. 197-203.

Research output: Contribution to journalArticle

Duarte-Rojo, A, Veldt, BJ, Goldstein, DD, Tillman, HL, Watt, KD, Heimbach, JK, McHutchison, JG, Poterucha, JJ, Vargas-Vorackova, F & Charlton, MR 2012, 'The course of posttransplant hepatitis c infection: Comparative impact of donor and recipient source of the favorable IL28B genotype and other variables', Transplantation, vol. 94, no. 2, pp. 197-203. https://doi.org/10.1097/TP.0b013e3182547551
Duarte-Rojo, Andres ; Veldt, Bart J. ; Goldstein, David D. ; Tillman, Hans L. ; Watt, Kymberly D. ; Heimbach, Julie K. ; McHutchison, John G. ; Poterucha, John J. ; Vargas-Vorackova, Florencia ; Charlton, Michael R. / The course of posttransplant hepatitis c infection : Comparative impact of donor and recipient source of the favorable IL28B genotype and other variables. In: Transplantation. 2012 ; Vol. 94, No. 2. pp. 197-203.
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abstract = "BACKGROUND AND AIMS: The IL28B genotype has been linked to sustained virological response (SVR) in hepatitis C virus (HCV). Its role on disease biology and progression is less clear. We characterized the effects of IL28B genotype on HCV recurrence, allograft histology, rate of SVR, and survival after liver transplantation (LT) in HCV. METHODS: Consecutive patients who underwent LT with HCV were studied. The rs12979860 genotype from both the donor was and recipient was determined. Measured endpoints included histologic HCV recurrence (inflammatory grade and fibrosis stage), acute cellular rejection, SVR, retransplantation, and death. RESULTS: The study cohort comprised 272 consecutive LT in 255 patients. C-allele frequency was 56{\%} in recipients and 70{\%} in donors (P<0.001). Recipient IL28B CC genotype was associated with lower alanine aminotransferase levels and viral load at recurrence and a lower frequency of F2 on liver biopsy at 1 year after LT, when compared with the non-CC genotype (P=0.012). The opposite was observed in LT with donor CC genotype (P=0.003). Both recipient and donor CC genotype favored SVR, and when the two of them occurred together, the SVR rate reached 90{\%}. Survival analysis after 5.5 years of follow-up showed a higher rate of progression to cirrhosis (hazard ratio, 5.96; 95{\%} confidence interval, 1.29-27.6), liver-related death, or retransplantation among liver transplant recipients with a CC genotype donor. CONCLUSIONS: The IL28B genotype is predictive not only of SVR but also of the histologic diagnosis of posttransplant hepatitis C, with donor CC genotype favoring inflammation and fibrosis, and adverse outcomes during long-term follow-up. A favorable effect of donor CC genotype is manifest only after antiviral therapy.",
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AU - Goldstein, David D.

AU - Tillman, Hans L.

AU - Watt, Kymberly D.

AU - Heimbach, Julie K.

AU - McHutchison, John G.

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