Interferon-lambda4 genetic polymorphism is associated with the therapy response for hepatitis C virus recurrence after a living donor liver transplant

H. Konishi, T. Motomura, Y. Matsumoto, N. Harimoto, T. Ikegami, T. Yoshizumi, Y. Soejima, K. Shirabe, T. Fukuhara, Y. Maehara

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Abstract

The standard therapy against hepatitis C virus (HCV) recurrence postliver transplantation includes interferon (IFN)α and ribavirin. IFNL4 ss469415590 polymorphism has been reported as a novel predictor of the response to IFN therapy for chronic HCV infection. We examined the impact of IFNL4 polymorphism on the responsiveness to IFN therapy after liver transplantation. Tissue specimens were collected from 80 HCV-infected recipients and 78 liver donors, and their IFNL4 ss469415590 genotype, hepatic IFNL4 and interferon-stimulated genes' mRNA expression levels were examined. The association of the polymorphism and expression levels in terms of the IFN therapy response to HCV recurrence was analysed. Most individuals who had rs8099917 risk alleles also had ss469415590 risk alleles (R2 = 0.9). Sustained virological response (SVR) rates were higher in both liver graft recipients and transplants with ss469415590 TT/TT alleles than in those with the risk ΔG allele (P = 0.003 and P = 0.005, respectively). In recipients with ss469415590 TT/TT, IFNL4 TT mRNA levels showed no significant differences between livers of patients who responded to therapy and those who did not (P = 0.4). In recipients with the risk ΔG allele, IFNL4 ΔG mRNA expression levels were significantly lower in SVR patients than in non-SVR patients (P = 0.02). Hepatic interferon stimulable genes and IFNL4 mRNA expression were correlated. Our findings suggest that analysing the ss469415590 genotype and IFNL4 ΔG expression provides a novel prediction strategy for the possible response to IFN therapy after liver transplantation.

Original languageEnglish
Pages (from-to)397-404
Number of pages8
JournalJournal of Viral Hepatitis
Volume21
Issue number6
DOIs
Publication statusPublished - Jun 2014

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Living Donors
Genetic Polymorphisms
Hepacivirus
Interferons
Transplants
Recurrence
Liver
Alleles
Messenger RNA
Liver Transplantation
Therapeutics
Genotype
Ribavirin
Chronic Hepatitis C
Virus Diseases
Transplantation
Tissue Donors
Gene Expression
Genes

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Infectious Diseases
  • Virology

Cite this

Interferon-lambda4 genetic polymorphism is associated with the therapy response for hepatitis C virus recurrence after a living donor liver transplant. / Konishi, H.; Motomura, T.; Matsumoto, Y.; Harimoto, N.; Ikegami, T.; Yoshizumi, T.; Soejima, Y.; Shirabe, K.; Fukuhara, T.; Maehara, Y.

In: Journal of Viral Hepatitis, Vol. 21, No. 6, 06.2014, p. 397-404.

Research output: Contribution to journalArticle

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AU - Ikegami, T.

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