title: Interferon-lambda4 genetic polymorphism is associated with the therapy response for hepatitis C virus recurrence after a living donor liver transplant.
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 (R(2) = 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.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Gotemba city, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Konishi
authors.forename: T
authors.initials: T
authors.lastname: Motomura
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: N
authors.initials: N
authors.lastname: Harimoto
authors.forename: T
authors.initials: T
authors.lastname: Ikegami
authors.forename: T
authors.initials: T
authors.lastname: Yoshizumi
authors.forename: Y
authors.initials: Y
authors.lastname: Soejima
authors.forename: K
authors.initials: K
authors.lastname: Shirabe
authors.forename: T
authors.initials: T
authors.lastname: Fukuhara
authors.forename: Y
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D020869:Gene Expression Profiling; D005838:Genotype; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007378:Interleukins / Q000235:genetics*; D016031:Liver Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use; D066027:Transplant Recipients; D016896:Treatment Outcome; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C579163:IFNL4 protein, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b
keywords: HCV; IFNL4; genetic polymorphism; interferon therapy; living donor liver transplantation