IL28B polymorphisms of both recipient and donor cooperate to influence IFN treatment response in HCV recurrence after liver transplantation, but IL28B SNPs of the recipient play a major role in IFN-induced blocking of HCV replication.
Single nucleotide polymorphisms (SNPs) of the IL28B locus are associated with a positive response to pegylated interferon-alpha and ribavirin (pegIFN-alpha/RBV) treatment of HCV-infected patients. This study evaluated the association between SNPs rs12980275, rs12979860 and rs8099917 and treatment outcome of HCV recurrent infection in HCV-positive patients who underwent liver transplant. We aimed to assess to what extent recipient and/or graft donor IL28B polymorphisms contribute to HCV clearance after transplantation influencing the response to the antiviral treatment. We found that the allele frequencies in donors were in agreement with the pattern expected in the European population. The frequency of favourable genotypes was significantly lower in recipients than in donors, reasonably because the recipients represented a group of patients affected by chronic Hepatitis C. Our study demonstrated that the positive outcome of the pegIFN-alpha/RBV treatment of HCV recurrence is associated with the co-presence of favourable genotypes of both donors and recipients. However, IL28B SNPs of the recipient seem to play a major role in this clinical setting. In particular, homozygosis of rs12979860 favourable genotype in recipients was associated with sustained virological response independently from the donor's genotype. Thus, identification of these SNPs may be useful to predict the response to IFN-based therapy of HCV recurrent infection in liver-transplanted patients.
Vita-Salute San Raffaele University, Milan, Italy; Regenerative Medicine and Biomedical Technologies Unit, ISMETT, Palermo, Italy.
Floriana
F
Barbera
Vita-Salute San Raffaele University, Milan, Italy; Regenerative Medicine and Biomedical Technologies Unit, ISMETT, Palermo, Italy.
Giovanna
G
Russelli
Department of Diagnostic and Therapeutic Services, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Palermo, Italy.
Loredana
L
Pipitone
Department for Care and Study of Abdominal Diseases and Abdominal Transplantation, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Palermo, Italy.
Giada
G
Pietrosi
Department for Care and Study of Abdominal Diseases and Abdominal Transplantation, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Palermo, Italy.
Sveva
S
Corsale
Department for Care and Study of Abdominal Diseases and Abdominal Transplantation, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Palermo, Italy.
Giovanni
G
Vizzini
Department for Care and Study of Abdominal Diseases and Abdominal Transplantation, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Palermo, Italy.
Bruno
B
Gridelli
Regenerative Medicine and Biomedical Technologies Unit, Department of Laboratory Medicine and Advanced Biotechnologies, ISMETT, Palermo, Italy; RiMed Foundation, Palermo, Italy.
Pier Giulio
PG
Conaldi
D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D001483:Base Sequence; D015331:Cohort Studies; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D014019:Tissue Donors; D014779:Virus Replication / Q000187:drug effects*; D055815:Young Adult; D000095022:Interferon Lambda
D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
Hepatitis C virus; Interferon; Interleukin 28B,; Liver transplantation; Polymorphisms