Role of cytokine gene polymorphism in recurrent HCV infection after liver transplantation

✍ Scribed by Ziv Ben-Ari

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 45 KB
• Volume: 12
• Category: Article
• ISSN: 1527-6465
• DOI: 10.1002/lt.20844

✦ Synopsis

We read with interest the work by Kimball and colleagues, "Allograft TNF␤ and IL16 Polymorphisms Influence HCV Recurrence and Severity After Liver Transplantation," which appears in the February 2006 issue of Liver Transplantation. 1 We would like to add a finding from our recent study that may shed more light on the mechanisms underlying the accelerated and aggressive course of hepatitis C virus (HCV) infection and the rapid progression of fibrosis in liver transplant recipients compared to immune-competent individuals. 2 Most patients acquire recurrent HCV within 5 years of transplantation. However, some maintain minimal to moderate liver damage, whereas others advance rapidly to end-stage disease and graft failure. 2,3 The rate of progression is affected by a range of virus-, host-, and environment-related variables 4 : donor and recipient age, sex, and histocompatibility; year of transplantation; pretransplantation HCV RNA levels; viral genotype and quasispecies; use of immunosuppressive agents; and histological findings on the first liver biopsy.

Allograft tumor necrosis factor (TNF)-␤ and interleukin (IL)-16 gene polymorphisms correlated with the l-year clinical outcome in HCV-positive recipients. In their recent study, Kimball et al. 1 reported that recipients of donor TNF-␤ 2,2 experienced less recurrence (P Ͻ 0.05), less fibrosis (P Ͻ 0.01), and less rejection (P Ͻ 0.01) than recipients of donor TNF-␤ 1,1 . Recipients of donor TNF-␤ 1,2 demonstrated an intermediate picture, with less fibrosis (P Ͻ 0.01) and less rejection (P Ͻ 0.01) than TNF-␤ 1,1 recipients. Recipients of donor IL16 TC showed less recurrence (P Ͻ 0.05), less fibrosis (P Ͻ 0.06), and less rejection (P Ͻ 0.06) than recipients of IL16 TT genotype. Recipients of the combination TNF-␤ 2,2 /IL16 TC donor genotype had the most benign clinical outcome, with less recurrence (P Ͻ 0.01), no fibrosis (P Ͻ 0.001), and fewer rejections (P Ͻ 0.01) than donor TNF-␤ 1,1 /IL16 TT recipients. The authors concluded that allograft TNF-␤ and IL16 gene polymorphisms may be useful predictors of the severity of disease recurrence among HCV-positive patients after liver transplantation.

Platelet-derived growth factor (PDGF) is reportedly involved in the pathogenesis of liver fibrosis. In the liver, PDGF is released by inflammatory cells and promotes the proliferation of hepatic stellate cells (HSCs), the main