YKL-40-gene polymorphism affects acute cellular rejection and fibrosis progression after transplantation for hepatitis C virus-induced liver disease.

Abstract

BACKGROUND AND AIM:

The development of end-stage graft disease is suspected to be partially determined by an individual genetic background. The aim of our study was to determine the prevalence of YKL-40-gene polymorphism in hepatitis C virus (HCV)-positive patients and its impact on the incidence of acute cellular rejection (ACR), graft fibrosis and antiviral treatment response.

METHODS:

A total of 149 patients, who underwent liver transplantation for HCV-induced liver disease, were genotyped for YKL-40 (rs4950928; G/C) by TaqMan Genotyping Assay. The results were correlated with 616 post-transplant graft biopsies regarding inflammation, fibrosis and evidence for ACR.

RESULTS:

No association of YKL-40-genotypes was observed regarding mean inflammation grade (P = 0.216) and antiviral treatment outcome (P = 0.733). However, the development of advanced fibrosis (F3-4) was significantly faster in patients with YKL-40-G-allele: t(CC) = 4.6 versus t(CG/GG) = 2.4 years; P = 0.006. Patients with lower fibrosis (F0-2) compared to advanced fibrosis (F3-4) received significantly more frequent dual immunosuppression (calcineurin inhibitors [CNIs]/mofetile mycophenolate [MMF] vs CNIs; P = 0.003). ACR-occurrence was associated with YKL-40-genotypes (ACR: CC = 60.4%, CG = 25.0% and GG = 14.6% vs non-ACR: CC = 74.2%, CG = 23.8% and GG = 2.0%; P = 0.009) and with gender compatibility between donor and recipient (P = 0.012).

CONCLUSION:

Fibrosis progression and ACR-incidence after transplantation for HCV-induced liver disease seem to be under genetic control. The negative impact of G-allele on post-transplant events observed in our study, deserves attention and should be verified in larger liver transplantation-cohorts.

• Authors: Dennis Eurich, Ulf P Neumann, Sabine Boas-Knoop, Ruth Neuhaus, Anja Kiessling, Ali Yahyazadeh, Christian Trautwein, Hermann Wasmuth, Gero Puhl, Peter Neuhaus, Marcus Bahra
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 28 Issue 1 Pg. 153-60 (Jan 2013) ISSN: 1440-1746 [Electronic] Australia
• PMID: 22989351 (Publication Type: Journal Article)
• Copyright: © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Chemical References

• Adipokines
• Antiviral Agents
• CHI3L1 protein, human
• Chitinase-3-Like Protein 1
• Immunosuppressive Agents
• Interferon alpha-2
• Interferon-alpha
• Lectins
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• Cyclosporine
• peginterferon alfa-2b
• Mycophenolic Acid
• Tacrolimus

Topics

• Adipokines (genetics)
• Adult
• Antiviral Agents (therapeutic use)
• Chitinase-3-Like Protein 1
• Cyclosporine (therapeutic use)
• Disease Progression
• Drug Therapy, Combination
• End Stage Liver Disease (surgery, virology)
• Female
• Genotype
• Graft Rejection (genetics, immunology, pathology)
• Hepacivirus
• Hepatitis C (complications, genetics, pathology)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Interferon alpha-2
• Interferon-alpha (therapeutic use)
• Lectins (genetics)
• Liver Cirrhosis (genetics, pathology)
• Liver Transplantation
• Male
• Middle Aged
• Mycophenolic Acid (analogs & derivatives, therapeutic use)
• Polyethylene Glycols (therapeutic use)
• Polymorphism, Single Nucleotide
• Recombinant Proteins (therapeutic use)
• Ribavirin (therapeutic use)
• Sex Factors
• Statistics, Nonparametric
• Tacrolimus (therapeutic use)
• Time Factors
• Young Adult