Killer cell immunoglobulin‐like receptor genotype and killer cell immunoglobulin‐like receptor–human leukocyte antigen C ligand compatibility affect the severity of hepatitis C virus recurrence after liver transplantation

• Published in: Liver transplantation Vol. 15; no. 4; pp. 390 - 399
• Main Authors: de Arias, Alejandro Espadas, Haworth, Simone Elizabeth, Belli, Luca Saverio, Burra, Patrizia, Pinzello, Giovambattista, Vangeli, Marcello, Minola, Ernesto, Guido, Maria, Boccagni, Patrizia, De Feo, Tullia Maria, Torelli, Rosanna, Cardillo, Massimo, Scalamogna, Mario, Poli, Francesca
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2009
• Subjects: Adult; Biopsy; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - surgery; Carcinoma, Hepatocellular - virology; Disease Progression; Female; Gene Frequency; Genotype; Graft Rejection - immunology; Graft Rejection - virology; Graft Survival; Hepatitis C virus; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - immunology; Hepatitis C, Chronic - surgery; Histocompatibility; HLA-C Antigens - immunology; Humans; Italy; Killer Cells, Natural - immunology; Killer Cells, Natural - virology; Ligands; Liver - immunology; Liver - pathology; Liver - virology; Liver Cirrhosis - immunology; Liver Cirrhosis - surgery; Liver Cirrhosis - virology; Liver Neoplasms - immunology; Liver Neoplasms - surgery; Liver Neoplasms - virology; Liver Transplantation; Male; Middle Aged; Receptors, KIR - genetics; Receptors, KIR - immunology; Receptors, KIR2DL3 - genetics; Recurrence; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Transplantation, Homologous; Treatment Outcome; Italy
• ISSN: 1527-6465; 1527-6473
• DOI: 10.1002/lt.21673

In 20% to 30% of infected individuals, hepatitis C virus (HCV) can cause cirrhosis and hepatocellular carcinoma, for which liver transplantation is the best treatment available. HCV re‐infection is universal, and hepatitis disease recurrence occurs in most cases with a 30% probability of progression to graft cirrhosis at 5 years post‐transplant. The immunological response to HCV involves natural killer (NK) cells and killer cell immunoglobulin‐like receptors (KIRs), which specifically recognize human leukocyte antigen (HLA) class I antigens present on target cells. The effector functions of NK cells are influenced by inhibitory KIR interaction with self‐HLA class I ligands, with HLA‐C being the most predominant. This study examines the roles of KIR genotypes and their HLA ligands in both HCV disease recurrence and its progression. A total of 151 patients were included in the cohort, and their clinical details were recorded. Liver biopsies were used to define the absence/presence of recurrent hepatitis, the degree of fibrosis, and the progression to cirrhosis over a 10‐year period. Mismatching of KIR–HLA‐C ligands between donor‐recipient pairs was associated with the recurrence of hepatitis (P = 0.008). The presence of KIR2DL3 in the recipient correlated with progression to liver fibrosis (P = 0.04). The mismatching of HLA‐KIR ligands favored the progression of the recurrent hepatitis to fibrosis only in the presence of KIR2DL3 (P = 0.04). These preliminary results indicate that the KIR genotype and KIR–HLA‐C ligand compatibility play roles in the recurrence and progression of hepatitis C disease in liver transplant recipients. Liver Transpl 15:390–399, 2009. © 2009 AASLD.