title: 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.
abstract: 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.
authors.affiliation: Department of Regenerative Medicine, Organ and Tissue Transplantation Immunology, Ospedale Maggiore Policlinico, Mangiagalli, Regina Elena, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy.
authors.forename: Alejandro Espadas
authors.initials: AE
authors.lastname: de Arias
authors.forename: Simone Elizabeth
authors.initials: SE
authors.lastname: Haworth
authors.forename: Luca Saverio
authors.initials: LS
authors.lastname: Belli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Burra
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Pinzello
authors.forename: Marcello
authors.initials: M
authors.lastname: Vangeli
authors.forename: Ernesto
authors.initials: E
authors.lastname: Minola
authors.forename: Maria
authors.initials: M
authors.lastname: Guido
authors.forename: Patrizia
authors.initials: P
authors.lastname: Boccagni
authors.forename: Tullia Maria
authors.initials: TM
authors.lastname: De Feo
authors.forename: Rosanna
authors.initials: R
authors.lastname: Torelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Cardillo
authors.forename: Mario
authors.initials: M
authors.lastname: Scalamogna
authors.forename: Francesca
authors.initials: F
authors.lastname: Poli