Association of polymorphisms in interleukin‐18 and interleukin‐28B with Hepatitis B recurrence after liver transplantation in Chinese Han population

Abstract

Interleukin-18 (IL-18) is a potent proinflammatory cytokine, which can promote hepatitis B virus clearance. The latest studies find that genetic polymorphisms near the IL-28B gene are strongly associated with sustained viral response and spontaneous viral clearance in patients with chronically infected hepatitis C and hepatitis B. We investigated the effect of rs187238 and rs1946518 in IL-18 gene and rs8099917 in IL-28B gene on HBV recurrence in liver transplant patients. A total of 200 liver transplant recipients and relevant donors were enrolled in this study. The patients' mean follow-up was 39 month (range 10-65 month). All liver transplant recipients were in a stable stage. The total recipients (n = 200) were divided into end-stage liver disease secondary to hepatitis B (n = 140) and end-stage liver disease secondary to other diseases (n = 60) before transplantation. Recipients (n = 140) with hepatitis B before transplantation were defined to nonHBV recurrence group (n = 119) or HBV recurrence group (n = 21), which was positive for HBsAg or elevatory in HBV DNA (>2.0 × 10(2) IU mL(-1)) after transplantation. For the recipients (n = 140) had hepatitis B before transplantation, we studied the single-nucleotide polymorphisms (SNPs) of IL-18 gene (rs187238 and rs1946518) and IL-28B gene (rs8099917) by high-resolution melting (HRM) curve analysis. The serum levels of IL-18 and IFN-γ were tested by ELISA. The serums levels of IFN-γ were lower in HBV recurrence group than that in nonHBV recurrence group (P < 0.01). The genotype of IL-28B gene rs8099917 was associated with alanine aminotransferase (ALT) levels and aspartate aminotransferase (AST) levels in HBV-related liver transplant recipients (n = 140). The recipients with allele G (GG+GT) had higher ALT and AST levels (P < 0.05). No association was found between IL-18 gene and IL-28B gene polymorphisms with HBV recurrence in the liver transplant recipients or the donors. We identified that the IFN-γ was a protective factor of HBV recurrence after liver transplantation. The allele G of rs8099917 was associated with hepatitis B-related hepatocytes injury. The rs8099917 G allele subgroup should reinforce antiviral therapy.

Association between gene polymorphisms of IL-28 and response to lamivudine in Chinese rural patients with chronic hepatitis B

“…Some studies have shown no correlation with the outcomes of HBV infection and responses to treatment [28,29]. Some studies stated that the allele G of rs8099917 was associated with hepatitis B-related hepatocyte injury and reinforced antiviral therapy [24,30,31]. In this study, a significant difference was observed between the responder and non-responder groups both in univariate and multivariate analyses (Table III, p = 0.013).…”

IL-18 and IL-1β Gene Polymorphisms: The Plausible Risk Factors for Chronic Hepatitis B

“…Bao et al also revealed that the polymorphisms at -607 promoter region were not associated with HCC in an HBV-infected Chinese population (6). The -137 and -607 promoter polymorphisms in the IL-18 gene also were not associated with HBV recurrence in the liver transplant patients (39).…”

Correlation of HLA-DP/DQ polymorphisms with transplant etiologies and prognosis in liver transplant recipients

“…As listed before, several studies evaluated the correlation of HLA-DQ rs7453920 with HBV susceptibility, [6,7,9–14] but quite conflicting results were obtained. To clarify this obscure association, we reappraised this experiment and found that HLA-DQ rs7453920 was not related to HBV susceptibility ( P  > .05).…”