Association of polymorphisms in interleukin-18 and interleukin-28B with hepatitis B recurrence after liver transplantation in Chinese Han population.
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.
Department of Clinical Immunological Laboratory, West China Hospital, Sichuan University, Chengdu, China.
Y
Y
Li
Y
Y
Shi
J
J
Chen
B
B
Cai
B
B
Ying
L
L
Wang
D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001219:Aspartate Aminotransferases / Q000097:blood; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006509:Hepatitis B / Q000235:genetics* / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000472:pathogenicity; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007372:Interferons; D020382:Interleukin-18 / Q000235:genetics*; D007378:Interleukins / Q000235:genetics*; D016031:Liver Transplantation / Q000208:ethnology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012008:Recurrence; D000095022:Interferon Lambda
D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D007371:Interferon-gamma; D007372:Interferons; D020382:Interleukin-18; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda