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Regulatory Polymorphism Of CXCL10 Rs1439490 With Seronegative Occult Hepatitis C Virus Infection And The Antiviral Efficacy

Posted on:2019-01-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:S WangFull Text:PDF
GTID:1364330548458976Subject:Internal Medicine
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Part 1 Regulatory Polymorphism of CXCL10 rs1439490 with seronegative occult hepatitis C virus infectionAIM:To examine the relationships between the single nucleotide polymorphism(SNP)CXCL10 G-201A(rs1439490)and seronegative occult occurrence in patients with HCV infection.METHODS:103 cases of seronegative OCI and 155 cases of seropositive CHC were diagnosed at the five Liver Centers in Northeastern China.CXCL10 rs1439490,rs1440802,and IL-28 B rs12979860 were analyzed by sequencing.Serum CXCL10 was measured by ELISA.Intrahepatic CXCL10 was determined by quantitative PCR and immunohistochemical semi-quantitative scoring.Liver necroinflammation and fibrosis were scored according to METAVIR system.RESULTS:OCI was found to occur in 20.3% of patients with cryptogenic hepatic disease.CXCL10 rs1439490 G/G was more prevalent in OCI patients(n=93/103;90.3%)than in CHC patients(n=116/155;74.8%;p=0.008).OCI patients had lower serum CXCL10 levels than CHC patients.Among IL-28 B rs12979860 C/C patients,OCI patients with rs1439490 G/G had lower serum and liver levels of CXCL10,lower levels of liver necroinflammation and fibrosis than non-G/G patients.Multivariate analysis indicated that rs1439490G/G significantly influenced the occurrence of OCI in HCV infection.CONCLUSION:CXCL10 rs1439490 G/G is positively associated with OCI in HCV infection.Part2 Regulatory Polymorphism of CXCL10 rs1439490 with the antiviral efficacy of seronegative occult hepatitis C virus infectionAIM: To examine the relationship between the single nucleotide polymorphism CXCL10 G-201A(rs1439490)and the antiviral efficacy of patients with OCI.METHODS: 71 cases of OCI patients from 5 liver disease centers in northeast China,who diagnosed by liver biopsy and received Peg-IFN combined with RBV therapy for a follow-up of 96 weeks.CXCL10 rs1439490,rs1440802,and IL-28 B rs12979860 were analyzed by sequencing.Serum CXCL10 was measured by ELISA.Intrahepatic CXCL10 was determined by quantitative PCR.Liver necroinflammation and fibrosis were scored according to METAVIR system.RESULTS: CXCL10 rs1439490 G/G was more prevalent in OCI patient than in CHC patients.OCI patients had lower serum CXCL10 levels than CHC patients.OCI patients showed higher ALT normalization rates after Peg-IFN treatment than CHC patients and serum CXCL10 decreased significantly.Liver necroinflammation and fibrosis were alleviated in 8 OCI patients after treatment.CONCLUSION: The single nucleotide polymorphism G-201 A in the promoter region of CXCL10 of the host is closely related to the antiviral efficacy.
Keywords/Search Tags:occult HCV infection, CXCL10, single nucleotide polymorphisms, rs1439490, OCI, G-201A, antiviral therapy
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