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Genetics Variants and Serum Levels of MHC Class I Chain-related A in Predicting Hepatocellular Carcinoma Development in Chronic Hepatitis C Patients Post Antiviral Treatment

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2016

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Elsevier
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Huang, C., C. Huang, M. Yeh, S. Wang, K. Chen, Y. Ko, C. Lin, et al. 2016. “Genetics Variants and Serum Levels of MHC Class I Chain-related A in Predicting Hepatocellular Carcinoma Development in Chronic Hepatitis C Patients Post Antiviral Treatment.” EBioMedicine 15 (1): 81-89. doi:10.1016/j.ebiom.2016.11.031. http://dx.doi.org/10.1016/j.ebiom.2016.11.031.

Abstract

Background/aims The genome-wide association study has shown that MHC class I chain-related A (MICA) genetic variants were associated with hepatitis C virus (HCC) related hepatocellular carcinoma. The impact of the genetic variants and its serum levels on post-treatment cohort is elusive. Methods: MICA rs2596542 genotype and serum MICA (sMICA) levels were evaluated in 705 patients receiving antiviral therapy. Results: Fifty-eight (8·2%) patients developed HCC, with a median follow-up period of 48·2 months (range: 6–129 months). The MICA A allele was associated with a significantly increased risk of HCC development in cirrhotic non-SVR patients but not in patients of non-cirrhotic and/or with SVR. For cirrhotic non-SVR patients, high sMICA levels (HR/CI: 5·93/1·86–26.38·61, P = 0·002) and the MICA rs2596542 A allele (HR/CI: 4·37/1·52–12·07, P = 0·002) were independently associated with HCC development. The risk A allele or GG genotype with sMICA > 175 ng/mL provided the best accuracy (79%) and a negative predictive value of 100% in predicting HCC. Conclusions: Cirrhotic patients who carry MICA risk alleles and those without risk alleles but with high sMICA levels possessed the highest risk of HCC development once they failed antiviral therapy.

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ALT, alanine aminotransferase, AST, aspartate aminotransferase, APRI, the aspartate aminotransferase-to-platelet ratio index, AFP, α-fetoprotein, CHC, chronic hepatitis C, EGF, epidermal growth factor, HCV, hepatitis C virus, IL-28B, interleukin-28B, MICA, MHC class I chain-related A, PNPLA3, patatin-like phospholipase domain-containing 3, SNP, single-nucleotide polymorphism, HCC, SVR, SNP, MICA, PNPLA3, IL-28, EGF, sMICA, Treatment

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