國家衛生研究院 NHRI:Item 3990099045/4604

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Title:	Pre-S mutant is a late-stage risk predictor of hepatocellular carcinoma
Authors:	Yang, HI;Su, IJ;Wang, HC;Wu, HC;Huang, WY;Yao, WJ;Chen, CJ
Contributors:	Division of Clinical Research
Abstract:	Introduction: Hepatitis B virus (HBV) is a major cause of hepato-cellular carcinoma (HCC). The mutants of large HBV surface antigen (HBsAg) with deletions at pre-S1 or pre-S2 regions may transactivate genes and induce nodular proliferation and trans-formation of hepatocytes. An increased prevalence of the pre-S mutants was reported in patients with advanced chronic hepatitis B. The aim of this study is to evaluate the association between pre-S mutants and HCC. Methods: A case-control study nested in a cohort of 4,155 HBsAg-seropositive residents in Taiwan was carried out to assess the risk of developing HCC in chronic carriers of HBsAg with or without pre-S mutants at enrolment. The cohort was enrolled in 1990-1991 from residents lived in seven townships in Taiwan. Serum sam-ples at enrollment were retrieved from male HBsAg-seropositive HCC cases and individually matched controls. Two healthy con-trols were matched to each HCC case on residential area, age (5 years intervals) and serostatus of HBeAg. Adequate serum sam-ples were available for 68 HCC cases and 132 controls. The prim-ers used for PCR ampliﬁcation were conserved among all the reported HBV sequence, which covered the whole region of pre-S1 and pre-S2 gene. Nested PCR was performed to further ampliﬁcation for whose ﬁrst PCR ampliﬁcation was insufﬁcient. Unconditional logistic regression models were used to assess odds ratios (ORa) with their 95% conﬁdence interval (CI) for pre-S mutants after adjustment for age and HBeAg serostatus. Results: A total of 14 HCC cases (20.6%) and 11 controls (8.3%) had detectable pre-S mutants in serum samples at cohort entry. The ORa for the development of HCC was 3.2 (95% CI, 1.3-7.9) for study participants with pre-S mutants as compared with those without the mutants. The percentage of incident HCC cases hav-ing pre-S mutants at enrolment were 29.2%, 17.7%, 16.7% and 11.1%, respectively, for those who developed HCC during four consecutive period of 2, 2-3, 4-5, and 6 years after enrolment. The corresponding ORa associated with pre-S mutants decreased from 5.5 (1.7-17.7), 3.7 (0.8-17.1), 2.6 (0.6-11.4), to 0.9 (0.1-7.9). Conclusion: The emergence of pre-S mutants may carry a high risk to develop HCC in subjects with chronic HBV infection. The relative HCC risk associated with pre-S mutants is most promi-nent at late stage of HCC development.
Date:	2005-10
Relation:	Hepatology. 2005 Oct;42(4):282A.
Link to:	http://onlinelibrary.wiley.com/doi/10.1002/hep.20923/abstract
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0270-9139&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000232480300214
Appears in Collections:	[Ih-Jen Su(2002-2015)] Conference Papers/Meeting Abstract

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