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Thromb Res. 2018 Jul;167:119-124. doi: 10.1016/j.thromres.2018.04.017. Epub 2018 Apr 19.

Impact of hepatitis B virus (HBV) infection on platelet response to clopidogrel in patients undergoing coronary stent implantation.

Author information

1
Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China; Department of Cardiology, The Affiliated Huai'an Hospital of Xuzhou Medical University and Huai'an Second People's Hospital, Huai'an, Jiangsu, China.
2
Department of Cardiology, Xuzhou Children's Hospital, Xuzhou, Jiangsu, China.
3
Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
4
Department of Cardiology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China.
5
Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address: lijay@njmu.edu.cn.

Abstract

BACKGROUND:

Hepatitis B virus (HBV) infection has been reported to down-regulate the expression of CYP2C19 gene, which may decrease the bioactivation of clopidogrel into active metabolites. We aimed to evaluate the impact of HBV infection on platelet response to clopidogrel in patients undergoing coronary stent implantation.

METHODS:

A total of 1805 patients who had received coronary stent implantation and taken aspirin 100 mg in combination with clopidogrel 75 mg daily ≥5 days were consecutively recruited. The serologic identifications for HBV, platelet aggregations in response to arachidonic acid (PLAA) and adenosine diphosphate (PLADP), as well as ABCB1, CYP2C19, CYP3A5, PON1 and P2RY12 genotypes were determined. Clopidogrel low response (CLR) was defined as PLADP > 40%.

RESULTS:

Among the recruited subjects, 102 patients showed hepatitis B surface antigen (HBsAg) positive and 1703 patients negative. PLADP was significantly higher in HBsAg positive group than that in HBsAg negative group [38 (24-48) % vs. 29 (20-39) %, p < 0.001] while the difference of PLAA was not statistically significant (p = 0.329). The incidence of CLR was significantly higher in HBsAg positive group compared with that in HBsAg negative group (43.1% vs. 23.4%, p < 0.001). After adjusted for CYP2C19 genotype and known risk factors, HBsAg positive patients exhibited a significantly higher risk of CLR (adjusted odds ratio: 2.81, 95% confidence interval: 1.73 to 4.58, p < 0.001).

CONCLUSIONS:

HBV infection is an independent risk factor of CLR, in addition to CYP2C19 gene mutations. (Pharmacogenetic and Pharmacokinetic Study of Clopidogrel; NCT01968499).

KEYWORDS:

Clopidogrel low response; Hepatitis B virus; Light transmission aggregometry

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