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慢性丙型肝炎基因4型患者肝硬化的诊断:ABCB11基因多态性和血浆胆汁酸水平的作用

Diagnosis of cirrhosis in patients with chronic hepatitis C genotype 4: Role of ABCB11 genotype polymorphism and plasma bile acid levels.

作者信息

Besheer Tarek, Arafa Mona, El-Maksoud Mohamed Abd, Elalfy Hatem, Hasson Amany, Zalata Khaled, Elkashef Wagdi, Elshahawy Heba, Raafat Doaa, Elemshaty Wafaa, Elsayed Eman, Zaghloul Hosam, Razek Ahmed Abdel, El-Bendary Mahmoud

机构信息

Department of Tropical Medicine, Mansoura University, Mansoura, Egypt.

Department of Pathology, Mansoura University, Mansoura, Egypt.

出版信息

Turk J Gastroenterol. 2018 May;29(3):299-307. doi: 10.5152/tjg.2018.17570.

Abstract

BACKGROUND/AIMS: Chronic hepatitis C (CHC)-related mortality generally results from cirrhosis and subsequent complications. We aimed to investigate the potential role of plasma bile acid levels and ABCB11 1331T > C (V444A, rs2287622) (ATP-binding cassette subfamily B, member 11) gene polymorphism in fibrosis prediction in CHC genotype 4 patients.

MATERIALS AND METHODS

This case control study included 85 healthy control and the following 225 subjects: 170 adult patients infected with hepatitis C virus (HCV) and categorized into three groups according to liver biopsy; no fibrosis group (F0) (n=33), early fibrosis group (F1-F2) (n=61), and advanced fibrosis group (F3-F4) (n=76). Fasting bile acid levels, hepatitis C virus (HCV) genotyping, and ABCB11 1331T > C gene polymorphism were assessed.

RESULTS

The frequency of the variant homozygote genotype CC in advanced fibrosis was significantly higher than that in early fibrosis (48.7% vs. 36.1%) (odd ratio, OR =2.58; 95% confidence interval, CI=1.07-6.20; p=0.03). C allele was significantly represented in advanced fibrosis (65.8%) compared with that in early fibrosis (51.6%) (OR=1.80, 95% CI=1.10-2.93, p=0.01). A significant elevation of plasma bile acid levels in advanced fibrosis was observed compared with those in early fibrosis (p≤0.001). Receiver operating characteristic curve for plasma bile acid levels at cutoff value of 75.5 μmol/L had a 59% specificity and 97.4% sensitivity as a predictor of advanced hepatic fibrosis (AUROC=0.78%).

CONCLUSION

We concluded that Egyptian patients having chronic hepatitis C genotype 4 with CC genotype of ABCB11 SNP 1331T > C and high plasma bile acid levels at cutoff value of 75.5 μmol/L were associated with advanced hepatic fibrosis.

摘要

背景/目的:慢性丙型肝炎(CHC)相关死亡率通常源于肝硬化及后续并发症。我们旨在研究血浆胆汁酸水平和ABCB11 1331T>C(V444A,rs2287622)(ATP结合盒亚家族B成员11)基因多态性在CHC 4型患者纤维化预测中的潜在作用。

材料与方法

本病例对照研究纳入85名健康对照者以及以下225名受试者:170名感染丙型肝炎病毒(HCV)的成年患者,根据肝活检结果分为三组;无纤维化组(F0)(n = 33)、早期纤维化组(F1 - F2)(n = 61)和晚期纤维化组(F3 - F4)(n = 76)。评估空腹胆汁酸水平、丙型肝炎病毒(HCV)基因分型以及ABCB11 1331T>C基因多态性。

结果

晚期纤维化组中变异纯合子基因型CC的频率显著高于早期纤维化组(48.7%对36.1%)(比值比,OR = 2.58;95%置信区间,CI = 1.07 - 6.20;p = 0.03)。与早期纤维化组(51.6%)相比,晚期纤维化组中C等位基因的占比显著更高(65.8%)(OR = 1.80,95% CI = 1.10 - 2.93,p = 0.01)。与早期纤维化组相比,晚期纤维化组血浆胆汁酸水平显著升高(p≤0.001)。血浆胆汁酸水平在截断值75.5μmol/L时的受试者工作特征曲线作为晚期肝纤维化预测指标,特异性为59%,敏感性为97.4%(曲线下面积,AUROC = 0.78%)。

结论

我们得出结论,埃及慢性丙型肝炎4型患者中,ABCB11 SNP 1331T>C的CC基因型且血浆胆汁酸水平在截断值75.5μmol/L时与晚期肝纤维化相关。

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