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开发一种基因特征,用于预测埃及人 HCV 感染相关慢性肝病的肝硬化风险评分。

Development of a gene signature for predicting cirrhosis risk score of chronic liver disease associated with HCV infection in Egyptians.

机构信息

Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, 33 EL Bohouth Street Dokki, Giza, 12622, Egypt.

Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, 33 EL Bohouth Street Dokki, Giza, 12622, Egypt.

出版信息

Microb Pathog. 2021 Apr;153:104805. doi: 10.1016/j.micpath.2021.104805. Epub 2021 Feb 18.

DOI:10.1016/j.micpath.2021.104805
PMID:33609649
Abstract

BACKGROUND

Complex diseases such as fibrosis are likely polygenic. Lately, cirrhosis risk score (CRS) clearly discriminated Chronic HCV patients with high-risk versus those with low-risk for cirrhosis better than clinical factors.

METHODS

Herein, the CRS was assessed via genotyping by allelic discrimination assays in 243 HCV Egyptian patients categorized into 164 patients didn't develop HCC (93 mild, 71 advanced fibrosis); and 79 patients developed HCC. APRI and FIB-4 scores were calculated, compared with CRS and correlated with degree of fibrosis progression.

RESULTS

Median of the three CRS, APRI and FIB-4 scores were significantly elevated in late fibrotic and HCC patients (p < 0.001); however CRS displayed proper discrimination (mild fibrosis (0.59; 0.4-0.75), advanced fibrosis (0.75; 0.7-0.86) and HCC (0.73; 0.57-0.77); (p < 0.001)). The ROC analysis of CRS score displayed modest accuracy to discriminate between mild and advanced fibrotic patient; AUC was 0.73; p < 0.0001), while AUC was only 0.57 (p = 0.05) for the discrimination between HCC and no HCC. Moreover, the combination of CRS, APRI and FIB4 lessened the power of correlation (AUC, 0.63 (p < 0.0001)) in fibrosis prognosis. In HCC prognosis, the combination of CRS, APRI and FIB4 in HCC patients showed modest accuracy with AUC, 0.59 (p = 0.0001).

CONCLUSION

The diagnostic accuracy of FIB-4 for predicting liver fibrosis was nearly identical to that of CRS, however the strength of CRS score stemmed from that it is built on 7 SNPs host genetic factor. Our study validates non invasive algorithms for fibrosis prognosis purposes which may aid in decision making for therapeutic intervention.

摘要

背景

纤维化等复杂疾病可能是多基因的。最近,肝硬化风险评分(CRS)在区分慢性 HCV 患者的肝硬化高危与低危方面明显优于临床因素。

方法

在此,通过等位基因区分检测对 243 名埃及 HCV 患者进行基因分型,评估 CRS,这些患者分为未发生 HCC 的 164 例患者(93 例轻度,71 例进展性纤维化);以及发生 HCC 的 79 例患者。计算 APRI 和 FIB-4 评分,与 CRS 进行比较,并与纤维化进展程度相关。

结果

三个 CRS、APRI 和 FIB-4 评分的中位数在晚期纤维化和 HCC 患者中显著升高(p<0.001);然而 CRS 显示出适当的区分能力(轻度纤维化(0.59;0.4-0.75)、进展性纤维化(0.75;0.7-0.86)和 HCC(0.73;0.57-0.77);(p<0.001))。CRS 评分的 ROC 分析显示,在区分轻度和进展性纤维化患者方面具有中等准确性;AUC 为 0.73;p<0.0001),而在区分 HCC 和无 HCC 患者方面,AUC 仅为 0.57(p=0.05)。此外,CRS、APRI 和 FIB4 的组合降低了相关性的能力(AUC,0.63(p<0.0001))在纤维化预后中的作用。在 HCC 预后中,CRS、APRI 和 FIB4 在 HCC 患者中的组合具有中等准确性,AUC 为 0.59(p=0.0001)。

结论

FIB-4 预测肝纤维化的诊断准确性与 CRS 几乎相同,然而 CRS 评分的优势在于它基于 7 个 SNP 宿主遗传因素。我们的研究验证了用于纤维化预后目的的非侵入性算法,这可能有助于治疗干预决策。

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