单核苷酸多态性对接受直接抗病毒药物治疗慢性丙型肝炎患者疗效的预测价值

doi:10.3760/cma.j.issn.1007-1245.2024.20.016

摘要/Abstract

摘要：

目的　探讨单核苷酸多态性对接受直接抗病毒药物（DAAs）治疗的慢性丙型肝炎（CHC）患者疗效的预测价值。方法　前瞻性收集2020年6月至2022年6月宝鸡市中心医院收治的CHC患者112例，其中男64例，女48例，≥60岁41例，<60岁61例。所有患者均给予索磷布韦片，400 mg/次，1次/d，口服；盐酸达拉他韦片，60 mg/次，1次/d，口服。连续治疗12周。患者治疗结束后依据有无病毒学应答分为有应答组和无应答组。比较两组患者IL-28B基因多态性，分析CHC患者预后与临床特征的关系，采用多因素logistic回归分析确定CHC患者预后的影响因素。绘制受试者操作特征曲线（ROC）评估影响因素对患者预后的预测效能。结果　112例CHC患者中89例（79.46%）存在病毒学应答，23例（20.54%）患者无应答。有应答组中rs8099917TT、rs12979860CC分别有79例（88.76%）、78例（87.64%），无应答组分别有10例（43.48%）、11例（47.83%），差异均有统计学意义（χ²=22.969、17.754，均P<0.001）；有应答组患者中无脂肪肝、Child肝功能分级A级分别有85例（95.51%）、35例（39.32%），无应答组分别有17例（73.91%）、6例（26.09%），差异均有统计学意义（均P<0.05）。多因素logistic回归分析结果显示，脂肪肝、Child肝功能分级C级、rs8099917TG、rs12979860CT均为CHC患者预后的影响因素（RR=4.513、3.666、2.998、3.575，均P<0.05）。ROC分析结果显示，脂肪肝、Child肝功能分级C级、rs8099917TG、rs12979860CT在预测CHC患者预后中具有极高价值。结论　脂肪肝、Child肝功能分级C级、rs8099917TG、rs12979860CT均为CHC患者预后的影响因素，可根据以上指标指导临床治疗。

关键词:

慢性丙型肝炎, 单核苷酸多态性, 直接抗病毒药物, 疗效, 预测

Abstract:

Objective　To investigate the efficacy of single nucleotide polymorphisms in predicting the outcomes in patients with chronic hepatitis C (CHC) treated by direct-acting antivirals (DAAs). Methods　A total of 112 patients with CHC admitted to Baoji Central Hospital from June 2020 to June 2022 were collected, including 64 males and 48 females, 41 cases aged ≥60 years and 61 cases aged <60 years. All patients were treated with DAAs for 6 months, and IL-28B gene polymorphism was detected before treatment. After treatment, the patients were divided into a response group and a non-response group according to whether there was a virologic response. The IL-28B gene polymorphism of the two groups was compared, and the relationships between prognosis and clinical features of CHC patients were analyzed. The influencing factors of prognosis in CHC patients were analyzed by multivariate logistic regression analysis. The receiver operator characteristic curve (ROC) was drawn to evaluate the predictive efficacies of influencing factors for patients' prognosis. Results　Of the 112 CHC patients, 89 patients (79.46%) had a virologic response and 23 patients (20.54%) had no response. There were 79 cases (88.76%) of rs8099917TT and 78 cases (87.64%) of rs12979860CC in the response group, and 10 cases (43.48%) and 11 cases (47.82%) in the non-response group, with statistically significant differences (χ²=22.969 and 17.754, both P<0.001). There were 85 cases (95.51%) without fatty liver and 35 cases (39.32%) with Child liver function grade A in the response group, and 17 cases (73.91%) and 6 cases (26.09%) in the non-response group, with statistically significant differences (both P<0.05). Multivariate logistic regression analysis showed that fatty liver, Child liver function grade C, rs8099917TG, and rs12979860CT were all prognostic factors in CHC patients (RR=4.513, 3.666, 2.998, and 3.575, all P<0.05). ROC analysis results showed that fatty liver, Child liver function grade C, rs8099917TG, and rs12979860CT had high value in predicting the prognosis of CHC patients. Conclusion　Fatty liver, Child liver function grade C, rs8099917TG, and rs12979860CT are all prognostic factors of CHC patients, and we can guide clinical treatment according to the above indicators.

Key words:

Chronic hepatitis C, Single nucleotide polymorphisms, Direct-acting antivirals, Curative effect, Forecast

吴列秀宁博杨建军张莹莹杜锋.

单核苷酸多态性对接受直接抗病毒药物治疗慢性丙型肝炎患者疗效的预测价值 [J]. 国际医药卫生导报, 2024, 30(20): 3428-3432.

Wu Liexiu, Ning Bo, Yang Jianjun, Zhang Yingying, Du Feng.

Efficacy of single nucleotide polymorphisms in predicting the outcomes in patients with chronic hepatitis C treated by direct-acting antivirals [J]. International Medicine and Health Guidance News, 2024, 30(20): 3428-3432.

参考文献

[1] Hüppe D, Stoehr A, Buggisch P, et al. The changing characteristics of patients infected with chronic hepatitis C virus from 2014 to 2019: real-world data from the German Hepatitis C-Registry (DHC-R)[J]. J Viral Hepat, 2021, 28(10): 1474-1483. DOI: 10.1111/jvh.13586.
[2] Mushtaq S, Mansoor A, Umar M, et al. Direct-acting antiviral agents in the treatment of chronic hepatitis C-Real-life experience from clinical practices in Pakistan[J]. J Med Virol, 2020, 92(12): 3475-3487. DOI: 10.1002/jmv.25745.
[3] Gayam V, Tiongson B, Mandal AK, et al. Real-world study of hepatitis C treatment with direct-acting antivirals in patients with drug abuse and opioid agonist therapy[J]. Scand J Gastroenterol, 2019, 54(5):646-655. DOI: 10.1080/00365521.2019.1617893.
[4] Ahsam S, Lail G, Kumar SK, et al. S3263 efficacy of direct-acting anti-viral agents in patients infected with chronic hepatitis C infection: single center experience, karachi, pakistan[J]. Am J Gastroenterol, 2020, 115(1): S1705-S1706. DOI: 10.14309/01.ajg.0000715100. 06232.d8.
[5] 中华预防医学会医院感染控制分会,中华医学会感染病学分会,中华预防医学会感染性疾病防控分会. 中国丙型病毒性肝炎医院感染防控指南(2021年版)[J]. 中国感染控制杂志,2021,20(6):487-493. DOI:10.12138/j.issn.1671-9638. 20216197.
[6] Shah R, Ahovegbe L, Niebel M, et al. Non-epidemic HCV genotypes in low-and middle-income countries and the risk of resistance to current direct-acting antiviral regimens[J]. J Hepatol, 2021, 75(2):462-473. DOI: 10.1016/j.jhep.2021.04.045.
[7] Chi X, Wang M, Pan Y, et al. Inosine triphosphate pyrophosphatase polymorphisms are predictors of anemia in Chinese patients with chronic hepatitis C during therapy with ribavirin and interferon[J]. J Gastroenterol Hepatol, 2020, 35(1): 97-103. DOI: 10.1111/jgh.14812.
[8] Hanif F, Mandhwani R, Lail G,et al. Virological response and safety of sofosbuvir-based direct antiviral agents in chronic hepatitis C infection in hemodialysis patients: 873[J]. Am J Gastroenterol, 2018, 113 Suppl 2: S485-S485.
[9] Ohlendorf V, Schäfer A, Christensen S, et al. Only partial improvement in health-related quality of life after treatment of chronic hepatitis C virus infection with direct acting antivirals in a real-world setting-results from the German Hepatitis C-Registry (DHC-R) [J]. J Viral Hepat, 2021, 28(8): 1206-1218. DOI: 10.1111/jvh.13546.
[10] 曹欣,冯倩嫦,余卫华,等. 索磷布韦/维帕他韦治疗慢性丙型肝炎患者的临床疗效及安全性分析[J]. 国际医药卫生导报,2021,27(16):2486-2489. DOI:10.3760/cma.j.issn.1007- 1245.2021.16.014.
[11] Weil C, Mehta D, Koren G, et al. Sustained virological response to ombitasvir/paritaprevir/ritonavir and dasabuvir treatment for hepatitis C: real-world data from a large healthcare provider[J]. J Viral Hepat, 2018, 25(2): 144-151. DOI: 10.1111/jvh.12800.
[12] 杨洋,金津,王丽亮,等. 基于索磷布韦的直接抗病毒药物治疗基因1型慢性丙型肝炎疗效与安全性的Meta分析[J]. 重庆医学,2020,49(10):1687-1692. DOI:10.3969/j.issn.1671-8348.2020.10.032.
[13] 沈超,姚敏,尹荣,等. KIR3DL1 rs35974949和rs35656676位点基因多态性与HCV易感性和慢性化关系[J]. 中国公共卫生,2022,38(7):852-855. DOI:10.11847/zgggws1135392.
[14] 张立婷,张璨,李俊峰,等. 聚乙二醇干扰素治疗IL28B rs12979860 C/C基因型慢性丙型肝炎的远期疗效评价[J]. 西安交通大学学报(医学版),2018,39(4):609-612. DOI:10.7652/jdyxb201804031.
[15] 陈海艳,童照威,张龙琪,等. 浙江省湖州地区白细胞介素-28B单核苷酸多态性与丙型肝炎病毒自发清除和抗病毒疗效的关系[J]. 中华传染病杂志,2019,37(5):275-279. DOI:10.3760/cma.j.issn.1000-6680.2019.05.005.
[16] El-Fattah MA. Predictive power of Interleukin-28B gene variants for outcome of hepatitis C virus genotype 4 in Egyptians: a systematic review and meta-analysis[J]. Clin Res Hepatol Gastroenterol, 2021, 45(2): 101480. DOI: 10.1016/j.clinre.2020.06.006.
[17] 李国保,欧敏,王召钦,等. 白细胞介素1β基因rs1143627位点单核苷酸多态性与活动性结核病易感性的关系[J]. 中华结核和呼吸杂志,2020,43(5):444-449. DOI:10.3760/cma.j.cn112147-20200316-00345.
[18] Moradi M, Naeimi S, Asadzade S, et al. Genetic association study of promoter variation rs3761549 in the FOXP3 gene of Iranian patients diagnosed with brain tumour[J]. J Cell Biochem, 2019, 120(7): 11915-11920. DOI: 10.1002/jcb.28473.
[19] Okada S, Hata K, Shinagawa T, et al. A polymorphism in interleukin-1 beta gene is associated with the development of pouchitis in Japanese patients with ulcerative colitis[J]. Digestion, 2021, 102(3):489-498. DOI: 10.1159/000503283.
[20] El-Khazragy N, El Sayed N, Salem AM, et al. IL-28β gene polymorphism determines virological response to PEGylated interferon therapy in hepatitis C virus genotype 4 Egyptian patients[J]. J Cell Biochem, 2019, 120(5): 8154-8159. DOI: 10.1002/jcb.28096.
[21] Clarke WT, Miranda J, Neidich E, et al. Metabolic syndrome and liver steatosis occur at lower body mass index in US Asian patients with chronic hepatitis B[J]. J Viral Hepat, 2019, 26(10): 1164-1169. DOI: 10.1111/jvh.13147.
[22] Yang H, Wu J, Yuan Y, et al. Retrospectively seroprevalence study on anti-HEV-IgG antibody in patients with chronic hepatitis or liver cirrhosis in a Chinese teaching hospital[J]. J Med Virol, 2019, 91(3):437-443. DOI: 10.1002/jmv.25335.
[23] Iossa D, Vitrone M, Gagliardi M, et al. Anthropometric parameters and liver histology influence lipid metabolic changes in HCV chronic hepatitis on direct-acting antiviral treatment[J]. Ann Transl Med, 2021, 9(1):35. DOI: 10.21037/atm-20-669.
[24] Wang TJ, Chen MY, Lin YC, et al. High prevalence of fatty liver and its association with metabolic syndrome among rural adults with chronic hepatitis C: implications for primary healthcare[J]. BMC Public Health, 2024, 24(1):532. DOI: 10.1186/s12889-024-17851-0.
[25] Cespiati A, Petta S, Lombardi R, et al. Metabolic comorbidities and male sex influence steatosis in chronic hepatitis C after viral eradication by direct-acting antiviral therapy (DAAs): Evaluation by the controlled attenuation parameter (CAP) [J]. Dig Liver Dis, 2021, 53(10):1301-1307. DOI: 10.1016/j.dld.2020.11.001.