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核苷和核苷酸类药物抗HBV治疗过程中发生肝细胞癌的临床特征
Clinical features of patients developing primary hepatocellular carcinoma during anti-HBV therapy with nucleos(t)ide analogues
文章发布日期:2017年03月07日  来源:  作者:张英,刘明,彭晓华,等  点击次数:1313次  下载次数:248次

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【摘要】:目的总结核苷和核苷酸类药物(NAs)抗HBV治疗过程中发生肝细胞癌的临床特征。方法收集2008年1月-2014年9月在中山大学附属第三医院初次诊断为肝细胞癌的患者542例,均为慢性HBV感染者,按是否规范使用NAs治疗分为抗病毒组(130例)及未抗病毒组(412例),回顾性分析比较2组患者的临床资料,包括年龄、性别、肿瘤家族史、HBV感染时间、确诊肝硬化时间、饮酒史、糖尿病史、用药史及实验室检查指标、肝组织病理和影像学检查结果等。符合正态分布的计量资料2组间比较采用t检验,符合偏态分布的计量资料2组间比较采用 Mann-Whitney U检验,计数资料2组间比较采用χ2检验。结果与未抗病毒组比较,抗病毒组肝硬化患者的比例显著升高(90.0% vs 78.4%,χ2=8.528,P=0.003);HBeAg阳性率明显升高(29.4% vs 185%,χ2=6.794,P=0.009)。抗病毒组HBV DNA构成与未抗病毒组比较,差异有统计学意义(χ2=173.142,P<0.001)。抗病毒组ALT、GGT及AFP与未抗病毒组比较,差异均有统计学意义(P值均<0.001)。与未抗病毒组比较,抗病毒组肝癌多为早、中期肝癌,肝癌癌灶较小、数量较少,较少发生血管受侵或远处转移(P值均<0.001)。抗病毒组中,80%(104/130)的肝癌患者发生在NAs抗HBV治疗的5年内。结论长期使用NAs抗HBV治疗的部分慢性HBV感染者仍会发生肝癌,尤其是有肝硬化基础的患者;使用NAs抗HBV治疗的患者发生肝癌的病例多出现在抗HBV治疗的5年内;使用NAs治疗的患者发生肝癌时多在早期被诊断,提示规范随访十分重要。
【Abstract】:ObjectiveTo investigate the clinical features of patients developing hepatocellular carcinoma (HCC) during anti-hepatitis B virus (HBV) therapy with nucleos(t)ide analogues (NAs). MethodsA total of 542 patients who were diagnosed with HCC for the first time in The Third Affiliated Hospital of Sun Yat-Sen University from January 2008 to September 2014 were enrolled, and they all had chronic HBV infection. According to the presence or absence of standard therapy with NAs, they were divided into antiviral group (130 patients) and non-antiviral group (412 patients). A retrospective analysis was performed for their clinical data, including age, sex, family history of tumor, duration of HBV infection, the time when a confirmed diagnosis of liver cirrhosis was made, history of drinking, history of diabetes, history of medication, laboratory parameters, liver pathology, and imaging findings, and these data were compared between the two groups. The t-test was used for comparison of normally distributed continuous data between groups, the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. ResultsCompared with the non-antiviral group, the antiviral group had significant increases in the proportion of patients with liver cirrhosis(90.0% vs 78.4%, χ2=8.528, P=0.003) and HBeAg-positive rate(29.4% vs 185%, χ2=6.794, P=0.009). There was a significant difference in the constitution of HBV DNA between the two groups (χ2=173.142, P<0.001), as well as significant differences in alanine aminotransferase, gamma-glutamyl transpeptidase, and alpha-fetoprotein (all P<0.001). Compared with the non-antiviral group, the antiviral group had a higher proportion of patients with early- or intermediate-stage liver cancer, smaller and fewer cancer lesions, and a lower proportion of patients with vascular invasion or distant metastasis (all P<0.001). Among the patients in the antiviral group, 80% (104/130) developed HCC within 5 years of anti-HBV therapy. ConclusionSome patients with chronic HBV infection who receive long-term NAs as the anti-HBV therapy still develop HCC, especially those with liver cirrhosis, and most of these cases occur within 5 years of anti-HBV therapy. Most patients treated with NAs are diagnosed at the early stage of HCC, suggesting that standard follow-up is of vital importance.
【关键字】:肝炎病毒, 乙型; 癌, 肝细胞; 核苷类; 核苷酸类
【Key words】:hepatitis B virus; carcinoma, hepatocellular; nucleosides; nucleotides
【引证本文】:张英, 刘明, 彭晓华, 等. 核苷和核苷酸类药物抗HBV治疗过程中发生肝细胞癌的临床特征[J]. 临床肝胆病杂志, 2017, 33(4): 679-683.

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