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中国慢性乙型肝炎病毒感染患者长期抗病毒治疗后肝癌的发生:发病率、长期预后及预测因素

The development of hepatocarcinoma after long-term antivirus treatment of Chinese patients with chronic hepatitis B virus infection: Incidence, long-term outcomes and predictive factors.

作者信息

Li Zhi-Qin, Hu Chun-Ling, Yu Ping, Gu Xin-Yu, Zhang Jia-Jia, Li Hua, Zhang Hong-Yu, Lv Jun, Liu Yan-Min, Zeng Qing-Lei, Yan Jing-Ya, Yu Zu-Jiang, Zhang Yi

机构信息

Department of infectious disease, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China; Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China.

Department of infectious disease, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China.

出版信息

Clin Res Hepatol Gastroenterol. 2017 Jun;41(3):311-318. doi: 10.1016/j.clinre.2016.11.007. Epub 2017 Feb 23.

Abstract

BACKGROUND

Patients with chronic hepatitis B virus (HBV) infection are at high risk for progressing to decompensated cirrhosis and hepatocellular carcinoma (HCC). Although long-term treatment with nucleos(t)ide analogues (NAs) benefits patients with chronic hepatitis B (CHB), many develop HCC. Therefore, the clinical outcomes of patients CHB who undergo long-term treatment with NAs remain to be identified. The aim of this study therefore was to evaluate the risk and predictors of patients with CHB who develop hepatitis B-induced HCC.

METHODS

We investigated 1200 patients with CHB who were treated with NAs for at least four years and evaluated the association of the variables ALT, HBsAg, HBV DNA, age and platelet count with the occurrence of HCC. We used multivariable analysis to identify independent risk factors for the development of HCC.

RESULTS

HCC developed in 153 NA-treated patients. Serum HBV DNA levels of 18.17% (218/1200) patients were>2000IU/mL. The median level of liver stiffness measurement (LSM) of all patients was 8.3±6.7kPa vs. 19.8±10.1kPa in patients with HCC. Advanced age, lower platelet counts, positive HBV DNA load, lower ALB concentration and relatively advanced liver disease were associated with an increased risk of developing HCC. Further, TGF-β and IFN-γ levels were higher and lower in patients with HCC or CHB, respectively.

CONCLUSIONS

Hepato-carcinogenesis occurred more frequently in patients with a positive HBV DNA load and relatively advanced liver disease. Therefore, it is important to administer antiviral therapy to patients with CHB before they develop HBV-related cirrhosis.

摘要

背景

慢性乙型肝炎病毒(HBV)感染患者进展为失代偿期肝硬化和肝细胞癌(HCC)的风险很高。尽管核苷(酸)类似物(NA)长期治疗对慢性乙型肝炎(CHB)患者有益,但许多患者仍会发生HCC。因此,接受NA长期治疗的CHB患者的临床结局仍有待确定。本研究的目的是评估发生乙型肝炎相关HCC的CHB患者的风险及预测因素。

方法

我们调查了1200例接受NA治疗至少四年的CHB患者,并评估了丙氨酸转氨酶(ALT)、乙肝表面抗原(HBsAg)、HBV DNA、年龄和血小板计数等变量与HCC发生的相关性。我们采用多变量分析来确定HCC发生的独立危险因素。

结果

153例接受NA治疗的患者发生了HCC。18.17%(218/1200)的患者血清HBV DNA水平>2000IU/mL。所有患者的肝脏硬度测量(LSM)中位数为8.3±6.7kPa,而HCC患者为19.8±10.1kPa。高龄、较低的血小板计数、HBV DNA载量阳性、较低的白蛋白(ALB)浓度以及相对晚期的肝病与发生HCC的风险增加相关。此外,HCC患者的转化生长因子-β(TGF-β)和干扰素-γ(IFN-γ)水平较高,而CHB患者则较低。

结论

HBV DNA载量阳性且肝病相对晚期的患者肝癌发生更为频繁。因此,在CHB患者发展为HBV相关肝硬化之前对其进行抗病毒治疗很重要。

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