恩替卡韦经治乙肝肝硬化患者低病毒血症对肝癌发病的影响

doi:10.3969/j.issn.1004-583X.2024.11.003

摘要/Abstract

摘要：

目的探讨恩替卡韦经治乙肝肝硬化患者低病毒血症对肝癌发病的影响。方法选择2017年1-12月收治的乙肝肝硬化患者140例,均应用恩替卡韦治疗>1年,对患者进行为期5年的随访。根据患者乙肝病毒(hepatitis B virus,HBV)DNA检测情况,将其分为低病毒血症(low-level viremia,LLV)组68例与持续病毒学应答(maintained virological response,MVR)组72例,观察导致LLV的影响因素,对两组5年内肝癌发病与病死情况进行分析。结果 LLV组与MVR组年龄、治疗前基线乙肝病毒e抗原(hepatitis B e antigen,HBeAg)(阳性)、HBV DNA水平以及乙肝表面抗原(hepatitis B s antigen,HBsAg)滴度差异均有统计学意义(P<0.05),性别、身体质量指数(body mass index,BMI)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)及丙氨酸氨基转移酶(alanine aminotransferase,ALT)差异均无统计学意义(P>0.05);采用二元logistic回归模型进行分析,结果显示治疗前基线HBeAg(阳性)、HBV DNA水平以及HBsAg滴度为导致LLV的影响因素(P<0.05);经过对患者的5年随访,结果显示LLV组肝癌发生率为23.5%,MVR组肝癌发生率为9.7%,LLV组肝癌发生率明显高于MVR组(P<0.05);LLV组肝癌患者病死率为43.8%,MVR组肝癌患者病死率为42.8%,两组病死率差异无统计学意义(P>0.05)。结论 LLV导致肝癌风险增加,临床应重视恩替卡韦经治肝硬化患者,采用有效治疗方案,使LLV转变为持续病毒学应答,减少肝癌的发生风险。

关键词: 肝硬化, 恩替卡韦, 低病毒血症, 肝癌

Abstract:

Objective To investigate the effect of low-level viremia (LLV) on the incidence of hepatocellular carcinomas (HCC) in patients with hepatitis B cirrhosis treated with entecavir. Methods A total of 140 patients with hepatitis B cirrhosis admitted from January 2017 to December 2017 and treated with entecavir for more than one year were selected and followed up for five years. According to hepatitis B virus (HBV) DNA detection, patients were divided into LLV group (68 cases) and maintained virological response (MVR) group (72 cases). Factors influencing LLV were observed, and the incidence and mortality of HCC within five years were compared between groups. Results There were significant differences between LLV group and MVR group in age, baseline hepatitis B e antigen (HBeAg) (positive), HBV DNA level and hepatitis B surface antigen (HBsAg) titer before treatment (P<0.05), but no significant differences in gender, body mass index (BMI), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P>0.05). Binary Logistic regression showed that baseline HBeAg (positive), HBV DNA level and HBsAg titer before treatment were influencing factors for LLV (P<0.05). After five years of follow-up, the incidence of HCC was significantly higher in the LLV group than that of MVR group (23.5% vs 9.7%, P<0.05). The mortality of patients diagnosed with HCC in LLV group was comparable to that of MVR group (43.8% vs 42.8%, P>0.05). Conclusion LLV increases the risk of HCC. Patients with hepatitis B cirrhosis treated with entecavir should be highly concerned, and effective treatment should be adopted to transform LLV into a complete viral response and reduce adverse clinical effects.

Key words: liver cirrhosis, entecavir, low-level viremia, hepatocellular carcinoma

中图分类号:

R575.2

张沙沙, 赵迎春, 周红霞. 恩替卡韦经治乙肝肝硬化患者低病毒血症对肝癌发病的影响[J]. 临床荟萃, 2024, 39(11): 980-983.

Zhang Shasha, Zhao Yingchun, Zhou Hongxia. Effect of low-level viremia on the incidence of hepatocellular carcinomas in patients with hepatitis B cirrhosis treated with entecavir[J]. Clinical Focus, 2024, 39(11): 980-983.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2024.11.003

https://huicui.hebmu.edu.cn/CN/Y2024/V39/I11/980

图/表 3

表1 两组一般资料比较

Tab.1 General data between LLV group and MVR group

组别	例数	性别[例(%)]		年龄 (岁)	BMI (kg/m²)	ALT (U/L)	AST (U/L)	HBeAg(阳性) [例(%)]	HBV DNA (log₁₀IU/ml)	HBsAg (log₁₀IU/ml)
组别	例数	男	女	年龄 (岁)	BMI (kg/m²)	ALT (U/L)	AST (U/L)	HBeAg(阳性) [例(%)]	HBV DNA (log₁₀IU/ml)	HBsAg (log₁₀IU/ml)
LLV组	68	39(57.4)	29(42.6)	61.86±6.92	23.93±3.28	53.26±10.87	82.39±16.37	37(54.4)	5.46±0.87	3.07±0.34
MVR组	72	42(58.3)	30(41.7)	58.25±5.38	23.85±3.27	52.87±9.65	83.17±15.92	26(36.1)	4.42±0.69	2.88±0.25
统计值		χ²=0.014		$t$ =2.499	$t$ =0.114	$t$ =0.225	$t$ =0.288	χ²=4.732	$t$ =7.859	$t$ =3.782
P值		0.907		0.014	0.885	0.823	0.776	0.030	0.000	0.000

表1 两组一般资料比较

Tab.1 General data between LLV group and MVR group

组别	例数	性别[例(%)]		年龄 (岁)	BMI (kg/m²)	ALT (U/L)	AST (U/L)	HBeAg(阳性) [例(%)]	HBV DNA (log₁₀IU/ml)	HBsAg (log₁₀IU/ml)
组别	例数	男	女	年龄 (岁)	BMI (kg/m²)	ALT (U/L)	AST (U/L)	HBeAg(阳性) [例(%)]	HBV DNA (log₁₀IU/ml)	HBsAg (log₁₀IU/ml)
LLV组	68	39(57.4)	29(42.6)	61.86±6.92	23.93±3.28	53.26±10.87	82.39±16.37	37(54.4)	5.46±0.87	3.07±0.34
MVR组	72	42(58.3)	30(41.7)	58.25±5.38	23.85±3.27	52.87±9.65	83.17±15.92	26(36.1)	4.42±0.69	2.88±0.25
统计值		χ²=0.014		$t$ =2.499	$t$ =0.114	$t$ =0.225	$t$ =0.288	χ²=4.732	$t$ =7.859	$t$ =3.782
P值		0.907		0.014	0.885	0.823	0.776	0.030	0.000	0.000

表2 恩替卡韦经治肝硬化患者LLV的多因素logistic回归分析

Tab.2 Multivariate logistic regression analysis of influencing factors for LLV in patients with hepatitis B cirrhosis treated with entecavir

组别	回归系数	标准误	Wald χ²值	P值	OR值	95%CI
组别	回归系数	标准误	Wald χ²值	P值	OR值	下限	上限
年龄	0.001	0.008	0.014	0.864	0.953	0.942	1.015
HBeAg(阳性)	1.197	0.258	18.362	0.000	3.174	2.027	5.139
HBV DNA	0.183	0.064	6.348	0.000	1.197	1.042	1.418
HBsAg	0.794	0.349	22.387	0.000	2.419	1.756	3.387

表3 肝癌5年总发生率及病死率比较

Tab.3 The incidence and mortality of HCC during 5 years of follow-up

组别	例数	肝癌发生率 [例(%)]	肝癌患者病死率 [例(%)]
LLV组	68	16(23.5)	7(43.8)
MVR组	72	7(9.7)	3(42.8)
统计值		χ²=4.856	χ²=0.002
P值		0.028	0.968

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