HBV相关肝细胞癌患者经长期核苷(酸)类药物抗病毒治疗后HBV RNA的表达水平及临床意义

李静; 曹宇; 冯永美; 郭远强; 蒋贝; 王春妍

doi:10.3969/j.issn.1001-5256.2021.10.013

HBV相关肝细胞癌患者经长期核苷(酸)类药物抗病毒治疗后HBV RNA的表达水平及临床意义

DOI: 10.3969/j.issn.1001-5256.2021.10.013

李静¹,
曹宇^2a,
冯永美^2b,
郭远强³,
蒋贝^2a,
王春妍^2b, ,

1.
天津医科大学研究生院，天津 300192
2a.
天津市第二人民医院科研室，天津 300192
2b.
天津市第二人民医院肝病科，天津 300192
3.
南开大学药学院，天津 300192

基金项目:

天津市青年科学基金 (18JCQNJCH800)

详细信息

通信作者:
王春妍，water4645@sina.com

中图分类号: R735.7
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出版历程
- 收稿日期: 2021-02-28
- 录用日期: 2021-04-08
- 出版日期: 2021-10-20

HBV RNA level in patients with HBV-related hepatocellular carcinoma after long-term antiviral therapy with nucleos(t)ide analogues and its clinical significance

1.
Graduate School of Tianjin Medical University, Tianjin 300192, China
2a.
Department of Research, Tianjin Second People's Hospital, Tianjin 300192, China
2b.
Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300192, China
3.
School of Pharmacy, Nankai University, Tianjin 300192, China

Research funding:

Tianjin Youth Science Fund (18JCQNJCH800)

摘要

摘要: 目的分析HBV相关肝细胞癌患者经长期抗病毒治疗后HBV RNA水平及意义。方法本研究选取2019年6月—2020年8月天津市第二人民医院收治的HBV相关肝细胞癌患者60例。入组患者至少2年接受核苷(酸)类似物(NAs)抗病毒治疗，至少2次间隔3个月经罗氏试剂检测高敏HBV DNA＜20 IU/mL。所有患者均进行肝功能、HBV血清标志物及HBV RNA检测。多组间比较运用Kruskal-Wallis H检验，两组间比较采用Wilcoxon秩和检验。应用Pearson相关分析探讨HBV RNA影响因素。结果 60例HBV相关肝细胞癌经长期抗病毒治疗患者，HBV RNA检测阳性者9例，占比15%。根据AFP结果，分为AFP阳性组及AFP阴性组，两组HBV RNA水平分别为0(0~3.57)、0(0~2.00)，差异无统计学意义(Z=-1.474, P=0.141)；根据BCLC分期不同，分为BCLC A期、B+C+D期，两组HBV RNA水平分别为0(0~2.0)、0(0~2.0)，差异无统计学意义(Z=-0.607，P=0.544)；根据HBeAg水平不同，分为HBeAg阳性组和HBeAg阴性组，两组HBV RNA水平分别为2.99(0~4.80)、0(0~0.50), 差异有统计学意义(Z=-3.400，P=0.001)。根据HBsAg滴度不同，分为HBsAg≤100 IU/mL、100 IU/mL＜HBsAg＜1500 IU/mL、HBsAg≥1500 IU/mL 3组，3组HBV RNA水平分别为0 (0~0)、0 (0~0.20)、2.00 (0~4.54)，差异有统计学意义(H=-7.899，P=0.019)。纳入年龄、ALT、AST、GGT、ALP、AFP、HBsAg、HBeAg进行Pearson相关分析，HBsAg水平与HBV RNA定量相关(r=0.292，P＜0.05)。结论长期NAs抗病毒治疗的HBV相关肝细胞癌患者，在HBV DNA低于检测下限后，HBV RNA仍可检测到；HBsAg滴度可能与血清HBV RNA水平相关。
- 癌，肝细胞 /
- 乙型肝炎病毒 /
- 抗病毒药
Abstract: Objective To investigate HBV RNA level in patients with HBV-related hepatocellular carcinoma after long-term antiviral therapy and its clinical significance. Methods A total of 60 patients with HBV-related hepatocellular carcinoma who were admitted to Tianjin Second People's Hospital from June 2019 to August 2020 were enrolled in this study. These patients received antiviral therapy with nucleos(t)ide analogues (NAs) for at least two years, and high-sensitivity HBV DNA detection showed a HBV RNA level of < 20 IU/mL at least twice at an interval of 3 months. Liver function, HBV serum markers, and HBV RNA level were measured for all patients. The Kruskal-Wallis H test was used for comparison between multiple groups, and the Wilcoxon rank-sum test was used for comparison between two groups; a Pearson correlation analysis was used to investigate the influencing factors for HBV RNA. Results Among the 60 patients with HBV-related hepatocellualr carcinoma who received long-term antiviral treatment, 9 (15%) tested positive for HBV RNA. According to the level of alpha-fetoprotein (AFP), the patients were divided into AFP positive group and AFP negative group, and there was no significant difference in HBV RNA level between the two groups [0(0-3.57) vs 0(0-2.00), Z=-1.474, P=0.141). According to Barcelona Clinic Liver Cancer (BCLC) stage, they were divided into BCLC stage A group and BCLC stage B+C+D group, and there was no significant difference in HBV RNA level between the two groups [0(0-2.0) vs 0(0-2.0), Z=-0.607, P=0.544]. According to HBeAg level, the patients were divided into HBeAg positive group and HBeAg negative group, and there was a significant difference in HBV RNA level between the two groups [2.99(0-4.80) vs 0(0-0.50), Z=-3.400, P=0.001]. According to the titer of HBsAg, they were divided into HBsAg≤100 IU/mL group, 100 IU/mL < HBsAg < 1500 IU/mL group, and HBsAg ≥1500 IU/mL group, and there was a significant difference in HBV RNA level between the three groups [0(0-0.0) vs 0(0-0.20) vs 2.00(0.0-4.54), H=-7.899, P=0.019]. A Pearson correlation analysis was performed for age, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, alpha-fetoprotein, HBsAg, and HBeAg, and the results showed that HBsAg level was correlated with HBV RNA quantification (r=0.292, P < 0.05). Conclusion In patients with HBV-related hepatocellualr carcinoma receiving long-term antiviral therapy with NAs, HBV RNA can still be detected after HBV DNA is lower than the lower limit of detection. HBsAg titer may be correlated with serum HBV RNA level.
- Carcinoma, Hepatocellular /
- Hepatitis B Virus /
- Antiviral Agents

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表 1 入组患者一般资料

指标	数值
年龄(岁)	57.3±9.1
ALT(U/L)	26.5±7.6
AST(U/L)	29.4±10.1
GGT(U/L)	79.1±34.8
ALP(U/L)	94.2±28.2
Alb(g/L)	36.7±5.8
TBil(μmol/L)	32.2±8.6
HCC家族史[例(%)]
有	24(40.0)
无	36(60.0)
BCLC分期[例(%)]
A期	25(41.7)
B+C+D期	35(58.3)
抗病毒治疗药物[例(%)]
恩替卡韦	43(71.7)
替诺福韦	5(8.3)
丙酚替诺福韦	3(5.0)
拉米夫定	1(1.7)
替比夫定	1(1.7)
阿德福韦	1(1.7)
恩替卡韦联合替诺福韦酯	3(5.0)
恩替卡韦联合阿德福韦酯	2(3.3)
拉米夫定联合阿德福韦酯	1(1.7)
HBV RNA[例(%)]
阳性	9(15.0)
＜100 IU/mL	11(18.3)
检测不到	40(66.7)
HBeAg阴性[例(%)]
HBV RNA阳性	2(4.3)
HBV RNA＜100 IU/mL	9(19.6)
HBV RNA检测不到	35(76.1)

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