首次失代偿期乙型肝炎肝硬化患者获得再代偿的影响因素分析

阮佳佳; 温世飞; 王霞; 李丽; 傅涓涓; 潘修成

doi:10.3969/j.issn.1001-5256.2022.08.015

首次失代偿期乙型肝炎肝硬化患者获得再代偿的影响因素分析

DOI: 10.3969/j.issn.1001-5256.2022.08.015

徐州医科大学附属医院感染性疾病科，江苏徐州 221002

基金项目:

国家“十三五”科技重大专项课题 (2018ZX10302-206)

伦理学声明：本研究方案于2020年5月28日经由徐州医科大学附属医院伦理委员会审批，批号：XYFY2020-KL052-01。

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：阮佳佳负责撰写文章；温世飞负责收集数据，整理统计；王霞、李丽、傅涓涓负责写作指导及修改；潘修成负责审阅文章，指导修改并最终定稿。

详细信息

通信作者:
潘修成，xzpxc68@126.com

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出版历程
- 收稿日期: 2021-12-12
- 录用日期: 2022-02-10
- 出版日期: 2022-08-20

Influencing factors for recompensation in patients with first-time decompensated hepatitis B cirrhosis

Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China

Research funding:

National Science and Technology Major Project during the 13th Five-Year Plan Period (2018ZX10302-206)

More Information

Corresponding author: PAN Xiucheng, xzpxc68@126.com(ORCID: 0000-0001-9706-9458)

摘要

摘要: 目的分析实现再代偿的失代偿期乙型肝炎肝硬化患者的影响因素。方法纳入2011年9月1日—2019年12月31日就诊于徐州医科大学附属医院的初次失代偿乙型肝炎肝硬化患者438例，所有患者均接受包括抗病毒治疗在内的综合治疗。根据随访结束时患者的结局分为再代偿组和持续失代偿组，分析再代偿的独立影响因素。比较不同代偿状态的患者长期生存率方面的差异。计量资料两组间比较采用Mann-Whitney U检验；计数资料两组间比较采用χ²检验。采用多因素Cox风险比例回归模型分析再代偿的影响因素。采用Kaplan-Meier法绘制生存曲线，log-rank检验生存曲线。结果 438例失代偿期乙型肝炎肝硬化患者经过抗病毒治疗后最终有199例实现再代偿(45.4%)，与持续失代偿患者比较，持续病毒学应答(χ²=72.093，P＜0.001)、单个或多个并发症(χ²=9.834，P=0.002)、是否消化道出血(χ²=6.346，P=0.012)、血清肌酐(Z=-1.035，P=0.011)、血钠浓度(Z=-1.606，P=0.019)、Hb(Z=1.455，P=0.006)及ALT水平(Z=-2.194，P＜0.001)差异均有统计学意义。基线ALT水平(OR=1.002，95%CI：1.000~1.003，P=0.009)，是否获得SVR(OR=5.760，95%CI：3.634~9.129，P＜0.001)及血清肌酐(OR=0.990，95%CI：0.981~1.000，P=0.047)是再代偿的独立影响因素。再代偿患者的5年存活率显著高于持续失代偿患者(87.9% vs 72.0%，χ²=9.886, P=0.025)。结论经过抗病毒治疗等综合治疗后，大约有45.4%的患者可以实现再代偿。基线ALT升高及实现SVR的患者更容易实现再代偿，基线血清肌酐升高的患者难以实现再代偿，再代偿患者的长期预后较持续失代偿患者更好。
- 乙型肝炎, 慢性 /
- 肝硬化 /
- 危险因素
Abstract: Objective To investigate the influencing factors for recompensation in patients with first-time decompensated hepatitis B cirrhosis. Methods A total of 438 patients with first-time decompensated hepatitis B cirrhosis who attended The Affiliated Hospital of Xuzhou Medical University from September 1, 2011 to December 31, 2019 were enrolled, and all patients received comprehensive treatment including antiviral therapy. According to the outcome at the end of follow-up, the patients were divided into recompensation group and persistent decompensation group, and the independent influencing factors for recompensation were analyzed. Long-term survival rate was compared between the patients with different states of compensation. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data. A multivariate Cox proportional-hazards regression model analysis was used to investigate the influencing factors for recompensation. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison. Results Among the 438 patients with decompensated hepatitis B cirrhosis, 199 (45.4%) achieved recompensation after antiviral therapy. There were significant differences between the recompensation group and the persistent decompensation group in sustained virologic response (SVR) (χ²=72.093, P < 0.001), single or multiple complications (χ²=9.834, P=0.002), presence or absence of gastrointestinal bleeding (χ²=6.346, P=0.012), serum creatinine (SCr) (Z=-1.035, P=0.011), blood sodium concentration (Z=-1.606, P=0.019), hemoglobin (Z=1.455, P=0.006), and alanine aminotransferase (ALT) level (Z=-2.194, P < 0.001). Baseline ALT level (odds ratio [OR]=1.002, 95% confidence interval [CI]: 1.000-1.003, P=0.009), SVR (OR=5.760, 95%CI: 3.634-9.129, P < 0.001), and SCr (OR=0.990, 95%CI: 0.981-1.000, P=0.047) were independent influencing factors for recompensation. The recompensation group had a significantly higher 5-year survival rate than the persistent decompensation group (87.9% vs 72.0%, χ²=9.886, P=0.025). Conclusion After comprehensive treatment, including antiviral therapy, approximately 45.4% of patients can achieve recompensation.Patients with elevated baseline ALT and achieved SVR were more likely to achieve recompensation, patients with elevated baseline serum creatinine had difficulty achieving recompensation, and patients with recompensation had a better long-term prognosis than patients with persistent decompensation.
- Hepatitis B, Chronic /
- Liver Cirrhosis /
- Risk Factors

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图 1 不同代偿状态患者5年累积无移植生存率

Figure 1. The 5-year cumulative transplant free survival rate of patients with different compensated states

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表 1 再代偿患者与持续失代偿患者临床基线资料比较

Table 1. Clinical baseline data for recompensated patients and persistent decompensation patients

项目	再代偿组(n=199)	持续失代偿组(n=239)	统计值	P值
男/女(例)	127/72	155/84	χ²=0.005	0.941
年龄(岁)	50(44~59)	51(44~64)	Z=4.797	0.101
随访时间(月)	23.0(15.0~45.0)	20.5(9.0~60.8)	Z=-0.227	0.820
家族史[例(%)]	32(16.1)	41(17.2)	χ²=0.009	0.764
SVR(例)	162/37	99/140	χ²=72.093	＜0.001
首次失代偿事件
单个/多个并发症(例)	179/20	187/52	χ²=9.834	0.002
腹水[例(%)]	145(72.9)	155(64.9)	χ²=3.299	0.072
消化道出血[例(%)]	34(17.1)	65(27.2)	χ²=6.346	0.012
肝性脑病[例(%)]	13(6.5)	28(11.7)	χ²=0.438	0.064
自发性腹膜炎[例(%)]	14(7.0)	23(9.6)	χ²=0.941	0.332
Scr(μmol/L)	59(49~70)	62(51~76)	Z=-1.035	0.011
INR	1.44(1.23~1.62)	1.46(1.23~1.64)	Z=-0.545	0.461
Alb(g/L)	32.4(29.2~36.7)	31.7(27.7~36.4)	Z=0.793	0.119
TBil(μmol/L)	32.5(21.0~60.7)	30.7(18.3~54.8)	Z=-1.423	0.590
Na(mmol/L)	140.0(137.7~142.0)	139.0(136.6~141.6)	Z=-1.606	0.019
WBC(×10⁹/L)	3.6(2.7~5.0)	3.7(2.6~5.6)	Z=-0.735	0.620
Hb(g/L)	116(99~133)	112(88~127)	Z=1.455	0.006
NLR	2.06(1.36~3.53)	2.28(1.51~4.40)	Z=-0.965	0.087
PLT(×10⁹/L)	69(49~102)	64(46~96)	Z=-0.312	0.332
ALT(U/L)	56(32~110)	41(23~70)	Z=-2.194	＜0.001
AFP(ng/mL)	11.30(3.49~71.84)	10.25(3.19~70.46)	Z=-2.032	0.243
MELD评分	10.42(6.66~14.29)	10.77(7.18~15.50)	Z=0.384	0.251
CTP评分	7(6~9)	7(6~9)	Z=-0.085	0.160
CTP分级[例(%)]			χ²=4.297	0.117
A级	83(41.7)	77(32.2)
B级	74(37.2)	106(44.4)
C级	42(21.1)	56(23.4)
注：Scr，血清肌酐；NLR, 中性粒细胞与淋巴细胞比值。

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表 2 再代偿相关影响因素的多因素分析

Table 2. Multivariate analysis of the influencing factors related to recompensation

自变量	β值	SE	Wald	OR	95%CI	P值
ALT	0.002	0.001	6.802	1.002	1.000~1.003	0.009
单个并发症	-0.412	0.354	1.358	0.662	0.331~1.324	0.244
SVR	1.751	0.235	55.516	5.760	3.634~9.129	＜0.001
Scr	-0.010	0.005	3.955	0.990	0.981~1.000	0.047
Hb	0.004	0.004	1.065	1.004	0.996~1.012	0.302

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