HBV相关慢加急性肝衰竭TBil水平的合理界值分析

王红敏; 童晶晶; 许祥; 陈婧; 刘子凤; 陈静; 苏海滨; 刘晓燕; 胡瑾华

doi:10.3969/j.issn.1001-5256.2022.05.014

HBV相关慢加急性肝衰竭TBil水平的合理界值分析

DOI: 10.3969/j.issn.1001-5256.2022.05.014

王红敏¹,
童晶晶²,
许祥³,
陈婧^{2, 3},
刘子凤²,
陈静²,
苏海滨³,
刘晓燕³,
胡瑾华^{1, 2, 3, , ,}

1.
北京大学三〇二临床医学院，北京 100039
2.
中国人民解放军医学院，北京 100853
3.
中国人民解放军总医院第五医学中心肝病医学部，北京 100039

基金项目:

首都卫生发展科研专项 (2020-1-5031)

伦理学声明：本研究方案于2019年4月经由中国人民解放军总医院第五医学中心伦理委员会批准，批号：2019016D。

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：王红敏负责课题设计，资料分析，撰写论文；王红敏、童晶晶、许祥、陈婧、刘子凤、陈静、苏海滨、刘晓燕参与收集数据，修改论文；胡瑾华负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
胡瑾华，13910020608@163.com

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出版历程
- 收稿日期: 2021-11-04
- 录用日期: 2022-01-11
- 出版日期: 2022-05-20

Determination of a reasonable threshold of total bilirubin for the diagnosis of hepatitis B virus-associated acute-on-chronic liver failure

Hongmin WANG¹,
Jingjing TONG²,
Xiang XU³,
Jing CHEN^{2, 3},
Zifeng LIU²,
Jing CHEN²,
Haibin SU³,
Xiaoyan LIU³,
Jinhua HU^{1, 2, 3
, ,
,}

1.
Peking University 302 Clinical Medical School, Beijing 100039, China
2.
Chinese PLA Medical School, Beijing 100853, China
3.
Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China

Research funding:

The Capital's Funds for Health Improvement and Research, China (2020-1-5031)

More Information

Corresponding author: HU Jinhua, 13910020608@163.com(ORCID: 0000-0002-0647-9898)

摘要

摘要: 目的探讨HBV相关慢加急性肝衰竭(HBV-ACLF)患者的合理胆红素诊断阈值，以期更为精准地早期诊断。方法回顾性分析解放军总医院第五医学中心2008年9月—2018年9月收治的1232例HBV-ACLF患者，根据基线血清TBil水平分为A组(TBil＜205.2 μmol/L)和B组(TBil ≥ 205.2 μmol/L)，比较2组患者临床特征及28 d、90 d、1年及3年生存情况。计量资料两组间比较采用t检验或Mann-Whitney U秩和检验。计数资料组间比较采用χ²检验。使用Kaplan-Meier法分析2组患者的生存率，并应用log-rank检验进行比较。结果 2组间年龄(t=3.188，P=0.001)、男性(χ²=33.833，P＜0.001)、肝衰竭分型(χ²=39.987，P＜0.001)、WBC(Z=6.586，P＜0.001)、HGB(Z=4.272，P＜0.001)、PLT(Z=3.680，P＜0.001)、Cr(Z=4.505，P＜0.001)、TC(Z=8.644，P＜0.001)、Na(Z=2.335，P=0.020)、白蛋白(Z=2.592，P=0.010)、HBV DNA(Z=3.703，P＜0.001)、MELD评分(Z=11.828，P＜0.001)、MELD-Na评分(Z=8.410，P＜0.001)比较差异均有统计学意义。基线时2组间腹水、GIB发生率比较差异均有统计学意义(χ²值分别为12.036、4.342，P值均＜0.05)。28 d内最常见的新发并发症是感染, 其次为HE，2组间感染发生率比较差异有统计学意义(χ²=5.294，P＜0.05)。A组和B组HBV-ACLF患者28 d无移植病死率分别为21.2%和29.5%[HR=1.473(95%CI：1.151~1.886)，P=0.005]，均符合ACLF患者短期高死亡率的临床特征(＞15%)。尽管两组患者长期病死率存在差异，但生存曲线显示，两组患者无移植病死率在90 d后均无显著上升。结论在INR≥1.5的前提下，不建议将HBV-ACLF诊断标准中TBil水平的界值提高至205.2 μmol/L，确保更多ACLF患者早期诊断，从而获得更多救治机会，尽可能实现早期诊断增加救治机会。
- 慢加急性肝功能衰竭 /
- 乙型肝炎病毒 /
- 胆红素 /
- 诊断
Abstract: Objective To investigate a reasonable threshold of total bilirubin for the diagnosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), and to realize accurate early diagnosis. Methods A retrospective analysis was performed for the clinical data of 1232 patients with HBV-ACLF who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from September 2008 to September 2018, and according to the baseline serum level of total bilirubin (TBil), the patients were divided into group A (TBil < 205.2 μmol/L) and group B (TBil ≥205.2 μmol/L). the two groups were compared in terms of clinical features and 28-day, 90-day, 1-year, and 3-year survival. The t-test or the Mann-Whitney U rank sum test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to analyze survival rate, and the log-rank test was used for comparison. Results There were significant differences between the two groups in age(t=3.188, P=0.001) male sex(χ²=33.833, P < 0.001), liver failure classification(χ²=39.987, P < 0.001), white blood cell count(Z=6.586, P < 0.001), hemoglobin(Z=4.272, P < 0.001), platelet count(Z=3.680, P < 0.001), creatinine(Z=4.505, P < 0.001), total cholesterol(Z=8.644, P < 0.001), Na(Z=2.335, P=0.020), albumin(Z=2.592, P=0.010), HBV DNA(Z=3.703, P < 0.001), Model for End-Stage Liver Disease score(Z=11.828, P < 0.001), and MELD-Na score(Z=8.410, P < 0.001). At baseline, there were significant differences in the incidence rates of ascites and gastrointestinal bleeding between the two groups (χ²=12.036、4.342, P < 0.05). Infection was the most common new-onset complication within 28 days, followed by hepatic encephalopathy, and there was a significant difference in the incidence rate of infection between the two groups (χ²=5.294, P < 0.05). The 28-day transplant-free mortality rate was 21.2% in group A and 29.5% in group B(HR=1.473[95%CI: 1.151~1.886], P=0.005), which was consistent with the clinical feature of a high short-term mortality rate (> 15%) in patients with acute-on-chronic liver failure (ACLF). Although there was a difference in long-term mortality rate between the two groups, there was no significant increase in transplant-free mortality rate after 90 days in either group. Conclusion Under the premise of international normalized ratio ≥1.5, it is not recommended to increase the threshold of TBil to 205.2 μmol/L in the diagnostic criteria for HBV-ACLF, so as to ensure the early diagnosis of more ACLF patients and bring more opportunities for treatment and cure.
- Acute-On-Chronic Liver Failure /
- Hepatitis B virus /
- Bilirubin /
- Diagnosis

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图 1 HBV-ACLF患者入组流程图

Figure 1. Flow chart of HBV-ACLF patients included and excluded from the study

下载: 全尺寸图片幻灯片

图 2 HBV-ACLF患者生存分析

注：a，28 d; b, 90 d; c, 1年; d, 3年。

Figure 2. Survival analysis of HBV-ACLF patients

下载: 全尺寸图片幻灯片

表 1 不同血清TBil水平分组HBV-ACLF患者基线特征比较

Table 1. Comparison of baseline characteristics of HBV-ACLF patients in two groups with different TBil levels

指标	A组(n=306)	B组(n=926)	统计值	P值
年龄(岁)	46.43±11.92	44.06±11.07	t=3.188	0.001
男性[例(%)]	226(73.9)	813(87.8)	χ²=33.833	＜0.001
肝衰竭分型[例(%)]			χ²=39.987	＜0.001
A型	94(30.7)	386(41.7)
B型	135(44.1)	439(47.4)
C型	77(25.2)	101(10.9)
WBC(×10⁹/L)	5.71(4.08~7.66)	6.95(5.35~9.48)	Z=6.586	＜0.001
HGB(g/L)	116.00(99.00~135.00)	124.20(109.00~139.00)	Z=4.272	＜0.001
PLT(×10⁹/L)	73.00(46.00~113.50)	86.00(58.00~121.00)	Z=3.680	＜0.001
INR	1.92(1.58~2.24)	1.95(1.68~2.34)	Z=0.412	0.680
PTA(%)	33.00(27.15~39.18)	32.90(26.00~40.00)	Z=0.395	0.693
ALT(U/L)	144.00(49.00~574.00)	155.50(75.00~428.00)	Z=1.330	0.296
AST(U/L)	157.00(86.00~410.50)	168.00(105.00~344.75)	Z=1.044	0.183
Cr(μmol/L)	83.00(73.00~97.25)	88.50(78.00~104.00)	Z=4.505	＜0.001
TC(mmol/L)	0.77(0.56~1.19)	1.04(0.69~1.47)	Z=8.644	＜0.001
Na(mmol/L)	136.00(132.00~139.00)	135.00(132.00~138.00)	Z=2.335	0.020
白蛋白(g/L)	29.00(25.00~35.30)	29.00(27.00~32.00)	Z=2.592	0.010
血氨(mol/L)	65.00(45.15~90.00)	63.00(43.03~86.00)	Z=0.977	0.329
HBV DNA(log₁₀IU/mL)	5.37(3.73~6.91)	4.64(3.00~6.50)	Z=3.703	＜0.001
Child-Pugh评分	11.00(10.00~12.00)	11.00(10.00~12.00)	Z=0.274	0.784
MELD评分	22.07(19.76~24.70)	25.41(23.15~28.48)	Z=11.828	＜0.001
MELD-Na评分	23.91(20.71~29.50)	27.45(24.23~33.05)	Z=8.410	＜0.001

下载: 导出CSV

表 2 不同胆红素水平分组基线及28 d内并发症比较

Table 2. Comparison of complications at baseline and within 28 days

并发症	A组(n=306)	B组(n=926)	χ²值	P值
基线并发症[例(%)]
腹水	243(79.4)	810(87.5)	12.036	0.001
HE	37(12.1)	137(14.8)	1.386	0.239
AKI	39(12.7)	151(16.3)	2.237	0.135
GIB	11(3.6)	15(1.6)	4.342	0.037
感染	94(30.7)	270(29.2)	0.269	0.604
28天内新发并发症[例(%)]
腹水	17(5.6)	38(4.1)	1.137	0.286
HE	52(17.0)	167(18.0)	0.171	0.680
AKI	36(11.8)	147(15.9)	3.072	0.080
GIB	17(5.6)	66(7.1)	0.904	0.342
感染	60(19.6)	242(26.1)	5.294	0.021

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