Analysis of the therapeutic effect of HBV-ACLF intervention based on the "Yang Jaundice-Yin-Yang Jaundices-Yin Jaundice" syndrome differentiation and treatment model
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摘要: 目的 分析基于“阳黄-阴阳黄-阴黄”辨证论治模式干预乙型肝炎病毒相关慢加急性肝衰竭(hepatitis B virus related acute-on-chronic liver failure，HBV-ACLF)的短期疗效及远期预后情况。方法 回顾性分析2012年1月—2015年1月湖南中医药大学第一附属医院单中心国家中医临床研究基地重点病种项目(阳黄-阴阳黄-阴黄辨证论治模式对乙性肝炎相关性肝衰竭的干预作用及其预后的影响)的100例HBV-ACLF患者的临床资料，按COSSH研究诊断标准对100例患者重新分组，非头对头比较两个队列患者的28、90 d病死率；同时对100例患者进行长期疗效随访，通过生存分析及临床数据比较探究临床特征和远期生存率情况。结果 ① 中医干预组患者28、90 d病死率分别为12.19%、29.27%，与COSSH研究比较，本队列患者短期病死率更低；②生存分析结果显示，存活超过11周后患者死亡风险明显降低，度过高死亡风险期的患者远期(7~10年)生存率达77.40%，存活384周后无患者死亡；③多因素回归分析显示，年龄、PLT、总胆红素(TBIL)、低钠血症为影响患者远期预后的独立危险因素，年龄越大、PLT越低、TBIL水平越高、合并低钠血症的患者预后越差。结论 在西医治疗基础上，基于“阳黄-阴阳黄-阴黄”辨证论治模式干预HBV-ACLF能进一步降低患者短期病死率，且早期干预后患者的远期生存率高。高年龄、低水平PLT、高水平TBIL、并发低钠血症是HBV-ACLF的远期预后的独立危险因素。
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关键词:
- 乙型肝炎病毒相关慢加急性肝衰竭 /
- 中医药 /
- 阴阳黄 /
- 预后 /
- 疗效
Abstract: Objective Analyze the short-term efficacy and long-term survival rate of hepatitis B virus related acute-on-chronic liver failure(HBV-ACLF) patients based on the "Yang Jaundice-Yin-Yang Jaundices-Yin Jaundice"syndrome differentiation and treatment model, explore the appropriate standards for acute-on-chronic liver failure(ACLF), and provide some basis for clinical decision-making.Methods The clinical data of 100 patients with HBV-ACLF who were enrolled in the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from January 2012 to January 2015 under the project of the National Clinical Research Base of Traditional Chinese Medicine, "the intervention effect of the syndrome differentiation and treatment model of Yang Jaundice-Yin-Yang Jaundices-Yin Jaundice on hepatitis B virus related liver failure and its impact on the prognosis", were collected retrospectively. The survival of patients was followed up until November 30, 2022 or the end event occurred, analyze baseline data to determine clinical characteristics, group patients according to different diagnostic criteria, and calculate the 28 day mortality rate, 90 day mortality rate, and endpoint mortality rate of each group. Compare the 28 day and 90 day mortality rates of HBV-ACLF patients in the COSSH-ACLF diagnostic criteria group with those in the 2018 COSSH study queue, and evaluate the short-term efficacy of Traditional Chinese Medicine intervention based on the "Yang Jaundice-Yin-Yang Jaundices-Yin Jaundice" syndrome differentiation and treatment model; according to the endpoint outcome, patients were divided into survival group and death group, and clinical characteristics and long-term survival rate were explored through survival analysis and clinical data comparison.Results ① The 28 day mortality rate and 90 day mortality rate of patients in the traditional Chinese medicine intervention group were 12.19% and 29.27%, respectively. Compared with the short-term mortality rate of HBV-ACLF patients in the COSSH cohort, the short-term mortality rate of patients in this cohort decreased. ②The survival analysis results showed that the risk of death was significantly reduced after more than 11 weeks. The long-term(7-10 years) survival rate of 52 patients who passed the high risk of death period reached 77.40%, and there was no patient death after 384 weeks of survival. ③Multivariate regression analysis showed that age, PLT, TBIL, and hyponatremia were independent risk factors affecting the long-term prognosis of patients. The older the age, the lower the PLT, the higher the TBIL level, and the poorer the prognosis of patients with concomitant hyponatremia.Conclusion The Traditional Chinese and Western Medicine treatment plan based on the "Yang Jaundice-Yin-Yang Jaundices-Yin Jaundice" syndrome differentiation and treatment model reduces the short-term mortality rate of HBV-ACLF better than the simple Western medicine treatment plan, and the long-term survival rate of patients is high after early intervention. High age, low-level PLT, high-level TBIL, and concurrent hyponatremia are independent risk factors for long-term prognosis in HBV-ACLF patients. -
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表 1 本研究与COSSH研究不同ACLF分级患者的28、90 d病死率
分级 本研究PP统计 本研究ITT统计 COSSH研究 28 d病死率 90 d病死率 28 d病死率 90 d病死率 28 d病死率 90 d病死率 ACLF-1级 10.77%(7/65) 26.15%(17/65) 10.14%(7/69) 27.54%(19/69) 23.19%(64/276) 35.87%(99/276) ACLF-2级 21.43%(3/14) 50.00%(7/14) 20.00%(3/15) 46.67%(7/15) 60.54%(89/147) 73.47%(108/147) ACLF-3级 0(0/3) 100.00%(3/3) 0(0/3) 100.00%(3/3) 93.10%(27/29) 100.00%(29/29) 
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表 2 76例完成远期随访患者的基线资料
基线资料 例数 占比/% 男性 69 90.79 年龄/岁 青年(18~36) 28 36.84 中年(>36~60) 45 59.21 老年(>60~65) 3 3.95 肝硬化程度 非肝硬化 36 47.37 肝硬化代偿 15 19.74 肝硬化失代偿 25 32.89 疾病分期 早期 41 53.95 中期 28 36.84 晚期 7 9.21 器官衰竭 肝功能衰竭 61 80.26 凝血功能衰竭 12 15.79 肾功能衰竭 2 2.63 脑功能衰竭 1 1.32 呼吸功能衰竭 0 0 循环功能衰竭 0 0
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表 3 生存组与死亡组的基线特征比较
X±S，例(%)，例，M(Q1，Q3) 基线特征 死亡组(n=31) 生存组(n=45) t/χ2/Z P 年龄/岁 46.7±9.6 35.9±9.7 4.780 ＜0.001 男性 28(90.3) 41(91.1) 0.000 1.000 疾病特征 分型/(A型/B型/C型) 6/7/18 30/8/7 18.971 ＜0.001 分期/(早期/中期/晚期) 10/15/6 31/14/0 14.711 0.001 既往有失代偿 7(22.6) 1(2.2) 6.061 0.010 实验室指标 WBC/(×109/L) 6.4(4.2，7.1) 6.0(4.7，8.0) -0.238 0.812 RBC/(×109/L) 3.9±0.8 3.7±0.8 1.163 0.249 Hb/(g/L) 112(103，122) 128(121，131) -2.464 0.014 中性粒细胞/(×109/L) 69.7±10.5 63.4±10.7 2.526 0.014 PLT/(×109/L) 65(35，102) 119(87，140) -4.557 ＜0.001 ALB/(g/L) 32(28，35) 33(31，36) -1.353 0.176 ALT/(U/L) 119(89，262) 301(110，543) -2.246 0.025 AST/(U/L) 161(113，295) 163(106，333) -0.196 0.845 TBIL/(μmol/L) 391(327，519) 281(204，373) -3.493 ＜0.001 CHE/(U/L) 3 289(2 288，4 963) 4 171(3 473，5 477) -3.493 ＜0.001 Cr/(μmol/L) 79(69，106) 74(67，84) -1.750 0.080 K+/(μmol/L) 4.1±0.5 4.1±0.5 0.447 0.656 PTA/% 32(27，33) 37(33，38) -2.606 0.009 INR 2.1(2.0，2.5) 1.8(1.8，2.1) -2.622 0.090 并发症 腹水 15(48.4) 14(31.1) 2.322 0.128 自发性腹膜炎 17(54.8) 8(17.8) 11.421 0.001 其他感染 12(38.7) 9(20.0) 3.213 0.073 肝性脑病 6(19.4) 2(4.4) 2.894 0.089 消化道出血 1(3.2) 0(0) 0.036 0.850 低钠血症 19(61.3) 3(6.7) 26.628 ＜0.001 肝肾综合征 7(22.6) 1(2.2) 6.061 0.014
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表 4 HBV-ACLF远期预后影响因素的logistic回归分析
影响因素 单因素分析 多因素分析 P OR(95%CI) P OR(95%CI) 年龄/岁 ＜0.001 0.894(0.843~0.947) 0.011 0.907(0.841~0.978) 分型 B型(0=A型) ＜0.001 12.857(3.731~44.300) C型(0=A型) 0.114 2.939(0.771~11.205) 分期 中期(0=早期) 0.051 0.523(0.273~1.003) 晚期(0=早期) 0.267 0.322(0.043~2.386) 既往失代偿(0=否) 0.020 12.833(1.490~110.560) 实验室指标 中性粒细胞/(×109/L) 0.017 0.945(0.903~0.990) Hb/(g/L) 0.008 1.033(1.009~1.059) PLT/(×109/L) ＜0.001 1.033(1.017~1.050) 0.045 1.021(1.000~1.043) ALT/(U/L) 0.044 1.002(1.000~1.003) TBIL/(μmol/L) ＜0.001 0.993(0.989~0.997) 0.007 0.991(0.985~0.998) CHE/(U/L) 0.008 1.001(1.000~1.001) PTA/% 0.007 1.094(1.025~1.167) INR 0.014 0.329(0.136~0.797) 并发症 自发性腹膜炎 0.001 5.616(1.982~15.910) 低钠血症 ＜0.001 22.167(5.597~87.787) 0.012 11.770(1.729~80.266) 肝肾综合征 0.020 0.078(0.009~0.671)
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