乙型肝炎病毒相关慢加急性肝衰竭湿热瘀黄证和气虚瘀黄证临床转归的差异性分析

Difference analysis of clinical outcomes of hepatitis B virus-related acute-on-chronic liver failure with dampness-heat stasis jaundice syndrome and qi-deficiency stasis jaundice syndrome

目的 探讨乙型肝炎病毒(HBV)相关慢加急性肝衰竭(ACLF)瘀黄证亚型湿热瘀黄证与气虚瘀黄证在临床特征和转归方面的差异。方法 选择111例2017年12月—2021年12月就诊于中国人民解放军总医院第五医学中心的HBV-ACLF瘀黄证患者,未经中医药干预,按照中医证候分为湿热瘀黄证组(n=90)和气虚瘀黄证组(n=21),均采用标准内科治疗方案,对所有患者采集和记录基线资料、实验室检查指标、并发症情况、终末期肝病模型(MELD)评分、终末期肝病模型联合血清钠(MELD-Na)评分以及ACLF研究联盟(AARC)评分,并观察随访至入组后90 d,记录90 d累积病死率、并发症新发情况,比较2组患者基线临床特征、90 d内病死率和并发症的发生情况,通过多因素回归分析校正混杂因素,进而评估湿热瘀黄证与气虚瘀黄证对转归、并发症发生率等方面的影响。结果 HBV-ACLF湿热瘀黄证组和气虚瘀黄证组患者的年龄、临床指标、病情程度及转归等方面均存在差异。气虚瘀黄证组患者病情程度较为严重,其MELD评分、MELD-Na评分、AARC评分均高于湿热瘀黄证(均P<0.05);与湿热瘀黄证组相比,气虚瘀黄证组表现为年龄更长、肝脏合成及储备功能更差、炎症反应程度较轻、肝硬化的比例更高,差异均具有统计学意义(均P<0.05)。气虚瘀黄证组90 d累积病死率高于湿热瘀黄证人群(P=0.013);多因素分析显示,与湿热瘀黄证相比,气虚瘀黄证是HBV-ACLF 90 d死亡的独立影响因素(HR=1.57,P=0.014)。此外,年龄大(HR=1.06,P=0.006)、总胆红素升高(HR=1.11,P=0.003)、低钠血症(HR=1.86,P=0.004)、肾功能不全(HR=3.27,P=0.027)和肝硬化基础(HR=2.12,P=0.024)增加HBV-ACLF人群90 d死亡风险;凝血酶原活动度升高(HR=0.94,P=0.007)能降低HBV-ACLF人群90 d死亡风险。此外,气虚瘀黄证组患者90 d内新发生的自发性细菌性腹膜炎、肝性脑病、肾功能不全高于湿热瘀黄证组(均P<0.05)。HBV-ACLF湿热瘀黄证、气虚瘀黄证在病情程度、转归等方面均具有差异;与湿热瘀黄证比较,HBV-ACLF气虚瘀黄证病情更为严重,转归更差,90 d死亡风险更高,自发性细菌性腹膜炎、肝性脑病、肾功能不全的发生比例更高。结论 HBV-ACLF瘀黄证的辨识对于疾病病情、预后预判具有重要参考价值,一定程度反映HBV-ACLF瘀黄证“同病异证”的临床表现形式。

Objective We aimed to explore the discrepancies in clinical features and outcomes between damp-heat stasis jaundice syndrome and qi-deficiency stasis jaundice syndrome in patients with hepatitis B virus-associated acute-on-chronic liver failure(HBV-ACLF).Methods We performed an analysis including 111 HBV-ACLF patients recruited from December 2017 to December 2021 in the Fifth Medical Center of Chinese PLA General Hospital.According to traditional Chinese medicine syndromes,these patients were divided into the dampness-heat stasis jaundice syndrome group(n=90)and the qi-deficiency stasis jaundice syndrome group(n=21).All patients adopt the standard internal medicine treatment plan.Baseline data,laboratory indicators,complications,and disease scores,including the model for end-stage liver disease(MELD),MELD-Na,and Acute-on-Chronic Liver Failure(ACLF)Research Consortium(AARC)scores,were recorded.All patients were followed up to 90 days after enrollment.We compared the baseline demographic characteristics,90 d mortality,and complications of HBV-ACLF patients with different syndromes.The confounding factors were adjusted through Cox analysis to evaluate the impact of dampness-heat stasis jaundice syndrome and qi-deficiency stasis jaundice syndrome on the prognosis and the development of complications.Results There were differences in age,clinical indicators,and outcomes between HBV-ACLF patients with dampness-heat stasis jaundice syndrome group and the qi-deficiency stasis jaundice syndrome group.The patients with qi-deficiency stasis jaundice syndrome group had higher MELD scores,MELD-Na scores,and AARC scores.Compared to patients with dampness-heat stasis jaundice syndrome group,patients with qi-deficiency stasis jaundice syndrome group were older,had worse liver synthesis and reserve function of the liver,and had a milder inflammatory response,and the proportion of patients with cirrhosis was higher(P<0.05).Patients with qi-deficiency stasis jaundice syndrome group had a higher cumulative mortality rate within 90 days than patients with dampness-heat stasis jaundice syndrome group(P=0.013).Qi-deficiency stasis jaundice syndrome was dependently associated with a higher mortality risk than dampness-heat stasis jaundice syndrome(HR=1.57,P=0.014).Multivariate analysis showed that older age(HR=1.06,P=0.006),elevated total bilirubin levels(HR=1.11,P=0.003),hyponatremia(HR=1.86,P=0.004),renal dysfunction(HR=3.27,P=0.027),and a basis of cirrhosis(HR=2.12,P=0.024)were risk factors for 90-day mortality,and elevated prothrombin activity(HR=0.94,P=0.007)was a protective factor for 90-day mortality in HBV-ACLF patients.Additionally,patients with qi-deficiency stasis jaundice syndrome group had higher rates of new-onset spontaneous bacterial peritonitis,hepatic encephalopathy,and renal insufficiency than those with dampness-heat stasis jaundice syndrome group within 90 days(P<0.05).Conclusion Our study suggested that qi-deficiency stasis jaundice syndrome is more serious than damp-heat stasis jaundice syndrome.Our multivariate analysis indicated that patients with qi-deficiency stasis jaundice syndrome had higher rates of mortality,new-onset spontaneous bacterial peritonitis,hepatic encephalopathy,and kidney dysfunction than patients with damp-heat stasis jaundice syndrome.This study preliminarily demonstrated that dampness-heat stasis jaundice syndrome and qi-deficiency stasis jaundice syndrome may hold significant value for disease conditions and prognosis prediction for HBV-ACLF patients.