Study On Efficacy-Related Factors Of HBV-Related Acute-On-Chronic Liver Failure Treated By Integrative Medicine

ObjectiveWe investigated the clinical characteristics of HBV related acute-on-chronic liver failure (ACLF) patients, who were treated by integrative medicine, to find out the protocols that could improve the efficacy, and also to acquire the efficacy-related factors. Besides, by means of metabolomics, we investigated biomarkers with high specificity and sensitivity which could early predict the efficacy of integrative medicine. Thus, we might select the suitable therapeutic protocols for HBV related ACLF patients to reduce the fatality rate, improve life quality, and to save medical resources.MethodWe randomly divided 511 patients, who had HBV related ACLF at enrollment, into the experimental group and the control group. The experimental group was treated by fundamental+supporting+integrative medicine therapy, while the control group underwent fundamental+supporting treatment only. After the 8-week therapeutic session, efficacy evaluation was given to all patients. By means of SPSS software, we assessed the general data, epidemiological information, medical and treatment history, laboratory index, Chinese medical formula, therapeutic effects, etc., to summarize the related-factors of the efficacy, and the better integrative medicine protocols as well. Besides,33 fasting serum samples of HBV related ACLF patients treated by integrative medicine, who were enrolled in our study by 302 PLA hospital, were analyzed by ultra high performance liquid chromatography- mass spectrometry (UHPLC-MS), and counted by Principal Component Analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA), etc., to screen the distinguished metabolic products, which could early predict the efficacy of integrative medicine in HBV related ACLF with high specificity and sensibility.ResultsOur clinical study discovered that the differences were not statistically significant(P>0.05) between the efficacy and gender, blood types, diets, alcohol consumption, smoking habits, educational level, economical condition, route of transmission, family history, deterioration incentives(including seasons, emotions, etc.), therapies before enrollment, and whether or not had stopped or changed the nucleoside analogues. Meanwhile, differences between the efficacy and age, as well as stages, were statistically significant, with high negative correlation (P<0.001). Also, once the patients were suffered from other diseases besides of HBV related ACLF, their efficacies were possibly be poor (P=0.003). In our investigation of laboratory index, we found out that PTA, TC, TG, Na, CL were positively correlated with the efficacy, while TBil, DBil, INR negatively correlated. And regarding of the efficacy, precompounded prescriptions were better than those self-made ones, while changeable prescriptions better than no change all along(P<0.001).Metabolomics experiment discovered 27 distinguished metabolic products,3 of which were identified with precise molecular ion. C620, compound PI (20:4(5Z,8Z,11Z,14Z)/0:0), known as 1-Acylglycerophosphoinositol, and also C742, compound PA(20:2(11Z,14Z)/19:0), known as phosphatidic acid (PA), were positively correlated with therapeutic effects. The other C499, compound Taurochenodeoxycholate, were negtively correlated with efficacy. Combined with ROC curves, C620 was found to be the best correlated and predicting marker with ROC area 0.962, as well as 100% sensitivity and 83.3% specificity. Meanwhile, C742 and C499 might have a high specificity of 100%, but their sensitivity rates were relatively low.ConclusionsOur study proved the correlation between the efficacy of HBV related ACLF and age, stages, PTA, TC, TG, Na, CL, TBil, DBil, INR, medical history. We suggested the integrative medicine therapy with precompounded and changeable prescriptions based on syndrome differentiation, which could improve efficacy, then reduce the fatality rate. The 3 biomarkers we found might help to early predict the effects of integrative medicine, thus help the medical practitioners to select suitable protocols for patients to avoid treatment delay and massive waste of medical resources.