Traditional Chinese medicine syndromes of chronic hepatitis B with precore mutant

ABM: This study aims at exploring the distribution of TCM syndromes in CHB patients with HBV pre-core mutation (1896) and the relationship between pre-core mutation and T lymphocytes subgroup, through which to provide objective data on clinical syndrome differentiation of TCM, and further to suggest the therapeutic principle and guide clinical treatment. METHODS: One hundred and forty CHB patients were evenly divided into two study groups, HBV pre-core mutant group and HBV pre-core wild-type group. Besides, 30 healthy blood donors were selected as a healthy control group. HBV-labeled compound, T lymphocytes subgroup, and HBV-DNA pre-core mutant were tested in the study groups. T lymphocytes subgroup were also tested in the control group. All the patients were both diagnosed by syndrome differentiation of TCM and western medicine. RESULTS: The most common syndrome in mutant group was damp-heat combined with blood stasis, and the most common syndrome in the wild-type group was damp-heat stasis in the middle-jiao. There were more cases of medium and severe hepatitis in mutant group than that in wild-type group. The content of CD4+ lymphocytes and CD4+/CD8+ ratio were decreased gradually (healthy control group>wild-type group>mutant group). In the wild-type group, severe and medium CHB patients had considerably lower level of them than mild CHB patients. However, in the mutant group, the opposite result appeared. Meanwhile, the content of HBV-DNA in mutant group was higher than that in wild-type group. CONCLUSION: Damp, heat, toxin and blood stasis were the basic pathogens of CHB, whether pre-core mutant or not. CHB with precore mutant may lead to more severe hepatitis. The decreased content of CD4+ lymphocytes and ratio of CD4+/CD8+ may be taken as one of the indices in confirming the deficiency syndrome of CHB patients with pre-core mutation.

Clinical efficacy and safety of TCM prescriptions combined with nucleoside(acid)analogues in treating chronic hepatitis B:a meta-analysis

Objective There are many clinical reports on traditional Chinese medicine(TCM)combined with nucleoside(acid)analogues(NAs)for the treatment of chronic hepatitis B(CHB),but its efficacy and safety are not completely clear.This meta-analysis aims to evaluate the clinical efficacy and safety thus providing evidence for clinical applications.Methods We searched Chinese databases the China National Knowledge Infrastructure(CNKI),Wanfang Data,and China Science and Technology Journal Database(VIP),as well as English databases Pub Med and Cochrane Library,from time of establishment to April 14,2021.Literature quality was evaluated according to the bias risk assessment criteria of Cochrane Collaboration network.Rev Man 5.3 and Stata 12.0 software were used to perform this research.Results A total of 23 articles,3282 patients,and 25 TCM prescriptions were included in this study.NAs plus TCM remarkably improved the clinical total effective rate[Odds ratio(OR)=3.92,P<0.00001],TCM syndrome score(Mean difference=-3.73,P<0.00001),hepatitis B virus(HBV)DNA negative conversion rate(OR=1.49,P=0.0001),hepatitis Be antigen(HBe Ag)negative conversion rate(OR=2.03,P<0.00001),alanine aminotransferase levels[Std mean difference(SMD)=-0.95,P<0.00001],and aspartate aminotransferase levels(SMD=-0.70,P=0.0004).Adverse reaction rates did not increase in the combined treatment group(OR=0.97,P=0.84).A comprehensive analysis of the 25 TCM prescriptions suggested that the combination of spleen-strengthening prescriptions with NAs showed better effects than other prescriptions.Conclusion TCM in combination with NAs,demonstrated better clinical efficacy against CHB than NAs alone.In addition,the combination of spleen-strengthening prescriptions and NAs was identified as the best therapeutic strategy.However,more randomized controlled trials of high quality are needed to provide more reliable clinical basis for the application of TCM.

Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic Hepatitis B:Study Protocol for a Multi-Center,Double-Blind Randomized-Controlled Trial

Background： The domestic prevalence of chronic hepatitis B （CHB） in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot（s）ide analogues （NUCs） anti-hepatitis B virus （HBV） therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine （CHM） is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule （调肝益脾颗粒, TGYP） or Tiaogan-Jianpi-Jiedu Granule （调肝健脾解毒颗粒, TGJPJD） plus entecavir tablet （ETV） was superior over ETV monotherapy in enhancing HBeAg loss rate. Methods： The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1：1 ratio via central randomization system： experimental group （EG） and control group （CG）. Subjects in EG received CM formulae （TGYP or TGJPJD, 50 g per dose, twice daily） plus ETV tablet （or ETV placebo） 0.5 mg per day in the first 24 weeks （stage 1）, and CHM granule plus ETV tablet （0.5 mg per day） from week 25 to 108 （stage 2）. Subjects in CG received CHM Granule placebo plus E＇IV tablet （0.5 mg per day） for 108 weeks throughout the trial. The assessments of primary outcomes （HBV serum markers and HBV-DNA） were conducted by a third-party College of American Pathologists （CAP） qualified laboratory. Adverse effects were observed in the hospitals of recruitment. Discussion： The study was designed to compare the curative effect of CM plus E＇IV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as ＂a valuable endpoint＂. We believe this trial could provide a reliable status for patients＇ ＂joumey＂ towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry （No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23）.

Key Symptoms Selection for Two Major SyndromesDiagnosis of Chinese Medicine in Chronic Hepatitis B

To identify key symptoms of two major syndromes in chronic hepatitis B (CHB), which can be the clinical evidence for Chinese medicine (CM) doctors to make decisions. Standardization scales on diagnosis for CHB in CM were designed including physical symptoms, tongue and pulse appearance. The total of 695 CHB cases with dampness-heat (DH) syndrome or Pi (Spleen) deficiency (SD) syndrome were collected for feature selection and modeling, another 275 CHB patients were collected in different locations for validation. Key symptoms were selected based on modified information gain (IG), and 5 classifiers were applied to assist with models training and validation. Classification accuracy and area under receiver operating characteristic curves (AUC) were evaluated. (1) Thirteen DH syndrome key symptoms and 13 SD syndrome key symptoms were selected from original 125 symptoms; (2) The key symptoms could achieve similar or better diagnostic accuracy than the original total symptoms; (3) In the validation phase, the key symptoms could identify syndromes effectively, especially in DH syndrome, which average prediction accuracy on 5 classifiers could achieve 0.864 with the average AUC 0.772. The selected key symptoms could be simple DH and SD syndromes diagnostic elements applied in clinical directly. (Registration N0.: ChiCTR-DCC-10000759).

A Systematic Review of RCTs and quasi-RCTs on Traditional Chinese Patent Medicines for Treatment of Chronic Hepatitis B

Traditional Chinese patent medicines (TCPMs) are widely used for treatment of chronic hepatitis B (CHB) in China. To estimate the overall effectiveness of TCPMs for CHB, we performed a systematic review of clinical reports designed as randomized controlled trials (RCTs). One hundred and thirty-eight available RCTs and quasi-RCTs on 62 TCPMs, involving 16,393 patients, were included. The methodological quality of these trials was generally "poor". Few trials (6.52%) reported the methods of randomization correctly. Another common problem was the lack of allocation concealment, proper blinding, and the reporting of lost cases and dropouts. Forty-two trials (30.43%) on 27 TCPMs reported some anti-viral effect of TCPMs. Others reported beneficial aspects, including improvements of liver function (79.71% of the studies), liver fibrosis (29.99%), and CHB symptoms (92.75%). Forty-one articles (29.71%) reported mild adverse events with TCPMs but these occurred infrequently. In summary, the outcome of the report on currently registered TCPMs may be biased due to poor methodology. The data from these trials, therefore, is too weak to use in forming a recommendation for treatment of CHB. Nevertheless, five drugs (Dan Shen agents, Da Huang Zhe Chong pill/capsule, Shuang Hu Qing Gan granule, Fu Zheng Hua Yu granule and Cao Xian Yi Gan capsule) appear to be more effective than the other TCPMs.

Chinese Medicine for Treatment of Chronic Hepatitis B

Contemporary Western medicines approved by the U.S. Food and Drug Administration （FDA） for the treatment of chronic hepatitis B （CHB）, although available in China, have high costs, or major side effects and limited effectiveness. Research efforts have focused on looking for natural products as alternative medicines with low cost and good safety for CHB treatment. Chinese medicine （CM） has ancient, time-honored theories about methods of diagnosis and treatment for liver diseases. In recent decades, a large number of clinical trials and pre-clinical studies, which were performed in China and other countries, indicated that CM has potential benefit in several aspects of the treatment of CHB, e.g., anti-inflammatory, anticancer, antioxidant, immunomodulating, antifibrosis, and antiviral. However, there are many concerns regarding the study design and the quality of clinical trials. Further larger, stringently designed, double-blind, placebo control, randomized clinical trials and long-term follow-up are needed to provide conclusive evidence of their efficacy and safety. Components of CM deserve further study in pre-clinical models of HBV infection and in clinical trials world-wide.

DNA Methylation and Transcription of HLA-F and Serum Cytokines Relate to Chinese Medicine Syndrome Classification in Patients with Chronic Hepatitis B

Objective:To explore the molecular bases of Chinese medicine(CM) syndrome classification in chronic hepatitis B(CHB) patients in terms of DNA methylation,transcription and cytokines.Methods:Genome-wide DNA methylation and 48 serum cytokines were detected in CHB patients(DNA methylation:15 cases;serum cytokines:62 cases) with different CM syndromes,including dampness and heat of Gan(Liver) and gallbladder(CHB1,DNA methylation:5 cases,serum cytokines:15 cases),Gan stagnation and Pi(Spleen) deficiency(CHB2,DNA methylation:5 cases,serum cytokines:15 cases),Gan and Shen(Kidney) yin deficiency(CHB3,DNA methylation:5 cases,serum cytokines:16 cases),CHB with hidden symptoms(HS,serum cytokines:16 cases) and healthy controls(DNA methylation:6 cases).DNA methylation of a critical gene was further validated and its mRNA expression was detected on enlarged samples.Genome-wide DNA methylation was detected using Human Methylation 450 K Assay and further verified using pyrosequencing.Cytokines and mRNA expression of gene were evaluated using multiplex biometric enzyme-linked immunosorbent assay(ELISA)-based immunoassay and reverse transcription-quantitative polymerase chain reaction(RT-qPCR),respectively.Results:Totally 28,667 loci,covering 18,403 genes were differently methylated among CHB1,CHB2 and CHB3(P<0.05 and|△β value|> 0.17).Further validation showed that compared with HS,the hg19 CHR6:29691140 and its closely surrounded 2 CpG loci were demethylated and its mRNA expressions were significantly up-regulated in CHB1(P<0.05).However,they remained unaltered in CHB2(P>0.05).Levels of Interleukin(IL)-12 were higher in CHB3 and HS than that in CHB1 and CHB2 groups(P<0.05).Levels of macrophage inflammatory protein(MIP)-1αand MIP-1β were higher in CHB3 than other groups and leukemia inhibrtory factor level was higher in CHB1 and HS than CHB2 and CHB3 groups(P<0.05).IL-12,MIP-1α and MIP-1β concentrations were positively correlated with human leukocyte antigen F(HLA-F)mRNA expression(R;=0.238,P<0.05;R;=0.224,P<0.05;R;=0.447,P<0.01;respectively).Furthermore,combination of HLA-F mRNA and differential cytokines greatly improved the differentiating accuracy among CHB1,CHB2 and HS.Conclusions:Demethylation of CpG loci in 5’ UTR of HLA-F may up-regulate its mRNA expression and HLA-F expression was associated with IL-12,MIP-1α and MIP-1β levels,indicating that HLA-F and the differential cytokines might jointly involve in the classification of CM syndromes in CHB.(Registration No.ChiCTR-RCS-13004001)

Relationship of Anxiety State with Lymphocyte Subsets and the Effect of Chinese Medical Treatment on Anxiety in Patients with Chronic Hepatitis B

Objective：To analyze the relationship of anxiety state with CD4~＋ level and CD4~＋/CD8~＋ ratio and to observe the effect of Chinese medicine（CM） treatment on anxiety in chronic hepatitis B（CHB） patients. Methods：The anxiety state of 120 CHB patients was evaluated based on Hamilton Anxiety Scale（HAMA） scoring.According to the scores,63 patients with scores≥14 were classified to anxiety and 57 patients with scores14 to non-anxiety.The differences in CD4~＋ cells and CD4~＋/CD8~＋ ratio between patients with anxiety and non-anxiety were analyzed.Moreover,63 patients with anxiety were randomized into two groups：31 in the control group were treated with lamivudine（100 mg per day） alone and 32 in the observation group were given equal dosage lamivudine combined with CM treatment depending on syndrome differentiation,all for 12 weeks. The effects of treatment on anxiety state and T-lymphocyte subsets as well as its impact on some CHB-related indices were observed and compared.Results：The anxiety state of CHB patients was negatively correlated with CD4~＋ and CD4~＋/CD8~＋;the level of CD4~＋ in patients with anxiety was significantly lower than that in non-anxiety patients（P0.01 or P0.05）.After treatment,anxiety state in the observation group was significantly improved, with their HAMA scores significantly lowered（P0.01）,and the levels of CD4~＋ and CD4~＋/CD8~＋ were significantly higher than those in the control group（P0.05 or P0.01）.Moreover,the alanine transaminase recovery rate and the HBV-DNA-negative conversion rate in the observation group were significantly higher than those in the control group,respectively（P0.05）.Conclusions：The anxiety state of CHB patients was related to CD4~＋ and CD4~＋/CD8~＋ levels.CM treatment could improve the anxiety state and showed certain regulatory effect on the patients＇ immune system.

Evaluation on Quality of Life and Analysis on Its Correlation with TCM Syndromes in Patients of Chronic Hepatitis B

Objective:To evaluate the quality of life(QOL) in patients with chronic hepatitis B(CHB) and analyze its correlation with traditional Chinese medicine(TCM) syndrome types.Methods:With cross-sectional investigation adopted,the QOL of 335 CHB patients was studied by the World Health Organization Quality of Life BREF Questionnaire(WHOQOL-BREF) and the chronic liver disease questionnaire(CLDQ).The results was compared with that of 30 healthy persons.Results:The QOL of the patients with chronic hepatitis B was l...

Pathological Change of Chronic Hepatitis B Patients with Different Tongue Coatings by Circular Multi-omics Integrated Analysis

Objective:To compare the circular pathological changes of chronic hepatitis B(CHB)patients according to the tongue diagnosis.Methods:Totally 41 CHB patients with typical white tongue coating(WTC)or yellow tongue coating(YTC)were enrolled and 14 healthy volunteers with normal tongue manifestation served as controls.The mRNA expression of peripheral leukocytes was detected by GeneChips,and 9 genes were randomly selected for expression validation.Circular metabolites were detected by gas chromatographymass spectrometry.Biological information was analyzed based on ingenuity pathways analysis or metabolomics database and the integrated networks were constructed by ClueGO.Results:A total of 945 and 716 differentially expressed genes were found in patients with WTC and YTC relative to healthy volunteers respectively.The biological information analysis indicated that CHB patients had obviously increased functions in cell death,apoptosis and necrosis(Z-score 2,P<0.05)and decreased activation in T lymphocytes(Z-score–2,P<0.05),regardless of the tongue manifestation.Compared to patients with WTC,the YTC patients were predicted to be more active in functions related to virus replication(Z-score 2,P<0.05),and the content of circular fatty acids,such as oleic acid(P=0.098)and lauric acid(P=0.035),and citric acid cycle-related metabolites were higher in the YTC patients(P<0.1).The integrated analysis based on differential genes and metabolites indicated that the most difference in the biological function network between the WTC and YTC patients was tumor necrosis factor receptor associated factor 6 mediated-nuclear factor kappa-B activation process.Conclusions:CHB patients with YTC had more severe inflammation and fatty acids metabolism aberrant than patients with WTC.The results facilitate the modern pathological annotation of Chinese medicine tongue diagnosis theory and provide a reference for the interpretation of pharmacological mechanisms of Chinese medicine treatment.

Efficacy of Biejiajian Pill on Intestinal Microbiota in Patients with Hepatitis B Cirrhosis/Liver Fibrosis:A Randomized Double-Blind Controlled Trial

Objective:To analyze the efficacy of Biejiajian Pill(BJJP)on intestinal microbiota in patients with hepatitis B cirrhosis/liver fibrosis,and explore its relationship with liver fibrosis.Methods:This was a prospective,randomized double-blind controlled trial.Using the stratified block randomization method,35 patients with hepatitis B liver cirrhosis/liver fibrosis were randomly assigned(1:1)to receive entecavir(0.5 mg/d)combined with BJJP(3 g/time,3 times a day)or placebo(simulator as control,SC group,simulator 3 g/time,3 times a day)for 48 weeks.Blood and stool samples were collected from patients at baseline and week 48 of treatment,respectively.Liver and renal functions as well as hematological indices were detected.Fecal samples were analyzed by 16S rDNA V3-V4 high-throughput sequencing,and intestinal microbiota changes in both groups before and after treatment were compared,and their correlations with liver fibrosis were analyzed.Results:Compared with the SC group,there was no significant difference in liver function,renal function and hematology indices in the BJJP group,however,the improvement rate of liver fibrosis was higher in the BJJP group(94.4%vs.64.7%,P=0.041).Principal coordinate analysis(PCoA)based on weighted Unifrac distance showed significant differences in intestinal microbiota community diversity before and after BJJP treatment(P<0.01 and P=0.003),respectively.After 48 weeks'treatment,the abundance levels of beneficial bacteria(Bifidobacteria,Lactobacillus,Faecalibacterium and Blautia)increased,whereas the abundance levels of potential pathogenic bacteria,including Escherichia coli,Bacteroides,Ruminococcus,Parabacteroides and Prevotella decreased,among which Ruminococcus and Parabacteroides were significantly positively correlated with degree of liver fibrosis(r=0.34,P=0.04;r=0.38,P=0.02),respectively.The microbiota in the SC group did not change significantly throughout the whole process of treatment.Conclusion:BJJP had a certain regulatory effect on intestinal microbiota of patients with hepatitis B cirrhosis/liver fibrosis(ChiCTR1800016801).

白介素⁃15基因多态性与中西医结合治疗HBeAg阴性慢性乙型肝炎患者疗效的关联性分析

目的分析白介素-15(IL-15)基因多态性与中西医结合治疗乙型肝炎病毒e抗原(HBeAg)阴性慢性乙型肝炎(CHB)患者疗效的关联性。方法将312例HBeAg阴性CHB患者随机分为治疗组、对照组,每组156例,两组均给予西医抗病毒治疗,在此基础上,治疗组加用补肾健脾利湿颗粒,对照组加用补肾健脾利湿颗粒安慰剂,疗程为1年。比较两组的治疗应答率,观察血清IL-15水平的变化情况;挑选IL-15基因的标签单核苷酸多态性(SNPs),并进行基因分型,分析IL-15基因多态性与治疗应答的关联性。结果①最终完成试验者306例,其中治疗组155例、对照组151例。②两组治疗应答率比较,差异无统计学意义(P>0.05)。③治疗前后组内比较,治疗组血清HBsAg水平降低、IL-15水平升高(P<0.05),对照组血清HBsAg水平降低(P<0.05);组间治疗后比较,血清HBsAg、IL-15水平差异有统计学意义(P<0.05)。④治疗后,两组治疗应答患者血清IL-15水平升高、无应答患者血清IL-15水平降低(P<0.05),治疗组应答患者血清IL-15水平高于治疗组无应答患者(P<0.05)。⑤关联分析结果显示,有5个SNPs与治疗应答有显著性关联证据,分别为rs6819823、rs2857261、rs10519612、rs10519613、rs1057972(P<0.05)。⑥治疗前,治疗组应答患者rs6819823 TT基因型血清IL-15水平低于GG基因型、rs2857261 AA基因型血清IL-15水平低于GG基因型、rs1057972 AA基因型患者血清IL-15水平低于TT基因型(P<0.05);治疗后,携带rs6819823、rs2857261、rs10519612、rs10519613、rs1057972最小等位基因的纯合子和杂合子患者血清中IL-15水平上升(P<0.05)。结论IL-15基因遗传变异及IL-15表达水平变化与中西医结合治疗HBeAg阴性CHB的临床疗效存在关联。

Correlation between Traditional Chinese Medicine symptom patterns and serum concentration of zinc,iron,copper and magnesium in patients with hepatitis B and associated liver cirrhosis

OBJECTIVE:To investigate the correlation between the patterns of Traditional Chinese Medicine(TCM)syndromes and the serum concentration of zinc,iron,copper and magnesium of patients with chronic hepatitis B(CHB) and hepatitis B virus(HBV)-induced liver cirrhosis.METHODS:A total of 86 patients were included in the study between March 1,2009 and January 1,2010.All were diagnosed with CHB or HBV-induced liver cirrhosis according to the diagnosis standard of the Chinese Medical Association.Fasting serum concentrations of zinc,iron,copper and magnesium were measured.Patients were classified into different patterns of TCM symptoms according to TCM theory and clinical experience.RESULTS:In the HBV-induced liver cirrhosis group,the mean zinc concentration in patients with the TCM pattern of stagnation of fluid-Dampness was lower than that in patients with obstruction of collaterals by Blood stasis(P < 0.034).In the CHB group,the mean magnesium concentration in patients with toxic Heat flourishing was significantly lower than that in those with Damp-Heat in the Liver and Gallbladder,and those with Liver depression and Spleen deficiency(P < 0.021).The concentrations of iron and copper showed little difference among the different TCM symptom patterns.CONCLUSION:The serum zinc and magnesium concentrations correlated with certain TCM patterns of symptoms in patients with HBV-induced liver cirrhosis and CHB.It may be helpful to interpret the pathogenic change in the TCM symptom patterns in liver cirrhosis and CHB,and also to conduct clinical treatment of the diseases based on identified TCM patterns.

HBeAg阴性慢性乙型肝炎的中医治疗研究进展

慢性乙型肝炎(Chronic hepatitis B,CHB)由乙型肝炎病毒(Hepatitis B Virus,HBV)感染所致,可发展至肝纤维化、肝硬化、肝癌,严重威胁患者健康,给患者和社会带来沉重的负担。HBV感染呈世界性流行,现代医学尚未有治愈的药物,在防治其并发症的发生,特别是抑制肝纤维化发生和进展方面的研究具有重要意义。近年来中医药被发现在治疗HBeAg阴性CHB方面有独特优势。文章整理总结了HBeAg阴性CHB的病因病机、中医辨证论治等方面的研究进展,以期为HBeAg阴性CHB的临床治疗提供借鉴和参考。

T淋巴细胞亚群和肝功能指标与慢性乙型肝炎患者中医辨证分型的相关性

目的 分析T淋巴细胞亚群和肝功能指标与慢性乙型肝炎(CHB)患者中医辨证分型的相关性,为临床中医辨证分型、治疗方案选择和疗效观察提供科学依据。方法 选取2020年1—12月乐山市中医医院983例CHB患者,其中中医辩证分型实证270例(湿热中阻证75例、瘀血阻络证195例)、虚证713例(肝郁脾虚证662例、肝肾阴虚证28例、脾肾阳虚证23例)。检测各证型患者肝功能相关指标[丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总蛋白(TP)、白蛋白(Alb)、总胆红素(TB)、直接胆红素(DBil)]和T细胞(CD3~+、CD4~+、CD8~+)计数,分析各项指标与CHB中医证型的相关性。结果 肝郁脾虚证、瘀血阻络证、湿热中阻证、肝肾阴虚证、脾肾阳虚证临床CHB频率依次升高。CHB各证型中,脾肾阳虚证患者年龄最大,湿热中阻证患者年龄最小。各证型间肝功能相关指标和T淋巴细胞计数差异均有统计学意义(P<0.05);CD3~+、CD4~+T细胞计数与湿热中阻证呈正相关(P<0.05),与脾肾阳虚证呈负相关(P<0.05)。结论 T淋巴细胞亚群和肝功能相关指标与CHB患者中医辨证分型存在相关性,可为临床中医辨证分型、治疗方案选择和疗效观察提供客观依据。

茵陈蒿汤联合还原型谷胱甘肽治疗慢性乙型肝炎临床观察

目的探究茵陈蒿汤联合还原型谷胱甘肽对慢性乙型肝炎(CHB)患者的临床疗效。方法选取2020年5月—2022年5月宜丰县人民医院收治的CHB患者60例,依据不同治疗方式分为两组,观察组采用茵陈蒿汤联合还原型谷胱甘肽治疗,对照组采用还原型谷胱甘肽治疗。比较两组肝功能、生活质量评分、临床疗效、不良反应发生率、肝纤维化指标水平等。结果治疗后,两组总胆红素(TBil)比较,差异无统计学意义(P>0.05);观察组天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)低于对照组(P<0.05);观察组社会、环境、躯体、心理评分高于对照组(P<0.05);观察组的Ⅳ型胶原(Ⅳ-C)、层黏连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、透明质酸(HA)指标均明显低于对照组,差异有统计学意义(P<0.05)。观察组治疗总有效率96.67%(29/30)高于对照组的66.67%(20/30)(P<0.05);观察组不良反应低于对照组(P<0.05)。结论茵陈蒿汤联合还原型谷胱甘肽治疗CHB患者,对提升临床疗效、改善肝纤维化指标水平、提升生活质量的意义重大,同时能够改善肝功能指标,降低不良反应。

参苓健脾饮治疗脾虚湿盛型慢性乙型病毒性肝炎临床研究

目的观察参苓健脾饮治疗脾虚湿盛型慢性乙型病毒性肝炎患者的临床效果及对肝功能指标、乙型肝炎病毒(HBV)DNA水平、肝脏硬度的影响。方法将70例脾虚湿盛型慢性乙型肝炎患者随机平均分为两组,对照组给予保肝、降酶、抗病毒治疗,治疗组在对照组的基础上给予参苓健脾饮治疗。治疗3个月后观察两组患者中医证候评分、肝功能、肝脏硬度、血清病毒载量等情况。结果治疗后治疗组中医证候评分、肝功能各指标、肝脏硬度均低于对照组(P<0.05)。结论参苓健脾饮联合恩替卡韦分散片在改善脾虚湿盛型慢性乙型病毒性肝炎患者中医证候、肝功能、肝硬度值方面效果优于单用恩替卡韦分散片。

Short-Term Efficacy of Treating Hepatitis B Virus-Related Acute-on-Chronic Liver Failure Based on Cold Pattern Differentiation with Hot Herbs: A Randomized Controlled Trial

Objective： To evaluate the clinical efficacy and safety of Yinchen Zhufu Decoction（茵陈术附汤, YCZFD） in the treatment of acute-on-chronic liver failure caused by hepatitis B virus（HBV-ACLF） with cold pattern in Chinese medicine（CM）. Methods： This is a multi-center randomized controlled trial of integrative treatment of CM and Western medicine（WM） for the management of HBV-ACLF patients. A total of 200 HBV-ACLF patients with cold pattern were equally randomly assigned to receive YCZFD and WM（integrative treatment） or WM conventional therapy alone respectively for 4 weeks. The primary end point was the mortality for HBV-ACLF patients. Secondary outcome measures included Model for End-Stage Liver disease（MELD） score, liver biochemical function, coagulation function and complications. Adverse events during treatment were reported. Results： The mortality was decreased 14.28% in the integrative treatment group compared with WM group（χ^2=6.156, P=0.013）. The integrative treatment was found to significantly improve the MELD score（t=2.353, P=0.020）. There were statistically significant differences in aspartate transaminase, total bilirubin, indirect bilirubin, direct bilirubin and prothrombin time between the two groups（P〈0.05 or P〈0.01）. The complications of ascites（χ^2=9.033, P=0.003） and spontaneous bacteria peritonitis（χ^2=4.194, P=0.041） were improved significantly in the integrative treatment group. No serious adverse event was reported. Conclusions： The integrative treatment of CM and WM was effective and safe for HBV-ACLF patients with cold pattern in CM. The Chinese therapeutic principle ＂treating cold pattern with hot herbs＂ remains valuable to the clinical therapy.（Trial registration No. Chi CTR-TRC-10000766）

中西医结合治疗肝郁脾虚型乙型肝炎肝纤维化的研究进展

乙型肝炎病毒(HBV)是引起肝纤维化(HF)及肝硬化的最常见原因之一。虽然针对HBV引起的HF行病因治疗可以取得较好的病毒学应答,但HF仍然存在并不断进展,故抗HF的用药仍值得商榷。近年来,中医在其独有的辨证论治基础上治疗HF已获得一定的临床效果,中西医结合治疗慢性乙型肝炎HF已成为一大热点。研究表明肝郁脾虚型慢性乙型肝炎HF出现相对较早,主要见于HF早期(S1)以及肝组织病理分级G1、G2,是中医控制并逆转HF的重要节点。本文综述近十年中药复方联合恩替卡韦、阿德福韦酯、干扰素、替诺福韦抗病毒药物治疗肝郁脾虚型慢性乙型肝炎HF的研究进展,为临床用药与新药研发提供更多参考。

慢性乙型肝炎中医辨证分型的论证——血清和肝组织HBV抗原、HBVDNA以及病理变化与证型关系的研究

应用分子生物学和免疫组化等技术,对131例慢性乙型肝炎中医辨证分型进行了论证,发现肝郁脾虚型临床符合慢性迁延性肝炎(CPH)者占94.6%,肝组织病理呈CPH改变者为69.2%;血清HBeAg和(或)HBVDNA阳性占61.5%,肝组织HBsAg阳性率为69.2%,其中呈弥漫型者占44.4%,HBVDNA阳性率为33.3%。肝肾阴虚型临床符合慢性活动性肝炎(CAH)者占75.5%,肝脏病理呈CAH改变者占88.5%;血清HBeAg和(或)HBVDNA和肝组织HBsAg阳性率均为80.8%,后者弥漫型占阳性病例85.7%,高于肝郁脾虚型(P<0.05);肝内HBcAg阳性率为34.6%,其中浆型占阳性者55.6%,HBVDNA阳性率63.2%,高于肝郁脾虚型(P<0.05)。气滞血瘀型临床属CAH伴早期肝硬化者占75.0%,病变较重,HBV复制程度与肝郁脾虚型相近。