Treatment of HBeAg Positive Chronic Hepatitis B by Xiaoyao Powder Combined with Interferon-α: a Clinical Observation

目的研究逍遥散联合α干扰素(InTErfErOn-AlPHA,Ifn-α)治疗HbEAg阳性慢性乙型肝炎疗效及对生活质量的影响。方法 193例经肝穿刺活检证实的HbEAg阳性慢性乙型肝炎患者,按照随机数字表法分为单药治疗组(94例)和联合治疗组(99例),单药治疗组给予Ifn-α1b,50μg/次,皮下注射,每周3次;联合治疗组在单药治疗组的基础上,配伍逍遥散口服,两组疗程均为24周。通过评价两组AlT复常率、HbEAg阴转率、HbEAg转换率、HbV dnA阴转率、完全应答率、部分应答率以及症状积分变化等观察逍遥散联合Ifn-α疗效;采用慢性肝病问卷(CHrOnIC lIVEr dISEASE QuESTIOnnAIrE,CldQ)评分进行生活质量评定;观察两组患者的不良反应发生率。结果联合治疗组在AlT复常率、HbEAg阴转率、HbV dnA阴转率、完全应答率、部分应答率、中医症状积分、中医症状总有效率、CldQ评分和不良反应发生率方面均优于单药治疗组(P<0.05,P<0.01)。结论逍遥散可提高Ifn-α治疗HbEAg阳性慢性乙型肝炎的中医症状疗效、抗病毒疗效,改善生活质量,减少Ifn-α不良反应。Objective To study the efficacy of Xiaoyao Powder( XYP) combined with interferon alpha( IFN-α) in treating HBeAg positive chronic hepatitis B( CHB) patients and the effect on their quality of life( QOL).Methods Totally 193 patients with HBeAg-positive CHB confirmed by liver biopsy were randomly assigned to 2 groups,Group A( 94 cases) and Group B( 99 cases).IFN-α1b was subcutaneously injected to patients in Group A at the dose of 50 μg,thrice per week.Those in Group B additionally took XYP.The therapeutic course for all was 24 weeks.Clinical efficacy was observed by assessing ALT restoration rate,HBeAg negative rate,HBeAg conversion rate,HBV DNA negative rate,complete response rate,partial response rate,and symptoms integral.The evaluation of QOL was performed by using chronic liver disease questionnaire( CLDQ) score.Adverse reaction occurrence rate was observed in the two groups.Results Better effects were obtained in Group A on ALT restoration rate,HBeAg negative rate,HBV DNA negative rate,complete response rate,partial response rate,TCM symptoms integral,the total effective rate of TCM sysmptoms,CLDQ score,and adverse reaction rates,showing statistical difference when compared with Group B(P <0.05,P <0.01).Conclusion XYP could elevate the efficacy of TCM symptoms of HBeAg-positive CHB patients and anti-viral effect,improve their QOL,and reduce adverse reaction of IFN-α.福建省卫生厅青年科研课题基金资助项目(No.2012-2-105

Efficacy of Zaozhu Yinchen Recipe for Treating Non-alcoholic Steatohepatitis and Its Effect on Free Fatty Acid and TNF-α

目的观察皂术茵陈方治疗非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)患者的临床疗效,并探讨其对游离脂肪酸(free fatty acid,FFA)及TNF-α的影响。方法采用随机数字表法将120例NASH患者分为治疗组及对照组,每组60例。治疗组予中药皂术茵陈方,每日1剂;对照组予水飞蓟宾葡甲胺片200 mg口服,每日3次,两组均治疗24周。分别于治疗前后通过检测血清ALT、AST活性及TC、TG水平;行腹部CT计算肝脾CT比值;应用肝组织病理检查评价非酒精性脂肪性肝病活动度积分(NAFLD activity score,NAS)及纤维化程度以评价临床疗效;并检测血清FFA及TNF-α含量。结果与本组治疗前比较,两组治疗后血清ALT、AST、TC、TG、FFA、TNF-α水平、肝组织NAS积分及症状体征积分均明显降低,肝纤维化程度明显改善(P<0.05,P<0.01),且治疗组降低更明显(P<0.05)。治疗24周后,治疗组肝纤维化分期总有效率及临床总有效率分别为80.00%(48/60)、85.00%(51/60),明显高于对照组[60.00%(36/60)、73.33%(44/60)],两组比较,差异有统计学意义(P<0.05,P<0.01)。结论皂术茵陈方可改善NASH患者的临床疗效,其作用可能与抑制血清FFA及TNF-α水平有关。Objective To observe the efficacy of Zaozhu Yinchen Recipe(ZZYCR) on non-alcoholic steatohepatitis(NASH) patients, and to explore its effect on serum free fatty acid(FFA) and tumor necrosis factor α(TNF-α).Methods Totally 120 patients with NASH were randomly assigned to the treatment group(60 cases,treated with ZZYCR, one dose per day) and the control group(60 cases, treated with Silibin Meglumine Tablets, 20 mg each time, thrice per day). The therapeutic course for all was 24 weeks. Serum levels of ALT and AST activities, TC and TG levels were detected before and after treatment. Peritoneal CT was performed in all patients, and CT ratios of liver and spleen calculated. NAFLD activity score(NAS) and degree of hepatic fibrosis were assessed using pathological examinations of liver tissue, and efficacy also evaluated. Serum contents of FFA and TNF-αwere also detected. Results Compared with before treatment in the same group, activities of ALT and AST, serum levels of TC, TG, FFA, and TNF-α, NAS, scores of symptoms and signs all obviously decreased, degree of hepatic fibrosis was obviously improved in the two groups(P < 0. 05, P < 0. 01). These changes were more obviously seen in the treatment group(P < 0. 05). After 24-week treatment, the total effective rate and total clinical efficacy were 80. 00%(48/60 cases) and 85. 00%(51/60 cases) in the treatment group, obviously higher than those in the control group [60. 00%(36/60 cases) and 73. 33%(44/60 cases) respectively], with significant difference(P < 0. 05, P < 0. 01). Conclusion ZZYCR could improve the clinical efficacy of NASH patients, and its mechanism might be associated with inhibiting serum levels of FFA and TNF-α.国家自然科学基金资助项目(No.81503529,81274155);; 福建省自然科学基金面上资助项目(No.2014J01374);; 福建省卫生厅中医药项目(No.wzpw201308);; 厦门市科技计划项目(No.3502Z20134020

皂术茵陈方治疗非酒精性脂肪性肝炎的临床观察及其对肠道菌群的影响

目的评价皂术茵陈方调节肠道菌群治疗非酒精性脂肪性肝炎(NASH)的临床疗效及其作用机制。方法选取福建中医药大学附属厦门市中医院肝病中心门诊就诊的NASH患者80例,采用随机数字表法分为治疗组(40例)和对照组(40例)。治疗组予中药皂术茵陈方治疗,对照组予以枯草杆菌二联活菌肠溶胶囊治疗,两组疗程均为12周。评价治疗前后两组患者的症状、体征积分以及血清ALT、AST活性;检测两组患者血清内毒素水平以及肠道菌群变化。结果治疗12周后,治疗组的临床总有效率达87.5%(35/40),较之对照组的65%(26/40)有统计学意义(χ~2=7.966,P<0.05);两组患者ALT、AST活性以及血清内毒素水平较治疗前均有明显下降(P<0.05),且以治疗组的ALT、AST活性下降值大于对照组(t=2.254,t=2.325,P<0.05);两组患者肠道菌群中的双歧杆菌、乳酸杆菌、拟杆菌数量较治疗前显著升高,而肠球菌、肠杆菌显著降低(P<0.05)。结论皂术茵陈方具有改善肝功能、治疗NASH的临床疗效,其作用机制与调节肠道菌群紊乱、恢复肠道微生态平衡、减轻肠源性内毒素血症相关。国家自然青年科学基金资助项目(No.81503529);;福建中医药大学临床专项校管课题基金(No.XB2016080

皂术茵陈方治疗非酒精性脂肪性肝炎40例临床研究

目的:观察皂术茵陈方治疗非酒精性脂肪性肝炎的临床疗效。方法:将78例患者单盲法随机分为治疗组40例和对照组38例;治疗组予中药皂术茵陈方治疗,对照组采用水飞蓟宾葡甲胺片(西利宾安)治疗;两组均治疗2个月。检测治疗前后患者血清谷丙转氨酶(AlT)、谷草转氨酶(AST)活性、血清总胆固醇(TCH)、甘油三酯(Tg)含量;比较患者肝脏b超变化以及症状、体征积分等临床疗效。结果:经过2个月治疗,治疗组的临床总有效率达87.50%,较之对照组的73.68%,差异有统计学意义(P<0.05);两组治疗后症状、体征积分、肝脏b超改善情况、血清AlT、AST活性、血清TCH、Tg含量均较各自治疗前显著改善;较之对照组,治疗组上述改善更加显著(P<0.05)。结论:中药皂术茵陈方对改善非酒精性脂肪性肝炎有较好的临床疗效,可明显改善患者肝功能、血脂、b超影像指标及临床证候。国家自然科学基金(No.81274155); 福建省卫生厅中医药项目(No.wzpw201408); 厦门市重大科技计划项目(No.3502Z20100006

Clinical Observation on Kangshi Kangxian Formula Combined with Interferon and Ribavirin in 33 Cases of Chronic Hepatitis C

目的观察康氏抗纤方联合聚乙二醇化干扰素α-2A(PEg-Ifnα-2A)、利巴韦林对慢性丙型肝炎(CHC)患者抗病毒治疗应答及生活质量的影响。方法选择CHC患者64例,随机分为治疗组33例与对照组31例。对照组给予PEg-Ifnα-2A注射液180μg/次,皮下注射,每周1次;利巴韦林0.3 g/次,口服,每天3次。治疗组在对照组基础上口服康氏抗纤方,每日1剂。两组均治疗24周。观察两组患者治疗前后肝组织病理、肝纤维化瞬时弹性测定值、血清丙氨酸氨基转氨酶(AlT)水平、丙肝病毒定量(HCV rnA)及慢性肝病问卷(CldQ)积分的变化。结果两组患者病毒学应答与生化应答比较差异无统计学意义(P>0.05)。治疗后两组肝脏炎症及纤维化程度均较本组治疗前显著改善(P 0.05).Inflammation and fibrosis of the liver were significantly improved after treatment( P < 0.05) compared within each group before.Improvement of liver fibrosis in treatment group is greater than control group( P < 0.05).On the improvement of Fibro Scan value,treatment group was obviously better than control group( P < 0.05).Every aspect of CLDQ scores of treatment group had different levels of increases( P < 0.01),while control group only had some increases on systemic symptom,activity ability and emotion scores( P < 0.05).After treatment,treatment group' s CLDQ scores on abdomenal pain,sleepinese,emotion and anxiety were notedly better than contreol group( P < 0.01).Conclusion Using Kangshi Kangxian Formula combined with PEG-IFNα-2a and ribavirin to treat CHC not only increased patient's response to antiviral therapy,but also improve the condition of liver fibrosis and patient's quality of life.福建省卫生厅青年科研课题基金资助项目(2012-2-105

Clinical Observation on Yixuesheng Capsule( 益血生胶囊) Combined with Western Medicine Treating 40 Cases of Chronic Viral Hepatitis C

目的观察益血生胶囊联合聚乙二醇化干扰素α-2A(PEg-Ifnα-2A)、利巴韦林片治疗慢性丙型病毒性肝炎的临床疗效。方法 80例慢性丙型病毒性肝炎患者采用随机数字表法分为治疗组和对照组各40例,均给予PEg-Ifnα-2A(每次180μg,皮下注射,每周1次)以及利巴韦林片(每次300 Mg,口服,每天3次)治疗,疗程6个月。治疗组在此治疗的首3个月,加用益血生胶囊口服,每次1 g,每天3次。两组患者治疗结束后随访6个月。观察治疗前后两组患者血清丙氨酸氨基转移酶水平、丙型肝炎病毒定量、中性粒细胞计数、血红蛋白含量、血小板计数的变化,比较两组患者生化学应答及病毒学应答百分比及骨髓抑制发生率。结果两组患者治疗3、6个月及随访6个月时病毒学应答比较差异均无统计学意义(P>0.05);两组患者治疗6个月及随访6个月生化学应答比较差异亦无统计学意义(P>0.05);治疗3、6个月时,治疗组的骨髓抑制发生率分别为35.00%及22.50%,均低于对照组的80.00%与60.00%(P 0.05).There was also no significant difference in biochemical responses between the two groups in the 6th month of treatment and the 6th month of following up( P > 0.05).In the 3rd and 6th month of treatment,the incidence of myelosuppression in treatment group was 35.00% and 22.50%,respectively,both of which were lower than that in control group( 80.00% and 60.00%,P < 0.01).Conclusion Combined with Yixuesheng Jiaonang,the effect of myelosuppression of PEG-IFNα2a and ribavirin treating CHC is attenuated,but the antiviral effect is not improved.福建省卫生厅青年科研课题(2012-2-105

Clinical Observation on 35 Cases of Chronic Hepatitis B Complicated with Depression Treated with Changyu Xiaoyao Fang( 菖郁逍遥方) Combined with Entecavir Dispersible Tablets

目的观察菖郁逍遥方联合恩替卡韦分散片治疗慢性乙型病毒性肝炎伴抑郁症的临床疗效及可能的作用机制。方法 67例慢性乙型病毒性肝炎伴抑郁症患者随机分为治疗组35例、对照组32例。在口服恩替卡韦分散片每日0.5 Mg的基础上,对照组加服氟哌噻吨美利曲辛片,每日2次,每次1片;治疗组加服中药复方菖郁逍遥方,每日1剂,两组疗程均为8周。治疗前后分别观察两组患者17项汉密尔顿抑郁量表(HAMd)、慢性肝病问卷(CldQ)积分以及血清白细胞介素6(Il-6)、肿瘤坏死因子α(Tnf-α)水平;比较两组患者抑郁状态疗效、血清丙氨酸氨基转移酶(AlT)复常率及乙型肝炎病毒dnA(HbV dnA)阴转率。结果治疗组抑郁状态疗效总有效率、AlT复常率、HbV dnA阴转率分别为80.00%、80.00%、60.00%,对照组分别为65.63%、62.50%、46.88%,治疗组均优于对照组(P<0.05)。与治疗前比较,治疗后两组患者HAMd评分、Il-6、Tnf-α水平均降低,CldQ各项得分及总积分均增加(P<0.05或P<0.01);治疗后治疗组Il-6、Tnf-α水平和CldQ各项得分及总积分改善程度较对照组更显著(P<0.05)。结论菖郁逍遥方联合恩替卡韦分散片可显著改善慢性乙型病毒性肝炎伴抑郁症患者的抑郁状态,并能增强抗病毒疗效、提高患者生活质量,其作用机制可能与抑制炎症反应相关。Objective To observe the clinical effect and possible mechanism of Changyu Xiaoyao Fang combined with entecavir dispersible tablets in treating chronic hepatitis B accompanied with depression.Methods67 patients with chronic hepatitis B accompanied with depression were randomly divided into a treatment group of 35 cases and a control group of 32 cases.In addition to taking 0.5 mg of entecavir dispersible tablet orally,control group was given flupentixol( 0.5 mg) and melitracen( 10 mg) tablet,one tablet twice a day orally,and treatment group was given Changyu Xiaoyao Fang one dose a day orally,both for 8 weeks.The scores of Hamilton Depression Scale( HAMD) and Chronic Liver Disease Questionnaire( CLDQ),as well as serum levels of interleukin 6( IL-6) and Tumor Necrosis Factorα( TNF-α) were detected before and after treatment.The improvement of depression,the normalization rate of serum level of alanine aminotransferase( ALT),and negative conversion rate of Hepatitis B Virus DNA( HBV DNA) in patients in both groups were observed after treatment.Results After treatment,the total effective rate in depression improvement,the normalization rate of ALT,and the negative conversion rate of HBV DNA was 80.0%,80.00% and 60.00%,respectively in treatment group,65.6%,62.50% and 46.88%,respectively in control group.The effects of all indexes in treatment group were superior to those in control group( P <0.05).The scores of HAMD,and levels of IL-6 and TNF-αwere decreased,and the scores of every items and total score of CLDQ were increased after treatment( P < 0.05 or P < 0.01).The improvement of IL-6,TNF-αand the scores of every items and total score of CLDQ in treatment group were superior to those in control group( P < 0.05).Conclusion Changyu Xiaoyao Fang combined with entecavir dispersible tablets could improve depression condition in patients with chronic hepatitis B accompanied with depression,strengthen antiviral effect,and improve quality of life.The mechanism may relate to inhibiting inflammation reaction.福建省卫生厅青年科研课题资助计划(2012-2-105); 福建省自然科学基金(2014J01374

Efficacy of CHSGS combined with interferon-αagainst chronic hepatitis B and effects on serum TNF-α,IL-6

目的：探讨柴胡疏肝散、甘草酸二铵肠溶胶囊对α-干扰素（interferon-alpha,IFN-α）治疗慢性乙型肝炎（chronic hepatitis B,CHB）疗效的观察及对肿瘤坏死因子-α（tumor necrosis factorα,TNF-α）、白细胞介素-6（interleukin-6,IL-6）水平的影响。方法：524例慢性乙型肝炎,按随机数字表法随机分为单药治疗组174例,联合中药治疗组174例,联合西药治疗组176例。单药治疗组采用IFN-α治疗24周;联合中药治疗组在IFN-α治疗基础上,采用柴胡疏肝散口服,每日1剂,疗程24周;联合西药治疗组在IFN-α治疗基础上,采用甘草酸二铵肠溶胶囊150-mg tid口服,疗程24周。观察3组治疗前后的症状积分改变情况、中医症状疗效、ALT水平、HBV DNA定量、抗病毒治疗应答及治疗前、治疗8周、治疗24周的TNF-α、IL-6水平的变化。结果：治疗24周后,联合中药治疗组症状积分改善程度最明显、中医症状疗效总有效率最高,联合西药治疗组次之,而单药治疗组最低（P0.05）。结论：INF-α联合柴胡疏肝散治疗慢性乙型肝炎可改善患者症状,增加INF-α抗病毒疗效,值得推荐联用,而联合甘草酸二铵肠溶胶囊治疗可降低INF-α抗病毒疗效,不推荐联合使用,INF-α及柴胡疏肝散均可以通过上调TNF-α、IL-6水平通过免疫激活来清除病毒,二者联用可起到协同作用。OBJECTIVE To explore the efficacy of Chaihu Shugan San（CHSGS）or diammonium glycyrrhizinate enteric-coated capsules combined with interferonα（interferonα,IFN-α）against chronic hepatitis B（CHB）.METHODS Totally 524 cases of CHB were randomly divided into 3 groups,including single drug group（174 cases）,traditional Chinese medicine（TCM）combined group（174 cases）and western medicine combined group（176 cases）.Patients were treated with IFN-αin single drug treatment group,with IFN-αbased on CHSGS in traditional Chinese medicine combined group,with IFN-αtreatment based on the licorice diammonium glycyrrhizinate enteric-coated capsules in western medicine combined group.The course of treatment was 24 weeks.Symptom score,the curative effect of TCM,ALT level,HBV DNA quantitation,antiviral treatment response were observed in three groups before and after treatment,changes of TNF-αand IL-6 levels were observed before treatment,after 8 weeks and 24 weeks of treatment.RESULTS After 24 weeks of treatment,the symptoms improved most obviously in TCM combined group and least in single drug group（P0.01,P0.05）.After treatment,the complete response rate was highest in TCM combined group and the lowest in single drug group（P0.05）.After 8 weeks of treatment,the levels of TNF-αand IL-6 were increased in TCM combined group and in single drug group but decreased in western medicine combined group,the levels of TNF-αand IL-6 were decreased in TCM combined treatment group and single drug group in8 and24 weeks of treatment.CONCLUSION IFN-αcombined with CHSGS or CHB can improve the symptoms of the patients,increase the antiviral efficacy,and it is worthy to be recommended.Combination with diammonium glycyrrhizinate enteric-coated capsules can reduce interferon antiviral efficacy,and should not be recommended.国家自然科学基金（No.81503529,NO.81673660）;福建省卫生厅中医药项目（No.wzpw201308）;福建省自然科学基金面上资助项目（No.2014J01374）;福建省科技计划引导性项目（No.2016D012）;厦门市科技计划项目（3502Z20134020