N-乙酰半胱氨酸治疗慢性乙型肝炎重度患者的疗效

目的 观察N-乙酰半胱氨酸(NAC)和还原型谷胱甘肽(GSH)治疗慢性乙型肝炎重度患者的临床疗效和安全性.方法 75例慢性乙型肝炎重度患者随机分为NAC组(50例)和GSH组(25例),在综合治疗的基础上,分别静脉滴注NAC注射液8g或GSH 1.2g,1次/d,用药28 d.比较治疗前后两组患者的临床症状、血清总胆红素、凝血酶原活动度等,并以血清总胆红素和凝血酶原活动度两个指标的改善来评价综合疗效.观察两组患者用药后的不良反应情况.结果 NAC与GSH均有保肝、降胆红素的作用,总有效率分别为84%和72%,并且NAC降低胆红素的速度更快(P<0.05),在治疗的14d和21 d,总胆红素下降率分别为20.89%±12.36%和31.76%±17.41%.NAC组不良反应主要表现为恶心、呕吐、皮疹等,发生率为13%,未发生严重不良反应.结论 NAC与GSH均能降低患者血清总胆红素,提升凝血酶原活动度.NAC在降低胆红素速度上优于GSH,用药过程中患者耐受性好,无严重的不良反应.     

戊型肝炎与慢性乙型肝炎重叠戊型肝炎病毒感染的临床特征比较

目的分析比较戊型肝炎与慢性乙型肝炎重叠戊型肝炎病毒感染患者的临床特征,并初步探索戊型肝炎慢性化问题。方法对66例戊型肝炎与37例慢性乙型肝炎重叠戊型肝炎病毒感染患者的临床资料进行回顾性分析比较及统计。结果慢性乙型肝炎重叠戊型肝炎病毒感染患者较戊型肝炎患者丙氨酸氨基转移酶(ALT)、天门冬酸氨基转移酶(AST)、总胆红素(TBIL)、直接胆红素(DBIL)升高水平及发生率无显著差异,而在白蛋白(A)、白蛋白/球蛋白(A/G)及凝血酶原活动度(PTA)降低与肝纤维化系列各项指标增高方面更突出,消化道症状更重。结论慢性乙型肝炎重叠戊型肝炎病毒感染后肝功能损害更严重,凝血酶原时间长,慢性肝病特征常见,但单纯戊型肝炎患者慢性化问题也值得重视。     

影响重型肝炎预后的因素分析

目的研究重型肝炎的各种预后因素的重要性。方法选择2000年1月至2004年12月我院收治的重型肝炎患者358例,分为好转治愈组和恶化死亡组,将两组的临床资料进行单因素和多因素分析。结果两组之间在凝血酶原活动度、肝性脑病、总胆红素和天冬氨酸氨基转移酶/丙氨酸氨基转移酶等方面有显著性差异(P<0.05)。结论凝血酶原活动度、肝性脑病、总胆红素和天冬氨酸氨基转移酶/丙氨酸氨基转移酶比值等可以作为判断重型肝炎预后的指标,对指导临床有一定价值。     

外周血CD5+B细胞与HBV感染慢性化、严重化的关系

目的 探讨CD5 B细胞是否参与乙型肝炎的慢性化及严重化进程.方法 将慢性肝病患者分为慢性乙型肝炎、慢性重型肝炎、肝炎后肝硬化三组,并设健康对照.检测肝脏各项检测指标(丙氨酸转移酶、天冬氨酸转移酶、总胆红素、间接胆红素、碱性磷酸酶、γ-谷氨酰转肽酶、白蛋白、球蛋白、凝血酶原活动度、胆固醇及HBV-DNA定量),应用流式细胞仪检测外周血CD5 B细胞百分率.结果 肝硬化组CD5 B细胞百分率明显高于对照组;慢性乙肝组CD5 B细胞百分率与凝血酶原活动度有相关性(r=0.457,P<0.05),与肝功能其他各项指标均无相关性;其余各组与肝功能各项指标均无相关.结论 CD5 B细胞可能参与了乙型肝炎慢性化进程,但与病情严重程度无关.     

重型肝炎126例预后影响因素分析

目的对影响重型肝炎患者预后的因素进行分析和评估,对重型肝炎患者预后进行科学的预测。方法将2001-10~2004-06中国医科大学第二临床学院感染科收治的重型肝炎住院患者126例,分为死亡组(82例)与生存组(44例),比较两组在年龄、性别、亚型、生化指标、合并症上的差异。结果两组重型肝炎患者在性别、亚型方面比较差异无显著性(均为P>0.05)。≤40岁与>40岁患者的病死率比较差异有非常显著性(P<0.01);在生化指标上两组丙氨酸氨基转移酶与天门冬氨酸氨基转移酶的比值(ALT/AST)、总胆红素、直接胆红素与总胆红素比值、白蛋白、凝血酶原活动度、总胆固醇、胆碱脂酶、甲胎蛋白、钠离子比较差异具有显著性;死亡组合并症的发生率明显高于生存组(P<0.01)。结论年龄、ALT/AST、总胆红素、白蛋白、凝血酶原活动度、总胆固醇、胆碱脂酶、甲胎蛋白、钠离子及合并症是影响重型肝炎预后的重要因素。     

凝血酶原活动度与重型肝炎患者血浆置换疗效的关系

探讨凝血酶原活动度（PTA）与重型肝炎患者血浆置换（PE）疗效的关系。随机选取30例PTA〉30％和30例PTA〈30％的重型肝炎患者,观察血浆置换前后血清总胆红素和丙氨酸氨基转移酶（ALT）的变化。PTA〉30％组患者血浆置换后血清总胆红素和ALT均显著下降,PTA〈30％组的患者血浆置换后仅有ALT显著下降,而血清总胆红素下降不明显。PTA〉30％组患者血浆置换疗效优于PTA〈30％组患者,PTA可作为重型肝炎患者血浆置换疗效的预测因子。     

乙型重型肝炎患者血清HMGB1表达水平及其与肝生化指标相关性的研究

目的分析乙型重型肝炎患者血清高迁移率族蛋白1(HMGB1)表达水平及其与肝生化指标的相关性。方法将2015年7月至2016年12月期间我院收治的60例乙型重型肝炎患者(重型组)和60例慢性乙型肝炎患者(慢性组)以及门诊体检无异常的60名健康者(健康组)为研究资料。分析3组患者血清HMGB1水平差异和肝生化指标丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBil)、凝血酶原活动度(PTA)及白蛋白(Alb)水平差异,再将60例乙型重型肝炎患者血清HMGB1水平与肝生化指标ALT、AST、TBil、PTA及Alb进行Pearson相关性分析,以得出血清HMGB1水平与肝生化指标ALT、AST、TBil、PTA及Alb的相关性。结果健康组血清HMGB1水平低于慢性组,慢性组低于重型组(P0.05)。健康组血清ALT、AST、TBil水平均低于慢性组,慢性组低于重型组(均P0.05)。乙型重型肝炎患者血清HMGB1水平和ALT、AST、TBil水平均为正相关(均P0.05),和PTA、Alb水平均为负相关(均P0.05)。结论肝功能损伤越重,患者血清HMGB1水平越高。     

促肝细胞生长素治疗慢性乙型肝炎重度及重型的疗效评价

目的评价促肝细胞生长素治疗慢性乙型病毒性肝炎(重度及重症型)的临床疗效。方法将138例重度或重型慢性乙型肝炎患者随机分成观察组和对照组,两组基本用药相同,观察组加用促肝细胞生长素治疗25天,比较两组治疗前后总胆红素(TBIL)、凝血酶原活动度(PTA)和胆碱酯酶(CHE)的水平,统计病死率。结果疗程结束后。观察组与对照组的TBIL、PTA、CHE水平经统计学处理差异均无显著性(P>0.05);重症肝炎观察组病死率为43.2％,对照组为41.94％,两者比较亦无明显差异(P>0.05)。结论促肝细胞生长素治疗重度和重症型慢性乙型肝炎,疗效不确切。同时难以降低重症肝炎的病死率。     

影响慢性重型肝炎预后的因素分析

目的 探讨影响慢性重型肝炎预后的有关因素。方法 分析78例慢性重型肝炎的预后与年龄、血清总胆红素、凝血酶原时间、凝血酶原活动度、总胆固醇、并发症、病毒重叠感染、有无肝硬化的关系。结果 慢性重型肝炎的预后与血清总胆红素、凝血酶原时间、凝血酶原活动度、总胆固醇及并发症有关（P〈0．01或P〈0．05），而与年龄、病毒重叠感染、有无肝硬化无明显关系（P〉0．05）。结论 慢性重型肝炎患者血清总胆红素、凝血酶原时间、凝血酶原活动度、总胆固醇及并发症是判断预后的重要依据。     

恩替卡韦联合川芎嗪治疗慢性乙型重型肝炎疗效观察

目的观察恩替卡韦联合川芎嗪治疗慢性乙型重型肝炎的疗效。方法将72例慢性乙型重型肝炎患者,随机分为治疗组40例和对照组32例。对照组应用综合护肝治疗,治疗组在综合护肝治疗的基础上加用恩替卡韦和川芎嗪治疗。结果治疗6周后,治疗组血清总胆红素、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、白蛋白和凝血酶原时间明显改善,而对照组疗效不如治疗组好;治疗组HBVDNA为2．38±1．23 lgcopies／ml,而对照组血清总胆红素、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、白蛋白和凝血酶原时间为4．87±1．79 lgcopies／ml（P〈0．01）;治疗组住院时间为46．5±12．4天,而对照组为59．3±17．2天（P〈0．01）;治疗组死亡2例（5．0％）,而对照组死亡5例（15．6％）。结论恩替卡韦联合川芎嗪治疗慢性乙型重型肝炎可明显改善肝功能,降低HBVDNA载量。     

Evaluation of the effects of oral N-acetylcysteine and a placebo in paraclinical and oxidative stress parameters of patients with chronic hepatitis B

Background and Aims

The treatment of chronic hepatitis B (CHB) is a challenging problem today, and previous study has shown that oxidative stress causes the collective pathophysiological conditions of many hepatopathies, so other new therapeutic approaches are needed. Hence, in this study the paraclinical and oxidative stress parameters of the efficacy of N-acetyl cysteine (NAC) as an antioxidant in the treatment of CHB have been evaluated.

Methods

In this double-blind placebo-controlled clinical trial study, 43 patients with CHB were enrolled in 2008 in Tehran, Iran. The patients were randomly assigned to receive either 1200 mg/day NAC or a placebo for 45 days. Paraclinical tests and oxidative stress parameters were measured on experimental day 0 and on day 45.

Results

Liver function tests, i.e. alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels were not significantly different in the NAC group and in the placebo group. A reduction in catalase (CAT) activity and an increase in glutathione concentration were statistically significant in the NAC group (P < 0.05).

Conclusions

According to our results, oral NAC is not an effective adjuvant treatment for patients with CHB, but further research with a larger population is needed for the evaluation of the effectiveness of NAC in these patients.     

氧化苦参碱治疗慢性乙型肝炎的随机双盲对照多中心研究

目的 观察氧化苦参碱胶囊治疗慢性乙型肝炎的疗效及安全性。方法 进行多中心、随机、双盲、安慰剂对照设计的临床试验，选择慢性乙型肝炎患者144例，随机分为氧化苦参碱胶囊组72例和空白对照组72例完成52周治疗并随访12周。治疗前后及停药12周后观察患者临床症状、肝功能、血清乙型肝炎病毒(HBV)标志物和不良反应等。结果 所有入组患者中脱落和不符合入选标准剔除共14例，故共有130例患者纳入疗效统计，其中氧化苦参碱胶囊组65例，空白对照组65例。氧化苦参碱胶囊组治疗慢性乙型肝炎52周其HBVDNA和乙型肝炎e抗原(HBeAg)阴转率分别为43．08％(28／65)和33．33％(20／60)，丙氨酸氨基转移酶(ALT)复常率为70．77％(46／65)；空白对照组HBV DNA和HBeAg阴转率分别为12．31％(8／65)和3．33％(2／60)，ALT复常率为39．68％(25／63)。治疗后完全反应率．部分反应率和无反应率胶囊组分别为23．08％(15／65)，58．46％(38／65)和18．46％(12／65);而对照组分别为3．08％(2／65)、44．62％(29／65)和52．31％(34／65)。两组间比较胶囊组均明显高于对照组(QCMH=21．02，P=0．001)。氧化苦参碱胶囊组治疗慢性乙型肝炎停药12周后其HBV DNA和HBeAg阴转率分别为41．54％(27／65)和23．33％(14／60)，ALT复常率为60．00％(39／65);空白对照组HBV DNA和HBeAg阴转率分别为3．08％(2／65)和1．67％(1／60)，ALT复常率为31．75％(20／63)。完全反应率、部分反应率和无反应率胶囊组分别为21．54％(14／65)、47．69％(31／65)和30．77％(20／65)，而对照组分别为0，41．54％(27／65)和58．46％(38／65)，两组间比较胶囊组均明显高于对照组(QCMH=15．22，P=0．001)。氧化苦参碱胶囊组有5例(7．69％)发生不良反应，空白对照组有4例(6．15％)发生不良反应，主要表现为恶心、乏力、皮疹、上腹不适和口苦，均为轻，中度，无严重不良反应发生，不良反应发生率两组间比较差异无显著性。结论 氧化苦参碱胶囊是治疗慢性乙型肝炎有效，安全的药物。     

乙型肝炎患者血清高迁移率族蛋白-1含量的检测及临床意义

目的观察不同病情的乙型肝炎患者血清中晚期炎症介质高迁移率族蛋白-1（HMGB1）的含量，通过与肝炎病情评价指标TBil和PTA进行相关性比对，初步阐明晚期炎症介质HMGB1在慢性重型乙型肝炎患者肝衰竭发生中可能发挥的作用。方法收集慢性重型乙型肝炎患者23例，CHB患者31例，健康对照者10名，抽取外周血10ml，按常规方法检测肝炎病情指标TBil和PTA。超滤管去除血清中的大分子蛋白质，再浓缩血清小分子蛋白，然后用Western blot的方法检测样品中HMGB1。利用纯化出的GST-HMGB1融合蛋白进行相对定量，计算出不同患者血清中HMGB1的水平，最后与肝炎病情评价指标TBil和PTA进行相关性比对。结果23例慢性重型乙型肝炎患者血清中HMGB1检出率为100％（23／23），平均含量为（83．4±21．3）μg／L；10例重度CHB患者血清中HMGB1检出率为90％（9／10），平均含量为（78．1±19．5）μg／L；11例中度CHB患者的血清中HMGB1检出率为55％（6／11），平均含量为（60．6±14．3）μg／L；10例轻度CHB患者及12例恢复患者中均仅1例检出HMGB1，检出率分别为10％和8％，含量分别为28．9μg／L和39．7μg／L；健康对照者血清中未能检出HMGB1。血清中HMGB1的含量与TBil呈正相关，与PTA呈负相关。结论慢性重型乙型肝炎患者血清中HMGB1的含量与疾病的严重程度密切相关，晚期炎症介质HMGB1在慢性重型乙型肝炎患者肝衰竭的发生中可能起重要的作用。     

N-乙酰半胱氨酸和还原型谷胱甘肽治疗重型肝炎的临床对比观察

目的比较N-乙酰半胱氨酸（NAC）和还原型谷胱甘肽（GSH）治疗重型肝炎的疗效。方法将55例住院的重型肝炎患者随机分为GSH组（25例）和NAC组（30例）两组,分别在综合治疗的基础上加用GSH1．2g和NAC8．0g静脉点滴,连续用药28天,在用药过程中记录患者的临床症状、体征、血生化指标和凝血功能,并进行Child-push和MELD评分,同时观察不良反应。结果两组患者的肝功能和凝血功能均改善,两组比较无显著性差异（P〉0．05）;在治疗的第21天和28天,NAC组的TBbil和DBil下降率明显高于GSH组,差异有显著性（P〈0．05）;28天时NAC组的PTA提升率高于GSH组[（67．26±28．64）％vs（36．92±21．23）％,P〈0．05];NAC组的Child-Pugll评分和MELD评分均出现下降,并显著优于GSH组（P〈0．05）。NAC的不良反应主要为头晕、恶心、呕吐和皮肤瘙痒,无严重不良反应。结论与GSH组比较,NAC在减低重型肝炎患者的血清胆红素水平和改善凝血酶原活动度方面更具有优势,NAC治疗过程中患者耐受性较好,安全性较高。     

Early diagnosis of bacterial and fungal infection in chronic cholestatic hepatitis B

AIM: To investigate the early diagnostic methods of bacterial and fungal infection in patients with chronic cholestatic hepatitis B.METHODS: One hundred and one adult in-patients with chronic hepatitis B were studied and divided into 3 groups:direct bilirubin (DBil)/total bilirubin (TBil)≥0.5, without bacterial and fungal infection (group A, n=-38); DBil/TBil&lt;0.5, without bacterial and fungal infection (group B, n=23),DBil/TBil≥0.5, with bacterial or fungal infection (group C,rr=-40). The serum biochemical index and pulse rate were analyzed.RESULTS: Level of TBil, DBil, alkaline phosphatase (ALP) and DBiI/ALP in group A increased compared with that in group B. The level of ALP in group C decreased compared with that in group A, whereas the level of TBil, DBil and DBiI/ALP increased (ALP: 156+43, 199+68, respectively,P&lt;0.05, TBil: 370+227, 220+206, respectively, P&lt;0.01,DBil: 214+143, 146+136, respectively, P&lt;0.01, DBiI/ALP:1.65+1.05, 0.78+0.70, respectively, P&lt;0.001). The level of DBil and infection affected DBiI/ALP. Independent of theeffect of DBil, infection caused DBiI/ALP to rise (P&lt;0.05).The pulse rate in group A decreased compared with that in group B (63.7+6.4, 77.7+11.4, respectively, P&lt;0.001),and the pulse rate in group C increased compared withthat in group A (81.2+12.2, 63.7+6.4, respectively, P&lt;0.001).The equation (infection=0.218 pusle rate +1.064 DBiI/ALP-16.361), with total accuracy of 85.5%, was obtained from stepwise logistic regression. Pulse rate (≥80/min) andDBiI/ALP (≥1.0) were used to screen infection. The sensitivity was 62.5% and 64.7% respectively, and the specificity was 100% and 82.8% respectively.CONCLUSION: Bacterial and fungal infection deterioratejaundice and increase pulse rate, decrease serum ALP andincrease DBiI/ALP. Pulse rate, DBiI/ALP and the equation(infection=0.218 pusle rate+1.064 DBil/ALP-16.361) arehelpful to early diagnosis of bacterial and fungal infectionin patients with chronic cholestatic hepatitis B.     

Levamisole therapy in chronic type B hepatitis. Results of a double-blind randomized trial

A double-blind, randomized, controlled trial has been undertaken to evaluate treatment of chronic hepatitis type B with levamisole. Ten patients received levamisole (150 mg/day, 3 days/wk) and 10 received placebo until seroconversion to antibody to hepatitis B e antigen eventually occurred, or for a maximum of 18 mo. Final evaluation at 24 mo after starting treatment revealed that 60% of the patients in the levamisole group had become hepatitis B e antigen negative, 90% were hepatitis B virus-deoxyribonucleic acid negative in serum, and 8 of 9 (89%) patients had cleared hepatitis B core antigen from the liver. On the other hand, in the placebo group only 4 of the 10 subjects (40%) were hepatitis B e antigen and hepatitis B virus-deoxyribonucleic acid negative in serum and 3 of 8 (37.5%) of them became hepatitis B core antigen free in the liver. Moreover, in 8 patients of the treated group and in 4 of the control cases aminotransferase activities fell into the normal range. A liver biopsy specimen was obtained after treatment in 17 patients and 7 of 9 levamisole recipients showed marked improvement in hepatic histology, compared with 3 of 8 placebo recipients. These data show that patients treated with long-term levamisole therapy have a tendency toward normalization of aminotransferase activities and suppression of hepatitis B virus replication, suggesting that the drug may be of benefit in chronic hepatitis B e antigen-positive hepatitis.     

N-acetyl cysteine therapy in acute viral hepatitis

AIM: To investigate the effect of N-acetyl cysteine (NAC) on acute viral hepatitis (AVH). METHODS: We administered 200 mg oral NAC three times daily (600 mg/day) to the study group and placebo capsules to the control group. All patients were hospitalized and diagnosed as AVH. Blood total and direct bilirubin, ALT, AST, alkaline phosphatase, albumin and globulin levels of each patient were measured twice weekly until total bilirubin level dropped under 2 mg/dl, ALT level under 100 U/L, follow up was continued and then the patients were discharged. RESULTS: A total of 41(13 female and 28 male) AVH patients were included in our study. The period for normalization of ALT and total bilirubin in the study group was 19.7+/-6.9 days and 13.7 +/- 8.5 days respectively. In the control group it was 20.4 +/- 6.5 days and 16.9 +/- 7.8 days respectively (P>0.05). CONCLUSION: NAC administration effected neither the time necessary for normalization of ALT and total bilirubin values nor duration of hospitalization, so we could not suggest NAC for the treatment of icteric AVH cases. However, our results have shown that this drug is not harmful to patients with AVH.     

双环醇对慢性乙型肝炎患者血清丙二醛水平的影响

目的探讨双环醇对慢性乙型肝炎（CHB）患者血清丙二醛（MDA）水平的影响。方法选择85例CHB患者分为对照组及观察组,对照组40例,给予一般治疗,观察组45例,在一般治疗基础上加用口服双环醇片50 mg,每日3次。收集两组患者治疗前及治疗3个月后的血清,用化学方法检测MDA水平,并同时观察ALT、AST、TBil、Alb、HBV DNA、HBV M的变化。结果治疗3个月后两组MDA、ALT、AST、TBil均有所下降,观察组下降较显著,差异具有统计学意义;两组ALB均有所上升,部分患者HBV DNA水平下降,出现血清学转换,但差异无统计学意义（均为治疗后两组间前后比较）。结论双环醇能够降低CHB患者血清MDA水平,说明双环醇具有明显的抗脂质过氧化损伤作用,有助于CHB患者肝功能的恢复。