肝纤方配合拉米夫定治疗慢性乙型肝炎31例临床观察

目的 :评价肝纤方配合拉米夫定治疗慢性乙型肝炎 (慢性乙肝 )的疗效。方法 :采用肝纤方 (制大黄、鳖甲、首乌、赤芍等 )联合拉米夫定治疗慢性乙肝 31例 ,并与单用拉米夫定治疗 37例随机对照观察 1年。结果 :肝纤方配合拉米夫定治疗组总有效率 (完全应答 +部分应答 )达 90 .3% ,与对照组 70 .3%比较有显著性差异(P<0 .0 5 ) ;且无一例乙肝病毒基因型变异 (YMDD)阳性发生 ,而对照组出现阳性 5例 (占 16 .7% ) ;其他客观指标治疗组也略优于对照组。结论 :肝纤方弥补了拉米夫定的不足 ,联合使用具有明显的协同作用。

王氏抗肝纤方治疗肝纤维化的实验研究

目的:观察王氏抗肝纤方对肝纤维化的治疗作用及其作用机制。方法:采用二甲基亚硝胺诱导肝纤维化模型,从组织学改变观察王氏抗肝纤方的疗效,以γ干扰素及膈下退瘀汤作为对照组。结果:王氏抗肝纤方对肝歼堆化大鼠能显著降低血清ALT、AST及肝组织Hyp含重,减少肝组织中ColⅠ、ColⅣ的沉积和a-SMA的表达,提高肝组织间质胶原酶活性。其作用同γ干扰素而明显优于膈下逐瘀汤。结论:王氏抗肝纤方具有较好的抗肝纤维化作用,能抑制胶原纤维的形成,并通过提高肝组织间质胶原酶活性而促进胶原的降解。

肝纤方联合拉米夫定治疗对慢性乙型肝炎T细胞亚群及肝纤维化指标的影响

目的:评价联合应用肝纤方和拉米夫定治疗慢性乙型肝炎肝纤维化患者T细胞亚群及肝纤维化指标的影响。方法:72例慢性乙型肝炎采用肝纤方(制大黄、鳖甲、首乌、赤芍等)联合拉米夫定治疗,并与单用拉米夫定治疗86例随机对照观察2年。结果:慢性乙型肝炎采用联合应用肝纤方和拉米夫定治疗后各项肝纤指标含量下降幅度明显优于单用拉米夫定治疗组,(P <0. 0 1或<0 . 0 5 ) :CD+4、CD+4 CD+8上升的幅度较对照组大,CD+8下降的幅度也较对照组大(P <0 .0 1)。结论:联合用药改善了患者的免疫状态,更有利于阻断或逆转肝纤维化的形成与发展,具有一定的临床试用价值。

抗肝纤方治疗肝炎后肝纤维化疗效观察

目的 :观察抗肝纤方治疗肝纤维化及早期肝硬变的效果。方法 :选择肝炎后肝纤维化患者 78例 ,随机分为中药组、对照组 ,观察治疗前后及两组间临床症状、肝功能、脾厚径、门静脉主干内径及血清肝纤维化指标透明质酸 (HA)、 型前胶原 (PC )、转化生长因子 - β1(TGF-β1)的变化。结果 :中药组治疗前后症状、肝功能、 HA、 PC 、 TGF-β1变化有显著性差异 (P<0 .0 5) ;两组间治疗后症状、肝功能、脾厚径、门静脉主干内径、HA、PC 、TGF- β1的变化有显著性差异 (P<0 .0 5～ 0 .0 1 )

抗肝纤方联合γ-干扰素治疗慢性乙型肝炎肝纤维化的临床研究

目的:观察抗肝纤方联合γ-干扰素对慢性乙型肝炎肝纤维化标志物的影响。方法:将110例患者随机分为3组。对照组30例,采用一般护肝治疗;治疗1组40例,采用γ-干扰素治疗;治疗2组40例,采用抗肝纤方加γ-干扰素治疗。主要观察治疗前后影像学指标及肝纤维化标志物血清Ⅲ型前胶原肽(PIIIP)、透明质酸(HA)、Ⅳ型胶原(Ⅳ-C)、层粘蛋白(LN)和肝纤维化程度等的变化。结果:治疗后治疗1、2组脾脏厚度恢复正常,门静脉内径明显缩小,与治疗前比较,差异均有显著性意义 (P<0．05);其中治疗2组与对照组比较,差异有显著性意义(P<0．05)。治疗后治疗1、2组肝纤维化各项指标与治疗前比较,差异均有显著性意义(P<0．05);治疗2组HA、PIIIP与治疗1组比较,差异均有显著性意义(P<0．05)。治疗后2组炎症分级、炎症计分、肝纤维化分期及肝纤维化计分与治疗前比较,差异均有显著性意义(P<0．05);治疗2组与治疗1组比较,差异均有显著性意义(P<0．05)。结论:干扰素联合中药复方抗肝纤方可能具有更好的抗肝纤维化功效。

抗肝纤方对肝硬化门静脉血流动力学的影响观察

目的观察抗肝纤方对肝硬化门静脉血流动力学的改善效果。方法将2016年1月—12月在我院接受治疗的肝硬化患者随机分为2组,对照组进行普通治疗,试验组在对照组基础上加用抗肝纤方治疗。在治疗前和治疗8周后对患者进行彩色多普勒超声观察。结果治疗8周后,试验组门静脉内径小于对照组,门静脉最大血流速度和平均血流速度大于对照组,差异均有统计学意义(P<0.05)。结论抗肝纤方对于肝硬化患者的门静脉血流动力学改善明显,适合在临床上推广。

肝纤方联合西药治疗慢性乙型肝炎肝纤维化随机平行对照研究

[目的]观察肝纤方联合西药治疗慢性乙型肝炎肝纤维化疗效。[方法]使用随机平行对照方法,将148例住院患者按掷骰子法简单随机分为两组。对照组74例复合维生素B,1片/次,3次/d;维生素C,0.1g/次,3次/d;肌苷,0.4g/次,3次/d;联苯双酯,7.5mg/次,3次/d;拉米夫丁,0.1g/次,1次/d。治疗组74例肝纤方(白花蛇舌草、半枝莲各30g,鳖甲、桃仁、当归、赤芍、海藻各20g,大黄制、水飞蓟、黄芪、丹参、鸡血藤各15g,生地、柴胡、甘草、三七粉各10g),1剂/d,水煎200m L,早晚分服,100m L/次;西药治疗同对照组。连续治疗1年为1疗程。观测临床症状、HA、P-CⅢ、Ⅳ-C、LN、不良反应。治疗1疗程,判定疗效。[结果]治疗组痊愈22例,显效25例,有效25例,无效2例,总有效率97.30%。对照组痊愈19例,显效24例,有效23例,无效8例,总有效率89.19%。治疗组疗效优于对照组(P<0.05)。肝纤维指标两组均有改善(P<0.01),治疗组改善优于对照组(P<0.01)。[结论]肝纤方联合西药治疗慢性乙型肝炎肝纤维化疗效满意,无严重不良反应,值得推广。

化肝纤方联合恩替卡韦对慢乙肝肝纤维化患者的血清壳多糖酶3样蛋白1及临床疗效观察

目的:基于以壳多糖酶3样蛋白1(chitinase-3-like protein 1,CHI3L1)为主要评价指标,观察化肝纤方联合恩替卡韦治疗慢性乙型肝炎肝纤维化的临床疗效。方法:将80例确诊为慢性乙型肝炎肝纤维化的患者采用随机数字表法的方式分为对照组和治疗组各40例,2组均采用一般西医综合治疗,治疗组在此基础上仅加用化肝纤方,疗程为8周,比较2组治疗前后的血清CHI3L1水平、肝功能(转氨酶、总胆红素)、肝纤4项、Fibrosis 4 Score(FIB-4指数)、肝脏硬度值(liver stiffness measurement,LSM)、乙肝病毒DNA(hepatitis B virus-DNA,HBV-DNA)转阴率、中医症状评分等观察指标。结果:治疗后治疗组血清CHI3L1水平、肝功能(转氨酶、总胆红素)、肝纤4项、FIB-4指数、肝脏硬度值、HBV-DNA转阴率、中医症状评分均低于对照组,差异有统计学意义。结论:化肝纤方联合恩替卡韦治疗慢性乙型肝炎相关肝纤维化有较好的临床疗效,可改善慢性乙型肝炎肝纤维化患者肝脏生理水平及肝纤维化程度,降低血清CHI3L1、肝纤4项、FBI-4指数、肝脏硬度值,提高乙肝病毒DNA转阴率,改善肝功能及临床症状,延缓疾病的进展,提高患者生存质量。

抗肝纤方对早期肝硬化门脉高压症患者血流动力学的影响

目的：探讨抗肝纤方对早期肝硬化门脉高压症患者血流动力学的影响。方法2013年1月~2014年5月，将符合诊断标准的60例患者，按照随机数字表法分为治疗组和对照组各30例，治疗组采用抗纤方治疗，对照组使用盐酸普萘洛尔配合大黄蟅虫胶囊进行治疗。观察两组治疗前后的门静脉内径（DPV）、脾静脉内径（DSV）、脾静脉血流量（SVF）、门静脉血流量（PVF）及肝纤维化指标变化情况。结果治疗后，两组均能明显降低血清中HA、PCⅢ、LN、CⅣ值，但两组差异无统计学意义（P〉0.05）；两组均能降低DPV、DSV、PVF值，且治疗组的SVF值明显降低（P〈0.01），治疗后，两组患者的DSV、PVF、SVF值比较，差异有统计学意义（P〈0.05）。结论抗肝纤方能有效地缓解患者的肝纤维化病情，且可改善其血流动力学指标，值得在临床推广。

抗肝纤方对大鼠肝纤维化防治作用的实验研究

目的 :通过大鼠肝纤维化动物模型 ,研究抗肝纤方预防肝纤维化的作用 ,并探讨其作用机制。方法 :采用二甲基亚硝胺(DMN)诱导大鼠制备肝纤维化模型 ,以秋水仙碱为阳性对照 ,采用光镜观察组织学改变并测定血清谷丙氨酸转移酶 (ALT)、谷草氨酸转移酶 (AST)、白蛋白 (ALB)、球蛋白 (GLB)、透明质酸 (HA)、层粘连蛋白 (LN)、III型前胶原 (PCIII)、和IV型胶原(IV C) ,以反映肝细胞损伤及肝纤维化的程度。结果 :抗肝纤方能显著降低大鼠血清中ALT、AST、HA、LN、PCIII、IV C的水平 ,升高ALB。病理组织学检查亦表明 ,抗肝纤方能明显减轻实验大鼠肝脏纤维化程度。结论

抗肝纤方治疗早中期乙肝肝硬化临床研究

目的:用自拟抗肝纤方治疗早中期乙肝肝硬化的疗效观察,寻找治疗早中期乙肝肝纤维化的有效方法。方法:治疗组46例患者服用抗肝纤方汤剂,1剂/d,水煎服。对照组口服一般护肝药。结果:抗肝纤方治疗后血清透明质酸酶(HA)、层粘蛋白(LN)和Ⅲ型前胶原(PC-Ⅲ)均明显下降,两组比较有极显著差异(P<0.01)。治疗后肝脾影像学明显好转,两组比较有明显差异。症状、体征及肝功能均有明显改善,但无显著差异。结论:抗肝纤方对早中期乙肝肝硬化患者有明显的抗肝纤维化、降低门脉压、缩小肿大之脾脏;同时有护肝和改善症状与体征之功效,值得临床进一步研究与推广。

肝纤方联合拉米夫定治疗慢性乙型肝炎肝纤维化疗效观察

[目的] 评价肝纤方联合拉米夫定治疗慢性乙型肝炎肝纤维化的疗效。[方法] 采用肝纤方(制大黄、鳖甲、首乌、赤芍等)联合拉米夫定治疗慢性乙型肝炎72例,并与单用拉米夫定治疗 86 例随机对照观察 2 a。[结果]联合治疗组治疗后患者各项肝纤维化指标下降幅度明显大于单用拉米夫定治疗组(P<0.01或<0.05)。[结论]联合用药更有利于阻断或逆转肝纤维化的形成与发展,具有一定的临床试用价值。

“抗肝纤268方”对肝纤维化的治疗作用

目的 探讨“抗肝纤 2 6 8方”对肝纤维化的影响及机理。方法 制备肝纤维化模型鼠 ,采用“抗肝纤 2 6 8方”高、低剂量治疗 3周 ,对照组用秋水仙碱治疗 ,Masson染色后光镜下统计肝内纤维成分的数量 (IOD值 ) ,免疫组化染色后统计肝内 TGF-β1 、α- SMA、FN、L N、 型胶原、 型胶原等的数量 (IOD值 )。结果 模型组大鼠 FN、L N、 型胶原、 型胶原、TGF- β1 、α- SMA,以及肝内纤维成分等的 IOD值与正常组比较均增高 ,差异有显著性 (P<0 .0 5或 P<0 .0 1 )。“抗肝纤 2 6 8方”低、高剂量以及秋水仙碱治疗 3周后 ,以上指标的 IOD值与模型组比较 ,差异有显著性(P<0 .0 5或 P<0 .0 1 )。低剂量组与高剂量组、对照组比较 ,差异有显著性 (P<0 .0 5 )。结论 “抗肝纤 2 6 8方”可调节 TGF- β1 的数量、进而影响 α- SMA的数量、从而减少细胞外基质 (ECM)数量 。

自拟软肝降纤方联合阿德福韦酯治疗慢性乙型肝炎疗效观察

目的:观察自拟软肝降纤方联合阿德福韦酯治疗慢性乙型肝炎肝纤维化指标和HBV-DNA的变化。方法:对本科2008年、2009年慢性乙型肝炎60例采用软肝降纤方联合阿德福韦酯治疗对肝纤维化指标(肝纤四项)和HBV-DNA检测,并与同期单用阿德福韦酯治疗50例对照。结果:治疗组与对照组的肝纤四项指标治疗前后(6个月)比较有显著差别,而HBV-DNA两组无统计学意义。结论:自拟软肝降纤方联合阿德福韦酯治疗慢性乙型肝炎对降低肝纤四项指标有较好疗效。

Transient elastography for the assessment of chronic liver disease: Ready for the clinic?

Transient elastography is a recently developed non- invasive technique for the assessment of hepatic fi brosis. The technique has been subject to rigorous evaluation in a number of studies in patients with chronic liver disease of varying aetiology. Transient elastography has been compared with histological assessment of percutaneous liver biopsy, with high sensitivity and specificity for the diagnosis of cirrhosis, and has also been used to assess pre-cirrhotic disease. However, the cut-off values between different histological stages vary substantially in different studies, patient groups and aetiology of liver disease. More recent studies have examined the possible place of transient elastography in clinical practice, including risk stratifi cation for the development of complications of cirrhosis. This review describes the technique of transient elastography and discusses the interpretation of recent studies, emphasizing its applicability in the clinical setting.

Is it better to use two elastographic methods for liver fibrosis assessment?

AIM:To find out if by combining 2 ultrasound based elastographic methods:acoustic radiation force impulse(ARFI)elastography and transient elastography(TE),we can improve the prediction of fibrosis in patients with chronic hepatitis C.METHODS:Our study included 197 patients with chronic hepatitis C.In each patient,we performed,in the same session,liver stiffness(LS)measurements by means of TE and ARFI,respectively,and liver biopsy(LB),assessed according to the Metavir score.10 LS measurements were performed both by TE and ARFI;median values were calculated and expressed in kilopascals(kPa)and meters/second(m/s),respectively.Only TE and ARFI measurements with IQR<30%andSR≥60%were considered reliable.RESULTS:On LB 13(6.6%)patients had F0,32(16.2%) had F1,52(26.4%)had F2,47(23.9%)had F3,and 53(26.9%)had F4.A direct,strong correlation was found between TE measurements and fibrosis(r=0.741),between ARFI and fibrosis(r=0.730)and also between TE and ARFI(r=0.675).For predicting significant fibrosis(F≥2),for a cutoff of 6.7 kPa,TE had 77.5% sensitivity(Se)and 86.5%specificity(Sp)[area under the receiver operating characteristic curve(AUROC)0.87] and for a cutoff of 1.2 m/s,ARFI had 76.9%Se and 86.7%Sp(AUROC 0.84).For predicting cirrhosis(F=4),for a cutoff of 12.2 kPa,TE had 96.2%Se and 89.6% Sp(AUROC 0.97)and for a cutoff of 1.8 m/s,ARFI had 90.4%Se and 85.6%Sp(AUROC 0.91).When both elastographic methods were taken into consideration,for predicting significant fibrosis(F≥2),(TE≥6.7 kPa and ARFI≥1.2 m/s)we obtained 60.5%Se,93.3% Sp,96.8%positive predictive value(PPV),41.4%negative predictive value(NPV)and 68%accuracy,while for predicting cirrhosis(TE≥12.2 kPa and ARFI≥1.8 m/s) we obtained 84.9%Se,94.4%Sp,84.9%PPV,94.4% NPV and 91.8%accuracy.CONCLUSION:TE used in combination with ARFI is highly specific for predicting significant fibrosis;therefore when the two methods are concordant,liver biopsy can be avoided.

FEASIBILITY OF DIAGNOSING AND STAGING LIVER FIBROSIS WITH DIFFUSION WEIGHTED IMAGING

Objective To assess the clinical feasibility of diagnosing and staging liver fibrosis by apparent diffusion coefficient (ADC). Methods Totally, 43 patients (mean age 29.3 years) with chronic hepatitis by liver biopsy and 7 healthy controls (mean age 39.9 years) underwent liver diffusion weighted imaging (DWI) with four b values: 0, 200, 500, and 1000 s/mm2 respectively. The liver fibrosis was staged according to Ishak fibrosis stage. The ADC value of liver fibrosis patients and healthy controls was compared. The correlation of ADC value and liver fibrosis staging was analyzed. Result The histological staging showed 8 stage 1 patients, 10 stage 2 patients, 6 stage 3 patients, 9 stage 4 patients, 8 stage 5 patients and 2 stage 6 patients. The mean ADC value of liver fibrosis patients was significantly lower than that of healthy controls except for stage 1 group (P < 0.05). There was a negative correlation between liver fibrosis staging and ADC value (r = -0.697 with b=500 s/mm2, P < 0.01). Receiver operating characteristic (ROC) curve of ADC value of advanced liver fibrosis (Ishak stage F3 and higher) showed that area under curve = 0.913, 0.825, and 0.794 with b = 500, 1000, and 200 s/mm2, respectively (95% confidence interval: 83.6%-99.0%, 70.7%-94.3%, 66.5%- 92.4%; P < 0.05). When b value was 500 s/mm2, the sensitivity (84%) and specificity (80%) of DWI for diagnosis of advanced liver fibrosis were the highest. Conclusion DWI is proved to be a useful clinical tool in the quantitative evaluation of liver fibrosis and in the prediction of the process of liver fibrosis with the recommendable b value (500 s/mm2).

Rosiglitazone prevents murine hepatic fibrosis induced by Schistosoma japonicum

AIM: To evaluate the effect of rosiglitazone in a murine model of liver fibrosis induced by Schistosoma japonicum infection. METHODS: A total of 50 mice were randomly and averagely divided into groups A, B, C, D and E. The mice in group A served as normal controls, while those in the other four groups were infected with Schistosoma japonicum to induce the model of liver fibrosis. Besides, the mice in groups C, D and E were treated with praziquantel, rosiglitazone and praziquantel plus rosiglitazone, respectively. NF-κB binding activity and expression of PPARγ-mRNA were determined by Western blot assay and real-time quantitative PCR. Radioimmunonassay technique was used to detect the serum content changes of TNF-α and IL-6. Histological specimens were stained with HE. Expression of TGF-β1, a-smooth muscle actin and type ?Ⅰ?and type Ⅲ collagen was detected by immunohistochemistry and multimedia color pathographic analysis system. RESULTS: Inflammation and fibrosis in the rosiglitazone plus praziquantel treatment group (group E) were lightest among the mice infected with Schistosoma (P < 0.05). To further explore the mechanism of rosiglitazone action, we found that rosiglitazone can significantly increase the expression of PPARγ [E: -18.212 ± (-3.909) vs B: -27.315 ± (-6.348) and C: -25.647 ± (-5.694), P < 0.05],reduce the NF-κB binding activity (E: 88.89 ± 19.34 vs B: 141.11 ± 15.37, C: 112.89 ± 20.17 and D: 108.89 ± 20.47, P < 0.05), and lower the serum level of TNF-α (E: 1.613 ± 0.420 ng/mL vs B: 2.892 ± 0.587 ng/mL, C: 2.346 ± 0.371 ng/mL and D: 2.160 ± 0.395 ng/mL, P < 0.05) and IL-6 (E: 0.106 ± 0.021 ng/mL vs B: 0.140 ± 0.031 ng/mL and C: 0.137 ± 0.027 ng/mL, P < 0.05) in mice with liver fibrosis. Rosiglitazone can also substantially reduce the hepatic expression of TGF-β1, α-SMA type Ⅰand type Ⅲ collagen in mice with liver fibrosis. CONCLUSION: The activation of PPARγ by its ligand can retard liver fibrosis and suggest the use of rosiglitazone for the treatment of liver fibrosis due to Schistosoma japonicum infection.

Non-invasive assessment of liver fibrosis in chronic liver diseases:Implementation in clinical practice and decisional algorithms

Chronic hepatitis B and C together with alcoholic and non-alcoholic fatty liver diseases represent the major causes of progressive liver disease that can eventually evolve into cirrhosis and its end-stage complications,including decompensation,bleeding and liver cancer.Formation and accumulation of fibrosis in the liver is the common pathway that leads to an evolutive liver disease.Precise definition of liver fibrosis stage is essential for management of the patient in clinical practice since the presence of bridging fibrosis represents a strong indication for antiviral therapy for chronic viral hepatitis,while cirrhosis requires a specif ic follow-up including screening for esophageal varices and hepatocellular carcinoma.Liver biopsy has always represented the standard of reference for assessment of hepatic fibrosis but it has some limitations being invasive,costly and prone to sampling errors.Recently,blood markers and instrumental methods have been proposed for the non-invasive assessment of liver fibrosis.However,there are still some doubts as to their implementation in clinical practice and a real consensus on how and when to use them is not still available.This is due to an unsatisfactory accuracy for some of them,and to an incomplete validation for others.Some studies suggest that performance of non-invasive methods for liver fibrosis assessment may increase when they are combined.Combination algorithms of non-invasive methods for assessing liver fibrosis may represent a rational and reliable approach to implement non-invasive assessment of liver fibrosis in clinical practice and to reduce rather than abolish liver biopsies.

Liver fibrosis identification based on ultrasound images captured under varied imaging protocols

Diagnostic ultrasound is a useful and noninvasive method in clinical medicine. Although due to its qualitative, sub- jective and experience-based nature, ultrasound image interpretation can be influenced by image conditions such as scanning frequency and machine settings. In this paper, a novel method is proposed to extract the liver features using the joint features of fractal dimension and the entropies of texture edge co-occurrence matrix based on ultrasound images, which is not sensitive to changes in emission frequency and gain. Then, Fisher linear classifier and support vector machine are employed to test a group of 99 in-vivo liver fibrosis images from 18 patients, as well as other 273 liver images from 18 normal human volunteers.