拉米夫定治疗乙型肝炎后活动性肝硬化的临床应用

目的 应用拉米夫定抑制乙型肝炎病毒复制,从而缓解肝脏炎症.方法 拉米夫定100 mg/d,口服,1年后观察ALT、AST、TBIL、ALB、肝纤维化指标(HA、PCⅢ)、HBV DNA定量(PCR法)等指标,数据均以均值±标准差(-x±s)表示,所得均数比较用t检验处理;并对30例乙型肝炎后活动性肝硬化患者治疗前后用Child-Pugh评分,以观察疗效.结果 治疗结束后,HBeAg转阴6例(20.0%),HBV DNA转阴27例27%),ALT、AST、TBIL、ALB、肝纤维化指标(HA、PCⅢ)治疗前后相比,P＜0.01,有显著性差异,Child-Pugh评分得到提高,A级病例人数由治疗前的8例提高到19例.结论 拉米夫定治疗乙型肝炎后活动性肝硬化1年,患者生化指标明显改善,病毒载量明显下降,而且在治疗中未发现对肝脏功能的明显损害,可作为治疗乙型肝炎后活动性肝硬化的抗病毒药物.     

阿德福韦酯联合软肝汤治疗活动性肝硬化临床观察

95例活动性乙型肝炎肝硬化患者随机分为治疗组52例和对照组43例,两组均在保肝、对症等常规治疗基础上接受阿德福韦酯胶囊10mg／d治疗,治疗组在对照组基础上联合软肝汤治疗,1剂／d,3个月为一疗程。发现两组治疗后肝功能、肝纤维化指标明显改善,HBV DNA明显下降;治疗组肝功能、肝纤维化指标改善优于对照组。提示阿德福韦酯联合软肝汤治疗活动性肝硬化能显著提高肝纤维化的治疗效果,改善肝功能,临床应用安全。     

复方鳖甲软肝片联合拉米夫定治疗慢性乙型肝炎肝纤维化的疗效观察

目的：探讨复方鳖甲软肝片联合拉米夫定治疗慢性乙型肝炎肝纤维化的疗效。方法：选择90例慢性乙型肝炎肝纤维化的患者按治疗先后以1：1：1随机分为A、B、C组各30例,A组采用拉米夫定及复方鳖甲软肝片;B组采用拉米夫定及甘利欣胶囊;C组采用甘利欣胶囊及复合维生素或复方益肝灵片,疗程均为12月。主要观察3组患者HBV DNA阴转情况及肝纤维化指标改善情况。结果：A、B两组患者在抑制HBV DNA复制指标方面与C组比较,有非常显著的统计学差异（P〈0．001）,A组与B组比较也有统计学意义（P〈0．05）。A、B两组治疗后肝纤维化指标改善情况均明显优于C组（P〈0．01）。在治疗后A组的各项肝纤维化指标的改善也优于B组（P〈0．01）。结论：复方鳖甲软肝片与拉米夫定的联合,不仅能增强抑制HBV DNA的复制作用,更能显著提高抗肝纤维化的治疗效果。     

拉米夫定联合扶正化瘀胶囊治疗代偿期乙型肝炎肝硬化疗效分析

目的探讨拉米夫定联合扶正化瘀胶囊治疗代偿期乙型肝炎肝硬化的临床疗效及安全性。方法选取本院2011年3月至2013年9月门诊和住院诊断为代偿期乙型肝炎肝硬化的患者90例,随机分为2组,每组45例。联合治疗组给予拉米夫定加扶正化瘀胶囊治疗,对照组给予拉米夫定治疗,2组疗程均为1年。随诊记录2组丙氨酸氨基转移酶(ALT)、HBV DNA、总胆红素(TBil)及肝纤维化指标(HA、PⅢNP、LN、CⅣ)变化情况,将2组ALT复常率、HBV DNA低于检测下限的比率、HBe Ag血清学转换率以及耐药情况进行对比分析。结果随诊观察2组ALT、HBV DNA、TBil及肝纤维化指标(HA、PⅢNP、LN、CⅣ)水平较治疗前均明显下降,差异均有统计学意义(P0.05),其中联合治疗组的ALT复常率、HBV DNA转阴率及耐药率改善明显,与对照组对比差异均有统计学意义(P0.05),HBe Ag血清学转换率两组对比差异无统计学意义。结论拉米夫定联合扶正化瘀胶囊治疗乙型肝炎肝硬化可明显改善肝功能,延缓肝纤维化进程,减少耐药发生。     

拉米夫定联合苦参素抗肝纤维化的临床观察

乙型肝炎病毒（HBV）DNA在肝细胞内复制引起肝细胞病理损伤是肝纤维化形成的启动因素，拉米夫定通过抑制HBVDNA复制而间接阻断肝纤维化形成，苦参素（氧化苦参碱）有抗肝纤维化作用。我们对139例HBV复制的不同肝病患者采用联合治疗（拉米夫定联合苦参素）／单一拉米夫定治疗6个月后血清肝纤维化指标的含量变化，并初步探讨其抗肝纤维化的临床疗效。     

胸腺素α1治疗活动性肝炎肝硬化疗效研究

探讨胸腺素α1治疗活动性乙肝后肝硬化的临床疗效.21例乙肝后肝硬化在保肝对症治疗基础上均给予胸腺素α11.6毫克皮下注射,每日一次;14天后改为每周3次;自第5周起,每周2次,总疗程为26周.观察治疗前后临床症状、体征、肝功能、乙肝病毒指标、肝纤维化指标的变化;并观察不良反应.21例肝硬化患者临床症状有不同程度的改善,肝功能有72.2%的患者ALT恢复正常;40%的患者HBeAg阴转;35.3%的患者HBV DNA阴转;肝纤维化三项指标(HA、LN、Ⅳ-C)有不同程度下降,以HA下降明显,与治疗前比较P＜0.05.未见严重不良反应.胸腺素α1治疗活动性乙肝后肝硬化具有抑制乙肝病毒复制和抗肝纤维化作用,且安全有效.     

阿德福韦酯和拉米夫定治疗乙型肝炎肝硬化失代偿期的临床观察

目的观察阿德福韦酯和拉米夫定治疗肝炎肝硬化失代偿期患者48周的疗效和不良反应。方法采用随机分组法,将62例肝炎肝硬化失代偿期患者,随机分为阿德福韦酯组32例,给予阿德福韦酯10mg/d,拉米夫定组30例,给予拉米夫定100mg/d,疗程均为48周。均给予常规护肝及支持、对症治疗。观察两组患者的肝功能、HBeAg、HBV DNA、肝纤维化标志物Ⅲ型前胶原、Ⅳ型胶原、层黏连蛋白、透明质酸、肾功能及Child-Pugh分级、药物不良反应。结果两组患者肝功能各项指标的复常率、血清HBV DNA下降水平及转阴率、HBeAg转阴率及HBeAg/抗-HBe转换率均随着治疗疗程的延长而增加,但两组比较,差异无统计学意义。治疗至48周时拉米夫定组有2例发生YMDD变异,变异率6.7%,阿德福韦酯组无病毒变异发生。两组患者血清肝纤维化标志物治疗至24周时与治疗前相比明显下降,且随着疗程的延长进一步降低,两组比较差异无统计学意义。两组患者治疗前后Child-Pugh分级比较,差异无统计学意义。两组患者均未发现药物相关的肾功能损害,两组中各有2例患者出现轻度不良反应,但均能耐受。结论肝炎肝硬化失代偿期患者48周的抗病毒治疗,阿德福韦酯的疗效与安全性均与拉米夫定相似,而病毒耐药突变率较拉米夫定低。     

拉米夫定联合安络化纤丸治疗乙型肝炎肝硬化30例临床观察

目的 探讨乙型肝炎肝硬化患者通过拉米夫定和安络化纤丸联合治疗的效果.方法 随机选择45例乙型肝炎肝硬化患者,分别给予拉米夫定联合安络化纤丸和拉米夫定治疗1年6个月.结果 治疗结束时,联合组的血清谷丙酶和透明质酸水平下降比单用拉米夫定组优;治疗组30例中17例(56.7%)HBV DNA阴转,17例HBeAg阴转,7例出现抗-HBc(+);对照组15例中8例HBV DNA阴转(53.3%),8例HBeAg阴转,2例出现抗-HBc(+).结论 拉米夫定联合安络化纤丸治疗慢性乙型肝炎肝硬化疗效确切,安络化纤丸有较好抗肝纤维化及改善肝功能,缓解临床症状作用.但抗乙型肝炎毒复制作用不突出.     

拉米夫定治疗失代偿期乙型肝炎肝硬化的临床观察

目的　研究拉米夫定对失代偿期乙型肝炎肝硬化的临床疗效和安全性。方法　 2 8例乙型肝炎肝硬化患者给予拉米夫定 10 0mg/d口服 ,连用 2 4个月 ,设立对照组。在治疗开始前、治疗开始后 6个月、12个月和 2 4个月分别记录Child Pugh得分 ,并进行肝功能、肝纤维化标志物、HBV血清标志物以及血清HBVDNA定量检测。结果　 2 8例肝硬化患者拉米夫定治疗后 ,血浆白蛋白显著升高 ,血清丙氨酸转氨酶和胆红素明显降低 ,血清Ⅲ型前胶原、Ⅳ型胶厚、层粘连蛋白和透明质酸水平较治疗前显著降低 ,血清HBVDNA阴转率明显高于对照组 (P <0 .0 0 5 ) ,HBVDNA水平较治疗前显著降低。治疗组Child Pugh计分平均降低 2 .5 ,5 4.2 %患者提高了分级 (12例从B到A ,1例从C到B) ,而对照组仅有10 .5 %的患者Child Pugh分级得到了改善 ,治疗组显著高于对照组 (P <0 .0 1)。不良反应的发生率为 3 2 .1% (9/2 8)。结论　拉米夫定能使HBV复制指标阳性的活动性肝硬化患者的病毒复制受到抑制 ,肝功能改善 ,肝纤维化程度降低 ,病情缓解。应用拉米夫定治疗肝硬化患者安全可靠。     

六味五灵片联合阿德福韦酯治疗慢性乙型肝炎肝硬化疗效分析

目的：观察六味五灵片联合阿德福韦酯治疗慢性乙型肝炎（CHB）肝硬化的临床效果.方法：将55例CHB肝硬化患者随机分成两组,治疗组28例,口服六味五灵片和阿德福韦酯;对照组27例,单纯口服阿德福韦酯;均治疗48W,观察治疗前后两组患者临床症状、肝功能、HBV DNA、肝纤维化指标的变化.结果：治疗组患者治疗48W ALT的复常率为95％,HBV DNA转阴率为78.9％,肝纤维化指标明显降低,主要临床症状明显改善,优于对照组,治疗组总有效率为88.5％,对照组总有效率为61.3％.结论：六味五灵片联合阿德福韦酯治疗CHB肝硬化能够降低患者血清肝纤维化指标,提高临床疗效.     

慢性乙型肝炎肝纤维化分期与血清肝纤维化标志物的相关性分析

目的 探讨血清透明质酸、Ⅲ型前胶原、层粘蛋白、Ⅳ型胶原等血清肝纤维化标志物与慢性肝炎肝组织炎症活动度及纤维化程度的相关性。方法 278例慢性肝炎患者经肝脏活栓后常规病理检查,肝活检前同时采血检测血清透明质酸、Ⅲ型前胶原、层粘蛋白、Ⅳ型胶原,结果应用x^2检验及t检验进行统计学处理。结果 肝组织纤维化程度与炎症活动度呈正相关关系,透明质酸可反映中度以上慢性肝炎炎症活动度及纤维化程度,且呈正相关;肝脏存在纤维化时层粘蛋白水平升高,与纤维化程度正相关;Ⅲ型前胶原、Ⅳ型胶原水平升高与炎症活动度有关。结论 血清透明质酸、Ⅲ型前胶原、层粘蛋白、Ⅳ型胶原可不同程度反映肝纤维纤维化程度,可作为血清肝纤维化检测指标,透明质酸更可反映肝硬化发展趋势。     

拉米夫定联合卡托普利治疗166例慢性乙型肝炎患者的抗肝纤维化疗效分析

目的研究联合使用拉米夫定和卡托普利治疗慢性乙型肝炎的抗肝纤维化疗效,探索作用显著的治疗方案。方法对经单纯降酶治疗、单用拉米夫定、单用卡托普利、联合拉米夫定和卡托普利治疗至少1年的慢性乙型肝炎患者共166例的临床资料进行回顾性分析,比较不同治疗方案患者治疗前后肝纤维化血清标志物下降及肝组织纤维化分期变化情况以评价不同治疗方案的抗肝纤维化疗效。结果联合用药组、拉米夫定组、卡托普利组治疗后血清肝纤维化标志物（肝纤4项）水平与治疗前相比分别有4、2、3项降低,治疗后肝组织均显示S0～S1期比例明显增加,S2-S3期、S4期比例显著下降,以联合用药组变化最为显著,而降酶组治疗前后肝纤4项水平及肝组织纤维化分期变化不明显,差异无统计学意义。结论慢性乙型肝炎使用拉米夫定、卡托普利治疗均具有抗肝纤维化作用,两者联合使用抗肝纤维化效果更加明显。短期临时性降酶治疗无明显抗肝纤维化作用。     

加味小柴胡汤对乙型肝炎病毒转基因小鼠血清和肝组织中HBV-DNA及乙肝抗原影响的研究

[目的]观察加味小柴胡汤对乙型肝炎病毒（HBV）转基因小鼠血清和肝组织中HBV-DNA及乙肝抗原含量的影响。[方法]36只经筛选HBV-DNA阳性的转基因小鼠随机分为3组,每组12只,中药组给予加味小柴胡汤水煎剂,西药组给予拉米夫定,空白对照组给予0.85%氯化钠治疗。观察治疗后各组动物血清和肝组织中HBV-DNA含量的变化。[结果]血清HBV-DNA水平变化,与治疗前和空白组比较,中药组与西药组均有显著性改善,且两者均以西药组的改善效果显著（P〈0.05,〈0.01）。肝组织中HBV-DNA含量变化,与空白组进行比较,中药组对HBV-DNA含量无明显改善作用,而对HBeAg和HBsAg改善显著（P〈0.05,〈0.01）;西药组则只对HBV-DNA有显著影响（P〈0.01）,对HBsAg和HBeAg的改善不显著。[结论]加味小柴胡汤能降低血清HBV-DNA水平,虽作用不及西药,但其降低HBsAg、HbeAg却明显优于西药。     

Taurine inhibits deposition of extracellular matrix in experimental liver fibrosis in rats]

OBJECTIVE: To study the effect of taurine on liver fibrosis and its mechanism. METHODS: Fibrosis was induced by the administration of carbon tertrachloride(CCl4) in rats. Some of the animals were treated with taurine. The rats were killed after 12 weeks of CCl4 treatment. Depositions of type I, III and IV collages, laminin and hyaluronic acid were studied in liver sections by immunohistochemical technique using specific antibody. The hepatic contents of type I, III procollage and tissue inhibitor of metalloproteinase-1(TIMP-1) mRNA were determined by Northern blot hybridization. RESULTS: A significant elevations of hepatic collagen I, III, IV, laminin and hyaluronic acid were observed after 12 weeks of liver injury in animals without taurine treatment, and a definite increase in the amounts of hepatic type I, III procollagen and TIMP-1 mRNA was noted. Taurine prevented increases in type I, III procollagen mRNA expression as well as the accumulation of the collagens, laminin and hyaluronic acid in the liver. CONCLUSION: The data indicate that taurine has a protective effect in CCl4-induced hepatic fibrosis. The results suggest taurine might be of potential value in clinical practice.     

肝爽颗粒联合阿德福韦酯治疗肝纤维化的疗效分析

目的观察肝爽颗粒抗肝纤维化的疗效。方法选取本院2010年7月-2013年1月收治的68例慢性乙型肝炎肝硬化患者,分为试验组和对照组,每组34例。2组患者均治疗12个月,在单独使用阿德福韦酯治疗6个月后,试验组同时使用肝爽颗粒6个月,而对照组不用肝爽颗料。观察比较2组患者治疗前后肝纤维化血清指标:透明质酸(HA),层粘连蛋白(LN),Ⅳ型胶原(CⅣ),Ⅲ前胶原(PCⅢ)水平及肝脏硬度指标的变化。治疗前后比较采用配对t检验。结果试验组治疗前后血清HA、LN、CⅣ和PCⅢ值分别下降37.5%、34.2%、35.4%和39.9%,肝硬度值下降40.6%,治疗前后差异有统计学意义(t=2.238、2.151、2.148、2.189、2.189,P均0.05),而对照组治疗前后上述指标差异无统计学意义。结论肝爽颗粒可改善乙型肝炎肝硬化患者血清肝纤维化标志物水平及降低肝硬度值,表明其有抗肝纤维化疗效。     

Different doses of recombinant alpha interferon in the treatment of chronic hepatitis B patients without antibodies against the human immunodeficiency virus

A total of 24 chronic carriers of HBsAg, HBeAg and hepatitis B virus (HBV)-DNA were included in a controlled trial. The patients were randomly assigned to four groups: Group I (n = 6): control; group II (n = 6): 2.5 MU; group III (n = 6): 5 MU and group IV (n = 6): 10 MU rIFN-alpha/m2 body surface 3 times weekly i.m. during 6 months. At the end of the treatment, all patients under therapy, as well as 4 belonging to the control group, lost HBV-DNA polymerase. HBV-DNA became negative in 3 (50%), 1 (17%), and 2 (33%) patients from groups II, III, and IV, respectively, while all patients from the control group maintained HBV-DNA. At 15 months of follow-up, 6 patients (33%) under therapy (2 from each group) and 1 from the control group remained HBV-DNA-negative. Knodell's index decreased significantly on comparing basal and final liver biopsies among patients in group IV (16.0 +/- 1.9 vs 7.0 +/- 1.9, p less than 0.01), while no changes were observed in the other groups. Five patients (27%) developed anti-IFN antibodies during treatment. In summary, although low doses of rIFN-alpha (2.5-5 MU) had an antiviral effect on HBV replication, only patients treated with 10 MU showed a significant decrease in liver histological activities. In addition, the effectiveness of rIFN-alpha therapy may be negatively influenced by the appearance of anti-IFN antibodies.     

人脐带间充质干细胞肝内移植联合苦参素治疗失代偿期乙型肝炎肝硬化患者疗效与转归分析

目的 探讨人脐带间充质干细胞（UC-MSCs）联合苦参素治疗失代偿期乙型肝炎肝硬化患者的疗效。方法 采用随机数字表法将68例失代偿期乙型肝炎肝硬化患者分为对照组34例和观察组34例,分别给予经肝动脉行UC-MSCs移植或在UC-MSCs移植后给予苦参素口服治疗,观察12个月。结果 在治疗期间,观察组3例死亡,对照组4例死亡;在治疗12月末,观察组血清ALT为（39.3±15.6） U/L、TBIL为（26.3±10.2） μmol/L,均显著低于对照组【（71.2±17.2） U/L和（39.2±11.2） μmol/L,P<0.05】;血清层粘连蛋白为（81.2±24.1） ng/ml,透明质酸为（135.7±48.5） ng/ml,Ⅳ型胶原为（106.3±32.1） ng/ml,Ⅲ型前胶原为（98.7±25.6） ng/ml,均显著低于对照组【（113.3±29.6） ng/ml、（174.8±51.2） ng/ml、（158.4±35.6） ng/ml、（124.2±30.3） ng/ml,P<0.05】;外周血CD4+细胞百分比为（34.0±4.6）%,CD4+/CD8+比值为（1.2±0.6）,均显著高于对照组【（29.3±4.1）%和（0.9±0.6）,P<0.05】,CD8+为（26.5±4.9）%,显著低于对照组【（31.2±3.9）%,P<0.05】;肝移植和肝癌发生率分别为2.9%和5.9%,与对照组的5.9%和11.8%比较无显著性差异（P>0.05）。结论 HU-MSCs肝内移植联合苦参素胶囊口服治疗失代偿期肝硬化患者可明显减轻肝纤维化,改善肝功能。     

Serum procollagen peptides and collagen type VI for the assessment of activity and degree of hepatic fibrosis in schistosomiasis and alcoholic liver disease.

Schistosomiasis, in contrast to alcoholic liver disease, leads to presinusoidal hepatic fibrosis, which determines the prognosis of the disease. Because conventional liver function tests and liver biopsy specimens provide little information about the dynamics of the fibrotic process, we measured the serum concentrations of procollagen type III N-propeptide and procollagen type I C-propeptide, believed to mainly reflect collagen synthesis, and procollagen type IV C-propeptide and collagen type VI, two presumptive markers of collagen degradation. Determinations were performed in 15 healthy control subjects, 69 patients with various stages of infection with Schistosoma mansoni/Schistosoma haematobium (28 with an early active infection and no organ involvement, 27 with hepatosplenic involvement and 14 with complications of portal hypertension) and 16 patients with alcoholic cirrhosis. In addition, liver biopsy specimens were obtained from 30 schistosomal patients (18 with hepatosplenic involvement and 12 with complications of portal hypertension for histopathological grading and collagen histochemistry. Procollagen type III N-propeptide was significantly elevated in the three patient groups with schistosomiasis when compared with controls (p less than 0.01). Also, patients with higher histological grading showed significantly higher procollagen type III N-propeptide values (p less than 0.05). In alcoholic patients, procollagen type III N-propeptide was even higher and increased parallel to the severity of the disease, determined by using a combined clinical and laboratory index. Procollagen type I C-propeptide was only elevated in early infection (p less than 0.05) and steadily decreased with disease progression.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum aminoterminal type III procollagen peptide and the 7S domain of type IV collagen in patients with alcohol abuse Relation to ultrastructural fibrosis in the acinar zone 3 and to serum hyaluronan

ABSTRACT— Serum concentrations of the aminoterminal propeptide of type III procollagen and of the 7S domain of type IV collagen, presumed to reflect fibrotic activity in liver tissue, and of the glycosamonoglycan hyaluronan, were obtained from 40 alcohol abusers, at the time of liver biopsy. The serological results were related to morphological findings in liver tissue, i.e. no fibrosis, fibrosis without cirrhosis, micronodular cirrhosis and macronodular cirrhosis, and to ultrastructural indications of perisinusoidal fibrosis in the acinar zone 3. All patients with fibrosis and cirrhosis on light microscopy had elevated serum levels of the type III procollagen peptide as well as of the 7S domain of type IV collagen. However, due to a considerable overlap between the groups, no relations could be demonstrated to the severity of the fibrosis, supporting the assumption that these serological markers reflect the current fibrotic activity and not the amount of fibrotic tissue previously deposited. Among patients without fibrosis on light microscopy, a relation between the propeptide levels and ultrastructural perisinusoidal zone 3 fibrosis was observed, suggesting that type III procollagen peptide may be valuable in detecting very early liver fibrosis. A positive correlation was demonstrated between the serum concentrations of type III procollagen peptide and hyaluronan. As hyaluronan is degraded in the liver endothelial cells, it is suggested that the liver is involved, not only in the synthesis, but also in the degradation of the propeptide.