丙型和乙型肝炎合并感染患者的抗病毒治疗分析

目的：探讨HBV／HCV合并感染患者的临床特征以及对聚乙二醇干扰素α-2a（ PEGIFNα-2a）联合利巴韦林的抗病毒疗效。方法选取收治的HBV／HCV合并感染患者45例（ A组）,单纯HBV感染患者49例（ B组）,单纯HCV感染患者38例（ C组）,比较病毒感染和抗病毒疗效。结果 A组与B组HBeAg阳性率、HBV DNA阳性率、HBV DNA平均值以及HBV DNA量的患者分布差异有统计学意义（ P ＜0貂．05）;A组与C组HCV RNA平均值差异无统计学意义（ P ＞0．05）,HCV RNA量的患者分布差异有统计学意义（ P ＜0．05）;A组与C组基因型分布、HCV RNA和ALT差异无统计学意义（ P ＞0．05）,PLT、WBC、PTA和Alb差异具有统计学意义（ P ＜0．05）;Ⅰ基因型中,A组与C组pEVR、ETVR以及复发率差异有统计学意义（ P ＜0．05）,RVR、cEVR以及SVR差异无统计学意义（ P ＞0．05）;非Ⅰ基因型中,RVR、cEVR、pEVR、ETVR、SVR以及复发率差异均无统计学意义（ P ＞0．05）;A组与C组不良反应例数以及WBC和PLT减少例数差异有统计学意义（ P ＜0．05）,溶血以及甲状腺功能减退差异无统计学意义（ P ＞0．05）;未获得SVR患者和获得SVR患者阳转率差异具有统计学意义（ P ＜0．05）。结论丙型和乙型肝炎合并感染患者以HCV为优势病毒株为主,HBV复制受抑制。合并感染Ⅰ基因型患者复发率、部分早期病毒学应答和治疗结束时病毒学应答高于单纯HCV感染患者,持续病毒学应答相似,但合并感染对非基因Ⅰ型病毒学应答率无影响。     

Treatment of early stage chronic hepatitis C virus infection

Introduction: Treatment of Hepatitis C Virus (HCV) with direct acting antivirals (DAAs) is able to achieve the cure of infection in almost the totality of patients, independently of the characteristics of the individual and the virus, using short treatment schedules, and without the need of ribavirin. The high cost of DAAs is the main limiting factor for universal treatment of HCV. However, there is a strong evidence that treatment of infection at the early stage of disease may be the most rewarding approach.

Areas covered: This review evaluates the aspects underlying the benefit of treating chronic HCV infection at the early stage of disease. It outlines the considerations that have to be taken into account when planning treatment in patients with HCV and minimal liver disease, assessing the positive reflex of viral eradication on several HCV-associated extra-hepatic conditions such as the risk of lymphoma, insulin-resistance and glycaemic control, and renal function. Lastly, it also covers the improvement of patients’ quality of life and the pharmaco-economic aspects associated with early treatment.

Expert commentary: Treatment of patients with HCV and minimal liver disease is associated with a beneficial, pleiotropic effect of viral eradication that goes beyond the simplistic consideration of the improvement in liver disease-related outcomes.     

慢性丙型肝炎抗病毒治疗进展

近年慢性丙型肝炎抗病毒治疗的标准治疗方案优化和直接抗病毒药物研发均取得突破性进展。本文综述近年国内外相关研究进展以及新药研发趋势。     

丙型肝炎抗病毒药物治疗的现状与研究进展

干扰素(IFN)是丙型肝炎抗病毒治疗中一种非常重要的药物,单药治疗以及与利巴韦林联合用药都表现出较好的抗病毒疗效。IFN与利巴韦林联合用药已成为丙型肝炎的标准治疗方案,对丙型肝炎病毒(HCV)基因型和应答指标的研究有助于个体化给药。本文对聚乙二醇IFN、人血清清蛋白融合IFN以及特异性靶向HCV治疗药物的研究进展做一综述。     

前列腺素E1治疗慢性病毒性肝炎,肝硬化及重症肝炎的疗效

目的：进一步探讨前列腺Ｅ１（ＰＧＥ１）对病毒性肝炎的疗效。方法：对９５例慢性乙型肝炎、肝炎肝硬化及重症肝炎在综合护肝治疗的基础上加用ＰＧＥ１治疗,疗程１４～２１ｄ,另设对照组９０例。ＰＧＥ１治疗组中血清总胆红素（ＳＢ）的降低明显优于对照组（Ｐ〈０．０５）。在慢性肝炎病例组中,治疗组中ＡＬＴ的下降显著低于对照组（Ｐ〈０．０５）;而在重症肝炎组中,虽然两组的病死率无显著性差异,但治疗组中〖凝血〗因子Ⅱ     

Antiviral treatment of hepatitis C

Therapy of hepatitis C virus (HCV) infection may prevent progression to cirrhosis, hepatocellular carcinoma and end-stage liver disease. The cornerstone of treatment has long been standard IFN-α, the use of which was associated with a sustained biochemical and viral response in only a small proportion of patients. More recently, the success of interferon-based regimens has substantially improved due to the combination with the guanosine analogue ribavirin and to the advent of pegylated interferon formulations. However, even the most up-to-date regimens fail to cure the infection in many cases and are limited by side effects and high costs. A better understanding of the HCV genomic organisation, the elucidation of the three-dimensional structures of virally encoded enzymes and the recent development of a HCV-replicon system in human hepatoma (Huh-7) cells have led to significant advances in the development of new antiviral compounds, many of which are under evaluation in clinical trials. The aim of this review is to trace a brief overview of the progress made by interferon-based treatments for hepatitis C since their introduction in the early 1990s, and to highlight the results of recent clinical studies concerning new and emerging drugs.     

灯盏细辛与乙型病毒性肝炎患者肝纤维化指标关系的研究

目的研究灯盏细辛对乙型病毒性肝炎患者血清肝纤维化指标(透明质酸、层粘蛋白、人Ⅲ型前胶原、Ⅳ型胶原)的影响。方法116例乙型病毒性肝炎患者随机分为两组:治疗组70例和对照组46例。治疗组采用灯盏细辛治疗;对照组采用一般支持治疗。结果治疗组治疗后肝功能明显改善(P<0.05),对照组治疗前后血清白蛋白及γGT无明显改变(P>0.05);治疗组治疗后肝纤四项明显下降(P<0.01),对照组治疗前后改变不明显(P>0.05),肝纤四项两组治疗后相比,有显著性差异(P<0.05)。结论灯盏细辛可明显改善肝脏功能,降低肝脏纤维化,对乙型病毒性肝炎治疗有效且安全。     

肝炎灵对慢性乙型肝炎患者血清病毒标志的影响

为观察肝炎灵对慢性肝炎病人血清乙型肝炎病毒标志的影响。治疗组(34例)用肝炎灵,对照组(35例)用聚肌胞。该药对HBsAg阴转率为9％,抗-HBc为3％,疗效不显(P均>0.05);对HBeAg的阴转率为74％,疗效明显(P<0.005),经6mo-1yr随访,远期疗效为65％;对抗-HBe的阳转率为32％。说明肝炎灵对抑制乙肝病毒复制,使HBeAg转阴较聚肌胞为优,远期疗效较持久。该药价格低廉、毒副作用小,值得扩大临床使用和研究。     

Cyclophilin inhibitors in hepatitis C viral infection

Cyclophilins (Cyps) are proteins that are ubiquitously present with peptidyl-prolyl cis-trans isomerase activity and play an important role in de novo protein folding and in isomerization of native proteins in several cellular systems. There is growing evidence that indicates CypB is a positive modulator of the HCV RNA-dependent RNA polymerase in the replication complex. Early in vitro and animal data with selective Cyp inhibitors show a potent anti-HCV effect. This anti-HCV effect was confirmed in the first patient study with the selective Cyp inhibitor Debio-025. Preclinical data suggest that Cyp inhibitors may present a higher barrier to the selection of resistance than protease and polymerase inhibitors and that a combination of Cyp inhibitors with either of these drugs or interferon results in additive or synergistic anti-HCV activity. By interfering at the level of host–viral interaction, Cyp inhibition may open the way for a novel approach to anti-HCV treatment that could be complementary, not only to interferon-based treatment, but also to future treatments that directly target HCV replication enzymes such as protease and polymerase inhibitors.     

Treatment of viral hepatitis in pregnancy

Viral hepatitis can be caused by the hepatitis A, B, C, D and E viruses. In the Western world, hepatitis A, B or C do not seem to influence the course of pregnancy, whereas hepatitis E infection, when contracted during the second or third trimester, seems to have a higher risk of developing into a fulminant hepatitis. Mother-to-infant transmission of hepatitis A seems to be very uncommon. The majority of HBsAg-positive and HBeAg-positive mothers can transmit the disease vertically. The timing of transmission is predominantly peripartum, and newborns of HBsAg-positive mothers should receive hepatitis B immunoglobulins within 12 h of birth, with HBV vaccine at birth and 1 and 6 months later. Hepatitis C is more often a chronic disease. Vertical transmission of hepatitis C is considered to be relatively rare but high viraemia or coinfection with HIV can increase this risk. There is currently no treatment to prevent this vertical transmission and pregnancies among HCV-positive mothers should not be discouraged. Infants should be tested for anti-HCV at 1 year and followed for the development of hepatitis. Breast feeding does not seem to play an important role in the transmission of hepatitis B and C.     

复方卡尼汀治疗慢性病毒性肝炎

目的 :评估复方卡尼汀治疗慢性病毒性肝炎的作用。方法 :91例慢性病毒性肝炎病人分为 2组。对照组 30例 (男性 2 0例 ,女性 10例 ,年龄 4 1a±s 17a) ,给予甘草酸单铵 80mL加入 10 %葡萄糖注射液 50 0mL中iv ,gtt ,qd ,疗程 30d。治疗组61例 (男性 4 9例 ,女性 12例 ,年龄 4 0a± 13a) ,在甘草酸单铵治疗基础上 ,给予复方卡尼汀 2支加入10 %葡萄糖注射液 50 0mL中iv ,gtt ,qd ,疗程 30d。结果 :治疗组对改善病人乏力、纳差、降低ALT的总有效率分别为 93% ,10 0 % ,92 % ,均明显优于对照组 75% ,84 % ,70 % (P <0 .0 5)。对 2组部分病人治疗 6mo时的随访表明治疗组的ALT复常率为83% ,明显高于对照组 54% (P <0 .0 5) ,无明显不良反应。结论 :复方卡尼汀是一种有效的治疗慢性病毒性肝炎的药物     

Novel protease and polymerase inhibitors for the treatment of hepatitis C virus infection

Chronic hepatitis C virus (HCV) infection remains a global health concern with nearly 200 million carriers worldwide. Present treatment consists of the use of pegylated interferon plus the purine analogue ribavirin. Serious side effects and the fact that an overall 40 – 50% of patients do not accomplish sustained virological response with the present treatment warrant the need for novel anti-HCV therapies. The HCV serine protease and the RNA-dependent RNA polymerase have shown to be excellent targets for selective antiviral therapy. Early clinical studies have resulted in encouraging results. However, and not unexpectedly, preclinical evidence suggests that the virus may become rapidly resistant to such inhibitors. Therefore, combination therapy of drugs with different mode of action and resistance profiles may be required. This review focuses on the present status of these two families of HCV inhibitors that are in development.     

慢性乙型肝炎、肝硬化的多普勒超声和血清肝纤维化标志物检测的临床研究

目的本研究应用多普勒超声检测慢性乙型肝炎和肝硬化患者并检测其血清透明质酸(HA),层粘蛋白(LN)及Ⅳ型胶原(CⅣ),探讨肝脏血流动力学改变与肝纤维化的关系。方法通过对239例不同程度慢性乙型肝炎、肝硬化患者的彩色多普勒超声检测,选取与肝纤维化相关的血流动力学指标,即门静脉内径(Dpv)、门静脉血流速度(Vpv)、脾静脉内径(D sv)、脾静脉血流速度(Vsv)及肝静脉频谱变化,结合同期血清肝纤维化标志物HA、LN及CⅣ检测结果,利用SPSS 10.0统计软件进行统计学处理。结果Dpv、Vpv、D sv、肝静脉频谱变化及HA、LN、CⅣ与肝纤维化发展的阶段性一致,均与CHB时的肝损伤程度呈正相关。Dpv、Vpv、肝静脉频谱变化及HA在CHB的各阶段差异均有显著性;D sv在CHB的中、重度阶段及肝硬化阶段差异才有显著性;Qsv、LN及CⅣ只在CHB单个阶段差异有显著性,而且重叠较大。结论肝脏血流动力学改变和肝纤维化血清标志物能较好地反映慢性乙型肝炎和肝硬化的肝纤维化活动情况。     

硫普罗宁治疗慢性病毒性肝炎的临床疗效对照研究

目的:评价硫普罗宁治疗慢性病毒性肝炎的临床疗效。方法:将108例慢性病毒性肝炎患者随机分为A,B,C 3组,每组36例。分别接受4周的硫普罗宁针、还原型谷胱甘肽针、基础护肝(葡醛酸钠、肌苷)针治疗,检测患者治疗前后肝功能,临床症状和体征的改善情况。结果:A组改善肝功能及临床症状的总有效率(86.1%)明显优于B组(75.0%,P<0.01)和C组三组(61.1%,P<0.01)。A与B组肝功能ALT和ALB的改善差异无显著性(P>0.05),但对降低AST及TB IL方面A组优于B组(P<0.05)。结论:硫普罗宁能有效地改善肝功能及临床症状。     

干扰素联合利巴韦林治疗慢性丙型肝炎的疗效观察

目的 探讨干扰素联合利巴韦林治疗慢性丙型肝炎(chronic hepatitis C,CHC)的临床疗效及对肝功能和肝纤维化指标的影响.方法 将滨州市人民医院2011年3月～2012年3月收治的88例CHC患者按照随机数字表法分为2组,每组44例.对照组单用干扰素治疗,观察组采用干扰素联合利巴韦林治疗,比较治疗后2组临床疗效和治疗前后2组肝功能和肝纤维化指标变化情况.结果 观察组治疗总有效率为90.91％,明显高于对照组的68.18％,2组比较差异具有统计学意义(P＜0.05);观察组治疗后ALT和AST分别为(70.24±7.94) U/L和(79.45±9.72) U/L,HA、PCⅢ、CⅣ和LN分别为(76.87±10.32) μg/L、(79.45±9.72) μg/L、(79.76±8.00) μg/L和(118.41±16.97) μg/L,均明显高于治疗前和对照组,差异具有统计学意义(P＜0.05).结论 干扰素联合利巴韦林治疗慢性丙型肝炎疗效显著,可明显改善患者肝功能,具有较好的抗纤维化作用.     

The effect of direct acting antiviral agents on vascular endothelial function in Egyptian patients with chronic hepatitis C virus infection

Chronic hepatitis C virus (HCV) infection is correlated with cerebrovascular and cardiovascular disease (CVD). This study aimed to assess the effect of treatment with DAAs on vascular endothelial function in cirrhotic and non-cirrhotic HCV infected patients without any CVD risk factors. Fifty chronic HCV genotype 4 infected patients, without cardiovascular risks who have been listed to receive sofosbuvir/daclatasvir with ribavirin combination as triple therapy for 3 months were prospectively recruited. Endothelial dysfunction markers as soluble vascular cell adhesion molecule-1 (sVCAM-1) and Von willebrand factor (vWf) and inflammation marker (IL6) were estimated at baseline and 3 months post the end of therapy (SVR). All patients achieved SVR. VCAM1 level was significantly improved after HCV clearance with DAA in cirrhotic HCV patients (P = 0.002) compared to patients with mild liver fibrosis (P = 0.006). Levels of vWF also decreased significantly in cirrhosis and non-cirrhosis groups after SVR (P < 0.001 and P = 0.011, respectively). Systemic inflammatory marker (IL6) showed significant decrease in cirrhotic patients (P = 0.001). While, IL6 level did not change significantly in non-cirrhotic group (P = 0.061). Also at SVR, noninvasive liver fibrosis indices have been reduced significantly in the two groups (P < 0.001). HCV clearance by new DAA treatment improves the vascular endothelial dysfunction in Egyptian HCV infected patients with different levels of liver fibrosis and with no risk factors for endothelial dysfunction or CVD.     

慢性乙型肝炎血清胆碱酯酶与炎症分级及纤维化的临床关系研究

目的探讨慢性乙型肝炎(慢乙肝)患者血清胆碱酯酶与肝脏炎症分级及纤维化分期的关系。方法76例经肝活检证实的慢乙肝患者空腹时检测血清CHE、PT、TB等指标,结合肝活检组织炎症分级及纤维化分期,与健康组进行对照研究,分析PT、TB与CHE的相关性。结果肝脏病理组织炎症按程度分为G1～G4级,纤维化程度分为S1～S4期。本组资料显示,患者随着病变炎症程度的加重,CHE值递减,G4、G3、G2组分别与健康组比较,呈现显著性差异(P<0.001),G4、G3与G1组比较亦有显著性差异(P<0.001),但G2与G1组比较差异无显著性(P>0.05),G1组与健康组比较亦无显著性差异。随着纤维化程度的加重,CHE也逐渐下降,纤维化重组(S4+S3)与纤维化轻组(S1+S2)之间比较有显著性差异(P<0.001)。纤维化重组、轻组与对照组比较有显著性差异(P<0.001),PT、TB与CHE有良好相关性,随着PT延长及黄疸程度加深,CHE也逐渐下降。结论CHE与肝脏炎症分级及纤维化分期均有较好的相关性。CHE比TB、PT受病理生理及实验条件等因素的影响较小,能更准确地判断肝脏损害的严重程度,可作为判断慢性乙肝患者病情及预后...     

NS5A inhibitor,daclatasvir, for the treatment of chronic hepatitis C virus infection

Gonadal and adrenal steroidal hormones and their related neuropeptides affect seizures. Seizures, in their turn, may affect the functioning of these endocrine systems. Both these sets of effects may be clinically important and open to therapeutic manipulation. Recent advances in understanding the effects of these hormones and their metabolites on neuronal excitability have opened the way for a number of new, hormonally-based therapeutic approaches to seizure management. Some of these have reached various stages of clinical trials, while others are still in the preclinical stages of testing. Similarly, treatment of some of the hormonal consequences of seizures has recently been explored and will be discussed.