Short─Term Therapeutic Efficacy of Recombinant Alpha─2b Interferon on Patients with Posttransfusion Hepatitis C

Thebiochemicalandvirologicalefficaciesofrecombinantalpha-2bin-terferon(rINFα-2b)wereobservedon30patientswithpostransfusionhepatitisC.Theresultsshowedthatupto3monthsaftertheendoftherapytheALTnormalizationratewas72%andHCV-RNAdisappearanceratewas53.3%.Theresponsepredictoranal-ysisrevealedthatpatients′sex,ageandthedurationbetweenclinicalonsetandbegin-ningofIFNtherapywerenotmeaningfulfactors,whiletheinitialtiterofHCV-RNAandthedurationbetwenblodtransfusionandclinicalonsetbothafectedtheefficacysignificantly.HCVgenotypingshowedthat30patientswerealinfectedwithHCVgenotypeⅡ,indicatingthattheresponsetoIFNcouldbeinconsistentevenamongpa-tientswhoinfectedwithsamegenotypeofHCV.ItwasalsofoundthatthediscrepancybetwenbiochemicalandvirologicalresponsestoINFexistedandthatanti-HCVdetect-edbythesecondgenerationkitwasoflitlevalueinevaluatingtheeficacyofINFtherapy.

丙型病毒性肝炎发病机制中自身免疫反应的作用

目的探讨丙型肝炎病毒（ＨＣＶ）感染的发病机制．方法应用酶联免疫吸附法、间接免疫荧光法、放射免疫法测定了慢性ＨＣＶ感染者６６例，慢性ＨＢＶ感染者３７例和正常对照３９例的血清抗ＧＯＲ抗体（抗ＧＯＲ）、抗核抗体（ＡＮＡ）、抗甲状腺球蛋白抗体及抗甲状腺微粒体抗体（ＴＧＡ／ＴＭＡ）．结果ＨＣＶ感染者抗ＧＯＲ，ＡＮＡ，ＴＧＡ／ＴＭＡ的阳性率较正常对照组均明显增高（５３０％ｖｓ５１％，χ２＝２４６４９，Ｐ＜００１；４２４％ｖｓ２６％，χ２＝１９４９０，Ｐ＜００１；１３６％ｖｓ０％，χ２＝５８２０，Ｐ＜００１）；与慢性ＨＢＶ感染者比较，慢性ＨＣＶ感染者抗ＧＯＲ，ＡＮＡ阳性率显著增高（χ２＝２０５５０，Ｐ＜００１；χ２＝４５１３，Ｐ＜００５）．慢性ＨＣＶ感染中，血清谷丙转氨酶（ＡＬＴ）增高者抗ＧＯＲ阳性率及ＡＮＡ阳性率显著高于ＡＬＴ正常者（６５０％ｖｓ３４６％，χ２＝６１１０；５２５％ｖｓ２６９％，χ２＝５９１０，Ｐ＜００５），ＨＣＶＲＮＡ阳性者抗ＧＯＲ阳性率显著高于阴性者（χ２＝４８１０，Ｐ＜００５）．结论上述结果说明ＨＣＶ感染者存在自身免疫反应，这种自身免疫反应与病毒复制?

丙型肝炎肝组织Fas配体的免疫组化研究

以免疫组化法研究Fas配体（L）在丙型肝炎病人肝组织内的表达情况，发现在碎屑样坏死（PN）、桥样坏死（BN）及灶性坏死区浸润的单个核细胞有明显的FasL表达，阳性率为41．2％。FasL阳性细胞与肝脏炎症分级程度密切相关，G0－1；组与G3－4组比较有显著差异。FasL在肝细胞内亦有表达，表达程度似与炎症程度有关。不论是Fas或FasL在慢性丙肝中的表达均较急性肝炎显著，提示在病程慢性化中可能起着重要作用。

Systematic review: Preventive and therapeutic applications of metformin in liver disease

Metformin, a biguanide derivative, is the most commonly prescribed medication in the treatment of type 2 diabetes mellitus. More recently, the use of metformin has shown potential as a preventive and therapeutic agent for a broad spectrum of conditions, including liver disease and hepatic malignancies. In this systematic review,we critically analyze the literature behind the potential use of metformin across the spectrum of liver disease and malignancies. The Pub Med and Ovid MEDLINE databases were searched from 2000 to March 2015, using a combination of relevant text words and MeS H terms: metformin and mammalian target of rapamycin, hepatitis B virus(HBV), hepatitis B virus(HCV), nonalcoholic fatty liver disease(NAFLD), hepatocellular carcinoma(HCC) or cholangiocarcinoma. The search results were evaluated for pertinence to the issue of metformin in liver disease as well as for quality of study design. Metformin has a number of biochemical effects that would suggest a benefit in treating chronic liver diseases, particularly in the context of insulin resistance and inflammation. However, the literature thus far does not support any independent therapeutic role in NAFLD or HCV. Nonetheless, there is Level Ⅲ evidence for a chemopreventive role in patients with diabetes and chronic liver disease, with decreased incidence of HCC and cholangiocarcinoma. The use of metformin seems to be safe in patients with cirrhosis, and provides a survival benefit. Once hepatic malignancies are already established, metformin does not offer any therapeutic potential. In conclusion, there is insufficient evidence to recommend use of metformin in the adjunctive treatment of chronic liver diseases, including NAFLD and HCV. However, there is good evidence for a chemopreventive role against HCC among patients with diabetes and chronic liver disease, and metformin should be continued in patients even with cirrhosis to provide this benefit.

3.0T 1H magnetic resonance spectroscopy for assessment ofsteatosis in patients with chronic hepatitis C

AIM To investigate the utility of 1H magneticresonance spectroscopy （1H MRS） as a noninvasivetest for steatosis in patients infected with hepatitis Cvirus.METHODS： Ninety patients with chronic hepatitisC and pathology data underwent 3.0T 1H MRS, andthe results of MRS and pathological analysis werecompared.RESULTS： This group of patients included 26 peoplewith mild fatty liver （28.89%）, 16 people withmoderate fatty liver （17.78%）, 18 people with severefatty liver （20.0%）, and 30 people without fatty liver（33.33%）. The water peak was near 4.7 parts permillion （ppm）, and the lipid peak was near 1.3 ppm.Analysis of variance revealed that differences in thelipid peak, the area under the lipid peak, ratio of thelipid peak to the water peak, and ratio of the areaunder the lipid peak to the area under the waterpeak were statistically significant among the groups.Specifically, as the severity of fatty liver increased, thevalue of each index increased correspondingly. In thepairwise comparisons, the mean lipid peak, area underthe lipid peak, ratio of the lipid peak to the waterpeak, and ratio of the area under the lipid peak to thearea under the water peak were significantly differentbetween the no fatty liver and moderate fatty liver groups, whereas no differences were noted betweenthe severe fatty liver group and the mild or moderatefatty liver group. Area under the ROC curve （AUC） ofarea ratio in lipid and water and ratio in lipid and waterin the no fatty liver group to mild fatty liver group, mildfatty liver group to moderate fatty liver group, andmoderate fatty liver disease group to severe fatty livergroup, were 0.705, 0.900, and 0.975, respectively.CONCLUSION： 1H MRS is a noninvasive techniquethat can be used to provide information on the effectof liver steatosis on hepatic metabolic processes. Thisstudy indicates that the 1H MRS can be used as anindicator of steatosis in patients with chronic hepatitis C.

Chronic hepatitis C:This and the new era of treatment

Over the last years it has started a real revolution in the treatment of chronic hepatitis C. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in approximately 90% of cases. In the near future further progress will be achieved with the use of pan-genotypic drugs with high efficacy but without side effects.

抗病毒治疗对慢性丙型肝炎合并冷球蛋白血症患者肝功能的影响

目的:探讨抗病毒治疗对慢性丙型肝炎(CHC)合并冷球蛋白血症患者肝功能的影响。方法:选取CHC合并冷球蛋白血症患者61例,按是否自愿接受干扰素治疗,分为治疗组33例,对照组28例,治疗组在对照组保肝治疗基础上予以聚乙二醇干扰素α-2a(PEG-IFN-α-2a)联合利巴韦林抗病毒治疗,比较两组患者治疗前、治疗48周及停药后24周各指标的变化。结果:①治疗组患者治疗48周、停药后24周HCV RNA水平低于对照组,差异均有统计学意义(P<0.05)。②治疗组治疗结束、停药后24周ALT、TBil低于对照组、Alb、PTA含量高于对照组,两组比较差异均有统计学意义(P<0.05)。结论:抗病毒治疗可以降低HCV RNA水平并能明显改善CHC合并冷球蛋白血症患者的肝功能。

Hepatitis C cirrhosis: New perspectives for diagnosis and treatment

Chronic hepatitis C infection is the leading cause of chronic liver disease, cirrhosis, hepatocellular carcinoma as well as the primary indication for liver transplantation in the United States. Despite recent advances in drugs for the treatment of hepatitis C, predictive models estimate the incidence of cirrhosis due to hepatitis C infection will to continue to rise for the next two decades. There is currently an immense interest in the treatment of patients with fibrosis and early-stage cirrhosis as treatment can lead to decrease in the rates of decompensated cirrhosis, hepatocellular carcinoma and need for liver transplantation in these patients. The goal of this paper is to provide clinicians and health care professionals further information about the treatment of patients with hepatitis C infection and cirrhosis. Additionally, the paper focuses on the disease burden, epidemiology, diagnosis and the disease course from infection to treatment. We provide an overview of multiple studies for the treatment of chronic hepatitis C infection that have included patients with cirrhosis. We also discuss the advantages and disadvantages of treatment in cirrhotic patients and focus on the most up to date guidelines available for treatment.

Hepatitis C in human immunodeficiency virus co-infected individuals: Is this still a “special population”?

A substantial proportion of individuals with chronic hepatitis C virus(HCV) are co-infected with human immunodeficiency virus(HIV). Co-infected individuals are traditionally considered as one of the "special populations" amongst those with chronic HCV, mainly because of faster progression to end-stage liver disease and suboptimal responses to treatment with pegylated interferon alpha and ribavirin, the benefits of which are often outweighed by toxicity. The advent of the newer direct acting antivirals(DAAs) has given hope that the majority of co-infected individuals can clear HCV. However the "special population" designation may prove an obstacle for those with co-infection to gain access to the new agents, in terms of requirement for separate pre-licensing clinical trials and extensive drug-drug interaction studies. We review the global epidemiology, natural history and pathogenesis of chronic hepatitis C in HIV co-infection. The accelerated course of chronic hepatitis C in HIV co-infection is not adequately offset by successful combination antiretroviral therapy. We also review the treatment trials of chronic hepatitis C in HIV co-infected individuals with DAAs and compare them to trials in the HCV mono-infected. There is convincing evidence that HIV co-infection no longer diminishes the response to treatment against HCV in the new era of DAA-based therapy. The management of HCV co-infection should therefore become a priority in the care of HIV infected individuals, along with public health efforts to prevent new HCV infections, focusing particularly on specific patient groups at risk, such as men who have sex with men and injecting drug users.

慢性丙型病毒性肝炎中医证候要素及辨证分型Logistic回归分析

目的:探讨慢性丙型病毒性肝炎的证候要素及辨证分型的分布规律,为慢性丙肝的中医证候规范化研究提供依据。方法:对慢性丙肝患者证候要素进行中医证候学调查,应用SPSS 16.0软件进行频数统计及二值Logistic回归分析。结果:慢性丙型病毒性肝炎最常见证候有正虚邪恋型、脾肾阳虚型、湿热中阻型、肝郁脾虚型、肝肾阴虚型、瘀血阻络型等。证候要素有:气虚、阳虚、湿、热、气郁、阴虚、血瘀等。结论:通过总结该病的常见证候要素及辨证分型分布规律,为慢性丙型肝炎的中医证候研究提供依据。

丙型肝炎患者循环免疫复合物的检测及意义

采用Ｃ１ｑ—ＥｌＬＳＡ法对５１例丙型肝炎（丙肝）患者循环免疫复合物进行了检测，在３４例病人中检出循环免疫复合物（ＣＩＣ）；同时，我们还对丙肝患者免疫球蛋白和补体Ｃ３进行了检测，结果显示丙肝患者ＩｇＧ、ＩｇＭ、ＩｇＡ较正常人升高，而补体Ｃ３下降。

α2b干扰素治疗慢性丙肝患者的临床研究

目的 探讨α2 b干扰素对慢性丙肝患者外周血单个核细胞 (PBMC)内 HCV的治疗效果。方法 采用国产α 2 b干扰素 (30 0 MU / d)治疗 ,3个月为一疗程 ,共 2个疗程 ,并设常规治疗组(Vit C、门冬氨酸 )为对照。于疗程结束后分别检测患者 PBMC内 HCV- RNA和血清内 HCV- RNA、抗 - HCV。结果 α 2 b干扰素治疗组 2个疗程后慢性丙肝患者 PBMC、血清内 HCV - RNA和抗 -HCV转阴率分别为 4 2 .31% (11/ 2 6 )、5 7.6 9% (15 / 2 6 )、6 5 .38% (17/ 2 6 ) ,常规治疗组慢性丙肝患者 PBMC、血清内 HCV- RNA和抗 - HCV转阴率分别为 13.6 4 % (3/ 2 2 )、2 2 .73% (5 / 2 2 )、2 7.2 7%(6 / 2 2 ) ,两组相比 ,差异有显著性 (P <0 .0 5 )。结论 α 2 b干扰素对 PBMC内 HCV- RNA具有肯定的治疗作用 ,其疗效优于常规治疗组。

Management of telaprevir-based triple therapy for hepatitis C virus recurrence post liver transplant

AIM: To characterize management of telaprevir(TVR)-based triple therapy of hepatitis C virus(HCV) reinfection after liver transplantation(LT).METHODS: We retrospectively analyzed safety and efficacy of telaprevir- based triple therapy in a single center cohort of 19 patients with HCV genotype(GT) 1 recurrence after LT, with respect to factors possibly predicting sustained viral response(SVR) or non-SVR. All patients were treated with TVR, pegylated(PEG) and ribavirine(RBV) for 12 wk followed by a dual phase with PEG/RBV for 12 wk in 7 patients and for 36 wk in 5 patients. RESULTS: In total 11/19(58%) of patients achieved a sustained response. All(11/11) SVR patients showed a rapid viral response at treatment weeks 4 and 11/14 rapid virological response(RVR) patients achieved SVR. Notably, all(7/7) patients who completed 48 wk of therapy and 80%(4/5) patients who completed 24 wk of therapy achieved SVR24. Treatment failure was significantly(P > 0.049) more frequent in GT1 a infection(5/7) compared to GT1b(3/12) infection and was associated with emergence of resistance-associated mutations in the NS3 protease domain. Bilirubin level at baseline is also related to SVR(P > 0.030). None of the patients had to discontinue treatment due to side effects. CONCLUSION: RVR, GT and bilirubin are clearly related to achievement of SVR. Providing a thorough patient selection and monitoring, a full course of TVR-based triple therapy in LT patients is feasible and achieves high SVR rates.

HIV／HCV合并感染的流行病学、发病机制与治疗

随着人类免疫缺陷病毒（HIV）感染者和艾滋病（AIDS）病人不断增加，高效抗逆转录病毒治疗（HAART）的广泛使用，AIDS产生的机会性感染已相对减少，而由HIV与其它病原体引起的合并感染越来越引起人们的重视。丙型肝炎病毒（HCV）感染导致的肝脏疾病现在已成为发达国家HIV感染者死亡的主要原因之一。本文综述了HIV和HCV合并感染的流行病学、临床特点与治疗的研究进展。

Hepatitis C virus: Virology, diagnosis and management ofantiviral therapy

Hepatitis C virus (HCV) infects approximately 170 million individuals worldwide. Prevention of HCV infection complications is based on antiviral therapy with the combination of pegylated interferon alfa and ribavirin. The use of serological and virological tests has become essential in the management of HCV infection in order to diagnose infection, guide treatment decisions and assess the virological response to antiviral therapy. Anti- HCV antibody testing and HCV RNA testing are used to diagnose acute and chronic hepatitis C. The HCV genotype should be systematically determined before treatment, as it determines the indication, the duration of treatment, the dose of ribavirin and the virological monitoring procedure. HCV RNA monitoring during therapy is used to tailor treatment duration in HCV genotype 1 infection, and molecular assays are used to assess the end-of-treatment and, most importantly the sustained virological response, i.e. the endpoint of therapy.

Role of lipid rafts in liver health and disease

Liver diseases are an increasingly common cause of morbidity and mortality; new approaches for investigation of mechanisms of liver diseases and identification of therapeutic targets are emergent. Lipid rafts (LRs) are specialized domains of cellular membranes that are enriched in saturated lipids; they are small, mobile, and are key components of cellular architecture, protein partition to cellular membranes, and signaling events. LRs have been identified in the membranes of all liver cells, parenchymal and non-parenchymal; more importantly, LRs are active participants in multiple physiological and pathological conditions in individual types of liver cells. This article aims to review experimental-based evidence with regard to LRs in the liver, from the perspective of the liver as a whole organ composed of a multitude of cell types. We have gathered up-to-date information related to the role of LRs in individual types of liver cells, in liver health and diseases, and identified the possibilities of LR-dependent therapeutic targets in liver diseases.

Hepatitis C virus and ethanol alter antigen presentation in liver cells

Alcoholic patients have a high incidence of hepatitis C virus (HCV) infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCV-induced inability of the immune system to recognize infected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex (MHC) class-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC class and class in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine prof ile to the suppressive phenotype of interleukin-10 (IL-10) and transforming growth factor beta (TGFβ) predominance, preventing cell maturation and allostimulation capacity.The synergistic action of ethanol with HCV results in the suppression of MHC class-restricted antigen proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC class-restricted antigen presentation.Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.

慢性丙型肝炎患者血清甲状腺激素水平及甲状腺自身抗体的分析

目的探讨慢性丙型肝炎、代偿性丙型肝炎肝硬化、失代偿性丙型肝炎肝硬化时甲状腺激素水平的变化及甲状腺自身抗体存在状况。方法分别检测慢性丙型肝炎42例、肝硬化代偿期37例、肝硬化失代偿期36例、健康体检者30例的血清促甲状腺激素(TSH)、甲状腺素(T4)、三碘甲状腺原氨酸(T3)、游离甲状腺素(FT4)、游离三碘甲状腺原氨酸(FT3)、抗甲状腺过氧化物酶抗体(抗TPO)、抗甲状腺球蛋白抗体(抗TG)的含量。结果与正常对照组相比:T3,T4在各观察组均显著降低;FT3在肝硬化组,FT4在失代偿性肝硬化组显著降低;TSH在慢性丙型肝炎组降低,在肝硬化组升高;抗TPO、抗TG在各观察组均显著增高。结论慢性丙型肝炎患者甲状腺激素相关物质的检测可以帮助评估病情程度。

孕妇HIV、HBV、HCV及梅毒感染的调查与分析

目的评估孕妇产前检查HIV、HBV、HCV及梅毒的意义。方法对2003～2006年接受了此4项检查的孕妇资料进行回顾性分析。结果2807例孕妇中发现血清乙型肝炎HBsAg阳性224例(7.98%),抗-HCV阳性20例(0.71%),梅毒阳性(RPR及TPPA)阳性60例(2.13%),抗-HIV阳性2例(0.07%)。结论孕妇产前检查HIV、HBV、HCV及梅毒4项传染指标有重要意义。

100例HIV感染者乙肝、丙肝、戊肝和梅毒螺旋体感染状况研究

目的分析人类免疫缺陷病毒(HIV)感染者合并感染乙肝、丙肝、戊肝、梅毒螺旋体的情况。方法选取2014年1月至2017年1月某院治疗的100例HIV感染患者作为实验组,并选取同时期在某院进行健康体检的100例健康体检者作为对照组,两组受检者均接受乙肝感染、丙肝感染、戊肝感染、梅毒螺旋体感染检测,分析两组受检者的检测结果。结果 HIV感染者的梅毒螺旋体感染率明显高于对照组健康受检者,P<0.05,差异有统计学意义;经由血液和母婴传播的HIV感染者乙肝感染率、丙肝感染率明显高于经由性传播的HIV感染者,而梅毒螺旋体感染率明显低于经由性传播的HIV感染者,P<0.05,差异有统计学意义;男性和女性HIV感染者的乙肝感染率、丙肝感染率、戊肝感染率、梅毒螺旋体感染率比较,P>0.05,差异无统计学意义。结论HIV感染者易合并存在乙肝感染、丙肝感染、戊肝感染、梅毒螺旋体感染的情况,需要对HIV感染者进行定期病原学检测,对HIV的防治工作具有指导意义。