Inhibition of hepatitis viral replication by siRNA

Small interfering RNA (siRNA)-mediated sequence-specific gene silencing is a powerful tool to inhibit endogenous and exogenous gene expression, and it holds great potential to prevent and eradicate viral infection, for which existing therapy is inadequate, such as HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV). A number of studies have documented the effectiveness of siRNA against HBV or HCV at various regions of the viral genome in infected human hepatoma cell lines. Selected siRNA may reduce the production of viral replicons, as well as structural or non-structural proteins by > 90%. Only a few in vivo studies that demonstrated the efficacy of siRNA in the suppression of HBV replication in mice are available. Thus, reliable models of HBV and HCV infection in small animals or non-human primates are needed to evaluate the delivery and efficacy of siRNA as a therapeutic modality for viral hepatitis.     

Enlarged lymph nodes in porta hepatis: sonographic sign of chronic hepatitis B and C infections

PURPOSE: Enlarged lymph nodes in the hepatoduodenal ligament are prevalent in chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV); however, the clinical significance of this sonographic finding in an endemic area is unknown. METHODS: Six hundred outpatients were categorized into 4 groups (nonviral, HBV, HCV, and HBV and HCV) using viral markers. The prevalence and size of enlarged lymph nodes were compared. Correlation between clinical parameters and nodal size was evaluated. RESULTS: The incidence of detectable nodes in both the HBV group and the HCV group was significantly increased (56.9% and 69.4%, respectively; both p < 0.001) compared with the nonviral group; this rate was independent of aminotransferase levels. Nodal width was the only significant parameter when viral and nonviral groups were compared (p < 0.05). If a width of more than 5 mm was used to predict HBV or HCV infection, the positive predictive rate was 88% and the specificity was 89%. CONCLUSIONS: Lymph nodes in the hepatoduodenal ligament, especially those wider than 5 mm, suggest chronic HBV or HCV infection instead of only chronic hepatitis, especially in an endemic area such as Taiwan.     

Effects of alcohol consumption on viral hepatitis B and C

The liver is the main target organ for hepatitis viruses and the vital organ for alcohol metabolism. These two factors of viral hepatitis and alcohol abuse in combination can exert dual harmful actions, leading to enhanced damage to the liver. Epidemiological studies have revealed a higher prevalence of hepatitis C virus (HCV) infection among alcoholics than the general population. The interaction of alcohol with viral hepatitis [e.g., hepatitis B virus (HBV), HCV] and the underlying mechanisms are not fully understood. The effects of alcohol on viral hepatitis include promoted viral replication, weakened immune response, and increased oxidative stress. Clinically, alcohol abuse is correlated with an increased risk of developing end-stage liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B and C, suggesting that the combination of alcohol and HBV/HCV lead to more severe liver damage. The influence of mild to moderate alcohol drinking on the HBV-induced liver fibrosis, cirrhosis, and hepatocellular carcinoma among patients infected with HBV remains unclear. Unlike HBV infected patients, no safe level of alcohol intake has been established for patients with HCV. Even light to moderate alcohol use can exert a synergistic effect with viral hepatitis, leading to the rapid progression of liver disease. Furthermore, interferon-based therapy is less effective in alcohol drinkers than in control patients, even after abstinence from alcohol for a period of time. Therefore, abstaining from alcohol is highly recommended to protect the liver, especially in individuals with HBV/HCV infection, to improve the clinical efficacy of antiviral treatment and prevent the rapid progression of chronic viral hepatitis.     

某地区HIV、HCV、TP感染与HBV感染情况调查

目的 探讨成都地区乙型肝炎病毒(HBV)感染与HIV、丙型肝炎病毒(HCV)和梅毒(TP)感染及其相互合并感染的关系,为预防、控制和治疗相关疾病提供参考.方法 对近期半年内该院门诊、住院及体检者HBsAg、抗HIV抗体、抗HCV抗体和抗TP抗体检测结果进行回顾性分析,分析HBsAg阴、阳性结果与其他各项检测结果之间的关系.结果 HBsAg阳性者合并抗HIV抗体阳性率明显高于HBsAg阴性者(P<0.01),HBsAg阴性者TP感染率更高(P<0.01),HBV感染情况与合并抗HCV抗体阳性没有相关性(P>0.05);双重感染与HBV感染相关(P<0.05),以HCV/TP重叠感染与HBV感染相关性最为明显(P<0.05),HIV/HCV重叠感染和HIV/TP重叠感染均与HBV感染无明显相关性(P>0.05);未见HCV、HIV、TP三重感染.结论 HIV感染与HBV感染明显相关,HCV/TP重叠感染与HBV感染也有相关性.     

浙江省温州市吸毒人员中四种性传播疾病感染状况及影响因素调查

目的 了解浙江省温州市吸毒人员艾滋病病毒(HIV)、乙型病毒性肝炎病毒(HBV)、丙型病毒性肝炎病毒(HCV)以及梅毒螺旋体(TP)感染状况及影响因素,为开展干预工作,预防控制相关疾病在该类人群中流行提供依据。 方法 2011年新入住温州市强制戒毒所戒毒的人员作为本次调查对象进行匿名问卷调查,采集静脉血进行HIV、HBV、HCV、TP血清学检测,并对结果进行统计分析。 结果 403名吸毒人员HIV、HBV、HCV、TP阳性率分别为0.50%、16.87%、55.09%和9.68%。合并HBV/HCV、HBV/TP二重感染分别占60.49%和8.64%,HBV/HCV/TP、HIV/HBV/HCV三重感染分别占27.16%和2.47%,HIV/HBV/HCV/TP四重感染占1.23%。 结论 吸毒人员是HIV、HBV、HCV、TP感染的高危人群,应加强对该类人群的宣传教育和行为干预,以降低这几种疾病在该人群中的传播和扩散。     

维持性血液透析患者乙型肝炎和丙型肝炎病毒感染临床调查分析

目的 调查分析维持性血液透析患者乙型肝炎病毒(HBV)及丙型肝炎病毒(HCV)的感染情况.方法 回顾性分析镜湖医院1985年2月～2010年12月期间维持性血液透析3个月以上患者的临床数据,调查分析肝炎病毒感染的情况.结果 1155例患者,HBV阳性总数83例(7.18%),其中原有感染阳性者77例(6.66%),透析后感染阳性者6例(0.57%);HCV阳性总数59例(5.10%),其中原有感染阳性者38例(3.29%),透析后感染阳性者21例(2.01%).透析后感染率明显低于原有感染率( P＜0.05).透析后肝炎病毒感染,尤以HCV的感染多见,而HBV的感染则少见.原有感染组中,有7例HBV阳性者转阴,2例HCV的阳性者转阴.结论 有效隔离,防止交叉感染,广泛使用促红细胞生成素,使用一次性透析器,血液透析肝炎病毒感染可以得到有效控制.     

Pathological characterization of occult hepatitis B virus infection in hepatitis C virus-associated or non-alcoholic steatohepatitis-related hepatocellular carcinoma

Occult hepatitis B virus (HBV) infection, by definition, is a state in which infection with this virus does not manifest with the conventional diagnostic laboratory criteria reserved for the obvious form of HBV infection. As a result, occult HBV infection is commonly a surprise finding discovered accidently during the evaluation of other apparent liver diseases, such as hepatitis C virus (HCV) infection or non-alcoholic fatty liver disease and, more importantly, their evolution into life-threatening hepatocellular carcinoma. As infection with HCV and occult HBV is rarely considered when assessing these more obvious conditions, and in an attempt to offer a better understanding of this phenomenon, this study attempted to shed some light onto the uniqueness of occult HBV infection by addressing the natural history of HBV and HCV infections, as well as non-alcoholic fatty liver disease. This was carried out by taking into account the exclusive integration process undertaken by the HBV genome into infected host hepatocytes, with consideration given to conditions which afford reactivation of the occult infection and stress on the molecular mechanisms that underlie occult HBV infection. Finally, the clinical outcome of occult HBV infection and its relation to hepatocellular carcinoma is analyzed.     

Anti-cardiolipin antibodies in patients with chronic viral hepatitis are independent of beta2-glycoprotein I cofactor or features of antiphospholipid syndrome

BACKGROUND: Although controversial, some authorities have implicated hepatitis C virus (HCV) as a cause of anti-phospholipid syndrome (APLS). Anti-cardiolipin antibodies (anti-CLAbs) in APLS are cofactor-dependent ('pathogenic' antibodies). We conducted a study in order to determine the prevalence of anti-CLAbs in HCV patients, and furthermore to address whether these autoantibodies are cofactor-dependent or not and whether they are associated with features of APLS. Patients with hepatitis B virus (HBV) were also evaluated in order to assess whether there are differences in the prevalence and the clinical significance of anti-CLAbs between these two major types of chronic viral hepatitis. MATERIALS AND METHODS: One hundred and seventy-four consecutive HCV patients, 50 HBV patients and 267 healthy were investigated for the presence of anti-CLAbs and antibodies against beta2-glycoprotein I (beta2-GPI), which is the most important cofactor of the 'pathogenic' anti-CLAbs in APLS. IgG anti-CLAbs were determined by an in-house quantitative ELISA and anti-beta2-GPIAbs using a commercial ELISA kit. RESULTS: 21.3% of the HCV and 14% of the HBV patients tested positive for IgG anti-CLAbs (P < 0.0001 compared with healthy controls). Neither age, sex, certain epidemiologic and laboratory parameters nor the clinical status and the histologic findings were associated with anti-CLAbs detection in both diseases. 2.3% of the HCV (P < 0.05 compared with healthy controls) and 2% of the HBV patients tested positive for anti-beta2-GPIAbs. Presence of anti-CLAbs was not associated with features of APLS. CONCLUSIONS: A significant proportion of the HCV and HBV patients had detectable IgG anti-CLAbs. However, the anti-CLAbs titres were relatively low, and in most cases seem to be cofactor-independent ('nonpathogenic'). The latter is further supported by the lack of their association with clinical features of APLS. Furthermore, anti-CLAbs appear to be detected irrespective of the demographic, laboratory, clinical and histologic status in both HCV and HBV. However, prospective studies of longer duration may be required in order to address whether anti-CLAbs in patients with chronic viral hepatitis are or are not of clinical importance.     

T-regulatory lymphocytes and chronic viral hepatitis

Both hepatitis B virus (HBV) and hepatitis C virus (HCV) can cause persistent viral infection in humans. Chronic infection is associated with a risk of cirrhosis and hepatocellular carcinoma. The cause of chronic infection is unknown. A large body of evidence suggests that a failure of the adaptive immune response is critical in the establishment of chronic infection. Recently a new group of T cells (T-regulatory cells), that express CD4⁺CD25⁺ and Foxp3, which can inhibit the cellular (CD4⁺/CD8⁺) immune response have been described. In this review the authors explore the thoughts regarding immune responses to HBV and HCV infections and the role of these T-regulatory cells in relation to the pathogenesis of chronic HBV and HCV infection and the potential for therapeutic intervention.     

戊型肝炎病毒感染与胰腺癌发生的关系

目的 探讨戊型肝炎病毒(HEV)感染与胰腺癌发生的关系.方法 以住院患者为研究对象,包括2 900例病毒感染者(9例甲型肝炎、2 129例乙型肝炎、81例丙型肝炎、146例戊型肝炎和535例EB病毒感染)和5 569例对照,检测患者血清甲、乙、丙、戊型肝炎病毒标志物和EB病毒EB-VCA-IgA,收集相关临床资料包括CD4/CD8比值、总胆红素、糖类抗原(CA19-9)、γ-谷氨酰转肽酶(γ-GT)和脂肪酶等,比较HEV和其他病毒感染与胰腺癌的关系.结果 在HAV、HBV、HCV、HEV、EBV感染组中胰腺癌病例分别为0、5、1、12、1例,与对照组相比,HEV感染组罹患胰腺癌的风险增加约48倍(OR 49.16,CI 1.31～41.23),而其他病毒感染组和对照组之间差异无统计学意义(P＞0.05),而且HEV感染的胰腺癌患者血清CA19-9、总胆红素和γ-GT均增高,而CD4/CD8降低.结论 戊型肝炎病毒感染可能与胰腺癌的发生有一定的关系,HAV、HBV、HCV、EBV病毒感染与胰腺癌发生无关.     

Predictors of liver-related complications in patients with chronic hepatitis C

Chronic hepatitis C is the leading cause of decompensated liver disease requiring liver transplantation and a major cause of hepatocellular carcinoma (HCC). In liver clinic series, about 20% of those chronically infected with hepatitis C virus (HCV) develop cirrhosis over 20 years. From epidemiological data, however, it is clear that certain subgroups of patients are more likely to develop liver-related complications than others. Both host and viral factors have been implicated in individual susceptibility to adverse outcomes. The impact of host factors, such as alcoholism, is now well defined, and viral factors, such as genotype and viral load, appear to be less influential than previously considered. Coinfections with HIV, hepatitis A virus (HAV) and hepatitis B virus (HBV) may influence the rate of fibrotic progression and the subsequent development of complications in patients with chronic hepatitis C. The stage of fibrosis on biopsy and biochemical markers, such as a low serum albumin, can help identify patients who are more likely to develop complications. The role of the immune system in modifying the course of HCV is only now being defined. This editorial explores the role of host and viral factors in the development of liver-related complications in HCV-infected individuals.     

医务工作者乙型肝炎及丙型肝炎检测结果分析及对策

目的了解医务工作者的乙型肝炎(简称乙肝)两对半及丙型肝炎(简称丙肝)病毒感染情况,对医务工作者开展有效的乙肝、丙肝检测及预防控制工作提供依据。方法对医院在职及退休职工进行乙肝两对半及丙肝的实验室检测,并对检查结果进行分析。结果 768例医务工作者中乙肝感染7例(0.91%);丙肝感染9例(1.17%);乙肝病毒表面抗体阳性652例(阳性率84.89%);34例退休医务人员中乙肝感染3例(8.82%)、丙肝感染6例(17.6%),明显高于在职医务人员。结论医院总体乙肝及丙肝感染率低于全国感染率,但退休医务人员乙肝及丙肝感染率远远高于全国感染率。医务人员由于职业的特殊性,应通过一系列有效的措施降低职业暴露率,如有职业暴露的需及时上报相关职能科室,注射疫苗,重视自身防护。     

河南省驻马店市“艾滋病病毒单阳”家庭阴性配偶4种性病相关病毒感染调查

目的了解河南省驻马店市艾滋病病毒（HIV）单阳家庭阴性配偶HIV、病毒性乙型肝炎（乙肝）病毒（HBV）、病毒性丙型肝炎病毒（HCV）及梅毒感染现状及合并感染现状。 方法采用普查方法,对河南省驻马店市HIV单阳家庭阴性配偶进行血清流行病学调查,采集阴性配偶的血标本,检测其HIV、HBV、HCV及梅毒感染状况。结果本次调查共采集HIV单阳家庭中HIV抗体阴性配偶血样3619份,经检测HIV抗体阳性49例,HIV感染率为1.35%,抗-HCV感染率为31.20%,且随着年龄的增加而逐步升高（趋势2=-3.78,P0.01）、梅毒感染率为0.17%,但女性感染率高于男性（2=0.0061,P0.01）、乙肝表面抗原（HBsAg）感染率为5.40%、乙肝大三阳［HBsAg、乙肝病毒e抗原(HBeAg)、乙肝病毒核心抗体(抗-HBc)］阳性率为0.77%,乙肝小三阳（HBsAg、抗-Hbe、抗-HBc）阳性率为2.93%。HBsAg/HCV合并感染率最高为1.22%。HIV阳性者中,合并感染人数占的63.27%。结论驻马店市HIV单阳家庭阴性配偶的HIV感染率较高,已成为HIV感染的高危人群之一,4种传染病存在混合感染现象,建议加强对该人群的随访,定期检测HIV、HBV、HCV及梅毒,以控制4种传染病家庭内经性传播。     

HBV和HCV重叠感染患者生化免疫指标变化及临床意义

目的了解HBV和HCV重叠感染情况及其对肝功能及血清病毒载量的影响。方法常规检测3816例临床血清样本中的HBV及HcV血清标志物以及肝功能等指标,实时荧光定量PCR检测病毒载量。结果3816例送检样本中HBsAg阳性率8．9％（341／3816）,抗HCV抗体阳性率1．2％（46／3816）,其中HCVRNA检测阳性15例,现症感染率为0．39%。3816例样本中,HBV／HCV重叠感染15例,单纯HBV感染326例,单纯HCV感染31例。单纯HBV感染患者血清转氨酶（ALT和AST）及总胆红素（TBil）水平均明显高于重叠感染患者和单纯HCV感染患者。HBV／HCV重叠感染组患者HBVDNA栽量低于单纯HBV感染组,两组比较,差异有统计学意义（P〈0．05）;HBV／HCV重叠感染组患者HCVRNA载量也低于单纯HCV感染组,但两组比较,差异无统计学意义（P〉O．05）。结论重庆地区HBV／HCV感染情况与我国一般人群分布基本一致,重叠感染患者肝功能血清学指标改变低于单纯HBV感染患者。     

140例成人人类免疫缺陷病毒感染与丙型肝炎病毒感染相互影响

目的 了解经输血或单采浆献血感染人类免疫缺陷病毒(HIV)的患者中丙型肝炎病毒(HCV)的感染率；分析HIV与HCV感染的相互影响。方法 对140例经输血或单采浆献血感染HIV的患者血清抗HCV、HBV—M、肝脏生化功能、CD4^ 和CD8^ 细胞计数、纤维胃镜、肝胆脾B超进行分析。结果 140例HIV感染和获得性免疫缺陷综合征(AIDS)患者中HCV抗体阳性者占91．5％(128／140)；HIV和HCV混合感染者肝功能损害较轻，与单纯HIV感染者比较，其肝功能、B超改变、CD4^ 细胞计数之间差异无统计学意义。结论 经输血或单采浆献血感染的HIV感染者中存在着极高的HCV感染(91．5％)。HIV和HCV混合感染者与单纯HIV感染者比较，肝功能损伤并不严重，提示HIV可能并不加速丙型肝炎的进展。     

Screening serum biomarkers for early primary hepatocellular carcinoma using a phage display technique

Hepatocellular carcinoma (HCC) occurs mainly in chronically diseased livers following hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Early detection and diagnosis of HCC would be of great clinical benefit. In this study, we used a random phage display peptide library and sera from early-stage primary HCC patients (n = 30) to screen potential serum biomarkers for early primary HCC. Age- and sex-matched patients with HBV and/or HCV infection were used as controls. In the screening phase, 19 out of 20 randomly selected phage clones exhibited specific reaction with purified sera IgG from early primary HCC patients, among them 14 coming from the same phage clone with inserted peptidesequence RGWCRPLPKGEG (named HC1). In the validation phase, phage ELISA results showed that the positive reaction rate of the HC1 phage clone was 91.4% with the early HCC group (n = 70), significantly higher than that with the HBV infection group (20.0%) (n = 70), the HCV infection group (12.9%) (n = 70), the HBV + HCV infection group (24.3%) (n = 70), the cirrhosis group (17.1%) (n = 70), and the healthy control group (10.0%) (n = 70). In conclusion, the HC1 mimic peptide showed high diagnostic validity for early primary HCC, and thereby could be a candidate serum biomarker for early primary HCC.     

Molecular pathways in viral hepatitis-associated liver carcinogenesis: An update

Hepatocellular carcinoma (HCC) is the most common type of cancer among primary malignant tumors of the liver and is a consequential cause of cancer-related deaths worldwide. In recent years, uncovering the molecular mechanisms involved in the development and behavior of this tumor has led to the identification of multiple potential treatment targets. Despite the vast amount of data on this topic, HCC remains a challenging tumor to treat due to its aggressive behavior and complex molecular profile. Therefore, the number of studies aiming to elucidate the mechanisms involved in both carcinogenesis and tumor progression in HCC continues to increase. In this context, the close association of HCC with viral hepatitis has led to numerous studies focusing on the direct or indirect involvement of viruses in the mechanisms contributing to tumor development and behavior. In line with these efforts, this review was undertaken to highlight the current understanding of the molecular mechanisms by which hepatitis B virus (HBV) and hepatitis C virus (HCV) participate in oncogenesis and tumor progression in HCC and summarize new findings. Cumulative evidence indicates that HBV DNA integration promotes genomic instability, resulting in the overexpression of genes related to cancer development, metastasis, and angiogenesis or inactivation of tumor suppressor genes. In addition, genetic variations in HBV itself, especially preS2 deletions, may play a role in malignant transformation. Epigenetic dysregulation caused by both viruses might also contribute to tumor formation and metastasis by modifying the methylation of DNA and histones or altering the expression of microRNAs. Similarly, viral proteins of both HBV and HCV can affect pathways that are important anticancer targets. The effects of these two viruses on the Hippo-Yap-Taz pathway in HCC development and behavior need to be investigated. Additional, comprehensive studies are also needed to determine these viruses' interaction with integrins, farnesoid X, and the apelin system in malignant transformation and tumor progression. Although the relationship of persistent inflammation caused by HBV and HCV hepatitis with carcinogenesis is well defined, further studies are warranted to decipher the relationship among inflammasomes and viruses in carcinogenesis and elucidate the role of virus-microbiota interactions in HCC development and progression.     

Role of hepatitis C virus infection in German patients with fulminant and subacute hepatic failure

To investigate the possible role of hepatitis C virus (HCV) in fulminant and subacute liver failure, we tested serum and liver of 13 patients undergoing orthotopic liver transplantation for the presence of HCV RNA. HCV RNA was detected in specimens from two out of eight patients negative for all viral markers with suspected hepatitis non-A, non-B infection and in one out of four patients with hepatitis B virus infection. Only in this patient replication of HCV could be demonstrated. We conclude, that fulminant and subacute hepatic failure is induced by hepatitis C virus only in few patients with hepatitis non-A, non-B.     

丙肝病毒与乙肝病毒重叠感染几率观察

目的通过对查体人群及已感染丙肝病毒(HCV)病人的乙肝病毒(HBV)感染率进行比较分析,观察HCV重叠感染HBV的几率情况。方法利用酶联免疫吸附试验,对两组分别检测HBV感染情况。结果查体人群的HBV感染率为9.76%,HCV感染病人的HBV感染率为32.7%,两组间差异有显著统计学意义(P<0.05)。结论 HCV感染人群组中重叠感染HBV的几率较高,对抗-HCV阳性患者应注意警惕重叠感染。     

Occult hepatitis B — the result of the host immune response interaction with different genomic expressions of the virus

With over 40 years of history, occult hepatitis B infection (OBI) continues to remain an important and challenging public health problem. Defined as the presence of replication-competent hepatitis B virus (HBV) DNA (i.e., episomal HBV covalently closed circular DNA) in the liver and/or HBV DNA in the blood of people who test negative for hepatitis B surface antigen (HBsAg) in currently available assays, OBI is currently diagnosed using polymerase chain reaction (PCR) and real-time PCR assays. However, all efforts should be made to exclude a false negative HBsAg in order to completely follow the definition of OBI. In recent years, significant advances have been made in understanding the HBV lifecycle and the molecular mechanisms that lead to the persistence of the virus in the occult form. These factors are mainly related to the host immune system and, to a smaller proportion, to the virus. Both innate and adaptive immune responses are important in HBV infection management, and epigenetic changes driven by host mechanisms (acetylation, methylation, and microRNA implication) are added to such actions. Although greater genetic variability in the S gene of HBV isolated from OBIs was found compared with overt infection, the mechanisms of OBI are not mainly viral mutations.