HDV重叠感染可增加慢性乙型肝炎患者的肝细胞癌风险

HDV的重叠感染可加速慢性乙型肝炎患者的肝病进程,尤其肝细胞癌(HCC)的发生风险明显增高。但HDV的致癌机制有待进一步探索,治疗方式及效果也亟待突破。综述了HDV相关HCC流行病学新特点、致病机制的新认识和诊疗进展等,对推进研发更精准的HDV检测手段、更有效的治疗药物及减少HDV相关HCC具有重要意义。     

伴HDV感染的乙型肝炎患者的临床特征

目的　通过对丁型肝炎病毒（HDV）感染的乙型肝炎患者临床特点分析,了解HDV感染特征和HDV致病机理。方法　对合并HDV感染的507例乙型肝炎患者各临床类型肝炎的发生、预后、临床表现、生物化学指标、肝炎病毒标志物等作统计分析,以213例单纯HBV感染的乙型肝炎患者作对照。结果　HDV感染后重型肝炎、肝硬化的发生率和病死率、及发生出血、腹水、并发症和ALT反复增高及增高幅度均较HDV阴性者高（P＜0.01或P＜0.05）,重度慢性肝炎和重型肝炎患者的生物化学指标异常也较对照组明显（P＜0.01）。血清HBeAg检出率降低（P＜0.01）。急性肝炎、重型肝炎和肝硬化HDAg（+）、HBeAg（-）表达高于HDAg。HBeAg均阳性者（P＜0.01或P＜0.05）。结论　HDV感染后重度慢性肝炎、重型肝炎和肝硬化的发生率高,预后差;HDV感染可抑制HBV复制或HBeAg表达;HDV的直接细胞毒性作用在急性肝炎中可能起主要致病作用,在合并有HDV感染的乙型肝炎患者病情加重、病死率增高和慢性化过程中,HDV可能起主要促进作用。     

HBV,HCV及其重叠感染的临床观察

作者检测３９６例各类肝病患者ＨＢＶ－Ｍ及抗－ＨＣＶ，结果表明ＨＢＶ感染最多；单纯ＨＣＶ感染少；ＨＣＶ感染多与ＨＢＶ感染同时存在。重叠感染病情重，易发生重症肝炎。ＨＣＶ未干扰ＨＢＶ复制。     

各型肝炎病毒单纯及重叠感染的研究

目的 探讨病毒性肝炎患者甲～戊，庚型肝炎病毒(HAV-HEV，HGV)单纯感染及重叠感染情况。方法 采用EIA法检测病毒性肝炎患者血清抗-HAV IgM，HBV标志物、抗-HCV IgM、抗-HDV IgM、抗-HEV IgM、抗-HGV IgM。结果 共检测210例病毒性肝炎患者HAV-HEV、HGV血清标志物，20例未检出(9．5％)，190例患者检出标志物阳性(90．5％)。HBV感染率89，5％(188／210，其中有34例为既往感染，占16．2％，现症感染154例，占73．3％)；HAV感染率29．0％(61／210)，HCV、HDV感染率均为8．1％(17／210)、HEV、HGV感染率依次为10．0％(21／210)、7．1％(15／210)。各临床类型中单纯感染占61．4％(129／210)，二重感染占32．4％(68／210)，以HAV HBV、HBV HDV、HBV HEV感染模式最常见，三重感染占6．2％(13／210)，以HAV HBV HDV感染模式最常见；临床上以肝炎肝硬化、重型肝炎重叠感染常见，急性肝炎最少见。结论 病毒性肝炎中HBV感染最常见，其次为HAV感染；单纯感染、二重感染多见，三重感染少见；重叠感染发生率随病情加重而增加。     

慢性乙型肝炎重叠HCV,HDV感染80例分析

近几年来，由于免疫学和分子生物学技术的进展，病毒性肝炎病原学诊断逐步得以明确，临床上诊断肝炎病毒混合感染和重叠感染的报道增加．为探讨本地区慢性乙型肝炎重叠丙型肝炎病毒（ＨＣＶ）、丁型肝炎病毒（ＨＤＶ）感染的情况及其临床特点，笔者对我院１９９５０１／１９９８１２所收治的１４５１例各型肝炎中的２４６例慢性肝炎患者的血清标志物检测结果进行分析，其中对８０例慢性乙型肝炎重叠ＨＣＶ，ＨＤＶ感染的患者进行系统的临床观察，并与单纯慢性乙型肝炎８０例进行对比，现将结果报道如下．１　材料和方法１．１　材料　本…     

HBV/HCV重叠感染的现状与研究进展

乙型肝炎病毒(HBV)与丙型肝炎病毒(HCV)具有共同的传播途径,因此HBV/HCV重叠感染较为常见。HBV/HCV重叠感染时,两种病毒间存在相互抑制或干扰现象,加速了肝脏疾病的进展,预后不佳。为防止更严重的肝脏损伤,除了进行有效的预防外,应先针对优势病毒株及时进行有效的抗病毒治疗,并注意关注优势病毒株的转换,针对不同病毒模式的特点,及时调整治疗方案。     

乙型重叠丙型肝炎病毒与单纯乙型肝炎的临床对比分析

乙型重叠丙型肝炎病毒与单纯乙型肝炎的临床对比分析潘兆随，薛琪，方景森乙型肝炎重叠感染丙型肝炎病毒临床较多见，为了探索其重叠感染后的临床特点及其预后，本文作者进行了初步临床对比观察，现报告如下。临床资料一、一般资料本组病例均为１９９１年１月～１９９２年...     

HBV/HCV重叠感染的研究进展

HBV是一种嗜肝DNA病毒,HBV DNA和HBV特异P蛋白由核壳包裹成为核心颗粒,再由脂蛋白外膜包裹成完整的病毒颗粒。HCV是黄病毒科病毒,为单股正链RNA。HBV和HCV均由肠道外途径传播,2种病毒常可由相同途径发生感染。归纳了HBV/HCV重叠感染的发病机制、与隐匿性HBV感染和肝细胞癌以及器官移植、HBV疫苗之间的关系,同时介绍了重叠感染的治疗。指出存在于患者体内的HBV和HCV在病毒学方面相互干扰,在病变方面相互叠加。     

乙型肝炎表面抗原阳性血吸虫病患者HDV感染的血清学…

用酶联免疫吸附试验检测１２３例乙型肝炎表面抗原阳性的各期血吸虫病患者及５０例ＨＢｓＡｇ的阳性的非血吸虫病对照人群血清丁型肝炎病毒标志物，用斑点杂交检测晚期血吸虫病患者ＨＢＶ－ＤＮＡ。结果表明，ＨＢｓＡｇ阳性的晚血患者ＨＤＶ标志物检出率为率１４．５％显著高于急性血吸虫病，慢性血吸虫病患者及对照人群。随访观察发现，ＨＢＶ／ＨＤＶ双重感染的和晚血患者病死率４０％，显著高于单纯ＨＢＶ感染的晚血患者，提示晚     

乙丁型肝炎病毒重叠感染时HDV与HBV DNA定量的相关性研究

目的:明确在乙、丁型肝炎病毒重叠感染时HDV对HBV复制和HBVM表达有无抑制作用。方法:HBV DNA定量采用聚合酶链反应法,抗HD IgM采用CIA抗体捕获法,抗HD采用EIA竞争法,HDAg采用EIA夹心法,HBVM采用酶联免疫吸附法。结果:重叠感染组和单纯乙肝组的HBV DNA定量高滴度(≥10~6cps/ml)病例数比率分别为75％和67.74％,各型肝炎(慢性肝炎、肝硬变、慢性重型肝炎)HBV DNA定量高滴度病例数比率,重叠感染分别为68.42％、71.43％、100％,单纯乙肝组分别为65.38%、66.67％、100％。两组病例HBVM主要表达模式均为HBsAg( )、HBeAg( )、抗HBc( )或HBsAg( )、抗HBe( )、抗HBc( ),重叠感染组分别为57.14％、17.86％,单纯乙肝组分别为54.84％、16.13％,两组主要表达模式的HBV DNA定量高滴度病例数比半,重叠感染组分别为87.5％、60％,单纯乙肝组分别为88.24％、60％,均无显著性差异(P>0.05)。结论:HDV对HBV的复制和HBVM表达无明显抑制作用。     

慢性乙型肝炎肝组织ICAM-1 mRNA和ICAM-1表达及意义

目的探讨肝组织间粘附分子-1(ICAM-1)表达在慢性乙型肝炎(CHB)发病机理中的作用。方法用原位杂交和免疫组织化学技术检测11例正常人和50例慢性HBV感染者肝内ICAM-1 mRNA和ICAM-1表达情况。结果正常人和慢性无症状HBsAg携带者肝细胞无ICAM-1mRNA和ICAM-1表达,CHB患者肝细胞ICAM-1 mRNA和ICAM-1表达增强,阳性肝细胞多分布在汇管区周围和腺泡内炎症坏死区域;重度CHB患者肝细胞ICAM-1 mRNA和ICAM-1表达显著强于中、轻度CHB患者(P<0.05);肝细胞ICAM-1表达强度与肝组织炎症活动度呈显著正相关,p<0.01;肝细胞ICAM-1表达强的患者肝功能显著差于ICAM-1表达弱者,P<0.05。结论肝细胞ICAM-1表达在慢性乙型肝炎肝细胞坏死中起重要作用,肝细胞ICAM-1表达水平能较好反映其肝损害程度和肝功能状况。     

Hepatitis B Core Antigen Expression in Hepatocytes Reflects Viral Response to Entecavir in Chronic Hepatitis B Patients

Background/Aims

Hepatitis B core antigen is known to be a major target for virus-specific T cells and also reflects the progression of liver dissease and viral replication. Hepatitis B core antigen expression in hepatocytes leads to altered histological activity, viral replication, and immune response. The purpose of this study is to evaluate whether the topographical distribution of hepatitis B core antigen expression can predict the viral response to entecavir in patients with chronic hepatitis B.

Methods

We enrolled 91 patients with treatment-naïve chronic hepatitis B. All the patients underwent liver biopsy, and the existence and pattern of hepatitis B core antigen evaluated by immunohistochemistry. All patients received 0.5 mg of entecavir daily following a liver biopsy. We checked the viral response at 3, 6, and 12 months during antiviral therapy.

Results

Of the 91 patients, 64 (70.3%) had hepatitis B core antigen expression. Of the subcellular patterns, the mixed type was dominant (n=48, 75%). The viral response was significantly higher in the hepatitis B core antigen-negative group than in the hepatitis B core antigen-positive group (88.9% and 54.7%, respectively; p=0.001) after 12 months of entecavir therapy.

Conclusions

Chronic hepatitis B patients who are hepatitis B core antigen-negative have a better response to entecavir therapy than do hepatitis B core antigen-positive patients.     

Hepatitis B Splice-Generated Protein Antibodies in Syrian Chronic Hepatitis B Patients: Incidence and Significance

Background:

Previous studies have suggested hepatitis B splice-generated protein (HBSP), when expressed, is involved in the pathogenesis of HBV infection.

Objectives:

We aimed to evaluate anti-HBSP incidence and association with several HBV infection parameters in a group of Syrian chronic hepatitis B patients.

Patients and Methods:

Eighty treatment-naïve HBsAg-positive adult chronic hepatitis B patients'' sera were included in our prospective targeted study. Liver function, virological and histological tests results were obtained from patients’ medical files. Three variants of a 20-mer HBSP-derived peptide were designed based on HBV genome sequences obtained from Syrian patients'' sera (GenBank Accession No. {"type":"entrez-nucleotide-range","attrs":{"text":"JN257148-JN257217","start_term":"JN257148","end_term":"JN257217","start_term_id":"364505024","end_term_id":"364505559"}}JN257148-JN257217). Microtiter plate wells were coated with the synthetic peptides and used to detect anti-HBSP antibodies by an optimized indirect enzyme-linked immunosorbent assay (ELISA). Samples were considered positive when showed optical density (OD) values higher than the cut-off value for at least one peptide variant.

Results:

Seven out of eighty (9%) CHB patients were positive for anti-HBSP antibodies. Mean OD values were not significantly different between HBeAg-positive and -negative patients (P > 0.05). OD values showed weak positive correlation with ALT and AST values (P < 0.05), and weak to moderate positive correlation with liver biopsy staging ranks (P < 0.05). No significant correlation was revealed with viral load values or liver biopsy grading ranks (P > 0.05).

Conclusions:

We introduced an anti-HBSP antibodies ELISA, designed for locally circulating HBV strains. Correlation observed of Anti-HBSP with liver fibrosis staging regardless of viral replication and liver inflammation suggests anti-HBSP antibodies as possible indicator for HBV-associated liver fibrosis.     

Hepatitis B Virus Vaccine for Patients with Hepatitis C Virus Infection

Summary Hepatitis C is a disease with varying rates of progression. The role of hepatitis B virus (HBV) as a cofactor in the development of hepatitis C virus (HCV)-related cirrhosis and hepatocellular carcinoma (HCC) has been suggested and the use of HBV vaccine in all HCV-infected patients has been advocated. This review presents the implications of HBV and HCV coinfection and addresses the issues of HBV vaccine immunogenicity and safety in patients with chronic HCV infection. Received: December, 1999 · Revision accepted: July 1, 2000     

Prevalence of Hepatitis Delta Virus (HDV) Infection in Chronic Hepatitis B Patients with Unusual Clinical Pictures

Background

Probably 5% of the HBV carriers have HDV super infection. The risk of fulminant hepatitis, cirrhosis and hepatocellular carcinoma is higher in superinfection than the settings when HBV is alone.

Objectives

The aim of this study was to evaluate the prevalence of HDV in Iranian HBV isolates and to compare their clinical and virological pictures as well as their HDV genetic variations with other worldwide isolates.

Patients and Methods

81 carriers with positive results for HBsAg with upper limit ranges of ALT and low or undetectable levels of HBV viral load who did not respond to HBV therapy were selected. After RT amplification of HDV Delta antigen, direct sequencing and phylogenetic study were performed to explore the genotype(s) and nucleotide/amino acid variations.

Results

12 (14.8%) patients had positive results for both HDV RNA and anti-HDV. The mean ALT level was higher in HDV positive patients (75.9 U/ML) than HBV-mono-infected individuals; however, the mean HBV viral load was lower in coinfected patients than HBV-mono-infected patients. Phylogenetically, genotype I was the only detected genotype, and the most closely related isolates were of Turkish, Italian and Mongolian origin. Within the delta Ag, there were 326 nucleotide mutations, of which 111 and 215 were silent and missense, respectively. The total number of amino acid substitution was 148; most were located in known functional/epitopic domains. There was no correlation between the numbers of amino acid mutations, with clinical, virological status of the patients.

Conclusions

HDV should be suspected in HBV carriers with unusual clinical and virological pictures. Relatedness of Iranian HDV isolates to Italian and Turkish sequences proposed a common Caucasian origin for the distribution of HDV genotype I in this ethnic group.     

丙型肝炎病毒与甲乙型肝炎病毒重叠感染的研究

对485例病毒性肝炎患者进行了抗HCV、抗HAV-IgM、HBV-M检测.各型病毒性肝炎患者中抗HCV阳性率15.05％,慢性肝炎、肝硬变和重型肝炎阳性率高于急性肝炎;抗HCV阳性者中,27.40％有输血或血浆史;57.53％HBV-M阳性,其中HBsAg阳性占54.76％,抗HBc阳性达88.10％;既往有HBV感染者占33.33％.HBV与HCV重叠感染中慢性肝炎占58.06％,IAV与HCV重叠感染以急性肝炎多见(94.44％),HCV与甲乙型肝炎病毒三重感染可加速肝炎重症化的进程。     

肝毒清治疗慢性乙型肝炎的临床研究

目的：探讨纯中药浓缩胶囊肝毒清对慢性乙型肝炎的临床疗效。方法：４８例慢性乙型肝炎患者每次口服肝毒清胶囊８粒,每日３次;３０例对照组患者每次口服灭溴灵片６片,每日３次。两组均于治疗前和治疗后的０、３、６个月检查ＡＬＴ、ＡＳＴ、Ａ／Ｇ、ＴＢｉｌ、ＨＢＶ５项指标及ＨＢＶ－ＤＮＡ（ＰＣＲ法）进行对比。结果：肝毒清组总有效率８９．５％,对照组为６６．６％;ＨＢｅＡｇ、ＨＢＶ－ＤＮＡ阴转率,肝毒清组为４８．５