Occult hepatitis B virus infection in Egypt

The emerging evidence of the potentially clinical importance of occult hepatitis B virus (HBV) infection (OBI) increases the interest in this topic. OBI may impact in several clinical contexts, which include the possible transmission of the infection, the contribution to liver disease progression, the development of hepatocellular carcinoma, and the risk of reactivation. There are several articles that have published on OBI in Egyptian populations. A review of MEDLINE database was undertaken for relevant articles to clarify the epidemiology of OBI in Egypt. HBV genotype D is the only detectable genotype among Egyptian OBI patients. Higher rates of OBI reported among Egyptian chronic HCV, hemodialysis, children with malignant disorders, and cryptogenic liver disease patients. There is an evidence of OBI reactivation after treatment with chemotherapy. The available data suggested that screening for OBI must be a routine practice in these groups of patients. Further studies needed for better understand of the epidemiology of OBI among Egyptian young generations after the era of hepatitis B vaccination.     

隐匿性乙型肝炎病毒感染

大量研究通过对肝组织和血清乙型肝炎病毒（HBV）DNA或转录体的检测，证实隐匿性HBV感染是所谓“隐源性肝炎”及其它慢性肝病的常见病因。现就其发生率、形成机制、临床意义、诊断、治疗等方面作一综述。     

Previous hepatitis B virus infection is associated with worse disease stage and occult hepatitis B virus infection has low prevalence and pathogenicity in hepatitis C virus‐positive patients

Abstract: Background: Anti‐hepatitis C virus (anti‐HCV) patients with chronic liver disease (CLD) frequently show markers of previous hepatitis B virus (HBV) infection. Moreover, they may carry occult HBV infection. These features might influence clinical and biochemical features as well as stage of disease. Aim: To assess the prevalence and clinical associations of previous (positivity for anti‐HBs and/or anti‐HBc antibodies) and occult HBV infection (positivity for HBV‐DNA by nested‐PCR) in the serum of anti‐HCV‐positive, HCV‐RNA‐positive, HBsAg‐negative patients with various degrees of CLD seen at a tertiary referral centre. Patients: A total of 119 patients fulfilled the inclusion criteria (84 chronic hepatitis and 35 liver cirrhosis). Results: Forty‐eight patients (40.3%) showed markers of previous HBV infection. This feature was more frequent (P = 0.02) among cirrhotics (57%) as compared to chronic hepatitis patients (33%). Chronic hepatitis patients positive for markers of previous HBV infection had worse histology as compared to negative ones (grading: 6.4 ± 2.7 versus 4.6 ± 3.0, P = 0.004; staging: 1.6 ± 1.2 versus 1.0 ± 1.0, P = 0.01). Eight patients were positive for HBV‐DNA in serum (6.7%). No difference in the presence of occult HBV infection was seen between various degrees of liver disease (7.1% of chronic hepatitis, 5.7% of cirrhosis) and among patients who were positive (10.4%) or negative (4.2%) for markers of previous HBV infection. No significant biochemical, virological, or histological difference was observed between age, age at infection, duration of infection, marker patterns of previous HBV infection‐matched HBV‐DNA‐positive and negative chronic hepatitis patients. Conclusions: Our findings suggest that previous HBV infection among anti‐HCV patients is associated with worse disease stage. In these patients, the prevalence of occult HBV infection is low and there is no difference in distribution among patients with or without markers of previous HBV infection. Furthermore, it does not seem to be associated with disease stage. Lastly, at least among patients with chronic hepatitis, it does not seem to affect the severity of disease.     

慢性肝病者乙型和丙型肝炎病毒重叠感染的研究

对２１３例老年慢性肝病患者的乙型肝炎病毒（ＨＢＶ）和丙型肝炎病毒（ＨＣＶ）血清标志物检测发现：ＨＢＶ感染占７３．２４％、ＨＢＶ和ＨＣＶ重叠感染占重叠感染点１５．４９％、ＨＣＶ感染占７．０４％、其它占４．２６％；ＨＢＶ阴性者ＨＣＶ检出率高于ＨＢＶ阳性者，肝癌和肝硬化患者较慢性肝炎患者高；ＨＢＶ和ＨＣＶ重叠感染患者的血清血蛋白下降显著，γ－球蛋白升高明显，肝硬化并腹水和上消化道出血者了多。结果表明，老     

MiR-122 in hepatitis B virus and hepatitis C virus dual infection

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the most common causes of chronic liver diseases and hepatocelluar carcinomas. Over the past few years, the liver-enriched microRNA-122 (miR-122) has been shown to differentially regulate viral replication of HBV and HCV. It is notable that the level of miR-122 is positively and negatively regulated by HCV and HBV, respectively. Consistent with the well-documented phenomenon that miR-122 promotes HCV accumulation, inhibition of miR-122 has been shown as an effective therapy for the treatment of HCV infection in both chimpanzees and humans. On the other hand, miR-122 is also known to block HBV replication, and HBV has recently been shown to inhibit miR-122 expression; such a reciprocal inhibition between miR-122 and HBV suggests an intriguing possibility that miR-122 replacement may represent a potential therapy for treatment of HBV infection. As HBV and HCV have shared transmission routes, dual infection is not an uncommon scenario, which is associated with more advanced liver disease than either HBV or HCV mono-infection. Thus, there is a clear need to further understand the interaction between HBV and HCV and to delineate the role of miR-122 in HBV/HCV dual infection in order to devise effective therapy. This review summarizes the current understanding of HBV/HCV dual infection, focusing on the pathobiological role and therapeutic potential of miR-122.     

Occult hepatitis C virus infection is more common than hepatitis B infection in maintenance hemodialysis patients

Patients of end stage renal disease on maintenance hemodialysis were enrolled to study the prevalence of occult and dual hepatitis B virus （HBV） and hepatitis C virus （HCV） infection and non-occult hepatitis B and C virus infection. One hundred and two patients were enrolled. Thirty patients had HCV infection, three of them were positive in anti-HCV. So, 27 （90%） of HCV-positive patients had occult HCV infection. Eleven （11%） patients had HBV infection. Five patients were positive in anti-HBc or HBV-DNA, but negative in HBsAg （occult HBV infection）. Three （3%） patients had dual HBV and HCV infection. None of the patients showed changes in viral markers during the follow-up of 8 mo on average （1-12 mo）.     

Dual chronic hepatitis B virus and hepatitis C virus infection

Dual hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are common in HBV or HCV endemic areas. However, several clinical and pathogenetic issues remain unresolved. First, clinical and in vitro studies suggest the interactions between two viruses. The dynamics of the interaction in untreated setting versus treated setting and its influence on the long-term outcomes await further studies. A key issue regarding viral interactions is whether modulation of infection occurs in the same dually infected individual hepatocyte of the liver. Clarifying this issue may help to understand the reciprocal interference between HCV and HBV and provide clues for future immunopathogenetic studies. Second, the prevalence and clinical significance of coexisting occult HBV infection in patients with chronic HCV infection need further investigations. Third, combination therapy of peginterferon alfa-2a and ribavirin appears to be just as effective and safe for the treatment of hepatitis B surface antigen (HBsAg)-positive patients chronically infected with active chronic hepatitis C as it is in patients with HCV monoinfection. Nevertheless, one-third of dually infected patients with nondetectable serum HBV DNA-level pretreatment developed HBV reactivation posttreatment. How to prevent and treat this reactivation should be clarified. Furthermore, about 10% of the dually infected patients lost HBsAg. Underlying mechanisms await further investigations. Finally, the optimal treatment strategies for dually infected patients with hepatitis B e antigen-positive chronic hepatitis B should be identified in future clinical trials.     

Occult hepatitis B virus infection: A major concern in HIV-infected patients: Occult HBV in HIV

Human immunodeficiency virus (HIV)- infected patients are at risk of acquiring viral hepatitis, due to common routes of transmission. As the introduction of highly active antiretroviral therapy (HAART) reduced the frequency of opportunistic infections and improved survival, viral hepatitis emerged as an important cause of morbidity and mortality in HIV-infected cases. Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection without detectable hepatitis B surface antigen (HBsAg). There are conflicting reports on the impact of occult HBV infection on the natural history of HIV disease. In this review, we described the findings of studies on HIV and hepatitis B co-infection with focus on the prevalence of occult HBV infection. The results of this review demonstrated the importance of prevention, diagnosis and treatment of occult HBV infection in HIV-positive patients.     

Current therapy for hepatitis C or D or immunodeficiency virus concurrent infection with chronic hepatitis B

Concurrent hepatitis C virus (HCV), hepatitis delta virus (HDV), or human immunodeficiency virus (HIV) infection with chronic hepatitis B virus (HBV) appears to increase the risk of progressive liver disease including liver cirrhosis and hepatocellular carcinoma. There is a 10% prevalence of HCV infection in chronic HBV or HDV infection. Serological evidence of previous exposure to HBV is found in more than 80% of HIV-positive patients in the high risk group. Notably, the most recently acquired virus tends to suppress the pre-existing virus. In chronic HBV infection acquired perinatally or in early childhood, usually HCV is dominant and may suppress or even displace HBV and HDV. Less frequently, HBV or HDV suppresses HCV. It is generally agreed that the dominant virus should be identified in order to make appropriate treatment decisions. Studies with standard interferon (IFN) to treat patients with HCV dominantly dual HBV/HCV infection have showed only limited virological response. But high dose of IFN has been demonstrated with better response rate. Combined ribavirin with standard or pegylated IFN therapy could achieve a sustained HCV clearance rate comparable with those infected with HCV alone. On the contrary, patients with HBV dominantly dual viral infection might indicate more appropriate addition of lamivudine to IFN than ribavirin. Additionally, patients with concurrent infection of HBV and HDV, IFN seems to be the only effective agent. However, the efficacy of IFN is related to the dose. High dose of IFN [9 MU tiw (thrice per week)] and longer treatment duration (at least 2 years) have been shown to achieve adequate virological response. In patients with concurrently infected HBV and HIV, anti-HBV therapy should be considered for all patients with evidence of liver disease, irrespective of the CD4 cell count. In patients not requiring antiretroviral therapy, HBV therapy should be preferentially based on IFN, adefovir, or telbivudine. In contrast, in patients with CD4 cell counts <350 cells/μl or those already on antiretroviral therapy, agents with double anti-HBV and anti-HIV activity are preferred. At present, the evidence of therapeutic efficacy is not sufficient to make a recommendation in treating patients with dual HBV/HCV or HBV/HDV or HBV/HIV infection. Further studies of the well-designed, larger scale are needed to elucidate the role of different regimens or combination in the treatment of dual viral infection.     

Hepatitis C virus eradication associated with hepatitis B virus superinfection and development of a hepatitis B virus specific T cell response

BACKGROUND/AIMS: Specific T cell responses during acute hepatitis B and during chronic hepatitis C have been described in detail. However, the T cell responses during the rare setting of acute hepatitis B virus (HBV) infection in the course of chronic hepatitis C that eventually lead to clearance of both viruses are completely unknown. METHODS: We analyzed the virus specific CD4+ and CD8+ T cell response during an acute HBV superinfection in a patient with chronic hepatitis C. RESULTS: The patient eliminated hepatitis C virus (HCV)-RNA and HBV-DNA from serum soon after the clinical onset of acute hepatitis B. The HBV specific T cell response found in this patient corresponds to the typical response that has been described in acute hepatitis B without chronic HCV infection. In contrast the hepatitis C specific immune response was similar to that generally found in chronic hepatitis C despite the fact that the patient also eliminated HCV-RNA. CONCLUSIONS: We hypothesize that the acute HBV infection induced a HBV specific T cell response which was associated with elimination HBV DNA and HCV-RNA, the latter possibly by bystander mechanisms, e.g. via secretion of cytokines. If such a non-specific bystander mechanism which has proven to be effective in the experimental setting and which is formally described here for a single patient can be shown to be a more general phenomenon, it may support the approach with new antiviral strategies, e.g. the induction of non-specific defense mechanisms against HCV.     

乙型与丙型肝炎病毒感染对小肝癌患者预后的影响

目的 探讨HBV、HCV感染对小肝癌的外科治疗策略及其预后的影响.方法 回顾性分析1997年1月-2003年12月天津医科大学附属肿瘤医院413例手术根治切除治疗的小肝痛(≤3 cm)患者的临床资料,将其分为4组:HCV感染组75例、HBV感染组251例、HCV、HBV混合感染组33例和尢HCV、HBV感染组54例,对可能影响预后的因素采用Kaplan-Meier生存分析、log-rank时序检验.结果 413例患者术后1、3、5年尢瘤生存率分别为83%、66%和58%,术后共有168(40.8%)例患者出现肝内复发,5年复发率HCV感染组最高(64.2%),其次为HBV/HCV感染组(48.4%),HBV感染组(37.8%)及无感染组(32.3%).肝内复发肿瘤为多发者在HCV感染组发生率最高(占肝内复发肿瘤的66.0%),其次为HBV/HCV感染组(28.6%),HBV感染组(23.3%)及无感染组(17.6%).413例小肝癌患者术后1、3、5年总生存率分别为89%、70%和61%,HCV感染组预后最差.和其他组相比,HCV感染组肝硬化程度严重,肿瘤细胞分化低,更易发生血管侵犯.在随访过程中,HCV感染组肝内复发率高,且复发类型常为多结节型.结论 HCV感染相关肝癌的临床肝硬化症状更重,而且术后复发率较高,预后更差.     

合并乙型肝炎病毒感染对丙型肝炎病毒核心抗原检测的影响

目的 探讨合并HBV感染对慢性HCV感染者血清丙型肝炎病毒核心抗原(HCVcAg)检出情况的影响. 方法 收集2005年12月-2009年10月慢性丙型肝炎患者和HBV/HCV合并感染者资料,检测血清HCVcAg和HCV RNA,对后者血清进行HBV DNA、HBeAg检测,分析HCVcAg检出率与HBeAg、HBV DNA定量检测的关系.用独立两组多分类的X2检验方法进行统计学分析. 结果 共收集88例慢性丙型肝炎患者和62例HBV/HCV合并感染者资料,血清HCVcAg的检出率分别为72.7％(64/88)和38.7％ (24/62),两者比较,x2= 17.358,P＜0.01,差异有统计学意义.HCV RNA检出率分别为81.8％ (72/88)和53.2％ (33/62),两者比较,x2=20.110,P＜0.01,差异有统计学意义.62例HBV/HCV合并感染者血清中,HBeAg阳性和HBeAg阴性感染者HCVcAg检出率分别为28.6％ (12/42)和60.0％ (12/20),两者比较,x2=5.641,P=0.011,差异有统计学意义.HCV RNA阳性率分别为42.9％ (18/42)和80.0％ (16/20),两者比较,X2=7.547,P＜ 0.01,差异有统计学意义.HBV DNA阳性和阴性时HCVcAg检出率分别为39.1％ (18/46)和37.5％ (6/16),两者比较,P＞0.05,差异无统计学意义.与单纯HCV感染者血清HCVcAg检出率72.7％ (64/88)比较,HBeAg阴性合并感染者为60.0％ (12/20),x2=1.266,P=0.261,差异无统计学意义;HBV DNA阴性合并感染者为37.5％ (6/16),x2=7.635,P＜0.01,差异有统计学意义.结论 HBV/HCV合并感染时HCVcAg检出率较低,可能是由于HBeAg抑制HCV的复制,从而减少HCVcAg的表达所致.     

乙型肝炎病毒基因突变与临床疾病进展的关系

乙型肝炎病毒感染人体可以引起急性和慢性乙型肝炎病毒感染。慢性乙型肝炎病毒感染后疾病的转归包括慢性肝炎、肝硬化、肝细胞癌以及肝衰竭。宿主、病毒因素及它们相互作用影响着疾病的进程。HBV 基因突变导致病毒生物学特性改变是影响乙型肝炎病毒感染转归的重要因素之一。     

Subgenotypes of hepatitis B virus genotype C do not correlate with disease progression of chronic hepatitis B in Taiwan.

BACKGROUND: Hepatitis B virus (HBV) genotype C (HBV/C) has two subgenotypes: HBV/Cs and Ce. The prevalence and clinical implications of subgenotype Cs and Ce in Taiwanese HBV carriers remain unknown. METHODS: Subgenotypes of HBV/C were determined in 242 Taiwanese HBV carriers with various stages of liver disease. The clinical as well as virologic features between patients with HBV/Cs and HBV/Ce infection were further compared. RESULTS: HBV/Ce was the predominant subgenotype in Taiwan. The prevalence of HBV/Ce was 93.6% in the inactive carriers group, 84.2% in chronic hepatitis patients, 81.2% in cirrhosis patients, 92.5% in hepatocellular carcinoma (HCC) patients without cirrhosis and 91.9% in HCC patients with cirrhosis. There was no significant difference in the distribution of the HBV/C subgenotypes among patients with different stages of liver disease. CONCLUSIONS: Subgenotypes of HBV/C may not have a clinical impact on the disease progression of chronic hepatitis B in Taiwan.     

胎盘滋养层细胞的乙型肝炎病毒感染与宫内感染机制

目的：检测HBV对胎盘、胎肝和滋养层细胞的感染情况，探讨HBV的宫内感染机制。方法：研究对象包括20例孕妇胎盘组织、6例引产胎儿胎肝组织及体外培养的胎盘滋养层细胞。ELISA法检测孕妇外周血、胎儿脐血和6个月婴儿外周血HBV标志物；荧光定量PCR法检测血清和滋养层细胞中的HBV DNA；免疫组织化学法和免疫荧光法检测胎盘、胎肝组织及滋养层细胞中HBV标志物的表达；末端脱氧核糖核酸转移酶介导的缺口标记法（TUNEL）检测胎盘和滋养层细胞凋亡情况。结果：孕妇血清HBV DNA水平与胎儿脐血HBV DNA水平相关，脐血HBV DNA阳性者其母血HBV DNA〉1.0×10^7拷贝／mL；6例胎盘组织和3例引产胎儿胎肝组织中可见HBsAg免疫组织化学染色阳性细胞，其中1例胎肝组织中发现HBcAg阳性细胞；体外培养滋养层细胞与HBV DNA阳性血清共孵育后，可检测到HBsAg的表达，亦可检测到HBV DNA。体内和体外实验均检测到HBV感染后滋养层细胞凋亡呈增加趋势，且胎盘细胞的凋亡与脐血HBV DNA水平相关。体外实验结果显示，随感染时间的延长，滋养层细胞凋亡呈增加趋势。6个月后，12例新生儿有1例血清HBsAg、HBeAg和抗-HBc阳性，6例抗-HBs阳性。结论：HBV宫内感染的机制可能是通过HBV感染胎盘屏障而使胎儿发生HBV宫内感染。HBV在胎儿组织器官内的定位和复制可能是新生儿发生慢性HBV感染的重要因素。滋养层细胞凋亡可能是胎盘屏障阻断HBV宫内传播的一种保护性机制。     

HBV/HCV重叠感染的抗病毒治疗

从全球范围看,乙型肝炎病毒(hepatitis B virus,HBV)和丙型肝炎病毒(hepatitis C virus,HCV)重叠感染估计约有700-2000万人口感染.重叠感染和单一HBV或HCV感染比较,更易发展为肝硬化、肝细胞癌甚至肝衰竭的比例也高,HBV和HCV重叠感染可有四种不同的临床模式,即HCV活动...