Editorial
肝内动力学共价闭合环状DNA和血清乙型肝炎表面抗原在抗病毒治疗慢性乙型肝炎的教训
实验和临床研究
Kinetics of Intrahepatic Covalently Closed Circular DNA and Serum Hepatitis B Surface Antigen During Antiviral Therapy for Chronic Hepatitis B: Lessons From
Experimental and Clinical Studies
FABIEN ZOULIM, MD, PhD
BARBARA TESTONI, PhD
FANNY LEBOSSÉ, MD
INSERM U1052
and Hospices Civils de Lyon
and Lyon University
Lyon, France
Extracts
In a newly infected cell, cccDNA formation results from the
transport of relaxed circular DNA into the nucleus of hepatocytes
and a series of biochemical reactions that lead to the
formation of this episomal form of viral DNA. cccDNA is
bound to histones and organized as a viral minichromosome.
Its transcriptional activity is regulated by epigenetic mechanisms9
(Figure 1). The pool of cccDNA initially is amplified and
then maintained by the recycling of nucleocapsid to the nucleus
of chronically infected cells. NUCs, which inhibit the viral
polymerase activity, do not inhibit the initial formation of
cccDNA in newly infected cells.10 However, a decrease of the
total amount of intrahepatic cccDNA was observed during
long-term therapy as a consequence of the inhibition of the
intracellular recycling pathway11–13 (Figure 1). Furthermore, it
was shown that hepatocyte turnover during chronic hepatitis B
may contribute to dilution of cccDNA because it is lost by cell
division11,14 (Figure 1). There is currently no commercially available
assay for the quantification of cccDNA, which still requires
a liver biopsy and access to frozen tissue. This is one of the
reasons why investigators have examined whether the quantification
of serum HBsAg might be a noninvasive surrogate
marker. Indeed, several assays are commercially available for the
quantification of serum HBsAg. HBsAg is part of the small,
middle, and large envelope proteins and is found in the envelope
of infectious virions (ie, Dane particles) and subviral particles.
HBsAg expression from the Pre-S/S gene can originate
either from viral cccDNA and/or from viral sequences integrated
in the host genome15 (Figure 1).
In this study, Wong et al8 had access to paired liver biopsy
samples taken at baseline and after 1 year of therapy from a
large group of 124 patients who were treated with 1 of the 5
NUCs (lamivudine, adefovir, entecavir, telbivudine, or clevudine).
Among the 117 patients who did not develop resistance,
the evaluation of viral suppression showed an average reduction
of approximately 0.2 log10 IU/mL in HBsAg, 5 log10 IU/mL in
serum level of hepatitis B virus (HBV) DNA, 2 log10 copies/cell
in intrahepatic total HBV DNA, and 1 log10 copies/cell in
cccDNA. Although 88 of 117 patients (75%) had undetectable
serum levels of HBV DNA (12 IU/mL), all had detectable
levels of HBsAg, and only 5 (4%) had undetectable levels of
cccDNA. Patients with greater reductions in levels of cccDNA
had greater reductions in HBsAg, but these reductions did not
reach statistically significant correlations. 作者: StephenW 时间: 2013-8-17 20:42
Hepatology. 2001 Oct;34(4 Pt 1):817-23.
Acute exacerbations of chronic hepatitis B are rarely associated with superinfection of hepatitis B virus.
Kao JH, Chen PJ, Lai MY, Chen DS.
Source
Graduate Institute of Clinical Medicine, Department of Internal Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan. [email protected]
Abstract
There are 7 genotypes of hepatitis B virus (HBV). Whether superinfection of HBV carriers with different HBV genotypes occurs remains unknown. We therefore determined the HBV genotype and association between superinfection and acute exacerbation of disease in a cohort of 244 patients with chronic HBV infection who had elevated serum aminotransferase levels for at least 1 year. Within this group, 103 patients experienced acute exacerbation with an annual incidence of 13%, and 20 of the 103 patients had IgM antibody to hepatitis B core antigen (IgM anti-HBc). These 20 patients had a higher prevalence of genotype C infection (65%) than the remaining 83 anti-core IgM-negative patients (40%) who also had acute exacerbations (P <.05). Detailed analysis of HBV genotypes and sequences of the variable pre-S gene were determined in serial samples from 20 patients with IgM anti-HBc-positive acute exacerbations (group A), 20 patients with IgM anti-HBc-negative acute exacerbations (group B), and 20 patients without exacerbations (group C). Two (10%) of the group A patients had virologic evidence of HBV superinfection during acute exacerbation, one superinfected with heterotypic virus and the other with homotypic virus. The newly introduced virus disappeared after the exacerbation and the original virus resumed thereafter. The calculated prevalence of HBV superinfection in the hepatitis B carriers and those with acute exacerbations was 0.8% (2 of 244) and 1.9% (2 of 103), respectively. In conclusion, superinfection of HBV on hepatitis B carriers indeed occurs and may cause acute exacerbations, albeit at a low frequency even in hyperendemic areas of HBV infection.
有7个基因型的乙型肝炎病毒（HBV） 。无论不同HBV基因型的HBV携带者二重感染发生仍是未知的。因此，我们确定HBV基因型和二重感染和疾病的急性发作期在一组的244例慢性HBV感染者血清转氨酶水平升高至少1年之间的关联。在这一组中，103名患者出现急性发作，每年发病率13％ ，有20 103例IgM抗体，乙肝核心抗原（抗-HBc IgM ） 。这20名患者中有较高的患病率C基因型感染（65％）比其余的83抗核心IgM抗体阴性的患者（40％） ，也有急性发作（ P <0.05） 。详细分析串行样品与抗-HBc IgM阳性的急性发作（A组） ， 20例抗-HBc IgM阴性急性加重（B组20例HBV基因型和变量的pre-S基因序列测定） ， （C组） 20例，无病情加重。二（10％） ， A组患者HBV二重感染急性发作时有病毒学证据superinfected异型的病毒和其他同型病毒。新推出的病毒发作后消失，此后恢复原来的病毒。 HBV二重感染在乙肝病毒携带者和急性加重的计算患病率分别为0.8 ％（ 2 244 ）和1.9％（ 2 103 ） ，分别。最后，乙肝携带者的HBV重叠确实发生，并可能导致急性发作，虽然在低频率下，即使在高流行地区的HBV感染。 作者: 2011plan 时间: 2013-8-30 08:47
我谷歌搜索，发现这篇文章: http://www.virologyj.com/content/4/1/74
Hepatitis B virus (HBV) genotypes in Egyptian pediatric cancer patients with acute and chronic active HBV infection
Abdel-Rahman N Zekri1*, Mohamed M Hafez1, Nahed I Mohamed2, Zeinab K Hassan1, Manal H El-Sayed3, Mohsen M Khaled4 and Tarek Mansour1
"Double infections with two different HBV genotypes have been known since typing was done serologically [29]. Subsequently, evidence of super infection with HBV isolates of the same or different genotype was described in chronic HBV patients [30]. Super infection was accompanied by acute exacerbation of the chronic disease. Using different methods for genotyping, several reports described high rates of double infection with two different HBV genotypes in all parts of the world. Using these methods double infections have been found in a range from 4.4% [31] to 17.5% [32] of HBV infected patients. Even triple infections with HBV of genotype A, B and C have been described in 0.9% of HBV infected intravenous drug users [32]. "
已知的，因为有两个不同的HBV基因型的双重感染血清学打字[29]。随后，超HBV感染的证据隔离在慢性HBV患者的相同或不同的基因型进行了说明[30]。超级感染，伴有的慢性疾病的急性发作期。用不同的方法进行基因分型，一些报告描述了高利率的双重感染，在世界各地有两个不同的HBV基因型。使用这些方法双重感染已被发现[31]从4.4％至17.5％[32]乙肝病毒感染的患者在一定范围内。甚至三倍的A，B和C基因型与HBV感染已被描述在0.9％的乙肝病毒感染的静脉吸毒者[32]
参考文献:
[29]Tabor E, Gerety RJ, Smallwood LA, Barker LF: Coincident hepatitis B surface antigen and antibodies of different subtypes in human serum.
[30]Kao J, Chen HPJ, Lai MY, Chen DS: Acute exacerbations of chronic hepatitis B are rarely associated with superinfection of hepatitis B virus. Hepatology 2001, 34:817-823.
[31]Ding X, Gu H, Zhong ZH, Zilong X, Tran HT, waki Y, Li TC, Sata T, Abe K: Molecular epidemiology of hepatitis viruses and genotypic distribution of hepatitis B and C viruses in Harbin, China. Jpn J Infect Dis 2003, 56:19-22.
[32]Chen B, Kao FJH, Liu CJ, Chen DS, Chen PJ: Genotypic dominance and novel recombinations in HBV genotype B and C coinfected intravenous drug users.J Med Virol 2004, 73:13-22. PubMed Abstract | Publisher Full Text
