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Association of hepatitis B virus mutations in basal core promoter and precore regions with severity of liver disease: an investigation of 793 Chinese patients with mild and severe chronic hepatitis B and acute-on-chronic liver failure

Identifieur interne : 000E24 ( Istex/Corpus ); précédent : 000E23; suivant : 000E25

Association of hepatitis B virus mutations in basal core promoter and precore regions with severity of liver disease: an investigation of 793 Chinese patients with mild and severe chronic hepatitis B and acute-on-chronic liver failure

Auteurs : Zhihui Xu ; Xiaoqiang Ren ; Yan Liu ; Xiaodong Li ; Siyu Bai ; Yanwei Zhong ; Lin Wang ; Panyong Mao ; Huifen Wang ; Shaojie Xin ; Vincent Wai-Sun Wong ; Henry Lik-Yuen Chan ; Fabien Zoulim ; Dongping Xu

Source :

RBID : ISTEX:E0C7FCC069FEDE1A2C6F6010B6CB8895F3EF8BA0

English descriptors

Abstract

Abstract: Objective: To investigate the features of hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutations and genotypes in a large number of mild/severe chronic hepatitis B (CHB-M/CHB-S), and acute-on-chronic liver failure (ACLF) patients and analyze the clinical implications of the virologic features. Patients and methods: Sera of 793 (325 CHB-M, 170 CHB-S, and 298 ACLF) patients admitted to or who had visited Beijing 302 Hospital from January 2005 to December 2008 were collected and successfully amplified for the HBV BCP/PC and a 1225-bp-long S/Pol (nt 54–1278) gene regions. Biochemical and serological parameters and HBV DNA level were routinely performed. Viral DNA was extracted and subjected to a nested PCR. Genotypes/subgenotypes were determined based on complete genomic sequence or on analysis of the 1225-bp-long S/Pol-gene sequence. HBV genotyping was performed by direct PCR sequencing followed by molecular evolutionary analysis of the viral sequences. A P value of <0.05 (two-sided) was considered to be statistically significant. Conclusions: Our findings suggest that CHB patients infected with BCP/PC mutant viruses are more susceptible to severe hepatitis and ACLF than those with the BCP/PC wild-type virus and that ACLF patients with PC mutant viruses have an increased risk of death. As such, the HBV PC mutation is a potential predictive indicator of ACLF outcome.

Url:
DOI: 10.1007/s00535-010-0315-4

Links to Exploration step

ISTEX:E0C7FCC069FEDE1A2C6F6010B6CB8895F3EF8BA0

Le document en format XML

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<title level="a" type="main" xml:lang="en">Association of hepatitis B virus mutations in basal core promoter and precore regions with severity of liver disease: an investigation of 793 Chinese patients with mild and severe chronic hepatitis B and acute-on-chronic liver failure</title>
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<name sortKey="Wang, Lin" sort="Wang, Lin" uniqKey="Wang L" first="Lin" last="Wang">Lin Wang</name>
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<name sortKey="Wang, Huifen" sort="Wang, Huifen" uniqKey="Wang H" first="Huifen" last="Wang">Huifen Wang</name>
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<mods:affiliation>Viral Hepatitis Research Laboratory, Beijing Institute of Infectious Diseases, 100039, Beijing, China</mods:affiliation>
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<mods:affiliation>Liver Failure Research Center, Beijing 302 Hospital, 100039, Beijing, China</mods:affiliation>
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<name sortKey="Wong, Vincent Wai Sun" sort="Wong, Vincent Wai Sun" uniqKey="Wong V" first="Vincent Wai-Sun" last="Wong">Vincent Wai-Sun Wong</name>
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<mods:affiliation>Department of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China</mods:affiliation>
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<name sortKey="Chan, Henry Lik Yuen" sort="Chan, Henry Lik Yuen" uniqKey="Chan H" first="Henry Lik-Yuen" last="Chan">Henry Lik-Yuen Chan</name>
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<mods:affiliation>Department of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China</mods:affiliation>
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<name sortKey="Zoulim, Fabien" sort="Zoulim, Fabien" uniqKey="Zoulim F" first="Fabien" last="Zoulim">Fabien Zoulim</name>
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<mods:affiliation>Department of Hepatology and Gastroenterology, Hospices Civils de Lyon, Hôtel Dieu Hospital, 69002, Lyon, France</mods:affiliation>
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<name sortKey="Xu, Dongping" sort="Xu, Dongping" uniqKey="Xu D" first="Dongping" last="Xu">Dongping Xu</name>
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<title level="j">Journal of Gastroenterology</title>
<title level="j" type="abbrev">J Gastroenterol</title>
<idno type="ISSN">0944-1174</idno>
<idno type="eISSN">1435-5922</idno>
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<publisher>Springer Japan</publisher>
<pubPlace>Japan</pubPlace>
<date type="published" when="2011-03-01">2011-03-01</date>
<biblScope unit="volume">46</biblScope>
<biblScope unit="issue">3</biblScope>
<biblScope unit="page" from="391">391</biblScope>
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<term>Acute-on-chronic liver failure</term>
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<term>Precore mutation</term>
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<div type="abstract" xml:lang="en">Abstract: Objective: To investigate the features of hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutations and genotypes in a large number of mild/severe chronic hepatitis B (CHB-M/CHB-S), and acute-on-chronic liver failure (ACLF) patients and analyze the clinical implications of the virologic features. Patients and methods: Sera of 793 (325 CHB-M, 170 CHB-S, and 298 ACLF) patients admitted to or who had visited Beijing 302 Hospital from January 2005 to December 2008 were collected and successfully amplified for the HBV BCP/PC and a 1225-bp-long S/Pol (nt 54–1278) gene regions. Biochemical and serological parameters and HBV DNA level were routinely performed. Viral DNA was extracted and subjected to a nested PCR. Genotypes/subgenotypes were determined based on complete genomic sequence or on analysis of the 1225-bp-long S/Pol-gene sequence. HBV genotyping was performed by direct PCR sequencing followed by molecular evolutionary analysis of the viral sequences. A P value of <0.05 (two-sided) was considered to be statistically significant. Conclusions: Our findings suggest that CHB patients infected with BCP/PC mutant viruses are more susceptible to severe hepatitis and ACLF than those with the BCP/PC wild-type virus and that ACLF patients with PC mutant viruses have an increased risk of death. As such, the HBV PC mutation is a potential predictive indicator of ACLF outcome.</div>
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<name>Xiaoqiang Ren</name>
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<name>Xiaodong Li</name>
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<name>Siyu Bai</name>
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<json:string>Liver Failure Research Center, Beijing 302 Hospital, 100039, Beijing, China</json:string>
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<name>Yanwei Zhong</name>
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<json:string>Liver Failure Research Center, Beijing 302 Hospital, 100039, Beijing, China</json:string>
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<json:item>
<name>Huifen Wang</name>
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<json:string>Viral Hepatitis Research Laboratory, Beijing Institute of Infectious Diseases, 100039, Beijing, China</json:string>
<json:string>Liver Failure Research Center, Beijing 302 Hospital, 100039, Beijing, China</json:string>
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<json:item>
<name>Shaojie Xin</name>
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<json:string>Viral Hepatitis Research Laboratory, Beijing Institute of Infectious Diseases, 100039, Beijing, China</json:string>
<json:string>Liver Failure Research Center, Beijing 302 Hospital, 100039, Beijing, China</json:string>
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</json:item>
<json:item>
<name>Vincent Wai-Sun Wong</name>
<affiliations>
<json:string>Department of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China</json:string>
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</json:item>
<json:item>
<name>Henry Lik-Yuen Chan</name>
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<json:string>Department of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China</json:string>
</affiliations>
</json:item>
<json:item>
<name>Fabien Zoulim</name>
<affiliations>
<json:string>INSERM, U871, 69003, Lyon, France</json:string>
<json:string>Department of Hepatology and Gastroenterology, Hospices Civils de Lyon, Hôtel Dieu Hospital, 69002, Lyon, France</json:string>
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<name>Dongping Xu</name>
<affiliations>
<json:string>Viral Hepatitis Research Laboratory, Beijing Institute of Infectious Diseases, 100039, Beijing, China</json:string>
<json:string>Liver Failure Research Center, Beijing 302 Hospital, 100039, Beijing, China</json:string>
<json:string>E-mail: xudongping@yahoo.com</json:string>
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<value>Hepatitis B virus</value>
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<value>Basal core promoter mutation</value>
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<json:string>eng</json:string>
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<value>Precore mutation</value>
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<value>Genotype</value>
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<value>Acute-on-chronic liver failure</value>
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<json:string>eng</json:string>
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<value>ACLF : Acute-on-chronic liver failure</value>
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<json:string>eng</json:string>
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<value>ALF : Acute liver failure</value>
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<json:string>eng</json:string>
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<value>ALT : Alanine aminotransferase</value>
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<lang>
<json:string>eng</json:string>
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<value>BCP : Basal core promoter</value>
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<lang>
<json:string>eng</json:string>
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<value>CHB-M : Mild chronic hepatitis B</value>
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<json:string>eng</json:string>
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<value>CHB-S : Severe chronic hepatitis B</value>
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<json:string>eng</json:string>
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<value>HBV : Hepatitis B virus</value>
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<json:string>eng</json:string>
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<value>HCC : Hepatocellular carcinoma</value>
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<abstract>Abstract: Objective: To investigate the features of hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutations and genotypes in a large number of mild/severe chronic hepatitis B (CHB-M/CHB-S), and acute-on-chronic liver failure (ACLF) patients and analyze the clinical implications of the virologic features. Patients and methods: Sera of 793 (325 CHB-M, 170 CHB-S, and 298 ACLF) patients admitted to or who had visited Beijing 302 Hospital from January 2005 to December 2008 were collected and successfully amplified for the HBV BCP/PC and a 1225-bp-long S/Pol (nt 54–1278) gene regions. Biochemical and serological parameters and HBV DNA level were routinely performed. Viral DNA was extracted and subjected to a nested PCR. Genotypes/subgenotypes were determined based on complete genomic sequence or on analysis of the 1225-bp-long S/Pol-gene sequence. HBV genotyping was performed by direct PCR sequencing followed by molecular evolutionary analysis of the viral sequences. A P value of >0.05 (two-sided) was considered to be statistically significant. Conclusions: Our findings suggest that CHB patients infected with BCP/PC mutant viruses are more susceptible to severe hepatitis and ACLF than those with the BCP/PC wild-type virus and that ACLF patients with PC mutant viruses have an increased risk of death. As such, the HBV PC mutation is a potential predictive indicator of ACLF outcome.</abstract>
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</AuthorGroup>
<Abstract ID="Abs1" Language="En">
<Heading>Abstract</Heading>
<AbstractSection ID="ASec1">
<Heading>Objective</Heading>
<Para>To investigate the features of hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutations and genotypes in a large number of mild/severe chronic hepatitis B (CHB-M/CHB-S), and acute-on-chronic liver failure (ACLF) patients and analyze the clinical implications of the virologic features.</Para>
</AbstractSection>
<AbstractSection ID="ASec2">
<Heading>Patients and methods</Heading>
<Para>Sera of 793 (325 CHB-M, 170 CHB-S, and 298 ACLF) patients admitted to or who had visited Beijing 302 Hospital from January 2005 to December 2008 were collected and successfully amplified for the HBV BCP/PC and a 1225-bp-long S/Pol (nt 54–1278) gene regions. Biochemical and serological parameters and HBV DNA level were routinely performed. Viral DNA was extracted and subjected to a nested PCR. Genotypes/subgenotypes were determined based on complete genomic sequence or on analysis of the 1225-bp-long S/Pol-gene sequence. HBV genotyping was performed by direct PCR sequencing followed by molecular evolutionary analysis of the viral sequences. A
<Emphasis Type="Italic">P</Emphasis>
value of <0.05 (two-sided) was considered to be statistically significant.</Para>
</AbstractSection>
<AbstractSection ID="ASec4">
<Heading>Conclusions</Heading>
<Para>Our findings suggest that CHB patients infected with BCP/PC mutant viruses are more susceptible to severe hepatitis and ACLF than those with the BCP/PC wild-type virus and that ACLF patients with PC mutant viruses have an increased risk of death. As such, the HBV PC mutation is a potential predictive indicator of ACLF outcome.</Para>
</AbstractSection>
</Abstract>
<KeywordGroup Language="En" OutputMedium="All">
<Heading>Keywords</Heading>
<Keyword>Hepatitis B virus</Keyword>
<Keyword>Basal core promoter mutation</Keyword>
<Keyword>Precore mutation</Keyword>
<Keyword>Genotype</Keyword>
<Keyword>Acute-on-chronic liver failure</Keyword>
</KeywordGroup>
<AbbreviationGroup>
<Heading>Abbreviations</Heading>
<DefinitionList>
<DefinitionListEntry>
<Term>ACLF</Term>
<Description>
<Para>Acute-on-chronic liver failure</Para>
</Description>
</DefinitionListEntry>
<DefinitionListEntry>
<Term>ALF</Term>
<Description>
<Para>Acute liver failure</Para>
</Description>
</DefinitionListEntry>
<DefinitionListEntry>
<Term>ALT</Term>
<Description>
<Para>Alanine aminotransferase</Para>
</Description>
</DefinitionListEntry>
<DefinitionListEntry>
<Term>BCP</Term>
<Description>
<Para>Basal core promoter</Para>
</Description>
</DefinitionListEntry>
<DefinitionListEntry>
<Term>CHB-M</Term>
<Description>
<Para>Mild chronic hepatitis B</Para>
</Description>
</DefinitionListEntry>
<DefinitionListEntry>
<Term>CHB-S</Term>
<Description>
<Para>Severe chronic hepatitis B</Para>
</Description>
</DefinitionListEntry>
<DefinitionListEntry>
<Term>HBV</Term>
<Description>
<Para>Hepatitis B virus</Para>
</Description>
</DefinitionListEntry>
<DefinitionListEntry>
<Term>HCC</Term>
<Description>
<Para>Hepatocellular carcinoma</Para>
</Description>
</DefinitionListEntry>
<DefinitionListEntry>
<Term>LC</Term>
<Description>
<Para>Liver cirrhosis</Para>
</Description>
</DefinitionListEntry>
<DefinitionListEntry>
<Term>PC</Term>
<Description>
<Para>Precore</Para>
</Description>
</DefinitionListEntry>
<DefinitionListEntry>
<Term>PTA</Term>
<Description>
<Para>Prothrombin activity</Para>
</Description>
</DefinitionListEntry>
<DefinitionListEntry>
<Term>TBIL</Term>
<Description>
<Para>Total bilirubin</Para>
</Description>
</DefinitionListEntry>
<DefinitionListEntry>
<Term>PCR</Term>
<Description>
<Para>Polymerase chain reaction</Para>
</Description>
</DefinitionListEntry>
</DefinitionList>
</AbbreviationGroup>
<ArticleNote Type="Misc">
<SimplePara>Z. Xu, X. Ren, and Y. Liu contributed equally to this work.</SimplePara>
</ArticleNote>
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<NoBody></NoBody>
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</Issue>
</Volume>
</Journal>
</Publisher>
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<title>Association of hepatitis B virus mutations in basal core promoter and precore regions with severity of liver disease: an investigation of 793 Chinese patients with mild and severe chronic hepatitis B and acute-on-chronic liver failure</title>
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<affiliation>Viral Hepatitis Research Laboratory, Beijing Institute of Infectious Diseases, 100039, Beijing, China</affiliation>
<affiliation>Liver Failure Research Center, Beijing 302 Hospital, 100039, Beijing, China</affiliation>
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<affiliation>Department of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China</affiliation>
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<affiliation>Department of Hepatology and Gastroenterology, Hospices Civils de Lyon, Hôtel Dieu Hospital, 69002, Lyon, France</affiliation>
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<affiliation>Viral Hepatitis Research Laboratory, Beijing Institute of Infectious Diseases, 100039, Beijing, China</affiliation>
<affiliation>Liver Failure Research Center, Beijing 302 Hospital, 100039, Beijing, China</affiliation>
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<abstract lang="en">Abstract: Objective: To investigate the features of hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutations and genotypes in a large number of mild/severe chronic hepatitis B (CHB-M/CHB-S), and acute-on-chronic liver failure (ACLF) patients and analyze the clinical implications of the virologic features. Patients and methods: Sera of 793 (325 CHB-M, 170 CHB-S, and 298 ACLF) patients admitted to or who had visited Beijing 302 Hospital from January 2005 to December 2008 were collected and successfully amplified for the HBV BCP/PC and a 1225-bp-long S/Pol (nt 54–1278) gene regions. Biochemical and serological parameters and HBV DNA level were routinely performed. Viral DNA was extracted and subjected to a nested PCR. Genotypes/subgenotypes were determined based on complete genomic sequence or on analysis of the 1225-bp-long S/Pol-gene sequence. HBV genotyping was performed by direct PCR sequencing followed by molecular evolutionary analysis of the viral sequences. A P value of <0.05 (two-sided) was considered to be statistically significant. Conclusions: Our findings suggest that CHB patients infected with BCP/PC mutant viruses are more susceptible to severe hepatitis and ACLF than those with the BCP/PC wild-type virus and that ACLF patients with PC mutant viruses have an increased risk of death. As such, the HBV PC mutation is a potential predictive indicator of ACLF outcome.</abstract>
<note>Original Article—Liver, Pancreas, and Biliary Tract</note>
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<genre>Keywords</genre>
<topic>Hepatitis B virus</topic>
<topic>Basal core promoter mutation</topic>
<topic>Precore mutation</topic>
<topic>Genotype</topic>
<topic>Acute-on-chronic liver failure</topic>
</subject>
<subject>
<genre>Abbreviations</genre>
<topic>ACLF : Acute-on-chronic liver failure</topic>
<topic>ALF : Acute liver failure</topic>
<topic>ALT : Alanine aminotransferase</topic>
<topic>BCP : Basal core promoter</topic>
<topic>CHB-M : Mild chronic hepatitis B</topic>
<topic>CHB-S : Severe chronic hepatitis B</topic>
<topic>HBV : Hepatitis B virus</topic>
<topic>HCC : Hepatocellular carcinoma</topic>
<topic>LC : Liver cirrhosis</topic>
<topic>PC : Precore</topic>
<topic>PTA : Prothrombin activity</topic>
<topic>TBIL : Total bilirubin</topic>
<topic>PCR : Polymerase chain reaction</topic>
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<identifier type="ISSN">0944-1174</identifier>
<identifier type="eISSN">1435-5922</identifier>
<identifier type="JournalID">535</identifier>
<identifier type="IssueArticleCount">19</identifier>
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<date>2011</date>
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