A Complete Genomic Analysis of Hepatitis B Virus Genotypes and Mutations in HBeAg-Negative Chronic Hepatitis B in China

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FULL TEXT:http://www.medscape.com/viewarticle/579280?src=mp & spon=20 & uac=31238BR

From Journal of Viral Hepatitis

A Complete Genomic Analysis of Hepatitis B Virus Genotypes and Mutations in

HBeAg-Negative Chronic Hepatitis B in China

Posted 09/10/2008

L. Zhu; C.H. Tse; V.W.S. Wong; A.M.L. Chim; K.S. Leung; H.L.Y. Chan

Summary and Introduction

Summary

We aimed to study the distribution of hepatitis B virus (HBV)

genotypes/subgenotypes in different parts of China and their clinical impact on

the severity of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B.

Residual serum samples from a cohort of HBeAg-negative chronic hepatitis B

patients in Hong Kong, Shanghai and Beijing were studied. Complete HBV genomic

sequencing was performed for phylogenetic tree analysis and determination of HBV

mutations was carried out. Mutations associated with severe liver fibrosis

(Ishak score 4 or more) were selected by computerized information gain criteria.

Genotype B (all subgenotype Ba) HBV was present in 19 of 45 (42%), 12 of 31

(39%) and 5 of 25 (20%) patients in Hong Kong, Shanghai and Beijing,

respectively (P = 0.16). Ninety-seven per cent of genotype C HBV in Shanghai and

Beijing belonged to subgenotype Ce whereas 69% of genotype C patients in Hong

Kong belonged to subgenotype Cs (P < 0.001). Patients infected by subgenotype Cs

had the lowest serum albumin and highest alanine aminotransferase levels

compared with subgenotype Ce and Ba. Patients infected by subgenotype Cs also

had more severe histological necroinflammation than subgenotype Ce. Two HBV

mutations were identified to associate with severe liver fibrosis (G2858C and

C2289A) and one mutation was protective against severe liver fibrosis (T2201C).

The T2201C mutation was found exclusively among patients (21 of 46 patients,

45%) infected by HBV subgenotype Ce. The clinical differences in HBeAg-negative

chronic hepatitis B in China may be influenced by different distribution of

subgenotype C HBV.

Introduction

Spontaneous hepatitis B e antigen (HBeAg) seroconversion is usually regarded as

successful immune clearance of hepatitis B virus (HBV).[1] However,

HBeAg-negative chronic hepatitis B has been associated with liver cirrhosis and

hepatocellular carcinoma (HCC).[2–5] Patients suffering from HBeAg-negative

active liver disease are believed to have abortive immune clearance of the

virus.[6] In Asia, approximately 15% of patients are suffering from

HBeAg-negative chronic active hepatitis.[7] The precore stop codon mutation (G

to A at nucleotide 1896, G1896A) and basal core promoter mutations (mutations A

to T at nucleotide 1762 and G to A nucleotide 1764; A1762T and G1764A) are

associated with HBeAg loss, but their clinical significance in disease activity

in HBeAg-negative chronic hepatitis B is controversial.[8–10] Basal core

promoter mutations as well as mutations at other sites of the HBV genome (at

nucleotides 1485, 1653 and 1753) have been described to associate with the

development of HCC.[11,12] Whether these mutations are associated with more

severe liver disease in HBeAg-negative chronic hepatitis B is uncertain.

Hepatits B Virus can be classified into eight genotypes (A–H) based on a 8%

nucleotide sequence difference in the whole viral genome.[13] In Asia, HBV

genotype B and C are the predominant genotypes and HBV genotype C is associated

with more severe liver disease,[14–17] delayed HBeAg seroconversion[18] and a

high risk of HCC.[19,20] Within each HBV genotype, subgenotypes have been

identified based on a 4–8% difference in the complete nucleotide sequence. These

HBV subgenotypes may have differences in terms of prevalence of HBeAg and HCC

development.[12,21,22] In China, the majority of genotype B HBV belongs to the

subgenotype Ba and two subgenotypes, namely, Cs and Ce have been described in

HBV genotype C.[23,24]

As different geographical regions have different HBV genotypes/subgenotypes, we

aimed to study the distribution of different HBV genotypes/subgenotypes based on

a cohort of HBeAg-negative patients from three different parts of China

(Beijing, Shanghai and Hong Kong). We also investigated the impact of HBV

genotype/subgenotype and HBV mutations on the severity of HBeAg-negative chronic

hepatitis B in these patients.

[Guest guest]

FULL TEXT:http://www.medscape.com/viewarticle/579280?src=mp & spon=20 & uac=31238BR

From Journal of Viral Hepatitis

A Complete Genomic Analysis of Hepatitis B Virus Genotypes and Mutations in

HBeAg-Negative Chronic Hepatitis B in China

Posted 09/10/2008

L. Zhu; C.H. Tse; V.W.S. Wong; A.M.L. Chim; K.S. Leung; H.L.Y. Chan

Summary and Introduction

Summary

We aimed to study the distribution of hepatitis B virus (HBV)

genotypes/subgenotypes in different parts of China and their clinical impact on

the severity of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B.

Residual serum samples from a cohort of HBeAg-negative chronic hepatitis B

patients in Hong Kong, Shanghai and Beijing were studied. Complete HBV genomic

sequencing was performed for phylogenetic tree analysis and determination of HBV

mutations was carried out. Mutations associated with severe liver fibrosis

(Ishak score 4 or more) were selected by computerized information gain criteria.

Genotype B (all subgenotype Ba) HBV was present in 19 of 45 (42%), 12 of 31

(39%) and 5 of 25 (20%) patients in Hong Kong, Shanghai and Beijing,

respectively (P = 0.16). Ninety-seven per cent of genotype C HBV in Shanghai and

Beijing belonged to subgenotype Ce whereas 69% of genotype C patients in Hong

Kong belonged to subgenotype Cs (P < 0.001). Patients infected by subgenotype Cs

had the lowest serum albumin and highest alanine aminotransferase levels

compared with subgenotype Ce and Ba. Patients infected by subgenotype Cs also

had more severe histological necroinflammation than subgenotype Ce. Two HBV

mutations were identified to associate with severe liver fibrosis (G2858C and

C2289A) and one mutation was protective against severe liver fibrosis (T2201C).

The T2201C mutation was found exclusively among patients (21 of 46 patients,

45%) infected by HBV subgenotype Ce. The clinical differences in HBeAg-negative

chronic hepatitis B in China may be influenced by different distribution of

subgenotype C HBV.

Introduction

Spontaneous hepatitis B e antigen (HBeAg) seroconversion is usually regarded as

successful immune clearance of hepatitis B virus (HBV).[1] However,

HBeAg-negative chronic hepatitis B has been associated with liver cirrhosis and

hepatocellular carcinoma (HCC).[2–5] Patients suffering from HBeAg-negative

active liver disease are believed to have abortive immune clearance of the

virus.[6] In Asia, approximately 15% of patients are suffering from

HBeAg-negative chronic active hepatitis.[7] The precore stop codon mutation (G

to A at nucleotide 1896, G1896A) and basal core promoter mutations (mutations A

to T at nucleotide 1762 and G to A nucleotide 1764; A1762T and G1764A) are

associated with HBeAg loss, but their clinical significance in disease activity

in HBeAg-negative chronic hepatitis B is controversial.[8–10] Basal core

promoter mutations as well as mutations at other sites of the HBV genome (at

nucleotides 1485, 1653 and 1753) have been described to associate with the

development of HCC.[11,12] Whether these mutations are associated with more

severe liver disease in HBeAg-negative chronic hepatitis B is uncertain.

Hepatits B Virus can be classified into eight genotypes (A–H) based on a 8%

nucleotide sequence difference in the whole viral genome.[13] In Asia, HBV

genotype B and C are the predominant genotypes and HBV genotype C is associated

with more severe liver disease,[14–17] delayed HBeAg seroconversion[18] and a

high risk of HCC.[19,20] Within each HBV genotype, subgenotypes have been

identified based on a 4–8% difference in the complete nucleotide sequence. These

HBV subgenotypes may have differences in terms of prevalence of HBeAg and HCC

development.[12,21,22] In China, the majority of genotype B HBV belongs to the

subgenotype Ba and two subgenotypes, namely, Cs and Ce have been described in

HBV genotype C.[23,24]

As different geographical regions have different HBV genotypes/subgenotypes, we

aimed to study the distribution of different HBV genotypes/subgenotypes based on

a cohort of HBeAg-negative patients from three different parts of China

(Beijing, Shanghai and Hong Kong). We also investigated the impact of HBV

genotype/subgenotype and HBV mutations on the severity of HBeAg-negative chronic

hepatitis B in these patients.