The Analysis of Hepatitis B Virus Precore/core Mutations Arising in Different States of Infection

Abstract Background: In hepatitis B virus (HBV) infection, an association between Precore/Core variations and liver disease progression has been suggested. In this study, we aimed to determine the frequency of Precore/Core mutations in HBV-infected patients at various clinical stages. Methods: Totally, 73 HBV-infected patients including 26 inactive carriers, 20 chronic active and 27 patients with liver cirrhosis/hepatocellular carcinoma were randomly selected. The HBV DNA was extracted from the sera and subjected to nested PCR for amplification of pre-core/core region. The PCR product was then sequenced by Sanger method. Results: The stop codon of W/*28 was determined as the most prevalent mutation (55%) of pre-core region. The comparison of groups also demonstrated that core substitutions at residues of S21, E40 and I105 (<0.05) correlated with the development of inactive carrier state. Furthermore, the total substitutions in Th epitopes (117-131) were significantly higher in C/HCC group than IC and CA groups (P=0.001). Conclusion: Our results indicated a high frequency of W/*28 mutation in HBV studied patients. Moreover, variations including S21, E40 and I105 and R151 that were mapped onto cellular epitopes might be related to inactive state development.

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Expression of hepatitis B viral core region in mammalian cells

Molecular and Cellular Biology ◽

10.1128/mcb.6.5.1393-1400.1986 ◽

1986 ◽

Vol 6 (5) ◽

pp. 1393-1400

Author(s):

M J Roossinck ◽

S Jameel ◽

S H Loukin ◽

A Siddiqui

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Mammalian Cells ◽

Expression System ◽

Core Region ◽

Core Antigen ◽

Northern Blot Hybridization ◽

The Core ◽

B Virus ◽

Nuclease Mapping

We studied the expression of the core region of the hepatitis B virus genome in mammalian cells with recombinant plasmid vectors. Stably transformed rat fibroblast cell lines were established by transfection with vectors containing subgenomic and genome-length hepatitis B virus DNA, followed by G418 selection. The RNA transcripts directed by the core region were characterized by Northern blot hybridization and S1 nuclease mapping. Using the chloramphenicol acetyltransferase gene expression system, the promoter activity located upstream of the core open reading frame was confirmed. The synthesis of core and e polypeptides was studied with a commercial radioimmunoassay. These studies show that partial deletion of the precore sequences abolished secretion of the e antigen, but there was pronounced synthesis of the core antigen in transfected cells.

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Precore/core region mutations of hepatitis B virus related to clinical severity

World Journal of Gastroenterology ◽

10.3748/wjg.v22.i17.4287 ◽

2016 ◽

Vol 22 (17) ◽

pp. 4287 ◽

Cited By ~ 18

Author(s):

Hong Kim ◽

Seoung-Ae Lee ◽

Seung Yeon Do ◽

Bum-Joon Kim

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Core Region ◽

Clinical Severity ◽

B Virus

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DETECTION OF HEPATITIS B VIRUS DNA IN LIVER AND SERUM: A DIRECT APPRAISAL OF THE CHRONIC CARRIER STATE

The Lancet ◽

10.1016/s0140-6736(81)90182-3 ◽

1981 ◽

Vol 318 (8250) ◽

pp. 765-768 ◽

Cited By ~ 237

Author(s):

Christian Brechot ◽

Jacques Scotto ◽

Patrick Charnay ◽

Michelle Hadchouel ◽

Francoise Degos ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Carrier State ◽

Hepatitis B Virus Dna ◽

B Virus ◽

Chronic Carrier

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Novel Genetic Variants of Hepatitis B Virus in Fulminant Hepatitis

Journal of Pathogens ◽

10.1155/2017/1231204 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Jack Bee Chook ◽

Yun Fong Ngeow ◽

Kok Keng Tee ◽

Suat Cheng Peh ◽

Rosmawati Mohamed

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Predictive Value ◽

Fulminant Hepatitis ◽

Predictive Accuracy ◽

Stop Codon ◽

Acute Infection ◽

Support Vector ◽

Svm Model ◽

B Virus

Fulminant hepatitis (FH) is a life-threatening liver disease characterised by intense immune attack and massive liver cell death. The common precore stop codon mutation of hepatitis B virus (HBV), A1896, is frequently associated with FH, but lacks specificity. This study attempts to uncover all possible viral nucleotides that are specifically associated with FH through a compiled sequence analysis of FH and non-FH cases from acute infection. We retrieved 67 FH and 280 acute non-FH cases of hepatitis B from GenBank and applied support vector machine (SVM) model to seek candidate nucleotides highly predictive of FH. Six best candidates with top predictive accuracy, 92.5%, were used to build a SVM model; they are C2129 (85.3%), T720 (83.0%), Y2131 (82.4%), T2013 (82.1%), K2048 (82.1%), and A2512 (82.1%). This model gave a high specificity (99.3%), positive predictive value (95.6%), and negative predictive value (92.1%), but only moderate sensitivity (64.2%). We successfully built a SVM model comprising six variants that are highly predictive and specific for FH: four in the core region and one each in the polymerase and the surface regions. These variants indicate that intracellular virion/core retention could play an important role in the progression to FH.

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Prolonged and biphasic acute hepatitis A in hepatitis B virus carrier

Italian Journal of Medicine ◽

10.4081/itjm.2016.571 ◽

2016 ◽

Vol 10 ◽

Cited By ~ 1

Author(s):

Elena Garlatti Costa ◽

Michela Ghersetti ◽

Silvia Grazioli ◽

Pietro Casarin

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Acute Hepatitis ◽

Hepatitis A ◽

Hepatitis A Virus ◽

Inactive Carrier ◽

B Virus ◽

Acute Hepatitis A ◽

Hepatitis B Virus Carrier ◽

Life Threatening

Acute hepatitis A is generally a self-limited disease in healthy subjects within few weeks, but an uncommon type of prolonged and biphasic acute course of hepatitis A infection has been also described. This type of presentation is observed in about 6-10% of patients, but a small number of reports, concerning this topic, are available in literature. In addition hepatitis A virus (HAV) infection in hepatitis B virus (HBV) carriers has rarely been discussed. A 41-year-old Italian man, already known to our Department for HBV infection as an inactive carrier HBsAg(+)ve, experienced a prolonged and biphasic course of acute hepatitis A, lasting about 7 months. In this patient possible factors, causing the second flare of transaminases, were excluded (in particular autoimmunity). Liver biopsy as well HAV RNA search in blood/stools were not performed. In conclusion, the hepatologist should take into account this type of atypical course in patients with HAV-related hepatitis and should promote HAV vaccination in subjects with HBV-chronic hepatitis, to prevent possible life-threatening acute exacerbation of hepatic damage, mainly in HBV-carriers with more severe forms of liver diseases.

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