Analysis of the precore DNA sequence and detection of precore antigen in liver specimens from patients with anti-hepatitis b e—positive chronic hepatitis

Dienes, Hans Peter; Gerken, Guido; Goergen, Bernd; Heermann, Klaus-Hinrich; Gerlich, Wolfram H.; Büschenfelde, K H Meyer zum

doi:10.1002/hep.1840210102

Cited by 15 publications

(18 citation statements)

References 26 publications

(7 reference statements)

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“…The precore and basic core promoter (BCP) genetic variations of HBV lead to HBeAg loss and anti-HBe seroconversion [4, 29]. Principally, the stop codon mutation at base 1896 creates the truncated precore peptide that might represents an adaptation to immune pressure [30]. The function of innate immune response as the first line of defense against virus infection as well as its cooperation with adaptive immunity may induce the development of precore mutant variants of HBV [11, 31, 32].…”

Section: Discussionmentioning

confidence: 99%

The Possible Role of TLR2 in Chronic Hepatitis B Patients with Precore Mutation

Moradzadeh

Tayebi

Sayehmiri

et al. 2013

Advances in Virology

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Recognition mechanisms of innate immune response help to improve immunotherapeutic strategies in HBeAg-negative chronic hepatitis B (CHB). Toll-like receptor 2 (TLR2) is an important component of innate immunity. In this study, the frequency of precore mutations of the hepatitis B virus (HBV) and serum TLR2 were evaluated in CHB patients. Fifty-one patients with chronic hepatitis B, negative for HBeAg and detectable HBV DNA, were examined for the presence of mutations in pre-core region of HBV genome by direct sequencing. Serum TLR2 was measured by enzyme-linked immunosorbent assay. Interactions of truncated HBeAg and TLR2 proteins were evaluated with molecular docking software. The G1896A pre-core mutation were detected in 29 (57%) which was significantly associated with higher concentration of serum TLR2 in comparison with patients without this mutation (4.8 ± 2.9 versus 3.4 ± 2.2 ng/mL, P = 0.03). There was also a significant correlation between serum ALT and TLR-2 (r = 0.46; P = 0.01). Docking results illustrated residues within the N-terminus of truncated HBeAg and TLR2, which might facilitate the interaction of these proteins. These findings showed the dominance of G1896A pre-core mutation of HBV variants in this community which was correlated with serum TLR2. Moreover TLR2 is critical for induction of inflammatory cytokines and therefore ALT elevation.

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Section: Discussionmentioning

confidence: 99%

The Possible Role of TLR2 in Chronic Hepatitis B Patients with Precore Mutation

Moradzadeh

Tayebi

Sayehmiri

et al. 2013

Advances in Virology

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“…Summary of the precore and core protein processing pathways and their possible inter-relationship inside the hepatocyte. Note cleavage and transport of P25 sub-unit as outlined in Dienes et al (1995) and the P22 protein (Lainé et al, 2003). a ubiquitin-specific protease, a ubiquitin binding protein, a mitochondrial translocase, a transporter for the calcitonin receptor, a pro-apoptiticBc1-2 binding protein and a caspase homologue all point to a role for the P22-gC1qR interaction in regulation of mitochondrially-mediated apoptosis (Lainé et al, 2003).…”

Section: Discussionmentioning

confidence: 97%

“…The HBeAg is the major product of the pre C-C gene. The HBeAg is initially translated as a 25 kDa protein (the precore protein) and during translocation of the nascent polypeptide into the lumen of the endoplasmic reticulum (ER), its signal sequence is cleaved (Dienes et al, 1995), generating P22, which is further truncated at its C-terminal end by a cellular furin protease (Messageot et al, 2003) before secretion from the cell as HBeAg.…”

Section: Introductionmentioning

confidence: 99%

Cellular response to conditional expression of the hepatitis B virus precore and core proteins in cultured hepatoma (Huh-7) cells

Locarnini

Shaw

Dean

et al. 2005

Journal of Clinical Virology

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“…In the absence of the HBeAg, there is an escalated immune response against the HBcAg resulting in a more severe hepatitis [Milich et al, 1990]. Third, the peptide, produced as a result of the stop codon from mutation at nt 1896, in itself may be toxic to the hepatocytes [Dienes et al, 1995].…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B virus reactivation in patients undergoing cytotoxic chemotherapy for solid tumours: Precore/core mutations may play an important role

et al. 2000

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Reactivation of the hepatitis B virus (HBV) is a rare, but well described complication of cytotoxic chemotherapy that may result in hepatic failure. Patients who are chronic carriers of the HBV and who have a G to A mutation at nucleotide 1896 in the precore region may develop more severe liver disease, possibly because of rapid selection and enhanced replication ability of the mutant strain. Such mutant viruses have been implicated occasionally in chemotherapy induced reactivation of hepatitis B virus. In this report, 5 patients with solid tumours were identified to have developed severe hepatitis B virus related liver disease during treatment with cytotoxic agents (with dexamethasone as anti-emetic). All had clinical and serological evidence of reactivation of the HBV. Three patients developed icteric hepatitis; 2 fully recovered, and 1 had died from progressive metastatic disease while recovering from the reactivation. The other two died from progressive liver failure. Direct sequencing of the polymerase chain reaction (PCR) products of the precore (preC) and precore promoter region of the HBV-DNA was carried out on the patients' serum samples taken during the episode of reactivation. In each case, similar mutations (G to A) in nucleotide 1896 of the preC region were found, together with additional mutations in the preC promoter. The present findings suggest that reactivation involving a mutant hepatitis B virus may lead to liver failure, which is possibly more severe than that caused by wild type HBV, and can be triggered by cytotoxic chemotherapy, or the administration of corticosteroids. In Eastern Asia the HBV carriage rate in adults is high. HBV reactivation and severe liver disease during cytotoxic treatment may become a serious and common problem in this region as cytotoxic chemotherapy is more widely used. Patients should be screened routinely for HBsAg in endemic areas of chronic hepatitis B virus infection prior to receiving cytotoxic treatment. The possibility of HBV reactivation should be considered in patients developing liver dysfunction. Patients who are HBeAg negative/Anti-HBe positive, and are suspected to be having an HBV reactivation, should have HBV-DNA levels measured for confirmation as they may carry a mutant HBV.

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Analysis of the precore DNA sequence and detection of precore antigen in liver specimens from patients with anti-hepatitis b e—positive chronic hepatitis

Cited by 15 publications

References 26 publications

The Possible Role of TLR2 in Chronic Hepatitis B Patients with Precore Mutation

The Possible Role of TLR2 in Chronic Hepatitis B Patients with Precore Mutation

Cellular response to conditional expression of the hepatitis B virus precore and core proteins in cultured hepatoma (Huh-7) cells

Hepatitis B virus reactivation in patients undergoing cytotoxic chemotherapy for solid tumours: Precore/core mutations may play an important role

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