Influence of hepatitis B virus genotypes on the development of preS deletions and advanced liver disease

Sugauchi, Fuminaka; Ohno, Tomoyoshi; Orito, Etsuro; Sakugawa, Hiroshi; Ichida, Takafumi; Komatsu, Masafumi; Kuramitsu, Tomoyuki; Ueda, Ryuzo; Miyakawa, Yuzo; Mizokami, Masashi

doi:10.1002/jmv.10428

Cited by 100 publications

(129 citation statements)

References 37 publications

(59 reference statements)

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“…Our study showed a significantly higher rate of pre-S2 deletions in the children of the HCC group than in the group with chronic HBV infection. The meaning of our results is unique and not merely in agreement with the studies in adults, because we found that pre-S2 deletions in HBV genomes did not necessarily take decades to accumulate, as in adult patients with advanced liver diseases (1,(15)(16)(17)(18)(19)(20)(21)(22); they emerged in nearly half of the young children with HBV-related HCC that developed in a relatively short period of time.…”

Section: Discussionsupporting

confidence: 68%

Pre-S2 Deletions of Hepatitis B Virus and Hepatocellular Carcinoma in Children

et al. 2010

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ABSTRACT:The cause of early oncogenesis in hepatitis B virus (HBV)-related childhood hepatocellular carcinoma (HCC) remains unclear. This study investigated whether pre-S deletion of HBV is related to childhood HCC. By using nested polymerase chain reaction, we compared the pre-S sequence of HBV from sera of children with HCC against control children with similar chronic HBV infection. The HBV in sera of children with HCC had a significantly higher rate of pre-S deletion than that of children with chronic HBV infection (p ϭ 0.008). All except one of the pre-S deletions from the HCC group involved the pre-S2 region, whereas no pre-S2 deletion was found in the chronic HBV group (p ϭ 0.003). There was a trend whereby genotype-C sera had a higher rate of pre-S2 deletion than genotype-B sera (p ϭ 0.11). A multivariate logistic regression model revealed that pre-S deletion was an independent risk factor for HCC in children (odds ratio: 36.69, p ϭ 0.015). In conclusion, pre-S2 deletion does not need to take decades to occur; its presence in nearly half of children with HCC, in contrast to its absence in children with chronic HBV infection, suggests a link between pre-S2 deletion and HCC development in children. (Pediatr Res 67: 90-94, 2010)

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Section: Discussionsupporting

confidence: 68%

Pre-S2 Deletions of Hepatitis B Virus and Hepatocellular Carcinoma in Children

et al. 2010

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“…4) when a part of the CURS/CP of the wild-type HBV/E replication clone was replaced by the HNF1 binding tandem repeat of UK2. Pre-S deletion is observed in cases of long-lasting HBV chronic infection and advanced liver diseases (27,37). As the positions and lengths of pre-S deletions differ in each case, their effects on HBV replication have not been clearly elucidated.…”

Section: Discussionmentioning

confidence: 99%

Novel Type of Hepatitis B Virus Mutation: Replacement Mutation Involving a Hepatocyte Nuclear Factor 1 Binding Site Tandem Repeat in Chronic Hepatitis B Virus Genotype E

Fujiwara

Tanaka²,

Paulon

et al. 2005

J Virol

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The genetic diversity of hepatitis B virus (HBV) strains has evolved through mutations such as point mutations, deletions or insertions, and recombination. We identified and characterized a novel type of mutation which is a complex of external insertion, deletion, and internal duplication in sequences from one of six patients with chronic hepatitis B virus genotype E (HBV/E). We provisionally named this mutation a "replacement mutation"; the core promoter upstream regulatory sequence/basic core promoter was replaced with a part of the S1 promoter covering the hepatocyte nuclear factor 1 (HNF1) binding site, followed by a tandem repeat of the HNF1 site. A longitudinal analysis of the HBV population over 6 years showed the clonal change from wild-type HBV/E to replacement-mutant type, resulting in a lower hepatitis B (HB) e antigen titer, a high HBV DNA level in serum, and progression of liver fibrosis. In an in vitro study using a replication model, the replacement-mutant HBV showed higher replication levels than the wild-type HBV/E replicon, probably mediated by altered transcription factor binding. Additionally, this HNF1 site replacement mutation was associated with excessive HB nucleocapsid protein expression in hepatocytes, in both in vivo and in vitro studies. This novel mutation may be specific to HBV genotype E, and its prevalence requires further investigation.

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“…The deletion over pre-S gene may affect the expression of middle and small surface proteins, resulting in intracellular accumulation of large surface protein [86], and contribute to more progressive liver cell damage and finally hepatocarcinogenesis [87,88]. In our recent case-control study, pre-S deletion mutant of HBV were determined in 202 asymptomatic carriers and 64 HCC patients with chronic HBV genotype B or C infection.…”

Section: Naturally Occurring Mutantsmentioning

confidence: 99%

Role of viral factors in the natural course and therapy of chronic hepatitis B

Kao

2007

Hepatol Int

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Hepatitis B virus (HBV) infection is a global health problem that causes a wide spectrum of liver disease, including acute or fulminant hepatitis, inactive carrier state, chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis of hepatocyte damage associated with HBV is mainly through immune-mediated mechanisms. On the basis of the virus and host interactions, the natural history of HBV carriers who are infected in early life can be divided into four dynamic phases. The frequency, extent, and severity of hepatitis flares or acute exacerbation in the second immune clearance and/or fourth reactivation phase predict liver disease progression in HBV carriers. In the past decade, hepatitis B viral factors including serum HBV DNA level, genotype, and naturally occurring mutants predictive of clinical outcomes have been identified. The higher the serum HBV DNA level after the immune clearance phase, the higher the incidence of adverse outcomes over time. In addition, high viral load, genotype C, basal core promoter mutation, and pre-S deletion correlate with increased risk of cirrhosis and HCC development. As to the treatment of chronic hepatitis B, patients with high HBV DNA level and genotype C or D infection are shown to have a worse response to interferon therapy. In conclusion, serum HBV DNA level, genotype, and naturally occurring mutants are identified to influence liver disease progression and therapy of chronic hepatitis B. More investigations are needed to clarify the molecular mechanisms of the viral factors involved in the pathogenesis of each stage of liver disease and the response to antiviral treatments.

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Influence of hepatitis B virus genotypes on the development of preS deletions and advanced liver disease

Cited by 100 publications

References 37 publications

Pre-S2 Deletions of Hepatitis B Virus and Hepatocellular Carcinoma in Children

Pre-S2 Deletions of Hepatitis B Virus and Hepatocellular Carcinoma in Children

Novel Type of Hepatitis B Virus Mutation: Replacement Mutation Involving a Hepatocyte Nuclear Factor 1 Binding Site Tandem Repeat in Chronic Hepatitis B Virus Genotype E

Role of viral factors in the natural course and therapy of chronic hepatitis B

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