Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic infection of hepatitis B virus (HBV) is one of the major causes of hepatocellular carcinoma (HCC) in the world. The hepatitis B virus X protein (HBx) is implicated in HCC development, although its oncogenic role remains controversial. HBx is a multifunctional regulator that modulates transcription, signal transduction, cell cycle progress, and DNA repair by directly or indirectly interacting with host factors. We constructed the HBx stably expressing HepG2 cell line to investigate the impact of HBx on intra-S-phase checkpoint induced by mitomycin C (MMC). The HBx transformed HepG2 cells are more sensitive to MMC treatment and showed defective radioresistant DNA synthesis compared to the control cell line transformed with empty vector. With DNA content assay, HBx transformed cells showed defective S phase arrest and a consequent G2/M arrest after MMC treatment. HBx impaired the ATR dependent phosphorylation of Chk1 and monoubiquitination of FANCD2. Overexpression of ATR reverted the MMC induced phenotype of Chk1 and FANCD2 in HBx transformed cells. The defect of intra-S-phase checkpoint resulted in accumulation of genomic instability. In conclusion, HBx disrupts intra-S-phase checkpoint induced by MMC through ATR-Chk1 and ATR-FANCD2 pathways.
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PMID:Hepatitis B virus X protein disrupts DNA interstrand crosslinking agent mitomycin C induced ATR dependent intra-S-phase checkpoint. 1849 7

Chronic infection with hepatitis B virus can lead to liver disease, cirrhosis, and hepatocellular carcinoma. Treatment options include interferons and antiviral drugs. The interferons have immunomodulatory, antiproliferative, and antiviral effects. Nucleoside analogs, such as entecavir, lamivudine and telbivudine, and neucleotide analogs, such as adefovir and tenofovir, exhibit antiviral effects by inhibiting viral replication. Treatment is directed at suppressing viral replication and halting the progression of disease.
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PMID:Pharmacotherapy of hepatitis B infection: a brief review. 1885 82

Chronic infection with the hepatitis B virus (HBV) is a major cause of morbidity and mortality worldwide, necessitating accurate and timely diagnosis of infected patients coupled with optimal treatment strategies. Although the prevalence of HBV infection in the United States is low owing to the implementation of universal vaccination, growing immigration from areas where infection is more endemic means that prevalence is forecast to increase. Healthcare providers must be active in providing low-cost screening (hepatitis B surface antigen identification) and vaccination programs for high-risk communities, such as Asian Americans, with linked specialist referral schemes for patients found to carry the virus. Serologic technologies and improved nucleic acid testing techniques generate important information about the stage of disease, viral load, and disease subtype, including the presence of precore and core promoter variants that provide prognostic indicators and can guide patient management. Serial DNA monitoring is playing the major role in the assessment of therapeutic response and steering treatment approaches. More research is needed to further clarify the significance of HBV variants and their relation to therapeutic agents and strategies.
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PMID:Diagnosis of chronic hepatitis B and the implications of viral variants and mutations. 1918 70

Currently, >350 million people worldwide are affected by chronic infection with the hepatitis B virus (HBV). Chronic infection may cause cirrhosis and hepatocellular carcinoma; HBV infection is responsible for 328,000 cancer deaths per year. In areas of high HBV endemicity, most infections occur early in life; infected children do not mount an effective immune response and exhibit immune tolerance, so that the risk of chronic infection is high. In areas of low endemicity, infections tend to be in adults within defined risk groups, and the risk of chronicity is much lower. Population migration from areas of high endemicity to areas of low endemicity is creating pockets of HBV infection in areas of low general prevalence, necessitating improved efforts to screen, vaccinate, and treat. Chronic HBV infection is a complicated, nonlinear disease with a variable course of progression; predictors of progression include the duration of time in the immunoactive phase of disease that follows the immune tolerant phase when hepatocytes are attacked. Additionally, the duration of a high viremic state, with ongoing clinical hepatitis and possibly concurrent infections (e.g., hepatitis C, human immunodeficiency virus), influence outcome. Targeted vaccination of high-risk groups has many limitations. Universal childhood vaccination to prevent chronic infection and its sequelae is the only approach that will lead to the global elimination of chronic HBV infection.
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PMID:Demography and presentation of chronic hepatitis B virus infection. 1918 72

Chronic infection with the hepatitis B virus (HBV) is the most important risk factor for hepatocellular carcinoma (HCC). However, determinants of HCC risk in infected individuals are not well understood. We prospectively evaluated the association between acquired HBV 1762(T)/1764(A) double mutations and HCC risk among 49 incident HCC cases and 97 controls with seropositive hepatitis B surface antigen at baseline from a cohort of 18,244 men in Shanghai, China, enrolled during 1986 to 1989. Compared with HBV carriers without the mutations, chronic HBV carriers with the HBV 1762(T)/1764(A) double mutations experienced an elevated risk of HCC (odds ratio, 2.47; 95% confidence interval, 1.04-5.85; P = 0.04). Risk increased with increasing copies of the double mutations; men with > or =500 copies/microL serum had an odds ratio of 14.57 (95% confidence interval, 2.41-87.98) relative to those without the double mutations (P(trend) = 0.004). Thus, the HBV 1762(T)/1764(A) double mutation is a codeterminant of HCC risk for people chronically infected with HBV.
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PMID:Prospective evaluation of hepatitis B 1762(T)/1764(A) mutations on hepatocellular carcinoma development in Shanghai, China. 1919 Jan 66

Chronic infection with the hepatitis B virus has been linked epidemiologically to the development of hepatocellular carcinoma for more than 30 years. Although the mechanisms by which chronic hepatitis B viral infection results in hepatocellular carcinoma are unclear, there is good evidence that the virus itself exerts a direct hepatocarcinogenic effect, and this has implications for prevention. First, programs of universal infant vaccination have been shown to be effective in reducing the rate of hepatocellular carcinoma among children. This benefit should be translated into adulthood among vaccine recipients. Second, it has been suggested that antiviral therapy against hepatitis B may reduce the risk of hepatocellular carcinoma. Antiviral therapy against hepatitis B is effective in causing prolonged lowering of serum levels of hepatitis B virus DNA. There are emerging data showing that prolonged antiviral therapy may reduce the risk of hepatocellular carcinoma among certain patients with chronic hepatitis B.
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PMID:Hepatitis B and hepatocellular carcinoma. 1939 7

Chronic infection with hepatitis B virus (HBV) is an important cause of cirrhosis and cancer of the liver. HBV is currently classified into eight genotypes, A to H. Accumulated evidence shows that the genotype influences both the clinical course of infection and the response to treatment. We describe a new method for genotyping based on TaqMan real-time PCR, which identifies all HBV genotypes without post-PCR processing. In this assay, each sample is processed in four multiplex real-time PCRs, each targeting two or three genotype-specific segments of HBV. By analyzing 185 samples representing all genotypes and different proportions of genotype mixtures, we could validate high accuracy of the assay. We conclude that this new assay represents a significant advancement for both diagnostics and clinical research because it is accurate, practical, and based on a technique that is well established in many virological laboratories.
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PMID:Novel method for genotyping hepatitis B virus on the basis of TaqMan real-time PCR. 2010 90

Chronic infection with hepatitis B virus (HBV) is strongly associated with hepatocellular carcinoma (HCC), and the viral HBx protein plays a crucial role in the pathogenesis of liver tumors. Because the protooncogene pituitary tumor-transforming gene 1 (PTTG1) is overexpressed in HCC, we investigated the regulation of this protein by HBx. We analyzed PTTG1 expression levels in liver biopsies from patients chronically infected with HBV, presenting different disease stages, and from HBx transgenic mice. PTTG1 was undetectable in biopsies from chronic hepatitis B patients or from normal mouse livers. In contrast, hyperplastic livers from transgenic mice and biopsies from patients with cirrhosis, presented PTTG1 expression which was found mainly in HBx-expressing hepatocytes. PTTG1 staining was further increased in HCC specimens. Experiments in vitro revealed that HBx induced a marked accumulation of PTTG1 protein without affecting its messenger RNA levels. HBx expression promoted the inhibition of PTTG1 ubiquitination, which in turn impaired its degradation by the proteasome. Glutathione S-transferase pull-down and co-immunoprecipitation experiments demonstrated that the interaction between PTTG1 and the Skp1-Cul1-F-box ubiquitin ligase complex (SCF) was partially disrupted, possibly through a mechanism involving protein-protein interactions of HBx with PTTG1 and/or SCF. Furthermore, confocal analysis revealed that HBx colocalized with PTTG1 and Cul1. We propose that HBx promotes an abnormal accumulation of PTTG1, which may provide new insights into the molecular mechanisms of HBV-related pathogenesis of progressive liver disease leading to HCC development.
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PMID:Expression of pituitary tumor-transforming gene 1 (PTTG1)/securin in hepatitis B virus (HBV)-associated liver diseases: evidence for an HBV X protein-mediated inhibition of PTTG1 ubiquitination and degradation. 2019 33

The increase in immigration from less developed countries to Europe has led to an increase in the incidence of hepatitis B infection. The objective of this study was to describe the clinical, epidemiological characteristics and indications for treatment of chronic hepatitis B in a cohort of immigrants, given the relative lack of current evidence. We performed a noninterventional retrospective chart review; different characteristics depending on geographical origin were compared. A case-control study was also performed to describe factors potentially associated with chronic or past hepatitis B virus (HBV) infection. We selected a random sample of 436 patients out of the 2989 immigrants attending during the study period (1989-2008). Hepatitis B serology was performed in 74% (322/436): 10.6% had chronic HBV infection (95% CI: 7.4-13.7%), and 46.9% had evidence of past infection (95% CI: 41.7-52.0%). The average age was 31 years, 60% were men, and 70% were sub-Saharan Africans. Chronic infection was related to being men (OR 2.03; 95%CI: 1.29-3.18), younger (OR 0.98; 0.96-0.99) and sub-Saharan African (OR 5.41; 2.71-10.83). Past or current infection was related to male sex (OR 2.80; 1.81-4.30), longer time elapsed until first seen at the unit (OR 0.998; 0.997-1.000), HIV infection (OR 4.99; 1.15-21.60) and being sub-Saharan African (OR 15.46; 8.97-27.18). These associations were not confirmed after adjustment for geographical origin. In 27% and 29.5% of patients, liver biopsy and treatment, respectively, would have been indicated. Prevalence of chronic HBV infection amongst immigrants is high, especially in sub-Saharan Africans. Almost a third could be considered for liver biopsy or antiviral therapy.
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PMID:Clinical, epidemiological characteristics and indications for liver biopsy and treatment in immigrants with chronic hepatitis B at a referral hospital in Madrid. 2036 91

Chronic infection with hepatitis B virus (HBV) occurs in approximately 6% of the world's population and carriers of the virus are at risk for hepatocellular carcinoma and cirrhosis. Current treatment regimens, which include interferon-alpha and nucleoside/nucleotide analogs, are only partially effective and new treatment methods remain an important objective. Harnessing the RNA interference (RNAi) pathway to achieve post-transcriptional silencing of rogue genetic elements is an exciting avenue for development of novel therapeutic strategies. The specific and potent suppression of HBV gene expression and replication is an attractive option as a novel and effective approach for the treatment of chronic HBV infection. However, despite significant and rapid progress, existing RNAi technologies require further refinement before clinical applications can be realized. Here, we review current efforts aimed at improving the efficiency of anti-HBV RNAi-based delivery systems, at limiting the toxicities associated with RNAi modalities and at preventing reactivation of viral replication. We discuss the progress towards clinical implementation of anti-HBV RNAi therapies.
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PMID:Progress in the use of RNA interference as a therapy for chronic hepatitis B virus infection. 2042 60


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