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

Hepatitis B and C are diseases characterized by a high global prevalence, complex clinical course and limited efficacy of currently available antiviral therapy. Hepatitis B: local factors have a significant influence not only on the disease prevalence but also on the disease course. Vertical transmission of the infection in the areas of high prevalence results in perinatal infection, which universaly leads to the development of chronic disease. Factors associated with an increased risk of cirrhosis are older age, persistent viremia, coinfection with HCV, HDV and HIV, and consumption of alcohol, while the role of viral genotype is uncertain. Predictors of HCC development in cirrhotic liver are older age, male sex, alcohol abuse, exposure to aflatoxin, coinfection with HCV and HDV, continuously active inflammation, and potentially viral genotype. Survival predictors in cirrhotic patients are age, serum albumin, platelet count and splenomegaly as a reflection of portal hypertension. Hepatitis C: the risk of cirrhosis is low. Risk factors for cirrhosis are infection in older age, alcohol abuse, and coinfection with HBV and HIV. Obesity has negative impact on treatment efficacy.
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PMID:[Factors influencing clinical course of viral hepatitis]. 1638 Dec 33

Eight genotypes (A-H) of hepatitis B virus (HBV) have been identified. However, the impact of different genotypes on the clinical course of hepatitis B infection remains controversial. We investigated the frequency and clinical outcome of HBV genotypes and genotype mixtures in HBV-infected patients from Vietnam, Europe, and Africa. In addition, we analyzed the effects of genotype mixtures on alterations in in vitro viral replication. In Asian patients, seven genotypes (A-G) were detected, with A, C, and D predominating. In European and African patients, only genotypes A, C, D, and G were identified. Genotype mixtures were more frequently encountered in African than in Asian (P = .01) and European patients (P = .06). In Asian patients, the predominant genotype mixtures included A/C and C/D, compared to C/D in European and A/D in African patients. Genotype A was more frequent in asymptomatic compared with symptomatic patients (P < .0001). Genotype C was more frequent in patients with hepatocellular carcinoma (HCC; P = .02). Genotype mixtures were more frequently encountered in patients with chronic hepatitis in comparison to patients with acute hepatitis B (P = .015), liver cirrhosis (P = .013), and HCC (P = .002). Viral loads in patients infected with genotype mixtures were significantly higher in comparison to patients with a single genotype (P = .019). Genotype mixtures were also associated with increased in vitro HBV replication. In conclusion, infection with mixtures of HBV genotypes is frequent in Asia, Africa, and Europe. Differences in the replication-phenotype of single genotypes compared to genotype-mixtures suggest that co-infection with different HBV-genotypes is associated with altered pathogenesis and clinical outcome.
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PMID:Impact of the hepatitis B virus genotype and genotype mixtures on the course of liver disease in Vietnam. 1694 77

The purpose of this study was to compare the clinical features and survival in patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) and hepatitis C virus-related hepatocellular carcinoma (HCV-HCC). A total of 2820 HCC patients were included. The mean age of HBV-HCC patients was 52.5+/-13.4 years, while it was 64.8+/-8.7 years in HCV-HCC patients. The male/female ratio was 7.8 in HBV-HCC, while it was 1.7 in HCV-HCC. The mean alpha-fetoprotein level in HBV-HCC was 11,661+/-22,805 ng/mL, while it was 5079+/-15,005 ng/mL in HCV-HCC. The mean tumour size was 6.4+/-4.1 cm in HBV-HCC, while it was 4.6+/-3.1 cm in HCV-HCC. The median survival was 11.1 months in HBV-HCC, while it was 23.9 months in HCV-HCC. Compared with HBV-HCC patients, HCV-HCC patients were older, had a lower male/female ratio, lower white blood cell count, lower serum albumin level, higher serum ALT level, lower serum alpha-fetoprotein level, smaller tumour size and survived longer.
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PMID:Hepatitis B- and C-related hepatocellular carcinomas yield different clinical features and prognosis. 1692 Mar 52

Chronic hepatitis B is an important public health problem worldwide. In Poland the incidence rate decreased from 40,0 (in the year 1990) to 3,86 (in 2004) per 100,000 inhabitants. The goal of anti-chronic hepatitis B therapy is to prevent the progression of liver disease to cirrhosis which may effect in development of liver failure or HCC. The aims of treatment are: reduction of HBV viral load and normalization of ALT activity. Among HBeAg positive patients important marker is the loss of e antigenemia followed by seroconversion to anti-HBe positivity. Lamivudine is an oral nucleoside analogue with strong antiviral activity against hepatitis B virus. The objective of this study was to analyse the efficacy of lamivudine treatment of chronic hepatitis B patients positive for hepatitis B e antigen (HBeAg). 224 patients were treated in Hospital of Infectious Diseases in Warsaw in the years 2001-2002. Patients were treated for 48 weeks with 100 mg lamivudine once daily (50 mg in case of renal failure). Results obtained at the end of therapy: loss of HBeAg was observed in 33,4% and seroconversion to anti-HBe in 15,1% patients, normalization of ALT activity was noticed in 53,4% patients, inhibition of HBV DNA replication was observed in 37,9% patients. The results are comparable with known randomized clinical trials.
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PMID:[Results of 48 weeks lamivudine treatment of patients with chronic hepatitis B and HBeAg (+)]. 1696 76

Liver cancer is one of the leading causes of cancer death in Mongolia. Since 1982-1986 , when HCC became the most frequent cancer among the Mongolian population, the rate has been increasing continuously. In the period 2000-2005 years 35.3%of all newly registered cancer cases were liver cancers, with an incidence rate of 51.3 per 100,000 population. Compared to the previous 5 year period, the rate increased by 11%. The objective here was to analyze hepatitis B (HBV) and C virus (HCV)-related HCC cases and to evaluate the possibility of tumor marker (AFP) testing for early detection in Mongolia. Sera from a total of 513 patients with chronic liver diseases, liver cirrhosis and HCC were analyzed for liver function (ALAT, ASAT) and hepatitis virus markers (HBsAg, anti-HCV). Sera from 316 patients were also examined for alpha-fetoprotein (AFP) levels. The overall incidence of HBsAg or anti-HCV were very high ( 95.3%) among all patients. Some 33.5% (66/197) of patients with HCC were positive for HBsAg and 45.2% (89/197) for anti-HCV. Moreover, 17.3% ( 34/197) of HCC patients demonstrated co-infection with HBV and HCV. AFP levels were elevated in 4.6% (11/238) and 29.5% (23/78) of chronic hepatitis and cirrhosis patients, respectively. In HCC cases, 84.3% (166) of patients had increased level of AFP ranging from 32 ng/ml to more than 400 ng/ml. We conclude that HBV/HCV infection is the main factor related to development of HCC in Mongolia and that testing for AFP serum levels is a useful tool for early detection and diagnosis.
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PMID:Hepatocellular carcinoma and its early detection by AFP testing in Mongolia. 1705 45

Atiprimod is a novel anticancer and antiangiogenic drug candidate which is currently being evaluated in patients with liver carcinoid and multiple myeloma. In this study, we report that atiprimod selectively inhibited proliferation and induced apoptosis in HCC cells that expressed either hepatitis B virus (HBV) or hepatitis C virus, through deactivation of protein kinase B (Akt) and signal transducers and activators of transcription 3 (STAT3) signaling. In HepG2 AD38 cells, which express HBV genome under the control of a tetracycline-off promoter, both Akt and STAT3 were constitutively activated in response to HBV expression. However, this constitutive activation was not sensitive to lamivudine, a drug that inhibits HBV replication without affecting its gene expression, suggesting that HBV replication per se might not be responsible for the activation. Interestingly, the electrophoretic mobility of p-STAT3 protein bands on immunoblot was slower when AD38 cells were cultured in the absence of tetracycline, suggesting a differential phosphorylation in response to HBV expression. In HCC cells, interleukin 6 stimulates the phosphorylation of STAT3 both at serine 727 and at tyrosine 705 positions. The interleukin 6-stimulated activation of STAT3 and Akt was inhibited not only by atiprimod but also by LY294002, a phosphoinositide-3-kinase-specific inhibitor, and by NS398, a cyclooxygenase-2-selective inhibitor. The combination of these compounds did not produce any additive effect, implying that the mechanisms by which HBV activates Akt and STAT3 might also involve phosphoinositide-3-kinase and cyclooxygenase-2. Collectively, these results suggest that atiprimod could be useful as a multifunctional drug candidate for the treatment of HCC in humans.
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PMID:Deactivation of Akt and STAT3 signaling promotes apoptosis, inhibits proliferation, and enhances the sensitivity of hepatocellular carcinoma cells to an anticancer agent, Atiprimod. 1723 71

To determine the association between polycyclic aromatic hydrocarbon (PAH) exposure and risk of hepatocellular carcinoma, a case-control study nested within a community-based cohort was conducted in Taiwan. Baseline blood samples, collected from a total of 174 HCC cases and 776 matched controls, were used to determine the level of PAH-albumin adducts by competitive enzyme-linked immunosorbent assay. Conditional logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI) to assess the effect of PAH-albumin adducts on risk of HCC. When compared to subjects in the lowest quantile, there was an increase in risk of HCC, with adjusted ORs (95% CI) of 1.0 (0.5-2.0), 1.2 (0.6-2.4) and 2.0 (1.0-4.2: P(trend)=0.08) for subjects in the 2nd, 3rd and 4th quantile, respectively. The corresponding adjusted ORs (95% CI) were 1.9 (0.6-6.1), 1.7 (0.6-4.9) and 2.1 (0.5-8.2; P(trend)=0.22), respectively, among subjects with high AFB(1)-albumin adducts; and 0.8 (0.3-2.7), 1.5 (0.6-3.5) and 2.9 (1.0-8.6; P(trend)=0.06), respectively, for those who were chronically infected with hepatitis B virus (HBV). The combination of PAH- and AFB(1)-albumin adducts above the mean and chronic HBV infection resulted in an OR of 8.2 (95% CI, 3.6-19.0; p<0.0001), compared to those with low adducts and no viral infection. These results demonstrate that PAH-albumin adducts are associated with an increased risk of HCC, especially among those with high aflatoxin exposure and chronic HBV infection. Environmental PAH exposure seems to enhance the hepatocarcinogenicity of chronic HBV infection.
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PMID:Polycyclic aromatic hydrocarbon- and aflatoxin-albumin adducts, hepatitis B virus infection and hepatocellular carcinoma in Taiwan. 1725 Sep 58

It is known that the hepatitis B virus X protein (HBx) plays a crucial role in the pathogenesis of HCC, but the exact functions and molecular mechanisms of HBx in HCC are not well understood. In the present study, HepG2 cell lines were cultured and transfected with pEGFP-N1 and pEGFP-N1-X. Twenty-four hours after transfection, cells were harvested and total RNA was extracted using TRIzol reagent. The expression of HBx in HepG2 cell line was assayed by real-time polymerase chain reaction and was detected by Western blotting. Moreover, proteomic analysis was performed for the HepG2-pEGFP-X cells and HepG2-pEGFP control cells. The combination of 2DE and MALDI-TOF-MS/MS revealed that SEC13L1 (SEC13-like 1 isoform b), PA28 alpha (proteasome activator REG alpha), serine-threonine kinase receptor-associated protein (STRAP) and nm23/nucleoside diphosphate kinase (NME) were upregulated in HepG2-pEGFP-X cells. STRAP is known to be a WD40 domain-containing protein, which interacts with TbetaR-I and TbetaR-II and negatively regulates TGF-beta signalling, was also found increased in human cancers. NME is known to be involved in the regulation of cancer cell progression and metastasis. These results would help the understanding of how HBx maintains tumorigenicity and progression of HCC.
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PMID:The upregulation of expressed proteins in HepG2 cells transfected by the recombinant plasmid-containing HBx gene. 1730 79

The molecular mechanisms underlying hepatitis B virus encoded HBx protein-mediated tumorigenesis are not fully understood. In order to gain a better view of the effects of HBx on transcriptional regulation and hepatocarcinogenesis, the expression profiles of liver and tumor tissues from 6- and 18-month-old p21-HBx transgenic and control mice were monitored using oligo microarrays. Data analysis demonstrated that 42 genes were deregulated in both 6- and 18-month-old HBx transgenic mouse tissues. Gene ontology assisted analysis classified these genes into functionally related clusters that encode proteins related to metabolism, signal transduction, transcription regulation and stress responses. Among them, cytoskeletal genes, including microtubule genes tubulinbeta2 (Tubb2), tubulinbeta3 (Tubb3) and tubulinbeta6 (Tubb6), intermediate filament genes periplakin, keratin 8 (K8) and keratin 18 (K18) and actingamma1 (Actg1), were closely clustered and upregulated in liver tissues. These results were validated by semi-quantitative RT-PCR in both mouse and human HCC tissues. The upregulation of K8 and K18 was only detected in p21-HBx but not p21-HBsAg liver tissues, suggesting that the global change in the expression of cellular cytoskeletal genes was correlated with the expression of HBx transgene. These findings propose for the first time that systemic dysregulation of cellular cytoskeletal genes is involved in HBx-induced hepatocarcinogenesis.
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PMID:Expression profiling reveals dysregulation of cellular cytoskeletal genes in HBx-induced hepatocarcinogenesis. 1787 14

Hypoxia inducible factor-1alpha (HIF-1alpha) was well correlated with carcinogenesis and tumor progression in many kinds of cancer. In this study, high expression of HIF-1alpha was found in 37 of the 72 (51.39%) tumor specimens, and significantly correlated with venous invasion and lymphonode invasion. Patients with high expression of HIF-1alpha had a significantly shorter overall survival rate and disease-free survival rate than those with low expression. Multivariate analysis showed high HIF-1alpha expression was a borderline independent factor of overall survival. HIF-1alpha expression was also found to be significantly correlated with the expression of hepatitis B virus X protein (HBx), and over-expressed HBx upregulated HIF-1alpha protein expression in vitro. These results suggested that HIF-1alpha, which was partially regulated by HBx, might be a prognostic marker of HBV-related HCC patients.
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PMID:The expression of hypoxia-inducible factor-1alpha in hepatitis B virus-related hepatocellular carcinoma: correlation with patients' prognosis and hepatitis B virus X protein. 1846 38


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