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Hepatitis B [keywords]
- Influencing elements and treatment strategies associated with the relapse of hepatocellular carcinoma after surgery. [Journal Article, Research Support, Non-U.S. Gov't]
- Hepatogastroenterology 2013 Jul-Aug; 60(125):1148-55.
BACKGROUND/ AIMS: Long-term prognosis after surgical resection of Hepatocellular Carcinoma remains unsatisfactory, mainly because of the high postoperative incidence of recurrence and metastasis. An updated knowledge on the influencing factors of recurrence and treatment strategies of postoperative recurrence is important for clinicians in designing a strategy to optimize the chance of long-term survival in patients undergoing hepatic resection for HCC.Using key words “Hepatocellular Carcinoma”, “liver cancer”, “resection”, “postoperative recurrence”, “treatment strategy”, “therapy”, “influencing factors”, “risk factors”, we performed a review of relevant English articles based on based on a Medline search before May 2012.Influencing factors include tumor size, venous invasion, satellite nodules, cirrhosis, alpha-foetoprotein, aspartate aminotransferase, alkaline phosphatase levels, hepatitis B virus and hepatitis C virus infection, Alpha-foetoprotein mRNA and some surgical factors. Treatment strategies include re-resection, transarterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection, salvage liver transplantation, radioactive seed 125I implantation and other new treatment modalities of postoperative recurrent HCC are all used to prolong survival in patients with recurrence, and multimodality therapy of above mentioned therapies may offer additional beneﬁt.With advances in perioperative detection and therapeutic modalities, results of recurrence after resection of HCC will greatly improved.
- Co-Infection: Weil's Syndrome with Hepatitis B Infection- A Diagnostic and Therapeutic Hitch. [JOURNAL ARTICLE]
- J Clin Diagn Res 2013 Oct; 7(10):2270-2271.
Undifferentiated Acute Febrile Illness (AFI) is a common clinical syndrome among patients seeking hospital care. Detection of co-infections at the time of presentation is a diagnostic challenge, especially with limited laboratory support. Even if detected, early treatment and cure of these co-infections can be difficult for the clinicians. We are presenting a rare case of Hepatitis B and leptospirosis co-infection with high titres of Salmonella paratyphi A and scrub typhus. There are a few reports of leptospirosis in Hepatitis -B infected individuals but no generalization can be made due to limited data. Prompt and accurate serological diagnosis of multiple infectious agents have becomes mandatory in a healthcare set-up.
- The metabolic sensors FXRα, PGC-1α, and SIRT1 cooperatively regulate hepatitis B virus transcription. [JOURNAL ARTICLE]
- FASEB J 2013 Dec 2.
Hepatitis B virus (HBV) genome transcription is highly dependent on liver-enriched, metabolic nuclear receptors (NRs). Among others, NR farnesoid X receptor α (FXRα) enhances HBV core promoter activity and pregenomic RNA synthesis. Interestingly, two food-withdrawal-induced FXRα modulators, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and deacetylase SIRT1, have been found to be associated with HBV genomes ex vivo. Whereas PGC-1α induction was shown to increase HBV replication, the effect of SIRT1 on HBV transcription remains unknown. Here, we showed that, in hepatocarcinoma-derived Huh-7 cells, combined activation of FXRα by GW4064 and SIRT1 by activator 3 increased HBV core promoter-controlled luciferase expression by 25-fold, compared with a 10-fold increase with GW4064 alone. Using cell lines differentially expressing FXRα in overexpression and silencing experiments, we demonstrated that SIRT1 activated the core promoter in an FXRα- and PGC-1α-dependent manner. Maximal activation (>150-fold) was observed in FXRα- and PGC-1α-overexpressing Huh-7 cells treated with FXRα and SIRT1 activators. Similarly, in cells transfected with full-length HBV genomes, maximal induction (3.5-fold) of core promoter-controlled synthesis of 3.5-kb RNA was observed in the same conditions of transfection and treatments. Thus, we identified a subnetwork of metabolic factors regulating HBV replication, strengthening the hypothesis that transcription of HBV and metabolic genes is similarly controlled.-Curtil, C., Enache, L. S., Radreau, P., Dron, A.-G., Scholtès, C., Deloire, A., Roche, D., Lotteau, V., André, P., and Ramière, C. The metabolic sensors FXRα, PGC-1α, and SIRT1 cooperatively regulate hepatitis B virus transcription.
- A Rationalized Approach to the Treatment of Patients Infected with Hepatitis B. [JOURNAL ARTICLE]
- Mol Diagn Ther 2013 Dec 3.
It is estimated that there are 350-400 million individuals with chronic hepatitis B virus infection (HBV) worldwide. The natural course of HBV infection is variable with a number of individuals developing no or only mild disease, while others will die from liver-associated complications if left untreated. It is estimated that 25 % of individuals with HBV infection will eventually die from the complications of HBV-associated liver disease. Several viral and host variables including hepatitis B e antigen status, HBV genotype, viral load, hepatitis B surface antigen and transaminase levels, and viral mutations have been identified as determinants of disease outcomes. The personalized approach to the treatment of chronic hepatitis B might include mere monitoring of the disease in some patients but aggressive treatment in others. Individuals who require treatment should have close monitoring to help ensure maximum medication compliance, to watch for adverse events, and to monitor virologic and biochemical responses. Therefore, management of patients with chronic HBV infection requires a practical setting to demonstrate the relevance of personalized medicine, the roles and limitations of genetic and non-genetic factors, and the risks and benefits of individualized patient care. This article provides an overview of the viral and host genetics of chronic HBV and reviews the clinical utility of serum quantitative hepatitis B surface antigen in the management of patients with chronic HBV infection.
- Inhibition of hepatitis B virus replication in vivo using helper-dependent adenovirus vectors to deliver antiviral RNAi expression cassettes. [JOURNAL ARTICLE]
- Antivir Ther 2013 Dec 3.
Hepatitis B virus (HBV) is hyperendemic to southern Africa and parts of Asia, but licensed antivirals have little effect on limiting life-threatening complications of the infection. Although RNA interference- (RNAi-) based gene silencing has shown therapeutic potential, difficulties with delivery of antiHBV RNAi effecters remain an obstacle to their clinical use. To address concerns about the transient nature of transgene expression and toxicity resulting from immunostimulation by recombinant adenovirus vectors (Ads), utility of RNAi-activating antiHBV helper-dependent (HD) Ads were assessed in this study.Following intravenous administration of 5×10(9) unmodified and PEGylated HD Ad vectors to HBV transgenic mice, HBV viral loads and serum hepatitis B virus surface antigen levels were monitored for 12 weeks. HD Ads' immunostimulation was assessed by measuring inflammatory cytokines, hepatic function and immune response to the co-delivered LacZ reporter gene.Unmodified and PEGylated HD Ads transduced 80-90% of hepatocytes and expressed short hairpin RNAs (shRNAs) were processed to generate intended HBV-targeting guides. Markers of HBV replication were decreased by approximately 95% and silencing was sustained for 8 weeks. Unmodified HD Ads induced release of proinflammatory cytokines and there was evidence of an adaptive immune response to LacZ. However the HD Ad-induced innate immune response was minimal in preparations that were enriched with infectious particles.HD Ads have potential utility for delivery of therapeutic HBV-silencing sequences and alterations of these vectors to attenuate their immune responses may further improve their efficacy.
- Presence of anti-interferon antibodies is not associated with non-response to peginterferon treatment in chronic hepatitis B. [JOURNAL ARTICLE]
- Antivir Ther 2013 Dec 3.
Several factors have been related to response to PEG-IFN in chronic hepatitis B (CHB). The occurrence of anti-IFN antibodies are associated with non-response to PEG-IFN in chronic hepatitis C. This study investigated the association between anti-IFN antibodies and response to PEG-IFN in CHB.Presence of anti-IFN antibodies was assessed at baseline and at 3 and 6 months post-treatment in 323 CHB patients treated with PEG-IFN for one year.At baseline anti-IFN antibodies were detected in 112 patients (35%). Prevalence was higher in HBeAg negative compared to HBeAg positive CHB (43% vs. 31%, respectively, p=0.03). Detection of anti-IFN antibodies was not associated with age, sex or HBV genotype. Presence of anti-IFN antibodies at baseline was associated with previous IFN therapy failure (p=0.04), which remained after adjustment for HBeAg status (OR 2.0, 95%CI 1.1-3.7, p=0.03). Presence of anti-IFN antibodies at baseline was not associated with response, nor with HBV DNA or HBsAg decline (all p-values>0.3). Fifty-six of 211 (27%) patients without anti-IFN at baseline developed anti-IFN antibodies after PEG-IFN treatment. Response rates did not differ between patients who developed anti-IFN antibodies and patients who did not develop anti-IFN antibodies during treatment (p=0.1).Anti-IFN antibodies may frequently be detected in CHB patients, and presence is associated with previous IFN therapy. However, presence or development of anti-IFN antibodies after PEG-IFN therapy is not associated with non-response to PEG-IFN treatment in CHB. There appears to be no future role for anti-IFN antibodies in predicting response to PEG-IFN in CHB.
- Adherence to Hepatitis B Immunoglobulin (HBIG) After Liver Transplantation. [Journal Article]
- Transplantation 2013 Dec 15; 96(11):e84-5.
- Long-term efficacy and safety of emtricitabine plus tenofovir DF vs tenofovir DF monotherapy in adefovir-experienced chronic hepatitis B patients. [JOURNAL ARTICLE]
- J Hepatol 2013 Nov 29.
Suboptimal virologic response to nucleos(t)ide analogs may represent a significant risk factor for resistance development in patients with chronic hepatitis B virus infection; treatment options have not been well studied. We evaluated long-term efficacy and safety of tenofovir alone and in combination with emtricitabine in a prospective, placebo-controlled trial in patients who remained viremic on adefovir therapy.Hepatitis B e antigen-positive and -negative patients with hepatitis B virus DNA ⩾1000 copies/mL despite up to 96 weeks of adefovir were randomized to double-blind tenofovir or emtricitabine/tenofovir for 168 weeks. Patients with hepatitis B virus DNA ⩾400 copies/mL (⩾69 IU/mL) at or after week 24 could switch to open-label emtricitabine/tenofovir.Overall, 90/105 (86%) patients (46/53 tenofovir and 44/52 emtricitabine/tenofovir) completed the 168-week study period, including 74/105 (70%) patients (35/53 tenofovir and 39/52 emtricitabine/tenofovir) who completed the study on their initial randomized treatment. Long-term viral suppression (hepatitis B virus DNA <400 copies/mL) was maintained at week 168 in 84% and 82% of patients receiving either emtricitabine/tenofovir combination or tenofovir monotherapy, respectively (non-completer equal to failure analysis). Baseline viral load as well as the presence of lamivudine and/or adefovir resistance-associated mutations at baseline had no impact on long-term treatment response. No resistance to tenofovir was observed through 168 weeks. Both treatments had a favorable safety profile.Tenofovir monotherapy is as effective as emtricitabine/tenofovir combination therapy in maintaining long-term viral suppression in patients with a suboptimal response to adefovir, and is well tolerated in this population.
- Cyclosporin A inhibits Hepatitis B and Hepatitis D Virus entry by Cyclophilin-independent interference with the NTCP receptor. [JOURNAL ARTICLE]
- J Hepatol 2013 Nov 29.
Chronic hepatitis B and hepatitis D are global health problems caused by the human hepatitis B and hepatitis D virus. The myristoylated preS1 domain of the large envelope protein mediates specific binding to hepatocytes by sodium taurocholate co-transporting polypeptide (NTCP). NTCP is a bile salt transporter known to be inhibited by Cyclosporin A. This study aimed to characterize the effect of Cyclosporin A on HBV/HDV infection.HepaRG cells, primary human hepatocytes and susceptible NTCP-expressing hepatoma cell lines were applied for infection experiments. The mode of action of Cyclosporin A was studied by comparing the effect of different inhibitors, cyclophilin A/B/C-silenced cell lines as well as NTCP variants and mutants. Bile salt transporter and HBV receptor functions were investigated by taurocholate uptake and quantification of HBVpreS binding.Cyclosporin A inhibited hepatitis B and D virus infections during and - less pronounced - prior to virus inoculation. Binding of HBVpreS to NTCP was blocked by Cyclosporin A concentrations at 8M. An NTCP variant deficient in HBVpreS binding but competent for bile salt transport showed resistance to Cyclosporin A. Silencing of cyclophilins A/B/C did not abrogate transporter and receptor inhibition. In contrast, tacrolimus, a cyclophilin-independent calcineurin inhibitor, was inactive.HBV and HDV entry via sodium taurocholate co-transporting polypeptide is inhibited by Cyclosporin A. The interaction between the drug and the viral receptor is direct and overlaps with a functional binding site of the preS1 domain, which mediates viral entry.
- Vector-mediated expression of interferon gamma inhibits replication of hepatitis B virus in vitro. [Journal Article]
- Acta Virol 2013; 57(4):421-8.
Despite the existence of efficient vaccines against hepatitis B virus (HBV) infections, these still represent a serious threat to human health worldwide. Acute HBV infections often become chronic, marked by liver cirrhosis and hepatocellular carcinoma. Promising results with interferons alpha or gamma (IFN-α, γ) or nucleoside/nucleotide analogs in inhibiting HBV replication in vitro have led to therapeutic applications to chronic HBV patients, however, their results so far have not been satisfactory. The treatments were either not effective in all patients or had adverse effects. Certain progress was expected from expression of interferons targeted to liver by adenovirus vectors, however, this approach turned out to be limited by undesired expression of toxic viral genes and high production costs. Therefore, in this study, we attempted to inhibit HBV replication in HepG2.2.15 cells by human IFN-γ expressed through a non-viral vector, an eukaryotic plasmid. The results demonstrated that IFN-γ, targeted to HBV-replicating cells, significantly inhibited the virus growth without inducing apoptosis and indicated that local expression of this kind of cytokine may be a promising strategy of gene therapy. Keywords: hepatitis B virus; interferon gamma; HepG2.2.15 cells; apoptosis.