Improving communication about viral hepatitis in Africa.

Posted by on 21 Sep 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Improving communication about viral hepatitis in Africa. Lancet Infect Dis. 2017 07;17(7):688-689 Authors: Shimakawa Y, Pourette D, Bainilago L, Enel C, Sombié R, Rado R, Lemoine M, Giles-Vernick T PMID: 28653627 [PubMed – indexed for MEDLINE]

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Improving communication about viral hepatitis in Africa.

Identification of Retinoic Acid Receptor Agonists as Potent Hepatitis B Virus Inhibitors via a Drug Repurposing Screen.

Posted by on 19 Sep 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Identification of Retinoic Acid Receptor Agonists as Potent Hepatitis B Virus Inhibitors via a Drug Repurposing Screen. Antimicrob Agents Chemother. 2018 Sep 17;: Authors: Li B, Wang Y, Shen F, Wu M, Li Y, Fang Z, Ye J, Wang L, Gao L, Yuan Z, Chen J Abstract Currently available therapies for chronic hepatitis B virus (HBV) infection can efficiently reduce viremia, but induce hepatitis B surface antigen (HBsAg) loss in a very few patients and do not much affect the viral covalently closed circular DNA (cccDNA). To discover new agents with complementary anti-HBV effects, we performed a drug repurposing screen of 1,018 Food and Drug Administration (FDA)-approved compounds using HBV-infected primary human hepatocytes (PHH). Several compounds belonging to the family of retinoic acid receptor (RAR) agonists were identified that reduced HBsAg levels in a dose-dependent manner without significant cytotoxicity. Among them, Tazarotene exhibited the most potent anti-HBV effect with an IC50 for HBsAg of less than 30 nM in PHH. The inhibitory effect was also observed in HBV-infected dHepaRG models, but not in HepG2.215 cells, and HBV genotype A to D were similarly inhibited. Tazarotene was further demonstrated to repress HBV cccDNA transcription, as determined by the levels of HBV cccDNA, RNAs and the activation of HBV promoters. Moreover, RNA-sequence analysis showed that Tazarotene did not induce an interferon response, but altered the expression of a number of genes associated with RAR and metabolic pathways. Inhibition of RARβ, but not RARα, by specific antagonist significantly attenuated the anti-HBV activity of Tazarotene, suggesting Tazarotene inhibits HBV in part through RARβ. Finally, a synergistic effect of Tazarotene and Entecavir on HBV-DNA levels was observed. Therefore, RAR agonists as represented by Tazarotene were identified as potential novel anti-HBV agents. PMID: 30224536 [PubMed – as supplied by publisher]

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Identification of Retinoic Acid Receptor Agonists as Potent Hepatitis B Virus Inhibitors via a Drug Repurposing Screen.

Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic Hepatitis B: Study Protocol for a Multi-Center, Double-Blind…

Posted by on 14 Sep 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic Hepatitis B: Study Protocol for a Multi-Center, Double-Blind Randomized-Controlled Trial. Chin J Integr Med. 2018 Sep;24(9):653-660 Authors: Ye YA, Li XK, Zhou DQ, Chi XL, Li Q, Wang L, Lu BJ, Mao DW, Wu QK, Wang XB, Zhang MX, Xue JD, Li Y, Lu W, Guo JC, Jiang F, Zhang XW, Du HB, Yang XZ, Guo H, Gan DN, Li ZG Abstract BACKGROUND: The domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP) or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate. METHODS: The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment. DISCUSSION: The study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as “a valuable endpoint”. We believe this trial could provide a reliable status for patients’ “journey” towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23). PMID: 30209792 [PubMed – in process]

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Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic Hepatitis B: Study Protocol for a Multi-Center, Double-Blind…

The changing epidemiology of liver diseases in the Asia-Pacific region.

Posted by on 31 Aug 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles The changing epidemiology of liver diseases in the Asia-Pacific region. Nat Rev Gastroenterol Hepatol. 2018 Aug 29;: Authors: Wong MCS, Huang JLW, George J, Huang J, Leung C, Eslam M, Chan HLY, Ng SC Abstract This Review presents current epidemiological trends of the most common liver diseases in Asia-Pacific countries. Hepatitis B virus (HBV) remains the primary cause of cirrhosis; despite declining prevalence in most Asian nations, this virus still poses a severe threat in some territories and regions. Mortality resulting from HBV infection is declining as a result of preventive measures and antiviral treatments. The epidemiological transition of hepatitis C virus (HCV) infection has varied in the region in the past few decades, but the medical burden of infection and the prevalence of its related cancers are increasing. The lack of licensed HCV vaccines highlights the need for novel treatment strategies. The prevalence of nonalcoholic fatty liver disease (NAFLD) has risen in the past decade, mostly owing to increasingly urbanized lifestyles and dietary changes. Alternative herbal medicine and dietary supplements are major causes of drug-induced liver injury (DILI) in some countries. Complications arising from these chronic liver diseases, including cirrhosis and liver cancer, are therefore emerging threats in the Asia-Pacific region. Key strategies to control these liver diseases include monitoring of at-risk populations, implementation of national guidelines and increasing public and physician awareness, in concert with improving access to health care. PMID: 30158570 [PubMed – as supplied by publisher]

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The changing epidemiology of liver diseases in the Asia-Pacific region.

Identification of TRIM14 as a Type I IFN-Stimulated Gene Controlling Hepatitis B Virus Replication by Targeting HBx.

Posted by on 29 Aug 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Identification of TRIM14 as a Type I IFN-Stimulated Gene Controlling Hepatitis B Virus Replication by Targeting HBx. Front Immunol. 2018;9:1872 Authors: Tan G, Xu F, Song H, Yuan Y, Xiao Q, Ma F, Qin FX, Cheng G Abstract Hepatitis B virus (HBV) remains a major cause of hepatic disease that threatens human health worldwide. Type I IFN (IFN-I) therapy is an important therapeutic option for HBV patients. The antiviral effect of IFN is mainly mediated via upregulation of the expressions of the downstream IFN-stimulated genes. However, the mechanisms by which IFN induces ISG production and inhibits HBV replication are yet to be clarified. TRIM14 was recently reported as a key molecule in the IFN-signaling pathway that regulates IFN production in response to viral infection. In this study, we sought to understand the mechanisms by which IFN restricts HBV replication. We confirmed that TRIM14 is an ISG in the hepatic cells, and that the pattern-recognition receptor ligands polyI:C and polydAdT induce TRIM14 dependent on IFN-I production. In addition, IFN-I-activated STAT1 (but not STAT3) directly bound to the TRIM14 promoter and mediated the induction of TRIM14. Interestingly, TRIM14 played an important role in IFN-I-mediated inhibition of HBV, and the TRIM14 SPRY domain interacted with the C-terminal of HBx, which might block the role of HBx in facilitating HBV replication by inhibiting the formation of the Smc-HBx-DDB1 complex. Thus, our study clearly demonstrates that TRIM14 is a STAT1-dependent ISG, and that the IFN-I-TRIM14-HBx axis shows an alternative way to understand the mechanism by which IFN-I inhibits virus replication. PMID: 30150992 [PubMed – in process]

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Identification of TRIM14 as a Type I IFN-Stimulated Gene Controlling Hepatitis B Virus Replication by Targeting HBx.

Treatment of chronic hepatitis B naïve patients with a therapeutic vaccine containing HBs and HBc antigens (a randomized, open and treatment…

Posted by on 23 Aug 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Treatment of chronic hepatitis B naïve patients with a therapeutic vaccine containing HBs and HBc antigens (a randomized, open and treatment controlled phase III clinical trial). PLoS One. 2018;13(8):e0201236 Authors: Al Mahtab M, Akbar SMF, Aguilar JC, Guillen G, Penton E, Tuero A, Yoshida O, Hiasa Y, Onji M Abstract CONTEXT: Current drugs for chronic hepatitis B therapy have a poor efficacy in terms of post-treatment sustained viral suppression and generate important side effects during and after therapy. Therapeutic vaccination with HBV antigens is an attractive alternative to test. OBJECTIVE: Evaluating the efficacy of a therapeutic vaccine candidate (designated NASVAC) containing both hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) versus pegylated interferon (Peg-IFN) in naïve chronic hepatitis B patients. DESIGN, SETTING, PARTICIPANTS: An open phase III, randomised and treatment controlled clinical trial was conducted in a total of 160 CHB patients, allocated into two groups of 80 patients each to receive NASVAC or Peg-IFN. The vaccine formulation comprised 100 μg of each HBsAg and HBcAg, and was administered in 2 cycles of 5 doses. The control group received 48 subcutaneous injections of Peg-IFN alfa 2b, 180 μg per dose, every week, for 48 consecutive weeks. MAIN OUTCOME MEASURE: The primary outcome measure was in relation with the proportion of patients showing reduction of the viral load under the limit of detection (250 copies/mL) after 24 weeks of treatment completion. RESULTS: Sustained control of HBV DNA was significantly more common in NASVAC group (p<0.05) at 24 weeks of follow up. NASVAC-induced increases of alanine aminotransferases (ALT) were detected in 85% patients after 5 nasal vaccinations, although seen in only 30% of patients receiving Peg-IFN. At the end of treatment (EOT) antiviral effect was comparable in both NASVAC and Peg-IFN groups. Clearance of Hepatitis B e antigen (HBeAg) was also more frequent in NASVAC group compared to Peg-IFN recipients. A lower progression to cirrhosis was found in NASVAC group compared to Peg-IFN group. CONCLUSION: Nasvac induced a superior reduction of the viral load under the limit of detection compared to Peg-IFN treatment. It is a safe and efficacious finite alternative of antiviral treatment for CHB patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT 01374308. PMID: 30133478 [PubMed – in process]

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Treatment of chronic hepatitis B naïve patients with a therapeutic vaccine containing HBs and HBc antigens (a randomized, open and treatment…

Efficacy of Arsenicum album 30cH in preventing febrile episodes following DPT-HepB-Polio vaccination – a randomized, double-blind, placebo-controlled…

Posted by on 21 Aug 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Efficacy of Arsenicum album 30cH in preventing febrile episodes following DPT-HepB-Polio vaccination – a randomized, double-blind, placebo-controlled clinical trial. Complement Ther Med. 2018 Feb;36:59-62 Authors: Ghosh S, Ghosh T, Mondal R, Patra S, Das S, Ali SS, Koley M, Saha S Abstract BACKGROUND: Among the post-immunization adverse events, especially of Diphtheria-Pertusis-Tetanus (DPT), fever is a common systemic reaction. There is anecdotal support for the use of the homeopathic medicine Arsenicum album in preventing post-vaccination fever. The investigators intended to evaluate its efficacy in preventing febrile episodes following vaccination. METHODS: In the community medicine out-patient of Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, West Bengal, India, between August 2014 and January 2017, a double-blind, randomized, placebo-controlled trial was conducted on 120 children (verum: 60, placebo: 60) who presented for the 2nd and 3rd dose of DPT-HepB-Polio vaccination and reported febrile episodes following the 1st dose. Intervention used was Arsenicum album 30cH 6 doses or placebo (indistinguishable from verum), thrice daily for two subsequent days. Parents were advised to report any event of febrile attacks within 48h of vaccination, either directly or over telephone. RESULTS: The groups were comparable at baseline. Children reporting fever after the 2nd dose was 29.8% and 30.4% respectively for the homeopathy group and control group respectively [Relative Risk (RR)=1.008] with no significant difference (P=0.951) between groups. Again after the 3rd dose, children reporting fever were 31.5% and 28.3% respectively for the homeopathy group and control group respectively (RR=0.956) with no significant difference (P=0.719) between groups. CONCLUSION: Empirically selected Arsenicum album 30cH could not produce differentiable effect from placebo in preventing febrile episodes following DPT-HepB-Polio vaccination. [Trial registration: CTRI/2017/02/007939]. PMID: 29458932 [PubMed – indexed for MEDLINE]

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Efficacy of Arsenicum album 30cH in preventing febrile episodes following DPT-HepB-Polio vaccination – a randomized, double-blind, placebo-controlled…

Development and application of a multiplex assay for the simultaneous measurement of antibody responses elicited by common childhood vaccines.

Posted by on 09 Aug 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Development and application of a multiplex assay for the simultaneous measurement of antibody responses elicited by common childhood vaccines. Vaccine. 2018 Aug 04;: Authors: Itell HL, McGuire EP, Muresan P, Cunningham CK, McFarland EJ, Borkowsky W, Permar SR, Fouda GG Abstract Because vaccine co-administration can affect elicited immune responses, it is important to evaluate new vaccines in the context of pre-existing vaccination schedules. This is particularly necessary for new pediatric vaccines, as the World Health Organization’s infant immunization program already schedules several vaccines to be administered during the first months of life. To facilitate the assessment of inter-vaccine interference, we developed a pediatric vaccine multiplex assay (PVMA) to simultaneously measure antibodies against vaccines commonly administered to infants, including hepatitis B, Haemophilus influenzae type B, diphtheria, tetanus, pertussis, rubella, and respiratory syncytial virus (RSV). Comparison of antibody concentrations determined by enzyme-linked immunosorbent assays (ELISAs) and the PVMA demonstrated that the PVMA is highly sensitive, specific, reproducible, and accurate. Moreover, the PVMA requires half the time to assess a cohort compared to ELISAs, and only costs marginally more. Demonstrating the utility of the assay, we employed the PVMA to assess vaccine interference in the setting of a candidate vaccine, using the infant HIV vaccines from the completed Pediatric AIDS Clinical Trials Group (PACTG) protocols 230 and 326 as examples. There was no substantial difference in antibody concentrations between vaccine and placebo recipients, which suggests that HIV vaccination did not disrupt antibody responses elicited by routine pediatric vaccines. Thus, the PVMA is a reliable, high-throughput technique that requires minimal sample volume to measure multiple antibody concentrations concurrently, and is an efficient alternative to ELISAs for the measurement of vaccine-elicited antibody responses in large cohorts. PMID: 30087048 [PubMed – as supplied by publisher]

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Development and application of a multiplex assay for the simultaneous measurement of antibody responses elicited by common childhood vaccines.

Lamivudine plus tenofovir versus lamivudine plus adefovir for the treatment of hepatitis B virus in HIV-coinfected patients, starting antiretroviral…

Posted by on 08 Aug 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Lamivudine plus tenofovir versus lamivudine plus adefovir for the treatment of hepatitis B virus in HIV-coinfected patients, starting antiretroviral therapy. Indian J Med Microbiol. 2018 Apr-Jun;36(2):217-223 Authors: Sarkar J, Saha D, Bandyopadhyay B, Saha B, Chakravarty R, Guha SK Abstract Background: Combination of tenofovir disoproxil fumarate (TDF), lamivudine (3TC) and efavirenz (EFV) is preferred in the treatment of HIV/hepatitis B virus (HBV) coinfection. We postulated that a HBV active nucleoside reverse transcriptase (RT) inhibitor/nucleotide RT inhibitor backbone of adefovir dipivoxil (ADV) +3TC would be as effective as TDF +3TC for the Indian population. Objective: ADV + 3TC could be an alternative option for these HIV/HBV coinfected individuals, preserving the dually active TDF + 3TC as second-line nucleoside backbone following failure of the first-line ART. Materials and Methods: This randomised control trial (CTRI/2012/03/002471) was carried out at the ART Centre of Calcutta School of Tropical Medicine, India. Seventy-eight (39 on each arm) treatment-naïve HIV/HBV coinfected patients were randomised to receive either the combination of lamivudine + tenofovir + EFV or lamivudine + adefovir + zidovudine + EFV and followed up for 120 weeks. Results: Median age of the study participants was 36 years (21-62), majority were male (61/78; 78.2%) and heterosexually (39/78; 50%) infected. Baseline characteristics were identical in both arms. There was no statistically significant difference in median aspartate aminotransferase (37 vs. 29.5 U/L), alanine aminotransferase (ALT) (36 vs. 34.5 U/L), ALT normalisation rate (80 vs. 70%), AST to platelet ratio index (0.45 vs. 0.33), CD4 count (508 vs. 427 cells/mm3), HBV DNA suppression (81.8 vs. 70%), hepatitis B e antigen loss (9 vs. 5%), hepatitis B surface antigen seroclearance rate (6.06 vs. 18.75%) and death (3 vs. 3) at 120 weeks between TDF (n = 33) and ADV (n = 32), respectively. Conclusions: Adefovir plus lamivudine is an effective alternative of tenofovir plus lamivudine in long-term HBV treatment outcome in HIV/HBV coinfected patients. PMID: 30084414 [PubMed – in process]

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Lamivudine plus tenofovir versus lamivudine plus adefovir for the treatment of hepatitis B virus in HIV-coinfected patients, starting antiretroviral…

Deregulation of Frizzled Receptors in Hepatocellular Carcinoma.

Posted by on 04 Aug 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Deregulation of Frizzled Receptors in Hepatocellular Carcinoma. Int J Mol Sci. 2018 Jan 21;19(1): Authors: Chan KK, Lo RC Abstract G protein-coupled receptors (GPCRs) have a substantial role in tumorigenesis and are described as a “cancer driver”. Aberrant expression or activation of GPCRs leads to the deregulation of downstream signaling pathways, thereby promoting cancer progression. In hepatocellular carcinoma (HCC), the Wnt signaling pathway is frequently activated and it is associated with an aggressive HCC phenotype. Frizzled (FZD) receptors, a family member of GPCRs, are known to mediate Wnt signaling. Accumulating findings have revealed the deregulation of FZD receptors in HCC and their functional roles have been implicated in HCC progression. Given the important role of FZD receptors in HCC, we summarize here the expression pattern of FZD receptors in HCC and their corresponding functional roles during HCC progression. We also further review and highlight the potential targeting of FZD receptors as an alternative therapeutic strategy in HCC. PMID: 29361730 [PubMed – indexed for MEDLINE]

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Deregulation of Frizzled Receptors in Hepatocellular Carcinoma.

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