SYSTEMATIC REVIEW: Drug induced liver injury: Alternative causes in case series as confounding variables.

Posted by on 03 Apr 2018 | Tagged as: Hepatitis B Alternative Medicine

SYSTEMATIC REVIEW: Drug induced liver injury: Alternative causes in case series as confounding variables. Br J Clin Pharmacol. 2018 Apr 01;: Authors: Teschke R, Danan G Abstract AIMS: Drug-induced liver injury (DILI) is rare as compared to the worldwide frequent acute or chronic liver diseases. Therefore, patients included in series of suspected DILI are at high risk of not having DILI, whereby alternative causes may confound the DILI diagnosis. The aim of this review is to evaluate published case series of DILI for alternative causes. METHODS: Pertinent studies were identified using a computerized search of the Medline database for publications from 1993 through 30 October 2017. We used the following terms: drug hepatotoxicity, drug induced liver injury, hepatotoxic drugs combined with diagnosis, causality assessment, and alternative causes. RESULTS: Alternative causes as variables confounding the DILI diagnosis emerged in 22 published DILI case series, ranging from 4% to 47%. Among 13,335 cases of suspected DILI, alternative causes were found more likely in 4,555 patients (34.2%), suggesting that DILI was probably not DILI. Biliary diseases such as biliary obstruction, cholangitis, choledocholithiasis, primary biliary cholangitis, and primary sclerosing cholangitis were among the most missed diagnoses. Alternative causes included hepatitis B, C, and E, CMV, EBV, ischemic hepatitis, cardiac hepatopathy, autoimmune hepatitis, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and alcoholic liver disease. CONCLUSIONS: In more than one third of published global DILI case series, alternative causes as published in these reports confounded the DILI diagnosis. In the future, published DILI case series should include only patients with secured DILI diagnosis, preferentially established by prospective use of scored items provided by robust diagnostic algorithms such as the updated RUCAM (Roussel Uclaf Causality Assessment Method). PMID: 29607530 [PubMed – as supplied by publisher]

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SYSTEMATIC REVIEW: Drug induced liver injury: Alternative causes in case series as confounding variables.

No longer ‘written off’ – times have changed for the BBV-infected dental professional.

Posted by on 13 Mar 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles No longer ‘written off’ – times have changed for the BBV-infected dental professional. Br Dent J. 2017 Jan 13;222(1):47-52 Authors: Bagg J, Roy K, Hopps L, Black I, Croser D, O’Halloran C, Ncube F Abstract There is a recognised potential risk of transmission of blood-borne viruses (BBVs) from infected healthcare workers to patients during exposure prone procedures (EPPs). The restrictions placed on performance of EPPs by infected clinicians in the UK have had a particularly significant impact on dentists because of the exposure-prone nature of most dental procedures and the difficulties in identifying alternative career pathways in the profession that do not involve EPPs. More recently, the significant positive impact of antiviral drugs on viral load, together with a re-categorisation of EPPs in dentistry have resulted in evolution of the guidance with a consequent significant improvement to the career prospects of dentists infected with BBVs. This paper provides an update for practitioners on the progress that has been made and outlines the current position with respect to practice restrictions. PMID: 28084394 [PubMed – indexed for MEDLINE]

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No longer ‘written off’ – times have changed for the BBV-infected dental professional.

Safety and Immunogenicity of Seven Dosing Regimens of the Candidate RTS,S/AS01E Malaria Vaccine Integrated within an Expanded Program on Immunization…

Posted by on 13 Feb 2018 | Tagged as: Hepatitis B Alternative Medicine

Safety and Immunogenicity of Seven Dosing Regimens of the Candidate RTS,S/AS01E Malaria Vaccine Integrated within an Expanded Program on Immunization Regimen: A Phase II, Single-Center, Open, Controlled Trial in Infants in Malawi. Pediatr Infect Dis J. 2018 Feb 09;: Authors: Witte D, Cunliffe NA, Turner AM, Ngulube E, Ofori-Anyinam O, Vekemans J, Chimpeni P, Lievens M, Wilson TP, Njiramʼmadzi J, Mendoza YG, Leach A Abstract BACKGROUND: In a phase III trial, the RTS,S/AS01 malaria vaccine produced lower anti-circumsporozoite (CS) antibody titres when co-administered with Expanded Programme on Immunisation (EPI) vaccines (0,1,2-month schedule) at 6-12 weeks compared to 5-17 months at first vaccination. Alternative infant immunisation schedules within the EPI were investigated. METHODS: This phase II, open, single site (Blantyre, Malawi) trial was conducted in infants aged 1-7 days. Subjects were equally randomised across seven groups to receive three doses of RTS,S/AS01E at time points that included ≤7 days, 6, 10, 14, 26 weeks, and 9 months. All RTS,S/AS01E groups plus a control group (without RTS,S/AS01E) received BCG+OPV at ≤7 days, DTPwHepB/Hib+OPV at 6,10,14 weeks and measles vaccine at 9 months; one RTS,S/AS01E group and the control additionally received hepatitis B vaccination at ≤7 days. Serum anti-CS antibody geometric mean concentration (GMC; ELISA) and safety were assessed up to age 18 months. RESULTS: Of the 480 infants enrolled, 391 completed the study. No causally related serious adverse event was reported. A higher frequency of fever within 7 days of RTS,S/AS01E vaccination compared to control was observed. Compared to the standard 6,10,14 week schedule, anti-CS antibody GMC ratios post-Dose 3 were significantly higher in the 10,14,26 week group only (ratio 1.80; 95%CI:1.24, 2.60); RTS,S/AS01E vaccination at ≤7 days, 10,14 weeks produced significantly lower anti-CS GMCs (ratio 0.59; 95%CI:0.38, 0.92). CONCLUSIONS: Initiation of RTS,S/AS01E vaccination above six weeks of age tended to improve anti-CS antibody responses. Neonatal vaccination was well tolerated, but produced a comparatively lower immune response. REGISTRATION: Clinical Trials.gov identifier: NCT01231503GlaxoSmithKline Study ID number: 111315 (Malaria-057). PMID: 29432383 [PubMed – as supplied by publisher]

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Safety and Immunogenicity of Seven Dosing Regimens of the Candidate RTS,S/AS01E Malaria Vaccine Integrated within an Expanded Program on Immunization…

Chemical array system, a platform to identify novel hepatitis B virus entry inhibitors targeting sodium taurocholate cotransporting polypeptide.

Posted by on 11 Feb 2018 | Tagged as: Hepatitis B Alternative Medicine

Chemical array system, a platform to identify novel hepatitis B virus entry inhibitors targeting sodium taurocholate cotransporting polypeptide. Sci Rep. 2018 Feb 09;8(1):2769 Authors: Kaneko M, Futamura Y, Tsukuda S, Kondoh Y, Sekine T, Hirano H, Fukano K, Ohashi H, Saso W, Morishita R, Matsunaga S, Kawai F, Ryo A, Park SY, Suzuki R, Aizaki H, Ohtani N, Sureau C, Wakita T, Osada H, Watashi K Abstract Current anti-hepatitis B virus (HBV) agents including interferons and nucleos(t)ide analogs efficiently suppress HBV infection. However, as it is difficult to eliminate HBV from chronically infected liver, alternative anti-HBV agents targeting a new molecule are urgently needed. In this study, we applied a chemical array to high throughput screening of small molecules that interacted with sodium taurocholate cotransporting polypeptide (NTCP), an entry receptor for HBV. From approximately 30,000 compounds, we identified 74 candidates for NTCP interactants, and five out of these were shown to inhibit HBV infection in cell culture. One of such compound, NPD8716, a coumarin derivative, interacted with NTCP and inhibited HBV infection without causing cytotoxicity. Consistent with its NTCP interaction capacity, this compound was shown to block viral attachment to host hepatocytes. NPD8716 also prevented the infection with hepatitis D virus, but not hepatitis C virus, in agreement with NPD8716 specifically inhibiting NTCP-mediated infection. Analysis of derivative compounds showed that the anti-HBV activity of compounds was apparently correlated with the affinity to NTCP and the capacity to impair NTCP-mediated bile acid uptake. These results are the first to show that the chemical array technology represents a powerful platform to identify novel viral entry inhibitors. PMID: 29426822 [PubMed – in process]

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Chemical array system, a platform to identify novel hepatitis B virus entry inhibitors targeting sodium taurocholate cotransporting polypeptide.

Serum levels of angiotensin converting enzyme as a biomarker of liver fibrosis.

Posted by on 24 Jan 2018 | Tagged as: Hepatitis B Alternative Medicine

Serum levels of angiotensin converting enzyme as a biomarker of liver fibrosis. World J Gastroenterol. 2017 Dec 28;23(48):8439-8442 Authors: Miranda AS, Simões E Silva AC Abstract The renin angiotensin system (RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues, including the liver, pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme (ACE)-angiotensin (Ang) II-Ang type 1 (AT1) receptor mediates pro-inflammatory, pro-thrombotic, and pro-fibrotic processes. On the other hand, the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang II action. Chronic hepatitis B (CHB) is one of the leading causes of liver fibrosis, accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However, the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36th issue of the World Journal of Gastroenterology, Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate, non-invasive, widely available, and easy method to evaluate fibrosis related to CHB. Moreover, therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis. PMID: 29358853 [PubMed – in process]

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Serum levels of angiotensin converting enzyme as a biomarker of liver fibrosis.

Acute-on-chronic liver failure in chronic hepatitis B: an update.

Posted by on 18 Jan 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Acute-on-chronic liver failure in chronic hepatitis B: an update. Expert Rev Gastroenterol Hepatol. 2018 Jan 16;:1-10 Authors: Zhao RH, Shi Y, Zhao H, Wu W, Sheng JF Abstract INTRODUCTION: Acute-on-chronic liver failure is a common pattern of end-stage liver disease in clinical practice and occurs frequently in patients with chronic hepatitis B or HBV-related cirrhosis. New progress in recent years leads to a better understanding of this disease. Areas covered: This review updates the current comprehensive knowledge about HBV-ACLF from epidemiological studies, experimental studies, and clinical studies and provide new insights into the definition, diagnostic criteria, epidemiology, nature history, pathogenesis, treatment and prognostication of HBV-ACLF. Expert commentary: Patients with chronic hepatitis B or HBV-related cirrhosis are at risk of developing acute-on-chronic liver failure, with multi-organ failure and high short-term mortality. The precipitating events can be intra-hepatic or extra-hepatic and the underlying chronic liver injury can be cirrhotic or non-cirrhotic. Host and viral factors contribute to the susceptibility of developing HBV-ACLF. Systemic inflammation is the driver of HBV-ACLF, which can be attributed to non-sterile and sterile factors. Liver transplantation is the definitive treatment for HBV-ACLF. Cell therapy is a promising alternative to LT, but requires validation and still has concern of long-term safety. Other medical therapies, such as nucleoside analogue, artificial liver supporting and glucocorticoid may improve survival in a specific subgroup. New scoring systems improve the accuracy of prognostication in HBV-ACLF, which is critical for early identification of candidates for LT. PMID: 29334786 [PubMed – as supplied by publisher]

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Acute-on-chronic liver failure in chronic hepatitis B: an update.

[Effects of Anluohuaxianwan on transforming growth factor-β1 and related signaling pathways in rats with carbon tetrachloride-induced liver…

Posted by on 06 Jan 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles [Effects of Anluohuaxianwan on transforming growth factor-β1 and related signaling pathways in rats with carbon tetrachloride-induced liver fibrosis]. Zhonghua Gan Zang Bing Za Zhi. 2017 Apr 20;25(4):257-262 Authors: Lu W, Gao YH, Wang ZZ, Cai YS, Yang YQ, Miao YQ, Pei F, Liu XE, Zhuang H Abstract Objective: The traditional Chinese medicine Anluohuaxianwan (ALHXW) has been used to treat liver fibrosis induced by chronic hepatitis B virus (HBV) infection. However, the anti-fibrosis mechanisms of ALHXW remain to be investigated. This study used a rat model of carbon tetrachloride (CCl(4))-induced liver fibrosis to explore the potential antifibrogenic mechanisms of ALHXW. Methods: Twenty-seven male Wistar rats were randomly assigned to control group, model group, and treatment group (n = 9 per group). Rats in the model and treatment group were injected intraperitoneally with 40% CCl(4)(2 ml/kg), and rats in the control group were administered saline twice a week for 6 weeks. Starting at week 4 following model construction, rats in the treatment group received daily gavages with ALHXW solution (concentration 0.15 g/ml) daily, while rats in the control and model groups were given saline for a total of 6 weeks. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured from blood samples collected at the end of weeks 3, 6 and 9. Histopathological examination of liver tissue was performed to evaluate liver fibrosis at week 9. At the same time, the mRNA expression of TGF-β1 and Smads in liver tissues was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR), and TGF-β1 protein level in the liver was measured by Western blot. Inter-group comparison was performed using analysis of variance (ANOVA) when the continuous data were normally distributed and satisfied the homogeneity of variance; otherwise, nonparametric tests were used. Categorical data were compared between groups using nonparametric tests. Results: ALHXW markedly alleviated liver injury in the treatment group after 3 weeks of therapy as indicated by a significantly reduced level of ALT compared with the model group [(162.98 ± 73.14)U/L vs (322.52 ± 131.76)U/L, P = 0.047], and a 39.8% reduction in AST level compared with the model group[ (537.56 ± 306.06)U/L vs (892.98 ± 358.19)U/L, P = 0.053]. Moreover, at the end of the 6-week therapy, histopathological diagnosis showed that liver fibrosis was significantly reduced in the ALHXW-treated group compared with that in the model group (P = 0.002). The relative expression of TGF-β1 mRNA and protein in the liver were significantly lower in ALHXW-treated rats than that in model rats (1.34 ± 0.31 vs 1.78 ± 0.45, P = 0.025; 0.39 ± 0.02 vs 0.57 ± 0.04, P = 0.003). Conclusion: ALHXW treatment can reverse CCl(4)-induced liver fibrosis in rats. Its mechanisms of anti-fibrosis may occur through the inhibition of TGF-β1 synthesis and TGF-β1/Smads signaling pathway, which in turn suppress the activation of hepatic stellate cells and thereby reverses fibrosis. PMID: 28494543 [PubMed – indexed for MEDLINE]

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[Effects of Anluohuaxianwan on transforming growth factor-β1 and related signaling pathways in rats with carbon tetrachloride-induced liver…

Isolation and Characterization of Antigen-Specific Plasmablasts Using a Novel Flow Cytometry-Based Ig Capture Assay.

Posted by on 30 Dec 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Isolation and Characterization of Antigen-Specific Plasmablasts Using a Novel Flow Cytometry-Based Ig Capture Assay. J Immunol. 2017 Dec 15;199(12):4180-4188 Authors: Pinder CL, Kratochvil S, Cizmeci D, Muir L, Guo Y, Shattock RJ, McKay PF Abstract We report the development of a novel flow cytometry-based Ig capture assay (ICA) for the identification and sorting of individual Ab-secreting cells based on their Ag reactivity. The ICA represents a fast and versatile tool for single-cell sorting of peripheral plasmablasts, streamlining subsequent Ab analysis, and cloning. We demonstrate the utility of the assay by isolating Ag-reactive plasmablasts from cryopreserved PBMC obtained from volunteers vaccinated with a recombinant HIV envelope protein. To show the specificity of the ICA, we produced Ag-specific Abs from these cells and subsequently verified their Ag reactivity via ELISA. Furthermore, we used the ICA to track Ag-specific plasmablast responses in HIV-vaccine recipients over a period of 42 d and performed a head-to-head comparison with a conventional B cell ELISpot. Results were highly comparable, highlighting that this assay is a viable alternative for monitoring Ag-specific plasmablast responses at early time points after infection or vaccination. The ICA provides important added benefits in that phenotypic information can be obtained from the identified Ag-specific cells that can then be captured for downstream applications such as B cell sequencing and/or Ab cloning. We envisage the ICA as being a useful tool in Ab repertoire analysis for future clinical trials. PMID: 29118244 [PubMed – indexed for MEDLINE]

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Isolation and Characterization of Antigen-Specific Plasmablasts Using a Novel Flow Cytometry-Based Ig Capture Assay.

Evaluation of alternative serum biomarkers to monitor the progression of chronic HBV and HCV infection.

Posted by on 10 Dec 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Evaluation of alternative serum biomarkers to monitor the progression of chronic HBV and HCV infection. Infect Genet Evol. 2017 Dec 05;: Authors: Tsiomita S, Georgopoulou U, Doumba PP, Koskinas J, Adamidis K, Papaloukas C, Thyphronitis G Abstract Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are among the most serious health conditions affecting about 600 million people worldwide leading to a number of severe liver diseases. Due to the lack of warning signs or mild symptoms during the early stage of the infection, a molecular signature associated with disease progression would be useful. Based on our recent paper where candidate biomarkers were determined through topological and modularity analysis of protein interaction networks (PINs), this study was focused on the evaluation of MIF, TNFRSF1A, FAS and TMSB4X as diagnostic biomarkers in chronic HBV and HCV infections. The aim was to establish a molecular profile, by combining those markers, that would discriminate the different stages during the progression of chronic hepatitis. One hundred and fifteen patients infected with HBV or HCV categorized into three groups: non-cirrhotic, cirrhotic and with HCC, and 20 healthy subjects were enrolled in this study. Serum levels of the aforementioned factors were measured by ELISA. TNFRSF1A serum levels appeared statistically significantly increased in all patient groups compared to control group with a p-value of <0.05. Furthermore, the combination of TNFRSF1A and TMSB4X serum levels successfully classified 63, 47% of patients indicating an association with HBV and HCV infections. Thus, variations of serum levels of TNFRSF1A and TMSB4X could be associated with the different stages of the disease and may be utilized for further research. On the other hand, we found no contribution of MIF and FAS serum levels for successful classification of patients. PMID: 29221787 [PubMed – as supplied by publisher]

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Evaluation of alternative serum biomarkers to monitor the progression of chronic HBV and HCV infection.

Pathogen reduction and blood transfusion safety in Africa: strengths, limitations and challenges of implementation in low-resource settings.

Posted by on 02 Dec 2017 | Tagged as: Hepatitis B Alternative Medicine

Pathogen reduction and blood transfusion safety in Africa: strengths, limitations and challenges of implementation in low-resource settings. Vox Sang. 2017 Nov 30;: Authors: Ware AD, Jacquot C, Tobian AAR, Gehrie EA, Ness PM, Bloch EM Abstract Transfusion-transmitted infection risk remains an enduring challenge to blood safety in Africa. A high background incidence and prevalence of the major transfusion-transmitted infections (TTIs), dependence on high-risk donors to meet demand, suboptimal testing and quality assurance collectively contribute to the increased risk. With few exceptions, donor testing is confined to serological evaluation of human immunodeficiency virus (HIV), hepatitis B and C (HBV and HCV) and syphilis. Barriers to implementation of broader molecular methods include cost, limited infrastructure and lack of technical expertise. Pathogen reduction (PR), a term used to describe a variety of methods (e.g. solvent detergent treatment or photochemical activation) that may be applied to blood following collection, offers the means to diminish the infectious potential of multiple pathogens simultaneously. This is effective against different classes of pathogen, including the major TTIs where laboratory screening is already implemented (e.g. HIV, HBV and HCV) as well pathogens that are widely endemic yet remain unaddressed (e.g. malaria, bacterial contamination). We sought to review the available and emerging PR techniques and their potential application to resource-constrained parts of Africa, focusing on the advantages and disadvantages of such technologies. PR has been slow to be adopted even in high-income countries, primarily given the high costs of use. Logistical considerations, particularly in low-resourced parts of Africa, also raise concerns about practicality. Nonetheless, PR offers a rational, innovative strategy to contend with TTIs; technologies in development may well present a viable complement or even alternative to targeted screening in the future. PMID: 29193128 [PubMed – as supplied by publisher]

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Pathogen reduction and blood transfusion safety in Africa: strengths, limitations and challenges of implementation in low-resource settings.

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