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| Probiotics found to reduce hepatic encephalopathy Posted: 24 Apr 2013 09:00 PM PDT Amsterdam, The Netherlands,Thursday 25 April 2013: Probiotics could emerge as a treatment plan to manage hepatic encephalopathy (HE) therapy after a new study announced at the International Liver Congress? 2013 found they significantly reduced development of the notoriously difficult-to-treat disease.
The study analysed the efficacy of probiotics in preventing the development of HE in 160 cirrhotic patients over a period of approximately nine months and found significant improvements in reducing patients’ arterial ammonia levels after three months of treatment with probiotics. Ammonia, produced by gut bacteria, is thought to be one of the main mediators of cerebral dysfunction in HE. Probiotics work by enriching the gut flora with a non-urease producing microorganisms, which decrease ammonia production. Probiotics are live microorganisms (mostly bacteria) that produce a health benefit on the host when administered in adequate amounts. Twice as many patients taking a placebo developed overt HE (the study’s primary endpoint) compared to patients taking probiotics in the form of a capsule. EASL’s Treasurer, Prof. Mauro Bernardi welcomed the findings and said they would provide a positive impact for cirrhotic patients at risk of developing HE for whom the prognosis is typically very poor. Prof. Bernardi said: “Hepatic encephalopathy is an insidious disease that’s caused by an accumulation of toxins in the blood that are normally removed by the liver. Treatment normally involves the use of antibiotics or laxatives to suppress the production of toxic substances in the intestine but there is still a great deal of room for improvement so it will be exciting to see the results of further studies to determine if clinicians have a new form of treatment on the cards.” Hepatic encephalopathy is a spectrum of neuropsychiatric abnormalities including personality changes, intellectual impairment and reduced levels of consciousness in patients with liver failure, after exclusion of other known brain disease. ### Disclaimer: the data referenced in this release is based on the submitted abstract. More recent data may be presented at the International Liver Congress? 2013. Notes to Editors About EASL EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy. EASL’s main focus on education and research is delivered through numerous events and initiatives, including:
About The International Liver CongressTM 2013 The International Liver Congress? 2013, the 48th annual meeting of the European Association for the study of the Liver, is being held at the RAI Convention Centre in Amsterdam from April 24 ? 28, 2013. The congress annually attracts in excess of 9,000 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field. References: 1 M.K Lunia, AN OPEN LABEL RANDOMISED CONTROLLED TRIAL OF PROBIOTICS FOR PRIMARY PROPHYLAXIS OF HEPATIC ENCEPHALOPATHY IN PATIENTS WITH CIRRHOSIS. Presented at the International Liver CongressTM 2013 2 A. Agrawal, Secondary Prophylaxis of Hepatic Encephalopathy in Cirrhosis, An Open-Label, Randomized Controlled Trial of Lactulose, Probiotics, and No Therapy. Available http://www.medscape.com/viewarticle/767674_3 [Accessed 9/4/13] 3 World Health Organization and Food and Agriculture Organizationof the United Nations. Health and Nutritional Properties of Probiotics in Food including Powder Milk with Live Lactic Acid Bacteria. Ava http://www.who.int/foodsafety/publications/fs_management/en/probiotics.pdf [Accessed 9/4/13] Contact: Dimple Natali |
| Novel therapeutic approaches to cure chronic HBV infection Posted: 24 Apr 2013 09:00 PM PDT Exciting new data presented today at the International Liver Congress? 2013 include results from early in vitro and in vivo studies targeting covalently closed circular DNA (cccDNA), which may form the basis of a cure for chronic hepatitis B virus (HBV) infection.
HBV cccDNA is organized into mini-chromosomes within the nucleus of infected cells by histone and non-histone proteins. Despite the availability of efficient therapies against HBV, long-term persistence of cccDNA necessitates life-long treatments to suppress the virus. The following three experimental studies demonstrate effective HBV-cccDNA targeting/depletion using novel therapeutic approaches which offer the potential of a cure. Liver regeneration induces strong reduction of viral replication and cccDNA levels, but not complete cccDNA eradication; without antiviral treatment, de novo HBV infection can be re-established. Key findings of research in HBV-infected human hepatocytes using the uPA/SCID chimeric mouse system show that liver regeneration induces strong reduction of viral replication and cccDNA levels, with rapid formation of cccDNA-free hepatocytes. However, because complete cccDNA eradication is not achieved, in the absence of antiviral treatment, de novo HBV infection could be re-established in quiescent (non-dividing) human hepatocytes. This suggests that induction of hepatocyte turn-over together with antiviral drugs inducing viral suppression, such as nucleoside analogues and IFN, or blocking cell entry, may accelerate the clearance of the viral minichromosome. Targeting epigenetic control of nuclear cccDNA minichromosome to suppress HBV transcription and replication may form basis for other therapeutic approaches to curing chronic HBV infection. In the infected liver cell the rate of replication of HBV is regulated by the acetylation or methylation of histone proteins which surround the cccDNA minichromosome ? so called epigenetic regulation. In a separate innovative study, the suppression of HBV transcription and replication by small molecules that target the epigenetic control of nuclear cccDNA minichromosome was investigated. The different classes of small molecules studied included: Class I, II and III histone deacetylase inhibitors (HDACi); p300 and PCAF histone acetyltransferases (HAT) inhibitors; hSirt1 activators; JMJD3 histone demethylase inhibitors. The combined inhibition of p300 and PCAF HATs resulted in an evident reduction of HBV replication which mirrored the decrease of pgRNA transcription. The hSirt1/2 activator MC2791 and the JMJD3 inhibitor MC3119, albeit with different efficiency, inhibited both HBV replication and cccDNA transcription. Results represent a proof of concept that activation of hSirt1 and Ezh2 (through the inhibition of its functional antagonist JMJD3) by small molecules can induce an active epigenetic suppression of HBV cccDNA minichromosome similar to that observed with IFN?, and lead to persistent cccDNA silencing. Lymphtoxin beta receptor (LTbR) agonisation represents basis for novel alternative therapeutic approach to curing chronic HBV infection. The final study demonstrated that stimulating the lymphtoxin beta receptor (LTbR) provides an effective, long lasting and non-cytopathic mechanism for achieving effective HBV-cccDNA depletion in infected hepatocytes. Cell culture models including HBV-infected HepaRG cells and primary human hepatocytes were used to test the effect of antibodies stimulating human LTbR (BS1 or CBE11). Results show that a strong and dose-dependent anti-HBV effect was achieved by activation of the LTbR. All HBV replication markers were decreased with this treatment, including cccDNA in cells where HBV infection was already established. Hepatitis B is the most prevalent cause of chronic viral hepatitis and a major global health problem. Prof. Fabien Zoulim, EASL Educational Councillor commented on the exciting new data: “In chronic hepatitis B infection, the viral genome forms a stable minichromosome – the covalently closed circular DNA (cccDNA) – which can persist throughout the lifespan of the hepatocyte.” “Current treatments focus on suppression of HBV and discovery of compounds directly targeting cccDNA has been one of the major challenges to curing HBV infection; but these preliminary data show novel therapeutic approaches can be applied to successfully target cccDNA with the long-term aspiration of finding a cure” added Prof. Fabien Zoulim. Disclaimer: the data referenced in this release is based on the submitted abstract. More recent data may be presented at the International Liver Congress? 2013. ### Notes to Editors
About EASL EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy. EASL’s main focus on education and research is delivered through numerous events and initiatives, including:
About The International Liver CongressTM 2013 The International Liver Congress? 2013, the 48th annual meeting of the European Association for the study of the Liver, is being held at the RAI Convention Centre in Amsterdam from April 24 ? 28, 2013. The congress annually attracts in excess of 9000 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field. References:
1 Allweiss L et al, PROLIFERATION OF HEPATITIS B VIRUS INFECTED HUMAN HEPATOCYTES INDUCES SUPPRESSION OF VIRAL REPLICATION AND RAPID CCCDNA DECREASE IN HUMANIZED MICE. Presented at the International Liver Congress? 2013 2 Palumbo GA et al, SUPPRESSION OF HEPATITIS B VIRUS (HBV) TRANSCRIPTION AND REPLICATION BY SMALL 3 MOLECULES THAT TARGET THE EPIGENETIC CONTROL OF NUCLEAR CCCDNA MINICHROMOSOME. Presented at the International Liver Congress? 2013 4 Lucifora J et al, LYMPHOTOXIN BETA RECEPTOR ACTIVATION LEADS TO DEGRADATION OF HBV CCCDNA FROM INFECTED HEPATOCYTES. Presented at the International Liver Congress? 2013 Contact: Dimple Natali |
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