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Our study highlights the possible negative cardiovascular and hepatic impact associated with high-intensity binge drinking....
MedicalResearch.com Interview with: [caption id="attachment_47495" align="alignleft" width="133"] Prof. Carrat,[/caption] Prof. Fabrice Carrat, MD, PhD Institut Pierre Louis d'Épidémiologie et de Santé Publique, Paris, France MedicalResearch.com:...
Late post- liver transplantation survival after 5-years is 11% lower for alcohol-associated liver disease (vs. non-ALD). ...
Prof. Dr. F. Nevens, MD, PhD
Professor of Medicine
Hepatology and liver transplantation
University Hospitals KU Leuven, Belgium
MedicalResearch.com: What is the background for this study?
Response: Primary biliary cholangitis (PBC) is a rare, autoimmune cholestatic liver disease that puts patients at risk for life-threatening complications. PBC is primarily a disease of women, affecting approximately one in 1,000 women over the age of 40. If left untreated, survival of PBC patients is significantly worse than the general population.
The POISE trial evaluated the safety and efficacy of once-daily treatment with Ocaliva® (obeticholic acid) in PBC patients with an inadequate therapeutic response to, or who are unable to tolerate, ursodeoxycholic acid (UDCA), the current standard of care. Ocaliva is the first PBC therapy that targets the farnesoid X receptor (FXR), a key regulator of bile acid, inflammatory, fibrotic and metabolic pathways.
The trial’s primary endpoint was an alkaline phosphatase (ALP) level of less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% from baseline, and a total bilirubin level at or below the upper limit of the normal range after 12 months of obeticholic acid therapy. These liver biomarkers have been shown to predict progression to liver failure and resulting liver transplant or premature death in patients with PBC.
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MedicalResearch.com Interview with:
Andrew L. Mason MBBS MRCPI
Professor of Medicine,
Senior Scholar, Alberta Heritage Foundation for Medical Research
Director, The Applied Genomic Core,
Division of Gastroenterology and Hepatology
University of Alberta, Edmonton
Medical Research: What is the background for this study? What are the main findings?
Response: The study of viruses resembling mouse mammmary tumour virus (MMTV) dates back to the 1970s when virus like particles were discovered in breast milk of breast cancer patients. The virus was detected at low levels and ultimately researchers met a stalemate by the 1980s because no one could prove the existence of this agent. Interest waned in the study of betaretroviruses in humans when HIV was discovered in the 1980s.
We first found a similar agent in patients with primary biliary cirrhosis, an autoimmune liver disease in 2003. History repeated itself in as much as others could not find the virus and challenged us to show that a significant amount of patients had evidence of proviral integrations into the human genome, the gold standard for providing proof of retroviral infection. This we achieved by isolating biliary epithelium from patients undergoing liver transplantation and then investigating the presence of betaretrovirus proviral integrations in DNA extracted from liver, lymph nodes and biliary epithelial cells using a ligation mediated PCR technique coupled with next generation sequencing. The majority of patients with primary biliary cirrhosis had viral integration and RNA detected in their biliary epithelium, the site of disease and lymph nodes; however, the virus was difficult to detect in whole liver, reflecting the problem with prior studies.
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MedicalResearch.com Interview with:
Norbert Stefan, MD
Heisenberg Professorship for Clinical and Experimental Diabetology
Department of Internal Medicine IV
University Hospital Tübingen
Tübingen, Germany
MedicalResearch.com: What are the main findings of the study?
Dr. Stefan: Currently there is little evidence for an effective and safe pharmacological treatment of nonalcoholic fatty liver disease (NAFLD). Based on the fact that inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), the enzyme, that converts inactive cortisone into active cortisol in metabolic tissues such as liver and adipose, was found to be effective to improve lipid metabolism in animals, we hypothesized that inhibition of 11β-HSD1 may also prove to be effective to decrease liver fat content in patients with NAFLD. In our 12 week trial in 82 patients with NAFLD, inhibition of 11β-HSD1 with RO5093151 resulted in a 14 % decrease of liver fat content and in a resolution of NAFLD in 20 % of the patients. This was accompanied by a decrease of liver enzymes. Furthermore, inhibition of 11β-HSD1 brought about a reduction of body weight and total body- and visceral adipose tissue mass, while insulin sensitivity did not change. In agreement with findings from other trials, also in our study 11β-HSD1 inhibition was well tolerated and safe.
(more…)DETROIT – Kezhong Zhang, Ph.D., assistant professor of molecular medicine and genetics and of immunology and microbiology in the School...