Liver Key To Development of Diabetic Vascular Complications

MedicalResearch.com Interview with:

Dr. Mauricio Berriel Diaz Deputy Director & Head of Division Metabolic Dysfunction and Cancer Institute for Diabetes and Cancer IDC Helmholtz Center Munich and Joint Heidelberg-IDC Translational Diabetes Program Heidelberg University Hospital, Molecular Metabolic Control Medical Faculty, Technical University Munich Neuherberg, Germany

Dr. Berriel Diaz

Dr. Mauricio Berriel Diaz
Deputy Director & Head of Division Metabolic Dysfunction and Cancer
Institute for Diabetes and Cancer IDC
Helmholtz Center Munich and
Joint Heidelberg-IDC Translational Diabetes Program
Heidelberg University Hospital, Molecular Metabolic Control
Medical Faculty, Technical University Munich
Neuherberg, Germany 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Our institute takes part in a german collaborative research consortium (https://www.klinikum.uni-heidelberg.de/index.php?id=132204&L=1), in which the key objective is to understand why in diabetes mellitus late complications occur even when blood sugar is well controlled.

Our study focused the role of the liver and of inflammatory signaling, as the latter is known to be increased in metabolic diseases such as obesity and diabetes mellitus. We found that TNF-α-induced reactive oxygen species (ROS) formation in the liver abolished the function of the transcription factor GAbp. Impaired hepatic GAbp function resulted in transcriptional inactivation of the cellular energy sensor AMPK, which in turn induced hepatic cholesterol secretion, hypercholesterolemia and eventually atherosclerotic lesion formation.

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Genetic Marker Can Determine Cirrhosis Patients Who Do Not Benefit From Hepatitis C Cure

MedicalResearch.com Interview with:

Dr. Winston Dunn, MD Assistant Professor The University of Kansas Medical Center

Dr. Dunn

Dr. Winston Dunn, MD
Assistant Professor
The University of Kansas Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It is widely believed that everyone with HCV can be cured with the medications now a day. But sadly, about 5% of the patients already have very bad damage done to the liver. We call this decompensated cirrhosis. Our medication is still very effective in curing the virus, but in decompensated cirrhosis, curing the virus is not always enough.

Only about half to two-thirds of patients with decompensated cirrhosis clinically gets better, but the remaining struggles along or even gets worse after the cure. That is the problem. So, our research was to understand why that was.

We used genetic factor to predict which patient would get better and which patient would not. We found that a gene previous found to be predictive of fatty liver and fibrosis is also predictive of recovery in this setting.

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Metformin Associated With Lower Mortality in CKD, CHF and Chronic Liver Disease

MedicalResearch.com Interview with:

Matthew J. Crowley, MD, MHS Assistant Professor of Medicine Member in the Duke Clinical Research Institute Duke University Medical Center

Dr. Matthew Crowley

Matthew J. Crowley, MD, MHS
Assistant Professor of Medicine
Member in the Duke Clinical Research Institute
Duke University Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Although metformin is widely considered to be the first-line drug for type 2 diabetes, concerns about lactic acidosis have traditionally limited its use in some populations. However, FDA now indicates that metformin may be used safely for patients with mild-moderate chronic kidney disease and other historical contraindications like congestive heart failure. With the lactic acidosis question addressed for these groups, this review asked “what do we know about how metformin affects mortality and other outcomes for patients with historical contraindications and precautions?”

The main take-home message is that metformin appears associated with lower mortality in patients with mild-moderate chronic kidney disease, congestive heart failure, and chronic liver disease.

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Many High Risk Patients Not Screened for Hepatitis B

MedicalResearch.com Interview with:

Robert Wong MD, MS OakCare Medical Group Assistant Clinical Professor UCSF

Dr. Robert Wong

Robert Wong MD, MS
Assistant Clinical Professor of Medicine
Director of Research and Education
Division of Gastroenterology and Hepatology
Alameda Health System – Highland Hospital

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Hepatitis B Virus infection is a leading cause of chronic liver disease leading to hepatocellular carcinoma and cirrhosis worldwide. Early detection of chronic HBV through implementation of effective screening programs can improve early treatment to reduce disease progression and risk of hepatocellular carcinoma. Sub-optimal awareness of the importance of HBV screening among patients and providers and sub-optimal awareness of who constitutes as high risk may further contribute to low HBV screening rates. Our current study prospectively evaluated rates of HBV screening and awareness of HBV screening results among patients at high risk for chronic HBV among an ethnically diverse underserved safety-net hospital population.

Among nearly 900 patients that were evaluated, 62% were high risk and eligible for Hepatitis B screening. However, among this high risk population, less than 25% received HBV screening. Furthermore, among patients that have undergone previous HBV testing only 22% of patients were aware of those results.

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Fatty Liver At Least Partially Mediated By Epigenetic Influences

MedicalResearch.com Interview with:

Annette Schürmann PhD Department of Experimental Diabetology German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) Nuthetal Germany German Center for Diabetes Research (DZD München-Neuherberg Germany

Dr. Annette Schürmann

Annette Schürmann PhD
Department of Experimental Diabetology
German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE)
Nuthetal
Germany German Center for Diabetes Research (DZD
München-Neuherberg Germany

MedicalResearch.com: What is the background for this study?

Response: The aim of our study was to clarify why genetically identical mice respond very different to a high fat diet. Some of the mice react with an elevated body weight, others not. We analyzed the expression pattern
of liver at two time points, at the age of 6 weeks, (the earlierst time
point to distiguish between those that respond to the diet (responder
mice) and those that did not (non-responders)), and at the age of 20
weeks. One transcript that was significantly reduced in the liver of
responder mice at both time points was Igfbp2. The reason for the
reduced expression was an elevated DNA-methylation at a position that is
conserved in the mouse and human sequence. The elevated DNA-methylation
of this specifc site in human was recently described to associate with
elevated fat storage (hepatosteatosis) and NASH. However, as 6 weeks old
mice did not show differences in liver fat content between responder and
non-responder mice we conclude that the alteration of Igfbp2 expression
and DNA metyhlation occurs before the development of fatty liver.

Our data furthermore showed that the epigenetic inhibition of Igfbp2
expression was associated with elevated blood glucose and insulin
resistance but not with fatty liver.

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POISE Data Support New Medication Ocaliva For Primary Biliary Cholangitis

MedicalResearch.com Interview with:

Prof. Dr. F. Nevens, MD, PhD Professor of Medicine Hepatology and liver transplantation University Hospitals KU Leuven, Belgium

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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Pioglitazone Is Safe and Effective Option For Patients with Type 2 Diabetes and NASH

MedicalResearch.com Interview with:

Kenneth Cusi, M.D., F.A.C.P., F.A.C.E. Professor of Medicine VAMC staff Chief, Division of Endocrinology, Diabetes and Metabolism The University of Florida Gainesville, FL 32610-0226

Dr. Kenneth Cusi

Kenneth Cusi, M.D., F.A.C.P., F.A.C.E.
Professor of Medicine
VAMC staff
Chief, Division of Endocrinology, Diabetes and Metabolism
The University of Florida
Gainesville, FL 32610-0226

MedicalResearch.com: What is the background for this study?

Dr. Cusi: Many patients with prediabetes or Type 2 Diabetes Mellitus (T2DM) are not diagnosed with Nonalcoholic steatohepatitis (NASH), a disease that is the second cause of liver transplantation in the United States. It is also associated with worse cardiovascular disease and harder to control T2DM. We had done in this population a proof-of-concept study published in Nov 2006 in the NEJM. But we lacked a larger, long-term study for definitive proof. This is the largest SINGLE center study, and the longest ever (3 years).

NASH is an overlooked problem for perhaps as many as one-third of patients with Type 2 Diabetes Mellitus. There is now a safe and effective treatment option for patients with T2DM and NASH – pioglitazone will become for NASH what metformin is to the treatment of T2DM: a safe, effective, the “backbone therapy” to which other treatments will be added.

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Caffeine May Slow Progression of Liver Fibrosis in Chronic Hepatitis C

MedicalResearch.com Interview with:

Sikarin Upala MD, MS, LLB Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, New York Preventive and Social Medicine Mahidol University, Bangkok, Thailand

Dr. Sikarin Upala

Sikarin Upala MD, MS, LLB
Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, New York
Preventive and Social Medicine
Mahidol University, Bangkok, Thailand

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Upala: Chronic hepatitis C virus infection is the most common cause of chronic liver disease and cirrhosis as well as the most common cause of liver transplantation in the United States. As caffeine has been found to be related to decreased liver enzymes, chronic liver disease,cirrhosis, and risk of hepatocellular carcinoma in several liver disease pathologies. There is inconclusive findings on the effect of caffeine on hepatitis C infected patients. Thus, we conducted a systematic review and meta-analysis to summarize the effect of caffeine consumption in patients with chronic hepatitis C.

We found that caffeine consumers have a 61% reduced risk of developing advanced hepatic fibrosis, which is one of the consequence of chronic hepatitis C. Our meta-analysis result is in the same way with other studies who found that coffee consumption could prevent the development of hepatic fibrosis in patients with liver disease. However, we cannot conclude about the effect of caffeine on HCV viral load as there is not enough information.

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Epigenetic Factors Linked to Glucose Tolerance and Fatty Liver Development

MedicalResearch.com Interview with:

Prof-Dr. Annette Schürmann Department of Experimental Diabetology German Institute of Human Nutrition Potsdam-Rehbruecke Nuthetal, Germany

Dr. Annette Schürmann

Prof-Dr. Annette Schürmann
Department of Experimental Diabetology
German Institute of Human Nutrition Potsdam-Rehbruecke
Nuthetal, Germany

MedicalResearch.com: What is the background for this study?

Dr. Schürmann: The aim of our study was to clarify why genetically identical mice respond very different to a high fat diet. Some of the mice react with an elevated body weight, others not. We analyzed the expression pattern
of liver at two time points, at the age of 6 weeks, (the earliest time
point to distinguish between those that respond to the diet (responder
mice) and those that did not (non-responders)), and at the age of 20
weeks. One transcript that was significantly reduced in the liver of
responder mice at both time points was Igfbp2. The reason for the
reduced expression was an elevated DNA-methylation at a position that is
conserved in the mouse and human sequence. The elevated DNA-methylation
of this specific site in human was recently described to associate with
elevated fat storage (hepatosteatosis) and NASH. However, as 6 weeks old
mice did not show differences in liver fat content between responder and
non-responder mice we conclude that the alteration of Igfbp2 expression
and DNA methylation occurs before the development of fatty liver.
Our data furthermore showed that the epigenetic inhibition of Igfbp2
expression was associated with elevated blood glucose and insulin
resistance but not with fatty liver.

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New HCV Treatment Improves Hepatitis C Cirrhosis

Dr. Michael P. Curry, MD Medical Director for Liver Transplantation Harvard Medical Faculty Physicians Beth Israel Deaconess Medical Center

Dr. Curry

MedicalResearch.com Interview with:
Dr. Michael P. Curry, MD
Medical Director for Liver Transplantation
Harvard Medical Faculty Physicians
Beth Israel Deaconess Medical Center

Medical Research: What is the background for this study? What are the main findings

Dr. Curry: As the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase. For many years, the only treatment option for these patients was liver transplantation. Recently, however, clinical trials of newly approved direct-acting antiviral agents (DAAs) have shown that it is possible to treat HCV infection safely and effectively in patients with decompensated cirrhosis. We conducted this Phase 3, open-label trial to assess the efficacy and safety of a fixed dose combination of sofosbuvir/velpatasvir with or without ribavirin for 12 weeks or sofosbuvir/velpatasvir for 24 weeks in patients infected with hepatitis C virus genotypes 1 through 6 and with decompensated cirrhosis. We found that treatment with sofosbuvir/velpatasvir resulted in high rates of sustained virologic response (SVR) and early improvements in hepatic function in this patient population. SVR rates were 83 percent  in patients who received sofosbuvir/velpatasvir for 12 weeks, 94 percent among those who received sofosbuvir/velpatasvir plus ribavirin, and 86 percent among those who received sofosbuvir/velpatasvir for 24 weeks.

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