Saturday, August 25, 2012

News Ticker-Hepatitis C And Vitamin D, New Hepatitis C Drugs And More

HCV News Ticker

 Vitamin D for Your Patients with Chronic Hepatitis C?

PII: S0168-8278(12)00602-2
Reference: JHEPAT 4348

To appear in: Journal of Hepatology
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Vitamin D is increasingly becoming recognized as an important physiological regulator with pleiotropic functions outside of its classical role in skeletal homeostasis. A growing body of clinical evidence highlights the prevalence and risks of vitamin D deficiency in patients suffering from chronic hepatitis C infection, and vitamin D supplementation has been proposed as an adjunct to current standards of care. This review considers the experimental evidence for the anti-inflammatory, anti-fibrotic and anti-viral effects of vitamin D, and discusses the therapeutic potential of vitamin D supplementation to protect against liver disease progression and improve responses to treatment.

Advances in hepatitis C virus (HCV) pharmaceutical development are being made at a blistering pace; however, highly effective, non-toxic therapies remain a hope for the future. This leaves an immediate need for interventions that can minimize disease progression and/or improve sustained virological response (SVR) rates in the short term.

The aging of the HCV-positive population is creating an epidemic of end stage liver disease. Many patients cannot wait for second and third generation direct acting antiviral drugs to reach the clinic. As an interim measure, vitamin D supplements have been proposed as an adjunct to pegylated-interferon and ribavirin. This review integrates the known biological effects of the vitamin D system with recent clinical findings and discusses the therapeutic potential of vitamin D supplementation in HCV-positive patients. 
Given the importance of viral clearance in the pre and post transplant setting such results have been thought to be somewhat unsatisfactory and the liver transplant community has been eagerly awaiting new anti- HCV therapies....

Despite some enthusiasm for the best of the second wave therapies, the third “wave” is likely to be the most significant and certainly most exciting. This wave aims to replace Interferon altogether. The regimes use DAAs in combination without Interferon but sometimes with Ribavirin eg: a HCV NS5A polymerase Inhibitor combined with second (or third generation) NS3/4 Protease Inhibitors or an NS5A inhibitor .....
Continue reading here....

J Hepatol. 2012 Aug 10. [Epub ahead of print]

Myocardial injury in patients with chronic hepatitis C infection
Maruyama S, Koda M, Oyake N, Sato H, Fujii Y, Horie Y, Murawaki Y.
Source - Maruyama Medical Clinic, Hamada, Japan.

*myocardial [mi″o-kahr´de-al] -pertaining to the muscular tissue of the heart


The existence of a direct pathogenic link between hepatitis C virus (HCV) infection and myocardial injury has not been confirmed. We investigated the association between myocardial conditions and HCV in patients with HCV-related chronic hepatitis using thallium-201 myocardial scintigraphy.

In 217 consecutive cases of chronic HCV infection without overt heart disease, we performed electrocardiography (ECG), echocardiography, serum tests on myocardial injury and thallium-201 myocardial scintigraphy. Myocardial injury was confirmed by severity score (SS), which was calculated as the sum of thallium-201 perfusion defect scores. SS was followed prior to and after interferon (IFN) therapy in 200 patients with chronic hepatitis C.

An abnormal ECG was found in 9% of the patients with chronic hepatitis C. Abnormal severity score -SS was found in 87% of chronic hepatitis C patients. Independent factors related to higher pretreatment severity score-SS were histology activity index score, serum HCV RNA titer and indocyanine green disappearance rate.

After IFN therapy, SS was improved in patients with sustained virologic response. Among relapsers, the SS improved at the initial disappearance of HCV RNA, but SS worsened with reappearance of HCV RNA. The SS in non-viral responders did not change with IFN therapy.

Myocardial perfusion defects were found in 87% of the patients with chronic hepatitis C and improved with viral eradication from IFN therapy.

Copyright © 2012. Published by Elsevier B.V.
New at NATAP

New HCV Drugs: non nucleoside polymerase inhibitors

 Written by Jules Levin, NATAP

Many observers have written off the class of HCV drugs non nucleoside polymerase inhibitors because resistance can develop quickly but does it really matter if this drug is used in combination with 2 other potent HCV drugs???

HCV protease is a potent class (3-4.5 or even 5 logs for a few proteases), as well HCV nucleotide is also a potent class (4.5 logs) and of course a big reason it's liked is because resistance is very hard to develop or won't at all. And of course NS5A is a potent class of drug (4-5 logs).

The non nucleoside polymerase inhibitors in development have shown a wide range of potency from 1.3 logs to 3.5 logs on average). Here is a review of this 'can't get no respect' class. What is interesting about this class is several of these drugs are fairly well along in development and are not far at all away from becoming avaliable. In phase 3 right now however.....Continue reading..

NH hospital workers urged to get tested following hepatitis C outbreak blamed on lab worker

MANCHESTER, N.H. — A New Hampshire hospital says it’s notifying about 500 employees and affiliated clinicians the state is recommending they be tested for hepatitis C after an outbreak of the disease linked to a lab worker there.

Exeter Hospital will be coordinating testing over the next two weeks.

The state public health department has held numerous testing clinics for patients of the hospital, where a former worker has been accused of stealing drugs and contaminating needles used on patients in the cardiac catheterization lab. Thirty-two former lab patients have been diagnosed with the same strain of hepatitis C as David Kwiatkowski (kwiht-KOW’-skee) since the investigation began in May.
Continue reading....

Healthy You

Elderly patients get inappropriate scripts
By Kirsty Oswald
23 August 2012 -PLoS ONE7: e43617

medwireNews: One in five prescriptions in primary care for the elderly is inappropriate, say the authors of a systematic review.
The review, which included data from 11 countries, including the UK, showed that both high- and low-risk medications were subject to inappropriate prescriptions.
"In spite of increasing attention to the quality of medication prescription among elderly persons presenting to the primary care setting, there are still high overall rates of inappropriate medication prescription [IMP]," say Dedan Opondo (University of Amsterdam, the Netherlands) and colleagues.

The systematic review included 19 English-language studies, which analysed rates of IMPs in patients aged over 65 years. They used the Beers criteria, which lists medications appropriate for elderly patients, and other tools to assess rates of IMP.
The authors found that the median rate of IMPs was 20.0%. However, it varied highly between studies, ranging from 2.9% to 38.5%.
The four most common IMPs were the pain reliever propoxyphene (4.5%), the antihypertensive doxazosin (4.0%), the antihistamine diphenhydramine (3.3%), and the antidepressant amitriptyline (3.2%).
Additionally, the authors found that some high-risk medications, such as diazepam and nifedipine, had high rates of IMPs compared with other medications in their therapeutic classes.

Writing in PloS One, they say that their results show a need for interventions in primary care to improve the quality of prescriptions for the elderly: "Prescription of high-risk medication exposes the elderly to frequent and severe adverse drug events. Alternative low-risk medications should be prescribed when available."
medwireNews ( ) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012

Monday Aug 20 2012

One-in-four over-65s 'will have had cancer by 2040', according to the Daily Mail. The news is based on a study that estimated the number of people expected to be living with cancer in the UK by the year 2040
Continue reading...

HDL: Not So “Good” After All?
After years of having it drilled into their heads, most people now know that LDL (low-density lipoprotein) is the “bad” cholesterol package that increases the risk of cardiovascular disease, and HDL (high-density lipoprotein) is the “good” type that helps reduce it by removing cholesterol from artery walls. So if your HDL number is high, you’ve probably patted yourself on the back; if it’s low, you may have tried to raise it by, for instance, exercising more, losing weight, drinking a daily glass of wine, or even taking medication, such as high-dose niacin.
But before you get too hung up on HDL, you should know that while the benefits of lowering elevated LDL are proven, the evidence for raising HDL by itself remains uncertain. That’s why standard cholesterol guidelines have focused almost exclusively on lowering LDL, which is the main purpose of statin drugs (they have little effect on HDL). And recently a study in the Lancet raised fundamental questions about the supposed benefits of raising HDL.
Genetic factors help determine HDL levels, sometimes very strongly. In the Lancet paper, an international team of researchers analyzed data from 20 studies involving people with genetic variants that raise HDL but do not affect LDL, triglycerides, or related blood lipids. They did a special kind of genetic analysis (called Mendelian randomization) that allowed them to determine whether high HDL, in and of itself, reduces coronary risk. Surprisingly, the evidence indicated that it does not.
An iffy link
Researchers and doctors have focused on HDL for good reason: observational studies have consistently found that people with high HDL levels are at decreased cardiovascular risk. But just because there’s an association between low HDL and heart disease, that doesn’t mean that low HDL causes it—or that raising HDL will help prevent it. Many factors in the blood can be higher or lower with certain diseases, but relatively few actually cause the diseases. Low HDL tends to go along with other metabolic abnormalities that could directly increase risk for coronary disease, such as high levels of smaller LDL particles and increased triglycerides (fats in the blood).
So the question remains, is low HDL an independent risk factor for cardiovascular disease or merely a marker for it?
What about drugs to raise HDL?
The Lancet study was not the first disappointing finding about the potential benefits of raising HDL. According to the accompanying commentary, the study confirms previous genetic analyses that “refute a causal role of HDL in coronary heart disease.”
Moreover, in recent years two high-profile HDL-boosting drugs were scrapped after they failed to produce the expected benefits in pre-approval studies; one actually increased cardiovascular risk. And as we reported last year, a major study called AIM-HIGH found that prescription niacin did not further reduce the risk of heart attacks or other cardiovascular events in high-risk people who had already lowered their LDL levels via high-dose statins—even though niacin raised HDL. (Niacin also lowers LDL and triglycerides, which may explain why it was shown to be beneficial in prior studies.) Other drugs are being developed to raise HDL substantially, but in ways different from the previous drugs.
The relationship between HDL and cardiovascular disease is complicated, largely because the biochemistry of HDL is so complex. Not only does HDL interact with other lipids in the blood, but all HDL is not alike. Some HDL may do a good job at keeping arteries healthy, while other HDL may not. HDL particle size and levels of various subparticles, as well as levels of inflammation and oxidative stress in the body, may determine if, and how much, HDL is cardioprotective.
Bottom line
There are many unanswered questions about HDL. It’s becoming increasingly clear that there’s more to it than that single number from a basic blood test. Still, low HDL is, at the very least, a marker for increased cardiovascular risk, and should be considered in the context of your other risk factors. It may, for instance, lead your doctor to order advanced blood tests for additional cholesterol-related components such as small LDL particles. A low HDL number may also lead your doctor to more aggressively lower your LDL by medication. If you have low HDL, you should still exercise, quit smoking, and lose excess weight. Such steps help protect the heart in many ways, regardless of their effect on HDL.
Issue: September 2012

No comments:

Post a Comment