Uploaded by CBCTheNational on Mar 2, 2012
New statistics in Canada and the U.S show more people are now dying from Hepatitis-C than from H-I-V.
Cirrhotic patients experience increased daytime sleepiness from higher ammonia levels
Source
Italian and Swiss researchers confirm that induced hyperammonaemia significantly increases daytime sleepiness in patients with cirrhosis. The findings available in the March issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases, show that higher blood levels of ammonia reduced the ability of cirrhotic patients to produce restorative sleep.
In patients with chronic liver failure neuropsychiatric abnormalities may arise—termed hepatic encephalopathy (HE)—which experts believe to be due to neurotoxic substances that originate in the gut and are not cleared by the liver, such as ammonia. HE is common following a gastrointestinal bleed, which can be simulated by the oral administration of a mixture of protein mimicking that contained in blood ('amino acid challenge'; AAC).
To investigate the effects of excess ammonia and HE on sleep-wake patterns in patients with cirrhosis, Dr. Sara Montagnese and colleagues from the Dipartimento di Medicina in Padova, Italy and the Institute of Pharmacology and Toxicology in Zurich, Switzerland, induced hyperammonaemia in participants by an AAC. Ten cirrhotic patients and ten healthy controls underwent eight days of sleep quality monitoring, neuropsychiatric/wake and sleep EEG assessment prior to and following the AAC, and hourly ammonia and sleepiness assessments for eight hours post-AAC.
"Our study found that induced hyperammonaemia led to a significant increase in daytime sleepiness in both patients and healthy volunteers," said Dr. Montagnese. The authors also report changes to the EEG architecture of a sleep episode (nap) in patients with cirrhosis, which they believe points to a reduced ability to produce restorative sleep.
Dr. Montagnese concludes, "Our findings have important clinical implications in that subjective sleepiness may be used as a surrogate marker for HE." The authors also suggest that strategies aimed at reducing daytime sleepiness may result in improved sleep at night.
More information: "Induced Hyperammonaemia may Compromise the Ability to Generate Restful Sleep in Patients with Cirrhosis." A Bersagliere, ID Raduazzo, M Nardi, S Schiff, A Gatta, P Amodio, P Achermann and S Montagnese. Hepatology; January 19, 2012 (DOI: 10.1002/hep.24741); Print Issue Date: March 2012
Provided by Wiley (news : web)
Hypoferremia Predicts Treatment Response to IFN-α
Last Updated: March 01, 2012.
Induction of hepcidin, subsequent drop in serum iron may be marker of treatment efficacy in HCV
Source
For patients with hepatitis C virus, hepcidin, a regulator of iron homeostasis, is induced following a single dose of pegylated interferon-α, and may be a surrogate marker of immediate efficacy of interferon-α, according to a study published online Feb. 15 in Hepatology.
THURSDAY, March 1 (HealthDay News) -- For patients with hepatitis C virus (HCV), hepcidin, a regulator of iron homeostasis, is induced following a single dose of pegylated interferon-α (PEG-IFNα), and may be a surrogate marker of immediate efficacy of IFN-α, according to a study published online Feb. 15 in Hepatology.
John D. Ryan, M.D., of the Mater Misericordiae University Hospital in Dublin, and associates analyzed blood samples of HCV patients to assess the clinical importance of the changes in iron homeostasis during the first 24 hours of treatment with PEG-IFNα.
The researchers found that a single dose of PEG-IFNα triggered a significant increase in serum hepcidin that peaked at 12 hours. This coincided with a 50 percent drop in serum iron and transferrin saturation over 24 hours. Significantly lower levels of serum iron and transferring saturation were seen at 12 and 24 hours in patients with a ≥2 log decrease in HCV viral load over the first 24 hours. Serum iron levels at 24 hours were an independent predictor of immediate HCV viral decline. Direct induction of hepcidin by IFN-α was seen in cell culture, and was controlled by the STAT3 transcription factor.
"Hepcidin induction occurs following the initiation of PEG-IFNα treatment for HCV, and is mediated via STAT3 signaling," the authors write. "The subsequent hypoferremia was greatest in those with the most significant decline in viral load, identifying systemic iron withdrawal as a marker of immediate IFN-α efficacy in HCV patients."
Addressing Vertex / Gilead Confusion
Source - Seeking Alpha
Hepatitis C virus (HCV) treatments are moving stocks of HCV developers up and down in a chaotic way that makes no sense. While Vertex’ (VRTX) Incivek sales have been breaking the record of drug sales, investors who have been fed immature and unconfirmed knowledge that Pharmasset’s oral HCV therapeutics combination will render Incivek obsolete caused a sell-off in VRTX. Investor logic that patients would definitely prefer all oral drugs over a combination that has injectable alfa interferon is undisputable, that’s we too are waiting for a successful all oral HCV treatment, which has yet to emerge.
With the media stressing that Pharmasset was the firm that will put the magic combination on the market, Pharmasset's stock doubled from over $20 in January 2010, to around $45 at the end of December. In 2011, the stock rallied again from $45 in January to $135 in August, split 2 to 1 and started climbing back from around $66 to $72. The firm was then acquired by Gilead (GILD), which paid an additional 67% premium over its obese market price, i.e., around over $130 per share.
This scenario does not make sense to us. Contrary to the market’s culture, investors, for one reason or another, sold a real present to buy a future designed on mere speculation. They sold VRTX, a company that had a marketed HCV drug, which is the first ever to represent a cure for the life-threatening HCV infection and whose sales have been actually generating record revenues to buy into Pharmasset’s oral combination while still in mid-trial and requires more lengthy experimentation before confirming the all-oral combination’s safety and long-term efficacy.
Just before concluding the acquisition deal, on December 16, 2011, Pharmasset surprisingly announced its decision to discontinue all treatment arms with a regimen containing its drug PSI-938 because of laboratory abnormalities associated with liver function in subjects receiving the drug at a dose of 300 mg/day. This news surprised investors, especially Gilead’s shareholders who began to question the value of the deal with Pharmasset. The news did not alter Gillead’s decision to acquire the company. After the acquisition, Gilead’s stock experienced a temporary retreat. Many investors believed that $11 billion was an unprecedented high amount of money to be paid for molecules that have yet to complete clinical trials, confirming their superiority as described by the media since 2009. Investors’ temporary negative reaction toward the deal was the only understandable action in this story.
It did not take time for GILD to fiercely rebound after the firm announced its financial results. The stock was up to $56, matching its new high for the past three years. Less than two months later, though, other trial results with Pharmasset’s combination on HCV genotype 1 patients with a prior “null” response to an interferon-containing regimen demonstrated that the majority of patients experienced viral relapse within four weeks of completing 12 weeks of treatment with what has become Gilead’s combination of GS-7977 plus ribavirin (RBV). GILD tumbled, trading now at around $45, after loosing around 15% of its value.
In the mean time, Vertex is generating millions of dollars selling its selective HCV protease inhibitor. Its stock, though, remained boxed - sold every time it makes an attempt to rally even though Vertex is also trying its own all-oral combination. The stock remained boxed even after data from two treatment arms of the Phase 2 ZENITH study evaluating an interferon-free (all-oral) treatment regimen of the non-nucleoside polymerase inhibitor VX-222 in combination with INCIVEK (telaprevir) tablets and ribavirin in people with genotype 1a or 1b hepatitis C who were new to treatment have demonstrated promising safety and efficacy and after learning that the data from this study will be used to design a Phase 3 program with the goal of submitting a New Drug Application (NDA) to the FDA for the first interferon-free regimen for genotype 1 (1a and 1b) patients by the end of 2014 or beginning of 2015.
Investors didn’t even bother considering the fact that Vertex and its collaborator Alios BioPharma are conducting Phase 1 studies of two structurally-distinct nucleotide polymerase inhibitors, ALS-2200 and ALS-2158. Vertex has begun the first seven-day viral kinetic studies of ALS-2200 and ALS-2158 in people with genotype 1 hepatitis C, whose safety and viral kinetic data expected in the second quarter of 2012. Positive results would enable the initiation of Phase 2 studies in the second half of 2012 to evaluate multiple interferon-free combination regimens of ALS-2200, ALS-2158, INCIVEK, VX-222 and/or ribavirin.
What continued to make no sense at this stage is that investor pessimism with Gilead's all-oral combination that erased 15% of GILD price, did not transform into optimism for VRTX, which was cremated by the enthusiasm for Gilead’s drug that investors are now experiencing doubt about. It looks as if investors are sensitized to not appreciate the firm that introduced the first HCV cure and the first approved cystic fibrosis drug that works at the root cause of the disease, knowing in fact that Vertex has plans ready to bring breakthrough treatments to all cystic fibrosis patients.
Gilead is a great firm and at the end of the day it will probably succeed in bringing an HCV breakthrough treatment to the market. But this does not mean that Vertex will not succeed reaching the same goal. Vertex is also a great firm that has already changed the way chronic life-threatening diseases have been treated. Gilead has a lot of current and upcoming good news and so does Vertex. The HCV market is huge. It requires more than one, or two treatments to satisfy its needs.
Disclosure: We are long both firms.
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