February 15, 2011

What Would You Do If You Witnessed AIDS Discrimination?

Feb. 15, 2011
Customers React as HIV-Positive Actor Faces Prejudice at Diner in WWYD Scenario
It's been exactly thirty years since AIDS -- the acquired immune deficiency syndrome -- was first recognized in the United States. Since then, more than half a million people have died from the disease in this country alone, and more than a million Americans are currently living with HIV, the virus that causes AIDS.
In the early days of the epidemic, little was known about what caused the illness or how it was transmitted, and rumors soon circulated that it could be spread by sneezing, a handshake, kissing or even sharing utensils. Growing public fear led some to call for a quarantine of those diagnosed with the disease. And in 1985, a 13-year-old boy named Ryan White, who contracted AIDS from a blood transfusion, made headlines when he was banned from attending school. It was just one of many instances of people living with AIDS being stigmatized and ostracized. Three decades later, we wanted to see if people still misunderstood the disease. Would they feel uneasy if they were near an individual who they knew was carrying the AIDS virus? We decided to find out and brought our hidden cameras to the Colonial Diner in Lyndhurst, N.J.
In our first scene, our hired actress playing the waitress engages in conversation with another actor, who is playing a customer who happens to be HIV positive. It's only partly an act: the actor, Daniel Logan, is HIV positive in real life. In conversation, Daniel reveals to the waitress that he is HIV positive. Vince, another actor hired by "WWYD" to play a customer, seated at the next stool at the counter, is alarmed.
"You have AIDS?" Vince asks. "No. That's different, it's HIV," Daniel replies. Vince then gets up from his seat and moves away from Daniel. Reactions like this were not uncommon 30 years ago. So how will it play today? Customer Joe Smith comforts Daniel and encourages him to ignore our rude actor, saying, "Don't talk to him. It doesn't pay. He doesn't understand."
Man Agrees That AIDS Might Be Spread Like Common Cold
But another customer seems to agree with our hypochondriac actor, Vince, who argues that the disease could be spread the same way a common cold or flu is: by sneezing or coughing. "He's right in a way," the customer tells Vince. "Think about it. If I get the flu and I sneeze on you, you're going to get the flu," and he wonders if HIV is spread the same way.
He is not the only one who's not sure how HIV is spread. A recent nationwide study from the Kaiser Family Foundation found that more than a quarter of adults still believe the virus can be transmitted simply by sharing a drinking glass. This, despite decades of scientific evidence that shows that HIV is primarily spread through infected blood.

That lack of awareness doesn't surprise our actor, Daniel, who says he's heard it all. "Growing up in Long Island in the suburbs," says Daniel, "you hear, you know, ignorance like that all the time. I mean there's some people out there that either refuse to accept it and learn about it more," he says.

Back at the diner, as soon as our waitress, Traci, tries handing Vince the same menu Daniel was holding, Vince starts hurling inappropriate comments. This time, the restaurant is all ears.

"C'mon he touched it," Vince complains. "I don't want it."

"You think you can get this from something I touched?" Daniel asks. "I'm just telling you I don't want to take any chances," Vince says.

But not everyone feels the way our actor, Vince, does. In fact, fellow diner Kelly Rivera not only consoles Daniel, she invites him to sit and have lunch with her and her neighbor. Later, she tells John Quinones, "I thought he was being treated really badly, and nobody should be treated like that. That's terrible."

In another scene, we have our female actress play the role of the anxious diner to see how people will react. As she informs other diners sitting nearby that Daniel has AIDS, they seem more irritated with her.

Traci asks, "Nobody has a problem with this?" "No one has a problem with this!" customer Rick Gimello responds. "You should just leave," adds customer Janis Mitchell.

When we caught up with Rick Gimello later to get his thoughts, he tells Quinones, "This is 2011. You know? The world ought to be educated enough to know what's going on."


February 14, 2011

Suicide risk in hepatitis C and during interferon-alpha therapy: a review and clinical update

Journal of Viral Hepatitis
Volume 18, Issue 3, pages 153–160, March 2011

S. Sockalingam 1,2,3, P. S. Links 3,4, S. E. Abbey 1,2,3

Article first published online: 10 NOV 2010
DOI: 10.1111/j.1365-2893.2010.01393.x
© 2010 Blackwell Publishing Ltd

Author Information
1 University Health Network, Toronto General Hospital, Toronto, ON, Canada
2 Medical Psychiatry Program, Toronto, ON, Canada
3 Department of Psychiatry, University of Toronto, Toronto, ON, Canada
4 Arthur Sommer Rotenberg Chair in Suicide Studies, Toronto, ON, Canada

* Correspondence: Sanjeev Sockalingam, University Health Network, Toronto General Hospital, 200 Elizabeth Street – 8EN-228, Toronto, ON M5G 2C4, Canada. E-mail: sanjeev.sockalingam@uhn.on.ca


Keywords: depression; hepatitis C; interferon-alpha; suicide

Summary.Chronic hepatitis C (CHC) affects over 170 million individuals worldwide and is a growing public health concern. Despite the availability of CHC treatment, specifically interferon-α and ribavirin, treatment of CHC is limited by concerns about psychiatric side effects including risks of suicide. Although depression has been the focus of neuropsychiatric complications from interferon-alpha (IFNα), emerging evidence has contributed to our understanding of IFNα-induced suicidal ideation and attempts. Using Pubmed, we performed a literature review of all English articles published between 1989 and April 1, 2010 on suicide in untreated and IFNα-treated patients with CHC. References in all identified review articles were scanned and included in our review. A total of 17 articles were identified. Studies have suggested that the first 12 weeks of IFNα therapy are the high-risk period. Moreover, the emergence of suicidal ideation can be linked to neuropsychiatric abnormalities, specifically serotonin depletion. Pretreatment with antidepressant treatment should be reserved for high-risk groups, as this may reduce the risk of depression and thus decrease the suicide risk indirectly. Although there is a paucity of literature on suicide and suicide risk during IFNα therapy for CHC, recent studies on IFNα-induced depression have provided some potential insights into suicide in this patient population. Further research examining the effects of pharmacological and nonpharmacological interventions on suicide risk during IFNα treatment is needed.


HIV Regimens Similar but Not Equivalent

By Michael Smith, North American Correspondent, MedPage Today
Published: February 14, 2011
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.

A large clinical trial fell short of showing that two commonly used approaches to a first anti-HIV treatment regimen are formally equivalent.

But the two -- based on either the ritonavir-boosted protease inhibitor atazanavir (Reyataz) or the non-nucleoside reverse transcriptase inhibitor efavirenz (Sustiva) -- still appeared to have similar efficacy, according to Eric Daar, MD, of Harbor-UCLA Medical Center in Torrance, Calif., and colleagues.

The failure to reach formal equivalence -- as defined before the study started -- was probably the result of a lower than expected rate of virologic failure two years into the study, Daar and colleagues reported online in Annals of Internal Medicine.

But a post-hoc analysis of the data suggested the probability of remaining free of failure differed by less than 10%, a threshold commonly used for defining equivalence, the researchers argued.

Treatment guidelines for initial HIV therapy suggest two nucleoside reverse transcriptase inhibitors combined with either a non-NRTI, a ritonavir-boosted protease inhibitor, or an integrase inhibitor, the researchers noted.

But there are limited data comparing atazanavir/ritonavir with efavirenz, they noted.

To help fill the gap, they conducted a randomized trial, in which the two lead compounds were added to common, once-daily combinations of nucleoside reverse transcriptase inhibitors -- either abacavir/lamivudine (Kivexa) or tenofovir/emtricitabine (Truvada).

The trial ran from September 2005 to November 2007, with a median of 138 weeks of follow-up, and the primary outcomes were time to virologic failure, safety, and tolerability.

All told, 1,857 patients were randomly assigned to one of the four treatment regimens and 1,331 completed the follow-up.

The primary efficacy hypothesis was that, within each of the NRTI arms, boosted atazanavir would be equivalent to efavirenz, Daar and colleagues noted.

The drugs were specified to be equivalent if a Cox proportional hazards model, using efavirenz as the reference, found the two-sided 95% confidence interval for the hazard ratio to be between 0.71 and 1.40.

But analysis showed:

• Among those randomized to the abacavir/lamivudine arms, the hazard ratio for time to virologic failure was 1.13 with a 95% confidence interval from 0.82 to 1.56. The difference was not statistically significant, at P=0.147.

• For those assigned to the tenofovir/emtricitabine arms, the hazard ratio was 1.01 with a 95% confidence interval from 0.70 to 1.46, which again was not significant, at P=0.37.

Although neither hazard ratio showed a significant difference, "neither met prespecified equivalence boundaries," the researchers reported.

However, analysis also showed that the probability of remaining free of virologic failure at week 96 was 83.4% for boosted atazanavir and 85.3% for efavirenz when they were combined with abacavir/lamivudine. The difference was -1.9 with a 95% confidence interval from -6.8 to 2.9, or 9.7 percentage points.

Values in the tenofovir/emtricitabine arms were 89% for boosted atazanavir and 89.8% for efavirenz, with a difference of -0.8 and a 95% confidence interval from -4.9 to 3.3, or 8.2 percentage points, the researchers reported.

Although the results did not meet the specified equivalence mark, the results suggest "for the first time in a large randomized study" that the two drugs have similar efficacy, the researchers argued.

They also found that safety and tolerability were slightly better for atazanavir than efavirenz when combined with abacavir/lamivudine, but there were no differences when they were combined with tenofovir/emtricitabine.

Daar and colleagues cautioned that when the study started it was not routine practice to test for HLA-B*5701 before using abacavir -- something that might have affected safety and tolerability results.

They also noted that study limitations include baseline drug resistance testing in only 40% to 50% of patients because of changing practices over time, premature unblinding of the NRTIs in the group of patients with high baseline viral loads, and change or discontinuation of the third drug in almost a third of patients.

The study was supported by the National Institute of Allergy and Infectious Diseases, and the National Center for Research Resources. Abbott Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences, and GlaxoSmithKline provided the study medications.

Daar reported financial links with Abbott Laboratories, Merck Laboratories, GlaxoSmithKline, Pfizer, Gilead Sciences, Bristol Myers Squibb, Tibotec, Schering-Plough, and Ardea Biosciences. Several authors reported being employed by the companies that supplied the study drugs.

Primary source: Annals of Internal Medicine
Source reference:
Daar ES, et al "Atazanavir plus ritonavir or efavirenz as part of a three drug regimen for initial treatment of HIV-1: A randomized trial " Ann Intern Med 2011.


New hepatitis C drug

14 February 2011

Scientists in the UK have developed a compound to combat the hepatitis C virus that could be taken as a pill.

David Pryde and his team from Pfizer Global Research and Development, Sandwich, have made new compounds to activate a protein in the immune system called TLR7 - toll-like receptor 7 - which fights the infection. Toll-like receptors identify foreign DNA, such as a virus, and produce proteins that inhibit the virus' replication.

300 million people suffer from hepatitis C worldwide. The virus that causes the disease resides in the liver and can lead to cirrhosis, with some sufferers requiring liver transplants. Current treatments only cure half of patients and are administered intravenously. Recent research has focused on increasing the effectiveness of the drugs and on developing oral treatments.

Pryde's team made heterocyclic analogues based on the structure of purines, known activators of TLR7 and the basis of current oral drugs. 'The most potent TLR7 agonists are purine-based,' explains Pryde. 'But we wanted to design potent non-purine based agonists to maximise the chances of avoiding any unwanted off-target pharmacology.'

The compounds activate a protein in the immune
system, which fights hepatitis C

When they tested the compounds against a hepatitis C cell line, the team found that one of the compounds, a trifluoromethyl derivative, was highly selective for TLR7. The agonist also had comparable performance to injected alternatives at doses below 50mg.

'Medicinal chemistry is often castigated for surrendering synthetic elegance in order to gain compound access. Pryde elegantly repudiates this, accomplishing both elegance and access,' says Adam McCluskey, an expert in drug design and discovery from the University of Newcastle, Australia.

Pryde and his team hope to make the agonist more soluble and to increase its potency further before moving on to human trials.

Catherine Bacon

Link to journal articleThe discovery of a novel prototype small molecule TLR7 agonist for the treatment of hepatitis C virus infection
David C. Pryde, Thien-Duc Tran, Peter Jones, Gemma C. Parsons, Gerwyn Bish, Fiona M. Adam, Mya C. Smith, Donald S. Middleton, Nick N. Smith, Frederick Calo, Duncan Hay, Michael Paradowski, Katie J. W. Proctor, Tanya Parkinson, Carl Laxton, David N. A. Fox, Nigel J. Horscroft, Giuseppe Ciaramella, Hannah M. Jones, Jonathan Duckworth, Neil Benson, Anthony Harrison and Rob Webster, Med. Chem. Commun., 2011
DOI: 10.1039/c0md00197j


Success rates for experimental drugs falls: study

By Bill Berkrot
Mon Feb 14, 2011 8:09am EST

NEW YORK (Reuters) - The success rate in bringing new medicines to market in recent years is only about half of what it had been previously, but biotech drugs are twice as likely to gain U.S. approval than more traditional chemical drugs, according to a new study released on Monday.

And while oncology has been one of the hottest and most active therapeutic areas for drug development, drugmakers may want to take note of a finding that new cancer drugs have proven far more difficult to gain approval than medicines for infectious and autoimmune diseases.

Drugmakers have been complaining about the difficulty of bringing new products to market in a regulatory climate that has become increasingly unpredictable and more likely to err on the side of safety in deciding risk/benefit ratios of experimental medicines.

Data from this new study appears to bear that out.

"It ain't getting any easier to develop new therapies." said Alan Eisenberg, head of emerging companies and business development for the biotech trade group Biotechnology Industry Organization (BIO), putting the findings succinctly.

"Knowing more about the magnitude of risk can lead to smarter drug development as well as smarter investing," he said.

The study, covering 2004 through 2010, found the overall success rate for drugs moving from early stage Phase I clinical trials to FDA approval is about one in 10, down from one in five to one in six seen in reports involving earlier years.

The study, conducted by BIO and BioMedTracker, which collects data on drugs in development, reviewed more than 4,000 drugs from companies large and small and both publicly traded and private. It was released in conjunction with the annual BioCEO and Investor conference in New York.

Adding weight to the desire by major pharmaceutical companies to become increasingly involved in biotechnology was a finding that biologics had a 15 percent chance of going from Phase I through to FDA approval, compared with a 7 percent success rate for traditional small molecule chemical drugs.

When broken down by therapeutic categories, the highest overall success rate from Phase 1 through likelihood of approval was infectious diseases, such as hepatitis and HIV drugs, at 12 percent, followed by endocrine system drugs, featuring diabetes treatments, at 10.4 percent, and autoimmune diseases, such as rheumatoid arthritis, at 9.4 percent, the study found.

John Craighead, BIO's managing director for investor relations, said clinical trial goals and the approval pathways for infectious diseases and diabetes drugs are clear and very well-established.

"The Phase II results are very predictive of the Phase III outcomes and very predictive of approval," he said.

"The overall success rate in oncology was the lowest of the therapeutic areas that we looked at," he said, noting that cancer studies vary dramatically in design and extending survival sets a high bar for approval.

The cancer drug success rate was a mere 4.7 percent, with cardiovascular drugs second-worst at 5.7 percent, as regulators are increasingly demanding proof that heart drugs reduce heart attacks and strokes rather than just lower a risk factor, such as cholesterol levels.

The largest dropout rate along the clinical pathway came in advancing drugs from mid-stage Phase II studies to late-stage Phase III testing.

Some 63 percent of drugs in Phase I testing advanced to Phase II, but only 33 percent of Phase II drugs made it to Phase III, which requires a commitment to larger and much more expensive clinical trials. Phase III is typically the final stage of human testing before a new drug is submitted to regulators for an approval decision.

Not surprisingly, the numbers increase after that as the drugs had already shown success in the clinic.

Approval applications were filed for 55 percent of the drugs that made it to Phase III testing, and 80 percent of those gained eventual approval, although only about half were approved on their initial FDA review.

The 80 percent approval rate, while seemingly high, is down from 93 percent seen in studies of earlier years.


Caring Ambassadors Program Launches Unique New DVD Series "Hepatitis C: Choices in Care"

Feb 14, 2011 11:31 ET

OREGON CITY, OR--(Marketwire - February 14, 2011) - The Caring Ambassadors Program (CAP) proudly announces the release of the new DVD series "Hepatitis C: Choices in Care -- Distinctive Viewpoints on Choices for Your Hepatitis C Journey." The 2-disc set offers over nine hours of leading expert physician interviews, patient consultations, panel discussions, Power Point presentations and 30 minutes of Qi Gong exercises specifically geared towards people living with hepatitis C.

About five million Americans are infected with HCV, making hepatitis C the most common chronic blood-borne viral illness in the U.S. HCV is the leading cause of chronic liver disease and liver cancer in the U.S. and the most common indication for liver transplantation. In January 2010, the Institute of Medicine (IOM) released its report, "Hepatitis and Liver Cancer, A National Strategy for the Prevention and Control of Viral Hepatitis." The committee found that many health care providers lack an adequate knowledge of HCV and that chronic hepatitis C patients are often confused about their treatment and disease management options.

The DVD series addresses these knowledge gaps by providing a shorter version of the book, Hepatitis C Choices, 4th Edition. The book presents evidence-based conventional and alternative treatment options and is the collective effort of leading medical experts and hepatitis C patient advocates. It is still the only book, and now DVD, of its kind.

"I was scared and did not know which way to turn when I was diagnosed with hepatitis C. I had a lot of unanswered questions," said Randy Dietrich, Board Chair of the Caring Ambassadors Program. "This information combined with the book was what I wanted to make an informed decision about my care."

The Caring Ambassadors Program produced "Hepatitis C: Choices in Care" to educate the public and health care community about hepatitis C. CAP believes it is vitally important that everyone with hepatitis C virus (HCV) know their disease status and have accurate and ample information to make the best health care decisions. Education is essential for making informed choices and taking charge of one's health.

"Hepatitis C: Choices in Care" is available for free viewing at the Caring Ambassadors Program Hepatitis C website at http://www.hepcchallenge.org/. The entire DVD series "Hepatitis C: Choices in Care" can also be purchased for $10.00 plus shipping and handling.

Lorren Sandt


February 13, 2011

HCV: Genotype & Quasispecies

Alan Franciscus Editor-in-Chief
Hepatitis C Support project
HCV Advocate

The term genotype refers to different genetic variations or strains of hepatitis C. The variance in genetic differences is approximately 1/3 between the different genotypes. There are six major groups or genotypes numbered 1 to 6 although some experts believe that there may be as many as 11. Within each genotype are further divisions called subtypes (for example 1a and 1b) and quasispecies.

HCV constantly changes and mutates as it replicates—more than 1 trillion hepatitis C virions replicate each day. During the replication process, the hepatitis C virus will make ‘bad’ copies or errors in the genetic make-up of the newly replicated viruses. The process of constant mutation helps the virus evade the body’s immune response---when the dominant quasi-species is eradicated, another quasi-species emerges. This requires the immune system to constantly identify and kill the newly emerged variants. This is one of the reasons why so many people develop chronic disease. Scientists believe there are literally millions of different HCV quasispecies in everyone infected with hepatitis C, which are unique to everyone because of the individual’s immune response to HCV and quasispecies constantly change over time. In addition, it has been suggested that quasispecies play a role in disease progression and treatment response, but this is still controversial and more studies are needed to fully appreciate the role of quasi-species.

This variability (genotype, subtypes and quasispecies) of hepatitis C has made it difficult to treat and to develop a vaccine that will protect against all HCV strains although recent advances in vaccine development have been encouraging.

Testing for Genotype, Subtype & Quasispecies

A blood test is required for the genotype test. Generally, a quasispecies test is only performed for research purposes. HCV genotype testing is only done once since the genotype does not change.

Genotype Distribution

HCV genotypes and subtypes are distributed differently in different parts of the world, and certain genotypes predominate in certain areas. Genotypes 1-3 are widely distributed throughout the world. Subtype 1a is prevalent in North and South America, Europe, and Australia. Subtype 1b is common in North America and Europe, and is also found in parts of Asia. Genotype 2 is present in most developed countries, but is less common than genotype 1. Some studies suggest that different types of HCV may be associated with different transmission routes. Subtype 3a appears to be prevalent among injection drug users and it is believed that they were introduced into North American and the United Kingdom with the widespread use of heroin in the 1960s.

Importance of Genotype Information

HCV Genotype information is important because of the role it plays in predicting HCV medical treatment response, treatment duration and the dose of ribavirin. However, it should never be used as a reason to deny treatment.

Prediction of Treatment Response

Genotype information is important because it can be used as a predictor of a positive treatment outcome or response. The sustained virological response rates for pegylated interferon plus ribavirin are much higher in genotype 2 and 3 compared with genotype 1.

Other predictors of treatment response include:

• Age of Patient – younger patients respond more favorably especially people under 30 years old.

• Sex of Patient – women are more likely to respond to therapy than men

• Histological (health of the liver) – people with minimal damage respond better to treatment

• Viral Load – the lower the viral load (less than 800,000 IU/mL) the more likely one is to respond to current medications

• Obesity or high Body Mass Index is associated with lower treatment response rates

• Steatosis or fatty liver reduces the chance of responding to treatment.

• Race—Caucasians and Asians respond better to current HCV medications.

Genotype and Treatment Response

Genotype 1 is considered the most difficult to treat with current HCV medications. However, treatment response rates with the newer forms of pegylated interferon plus ribavirin have been remarkably high--up to a 51% sustained virological response rate (SVR – undetectable viral load six months post treatment). Genotype 2 and 3 respond even better to current medications—up to 80%. There is some evidence that genotype 2 responds better to current HCV therapies than genotype 3, but this needs to be confirmed in prospective studies. The reason that a particular genotype responds to treatment differently is unknown, but it is speculated that specific genotypes of the hepatitis C virus live longer or shorter than others. For example, it has been theorized that genotype 2 and 3 of the hepatitis C virus do not live as long (viral lifecycle) as genotype 1 thus making eradication of genotype 2 and 3 easier.

Genotype and Treatment Duration

Genotype is also a factor in the period of time required to treat with current HCV medications. Generally, genotype 1 is treated for 48 weeks and genotype 2 and 3 are treated for 24 weeks. However, there are studies underway to determine the most optimal treatment duration based on certain factors. For instance, some experts believe that people with genotype 1, high viral load should be treated for 72 weeks instead of 48 weeks to maximize treatment response rates. There are also studies evaluating treating people with genotype 2 for 12 weeks and genotype 3 for 48 weeks.

Genotype and HCV Medication Dosage

Genotype information is also important for establishing the appropriate dose of ribavirin. For instance, people with genotype 2 and 3 are given 800 mg a day of ribavirin (flat dose), whereas the ribavirin dose for people with genotype 1 is dosed by body weight.

Mixed Genotypes

A person can become infected with more than one genotype. Data is almost non-existent on being infected with more than one genotype, but some experts believe it may effect treatment response and HCV disease progression.

Steatosis and Genotype

Steatosis (fatty infiltrates of the liver) is a well recognized feature of hepatitis C infection. Steatosis can contribute to HCV disease progression and lower treatment response although the exact mechanism is not completely understood. People with HCV genotype 3 are more likely to develop steatosis and it is believed that HCV genotype 3 is an independent risk factor and may actually play a direct role in the development of steatosis. It has been reported that when genotype 3 individuals are successful treated that steatosis will generally improve and for some steatosis will disappear.

Genotype and HCV Disease Progression

In regards to genotype and HCV disease progression, early limited data suggested that genotype 1b was associated with a more severe disease progression than in genotype 1a or 2, but further studies have not been able to confirm this observation.

Genotype and Liver Transplantation

Genotype 1 (especially 1b) has been associated with a more rapid fibrosis progression in people who have received a liver transplant.


Loving your liver: Organ crucial to good health

Published: Friday, February 11, 2011
By Dr. Allen Yudovich
Henry Ford Health System

Of all the body’s vital organs, the heart is the one that gets the most attention this month. But right underneath it is one of the hardest-working organs we have, our liver. It doesn’t carry the touch of romance the heart does, but it is crucial to our well-being.

Our livers change food into nutrients and filter out harmful substances. The vital functions it performs include:

• converting nutrients into energy, hormones and other essential chemicals;
• cleansing toxic substances (including alcohol) from the blood, then neutralizing or rerouting them for disposal;
• processing drugs;
• storing vitamins, minerals, sugars and iron;
• regulating fat and cholesterol; and
• manufacturing bile -- a fluid that helps digest food.

The liver is also generally very good at keeping itself healthy. When it stops functioning well, the term liver disease is often used. But there are actually many forms of liver disease. When symptoms appear, they may include jaundice (a yellowing of the skin or eyes), abdominal pain, lose of appetite and weight loss, dark urine and pale bowel movements. Sometimes the first indication of a problem is found in the results of liver function tests ordered by a physician.


Some forms of liver disease are more common in older adults. Cirrhosis most frequently develops after years of alcohol abuse, although moderate drinkers sometimes develop it as well. Over time, the liver becomes scarred and loses its ability to do what it was designed to. Other liver diseases, including hepatitis B, C and D, can also lead to cirrhosis.

As the disease progresses, symptoms that may develop include nausea, fatigue, itching, vomiting blood and a swollen abdomen.

When cirrhosis is caused by excessive drinking, avoiding alcohol and eating a healthy diet may be beneficial because of the liver’s ability to regenerate itself. Medication is used to treat cirrhosis caused by viral hepatitis.

Cirrhosis is also one of the risk factors for liver cancer, which most often affects people older than 40. It also affects men more frequently than women. Other risk factors include smoking, heavy drinking, hepatitis B and C and cancer in another area of the body.

Liver cancer

Liver cancer can be either primary (meaning it started in the liver) or secondary (beginning elsewhere in the body and spreading to the liver). Secondary liver cancer is far more common than primary, because blood that may carry cancer cells is filtered through the liver.

Symptoms include abdominal pain or swelling, jaundice and weight loss, but these rarely appear in the early stages of the disease. Various tests are used to confirm a cancer diagnosis. These may include a biopsy, CT scan, an MRI, ultrasound and blood tests.

Treatment options include surgery, chemotherapy and radiation, along with newer treatments such as radiofrequency ablation, which uses heat to destroy tumors, and cryosurgery, which uses cold to do the same thing. A liver transplant could also be necessary.

Treatment is most successful when the cancer is diagnosed in an earlier stage and when the patient does not also have cirrhosis.


All forms of hepatitis are inflammations of the liver. The symptoms are similar to other forms of liver disease, but are often mild. A blood test is needed to confirm a hepatitis diagnosis. Treatment ranges from bed rest and avoiding alcohol to medication, depending on the form of hepatitis someone has.

Primary biliary cirrhosis

This is a chronic inflammation of the liver’s bile ducts that affects women more than men. Those who contract it are usually between 40 and 60 years old. It can lead to cirrhosis and eventually destroy the bile ducts. A healthy diet and medication can alleviate the symptoms, which include itching, fatigue and jaundice. A liver transplant may eventually be recommended.

Alcoholic liver disease

As its name implies, this disease is tied to alcohol abuse, although not all heavy drinkers develop it. Alcoholic liver disease generally develops over a period of years and leads to cirrhosis. Symptoms often don’t appear in the early stages of the disease. When they are present they may include abdominal pain, jaundice, fever, excessive thirst and a loss of appetite. They may also worsen after heavy drinking.

All of the above symptoms could also be indicators of a different illness. Anyone who experiences these symptoms should discuss them with their physician.

Allen Yudovich, M.D., is a gastroenterologist at the Henry Ford Medical Center - Fairlane in Dearborn. For an appointment call (800) HENRYFORD.


New Opportunities in Anti-Hepatitis C Virus Drug Discovery: Targeting NS4B

Antiviral Res. 2011 Feb 1. [Epub ahead of print]

Rai R, Deval J.

Alios BioPharma, South San Francisco, USA.


Current therapy for chronic hepatitis C virus (HCV) infection constitutes a combination of pegylated interferon alfa-2a or alpha-2b and ribavirin. Although successful for many patient populations, this regimen has numerous limitations, including non-response, relapse, poor tolerability and long duration of treatment. To address these shortcomings, new small molecule agents are advancing in clinical development. Most of the current clinical candidates act by directly inhibiting key enzymes in the viral life-cycle: the NS5B polymerase, or the NS3/4A protease. Less well-studied, the non-structural 4B (NS4B) protein has recently emerged as an alternative target for Direct-acting Antiviral Agents (DAAs). NS4B is a 27-kDa membrane protein that is primarily involved in the formation of membrane vesicles-also named membranous web-used as scaffold for the assembly of the HCV replication complex. In addition, NS4B contains NTPase and RNA binding activities, as well as anti-apoptotic properties. This review summarizes the current understanding of the structure and functions of NS4B, an essential component of the replication machinery of HCV. In this literature and patent review, we report the recent developments in anti-NS4B drug discovery. These advances open the possibility for future combination therapies with other DAAs.

Copyright © 2011. Published by Elsevier B.V.

PMID: 21295075 [PubMed - as supplied by publisher]


Cirrhosis Patients at Increased Risk of Extrahepatic Cancer

Last Updated: February 07, 2011

Patients with liver cirrhosis have more than double the risk of developing extrahepatic cancer than the general population, and they also have a significantly increased risk of hepatocellular carcinoma, according to a study published in the February issue of Clinical Gastroenterology and Hepatology.

MONDAY, Feb. 7 (HealthDay News) -- Patients with liver cirrhosis have more than double the risk of developing extrahepatic cancer than the general population, and they also have a significantly increased risk of hepatocellular carcinoma (HCC), according to a study published in the February issue of Clinical Gastroenterology and Hepatology.

Evangelos Kalaitzakis, M.D., of the University of Gothenburg in Sweden, and colleagues investigated the incidence of malignant neoplasms in patients diagnosed with cirrhosis between 1994 and 2005. Of the 1,019 patients, 68 percent were men, 48 percent had alcoholic liver disease (ALD), 10 percent had hepatitis C virus (HCV), and 12 percent had both ALD and HCV.

The researchers found that, compared to the general population, patients with cirrhosis were at increased risk of HCC (26-fold); cholangiocarcinoma (13-fold); colorectal cancer (four-fold); and cancers of the esophagus (eight-fold), pancreas (five-fold), and lung (five-fold). HCC occurred more frequently among patients with HCV than other diseases, and the risk of HCC among patients with HCV was similar whether they had ALD or not. Patients with non-ALD cirrhosis were at increased risk for cholangiocarcinoma; whereas, the risk for extrahepatic cancers increased mainly among patients with ALD and cirrhosis.

"This study confirms the association of liver cirrhosis with HCC and further indicates that non-HCC malignant neoplasms may be more common in patients with cirrhosis compared with the general population," the authors write.

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HIV-Infected Men at Ongoing Risk for HCV Seroconversion, Study Finds

Norra MacReady

February 7, 2011 — Even with conscientious care and state-of-the-art medication, HIV-infected men are at risk for hepatitis C virus (HCV) seroconversion and should have access to ongoing HCV surveillance, the authors of a new study say. Their findings were published online January 31 and appear in the February print issue of Clinical Infectious Diseases.

HCV has become "a leading cause of non-AIDS related morbidity and mortality for HIV-infected persons in the highly active antiretroviral therapy (HAART) era," lead author Lynn E. Taylor, MD, from Brown University, Providence, Rhode Island, and coauthors write. They estimate that up to 30% of HIV-infected people in the United States are coinfected with HCV.

At this time, the US Public Health Service recommends testing for HCV when a patient is initially diagnosed with HIV infection, but not thereafter. However, reports are now surfacing of acute HCV outbreaks in Europe, Australia, New York, and California among HIV-infected men who have sex with other HIV-infected men and engage in potentially traumatic practices such as unprotected anal sex, use of sex toys, multiple partners, and manual insertion, which may involve some exchange of blood. Because HCV treatment is most effective during the acute stages of infection, "it is vital to diagnose incident HCV infection in HIV-infected persons," the authors say.

For a better idea of the risk for acute HCV infection among HIV-infected men, the researchers studied behavioral and demographic factors associated with HCV antibody seroconversion in men participating in the AIDS Clinical Trial Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) study. The ACTG was established in 1987 by the US Department of Health and Human Services, the National Institute of Allergy and Infectious Diseases, and the National Institutes of Health Division of AIDS, and is the largest HIV clinical trials organization in the world. ALLRT is a randomized cohort study of the long-term immunologic, virologic, pharmacologic, and clinical outcomes associated with the use of HAART by HIV-1-seropositive patients. It was started by ACTG in 2000.

Starting in 2002, patients participating in ALLRT have been tested for HCV on entry, with follow-up testing every 96 weeks beginning in 2006. Seventeen other ACTG-funded trials also test patients for HCV on entry and at various follow-up intervals, between 1996 and 2002. The authors determined the incidence of HCV infection from 1996 to 2008 among men participating in these studies. Of those 2848 patients, 2629 had at least 1 HCV antibody test result, with 264 (10%) of those individuals testing positive at baseline. Of the remaining 2365 patients, 1830 had at least 1 subsequent HCV antibody test and were included in this analysis. Their mean age at the time of the initial negative HCV antibody result was 42 years; other demographic information is shown in the table. The mean interval for HCV testing was 2.8 years for HCV seroconverters and 2.6 years for nonseroconverters.


Characteristic   Percentage

 * White 57%
 * Black 22%
 * Hispanic 18%
 * Asian/Pacific Islander 2%
 * Native American 1%

College-educated 70%

Using HAART 94%

Current or prior injection drug use at study entry 6%

HCV seroconversion occurred in 36 of the men studied (2%), for an overall incidence of .51 cases per 100 person-years. Twenty-five percent of the seroconverters reported a history of injection drug use compared with 5% of patients who remained seronegative (P < .001). However, the authors write, "compared with men with initial HCV antibody positivity, seroconverters were more likely to be white and less likely to be black and were more likely to have never injected drugs and to have attended college."

Patients who seroconverted also were more likely to have an HIV RNA level greater than 400 copies/mL compared with those who did not seroconvert. There is an association between less adherence to the HAART regimen and participation in risky sexual practices, and both of these may have figured in the higher seroconversion rate among patients with a higher viral load, the authors suggest. People in the acute stages of HCV infection are also less tolerant of HAART, which may have contributed to their poor compliance.

There were several study limitations. Only half of the participants underwent follow-up HCV testing at intervals shorter than 3 years, so the authors could not determine exactly when seroconversion occurred in these patients, making it impossible to report incidence trends over time. In addition, 23% of the participants did not undergo any follow-up HCV screening, which raises the possibility of selection bias. However, there was no difference in baseline data between those patients and the patients who did have follow-up testing, so "it is likely that the HCV seroconversions represent the true incidence among HIV-infected patients in care," the authors write.

These findings suggest that HIV-infected patients should undergo regular screening for HCV, the researchers conclude. Early detection "may permit more successful treatment and provide opportunity for intervention to mitigate disease spread among drug-using or sexual partners and education to limit liver damage."

This study was supported in part by the AIDS Clinical Trials Group funded by the National Institute of Allergy and Infectious Diseases; National Institute on Drug Abuse; Lifespan/Tufts/Brown Center for AIDS Research; Center for Drug Abuse and AIDS Research; and the National Institutes of Health. The Miriam Hospital is one of the Clinical 340 Research Sites under Harvard/Partners Clinical Trials Unit. Study authors report various financial relationships with Roche, Vertex, Genentech, BMS, Merck, SciClone, GlaxoSmithKline, Three Rivers, Johnson & Johnson, Regulus, and Tibotec.

Clin Infect Dis. Published online January 31, 2011.


Triplex nucleic acid testing detected HBV, HIV, HCV before seroconversion

Posted February 8, 2011

Stramer S. N Engl J Med. 2011;364:236-247.

A triplex nucleic acid assay detected potentially infectious hepatitis B virus, hepatitis C virus and HIV after analyzing the serologic, biochemical and molecular features of 3.7 million blood donations, according to study findings.

All blood donations in the US have been screened for hepatitis B surface antigen, but the researchers said a small proportion of donors with antibodies against hepatitis B core antigen in the absence of hepatitis B surface antigen have circulating hepatitis B virus (HBV) DNA and may have a risk of infectivity. Additionally, blood collected during the early window period of HBV infection is highly infectious, but the risk decreases as hepatitis B develops.

In 2008, 2,137,275 donors made a total of 3,694,858 donations. Using the Ultrio assay (Gen-Probe), researchers discovered 26 confirmed infections (nine HBV, 15 hepatitis C virus [HCV] and two HIV), giving the assay a positive predictive value of 35%.

The nine patients with HBV had seronegative HBV DNA-positive samples, and all but one was detected on mini-pool nucleic acid testing. Researchers had expected to find no more than four seronegative HBV DNA-positive samples.

Six infected donors had been vaccinated for HBV. Researchers said routine screening for hepatitis B surface antigen or antibodies against hepatitis B core antigen would not have uncovered those infections.

They said the infections were of “inconsequential clinical significance, but their potential for transmission remains unresolved.”

“Our findings show the efficacy of the HBV vaccine for the prevention of clinical disease but not infection, and the cost of interdicting donations that contain HBV DNA from seronegative donors is high in the face of unknown benefit,” they wrote.


Inhibitex Receives Fast Track Designation for INX-189 for the Treatment of Chronic Hepatitis C Infections

Posted on: Fri, 11 Feb 2011 07:00:01 EST

ATLANTA, Feb 11, 2011 (BUSINESS WIRE) --

Inhibitex, Inc. (Nasdaq: INHX
PowerRating) today reported that the U.S. Food and Drug Administration ("FDA") has designated the investigation of INX-08189 ("INX-189"), a potent guanosine nucleotide polymerase inhibitor for the treatment of chronic hepatitis C viral infection, as a Fast Track development program. Under the FDA Modernization Act of 1997, Fast Track programs are designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life threatening conditions and that demonstrate the potential to address unmet medical needs. The characteristics of INX-189 that contributed to it being granted Fast Track status include a high genetic barrier to resistance, its pan-genotypic activity, and once-daily oral dosing.

"The FDA's fast track designation for INX-189 is reflective of its unique features and the need for novel antiviral drugs that demonstrate the potential to provide better clinical outcomes and improved tolerability for the millions of individuals suffering from chronic hepatitis C infection," commented Dr. Joseph Patti, Inhibitex's Chief Scientific Officer and Senior Vice President of Research and Development.

The Company reported interim data from the first two cohorts of its ongoing Phase 1b clinical trial of INX-189 on January 9, 2011 and anticipates completing this trial by the end of the first quarter of 2011.

About HCV and INX-189

Hepatitis C is a disease of the liver caused by HCV. It is estimated that over 4 million Americans and 170 million individuals worldwide are infected with HCV, the majority of which represent chronic infections that can cause liver disease, cirrhosis and cancer. Chronic hepatitis C is the leading cause of liver transplants in the United States.

Inhibitex is developing a series of proprietary nucleotide inhibitors that target the RNA-dependent RNA polymerase (NS5b) of HCV. INX-189 is a protide of a 2'-C-methylguanosine analogue. The Company believes that preclinical and clinical studies of INX-189 completed to-date support its potential as a potent, once-daily, low dose oral therapy amenable to combination with other antivirals for the treatment of patients with all known genotypes of HCV.

About Inhibitex

Inhibitex, Inc. is a biopharmaceutical company focused on developing products to prevent and treat serious infectious diseases. In addition to INX-189, the Company's clinical stage antiviral pipeline includes FV-100, a bicyclic nucleoside inhibitor in Phase II development for the prevention and reduction of shingles-associated pain. The Company also has additional HCV nucleotide polymerase inhibitors in various stages of preclinical development and has licensed the use of its proprietary MSCRAMM(R) protein platform to Pfizer for the development of active staphylococcal vaccines. For additional information about the Company, please visit www.inhibitex.com.

Safe Harbor Statement

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than historical facts included in this press release, including statements regarding the Company's belief that the results of preclinical and clinical studies of INX-189 to-date support its potential as a highly potent, once-daily, oral therapy amenable to combination with other anti-virals for the treatment of patients with all known genotypes of HCV, are forward looking statements. These intentions, expectations, or results may not be achieved in the future and various important factors could cause actual results or events to differ materially from the forward-looking statements that the Company makes, including the risk that; the results of ongoing or future preclinical or clinical studies of INX-189 alone or in combination with other anti-viral compounds not supporting its further development for lack of safety, tolerability, anti-viral activity, or any other reason; either the Company, the FDA, a data safety monitoring board or an investigational review board suspending or terminating the clinical development of INX-189 at any time for lack of safety, tolerability, anti-viral activity, or any other reason; obtaining, maintaining and protecting the intellectual property incorporated into and supporting the commercial viability of the Company's product candidates; and other cautionary statements contained elsewhere herein and in its Annual Report on Form 10-K for the year ended December 31, 2009, as filed with the Securities and Exchange Commission, or SEC, on March 26, 2010, and its Quarterly Report on Form 10-Q for the quarter ended September 30, 2010, as filed with the SEC on November 15, 2010. Given these uncertainties, you should not place undue reliance on these forward-looking statements, which apply only as of the date of this press release.

There may be events in the future that the Company is unable to predict accurately, or over which it has no control. The Company's business, financial condition, results of operations and prospects may change. The Company may not update these forward-looking statements, even though its situation may change in the future, unless it has obligations under the Federal securities laws to update and disclose material developments related to previously disclosed information. The Company qualifies all of the information contained in this press release, and particularly its forward-looking statements, by these cautionary statements.

Inhibitex(R) and MSCRAMM(R) are registered trademarks of Inhibitex, Inc.

SOURCE: Inhibitex, Inc.

Inhibitex, Inc.
Russell H. Plumb, Chief Executive Officer, 678-746-1136
The Trout Group
Lee M. Stern, CFA, 646-378-2922


FDA removes full clinical hold on Idenix's HCV drug

Wed Feb 9, 2011 6:12pm EST

* Says to stop development of IDX320

* Says FDA places partial clinical hold on IDX184

* Says HIV drug licensed to Glaxo also put on hold (Adds details)

Feb 9 (Reuters) - Idenix Pharmaceuticals Inc (IDIX.O) said U.S. health regulators have removed the full clinical hold on one of its two experimental hepatitis C drugs, and it ceased the development of the other drug because of a toxicity issue.

In September, the U.S. Food and Drug Administration halted all trials of the experimental drugs after detecting liver function abnormalities in three healthy volunteers during an early-stage study of a combination of the compounds IDX184 and IDX320. [ID:nSGE6860G7]

The company said the observed toxicity in the drug-drug interaction study was likely caused by IDX320.

Idenix, which focuses on treating viral diseases, said the FDA has placed the IDX184 program on partial clinical hold.

It said it expects to initiate a Phase IIb trial of IDX184 in combination with pegylated interferon and antiviral pill ribavirin in the second half of 2011.

The company also said its HIV drug -- licensed to GlaxoSmithKline's (GSK.L) unit ViiV Healthcare -- was placed on a clinical hold by the FDA.

Idenix shares closed at $75.04 Wednesday on Nasdaq. (Reporting by Anand Basu in Bangalore; Editing by Joyjeet Das)


Medivir Announces Start of Phase 1a Trial of the Hepatitis C Polymerase Inhibitor TMC649128

HUDDINGE, Sweden, February 10, 2011 /PRNewswire/ -- Medivir AB (OMX: MVIR), the emerging research-based specialty pharmaceutical company focused on infectious diseases, today announces the start of a phase 1a clinical trial with TMC649128 intended for the treatment of chronic hepatitis C virus infection.

TMC649128 is a nucleoside NS5B polymerase inhibitor that has already demonstrated an attractive pre-clinical profile. It is anticipated that this profile would see TMC649128 be used in combination with HCV directly acting antiviral agents, given their high genetic barrier to resistance and antiviral activity across multiple HCV genotypes.

In pre-clinical studies, TMC649128 displayed in vitro activity across multiple HCV genotypes and a high genetic barrier to resistance.

The phase 1a trial is a double-blind, randomized, placebo-controlled single-ascending dose trial to assess the safety, tolerability and pharmacokinetics in healthy volunteers and will be conducted in Belgium. TMC649128 is being developed in collaboration with Tibotec Pharmaceuticals.

Milestone payment

Medivir entered a Research and Development agreement in the field of hepatitis C virus polymerase with Ortho Biotech Products LP, an affiliate of Tibotec in May 2008. The development of TMC649128 falls under this agreement and by entering clinical development, a milestone payment of Euro 7 million has been triggered for payment to Medivir.

"We are extremely excited to see TMC649128, our first HCV nucleoside inhibitor, move into clinical development", stated Bertil Samuelsson, CSO of Medivir. "The start of this phase 1a trial underlines Medivir's commitment to the development of novel and innovative hepatitis C treatments. We view nucleoside inhibitors as cornerstone components of future HCV treatment paradigms in combination with directly acting antiviral agents and a TMC649128 component could set them apart from other HCV drug classes."

About Hepatitis C

Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.

About Medivir's Commitment of the HCV Area

Medivir and Tibotec are also jointly developing the once daily protease inhibitor TMC435 for treatment of hepatitis C virus infections (HCV).

About Medivir

Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development. Medivir has a strong R&D portfolio and has recently launched its first product Xerese(TM)/Xerclear(R). Medivir's key pipeline asset, TMC435, a protease inhibitor, is in phase 2b clinical development for Hepatitis C and is partnered with Tibotec Pharmaceuticals.

Xerese(TM)/Xerclear(R) is an innovative treatment for cold sores, which has been approved in both the US and Europe. It is partnered with GlaxoSmithKline to be sold OTC in Europe and Russia and with Meda AB in North America. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.

For more information about Medivir, please visit the Company's website: http://www.medivir.se/

For more information about Medivir, please contact;

Medivir (http://www.medivir.se/)

Rein Piir, CFO & VP Investor Relations
Mobile: +46-708-537-292

Europe: Mary-Jane Elliott / Amber Bielecka /
Nick Francis

USA: Jason Marshall

SOURCE Medivir


February 5, 2011

Great summary of Hepatitis C from Black Poppy Magazine

Black Poppy Magazine

Hepatitis C

Once known as Hepatitis Non A Non B, Hepatitis C is being discussed a lot in the using community. Here, BP goes behind the ‘Hep C test’ where many of us stop, discovering why further tests are so important in getting to the bottom of your own Hep C diagnosis.

Research by M.M, B.L, EO

In the last issue, BP ‘introduced’ the liver, briefly discussing what it does and how it does it. This issue, we want to look more closely at a virus that has affected the livers of an estimated 250,000 – 600,000 people in the UK alone, 170 million people worldwide with some 3 million more joining the global ranks each year. BP wanted to find some straightforward answers to some essential questions on Hepatitis C and what you may want to consider if you have been diagnosed Hep C (HCV) positive. (BP will look into treatments for HCV next issue).

Hepatitis C is?…

The actual word “hepatitis’ means inflammation or swelling of the liver. This can be caused by chemicals, drugs, drinking too much alcohol or by different kinds of viruses. Hepatitis C is just one of a number of hepatitis viruses (including A, B,D, E, G) and they are all completely different from one another. It can be hard to get your bead around just how small viruses really are. HCV is estimated to be 80 nanometers in diameter (around 30 billion would fit on this dot {,} – another reason why handwashing before and after injecting is so important; be especially vigilant if someone injects you after they’ve just had a hit – they could have microscopic particles of blood on their fingers and then may place them on your injection site. HCV is known to be remain active outside the body for some time so wash your hands and tell others to wash theirs! The hepatitis C virus is in fact a group of viruses, similar enough to be called HCV virus, yet different enough to be classified into subgroups.


Several families of hepatitis C have been observed around The world and these are known as genotypes, because they differ in their genetic make up. They arc usually classified as HCV genotype 1 ,or 2, or 3, etc. Some genotypes respond better to treatment than others so it is important to identify your genotype when considering treatment for Hep C..


Within each genotype, there are subtypes. These are classified as HCV subtype la, or Ib, Ic, etc and within a subtype, incredibly minute differences will exist among individual viruses, called quasispecies – several million quasispecies would exist within a subtype.

How Might HCV Affect Me?

Hepatitis C affects people differently; some are not affected by it while others can be affected seriously. If you contract hepatitis C, your body will produce antibodies to try and destroy it A HCV lest (referred to as an anti-HCV test) will look for the presence of these antibodies and if found, your result will be HCV antibody positive. However, too many of us stop here, terrified that we now have Hep C. But an antibody positive test is only showing ‘exposure’ to the virus – it does not tell you whether you have ‘active’ virus in the blood. Research shows that of 100 people infected wilh HCV, 25 will clear the virus from their bodies completely with 2-6 months of infection but will continue to carry the antibodies for some time. (These are usually people who were infected when they were younger).

This is why if you have received an HCV antibody positive test, further tests are necessary to determine whether there is still an infection present (see PCR tests opposite) and of course, get yourself some follow up tests for your Hep C, certain discoveries might make all the difference. to help identify the extent of any liver complications or disease – and your suitability for the newer HCV treatments. (BP investigates this next issue). Research estimates the other 75 who do not clear the virus will have ongoing (chronic) infection and some arc at risk of developing complications or liver disease. Of these people, approximately 20 may never experience any noticeable symptoms and although they can still transmit HCV, they won’t develop illness or liver disease.

Symptoms Related to HCV

After 10-15 years, the majority of people with hepatitis C will have developed different levels of liver damage that will result in hepatitis C


These could include;

tiredness and fatigue, headaches, vagueness,

depression, altered sleep patterns, abdominal pain, itches and

rashes, nausea, vomiting

and/or loss of appetite, swelling of the ankles

and/or stomach area, red blotches occurring on the upper body, easy bruising.

Some aspects of the disease are still not fully understood and it can be difficult to predict what will happen for any one person. Symptoms can stay at a certain level and dont always get worse. They can come and go with no real pattern. Over a 40 year period of infection, it is believed that: less than 4% of people with chronic hepatitis C would develop liver failure or liver cancer.. Over a 40 year period, 20% of people with chronic (ongoing) HCV infection will develop cirrhosis of the liver.

I’m Hep C Positive – Now What?

After you receive your antibody positive diagnosis, you can be offered (or request) a referral lo see a specialist. They should then offer you a series of tests such as:

PCR Test, Blood Platelet Count, Liver Function Tests (LFTs), liver Biopsy, Ultrasound or doppler ultrasound, or CT scan

Many doctors advise people with hepatitis C to have the hepatitis A and B vaccinations. Although the viruses are unrelated, such vaccinations will help prevent possible additional liver complications caused by having more than one viral infection at the same time.

What is a PCR Test?

PCR stands for polymerase chain reaction. PCR tests detect or measure the actual hepatitis C virus in a sample of blood There are three types of PCR test – viral detection, viral load and viral genotype. These tests assist people to:

+ Determine whether you may have cleared the virus (but still have antibodies)
+ Determine your level of infectivity
+ Confirm inconclusive hepatitis C antibody test results
+ Assess your response to treatment

PCR viral detection test (Qualitative test)

The PCR viral detection test is mainly used as a confirmatory test when an antibody test result is inconclusive. It is important as you may have received an antibody positive test only to have cleared the virus at a later date. The PCR viral detection test can also be used by HCV positive pregnant women to determine the chance of them transmitting HCV to their child.

PCR viral load test (Quantitative Test)

This PCR lest measures the amount of HCV circulating in someone’s blood. Measuring the level of virus in someone’s blood before treatment can help determine whether a 6 or 12 month treatment regime is preferable.

PCR viral genotype test PCR genotype tests can determine what HCV genotype and subtype a person has. This is useful information as it has been shown that people who have particular genotypes generally respond better to drug treatment Important note: PCR tests look for virus in the blood. Levels of virus in people’s blood can fluctuate and, at times, the level of virus in someone’s blood might be too low for the PCR test to detect it. Therefore, a negative PCR test result may not always mean that a hepatitis C antibody positive person doesn’t have hepatitis C just that the test couldn’t detect the virus in (hat particular sample of blood. For this reason, people should rely on a series of at least two PCR tests done over a 4-6 month period, rather than a single PCR test.

How Can I Tell What’s Happening to my Liver?

Liver function tests (LFTs) (see BP Issue 1) are used to measure the general condition of the liver. Liver function tests measure levels of particular enzymes or proteins in a person’s blood. If liver cells are damaged, increased levels of these substances “leak out” into the bloodstream and show up as raised or abnormal results in liver function tests. The tests provide only a rough indication of possible liver damage. Liver function tests may be suggested monthly or up to once per year depending on a person’s condition. Liver function tests do not provide conclusive evidence of what is happening in the liven some people may feel quite ill yet have little liver damage. For other people, damage may be occurring even when liver enzyme levels arc normal. It is important to remember that raised liver function test results may be caused by medical conditions other than HCV In cases where ALT readings are consistently high for a long time, where they fluctuate greatly or when readings don’t seem to match with how a person feels, a specialist may suggest a liver biopsy be done. Some doctors recommend a routine liver biopsy after 15 years of infection and then every five years thereafter.

What is a Liver Biopsy?

A liver biopsy provides the most accurate report on the condition of someone’s liver. Using a special instrument, a specialist doctor takes a small sample which is then examined under a microscope. Ultrasound and other x-rays can indicate certain liver-related abnormalities but have difficulty distinguishing cirrhosis (scarring of the liver) from other conditions such as fat accumulation in the liver. This is particularly true in early cirrhosis. The diagnosis of cirrhosis can only really be made by liver biopsy. However, the presence or absence of cirrhosis is only part of the information available from liver biopsy. Apart from showing the amount of scar tissue (an indication of what has happened to the liver in the past), liver biopsies also show how active the hepatitis C is now and if there are other factors interacting with the hepatitis C to damage the liver such as excess alcohol or iron accumulation in the liver. (BP will cover biopsy’s in more detail in an upcoming issue).

How Accurate Are Liver Biopsy’s?

A liver biopsy sample is just a tiny piece of the liver and people have said it can be hit and miss depending on the bit of the liver taken, but a properly taken sample is generally representative of changes throughout the liver. Hepatitis C affects the whole liver and although there may be some variation within the liver,this would be a minor, rather than major, variation.A doctor will usually explore two major issues in looking at the liver biopsy: Firstly, are the features consistent with HCV as the cause of the liver test abnormalities? ie. Are there other Ever illnesses present? Secondly, if the biopsy is consistent with HCV, then how badly is the liver damaged? This can be estimated by studying three main parameters:

+ The amount of portal inflammation – this is the inflammation around liver cells, bile ducts and veins in parts of the liver

+ The amount of tabular inflammation – the amount of inflammation in separate lobules (the left, right and smaller subdivisions of the liver)

+ The amount of fibrosis – this is an early stage in the development of liver cell scarring (cirrhosis).

NOTE: Liver biopsies are not used as much in 2011 as they were around 2000 as a more modern, less invasive type of liver ultrasound is preferred.

Is Treatment Successful?

It is important that you develop a partnership with the healthcare professional who will be responsible for your cart. It may be your GP, specialist or alternative healthcare practitioner or better still, a combination of the three. There are some real strides being made in terms of treatment for HCV and treatment outcomes, though variable depending on each individual (lifestyle and viral factors and certain lifestyle changes made can also impact positively on your quality of life). The best course of treatment currently available involves a combination of two drugs; pegylated interferon and ribavirin. Treatment response rates using pegylated alpha interferon plus ribavirin are in the order of 55% (with genotype 1 results of 45%, and genotype 2 and 3 results of about 80%). For the few people unable to tolerate combination therapy, alpha interferon on its own is sometimes beneficial. However, not everyone is considered suitable for treatment Some people need only regular assessment to detect if damage to their liver is occurring or progressing. NB As of 2011, new treatment therapies for HCV are looking much more promising. It is well worth doing a bit of research into what is available through some of the excellent Hep C resources available these days. Treatment can be exhausting and hard work for your body so its important to be prepared and have support.

Discriminated Against for Being HCV+?

If you feel you have been discriminated against because of your status or treated unfairly, there is a group who may be able to advise you on your rights relating to almost any matter that you feel is connected with your hepatitis C.

NOTE: The Disability Rights Commission (DRC) closed on 28 September 2007. Its responsibility for helping secure civil rights for disabled people has transferred to the new Equality and Human Rights Commission which opened for business in 1 October 2007.

Or Call the HEP C Trust (UK) Helpline: 0845 223 4424 10.30 to 4.30 Monday to Fri – people affected by Hep C man the helplines and give good quality information and advice

Thanks to British Liver Trust & The Australian HEP C Council of NSW http://www.hepatitis.org.au/ for their excellent resources and information, some of which is represented here.

Related Articles

■ Scripps Research scientists identify key interaction in hepatitis C virus (scienceblog.com)

■ Hepatitis C – All Information (umm.edu)

■ New Hepatitis C Drugs in the Works (webmd.com)

■ Key interaction in hepatitis C virus identified (sciencedaily.com)


February 4, 2011

Tacere Therapeutics Reacquires Rights to Develop and Commercialize its Hepatitis C Compounds in Asia

SAN JOSE, Calif., Feb. 3, 2011 /PRNewswire/ -- Tacere Therapeutics, Inc., an RNA interference (RNAi)-based therapeutics company, announced today that it has reacquired the development and commercialization rights to its Hepatitis C Virus (HCV) compounds throughout Asia from its strategic partner, Tokyo-based Oncolys BioPharma Inc.

"We are very happy to have regained control of the Asian development and commercialization rights to our family of HCV compounds," said Sara Hall Renison, Chief Executive Officer of Tacere. Mike Catelani, Chairman, President and CFO, added, "With the continued promising development of our lead HCV compound in partnership with Pfizer, holder of the non-Asian worldwide development and commercialization rights, we believe that we are well-positioned to commence regulatory activities in Asia."

About Tacere's family of HCV compounds

Tacere's family of HCV compounds, are novel therapeutic products containing three separate RNAi elements targeted against the Hepatitis C virus itself and encapsidated in an adeno-associated virus (AAV) protein coat. AAV delivery methods have demonstrated clinical safety, and preclinical animal studies with TT-034, the lead compound in the family, have shown the ability to penetrate hepatocytes (the site of HCV replication) at high levels following a single intravenous administration. In preclinical animal studies, this "cocktail in one drug" monotherapy targeted and cleaved the Hepatitis C virus itself at three different sites simultaneously without toxicity.

About Tacere Therapeutics, Inc.

Tacere is an innovative biotechnology company focused on developing therapeutics to treat human diseases using its proprietary knowledge in the development of RNAi therapeutics. Tacere is located in San Jose, California, USA. For additional information, please visit http://www.tacerebio.com/.


Mike Catelani
Chairman, President & CFO
+1 408 839-1818

SOURCE Tacere Therapeutics, Inc.


Study shows cytokines lymphotoxin can lead to liver cancer

Thursday, February 03, 2011 1:21 PM

VIENNA, Feb. 3, 2011 (Xinhua News Agency) -- Austrian scientist Johannes Haybaeck discovered that increased levels of cytokines lymphotoxin could cause liver infection and develops to liver cancer later. The findings made him win the Pfizer (NYSE:PFE) Research Awards 2011 presented by Medical University Graz, Austria, on Thursday.

Accordingly, a high-level concentration of cytokines lymphotoxin (LT) alpha and beta and their receptor LT beta R can be found in the liver tissue of patients infected with hepatitis B- or hepatitis C virus.

The lymphotoxin ultimately led to a liver infection that developed to liver cancer later. In addition, the altered liver cells form metastases that spread within the liver.

In addition to chronic alcohol abuse, drug abuse or fungal toxins, virus infection was believed to be one of the most common causes of liver inflammation and liver cancer.

The scientists obtained the results by conducting tumor therapies in mice. They produced a lot of LTs to the liver tissues of the mice though a genetic material change and finally came to the experimental results.

Whether the observations in the mice can also play a role in the human liver tumor cells is still unclear. Hayb?ck and his research colleagues are underway.

(Source: )
(Source: Quotemedia)


Hepatitis C remains prominent among injection drug users

Updated: 2011-02-02 14:19:52 CST

While injection drug users may be contracting HIV at lower rates than they did two decades ago, they are receiving positive hepatitis C tests just as frequently as ever. These are the findings of a new study published in the Journal of Infectious Disease.

The Johns Hopkins University researchers who led the study said that the findings show that efforts to curb the spread of blood-borne diseases are showing some positive results. However, they said that more needs to be done to combat the dangerous spread of hepatitis C.

For the study, the researchers looked at infection rates among injection drug users of both HIV and hepatitis C, or HCV, dating back to 1988. While the numbers showed a significant decline in HIV cases, HCV infections remained more constant.

Given the fact that these infections generally spread from injection drug users into the general population, the researchers said that it is important to institute more effective programs for preventing the spread of infection, such as needle exchange programs.

"Current prevention efforts delay but do not prevent HCV at the population level and will need to be further intensified to reduce risk of HCV infection to the level of HIV," the researchers said

Astex Therapeutics Receives Milestone from Wellcome Trust for Pioneering HCV Research

2011-02-01, Source: Astex Therapeutics

Astex Therapeutics, the UK-based biotechnology company developing targeted therapies for oncology and virology, announced that it has received a milestone payment of £1 million from the Wellcome Trust to support the Company's pioneering work in the area of infectious disease caused by Hepatitis C Virus (HCV). The payment is the second installment of an award of £2 million made by Wellcome to Astex in 2009 under its ''Seeding Drug Discovery" initiative.

The milestone payment was triggered by the identification of potent, small molecule inhibitors of HCV NS3 - a key protein involved in viral replication. The compounds act as allosteric modulators of the NS3 protein resulting in inhibition of the enzyme activities of both protease and helicase in wild type and in drug resistant variants of HCV that have arisen in the clinic during treatment with active site inhibitors. As such the Astex compounds offer the potential to be differentiated from existing HCV protease inhibitors. Astex retains all commercial rights to the resulting drug candidates from this programme. Harren Jhoti, Chief Executive Officer of Astex said, "We anticipate that targeted agents like these will provide new therapeutic options for patients with HCV infections where current treatments are not optimal and where resistance to current treatments is a recurring problem."


Jeremy Carmichael, PhD Director of Business Development Astex Therapeutics Ltd 436 Cambridge Science Park Milton Road, Cambridge CB4 0QA, UK Tel: +44(0)1223 226200 Fax: +44(0)1223 226201 j.carmichael@astex-therapeutics.com http://www.astex-therapeutics.com/

About Astex Therapeutics

Astex is a UK-based biotechnology company that discovers and develops novel small molecule therapeutics. Using its pioneering fragment-based drug discovery platform Pyramid(TM), Astex has built a pipeline of molecularly-targeted oncology drugs, of which three are currently being tested in clinical trials with others in discovery and pre-clinical development. In addition to its proprietary research programmes, Astex's productivity in lead discovery has been endorsed through numerous partnerships with major pharmaceutical companies, including AstraZeneca, GlaxoSmithKline, Johnson and Johnson and Novartis.

For further information on Astex please visit the Company's website at http://www.astex-therapeutics.com/

About the Wellcome Trust

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. http://www.wellcome.ac.uk/

Vertex Urges CDC to Recommend Hep C Screening, To Nudge “Second Tsunami” of Patients

Luke Timmerman 2/2/11

If Vertex Pharmaceuticals gets its way in talks with U.S. public health officials, most people over 50 could soon get blood tests to screen for hepatitis C infections at the doctor’s office. If the U.S. Centers for Disease Control and Prevention (CDC) agrees this is a good idea, it could prompt another 1 million patients who don’t realize they are infected to come out of the woodwork and start clamoring for Vertex’s new hepatitis C drug over the next few years.

The Cambridge, MA-based biotech company (NASDAQ: VRTX), which has operations in San Diego, has joined other drugmakers in supporting studies they hope will persuade the CDC to recommend routine screening for hepatitis C, Vertex CEO Matt Emmens said in a recent interview. The company is one of the sponsors of what’s called the Viral Hepatitis Action Coalition, a public-private partnership with the CDC, which is conducting studies known as BEST-C. These studies could determine how effective it is to screen patients for hepatitis C infection more widely.

These studies, which are expected to cost a total of $3.6 million, could be worth billions to Vertex if they show that screening random Baby Boomers is worthwhile.

An estimated 600,000 patients in the U.S. are expected to seek treatment that could include Vertex’s drug, or a rival offering from Merck, if the FDA clears the new drugs for sale as analysts expect in the middle of this year. The two new protease inhibitors are being hailed as major steps forward, as they have been shown to roughly double cure rates of hepatitis C, a viral infection that damages the liver over many years. Vertex’s drug, telaprevir, has shown it can push the cure rate up as high as about 75 percent, while cutting the treatment time in half to about six months. That means patients don’t have to endure such a long period of flu-like symptoms, which has traditionally discouraged many patients from getting treatment.

The new advance from Vertex, demonstrated in a trio of pivotal clinical trials, has created this huge wave of pent-up demand from patients and doctors. Knowing this, many analysts have projected the product will be pretty much an instant hit, topping $2 billion in U.S. sales after just a couple years. But then, some expect sales to taper off, as many of the most motivated patients get cured, and don’t need the drug anymore. Essentially, they see Vertex possibly becoming a victim of its own success.

That’s not how it will play out, says Emmens, a marketing veteran who spent much of his career at Merck. An estimated 3.2 million to 3.9 million people in the U.S. have chronic hepatitis C infections. That’s a lot more than the initial wave of patients, which is mostly composed of people who sought treatment before but relapsed. Besides those patients, many more candidates are Baby Boomers who don’t know they contracted the hepatitis C infection decades ago through unprotected sex, IV drug use, or blood transfusions from contaminated supplies. Many of these infections lie dormant for about 20 years or more, but are just now starting to emerge over the decade to come, Emmens says. Some patients won’t see symptoms at all, and as the AP pointed out in this solid feature last month, it’s hard to tell which infected patients are likely to get the worst symptoms. The unluckiest ones will end up suffering severe liver scarring (cirrhosis), liver cancer, liver transplants, and ultimately, premature death.

Connecting with that massive crowd of patients, who aren’t motivated to seek treatment today because they don’t see any really bad symptoms yet, is one of the big marketing challenges Vertex faces. The company is planning to spend some of its $1.3 billion cash hoard on a public awareness campaign designed to urge people to get tested to see if they have the virus, Emmens says. But even more important than the ad campaign, Vertex is hoping the CDC will recommend routine hepatitis C screening, which would start turning up a lot more positive tests. If it does, Emmens he predicts it could prompt another 1 million patients to seek treat treatment around 2014 and later, right as the most people in the initial wave of highly motivated patients go home having been cured.

“You have an estimated 2 million people out there who are not aware they are infected,” Emmens says. “Some don’t know, or just don’t give a damn, or have other problems, and won’t seek treatment. But if you found 1 million new patients over a two or three-year period, there’s a second tsunami.”

As for analysts predicting telaprevir will rise and fall, Emmens shook his head. “That’s absurd. I understand they’ve got to do their job. But from a marketing guy’s perspective, that just doesn’t happen unless you lose your patent,” Emmens says. “Docs use what works. Patients will come in, and they will want the highest chance they can get of a cure. That’s what they really care about.” A shorter treatment period, and more convenient twice-daily dosing instead of thrice-daily are a couple of other features Vertex is hoping to incorporate into hepatitis C treatment, he adds.

Vertex has clearly been spending a lot of time lately thinking about making its case to insurers. The trick will be to persuade insurers that it’s worth spending quite a bit of money upfront on a potent new drug to attack a dormant infection, as opposed to waiting to see if patients get sick years later and rack up big hospital bills. Emmens notes that liver transplants cost around $300,000, and, obviously, not everyone who wants a new liver actually survives long enough to get to the top of the waiting list. Vertex, citing an actuarial study it sponsored to try to measure the cost of future treatment, says medical costs in the U.S. for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion—presumably when factoring in a lot of liver transplants.

I must say I’m personally wary of drugmakers who use their money and influence to rewrite health guidelines that end up favoring their bottom line. Companies that want to sell more drugs for high blood pressure, osteoporosis, and obesity have been known to push for new health guidelines that classify many more people as “Suddenly Sick” as a couple of my former Seattle Times colleagues wrote in a terrific investigative story in 2005. Whether this aggressive new treatment is really beneficial to people’s health over the long run is often unknown.

This case strikes me as somewhat different, though, because today’s available hepatitis C treatment is really so poor. Vertex and Merck are essentially coming along with drugs that represent a big leap ahead with potential to cure hundreds of thousands, maybe millions, of people. It will probably cost taxpayers a few billion dollars a year for many years to come, and it’s always hard to say for sure how many billions you might save down the road when people don’t end up in the hospital getting liver transplants. But you can be sure Vertex is working hard behind the scenes right now to convince officials that an ounce of prevention is worth a pound of cure.

Luke Timmerman is the National Biotech Editor of Xconomy, and the Editor of Xconomy Seattle. You can e-mail him at ltimmerman@xconomy.com, or follow him at twitter.com/ldtimmerman.