July 21, 2010

Hope Against Hepatitis C

Betty Stevenson, a hepatitis C patient and former heroin addict,
speaking about how the Oasis program helped save her life.


Published: July 21, 2010

New medicines are being developed that are expected to transform the care of patients with hepatitis C, making treatment far more effective and far less grueling.

The new drugs, which could start reaching the market as early as next year, could help subdue a virus that infects roughly four million Americans, most of them baby boomers, and 170 million people worldwide.

“I almost think this will be revolutionary, to be honest,” said Dr. Fred Poordad, chief of hepatology at Cedars-Sinai Medical Center in Los Angeles. “We are chomping at the bit to try to treat as many patients as we can.”

About two dozen pharmaceutical companies are now pursuing drugs for hepatitis C, which an executive at Vertex Pharmaceuticals recently called “one of the largest pharmaceutical opportunities this decade.”

That is because the toll of the disease, which now kills about 12,000 Americans a year, is expected to rise in the coming decade. Although new cases have dropped sharply, hundreds of thousands of people who were infected decades ago are expected to start experiencing the effects of liver damage.

New cases of liver cancer are already rising year by year. And hepatitis C is the leading cause of liver transplants, like the one recently received by the rock musician Gregg Allman.

Hopes for new treatments were buoyed in May by the first results from a late-stage clinical trial of one of the new drugs, telaprevir from Vertex. When added to the existing treatment — a combination of alpha interferon and ribavirin — telaprevir effectively cured 75 percent of patients, compared with 44 percent of those treated with the existing drugs alone. And for many patients, the course of treatment could be halved to 24 weeks.

Dr. Poordad, who is a consultant to some of the pharmaceutical companies, said that one-fifth of his patients were being “warehoused,” meaning they were forgoing treatment now to wait for the new drugs.

But even if the drugs do work, some experts and doctors warn that this virus may be particularly tough to vanquish. Three-quarters of the people who are infected do not know it because they are not tested for the virus and because the infection can be asymptomatic for years while it stealthily attacks the liver.

And because this disease is transmitted by blood, those infected largely are former or current IV-drug users — a population that characteristically has little or no health insurance — who may not be the most able to stick to a lengthy treatment regimen that can cause brutal side effects.

Pharmaceutical companies “completely ignore the real face of hepatitis C,” said Dr. Diana L. Sylvestre, who runs a clinic in Oakland, Calif., that treats drug addicts and former addicts with hepatitis C. “A minority of patients who have hepatitis C will benefit from these drugs.”

When she gave a recent talk at Vertex, Dr. Sylvestre’s first slide showed a man in a suit, meant to be a Vertex executive, with his head in the sand.

Dr. Camilla Graham, a senior director of medical affairs at Vertex, said that addicts accounted for less than 10 percent of people with hepatitis C. While many people got infected by trying drugs in the 1960s and 1970s, they have long since kicked the habit, she said.

Hepatitis C can also be transmitted sexually, particularly when men have sex with other men. And many people got the virus from blood transfusions before 1992, when donated blood began being tested for the virus.

Nevertheless, pharmaceutical companies realize that difficulties getting patients screened and treated could limit the use of their drugs. So they are contributing to a groundswell of activism to raise awareness of what has long been known as a silent epidemic. Also contributing to the new advocacy is the highly organized H.I.V. community, since 15 to 30 percent of those with H.I.V. also have hepatitis C.

A report issued by the Institute of Medicine in January urged a new national strategy to improve prevention, detection and treatment of hepatitis C and hepatitis B, which also causes liver disease. A hepatitis task force created by the Department of Health and Human Services is preparing an action plan by October. The House Oversight and Government Reform Committee held a hearing on hepatitis last month.

Drug makers contribute to the National Viral Hepatitis Roundtable, which helped pay for the Institute of Medicine report, and several companies have banded together into the Corporate Hepatitis Alliance to lobby for more government funding. In January, several companies started the Viral Hepatitis Action Coalition, to help finance research at the Centers for Disease Control and Prevention.

Vertex has commissioned studies projecting a rising toll from hepatitis C. One such study, done by Milliman, a health insurance consulting firm, projected that the number of people with advanced liver disease from hepatitis C would quadruple in 20 years if treatment did not improve.

Screening people for hepatitis C should become easier. In June, the Food and Drug Administration approved a rapid blood test developed by OraSure Technologies that gives an answer in 20 minutes rather than several hours needed if the sample is sent to a lab. Future versions might use a mouth swab, allowing screening to be done at churches, street fairs and other gatherings.

There is a risk that increased screening could result in treatment for people who will never need it. Only 5 to 20 percent of people with chronic infection develop cirrhosis in about 20 to 30 years, and doctors cannot predict which patients those will be.

“I think the companies have done a superb job of marketing this disease,” said Dr. Ronald L. Koretz, emeritus professor of clinical medicine at the University of California, Los Angeles. Dr. Koretz said there was no good evidence that treatment made a difference since many patients cured by the drugs might never have developed serious problems anyway.

The current treatment for hepatitis C consists of weekly injections of alpha interferon — the leading brands are Roche’s Pegasys and Merck’s PegIntron — combined with ribavirin, a generic oral drug. It is not quite clear how these drugs work.

The regimen usually lasts either 24 or 48 weeks and costs more than $30,000. It can be rough, causing flulike symptoms, depression, anemia and other problems. And the treatment fails to cure the patient about half the time, either because it cannot clear the virus from the body or because the patient cannot tolerate the drugs.

The new drugs generally inhibit enzymes needed by the virus, a strategy that has worked well against H.I.V. The two drugs that could conceivably make it to the market by next year, Vertex’s telaprevir and Merck’s boceprevir, are both pills that inhibit the protease enzyme.

For a few years at least, the new drugs would have to be used along with interferon. But doctors are hopeful that starting perhaps in five years, combinations of the new pills will do away with the need for interferon.

The drugs could offer new hope to an estimated 300,000 people for whom the existing treatment has not worked. Some early data suggests that telaprevir, when combined with the existing drugs, could cure half of them.

“I was willing to try yesterday,” said Kenny C. Charles, 58, of Woodbourne, N.Y., who said he got hepatitis C from blood transfusions and had undergone four unsuccessful treatment attempts with the existing drugs. Now, he said, his liver was starting to show signs of cirrhosis, or scarring.

Some people with hemophilia, who were infected more than 25 years ago by blood-clotting drugs derived from human plasma, are pressing the Food and Drug Administration to allow them to be treated with combinations of the new drugs, without interferon, even before the new drugs are approved. The F.D.A. held a public hearing on the request in April and is now formulating a policy.

Mark Antell of Rosslyn, Va., one of the organizers of the petition, said he had to stop taking interferon because of flulike symptoms, loss of hair and creaking joints. “It was as though I was aging very rapidly,” he said.

Mr. Antell, 63, a retired Environmental Protection Agency employee, said hemophiliacs were typically not allowed into clinical trials to test the new drugs, so they needed another way to obtain them.

“I think there’s a lot of guys in my situation, and we don’t have a lot of time,” he said.


Hep C Treatment Effective in HIV Patients With Normal Liver Enzymes

July 21, 2010

by Tim Horn

People infected with HIV and hepatitis C virus (HCV) who have normal liver alanine transaminase (ALT) levels may benefit from pegylated interferon/ribavirin treatment, according to new data presented Tuesday, July 21, at the XVIII International AIDS Conference in Vienna. These results are important, as people with HCV and normal ALT levels are frequently told that treatment is not necessary.

As explained by Miguel Angel Von Wichmann, MD, of the Hospital Donostia in Madrid, normal ALT levels in the setting of chronic HCV infection are typically considered a factor related to slow progression to end-stage liver disease. However, he said, 80 percent of people with chronic HCV and normal ALT levels eventually develop some degree of liver disease, including significant progression to fibrosis and the development of liver cancer.

At least one study in people infected with HCV, but not HIV, has demonstrated that sustained virologic responses (SVRs)—an undetectable viral load maintained for at least six months after discontinuing treatment—are comparable among those with normal ALT levels versus those with elevated ALT levels. Whether this observation also holds true for people coinfected with HIV and HCV has, until now, been virtually unknown.

Von Wichmann and his colleagues conducted a study involving 68 HIV/HCV coinfected patients, divided into two groups. The first group included 35 patients with at least five normal ALT values over a 24-month period; the second group included 33 patients with persistently elevated ALT levels. All patients received pegylated interferon plus ribavirin (1,000 to 1,200 mg a day).

Twenty-four weeks of data from the 72-week study were presented by Von Wichmann in Vienna. Patients were, on average, 43 years old at the time of study enrollment; 77 percent were men. Roughly 74 percent had HCV genotypes 1 or 4—the most difficult to treat—and slightly more than half of the patients in each group had high HCV viral loads (greater than 800,000). Most patients had undetectable HIV viral loads.

SVR rates will not be known until therapy is discontinued at week 48 and the week-72 follow-up period has been reached. Von Wichmann reported, however, that early virologic responses (EVRs) were comparable between the two groups.

About 52 percent of case patients, compared with 68 percent of control patients, had undetectable HCV viral loads after 12 weeks of treatment—both encouraging results believed to be highly predictive of SVRs once treatment is discontinued. But it’s important to note that the difference between the two groups was not statistically significant, meaning it could have been due to chance.

Another measure of EVR—a greater than 2-log reduction in HCV viral load—was also reported. This was documented in 80 percent of the case volunteers and 96.4 percent of the control volunteers. Again, the difference was not found to be statistically significant.

The incidence of moderate-to-severe side effects, including hair loss, white blood cell decreases, flu-like symptoms, chest pain and weakness, was similar in both groups—roughly 46 percent.

At week 24, people in the group had higher CD4s: 300 cells versus 224.5 cells in the control group. Though this difference was statistically significant, it is also worth pointing out that patients in the case group tended to have higher CD4s upon entering the study (557 cells), compared with controls (409.5 cells).

Not surprisingly, ALT levels decreased in both groups, with those in the case group maintaining ALT levels significantly lower than those in the control group.

“These preliminary data,” Von Wichmann’s group concluded, “suggest that combination pegylated interferon and ribavirin in HIV-HCV coinfected patients with persistently normal ALT levels achieves comparable response values to patients with elevated ALT, with an adequate safety profile. Further analysis are needed to confirm these data and support the use of pegylated interferon plus ribavirin in these patients in clinical practice.”

Search: hepatitis C, HCV, ALT, liver enzymes, coinfection, treatment, Von Wichmann, Vienna, International AIDS Conference


Hepatitis C and Insulin Resistance

Jul 21, 2010

This press release is an announcement submitted by Garvan Institute of Medical Research, and was not written by Diabetes Health.

We have known for several years that Hepatitis C, a common cause of liver cirrhosis and cancer, also makes people three to four times more likely to develop Type 2 diabetes. In studying the insulin resistance of 29 people with Hepatitis C, Australian researchers have confirmed that they have high insulin resistance, a precursor to diabetes. However, almost all insulin resistance occurs in muscle, with little or none in the liver, a very surprising finding given that Hepatitis C is a liver disease.

Dr Kerry Lee Milner and Professor Don Chisholm from Sydney's Garvan Institute of Medical Research, in collaboration with Professor Jacob George from the Storr Liver Unit, University of Sydney at Westmead Hospital, have published their study in the prestigious international journal, Gastroenterology, now online.

Insulin, a hormone made by the pancreas, helps the body use glucose for energy. The two most important organs that respond to insulin are the liver and muscle. A healthy liver responds to insulin by not producing glucose, while healthy muscle responds by using glucose. An insulin resistant liver produces unwanted glucose, while insulin resistant muscle cannot absorb it from the bloodstream, leading to high levels of sugar in the blood.

"Contrary to all expectations, not only did we find no significant insulin resistance in the liver of the patients in the study, half of them suffered from a strain of Hepatitis C that causes about three times the normal level of fat to accumulate in the liver," said Professor Chisholm.

"The fifteen people with very high levels of fat in the liver had the same degree of insulin resistance as the fourteen that didn't have fatty livers."

"A number of important investigators around the world have been arguing that fat in the liver is an extremely important determinant of insulin resistance, perhaps the most important. At least in this context, we've shown that not to be the case."

"Before you get Type 2 diabetes, you must become insulin resistant and your insulin producing cells must also fail to compensate. Insulin resistance alone will not give you diabetes."

"In our study, we gave intravenous glucose, a specific stimulus to insulin secretion, and showed that insulin secretion was not impaired in Hepatitis C patients compared to our control group."

"This finding tells us that people with Hepatitis C who develop diabetes probably have susceptible insulin-producing cells, and would probably get it anyway - but much later in life. The extra insulin resistance caused by Hepatitis C apparently brings on diabetes at 35 or 40, instead of 65 or 70."

"More work now needs to be done into why Hepatitis C causes insulin resistance in muscle. That will give us better insight into the behaviour of the disease."

"At this stage, it is helpful for people with Hepatitis C to understand insulin resistance and what it can mean for them. If they have relatives with Type 2 diabetes, they will be genetically prone to developing it themselves and so would be advised to manage their diets very carefully and take plenty of exercise - to slow onset."

About Hepatitis C

Hepatitis C is a blood-borne virus and in Australia is caused mainly by drug users sharing needles, but also by unsterile tattooing or body piercing. There is no vaccine for Hepatitis C, unlike Hepatitis A and B.

Around 212,000 Australians suffer from chronic Hepatitis C, 80,000 - 85,000 of them in NSW. Across Australia, there are roughly 10,000 new infections each year.

There are 6 strains of Hepatitis C - the participants in this study were selected because they had either of two common strains in Australia, Genotype 1 and Genotype 3. The latter strain causes significant fat deposits in the liver.

While it is not noted in the media release above, the study observed that the degree of insulin resistance is a negative predictor of anti-viral treatment. In other words, the greater the insulin resistance, the less responsive people will be to treatment.

Between 50-80% of people who are treated for Hepatitis C are successfully treated, leaving 20-50% who do not respond. Treating with lifestyle changes or an insulin sensitiser may reduce this percentage - as well as delaying onset of diabetes.

The study found that predictors of insulin resistance were viral load and subcutaneous fat. This suggests the possibility that the virus alters either fat supply or alters the cell signaling proteins released from subcutaneous fat, either of which could generate insulin resistance.

About Garvan

The Garvan Institute of Medical Research was founded in 1963. Initially a research department of St Vincent's Hospital in Sydney, it is now one of Australia's largest medical research institutions with nearly 500 scientists, students and support staff. Garvan's main research programs are: Cancer, Diabetes & Obesity, Immunology and Inflammation, Osteoporosis and Bone Biology, and Neuroscience. The Garvan's mission is to make significant contributions to medical science that will change the directions of science and medicine and have major impacts on human health. The outcome of Garvan's discoveries is the development of better methods of diagnosis, treatment, and ultimately, prevention of disease.

* * *
Garvan press release


Does nevirapine improve hepatitis C treatment outcomes in HIV/HCV co-infected individuals?

Liz Highleyman
Published: 21 July 2010


Mira J et al. Concomitant nevirapine therapy is associated with higher efficacy of pegylated interferon plus ribavirin among HIV/hepatitis C virus-coinfected patients. Eighteenth International AIDS Conference, Vienna, abstract TUAB0101, 2010.

HIV/hepatitis C (HCV) co-infected people who included nevirapine (Viramune) in their antiretroviral therapy (ART) regimen were more likely to achieve sustained response to interferon-based therapy for chronic hepatitis C, according to a Spanish study presented on Tuesday at the Eighteenth International AIDS Conference in Vienna.

The researchers suggested nevirapine may lower HCV viral load and thereby improve treatment response, but an alternative explanation is that people who are prescribed this drug are less sick at the outset, and therefore more likely to respond to HCV treatment in any case.

Jose Mira, from Valme University Hospital in Seville, and colleagues evaluated the effectiveness of chronic hepatitis C treatment using pegylated interferon plus ribavirin in HIV/HCV co-infected patients using different antiretroviral regimens.

Prior research suggested that certain nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) used to treat HIV are associated with poorer response to interferon, perhaps due to drug interactions or intensified side-effects.

The role of non-nucleoside reverse transcriptase inhibitors (NNRTIs) and HIV protease inhibitors is less well studied, and what research there is has produced conflicting findings. A study called RIBAVIC, for example, found that use of HIV protease inhibitors was associated with less successful hepatitis C treatment, but others have not seen a similar link.

Some reports suggest that co-infected patients on nevirapine-based ART have lower plasma HCV RNA levels than those treating their HIV with a protease inhibitor or an alternative NNRTI, efavirenz (Sustiva, Stocrin). Lower HCV viral load, in turn, is a predictor of better hepatitis C treatment outcomes.

Mira's team retrospectively compared the efficacy of hepatitis C treatment between 71 HIV/HCV co-infected individuals taking nevirapine and 94 taking lopinavir/ritonavir (Kaletra) at hospitals in Spain between 2002 and 2009. All participants rounded out their ART regimens with tenofovir (Viread) plus either 3TC (Epivir) or emtricitabine (Emtriva).

Baseline demographic factors were similar in both study arms. About three-quarters of participants were men, the median age was just over 40 years, and about 80% had a history of injecting drug use. Both groups had well-controlled HIV disease with a CD4 cell count of approximately 450 cells/mm3. About 60% in both groups had hard-to-treat HCV genotypes 1 or 4.

But significantly more participants in the lopinavir/ritonavir group had advanced liver fibrosis (stage F3 or greater; 52 vs 21%) and high baseline HCV viral load (> 600,000 IU/ml; 73 vs 44%).

Participants were treated for chronic hepatitis C for the first time using a standard regimen of pegylated interferon (Pegasys or PegIntron) plus weight-adjusted ribavirin. People with HCV genotypes 1 or 4 were treated for 48 weeks, whilst those with the more responsive genotypes 2 or 3 completed treatment after 24 weeks. About 90% of participants in both groups reported good adherence. They were permitted to use blood cell growth factors to manage the side-effects of neutropenia due to interferon and anaemia caused by ribavirin.

People taking nevirapine were significantly more likely than those taking lopinavir/ritonavir to achieve sustained virological response (SVR), or continued undetectable HCV viral load six months after finishing treatment. In an intent-to-treat analysis, overall SVR rates were 56 vs 37%, respectively (43 vs 25% for patients with genotypes 1 or 4; 78 vs 59% for those with genotypes 2 or 3).

Lack of SVR was mainly attributable to non-response, occurring in 8% of nevirapine recipients and with 23% of lopinavir/ritonavir recipients. Rates of relapse, viral breakthrough and discontinuation due to adverse events were similar in both arms.

When participants were classified according to viral load, however, divergent response associated with antiretroviral drug choice was only apparent amongst participants with high HCV viral load.

The researchers concluded that HIV/HCV co-infected people who use nevirapine for ART respond better to pegylated interferon plus ribavirin than those who use lopinavir/ritonavir. Mira proposed that the lower HCV viral load levels seen in nevirapine users might account for this difference in response rates.

Session moderator Jürgen Rockstroh called this interpretation into question, however. Whilst Mira credited nevirapine with lowering HCV viral load, another possible explanation is that participants taking lopinavir/ritonavir may be sicker on average, because traditional ART sequencing starts with a NNRTI-based regimen and moves on to protease-based therapy as HIV disease progresses.

People at later stages of HIV disease may have reduced immune response to hepatitis C and higher levels of inflammation or other factors that contribute to increased HCV viral load and accelerated liver fibrosis progression – both of which predict poorer response to interferon.

But Mira disagreed that the study was biased in this way, noting that differences in interferon response between nevirapine and lopinavir/ritonavir recipients was still apparent after adjusting for HCV viral load and extent of liver fibrosis.

Also See: Viramune Boosts Hep C Treatment Efficacy in People With HIV

Better Understanding of Diagnosis Facilitates the Rollout of Novel Treatments Options in the Hepatitis C Therapeutics Market in India, Finds Frost & Sullivan

Source: Frost & Sullivan

Wednesday, July 21, 2010 02:14 PM IST (08:44 AM GMT)

Editors: General: Consumer interest; Business: Accounting & management consultancy services, Business services, Healthcare, biotechnology & pharmaceutical; Healthcare

Mumbai, Maharashtra, India, Wednesday, July 21, 2010 -- (Business Wire India)
Ongoing efforts to raise disease awareness in India have both increased the number of diagnosed cases and expanded the base of patients available for the treatment of Hepatitis C. The prevalence of Hepatitis C virus (HCV) infection was 1.2 percent of the population in 2009. It is expected to grow at a compound annual growth rate (CAGR) of 1.6 percent from 13,770,000 persons with HCV in 2009 to 15,420,000 persons with HCV in 2016.

Increasing population and high prevalence of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) have contributed to growing prevalence in the country. Greater clarity of diagnosis has facilitated the introduction of new treatment options.

New analysis from Frost & Sullivan (http://www.pharma.frost.com/), Multi-client Study: Opportunities Assessment for Hepatitis C Therapeutics Market in India, finds that the market for Hepatitis C therapies is likely to increase manifold by 2017 with increasing awareness, better diagnosis, affordable pricing, and newer drug launches.

If you are interested in a virtual brochure, which provides a brief synopsis of the research and a table of contents, then send an e-mail to Anish Charles/ Nimisha Iyer, Corporate Communications, at anishc@frost.com/ niyer@frost.com, with your full name, company name, title, telephone number, company e-mail address, company website, city, state and country. Upon receipt of the above information, a brochure will be sent to you by e-mail.

“The diagnosed patient base is expected to expand in the future with the gradual build-up in awareness, the number of Hepatitis C carriers, and access to urban healthcare facilities due to the improving rural economy and road infrastructure connecting rural areas with the nearest urban locations,” says Frost & Sullivan Industry Analyst Supratim Majumdar. “The number of diagnosed patients has been on the rise since 2006 following mandatory screening and increasing detection facility in urban areas.”

Although screening has been enhanced, only 9 percent of diagnosed patients are placed under treatment. The high cost of therapy coupled with numerous side effects results in treatment not being extended to a larger patient pool. The often-debilitating side effects, frequent dosing, and lackluster efficacy of current HCV treatments have resulted in lack of compliance and have spurred the exploration of more effective treatments.

Therapy for chronic Hepatitis C is currently limited to pegylated interferon in combination with ribavirin. While this combination can effectively clear the infection in some patients, it has limited efficacy in patients with genotype 1, who comprise 20 percent of HCV patients in India. The side effects of this treatment include lowered blood platelet count, depression, and hemolytic anemia.

The low success rate of interferon, along with side effects, results in patients either avoiding or withdrawing from treatment. The combination of these factors represent missed treatment opportunities and thus, market share.

Public and private campaigns have been launched in India to ramp up disease awareness. However, more concerted efforts are required. Greater information outreach will enable patients to understand the treatment processes better and be more receptive toward those. The role of the government is minimal in raising the awareness level of public about Hepatitis C. The key opinion leaders (KOLs) and physicians involved in the treatment of Hepatitis C have emphasized that the government should take a more proactive role in educating the public on Hepatitis C.

“Companies on their part must offer treatment options that expedite efficiency, have fewer side effects and are cost efficient,” says Majumdar. “They must ensure that patients are aware of their disease status and compliant to treatment.”

Encouraging patients to remain compliant and providing incentives to stay on HCV treatment will increase the likelihood of future compliance, especially for improved treatments. Refined versions of current HCV drugs, oral formulations of small molecule inhibitors, and the new drug class known as protease inhibitors are in the development pipeline and represent the future of HCV treatment. New treatment options must be launched to capture this growing market.

Multi-client Study: Opportunities Assessment for Hepatitis C Therapeutics Market in India is part of the Pharmaceuticals & Biotechnology Growth Partnership Service program, which also includes research in the following markets: Opportunities Assessment of Hepatitis C Market in Taiwan, Opportunities Assessment of Hepatitis C in Philippines, Opportunities Assessment of Hepatitis C in Indonesia, Opportunities Assessment of Hepatitis C in Singapore, Opportunities Assessment of Hepatitis C in Australia, Opportunities Assessment of Hepatitis C in Thailand, Opportunities Assessment of Hepatitis C in Hong Kong, Opportunities Assessment of Hepatitis C in China, Opportunities Assessment of Hepatitis C in Korea, and Opportunities Assessment of Hepatitis C in Malaysia. All research services included in subscriptions provide detailed market opportunities and industry trends that have been evaluated following extensive interviews with market participants.

About Frost & Sullivan

Frost & Sullivan, the Growth Partnership Company, enables clients to accelerate growth and achieve best-in-class positions in growth, innovation and leadership. The company's Growth Partnership Service provides the CEO and the CEO's Growth Team with disciplined research and best-practice models to drive the generation, evaluation, and implementation of powerful growth strategies. Frost & Sullivan leverages over 45 years of experience in partnering with Global 1000 companies, emerging businesses and the investment community from 40 offices on six continents. To join our Growth Partnership, please visit http://www.frost.com/.

Multi-client Study: Opportunities Assessment for Hepatitis C Therapeutics Market in India

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Anish Charles, Corporate Communications – South Asia,
Frost & Sullivan,
+91 (22) 40013419,

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Frost & Sullivan,
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Nimisha Iyer, Corporate Communications – South Asia and Middle East,
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Prevention and treatment can block worldwide health threat hepatitis with many forms

BY Katie Charles
Wednesday, July 21st 2010, 4:00 AM

The specialist: Dr. Douglas Dieterich on viral hepatitis

As a professor of medicine with more than 30 years of experience, Dieterich is a gastroenterologist and internist who treats outpatient liver disease. He sees about 60 viral hepatitis patients a week.

Who's at risk

Viral hepatitis is an umbrella term for the disease that results from several specific viruses that primarily attack the liver and cause inflammation. Researchers have identified strains of hepatitis A, B, C, D and E, which have different modes of transmission.

"Hepatitis B and C are a huge problem," says Dieterich. "Hepatitis B is the biggest worldwide infection, with probably 1 billion people infected, and hepatitis C affects another 500 million or more people worldwide." About 3 million-5 million Americans have hepatitis B, and doctors speculate that as many as 10 million may have hepatitis C, with the majority of cases remaining undiagnosed.

Diagnosing and treating viral hepatitis is essential because it is the main cause of cirrhosis and liver cancer. "These are very preventable and treatable diseases," says Dieterich. "There's a vaccine for hepatitis B, which is most often passed from mother to infant or sexually transmitted."

There's no vaccine for hepatitis C, which is transmitted via blood, but doctors have increasingly effective medications for treating both hepatitis B and C.

The groups at highest risk of hepatitis B are people born in Asia and sub-Saharan Africa, where 10% of the population is infected. "The No. 1 method of transmission worldwide is maternal fetal transmission at birth," says Dieterich. "Even at a major hospital in New York last year; the transmission rate from infected mothers to their babies was almost 10%."

Less easily transmitted than hepatitis B, hepatitis C is spread through blood. "Its main risk factors are anything with blood-to-blood contact: IV drug use, intranasal cocaine, tattoos, body piercing, needle sticks for health-care professionals, manicures and pedicures," says Dieterich.

For Americans, a major risk is having received a transfusion before 1992, when effective screening for hepatitis C came into use. "Generally, it's transmitted by blood, not by sex, but there is an outbreak of hepatitis C in HIV-positive men who have sex with other men," says Dieterich.

Another risk factor for hepatitis C is being born in the developing world. As much as 25% of the population in Egypt and the former Soviet Union has hepatitis C, and 13% of the population in Pakistan has it.

"In the past, health organizations were giving out one vial of vaccine and one syringe for the whole village or the whole classroom" in some areas, says Dieterich.

About 2% of the population in the U.S. is infected, but because doctors think only 10% of cases have been diagnosed, the real number of hepatitis C cases in this country may be as many as 10 million.

Signs and symptoms

All the strains of hepatitis have the same signs and symptoms. "The most common manifestation is no signs and symptoms," says Dieterich. "This is why screening is the key to diagnosis." Doctors can do a simple blood test that screens for all hepatitis strains from one blood draw, for a total cost of $35. "It's my strongly held opinion that everyone should be screened for hepatitis," says Dieterich. "Then you can be vaccinated for A and B if you're not immune, and treated for B or C if you are infected."

During acute infection, some patients do experience hepatitis symptoms. The most common warning signs to look out for are fatigue and yellow eyes, pale-colored stools and cola-colored urine.

Traditional treatment

There are successful medical therapies available for both hepatitis B and C. "Hepatitis B is hard for us to understand but easy to treat," says Dieterich. "We have very good medicines that can prevent the virus from replicating, thus preventing it from causing cirrhosis and liver cancer."

However, doctors can't usually cure hepatitis B. "Right now we approach this disease like diabetes and hypertension — if we control it, the long-term complications can be prevented," adds Dieterich.

Early detection is key because it allows doctors to manage the virus before it causes liver damage. "The pills are oral and very effective, with virtually no side effects," says Dieterich. "But it can be hard for people to understand that they have to take the drugs for the rest of their life."

About 3% of people per year clear hepatitis B on treatment compared to less than 1% of those not on treatment.

In contrast, hepatitis C is easy to understand but more difficult to treat. It can, however, be cured. "Once it's cured, it's cured," says Dieterich. "However, the treatment is currently difficult, consisting of a once-a-week shot of interferon, accompanied by the pill ribavirin taken twice daily."

The therapy lasts for either 24 or 48 weeks, depending on what kind of hepatitis C is involved. The success rate is 40%-80%, but the side effects can be very taxing. "The good news is that a new wave of less-difficult treatment options is just over the horizon," says Dieterich.

Research breakthroughs

"We're about to have a huge revolution in the treatment of hepatitis C," says Dieterich. "There are about 26 new drugs converging on the disease right now."

Doctors expect the first two will be approved by the FDA in the third quarter of 2011. In clinical trials, one drug increased the cure rate by 40%-75%, and for half of the patients, it cut treatment from 48 to 24 weeks.

"Those are the first shots fired in this revolution," says Dieterich. "In 10 years, we'll probably be able to treat hepatitis C without using interferon, which has the worst side effects of these drugs."

It is important, though, not to delay treatment in anticipation of new therapies. The death rate from hepatitis C is expected to quadruple in the next 10 years in the U.S., and many people cannot afford to wait for treatment.

Questions for your doctor

Two good questions for your doctor are, "Have I been vaccinated for hepatitis A and B?" and "Am I immune?" The doctor can tell both things from a blood test. If your test for hepatitis B or C is positive, ask "Can you refer me to a specialist who treats hepatitis B and C aggressively?"

What you can do

Get informed.

The American Liver Foundation (liverfoundation.org) and Hepatitis B Foundation (hepb.org) have excellent Web sites that are easy to navigate.

Get tested and get vaccinated.

"One test should be enough, unless you have further risks," says Dieterich. "Everyone should be vaccinated against hepatitis A and B."

Having liver enzyme levels that are normal is no guarantee that you don't have hepatitis, and is not an effective way to test for hepatitis.

Protect your liver.

Don't drink alcohol or take over-the-counter medicines in excess. Practice safe sex, and don't share needles.

Be careful about instruments that can transmit blood.

"If you get a tattoo, make sure they change the needle and ink," says Dieterich. "Bring your own instruments for manicures and pedicures."


HIV-infected drug users at greater risk of viral hepatitis, tuberculosis, bacterial infections and mental illness

July 20, 2010

HIV-infected drug users have increased age-matched morbidity and mortality compared with HIV-infected people who do not use drugs. This includes an increased risk of viral hepatitis, tuberculosis (TB), bacterial infections, and mental illness. In a new paper in The Lancet Series on HIV in people who use drugs, Professor Frederick L Altice, Yale University, New Haven, CT, USA, and colleagues show that there are evidence based treatments for both HIV and these co-morbidities, and that antiretroviral treatment (ART) for HIV can improve not only the course of HIV infection but also these other conditions.

The authors say: "Evidence-based treatment for substance-use disorders improves the psychological and physiological disruptions that perpetuate the often unstable life of HIV-infected drug-dependent individuals. Treatment of HIV infection, substance-use disorders, and comorbidities in HIV-infected drug users is improved by comprehensive and multidisciplinary management of these disorders."

If appropriately dosed, medication-assisted therapies for opioid and alcohol dependence, such as methadone, buprenorphine and injectable naltrexone, enhance adherence to ART in patients with HIV, as well as treatment for the above mentioned co-morbidities. Furthermore, they improve retention in HIV care and decrease HIV risk behaviours.

The authors note that as and when ART becomes universally available to drug users with HIV, and their health status improves, so their other health problems will take on increased prominence, such as non-AIDS related comorbitities and TB, all of which will come with their own treatment priorities. HIV infected drug users with TB co-infection creates various clinical challenges since TB can be difficult to diagnose in HIV patients due to atypical chest radiographs, high-rates of TB in parts of the body outside the usual setting of the lungs, and the reduced sensitivity of skin tests used to diagnose TB in HIV patients. While people with latent TB but not HIV infection have a roughly 1 in 11 lifetime risk of having their TB develop into full blown disease, it becomes a 1 in 11 annual risk in patients with HIV co-infection. Concentration of people with HIV and substance use disorders behind bars facilitates transmission of TB, including multidrug resistant strains, due to overcrowding and increased numbers of people who are immunosuppressed. Despite available treatments for HIV and substance use disorders, little treatment is available within these settings.

Due to common routes of transmission, between 60% and 90% of HIV infected IDUs have hepatitis C, and few receive treatment for reasons including cost, physician reluctance, concern about poor treatment adherence, and misperception about potential harm of hepatitis C. Though effective treatments are available, treatment resources are limited due to expense and availability; if the person has hepatitis B, however, they can be treated with other oral antiviral agents that are also effective against HIV.

Mental illness and substance-use disorders are closely inter-related with HIV infection and concentrated especially among prison populations. If drug treatments such as antidepressants are warranted, then care must be taken in the selection of the medication. Some common antidepressants are associated with decreased metabolism of methadone in patients on OST, yet most are safe and effective.

"The concentration of HIV behind bars is a result of society's punitive rather than treatment-oriented approach to drug use," says Professor Altice*. "Despite society's failed policy of mass incarceration of drug users, many of whom are HIV-infected, these sites may be seminal places for the identification and treatment of HIV, but requires sufficient resources to continue care, not only for HIV but for the myriad of substance use disorders, mental illness and other complications, after release."

The authors conclude: "HIV-infected drug users have substantial HIV-related and non-HIV-related medical and psychiatric comorbidities. As a result, care is often complicated for the individual and for the health-care system. Several evidence-based interventions are available to improve treatment outcomes for this vulnerable population, but parity in treatment outcomes to reduce morbidity and mortality in HIV-infected drug users will be achieved only with further resources, expertise, political will, and commitment by the health-care establishment."

Provided by Lancet


Retreatment of hepatitis C patients with pegylated interferon combined with ribavirin in non-responders to interferon plus ribavirin. Is it different in real life?

More than 50% of hepatitis C viruses (HCV)-infected patients do not respond to the classical Interferon (IFN)/Ribavirin (RBV) combination therapy. The aim of this study was to evaluate the efficacy of retreatment with Peg-Interferon alpha-2b (PEG-IFN alpha-2b) plus RBV, in patients with HCV, genotypes 1 or 3, who were non-responders to the previous standard treatment with IFN/RBV.

Methods: In the period 2005-2007, a total of 238 HCV chronic patients were non-responders to previous treatment with IFN plus RBV.

Of these 130 agreed to be retreated with PEG-IFN alpha-2b and participated in this evaluation (90 with genotype 1 HCV and 40 with genotype 3 HCV). Patients were retreated at assisted IFN application hubs in compliance with the country's public health system rules.

They received subcutaneous PEG-IFN alpha-2b, 1.5ug, once weekly, associated with RBV, through the oral route, with doses determined according to weight (1,000mg if weight [less than or equal to] 75kg and 1,250mg if >75kg). Patients with genotype 1 HCV were retreated for over 48 weeks and patients with genotype 3 HCV for over 24 weeks.

HCV-RNA was tested by polymerase chain reaction (PCR) at baseline, at week 12, at the end of the treatment, and 6 months thereafter. The predictiveness of week 12 in the development of a sustained virologic response (SVR) was also evaluated.

Patients with negative HCV-RNA at week 12 were considered as early virologic responders (EVR).

Results: EVR was observed in 25% of the patients with genotype 1 HCV and in 64% of the patients genotype 3 HCV (risk = 2.075 and p-value = 0.0414). SVR was observed in 22.2% of the patients with genotype 1 HCV and in 40% with genotype 3 HCV (intention-to-treat analysis).

The positive predictive value (PPV) of the HCV-RNA testing at week 12, in order to obtain the SVR, was 65% for genotype 1 and 56% for genotype 3, and the negative predictive value (NPV) was 88% for genotype 1 and 89% for genotype 3.

Conclusion: PEG-IFN alpha-2b plus weight-based ribavirin is effective in re-treating previous interferon-alpha plus RBV failure; 22.2% of the patients with genotype 1 HCV and 40% of patients with genotype 3 HCV achieved SVR.

Author: Fernando GoncalesCamila MomaAline ViganiEduardo GoncalesAdriana AngeramiRaquel TozoMaria PavanNeiva Goncales

Credits/Source: BMC Infectious Diseases 2010, 10:212

Published on: 2010-07-20


Viramune Boosts Hep C Treatment Efficacy in People With HIV

July 20, 2010
by Tim Horn

People coinfected with HIV and hepatitis C virus (HCV) who receive Viramune (nevirapine) may respond better to pegylated interferon/ribavirin HCV treatment compared with those receiving Kaletra (lopinavir/ritonavir), according to a retrospective study reported Tuesday, July 20, at the XVIII International AIDS Conference in Vienna.

It is known that some nucleoside reverse transcriptase inhibitors—such as didanosine (Videx EC), zidovudine (found in Retrovir, Combivir and Trizivir) and abacavir (found in Ziagen, Epzicom and Trizivir)—may decrease the efficacy and tolerability of HCV therapy. This is likely due to different interactions and toxicities, explained Jose Mira, MD, of the Hospital Universitario de Valme in Seville, Spain.

The information about whether protease inhibitors and non-nucleoside reverse transcriptase inhibitors influence sustained virologic responses (SVRs) to HCV therapy—defined as undetectable HCV levels six months after discontinuing treatment—among coinfected patients is limited and contradictory.

According to Mira, the use of protease inhibitors during HCV therapy led to a worse rate of response to pegylated interferon/ribavirin—the standard treatment for HCV—in a previous clinical trial. However, this association was not found in other studies performed in populations of coinfected patients.

It has also been reported that patients receiving Viramune-based antiretroviral (ARV) therapy show lower HCV viral loads than those treated with regimens containing a protease inhibitor or Sustiva (efavirenz). This finding, Mira added, could have a positive influence on the response to HCV therapy among individuals taking Viramune.

Based on these observations, Mira’s group decided to compare the efficacy of pegylated interferon/ribavirin among HIV/HCV-coinfected patients taking either Viramune- or Kaletra-based ARV regimens. This wasn’t an actual clinical trial, but rather a retrospective review of coinfected patients taking either ARV, along with pegylated interferon and ribavirin, at one of 20 hospitals throughout Spain.

The review included 165 patients, averaging 42 years old. Seventy-one patients were treated with Viramune, and 94 were treated with Kaletra.

It’s important to note that there were imbalances in the study population. The proportion of patients who were either male or had advanced liver fibrosis or cirrhosis was higher among individuals who took Kaletra. On the other hand, the percentage of patients with low levels of pre-HCV treatment viral loads was greater in the Viramune group.

In the strict intention-to-treat analysis, 56 percent of patients treated with Viramune experienced SVRs, compared with 37 percent of those receiving Kaletra. Among those with HCV genotypes 1 and 4—the most difficult to treat forms of HCV—the results were 43 versus 25 percent, respectively. Among those with easier to treat genotypes 2 and 3, the results were 78 versus 59 percent, respectively. These differences, Mira reported, were statistically significant, meaning they were all too great to have occurred by chance.

Eight percent of the patients in the Viramune group, compared with 23 percent of patients in the Kaletra group, were HCV treatment non-responders. This difference was statistically significant.

However, the differences in the rates of relapse, HCV viral load breakthrough, discontinuations due to adverse events and voluntary dropout were similar in both groups.

Because both groups were different regarding baseline HCV viral loads and fibrosis state, Mira’s group analyzed SVR rates by stratifying the population according to these important parameters. Among patients with high HCV viral loads (600,000 copies or greater), 58 percent of those who were receiving Viramune, compared with 31 percent of those taking Kaletra, experienced an SVR. Among patients with advanced fibrosis (a score of F3 or F4), 60 percent of the subjects in the Viramune group, compared with 36 percent of patients in the Kaletra group, achieved an SVR.

Upon analyzing the data for the specific factors associated with an SVR, the following were found to be positive variables: HCV genotype 2 or 3, use of ARV therapy including Viramune, and greater than 80 percent adherence to HCV treatment.

In conclusion, Mira stressed that controlled clinical trials are warranted to confirm the positive effects of Viramune on the efficacy of HCV therapy in people living with HIV.

Search: Viramune, nevirapine, hepatitis C, HCV, pegylated interferon, ribavirin, treatment, Kaletra, lopinavir


HIV/HCV Coinfection Further Increases Risk of Bone Fractures

July 20, 2010

by Tim Horn

Compared with people living with HIV, people coinfected with HIV and hepatitis C virus (HCV) appear to face an even higher risk of bone fractures, according to new data reported Tuesday, July 20, at the XVIII International AIDS Conference in Vienna.

Decreased bone mineral density is increasingly reported in the aging HIV-positive population, explained Roger Bedimo, MD, of the VA North Texas Health Care System in his introductory remarks. The risk of fractures has also been found to be increased among people living with HIV, compared with non-HIV-infected patients.

The overall prevalence of fragility fractures—a broken vertebrae, hip or wrist after falling from standing height or less—is higher among women, but men face a greater risk of death associated with fractures and they account for the majority of HIV cases in the United States. According to Bedimo, the overall mortality is about 20 percent in the first 12 months after a hip fracture and is higher in men than women.

Bedimo also noted that 15 to 30 percent of people living with HIV are coinfected with HCV, which by itself is associated with osteoporosis.

To determine whether or not HCV coinfection adds to the risk of osteoporotic fractures among people living with HIV, Bedimo and his colleagues analyzed data from the Veterans Affairs’ Clinical Case Registry. Included in the analysis were patient data collected before the widespread use of combination ARV therapy (1988 to 1995) and the contemporary era of combination treatment (1996 to 2009).

More than 56,500 patients were included in the analysis; 98 percent were male, and about a third were HIV/HCV coinfected. The average age at entry was 45.

Patients were followed in the cohort for an average of 5.4 years. About 64 percent of those included in the analysis had been on antiretroviral therapy for at least one month, with an average treatment duration of four years.

According to the analysis, 951 patients sustained at least one osteoporotic fracture, including 106 vertebral factures, 451 wrist fractures and 308 hip fractures. The rate, per 1,000 patient-years of follow-up, was 2.54 among those only infected with HIV, compared with 3.25 among those coinfected with HIV and HCV.

Several known osteoporotic risk factors were echoed in the VA study, including older age, white race, tobacco use, diabetes and a low body mass index (less than 20). Bedimo also reported that while people with HCV coinfection only made up 31.2 percent of the study population, they accounted for more than 50 percent of the reported osteoporotic fractures.

Looking only at data collected between 1996 and 2006, the fracture rate—per 1,000 patient-years—was 2.86 among those with HIV monoinfection, compared with 4.06 among those with HIV/HCV coinfection. During the entire study period—1988 through 2009—the fracture rates were 2.54 and 3.35, respectively.

In conclusion, Bedimo reiterated that HCV coinfection is associated with a higher risk of osteoporotic fractures among people living with HIV. He added that the risk of osteoporotic fractures appears to be increasing in the modern-day treatment era among HIV/HCV-coinfected patients.

Bedimo also noted that, contrary to increasing rates of osteoporotic fractures in recent years, exposure to ARV therapy may be protective against bone breaks. The lower rates of fractures in the pre-combination ARV therapy era can likely be chalked up to premature death due to AIDS-related illnesses, which ultimately occurred before an osteoporotic fracture could be documented. Then again, he said, combination ARV therapy might not be protective, adding that a VA analysis exploring the positive—or potentially negative—effects of modern-day HIV treatment on osteoporotic fracture risk is in progress.

Search: hepatitis C, HCV, osteoporosis, bone mineral density, fracture, hip, wrist, vertebrae, bone, Vienna, International AIDS Conference, Bedimo


High doses of ursodeoxycholic acid ineffective for NASH patients

Public release date: 20-Jul-2010

Contact: Dawn Peters

Drug fails to improve overall liver histology compared to placebo

A study conducted by researchers at Johann Wolfgang Goethe University in Frankfurt, Germany found that high doses of ursodeoxycholic acid (UDCA), suggested by some studies to have a beneficial effect on nonalcoholic steatohepatitis (NASH), does not improve overall histology in these patients. Full findings of this study are published in the August issue of Hepatology, a journal of the American Association for the Study of Liver Diseases (AASLD).

According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NASH ranks as one of the major causes of cirrhosis in America, behind hepatitis C and alcoholic liver disease. Liver transplantation is the only treatment for advanced cirrhosis with liver failure, and transplantation is increasingly performed in people with NASH. Currently, there are no specific therapies for NASH.

Small, open label clinical studies have shown that UDCA positively influenced liver function tests and liver histology in NASH patients, but a two-year prospective double-blind trial with 166 patients at the dosage of 13󈝻mg/kg body weight per day failed to confirm these results. To determine if the dosage of UDCA may have been too low and a reduction of body weight could have contributed to the results, the German research team initiated a multicenter, placebo-controlled double-blind trial with a high dose of UDCA and without weight-lowering diet.

A UDCA dose of 23-28 mg/kg body weight or placebo was administered daily in three divided doses to 147 randomized patients of both sexes, aged 18 years and older. No special diet was recommended and the body weight of the patients remained constant during the study period. The total treatment time for each patient was 18 months. The primary objective was improvement of liver histology by at least 3 points. Secondary criteria were single histological variables and liver biochemistry.

Pre- and post-treatment liver biopsies from each patient were evaluated according to a modified Brunt score (including steatosis, hepatocellular ballooning, lobular inflammation, and portal/lobular fibrosis) as well as the nonalcoholic fatty liver disease activity score (NAS). Using the modified Brunt score, 185 patients with histologically proven NASH were randomized (intention to treat: ITT), 147 were treated per protocol (PP). Using the NAS, 137 patients were confirmed as having NASH, 48 were borderline NASH, and 1 was not NASH.

The results were the same for both scoring systems—no significant improvement in overall histology was detected. Of the single variables, only lobular inflammation improved using both the modified Brunt and NAS scores. In subgroup analyses, significant improvement of lobular inflammation was also observed in males, patients less than 50 years of age, slightly overweight patients, in patients with hypertension and an increased histology score. The fibrosis scores did not change.

"Our study has shown that the high dose of 23 to 28 mg UDCA/kg body weight per day, over a treatment time of 18 months, was unable to improve liver histology and overall liver function when compared to placebo and thus confirms the results of an earlier study using a lower dose over a period of 24 months," concluded study leader Dr. Ulrich F.H. Leuschner.

"Previous investigations may have shown positive results, because, first of all, in most of the studies the number of patients was too small, treatment time was too short, or a control group was missing," he explains. "Secondly, the positive effect of UDCA on the suggested pathogenetic mechanisms has been shown in only a few investigations with a small number of experimental animals and in few patients. Finally, the anticipation of an effect of UDCA in NASH probably depends on an incorrect assumption. Up to now positive effects of UDCA have only been observed in primary biliary cirrhosis, but NASH does not present with features of biliary liver diseases."


Article: "High-Dose Ursodeoxycholic Acid Therapy of Nonalcoholic Steatohepatitis. A Double-Blind, Randomized Placebo-Controlled Trial." Ulrich F.H. Leuschner, Birgit Lindenthal, Günter Herrmann, Joachim C. Arnold, Martin Rössle. Hepatology; Published Online: April 23, 2010 (DOI: 10.1002/hep.23727); Print Issue Date: August 2010.

This study is published in Hepatology. Media wishing to receive a PDF of this article may contact healthnews@wiley.com.

Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD).

Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, Inc., with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit http://www.wileyblackwell.com/.


Depression overlooked in patients with hepatitis C; compromising HCV therapy

Public release date: 20-Jul-2010

Contact: Dawn Peters

Lower patient productivity and higher healthcare benefit costs add to burden of HCV infection

Researchers from Denmark, Sweden, Norway and Finland (the NORDynamIC project group) have observed that depressive symptoms in patients with hepatitis C virus (HCV) infection are commonly overlooked in routine clinical interviews, and that treatment-induced depression compromises the outcome of HCV therapy. A second U.S. study found that patients with chronic infection had lower (work) productivity and incurred higher medical benefit costs than those without HCV. Both studies are available in the August issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases (AASLD).

HCV is a blood-born infection causing inflammation and destruction of liver cells. When inflammation lasts longer than six months there is ongoing liver cell injury which is defined as chronic HCV. The standard treatment protocol for chronic HCV is weekly injections of peg-interferon alfa-2a in combination with daily oral ribavirin for 24 to 48 weeks. However, this combination treatment can lead to major depression or other psychiatric complications in a number of HCV patients which may require premature termination of the antiviral therapy.

Peter Leutscher, M.D., Ph.D., and colleagues estimated the value of routine medical interviews in diagnosing depression in chronic HCV patients receiving peg-interferon/ribavirin therapy using the Major Depression Inventory (MDI). The MDI is a self-rating depression scale with a dual functionality in diagnosing major depression and in measurement of depression severity. Of the 325 HCV patients enrolled in the study, 6% were observed with major depression at baseline. Among the remaining 306 patients, 37% (n=114) developed depression while on HCV combination therapy. "According to the MDI criteria, we found that only 32% of the 114 patients with major depression were correctly diagnosed during routine medical interviews," noted Dr. Leutscher.

Researchers also noted that the emergence of major depression frequently led to premature discontinuation of the peg-interferon/ribavirin therapy. Those patients with higher MDI scores (30 and over) were more likely to have a diminished treatment outcome. "A self-report instrument such as the MDI scale may be a useful tool for health providers to identify patients at risk for depression during HCV therapy," recommended Dr. Leutscher.

Another HCV study published this month in Hepatology compared healthcare benefit costs and productivity issues for patients with and without chronic HCV infection. A total of 339,456 U.S. subjects were evaluated—1664 employees with HCV and 337,792 in the healthy control. Rich Brook, lead study author said, "We found that employees with HCV infection experience significant health-related work absences, greater health benefit costs, and further comorbidity than those without infection."

Research results found HCV infected workers had 4.15 more total annual absence days and processed 7.5% fewer units of work per hour than those in the control group. Healthcare benefit costs were also significantly higher in the HCV group with a total incremental difference of $8,352 per year, including $490 in indirect (absence) costs.

Prior studies estimate that 180 million people are affected by HCV worldwide, and currently a vaccine to treat this disease is not available. Experts project that HCV will lead to a substantial health and economic burden over the next 10 to 20 years. "Our research supports this finding and provides a real world evaluation of HCV's impact on productivity and healthcare benefit costs in the workplace," concluded Mr. Brook.


Article: "Evaluation of Depression as a Risk Factor for Treatment Failure in Chronic Hepatitis C." Peter Derek Christian Leutscher, Martin Lagging, Mads Rauning Buhl, Court Pedersen, Gunnar Norkrans, Nina Langeland, Kristine Mørch, Martti Färkkilä, Simon Hjerrild, Kristoffer Hellstrand, and Per Bech. Hepatology; Published Online: April 29, 2010 (DOI: 10.1002/hep.23699); Print Issue Date: August 2010.

Article: "The Impact of Hepatitis C Viral (HCV) Infection on Work Absence, Productivity, and Healthcare Benefit Costs." Jun Su, Richard A. Brook, Nathan L. Kleinman, Patricia Corey-Lisle. Hepatology; Published Online: May 26, 2010 (DOI: 10.1002/hep.23726); Print Issue Date: August 2010. This study is published in Hepatology. Media wishing to receive a PDF of this article may contact healthnews@wiley.com.

Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD).

Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, Inc., with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit http://www.wileyblackwell.com/.