Hepatitis C: A 21st Century Success Story (Op-Ed)

Credit: Dreamstime

Dr. David Bernstein, North Shore-LIJ Health System

Date: 22 May 2013 Time: 03:38 PM ET

Dr. David Bernstein is chief of the Division of Hepatology / Center for Liver Disease at the North Shore-LIJ Health System, and a professor of medicine at Hofstra North Shore-LIJ School of Medicine. He contributed this article to LiveScience's Expert Voices: Op-Ed & Insights.

Hepatitis C has been called a silent epidemic: As the most common blood-borne viral infection in the country, it affects more than 7 million Americans — yet, most don't know they have it. But the condition can lead to the development of cirrhosis and liver cancer, and is the leading indication for liver transplantation in the United States.

Baby boomers have the highest rate of hepatitis C infection, so the Centers for Disease Control and Prevention (CDC) recently recommended that all people born between 1945 and 1965 get tested at least once for it. People with other risk factors for hepatitis C (e.g., previous intravenous drug users, previous cocaine users, recipients of blood transfusions before 1992, and people with tattoos and body piercings in places other than the ears) should also get tested, regardless of age.

Once hepatitis C is diagnosed, it is curable, unlike other common blood-borne viruses , such as hepatitis B and HIV. Advances in hepatitis C therapies have been rapid. The first therapy for hepatitis C infection consisted of interferon injections alone, with a cure rate of less than 10 percent. In the mid-1990s, a pill called ribavirin was added to injectable interferon, and cure rates increased to about 40 percent. For more than 10 years, once-weekly injectable interferon plus oral ribavirin for a course of 24 to 48 weeks was the standard treatment method.

The high prevalence of hepatitis C has led to a considerable effort to improve cure rates with newer therapies. The first step was to understand the mechanism of hepatitis C viral replication. After researchers determined the disease's molecular structure, they identified the two main classes of enzymes involved in hepatitis C replication: protease and polymerase inhibitors. As a result of that research, direct-acting medications were manufactured to inhibit those enzymes — thus preventing replication and promoting higher cure rates.

In May 2011, the U.S. Food and Drug Administration approved the first new hepatitis C therapies in a decade. Two new oral agents — boceprevir and telaprevir, from the class of drugs called protease inhibitors — were approved for use in combination with pegylated interferon and ribavirin. These new, triple-therapy regimens have seen cure rates as high as 70 to 75 percent. Therapy lasts from 24 to 48 weeks. Boceprevir and telaprevir are both taken three times a day for a time period ranging from three months to 44 weeks, depending on clinical circumstance for each patient.

The new protease inhibitors increased efficacy — and side effects . Telaprevir is associated with a rash that generally appears in the first four to eight weeks of therapy, as well as anal pain that can manifest at any time during treatment. Most patients are easily treated with topical creams and antihistamine pills. Boceprevir is associated with a bad taste in the mouth in almost all patients — though this is more of an annoyance than a problem. Most patients barely notice it. Both telaprevir and boceprevir are associated with the development of significant anemia, which can limit their use. The anemia can lead to fatigue and may require the use of growth factors — compounds that affect cell growth, maturity and differentiation — to alleviate symptoms.

Since the approval of boceprevir and telaprevir, drug development has been progressing rapidly. Many studies are evaluating the use of second-generation protease inhibitors, polymerase inhibitors and NS5A inhibitors in various combinations to treat all different types of patients with hepatitis C. In addition to new agents, shorter durations of therapy (eight or 12 weeks) and interferon-free, all-oral regimens are in development.

It is highly probable that an all-oral regimen for the treatment of hepatitis C genotype 2 and 3 will become available late this year or in early 2014, with similar efficacy as that of interferon-based therapies, but with fewer side effects and a shorter course. It is also likely that a new, second-generation protease inhibitor — simeprevir — and a first-in-class oral nucleotide analogue polymerase inhibitor — sofosbuvir — will be approved in early 2014.

Both of those new agents are given once daily and will be approved for use in hepatitis C genotype 1 in combination with interferon and ribavirin. The treatment duration for the new simeprevir-containing regimen will likely be 24 to 48 weeks, while the regimen with sofosbuvir will likely last 12 weeks. Neither of those new agents have any significant side effects, and cure rates should be higher than currently approved triple therapies.

After simeprevir and sofosbuvir are approved, many even newer agents are likely to come to market. It seems clear that all-oral therapy for the treatment of genotype 1 should be available sometime in 2015 or 2016. Compared to current regimens, all of the newer therapies offer higher cure rates, shorter duration of therapy and fewer side effects. A lot of work is underway to determine the best possible therapy for specific groups of patients. For example, specific regimens will likely be developed for each genotype, for patients with cirrhosis, for patients with kidney disease and for those who have had a kidney transplant.

With any luck, in the next decade, medical science should be able to treat and cure more than 90 percent of hepatitis C patients. The greater challenge is identifying patients — because most remain undiagnosed — and educating medical providers about the new therapies. Hopefully, the CDC screening guidelines will help. In addition to their other advantages, the newer therapeutic regimens may prevent the development of cirrhosis, liver cancer and the need for liver transplantation. The treatment and cure of hepatitis C will be one of the 21st century's major medical success stories.

Bernstein's disclosures are as follows:

Clinical-trial sponsors: Abbott, BMS, Gilead, Janssen, Vertex, Merck, Genentech

Consultant/speaker bureau: Abbott, Gilead, Janssen, Vertex, Merck

The views expressed are those of the author and do not necessarily reflect the views of the publisher.

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AbbVie Says It Can Beat Gilead in Race for New Hepatitis C Drugs

Bloomberg News

By Drew Armstrong

June 13, 2013

AbbVie Inc. (ABBV) said it can win the race against Gilead Sciences Inc. (GILD) to bring to market a new generation of all-oral hepatitis C drugs.

AbbVie’s trial for an unnamed multidrug therapy is in the last of three stages typically required for U.S. approval and is moving quickly, Scott Brun, the company’s head of drug development, told investors (ABBV) today at a conference in New York. Gilead is seeking to bring its own multidrug regimen with its therapies sofosbuvir and ledipasvir to market next year.

“We’ve got a very good shot at being first,” Brun said at the conference hosted by Goldman Sachs Group Inc. “It is a very tight race.”

Multidrug regimens by AbbVie, Gilead and Bristol-Myers Squibb Co. (BMY) will offer hepatitis C patients more tolerable options that do away with weekly shots of interferon, a current standard of treatment that causes flu-like side effects. Gilead estimated in May that 150,000 patients may seek treatment in the U.S. once the new class of all-oral drugs is on the market, compared with 85,000 patients taking therapies last year.

“The idea is Gilead will be first, AbbVie will be on roughly the same timeline, Bristol-Myers will be somewhere after that,” said Marshall Gordon, a New York-based analyst with Legg Mason Inc.’s ClearBridge Investments affiliate.

With Gilead’s and AbbVie’s drugs possibly coming onto the market about the same time, their success may depend on what their effectiveness looks like in the final phase of trials, and how they’re priced.

“We don’t know where the efficacy is ultimately going to fall out,” Brun said on the two companies’ drugs.

Market Potential

Hepatitis C attacks the liver and can lead to liver cancer. The virus affects about 150 million people worldwide and the market for new pills is estimated at $20 billion. Gilead’s drug is projected to have annual sales of $6.03 billion by 2016, according to an average of 10 analysts’ estimates (GILD) compiled by Bloomberg.

AbbVie, spun off from Abbott Laboratories, has risen 26 percent since the shares began trading on the open market in January. The stock rose less than 1 percent today to close at $43.15 in New York. Gilead, the world’s largest maker of HIV medicines, increased 1.5 percent to $51.95.

“AbbVie is not getting nearly the credit that Gilead is,” ClearBridge’s Gordon said in a telephone interview. “It’s funny to me that it’s a foregone conclusion that Gilead has dominated the market.”

Phase II

In a Phase II trial, Gilead’s all-oral hepatitis C treatments sofosbuvir and ledipasvir cured 95 percent of patients after eight weeks of the therapy. The Foster City, California-based company is moving the drugs into a third of three stages of clinical trials. The treatment may be sold as a single pill taken once a day.

AbbVie’s treatment will require three pills in the morning and one at night, according to Brun. In a Phase II trial with the drugs, 90 percent of patients who completed the eight-week regimen had the virus cleared from their body.

“To be fair, Gilead’s drug looks better, but not that much better,” Gordon said.

To contact the reporter on this story: Drew Armstrong in New York at darmstrong17@bloomberg.net;

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

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CDC: 1-in-12 Asian-Americans, Pacific Islanders have hepatitis B

Wednesday, June 12, 2013 7:29 PM

CDC: 1-in-12 Asian-Americans, Pacific Islanders have hepatitis B

ATLANTA, June 12 (UPI) -- Know Hepatitis B is a U.S. multilingual public information campaign to inform Asian-Americans and Pacific Islanders to be tested for hepatitis B, officials say.

"If you or your parents were born in Asia or the Pacific Islands, it is critical that you get tested for hepatitis B," Dr. Howard Koh, assistant secretary for health at the U.S. Department of Health and Human Services, said in a statement.

"Everyone in the Asian-American community -- from individuals, to community leaders, to physicians -- can all help us put an end to this epidemic by getting tested and talking about hepatitis B."

In the United States, Asian-Americans and Pacific Islanders are one of the groups hardest hit by hepatitis B, which can cause potentially fatal liver damage, including liver cancer.

Hepatitis B-related liver cancer is a leading cause of death among many in these communities. Many with chronic hepatitis B became infected as infants or young children. It is usually spread when someone comes into contact with blood from someone who has the virus, Koh said.

It is estimated 1-in-12 Asian-Americans and Pacific Islanders live with hepatitis B. Yet, 2-in-3 do not know they are infected, because the disease often has no symptoms until serious liver damage has occurred, Koh said.

(Source: UPI )
(Source: Quotemedia)

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New Liver Disease Test Provided By Glowing Proteins From Eels

A new fluorescent protein from unagi eels, commonly found in sushi, is the basis for a revolutionary liver disease test.

By Nsikan Akpan, PhD | Jun 13, 2013 12:01 PM EDT

A newly discovered protein in eels glows when it comes in contact with bilirubin, a natural byproduct of liver damage, according to Japanese scientists from RIKEN Brain Science Institute. In their study, researchers adapted this fluorescent protein, the first found in vertebrate species, into a quick, ultra sensitive test for liver damage that could ultimately save lives.

If you've ever been to a fancy sushi restaurant, then you might already be familiar with unagi, the Japanese freshwater eel (Anguilla japonica). Unagi is Japanese delicacy, which spends most of its life swimming in the streams and rivers of Japan, but during adulthood, will venture thousand of miles into the Philippine Sea to breed.

While studying the eel in 2009, a separate research group found its muscle fibers glow yellow when a bluish-green light is shined on them.

Drs. Akiko Kumagai and Atsushi Miyawaki led a team of scientists who were able to extract the 'light-emitting' protein from the eel's muscles. But the luminescence from the protein, which they named UnaG, was very faint on its own.

Given that the eel's muscle tissue emitted a stronger glow, the researchers suspected 'a partner in shine.' In other words, UnaG might interact with another compound that helps it to glow.

They mixed UnaG protein with a variety of biological substances, and their test tubes lit up when the eel protein was combined with serum from cow or human blood. A series of tests revealed the co-partner was a yellow compound called bilirubin.

Bilirubin is a waste product generated by the breakdown of blood cells. The liver is in charge of packing bilirubin, so it can be excreted by urination or as bile in the gallbladder.

One of the first signs of liver disease, such a hepatitis or liver cancer, is jaundice or a yellowing of the skin and eyes. Jaundice is caused by an accumulation of too much biliruibin in the blood.

The authors found that UnaG protein could be used as quick, sensitive method for measuring small quantities of bilirubin in human blood. They propose that it can improve upon the current bilirubin test, which has been around since 1916.

The gene that makes the UnaG protein has been cloned and inserted into laboratory bacteria strains, so eels would not need to be sacrificed to mass produce a new bilirubin test.

UnaG protein could be processed and stored at room temperature, which would make it easy to ship to remote rural areas in Indonesia or Africa, where hepatitis is endemic.

This discovery could also mean great things for the unagi eel. Overfishing and possibly global warming have decimated its population, and the eel was added to the endangered species list in February.

The authors proposed that much more could be learned from unagi eels, as a separate experiment suggested that the UnaG protein may help the eels fight muscle fatigue during their long journeys to sea. They also found similar proteins in other species of eels.

These findings may lead to the eel becoming a protected species.

"We believe that UnaG provides an unexpected foothold into several important but currently obscure areas of human health including bilirubin metabolism and muscle physiology during endurance exercise," Miyawaki concluded. "Before the discovery of UnaG, I couldn't imagine that basic science could have such a direct impact on human health. From a simple eel, we found a new path to the clinic."

Source: Kumagai A, Ando R, Miyatake H, et al. A Bilirubin-Inducible Fluorescent Protein from Eel Muscle. Cell. 2013.

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Anna S. Lok, MD, on the future of hepatitis C treatment

Provided by Healio

June 13, 2013

ORLANDO, Fla. — Anna S. Lok, MD, discusses upcoming advancements in therapies for hepatitis C at Digestive Disease Week 2013.

Lok suggests that, with the emergence of new direct-acting antivirals within the next 5 years, the majority of patients with hepatitis C will be curable with a short course of once-daily, all-oral therapy with minimal side effects. Sustained virologic response rates of 80% to 90% will be possible with as few as 12 weeks of therapy, she estimated, with the lack of cross-resistance among new drugs of different classes allowing for potent, interferon-free treatment regimens. Lok anticipates FDA approval of two to three HCV medications by early 2014.

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Noncompliance with guidelines for the treatment of hepatitis C is frequent in daily practice

Eur J Gastroenterol Hepatol. 2013 Jun 6. [Epub ahead of print]

Niederau C, Mauss S, Böker K, Lutz T, Heyne R, Moog G, John C, Witthöft T, Alshuth U, Hüppe D.

aDepartment of Medicine, Katholische Kliniken Oberhausen, St Josef Hospital, Oberhausen bCenter for HIV and Hepatogastroenterology, Düsseldorf cCenter for Hepatology, Hannover dInfektiologikum Frankfurt, Frankfurt eLiver and Study Center Checkpoint fCenter of Gastroenterology, Berlin gMedical Office for Gastroenterology and Hepatology, Kassel hMedical Office for Gastroenterology and Hepatology, Stade iRoche Pharma AG, Virology, Grenzach-Wyhlen jCenter for Gastroenterology and Hepatology, Herne, Germany.

Abstract

PURPOSE: In trials of pegylated interferons (PEG-IFNs), the lack of an early virological response (EVR) was associated with sustained virological response (SVR) rates of only 0-3%. The rates were similarly low when hepatitis C virus (HCV)-RNA was positive at week 24. Treatment guidelines therefore recommend 'stop rules' on the basis of HCV-RNA levels at weeks 12 and 24 of treatment. We analyzed the use of these rules under 'real-life' conditions.

PATIENTS AND METHODS: This was a prospective, community-based cohort study involving 467 physicians from institutions throughout Germany, including 4727 treatment-naive genotype-1 patients who received a full course of treatment with PEG-IFN α-2a plus ribavirin between 2003 and 2009.

RESULTS: The overall SVR rate was 43.1%. Failure to determine EVR decreased from 20% in 2003-2004 to 10% in 2006-2007. Unexpectedly, treatment was continued in 86.1% of patients without an EVR and in those who had an EVR but were HCV-RNA positive at week 24 (67.5%), resulting in SVR rates of 15.7 and 40.9%, respectively. Between 77.5 and 95.3% of physicians did not follow prescribed recommendations to reduce PEG-IFN or ribavirin in cases of hematological abnormalities.

CONCLUSION: Although recommendations to assess EVR and HCV-RNA at week 24 were increasingly observed in daily practice, the corresponding 'stop rules' in nonresponders were neglected. The subsequent SVR was 5-10 times higher than that reported in controlled trials. This may partly be because of the fact that reductions in PEG-IFN or ribavirin dose were not performed despite recommendations. The issue of stop rules will gain even more interest since the first HCV protease inhibitors have been approved. Prolongation of treatment beyond the new stop rules is associated with risks of resistant HCV variants. Thus, the new stop rules are to be observed more strictly when compared with previous therapy with interferons and ribavirin.

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Hepatitis C and Dietary Supplements: What the Science Says

May 2013

Milk Thistle

Milk thistle (scientific name Silybum marianum) is a plant from the aster family. Silymarin is an active component of milk thistle believed to be responsible for the herb’s health-related properties. Milk thistle has been used in Europe for treating liver disease and jaundice since the 16th century. In the United States, silymarin is the most popular dietary supplement taken by people with liver disease.

Strength of Evidence

• Much research supports the conclusion that there little evidence of benefit for milk thistle as a treatment for hepatitis C.

Research Results

• A 2012 controlled clinical trial, cofunded by NCCAM and NIDDK, showed that two higher-than-usual doses of silymarin were no better than placebo in reducing the high blood levels of an enzyme that indicates liver damage. In the study, 154 people who had not responded to standard antiviral treatment for chronic hepatitis C were randomly assigned to receive 420 mg of silymarin, 700 mg of silymarin, or placebo three times per day for 24 weeks. At the end of the treatment period, blood levels of the enzyme were similar in all three groups.
• Results of the HALT-C study suggested that silymarin use by hepatitis C patients was associated with fewer and milder symptoms of liver disease and somewhat better quality of life, but there was no change in virus activity or liver inflammation. The researchers emphasized that this was a retrospective study (one that examined the medical and lifestyle histories of the participants). Its finding of improved quality of life in patients taking silymarin was not confirmed in the more rigorous 2012 study described above.
• A 2009 Cochrane systematic review assessed the beneficial and harmful effects of milk thistle in patients with alcoholic liver disease and/or hepatitis B or C liver diseases and found that there is not enough high-quality evidence to support the use of this intervention.

Safety

• Available evidence from clinical trials in people with liver diseases suggests that milk thistle is generally well-tolerated.
• Side effects can include a laxative effect, nausea, diarrhea, abdominal bloating and pain, and occasional allergic reactions.
• In NIH-funded studies of silymarin in people with hepatitis C that were completed in 2010 and 2012, the frequency of side effects was similar in people taking silymarin and those taking placebos. However, these studies were not large enough to prove that silymarin is safe for people with chronic hepatitis C.

Other Supplements

Other supplements have been studied for hepatitis C, but overall, no benefits have been clearly demonstrated.

Probiotics

Probiotics are live microorganisms that are intended to have a health benefit when consumed.

Strength of Evidence

• Only a few studies have examined the effects of probiotics on hepatitis C.

Research Results

• Research hasn’t produced any clear evidence that probiotics are helpful in people with hepatitis C.

Safety

• Most people can use probiotics without experiencing any side effects—or with only mild gastrointestinal side effects such as intestinal gas —but there have been some case reports of serious adverse effects in people with underlying serious health conditions.

Zinc

Strength of Evidence

• Preliminary studies, most of which were conducted outside the United States, have examined the use of zinc for hepatitis C.

Research Results

• Zinc supplements might help to correct zinc deficiencies associated with hepatitis C or reduce some symptoms, but the evidence for these possible benefits is limited.
• A few preliminary studies have looked at the effects of combining supplements such as lactoferrin, SAMe, or zinc with conventional drug therapy for hepatitis C. The evidence is not sufficient to draw clear conclusions about benefit or safety.

Safety

• Zinc is generally considered to be safe when used appropriately, but it can be toxic if taken in excessive amounts.

Glycyrrhizin

Glycyrrhizin (or glycyrrhizic acid) is a compound found in licorice root.

Strength of Evidence

• Glycyrrhizin has been tested in only a few clinical trials in patients with hepatitis C.

Research Results

• There is currently not enough evidence to determine if glycyrrhizin is helpful for hepatitis C.

Safety

• In large amounts, glycyrrhizin or licorice can be dangerous in people with a history of hypertension (high blood pressure), kidney failure, or cardiovascular diseases.

Colloidal Silver

Colloidal silver consists of tiny silver particles suspended in liquid. Colloidal silver products are often promoted for treating various diseases, including hepatitis C.

Strength of Evidence

• Scientific evidence does not support the use of colloidal silver to treat any disease, and serious, irreversible side effects can result from its use.

Research Results

• There is currently no research to support its use for hepatitis C.

Safety

• Colloidal silver is known to cause serious side effects, including a permanent bluish discoloration of the skin called argyria.

NCCAM Clinical Digest is a service of the National Center for Complementary and Alternative Medicine, NIH, DHHS. NCCAM Clinical Digest, a monthly e-newsletter, offers evidence-based information on CAM, including scientific literature searches, summaries of NCCAM-funded research, fact sheets for patients, and more.

The National Center for Complementary and Alternative Medicine is dedicated to exploring complementary and alternative healing practices in the context of rigorous science, training CAM researchers, and disseminating authoritative information to the public and professionals. For additional information, call NCCAM’s Clearinghouse toll-free at 1-888-644-6226, or visit the NCCAM Web site at nccam.nih.gov. NCCAM is 1 of 27 institutes and centers at the National Institutes of Health, the Federal focal point for medical research in the United States.

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New Hepatitis C Clinical Trial Now Enrolling at Avail Clinical Research near Orlando, Florida; Accepting M/F Patients with Hep C Age 18-65

Avail is conducting a 12-week, Phase 2, Randomized Study to Evaluate the Safety and Efficacy of a new drug in Subjects with Chronic Hepatitis C Infection.

DeLand, Florida (PRWEB) June 03, 2013

*To see if you qualify for this Hepatitis C Clinical Trial, visit Avail Clinical Research on the web or contact us directly at (386) 785-2404.

BACKGROUND

The Hepatitis C virus (HCV) infection is a global public health problem. The global prevalence of hepatitis C infection is estimated to average 3% resulting in approximately 170 million HCV-infected persons worldwide. Most of those infected develop persistent, chronic infection. An estimated 20-50% of patients with chronic HCV infection are at risk for developing such long-term complications as cirrhosis and hepatocellular carcinoma (HCC).

PRIMARY OBJECTIVES

The primary objectives of this Hep C Clinical Study are to evaluate the:

Safety and tolerability of a new Hep C drug and simeprevir when given in combination with RBV for up to 12 weeks.

Efficacy of a new Hep C drug and simeprevir when given in combination with RBV for up to 12 weeks.

SECONDARY OBJECTIVES

The secondary objectives are to evaluate the:

1. Pharmacokinetics (PK) of a new Hepatitic C drug and simeprevir when given in combination with RBV.

2. PK/Pharmacodynamics (PK/PD) of a new Hepatitic C drug and simeprevir when given in combination with RBV.

3. Emergence of resistance mutations over 12-weeks of combination treatment of a new Hepatitic C drug, simeprevir and RBV and in the post-treatment follow-up period.

INCLUSION CRITERIA

1. 18 (or the legal age of consent per local regulations, if greater than 18 years) to 65 years of age, inclusive.

2. Female subjects of both childbearing potential and non-childbearing potential may be included, unless the local regulatory authority requires that only females of non-childbearing potential be included. Non-childbearing potential is defined as one of the following:

Postmenopausal, defined as amenorrheic for at least 2 years and serum follicle stimulating hormone (FSH) level consistent with postmenopausal status at Screening, OR

A documented hysterectomy, bilateral oophorectomy or bilateral tubal ligation at least 6 months prior to study initiation.
3. All female subjects must have a negative serum beta-human chorionic gonadotropin (β-HCG) at Screening and a negative urine pregnancy test prior to the first dose of study medication on Day 1.

4. Women of childbearing potential and men must have agreed to use an acceptable double method of birth control (one of which must be a barrier method) from Screening through at least 6 months after the last dose of study drugs.

5. Male subjects must have agreed not to donate sperm from the first dose through at least 6 months after the last dose of study drugs.

6. QTcF interval ≤ _450 ms at Screening and prior to dosing on Day 1.

7. Documented clinical history compatible with chronic hepatitis C, including any one of the following:

a) anti- HCV antibody positive at least 6 months prior to Screening or dosing, OR

b) HCV RNA present in plasma by a sensitive and specific assay at least 6 months prior to Screening or dosing, OR

c) HCV genotype at least 6 months prior to Screening or dosing, OR

d) histologic evidence of chronic hepatitis C infection.

8. Must not have received prior antiviral treatment for HCV infection.

9. Plasma HCV RNA positive at Screening with minimal viral load according to genotype:

a) Genotype 1b HCV RNA ≥5 log10 IU/mL

b) Genotype 4 HCV RNA ≥ _4 log10 IU/mL

10. HCV genotype 1b or 4 by HCV genotyping performed at Screening (Note: mixed subtypes are not acceptable).

11. Documented absence of cirrhosis within 36 months of Screening or dosing (histology or non-invasive equivalent, according to local standard of care).

12. Subject is, in the opinion of the investigator, willing and able to comply with the protocol and all other study requirements.

13. Subject has provided written informed consent to participate in the study.

BENEFITS OF PARTICIPATION

• Receive medical care at No Cost
• Health Insurance is not required
• Receive Compensation for time & travel
• Help Advance medical research

*Achieve Clinical Research conducts Clinical Research Trials in Florida. For more information about participating in a Hep C Clinical Study, please visit our website or contact us directly at (386) 785-2404.

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CUHK-HCC Score Accurately Predicts Risk of Liver Cancer in Chronic Hepatitis B Patients Receiving Antiviral Therapy

(from left) Prof. Vincent Wong, Deputy Director, CUHK Center for Liver Health; Prof. Henry Chan, Director of the Center and Prof. Grace Wong, Associate Professor, Department of Medicine and Therapeutics, Faculty of Medicine of CUHK

3 hours 52 minutes ago

Chronic hepatitis B virus (HBV) infection is the most common cause of liver cirrhosis and hepatocellular carcinoma (HCC), affecting 8% of the adult population in Hong Kong. In 2010, The Chinese University of Hong Kong (CUHK) introduced the CUHK-HCC score, a simple index developed primarily for family doctors to assess the cancer risk of patients with chronic hepatitis B based on their age, albumin, bilirubin, viral load and cirrhosis.

The score classifies patients into high or low HCC risk group, and predicted their risk of developing HCC in the coming 5 years without taking antiviral therapy. Its performance among patients undergoing antiviral therapy remained untested. A longitudinal study recently conducted by Prof. Henry Lik Yuen CHAN, Director, Center for Liver Health, CUHK, and his team has further supported the use of CUHK-HCC score as an effective cancer risk predictor for patients with chronic hepatitis B receiving antiviral therapy, which will have great implication on clinical management and patient education.

According to the latest international guidelines, patients with active hepatitis (high liver enzymes and viral load) or liver cirrhosis should receive antiviral therapy because they are at risk of disease progression and complications. Antiviral drugs are reimbursable from the Hospital Authority Drug Formulary. However, according to a recent report by CUHK, 4.3% of the treated patients would further develop HCC in 5 years even after receiving antiviral treatment and the development was unpredictable.

During 2005-2012, Professor Chan and his team conducted a longitudinal study to evaluate the CUHK-HCC scores of 1,531 entecavir-treated patients with either active hepatitis or liver cirrhosis. Based on the CUHK-HCC scores, 47% (713) and 53% (818) of the patients were classified as low and high risk group respectively. In 5 years, only 0.4% of the patients in the low risk group developed HCC, compared to 8.1% in the high risk group. This indicates that patients in the low risk group essentially have their cancer risk eliminated with antiviral therapy while patients in the high risk group are still at risk of HCC after receiving antiviral therapy. It also reaffirms the effectiveness of using CUHK-HCC score in predicting cancer risk of patients.

CUHK’s research team recommends that patients in the high risk category should keep an eye on their CUHK-HCC score and perform regular cancer screening even they are already on antiviral medication, while patients with low cancer risk should be monitored with the prediction score once a year. The CUHK-HCC score will help directing resources of cancer screening toward high risk patients and substantially minimizing the waiting time for ultrasound cancer screening by approximately 50%.

For simple assessment of HCC risk factors, please visit the website of CUHK’s Center for Liver Health at: http://www.livercenter.com.hk/chi/p15.asp.

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Bananas as Hepatitis B Oral Vaccine?

Added by Janet Grace Ortigas on June 12, 2013.
Saved under Health, Janet Grace Ortigas, U.S.

Bananas are currently being considered by Ithaca, NY researchers as potential oral vaccine against HBV (Hepatitis B Virus).

HBV affects over 2 million people worldwide. The Roswell Park Cancer Institute (RPCI) estimated in 1996 that approximately 20,000 to 25,000 Americans are infected every year.  However, in 1998 the CDC estimated the new annual cases close to 200,000.

On July 20, 2012, Arizona State University plant biotechnologist Charles Arntzen pioneered the plant-based vaccine due to its genetic engineering and was highlighted in the Los Angeles Times article. Arntzen had high hopes that this concept would work but the hurdles for edible vaccines made it too complicated so he abandoned the efforts.

HBV is 50 to 100 times more infectious than AIDS because it is present in body fluids and blood of infected individuals and can be transmitted within households. HBV infection could lead to liver cancer, liver damage, and death. Since 1991, Hepatitis B vaccine has been advised as a regular adult vaccine since 1995.

WHO advocated that countries not immunizing against HBV should adopt it right away and countries currently immunizing against the infection should continue with the practice.

In 1996, Rockefeller Foundation approved the vaccine research grant to BTI (Boyce Thompson Institute) for plant research, a non-profit organization affiliated with Cornell University. The National Institute of Allergy and Infectious Diseases funded the preclinical trials. In 1999, Axis Genetics of Cambridge, England funded the clinical trial which paved the way for the edible Hepatitis B vaccine development.

According to the June1, 2007 issue of ACS’ Biotechnology Progress, bananas emerges as the best oral vaccine for Hepatitis B to millions of developing countries. The authors, India’s V. A. Bapat and colleagues, explained that the production of vaccine has economic advantages considering that at during those time, there has been 1 million new cases of HBV infection every year and an estimated 75 to 100 million individuals may die of liver cancer or liver cirrhosis. Further development and research was needed to exploit bananas against HBV global battle.

As of February 2013, approximately 350 million people are infected with Hepatitis B virus around the world and about a million people will die of the infection. Hepatitis B is an incurable disease and the current vaccines are very expensive, meaning, they are not available to remote areas like Africa. The easier and cheaper medium to transmit the vaccination antigen to people at risk of the disease around the world is through the banana vaccine.

Oral vaccines are theorized to be more effective because they create short and long germ benefits compared to injected vaccines, as they stimulate both systematic immune  and mucosal responses. The drawback of Banana Vaccines is that growing the bananas requires a lot of land and care and which government will take responsibility of growing vaccinated bananas and control the sale to consumer market. The safety and administration are also another concern because it will be determined by age, weight, and ripeness, meaning no two bananas have the same dosage.

Health practitioners may have to relearn their knowledge about vaccinations and training on the storage, dosage, and safety must be implemented which could be very expensive for health institutions practitioners. More researchers with high tech equipment, laboratory, and funding are needed to continue developing bananas as Hepatitis B oral vaccine.

Written by: Janet Grace Ortigas

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Boehringer Ingelheim's investigational all-oral interferon-free combination achieved 95% viral cure rates in genotype-1b hepatitis C patients

• In the Phase IIb SOUND-C3 study, all but one patient achieved viral cure with faldaprevir⁺ and deleobuvir⁺ (BI 207127) plus ribavirin, without a need for interferon
•The study included challenging-to-cure patients with advanced liver disease, all of  whom achieved viral cure

For media outside USA, UK and Canada only

INGELHEIM, 13 June 2013 – New data from Boehringer Ingelheim’s interferon-free SOUND-C3 study were presented during the APASL Liver Week in Singapore. The Phase IIb study investigated the efficacy and safety of faldaprevir⁺ and deleobuvir⁺ (BI 207127) plus ribavirin in treatment-naïve patients with genotype-1b (GT-1b) hepatitis C virus (HCV),¹ one of the most common types of HCV globally.²

Results showed that 95% of genotype-1b (GT-1b) infected patients (19/20) who received BI’s interferon-free combination therapy achieved viral cure after 16 weeks of treatment.¹ 20% (4/20) of GT-1b patients in the study had liver cirrhosis (an advanced form of liver disease), all of whom achieved viral cure.¹ Viral cure was defined as a sustained viral response 12 weeks after completion of treatment (SVR12).¹ In contrast, patients with genotype-1a (GT-1a) infection and host IL28b type CC (n=12) had a lower viral response of 17% SVR12 (2/12), suggesting a need for treatment of greater intensity for this population and confirming the decision to focus on GT-1b patients in Phase III trials.

Eliminating injectable interferon from treatment regimens is a highly desirable goal in HCV management as it can be challenging for patients due to the long treatment duration and often severe side-effects.² Up to 50% of patients may not be eligible for treatment with interferon and many patients who are eligible cannot tolerate the side-effects.

"These promising results indicate the potential of our interferon-free combination treatment to address an unmet medical need, and confirm our decision to focus on GT-1b patients in our pivotal Phase III interferon-free HCVerso™ trials," said Professor Klaus Dugi, Senior Vice President Medicine at Boehringer Ingelheim. "The inclusion of difficult-to-cure patients such as those with liver cirrhosis and those that are interferon ineligible demonstrates the comprehensive nature of our clinical trial programme and supports our ultimate goal of making an interferon-free future a reality for HCV patients."

In SOUND-C3, optimising treatment (by removing a deleobuvir⁺ first day loading dose and reducing treatment duration to 16 weeks) for GT-1b-infected patients resulting in higher efficacy compared with SOUND-C2.¹ The SOUND-C2 study, presented in November 2012 at the AASLD Congress, showed viral cure rates of up to 85% with different interferon-free regimens of faldaprevir, deleobuvir⁺ and ribavirin in HCV GT-1b infected patients.³

Overall tolerability in the SOUND-C3 trial was good with three patients (9%) discontinuing treatment due to intolerance, and mild rash or nausea being the most common side-effects.¹ Adverse events of a moderate or higher intensity were rare, with anaemia (16%), fatigue (9%), vomiting (9%) and nausea (9%) being the most frequent adverse events.¹

Boehringer Ingelheim‘s pivotal Phase III interferon-free HCVerso™ programme includes three trials aiming to enrol approximately 1,100 treatment-naïve HCV GT-1b patients.^4,5,6 The trial programme includes patients who are interferon ineligible and those with liver cirrhosis; results are expected in Q2 2014.

Other BI news at APASL
Results from Boehringer Ingelheim’s interferon-based Phase III STARTVerso™ trials were presented yesterday at the APASL congress by Professor Masao Omata. A post-hoc sub-analysis of patients from Asia in the STARTVerso™1 and 2 trials demonstrated that 88% (172/196) of GT-1a and GT-1b patients treated with faldaprevir (FDV 120mg or 240mg) plus PegIFN/RBV achieved viral cure compared with 62% (29/47) treated with placebo plus PegIFN/RBV.⁷ In addition, 94% of patients on faldaprevir were able to stop all treatments after 24 weeks of therapy.⁷ Currently, interferon treatment without protease inhibitors is still the standard treatment in most parts of Asia, lasting 48 weeks for GT-1 infected patients.

NOTES TO EDITORS

The Boehringer Ingelheim NewsHome: An innovative resource for journalists
The Boehringer Ingelheim hepatitis C www.NewsHome.com is available and is the one-stop-shop for clear, concise and easy to understand information about hepatitis C for media.

About Hepatitis C
Hepatitis C is a blood-borne infectious disease caused by the hepatitis C virus which lives and replicates in the liver. Hepatitis C is a leading cause of chronic liver disease, liver cancer and transplantation.² Chronic hepatitis C is a major public health issue and one of the most prevalent infectious diseases worldwide, affecting around 170 million people,⁸ with 3-4 million new cases occurring each year.⁹

It is common for hepatitis C patients to remain undiagnosed due to the initial unspecific symptoms of the disease. Consequently, a large number of patients first present to their physician when they experience symptoms or already have liver disease.¹⁰ Patients with advanced liver disease are challenging to cure, yet have the greatest need for more effective and better tolerated treatments.

Of patients with chronic hepatitis C, 20% will develop liver cirrhosis, of which 2-5% will die every year.¹¹ Advanced liver disease due to hepatitis C currently represents the main cause for liver transplantation in the western world.¹¹

About Boehringer Ingelheim in hepatitis C
Through pioneering science, Boehringer Ingelheim is striving to find answers to the pressing challenges still faced by the diverse population of hepatitis C patients. The company’s comprehensively designed hepatitis C clinical trial programme includes a broad range of patients, including the challenging to cure, that clinicians see every day in clinical practice.

Boehringer Ingelheim is developing faldaprevir⁺, an optimised second generation protease inhibitor, as the core component for both interferon-based and interferon-free treatment regimens.

Interferon-based therapy with faldaprevir⁺ has the potential to improve cure rates with the added convenience of once-daily dosing and no dietary requirements for intake. Faldaprevir⁺ has proven efficacy in a broad range of genotype-1a and 1b hepatitis C patients. The STARTVerso^TM trial programme, which includes treatment-naïve, treatment-experienced and HIV co-infected patients with hepatitis C virus, is nearly complete.

Deleobuvir⁺ (BI 207127) is a potent investigational non-nucleoside NS5B polymerase inhibitor, specifically optimised to treat patients with genotype-1b hepatitis C virus. Phase III HCVerso^TM trials, investigating the interferon-free regimen of deleobuvir in combination with faldaprevir⁺ and ribavirin, are well underway.

As part of Boehringer Ingelheim’s long-term commitment to hepatitis C, the company is also evaluating other combinations of investigational hepatitis C compounds that work in different ways. Boehringer Ingelheim’s recent collaboration with Presidio Pharmaceuticals, Inc. for a Phase II clinical study investigating an interferon-free, all-oral combination is part of the company’s continued exploration to discover and develop innovative options for the treatment of HCV.

Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

Social responsibility is a central element of Boehringer Ingelheim's culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.

In 2012, Boehringer Ingelheim achieved net sales of about 14.7 billion euro. R&D expenditure in the business area Prescription Medicines corresponds to 22.5% of its net sales.

⁺faldaprevir is an investigational compound and not yet approved. Its safety and efficacy have not yet been fully established

References
^1. Zeuzem, S. et al. Interferon-Free Treatment with Faldaprevir, BI207127 and Ribavirin in SOUND-C3: 95% SVR12 in HCV-GT1b. Presented at APASL Liver Week, 6-10 June, 2013
^2. World Health Organisation. Hepatitis C. 2002 http://www.who.int/csr/disease/hepatitis/Hepc.pdf  [Last accessed on 28/05/13]
^3. Zeuzem S. et al Interferon (IFN)-free combination treatment with the HCV NS3/4A protease inhibitor BI 201335 and the nonnucleoside NS5B inhibitor BI 207127 ± ribavirin (R): Final results of SOUND-C2 and predictors of response. Abstract#232 presented at the 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), 9 – 13 November
^4. ClinicalTrials.gov. IFN-free Combination Therapy in HCV-infected Patients Treatment-naive:HCVerso1. http://clinicaltrial.gov/ct2/show/NCT01732796?term=faldaprevir+bi+207127&rank=3  [Last accessed 06/06/13]
^5. ClinicalTrials.gov. Phase 3 Study of BI 207127 in Combination With Faldaprevir and Ribavirin for Treatment of Patients With Hepatitis C Infection, Including Patients Who Are Not Eligible to Receive Peginterferon: HCVerso2. http://clinicaltrial.gov/ct2/show/NCT01728324?term=faldaprevir+bi+207127&rank=2  [Last accessed 06/06/13]
^6. ClinicalTrials.gov. BI 207127 / Faldaprevir Combination Therapy in Hepatic Impairment (Child-Pugh B) Patients With Genotype 1b Chronic Hepatitis C Infection: HCVerso3 http://clinicaltrial.gov/ct2/show/NCT01830127?term=hcverso3&rank=1  [Last accessed 06/06/13]
^7. Omata, M. et al. Faldaprevir plus pegylated-interferon and ribavirin in chronic HCV genotype-1 treatment-naïve patients: subanalysis of patients from Japan, Taiwan and South Korea. Presented at APASL Liver Week, 6-10 June, 2013
^8. Centers for Disease Control and Prevention (2012) Hepatitis C available at: http://wwwnc.cdc.gov/travel/yellowbook/2012/chapter-3-infectious-diseases-related-to-travel/hepatitis-c.htm  [Last accessed on 28/05/13]
^9. World Health Organisation. Hepatitis C Fact Sheet. Updated July 2012 http://www.who.int/mediacentre/factsheets/fs164/en/index.html  [Last accessed on 28/05/13]
^10. Chen S.L., Morgan T.R. The Natural History of Hepatitis C Virus (HCV) Infection. Int J Med Sci 2006; 3:47-52. Available from http://www.medsci.org/v03p0047.htm  [Last accessed on 28/05/13]
^11. Soriano, Vincent et al. New Therapies for Hepatitis C Virus Infection. Clinical Infectious Disease, February 2009

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CDC Updates HIV Preexposure Prophylaxis Guidelines

Medscape Medical News

Troy Brown

Jun 12, 2013

The Centers for Disease Control and Prevention (CDC) has updated its recommendations on the use of preexposure prophylaxis (PrEP) in individuals at high risk of acquiring HIV to include its use in injection drug users (IDUs) as well as those with high-risk sexual behaviors, the agency announced today.

The recommendations follow the results of a clinical trial, published online June 12 in the Lancet, that showed that a daily oral dose of 300 mg of tenofovir disoproxil fumarate (TDF) is effective at reducing HIV infection acquisition among injection drug users.

On July 16, the US Food and Drug Administration approved the use of a fixed-dose combination of TDF 300 mg and emtricitabine (FTC) 200 mg (Truvada, Gilead Sciences) for the indication of PrEP against sexual transmission of HIV by men who have sex with men (MSM) and heterosexually active women and men. The recommendations were based on the results of clinical trials in MSM and heterosexually active men and women. Those trials did not evaluate the use of PrEP among IDUs.

On the basis of the trial results published today, the CDC recommends that PrEP be considered as one of several prevention options for persons at very high risk for HIV acquisition through the injection of illicit drugs.

Reported injection practices that place persons at very high risk for HIV acquisition include sharing of injection equipment, injecting 1 or more times a day, and injection of cocaine or methamphetamine.

PrEP Recommendation for Injection Drug Users

Daily TDF/FTC is the preferred PrEP regimen for IDUs for the following reasons:

• TDF/FTC contains the same dose of TDF (300 mg) that has been shown to be effective for IDUs,
• TDF/FTC demonstrated no additional toxicities when compared with TDF only in PrEP trials that studied both regimens,
• IDUs are at risk for sexual exposure to HIV for which TDF/FTC is indicated, and
• TDF/FTC is approved for PrEP to prevent sexual HIV transmission in the United States.

The use of TDF/FTC for prevention of HIV transmission in those without sexual acquisition risk is at present an off-label use. The CDC recommends providing services for IDUs that include PrEP as well as measures aimed at decreasing injection and risky sexual behaviors.

In all individuals, PrEP use:

• is contraindicated in those with positive or unknown HIV status or with an estimated creatinine clearance lower than 60 mL/minute,
• should be focused on adults at very high risk for HIV acquisition,
• should be given as part of comprehensive prevention services, and
• should be given with quarterly monitoring of HIV status, pregnancy status, adverse effects, medication adherence, and risk behaviors, as directed in previous interim guidance.

Adherence to daily PrEP is vital to decrease HIV infection risk, and achieving high adherence was challenging for many participants in PrEP clinical trials.

"Providing PrEP to IDUs at very high risk for HIV acquisition could contribute to the reduction of HIV incidence in the United States," the CDC notes in the statement. "In addition, if PrEP delivery is integrated with prevention and clinical care for the additional health concerns faced by IDUs (e.g., hepatitis B and C infection, abscesses, and overdose), substance abuse treatment and behavioral health care, and social services, PrEP will contribute additional benefits to a population with multiple life-threatening physical, mental, and social health challenges."

The CDC is collaborating with other federal agencies to prepare comprehensive US Public Health Service guidelines on PrEP use with MSM, heterosexually active men and women, and IDUs. Those guidelines are scheduled for release later this year.

The complete updated interim guidelines IDUs can be found here on the CDC Web site.

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Also See: Daily Pill Cuts HIV Risk in IV Drug Users