December 27, 2011

Liz Highleyman | Content provided by hivandhepatitis.com

Published Tuesday, 27 December 2011

People who have an increase in body temperature soon after starting interferon-based therapy for chronic hepatitis C virus (HCV) infection are more likely to experience early virological response, according to a presentation at the American Association for the Study of Liver Disease (AASLD) Liver Meeting last month in San Francisco.

Rather than directly targeting HCV, interferon works by stimulating the body's immune response. This can lead to a variety of flu-like symptoms including fever, loss of appetite, and muscle aches. But it is not known how these side effects relate to antiviral activity.

Hwalih Hanand colleagues from the National Institutes of Health evaluated whether temperature changes after starting interferon reflect responsiveness to pegylated interferon, as assessed by viral kinetics, serum cytokine levels, and treatment response.
The study included 60 previously untreated chronic hepatitis C patients who started standard therapy using pegylated interferon plus ribavirin. Half were men, nearly 60% were white, about 20% each were black and Asian, and the mean age was 52 years. A majority (57%) had difficult-to-treat HCV genotype 1, one-third had genotypes 2 or 3, and 10% had genotypes 4, 5, or 6.

The researchers measured body temperature with an oral thermometer before the first injection of pegylated interferon and at 8, 16, and 24 hours thereafter, and determined the maximum temperature increase from baseline within the first 24 hours, or Tmax.

Serum HCV viral load was measured at baseline, at 6, 24, 48, and 72 hours, and then weekly for the first 4 weeks of treatment, and used to calculate the first and second phase slope of HCV decline. Levels of interferon gamma-inducible protein 10 (IP-10) were also assessed for a subset of patients at baseline and at 6 and 24 hours after treatment initiation.
Results

  • The average maximum temperature increase after starting interferon was 1.1°C.
  • The average peak temperature was 37.9°C, and 33% of patients experienced fevers above 38.0°C within 24 hours.
  • Overall, 42% of participants experienced rapid virological response (RVR) at week 4, 83% showed early virological response (EVR) at week 12, and 38% achieved sustained virological response (SVR) at 24 weeks after the end of treatment.
  • There was a strong and significant positive correlation between maximum temperature (Tmax) and the first phase of viral decline.
  • However, Tmax did not correlate with the second phase of viral decline.
  • The correlation between Tmax and first phase viral decline was similar for people with genotype 1 and those with genotypes 2 or 3, with no difference in average Tmax across viral genotypes.
  • There was a significant positive correlation between Tmax and IP-10 induction at 6 and 24 hours.
  • Tmax was significantly higher on average for participants with the favorable IL28B rs129790860 "CC" gene pattern -- a known predictor of treatment response -- compared to those with the unfavorable "CT" or "TT" patterns (1.43 vs 0.84°C, respectively).
  • Tmax predicted RVR at week 4 and EVR at week 12, though the correlation was weak.

"Temperature increase after the initial injection of pegylated interferon is closely associated with interferon responsiveness, as reflected by the correlation with serum IP-10 increase, virological decline, and IL28B genotype," the researchers concluded. "The lack of difference between genotypes pinpoints its association with host-responsiveness factors."

As an easily measurable marker, they suggested, temperature "may be incorporated as a surrogate of more expensive and elaborate tests in future models of responsiveness to interferon-based treatment."

Investigator affiliation: Liver Diseases Branch, NIDDK, NIH, Bethesda, MD.

12/27/11

Reference

H Han, M Noureddin, YJ Park, et al. Changes in Oral Temperature After the Initial Injection of Peginterferon Alfa-2a in Patients with Chronic Hepatitis C Reflect Host-Interferon Responsiveness. 62nd Annual Meeting of the American Association for the Study of Liver Disease (AASLD 2011). San Francisco, November 4-8. 2011. Abstract 487.

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Liz Highleyman | Content provided by hivandhepatitis.com

Published Tuesday, 22 November 2011

Starting hepatitis C treatment with a double dose of ribavirin plus erythropoietin to manage anemia did not lead to higher rates of sustained response to interferon-based therapy in HIV/HCV coinfected people, researchers reported at the American Association for the Study of Liver Diseases Liver Meeting (AASLD 2011) this month in San Francisco.

An estimated one-third of HIV positive people are coinfected with hepatitis C virus (HCV), and dual infection is associated with faster liver disease progression and poorer response to interferon-based therapy.

Vincent Soriano from Hospital Carlos III in Madrid and colleagues conducted a study to determine whether increasing the usual dose of ribavirin might improve virological response in this patient population.

Ribavirin promotes sustained virological response (SVR) because it reduces the risk of relapse after the end of treatment. Studies have shown that 1000-1200 mg/day weight-adjusted ribavirin works better than a fixed 800 mg/day dose, but the effect of even higher doses is not well understood. Ribavirin can cause hemolytic anemia (destruction of red blood cells), so higher-than-normal doses must be used with caution.

The PERICO study included 357 HIV/HCV coinfected participants who had not previously received interferon for hepatitis C. About three-quarters were men and the average age was 43 years. About 60% had HCV genotype 1, 19% had genotype 3, 17% had genotype 4, and only 6% had genotype 2. About half had advanced liver fibrosis/cirrhosis, 43% had the favorable IL28B CC gene pattern, and 72% had high baseline HCV RNA > 500,000 IU/mL. Most were on antiretroviral therapy with undetectable HIV viral load, and the mean CD4 T-cell count was about 550 cells/mm3.

All participants received the standard 180 mcg/week dose of pegyalted interferon alfa-2a (Pegasys). In addition, they were randomly assigned to receive either standard 1000-1200 mg/day weight-adjusted ribavirin for the full course of treatment, or else a 2000 mg/day induction dose for the first 4 weeks along with weekly subcutaneous injections of 50,000 IU erythropoietin (Procrit or Epogen), then dropping down to the standard ribavirin dose and discontinuing erythropoietin.

Patients with rapid virological response (RVR) at week 4 were treated for the standard duration of 24 weeks for genotypes 2 and 3 or 48 weeks for genotypes 1 and 4. People without RVR were treated for 48 or 72 weeks, respectively. Participants with inadequate response at weeks 12 or 24 stopped treatment early.

Results

  • In an intent-to-treat analysis, 43% of participants in the high-dose ribavirin induction arm achieved SVR 24 weeks after the end of treatment, compared with 47% in the standard therapy arm, not a significant difference.
  • In an on-treatment analysis, the corresponding rates were 53% vs 57%, again not a significant difference.
  • Premature treatment discontinuation occurred with similar frequency in both arms -- 51% vs 53%, respectively -- mostly due to virological failure.
  • Other response predictors were associated with higher sustained response rates, as expected:
    • HCV genotype: 82% for genotypes 2 and 3, 42% for genotype 1b, 34% for genotype 4, and 31% for genotype 1a;
    • IL28B gene pattern: 74% for CC vs 35% for CT or TT;
    • Treatment completion: 80% for completion vs 31% for early discontinuation.
  • In a multivariate analysis, SVR was significantly associated with HCV genotypes 2 and 3, IL28B CC, and low baseline HCV RNA.
  • RVR was the best predictor of SVR.
  • Despite differing doses, ribavirin plasma trough levels (lowest between doses) at week 4 were the same in both arms, at 2.3 mcg/mL.

Based on these findings, the investigators concluded, "Induction therapy with high ribavirin dosing along with erythropoietin does not improve SVR rates in HIV/HCV coinfected patients."

To explain the unexpected similar ribavirin levels regardless of dose, they suggested that pre-emptive erythropoietin "might blunt the benefit of ribavirin overdosing by enhancing erythrocyte uptake of plasma ribavirin."

Investigator affiliations: Infectious Diseases, Hospital Carlos III, Madrid, Madrid, Spain; Hospital Clínico San Cecilio, Granada, Spain; Hospital San Pablo, Barcelona, Spain; Hospital Gregorio Marañón, Madrid, Spain; Hospital 12 de Octubre, Madrid, Spain; Hospital Clinico San Carlos, Madrid, Spain; Hospital Virgen de La Victoria, Malaga, Spain; H Virgen Macarena, Sevilla, Spain; Hospital Universitario de Valme, Sevilla, Spain; Hospital Txagorritxu, Vitoria, Spain; Hospital Gral de Jerez, Jerez, Spain; Hospital do Meixoeiro, Vigo, Spain; Hospital Xeral-Cies, Vigo, Spain; Hospital Cruces, Bilbao, Spain; Hospital La Princesa, Madrid, Spain; Hospital Central de Asturias, Oviedo, Spain.

11/22/11

Reference

P Labarga, M Téllez, P Barreiro, V Soriano, et al. The Perico Trial: A Multicenter Randomized Controled Trial Comparing High Ribavirin (RBV) Induction vs Standard RBV Dosing in the Treatment of Chronic Hepatitis C in HIV-Coinfected Patients. 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2011). San Francisco, November 4-8. 2011. Abstract 247.

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Dec. 27, 2011, 2:35 p.m. EST

MOUNTAINSIDE, NJ, Dec 27, 2011 (MARKETWIRE via COMTEX) -- PROTEONOMIX, INC. a biotechnology company focused on developing therapeutics based upon the use of human cells and their derivatives, announced today that it has completed all payments required from Proteonomix to commence a Clinical Study entitled "UMK-121 in Patients with Liver Disease."

As previously announced, the Company entered into an Agreement to conduct the clinical trial with the University of Miami. That Agreement required the University to pay expenses associated with the clinical study and The Company was required to assist financially with the clinical study.

Michael Cohen, President of the Company, stated: "The financing that was required to complete the Company's obligation with respect to the Trial was provided Friday, December 23, 2011. We previously thanked the University for its generous assistance in the agreement to conduct a clinical trial of UMK-121. The Company has previously described the terms of the agreement to license and develop and the patent application of the UMK-121 technology. The Company will work together with the University and the principal investigators to initiate the clinical study."

Mr. Cohen continued, "Our UMK-121 pharmaceutical therapy is advancing toward its first human clinical trial in ESLD ('End Stage Liver Disease') patients. We hope to provide patients who are suffering from this debilitating and mortal condition with alternatives. We believe that the commercialization of this technology can provide Proteonomix with significant revenue potential. According to United Network for Organ Sharing ('UNOS') there are over 100,000 patients on the transplant waiting list at any given time. According to the ('NIH') there are over 500,000 patients in end stage Kidney disease. According to Organ Donation and Transplantation ('NWHIC') over 60,000 Americans suffer from End Stage Liver Disease ('ESLD'). The Company will continue to provide information about the clinical study in the upcoming weeks and months consistent with our understanding with the University and ethical considerations."

About Proteonomix, Inc.:

Proteonomix is a biotechnology company focused on developing therapeutics based upon the use of human cells and their derivatives. The Proteonomix Family of companies includes Proteoderm, StromaCel, PRTMI and THOR Biopharma. Proteoderm, Inc. is a wholly owned subsidiary that has developed an anti-aging line of skin care products. StromaCel, Inc. develops therapeutic modalities for the treatment of Cardiovascular Disease (CVD). Proteonomix Regenerative Translational Medicine Institute, Inc. ("PRTMI") intends to focus on the translation of promising research in stem cell biology and cellular therapy to clinical applications of regenerative medicine. Proteonomix intends to create and dedicate a subsidiary to each of its technologies. Please also visit http://www.proteonomix.com/ , http://www.proteoderm.com/ , http://www.otcqb.com/ and http://www.sec.gov/ .

Forward-looking statements:

Certain statements contained herein are "forward-looking statements" (as defined in the Private Securities Litigation Reform Act of 1995). Proteonomix, Inc. cautions that statements made in this press release constitute forward-looking statements and makes no guarantee of future performance. Actual results or developments may differ materially from projections. Forward-looking statements are based on estimates and opinions of management at the time statements are made

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Celebrities and the Dormant Hepatitis C Virus

The Center for the Biology of Chronic Disease (CBCD) wishes to use the experience of certain celebrities to educate the public about the dormant hepatitis C virus.

Rochester, New York (PRWEB) December 26, 2011

Celebrities, such as Pamela Anderson, Naomi Judd, Steven Tyler, and Jim Nabors have all contracted the hepatitis C virus (HCV, hep C) and have all fought to regain their health. The Center for the Biology of Chronic Disease (CBCD) wishes to use their experience to educate the public about the dormant hepatitis C virus.

Celebrities fighting the hepatitis C virus are just the tip of the iceberg. The hepatitis C virus infects three times more people than AIDS, and, according to Dr. C. Everett Koop MD (hepfree.com), will kill more people than AIDS. The CDC says that in the US there are more than 3.2 million persons chronically infected with the hepatitis C virus.

Even worse.

The actual number of people infected with the hepatitis C virus is much higher. The reason is that many people have a dormant hepatitis C virus, or "latent," as scientists call it.

When the hepatitis C virus invades the body, it stores dormant, sleeping copies of itself (imagine clone soldiers) in a certain organ. When the virus is sleeping, the person is not sick. In fact, the Food and Drug Administration (FDA) says "Some viruses…can enter a state known as latency in which the virus is not being replicated. In the latent state, the virus does not cause disease."

However, dormant copies sometime "wake up" and begin to attack the host. Anyone who has had a fever blister or cold sore experienced an awakening of the herpes virus (HSV-1). Such awakening is called an oral herpes outbreak.

The same thing happens with the hepatitis C virus. It invades the body, settles in a dormant, sleeping condition, and then might wake up and attack the host.

What can one do against dormant hepatitis C viruses? The CBCD believes that Gene-Eden-Blue, developed by the biotechnology company polyDNA, might be an answer. Gene-Eden-Blue is a natural remedy that boosts the immune system against the army of sleeping (latent) hepatitis C viruses.

Most people may wonder whether Gene-Eden-Blue is an affordable, safe and effective hepatitis remedy.

In regard to affordability, Gene-Eden-Blue is sold exclusively online through the hepatitis-remedy.com website. A bottle costs $34.99 and includes a month's supply of Gene-Eden-Blue.

In regard to safety, according to polyDNA, in over a year of being on the market, there have been no reports of side effects. In addition, each bottle is GMP certified, which means that the product is keeping good manufacturing practices as outlined by the Food and Drug Administration (FDA).

In regard to effectiveness against dormant hepatitis C viruses, Gene-Eden capsule contains a patented formula of six natural ingredients including selenium, phylanthus amarus, curcumin, quercetin, cinnamon, and licorice, each at a uniquely selected dose. These ingredients were selected through a scientific method developed by Dr. Hanan Polansky. The method is based on electronic and manual analysis of thousands of scientific and medical papers published on the topic of research. The abstracts of these scientific papers are available on pubmed.gov.

"Gene-Eden combines several proven substances that work harmoniously to help boost the body’s own immune system or have other antiviral properties. The scientific data with regard to the immune enhancing and antiviral properties published in reputable sources on each individual compound in the Gene-Eden formula is impressive. Use of this product clearly has scientific merit based on published material." – Dr. Norman Cohen, MD

To learn more about Gene-Eden-Blue, the hepatitis remedy that boosts the immune system against the dormant hepatitis C virus (HCV), and which is based on thousands of scientific studies, please visit http://www.hepatitis-remedy.com.

The Center for the Biology of Chronic Disease (CBCD, http://www.cbcd.net) is a research center recognized by the IRS as a 501(c)(3) non-for-profit organization. The mission of the CBCD is to advance the research on the biology of chronic diseases, and to accelerate the discovery of treatments for these diseases.

The CBCD published the “Purple” book by Dr. Hanan Polansky. The book presents Dr. Polansky’s highly acclaimed scientific theory on the relationship between the DNA of latent (chronic) viruses and the onset of chronic diseases. Dr. Polansky’s book is available as a free download from the CBCD website.

References:

^ de Vries, Lloyd (2002-07-24). "Time Off for Pamela Anderson". CBS News. Retrieved 2007-08-26.

^ Morgan, John (2003-09-05). "Naomi Judd Helps Heal People with Hepatitis C". USA Today. Retrieved 2007-08-28.

^ Associated Press (2006-09-26). "Steven Tyler reveals he has hepatitis C". MSNBC.com. Retrieved 2007-08-29

^ "Jim Nabors Hospitalized with Throat Infection". Los Angeles Times (Reuters). 2011-07-20. Retrieved 2011-07-20.

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New powerful painkiller has abuse experts worried

DECEMBER 26, 2011, 2:03 P.M. ET

Associated Press

NEW YORK — Drug companies are working to develop a pure, more powerful version of the nation's second most-abused medicine, which has addiction experts worried that it could spur a new wave of abuse.

The new pills contain the highly addictive painkiller hydrocodone, packing up to 10 times the amount of the drug as existing medications such as Vicodin. Four companies have begun patient testing, and one of them — Zogenix of San Diego — plans to apply early next year to begin marketing its product, Zohydro.

If approved, it would mark the first time patients could legally buy pure hydrocodone. Existing products combine the drug with nonaddictive painkillers such as acetaminophen.

Critics say they are especially worried about Zohydro, a timed-release drug meant for managing moderate to severe pain, because abusers could crush it to release an intense, immediate high.

"I have a big concern that this could be the next OxyContin," said April Rovero, president of the National Coalition Against Prescription Drug Abuse. "We just don't need this on the market."

OxyContin, introduced in 1995 by Purdue Pharma of Stamford, Conn., was designed to manage pain with a formula that dribbled one dose of oxycodone over many hours.

Abusers quickly discovered they could defeat the timed-release feature by crushing the pills. Purdue Pharma changed the formula to make OxyContin more tamper-resistant, but addicts have moved onto generic oxycodone and other drugs that do not have a timed-release feature.

Oxycodone is now the most-abused medicine in the United States, with hydrocodone second, according to the Drug Enforcement Administration's annual count of drug seizures sent to police drug labs for analysis.

The latest drug tests come as more pharmaceutical companies are getting into the $10 billion-a-year legal market for powerful — and addictive — opiate narcotics.

"It's like the wild west," said Peter Jackson, co-founder of Advocates for the Reform of Prescription Opioids. "The whole supply-side system is set up to perpetuate this massive unloading of opioid narcotics on the American public."

The pharmaceutical firms say the new hydrocodone drugs give doctors another tool to try on patients in legitimate pain, part of a constant search for better painkillers to treat the aging U.S. population.

"Sometimes you circulate a patient between various opioids, and some may have a better effect than others," said Karsten Lindhardt, chief executive of Denmark-based Egalet, which is testing its own pure hydrocodone product.

The companies say a pure hydrocodone pill would avoid liver problems linked to high doses of acetaminophen, an ingredient in products like Vicodin. They also say patients will be more closely supervised because, by law, they will have to return to their doctors each time they need more pills. Prescriptions for the weaker, hydrocodone-acetaminophen products now on the market can be refilled up to five times.

Zogenix has completed three rounds of patient testing, and last week it announced it had held a final meeting with Food and Drug Administration officials to talk about its upcoming drug application. It plans to file the application in early 2012 and have Zohydro on the market by early 2013.

Purdue Pharma and Cephalon, a Frazer, Pa.-based unit of Israel-based Teva Pharmaceuticals, are conducting late-stage trials of their own hydrocodone drugs, according to documents filed with federal regulators. In May, Purdue Pharma received a patent applying extended-release technology to hydrocodone. Neither company would comment on its plans.

Meanwhile, Egalet has finished the most preliminary stages of testing aimed at determining the basic safety of a drug. The firm could have a product on the market as early as 2015 but wants to see how the other companies fare with the FDA before deciding whether to move forward, Lindhardt said.

Critics say they are troubled because of the dark side that has accompanied the boom in sales of narcotic painkillers: Murders, pharmacy robberies and millions of dollars lost by hospitals that must treat overdose victims.

Thousands of legitimate pain patients are becoming addicted to powerful prescription painkillers, they say, in addition to the thousands more who abuse the drugs.

Prescription painkillers led to the deaths of almost 15,000 people in 2008, more than triple the 4,000 deaths in 1999, the Centers for Disease Control and Prevention reported last month.

Emergency room visits related to hydrocodone abuse have shot from 19,221 in 2000 to 86,258 in 2009, according to data compiled by the Drug Enforcement Administration. In Florida alone, hydrocodone caused 910 deaths and contributed to 1,803 others between 2003 and 2007.

Hydrocodone belongs to family of drugs known as opiates or opioids because they are chemically similar to opium. They include morphine, heroin, oxycodone, codeine, methadone and hydromorphone.

Opiates block pain but also unleash intense feelings of well-being and can create physical dependence. The withdrawal symptoms are also intense, with users complaining of cramps, diarrhea, muddled thinking, nausea and vomiting.

After a while, opiates stop working, forcing users to take stronger doses or to try slightly different chemicals.

"You've got a person on your product for life, and a doctor's got a patient who's never going to miss an appointment, because if they did and they didn't get their prescription, they would feel very sick," said Andrew Kolodny, president of Physicians for Responsible Opioid Prescribing. "It's a terrific business model, and that's what these companies want to get in on."

Under pressure from the government, Purdue Pharma last year debuted a new OxyContin pill formula that "squishes" instead of crumbling when someone tries to crush it.

But Zogenix, whose drug is time-released but crushable, says there is not enough evidence to show that such tamper-resistant reformulations thwart abuse.

"Provided sufficient effort, all formulations currently available can be overcome," Zogenix said in a written response to questions by The Associated Press.

At a conference for investors New York on Nov. 29, Zogenix chief executive Roger Hawley said the FDA was not pressuring Zogenix to put an abuse deterrent in Zohydro.

"We would certainly consider later launching an abuse-deterrent form, but right now we believe the priority of safer hydrocodone — that is, without acetaminophen — is a key priority for the FDA," Hawley said.

FDA spokeswoman Erica Jefferson said the agency would not comment on its discussions with drug companies, citing the need to protect trade secrets.

Drug control advocates say they're worried the U.S. government is too lax about controlling addictive pain medications. The United States consumes 99 percent of the world's hydrocodone and 83 percent of its oxycodone, according to a 2008 study by the International Narcotics Control Board.

One 41-year-old loophole in particular has fed the current problem with hydrocodone abuse, critics say. The federal Controlled Substances Act, passed in 1970, puts fewer controls on combination pills containing hydrocodone and another painkiller than it does on the equivalent oxycodone products.

A Vicodin prescription can be refilled five times, for example, while a Percocet prescription can only be filled once.

The Drug Enforcement Administration and Food and Drug Administration have been studying whether to close this loophole since 1999 but have made no decision. Congress is now considering a bill that would force the agencies to tighten the controls.

"This is a problem that is fundamentally an oversupply problem," said Jackson, the drug-control advocate. "The FDA has kind of opened the floodgates, and they refuse to recognize the mistakes made in the past."

Pure hydrocodone falls into the stricter drug-control category than hydrocodone-acetaminophen medications, meaning patients would have to go to their doctors for a new prescription each time they needed more pills. But Jackson said that's no guarantee against abuse, noting that dozens of unscrupulous doctors have been caught churning out prescriptions in so-called "pill mills."

The Drug Enforcement Administration, which enforces controls on medicines along with the FDA, said it could not comment on drugs that have not yet been approved for sale.

However, Zogenix has acknowledged the abuse issue could become a liability.

"Illicit use and abuse of hydrocodone is well documented," it said in a filing with the Securities and Exchange Commission in September. "Thus, the regulatory approval process and the marketing of Zohydro may generate public controversy that may adversely affect regulatory approval and market acceptance of Zohydro."

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Liver Transplants for Cancer Patients

Liver

By Linda Fugate PhD December 26, 2011 - 7:42am

Liver cancer is one of the most common causes of cancer death. The American Cancer Society estimates 26,190 new cases in the United States and 19,590 deaths for 2011. Liver transplantation is the preferred treatment for most patients.

Dr. Ali Zarrinpar and colleagues at the David Geffen School of Medicine at UCLA, Los Angeles, California, provided a review.

Hepatocellular carcinoma is the medical term for most cancers of the liver. “It arises almost exclusively from a background of cirrhosis,” Zarrinpar reported. Cirrhosis is scarring of the liver and poor liver function.

The U. S. National Library of Medicine's PubMed Health web site lists common causes as infection by hepatitis B or C, autoimmune disease, alcohol abuse, hereditary hemochromatosis, disorders of the biliary system, medications, and nonalcoholic fatty liver disease. The presence of moderate to severe cirrhosis rules out surgery to remove the tumor alone.

“Liver transplantation is the most beneficial oncologic treatment,” Zarrinpar explained. The Milan criteria for transplant candidates include one tumor of 5 cm diameter or less, or 2 to 3 tumors of 3 cm diameter or less. Patients who meet these criteria have demonstrated 5-year survival rates of at least 70 percent.

Zarrinpar suggested that the Milan criteria may be too restrictive. Other research groups have demonstrated comparable results with larger tumors and with up to 10 total tumors.

Preoperative treatment can reduce the size of the tumor(s) and improve survival. Options include percutaneous ethanol injection (PEI), percutaneous acetic acid injection (PAI), radiofrequency ablation, transarterial embolization, chemoembolization, and transarterial radioembolization. These are considered locoregional therapies, and they are also used in patients who are not surgical candidates.

Immunosuppression is necessary for all organ transplant recipients. This poses special problems for cancer patients who may have microscopic metastases. Early immunosuppresive regimens were found to increase the risk of cancer recurrence.

However, newer drugs such as sirolimus and everolimus have demonstrated better results for liver transplant patients.

The National Digestive Diseases Information Clearinghouse provides detailed information online about what to expect from liver transplantation.

References:

1. American Cancer Society. Cancer Facts and Figures 2011. Web. Dec. 19, 2011.
http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/docume...

2. Zarrinpar A et al, “Liver transplantation for hepatocellular carcinoma: an update”, Hepatobiliary Pancreat Dis Int 2011; 10: 234-42. http://www.ncbi.nlm.nih.gov/pubmed/21669564

3. U. S. National Library of Medicine. PubMed Health. Cirrhosis. Web. Dec. 19, 2011.
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001301

4. National Digestive Diseases Information Clearinghouse. What I need to know about Liver Transplantation. Web. Dec. 19, 2011.
http://digestive.niddk.nih.gov/ddiseases/pubs/livertransplant_ez

Reviewed December 26, 2011
by Michele Blacksberg RN
Edited by Jody Smith

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HIV Worsens Bone Loss After Menopause

NEW YORK (Reuters Health) Dec 22 - Compared to a control group, postmenopausal women with HIV infection had higher rates of bone loss and could well have a higher risk for fracture as they age, according to the researchers who conducted the study.

Studies of mainly younger HIV-positive patients have shown that bone mineral density (BMD) often declines after the start of antiretroviral therapy but then seems to stabilize, suggesting that patients don't need additional screening or fracture prevention measures, the research team said in a November 16 online paper in the Journal of Clinical Endocrinology & Metabolism.

The older women in the current study were all Hispanic or African-American. Dr. Elizabeth Shane of Columbia University Medical Center, New York and colleagues had previously reported low BMD and higher levels of bone turnover markers in these women. Their new study focuses on a subset -- 73 HIV-positive and 55 HIV-negative women -- for whom they had an average of 16 months of longitudinal data.

On average, the HIV group was significantly younger (56 vs 59 years), with a significantly lower body mass index (28 vs 31). After allowing for this, they had increased rates of bone loss. Annualized, the increase was 2.4-fold at the lumbar spine, 3.7-fold at the one third radius, and 1.7-fold at the ultradistal radius.

Tenofovir therapy was associated with lower BMD. For example, in the tenofovir group, the drop at the lumbar spine was 2.8%, compared to 0.7% in those on a tenofovir-free regimen.

Rates of self-reported fracture were similar in the HIV and control groups (10% vs 8%).

The investigators say, "The higher rates of spine and forearm bone loss we observed in postmenopausal HIV positive women raise concern for rising fracture rates as our participants age."

The findings, they conclude, "merit risk stratification with dual-energy x-ray absorptiometry, assessment for modifiable secondary causes of osteoporosis, and appropriate treatment of osteoporosis for all postmenopausal HIV positive women."

SOURCE: http://bit.ly/v18g9E

J Clin Endocrinol Metab 2011.

Source

Posted on:23 Dec 11

Shortens the course of treatment for many (58%) treatment naive genotype-1 chronic hep C patients compared to current standard treatment2

High Wycombe, 12th December 2011 – Today the Scottish Medicines Consortium (SMC) has recommended that INCIVO® (telaprevir)* should be made available for the treatment of genotype-1 chronic hepatitis C (hep C), in combination with peginterferon alfa and ribavirin (i.e. current standard treatment), in adults in Scotland who have not previously had treatment and adult patients for whom treatment has previously failed1.

Telaprevir, a new direct acting antiviral (DAA) protease inhibitor (PI), one of a new class of medicines which directly targets the Hep C virus, now offers significantly more patients infected with genotype 1 chronic hep C in Scotland the chance of clearing the virus (achieving sustained virologic response, SVR)2,3,4 compared to current standard treatment.

“I welcome the news that telaprevir can now be prescribed for patients living with chronic genotype-1 hep C in Scotland. Before the introduction of protease inhibitors, of which telaprevir is the latest, treatment for hep C required a long duration and less than 50% of chronic genotype-1 hep C patients got rid of the virus” said Dr John F Dillon, Consultant Hepatologist and Gastroenterologist, University of Dundee Ninewells Hospital. “For many adults with chronic genotype-1 hep C, treatment with a telaprevir based regimen could provide a shorter treatment duration with improved response rates compared to standard treatment.”

In Scotland, it is estimated that 50,000 individuals are infected with hep C5. Hep C is a significant public health threat. It is highly infectious, often has no symptoms and can lead to fatal liver conditions. Of those who develop hep C an estimated 30% will develop cirrhosis (deterioration of the liver), others will develop liver cancer, some of whom may require liver transplantation6. Hep C is the most common reason for liver transplants in Europe7. A model, developed in Scotland, which looks at transmission rates for hep C has shown that effective treatment of the disease, assuming a 62.5% SVR rate, could reduce the onward transmission of the virus and its occurrence in the community. Taking this into account it could be expected that effective treatment of hep C with a treatment regimen that achieves a higher SVR rate will, in the longer term, reduce the risk of transmission among the population and lower the burden of hep C on NHS Scotland8. The standard treatment for hep C, peginterferon alfa and ribavirin, is successful in only about 50% of patients with genotype 1, leaving the other 50% without a successful treatment outcome6.

Clinical trials have shown that a telaprevir based regimen is significantly more effective than standard treatment in all genotype-1 patient types, including those with advanced liver disease such as cirrhosis. The addition of telaprevir cleared the Hep C virus in almost twice as many previously untreated patients (79% vs. 46%, p<0.0001) and almost four times as many who had previously relapsed following treatment (84% vs. 22%, p<0.001)3,4,9. It also offers the potential to halve the current total treatment duration to just six months in many (58%) previously untreated patients and prior treatment relapsers2,3,9.

The marketing authorisation for telaprevir was based on results from three phase III clinical trials, ADVANCE, REALIZE and ILLUMINATE3,4,9 which evaluated the efficacy and safety of telaprevir in combination with peginterferon alfa and ribavirin in more than 2,290 treatment-naïve and previously-treated chronic genotype 1 hep C patients. Data from ADVANCE and REALIZE were published in the 23rd June 2011 edition of the New England Journal of Medicine (NEJM). Data from the ILLUMINATE study were published in the 15th September 2011 edition of the NEJM. This marked the sixth paper to be published on telaprevir in the NEJM10,11,12.

The overall safety and tolerability profile of telaprevir is based on the phase II and III clinical development programme. The most frequently reported moderate adverse reactions (incidence = 5.0%) were anaemia, rash, pruritus, nausea, and diarrhoea, and the most frequently reported severe adverse reactions (incidence = 1.0%) were anaemia, rash, thrombocytopenia, lymphopenia, pruritus, and nausea2.Rash events were reported in 55% of patients with telaprevir based treatment compared with 33% in the control arm (peginterferon alfa and ribavirin only). More than 90% of rashes were of mild or moderate severity. Severe rashes were reported with telaprevir based treatment in 4.8% of patients. Rash led to discontinuation in 5.8% of patients. Anaemia was reported in 32.1% of patients compared with 15% in the control arm (peginterferon alfa and ribavirin only). It led to discontinuation in approximately 3% of patients2.

* INCIVO® (telaprevir), a direct acting antiviral protease inhibitor, was co-developed by Vertex Pharmaceuticals and Tibotec, an affiliate of Janssen Pharmaceutical Companies of Johnson & Johnson, and the company responsible for marketing telaprevir in Europe.

References
1.The Scottish Medicines Consortium (http://www.scottishmedicines.org.uk/Home ), accessed December 2011
2.Telaprevir Summary of Product Characteristics 2011
3.Jacobson, Ira M. Telaprevir for Previously Untreated Hepatitis C Virus Infection. N Engl J Med. 2011; 364; 2405-16.
4.Zeuzem, Stefan MD. Telaprevir for Retreatment of HCV Infection. N Engl J Med. 2011; 364; 2417-28.
5.Hepatitis C Action Plan for Scotland Phase II May 2008-March 2011
6.TA200: Peginterferon Alfa and Ribavirin for the treatment of chronic hepatitis C. Part review of NICE technology appraisal guidance 75 and 106. Issued September 2010
7.Lang K, Weiner DB. Immunotherapy for HCV infection: next steps. Expert Rev Vaccines. 2008;7(7): 915-923
8.Martin NK, Vickerman P, Foster GR, Hutchinson SJ, Goldberg DJ, Hickman M. Can antiviral therapy for hepatitis C reduce the prevalence of HCV among injecting drug user populations? A modeling analysis of its prevention utility. J Hepatol 2011 Jun;54(6):1137-44
9.Sherman et al. Duration of Initial Telaprevir Treatment for HCV Infection: A phase 3 study of treatment duration, N Engl J Med. 2011: 365; 1014-24.
10.McHutchinson et al. Telaprevir for Previously Treated Chronic HCV Infection. Engl J Med. 2010; 362; 1292-1303.
11.Hezode et al. Telaprevir and Peginterferon Alfa with or without Ribavirin for Chronic HCV. Engl J Med 2009; 360; 1839-50.
12.McHutchinson et al. Telaprevir with Peginterferon Alfa and Ribavirin for Chronic HCV Genotype 1 Infection 2009 N Engl J Med 2009; 360: 1827-38.

For more information:
http://www.janssen.co.uk

Editor's Details
Janssen Pharmaceutical
Janssen Pharmaceutical
http://www.janssen.co.uk

Last updated on: 23/12/2011 12:46:52

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By Kieryn Graham
Published: Dec 23, 2011 9:33 am

Results from a recent study show high rates of abnormal Pap smear test results among sexually active, HIV-positive, female teens. More than half of the Pap test results in the study were abnormal.

The study also showed that teens with HIV acquired from their mothers during pregnancy or childbirth were significantly less likely to get Pap smear tests than teens with behaviorally-acquired HIV.

The study investigators suggested that prevention of human papillomavirus, a primary cause of cervical cancer, through vaccination may be especially beneficial among HIV-positive, female teens who acquired HIV from their mothers. They also stated that clearer guidelines on initiation and frequency of Pap screening in this population of HIV-positive women may be necessary.

HIV in women is associated with an increased risk of acquiring human papillomavirus (HPV), one of the most common sexually transmitted infections. Previous research has shown that around 75 percent to 80 percent of HIV-positive women also have HPV.

In addition, women with both HIV and HPV are at an increased risk of cervical cancer (see related AIDS Beacon news), which is primarily caused by HPV. Researchers estimate that 20 percent to 60 percent of HIV-positive women show signs of pre-cervical cancer.

Pap tests, also called pap smears, detect the presence of abnormal or cancerous cells in the cervix. According to the study authors, these tests have been shown to reduce cervical cancer rates by 60 percent to 90 percent.

Although the American Cancer Society recommends regular Pap tests for women with HIV, it does not address the timing of initial Pap screening for teens with HIV acquired from their HIV-positive mothers at birth (called perinatally-acquired HIV). Guidelines for HIV-negative women recommend screening within three years of becoming sexually active or at age 21.

According to the study authors, most patients with perinatally-acquired HIV are seldom perceived as a high-risk group for HPV infection because most of them have been cared for since infancy in pediatric clinics. However, recent studies have shown that sexual activity, sexually transmitted infections, and pregnancy in this population are common.

In this study, the researchers compared cervical cancer screening rates in teens with perinatally- versus behaviorally-acquired HIV. They also monitored rates of abnormal Pap test results in both groups.

The study included 231 sexually active HIV-positive women aged between 13 and 24 years old from 20 clinical sites across the United States. About 46 percent had perinatally-acquired HIV. Thirteen percent had a record of HPV infection, over 36 percent had a current or past sexually transmitted infection, and 52 percent were pregnant at least once between 2001 and 2006.

Results showed that 58 percent of Pap test results were abnormal. However, most of the abnormalities identified in the study were low-grade lesions. Only 2 percent of patients had high-grade lesions.

Having a sexually transmitted infection was associated with an increased likelihood of abnormal Pap test results, although the authors noted that this may be because women with sexually transmitted infections are viewed as a high-risk group by clinicians, who are thus more likely to recommend cervical cancer screening.

In addition, patients with CD4 (white blood cell) counts less than 200 cells per microliter were twice as likely to have an abnormal Pap test result.

Results also showed that less than half the participants had one or more Pap test between 2001 and 2006. Women with perinatally-acquired HIV were 34 percent less likely to have undergone Pap tests than women with behaviorally-acquired HIV. African-American women were 26 percent less likely to have undergone Pap tests compared with Caucasians. The researchers suggested that the latter may be due to socioeconomic differences.

Patients 21 years or older and patients with a history of any sexually transmitted infection or pregnancy were more likely to get a Pap smear test. Participants managed at clinics with an on-site adolescent medicine specialist were 20 percent more likely to have a Pap test and 31 percent less likely to have an abnormal Pap test result as teens managed at pediatric clinics.

Nineteen percent of abnormal Pap test results had reverted to normal by the end of the study.

For more information, please see the study in the Journal of Pediatric and Adolescent Gynecology (abstract).

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Hepatitis B vaccine recommended for adults with diabetes

By Robert Preidt, HealthDay

Hepatitis B vaccination is recommended for all unvaccinated adults with type 1 and type 2 diabetes aged 19 to 59, say new guidelines from the U.S. Advisory Committee on Immunization Practices (ACIP).

The vaccination should be done as soon as possible after adults in this age group are diagnosed with diabetes.

Unvaccinated adults with diabetes who are older than 59 can receive hepatitis B vaccination at the discretion of their doctor, the ACIP advises.

The recommendations are outlined in the Dec. 23 issue of the Morbidity and Mortality Weekly Report, published by the U.S. Centers for Disease Control and Prevention.

Between 700,000 and 1.4 million people in the United States are infected with the hepatitis B virus (HBV), according to background information in the report.

Chronic HBV infection damages the liver and can lead to serious illness and death. More than 15 percent of adults with chronic HBV infection develop cirrhosis and liver cancer, the authors of the report noted.

People with diabetes are at increased risk for HBV infection, which can occur through exposure to small, even invisible, amounts of blood from an infected person who earlier used a shared medical or glucose-monitoring device, the article states.

The hepatitis B virus can survive outside the body and is easily transmitted. This means that virus transmission can occur if finger-stick devices or blood glucose monitors meant for one person are used by more than one person without appropriate cleaning or infection control measures.

"Initiatives are ongoing to improve infection control training of staff responsible for providing or assisting with diabetes care, and to improve the design and labeling of devices used in diabetes monitoring and treatment," according to a CDC news release.

On the Web:

The American Academy of Family Physicians has more about hepatitis B: http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.printerview.all.html

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FDA Hepatitis Update - Important updates to PegIntron labeling

You are receiving this message as a subscriber to the FDA hepatitis electronic list serve. The purpose of the list serve is to relay important information about viral hepatitis-related products and issues, including product approvals, significant labeling changes, safety warnings, notices of upcoming public meetings and alerts to proposed regulatory guidances for comment.

Please do not reply to this message.

On December 22, 2011, the Food and Drug Administration approved revisions to the product labeling for PegIntron to include the use of PegIntron with hepatitis C virus (HCV) NS3/4A protease inhibitors for the treatment of genotype 1, chronic hepatitis C (CHC) infection. Additionally, the product labeling was update to include revisions to the text regarding the use of PegIntron in patients with neuropsychiatric disorders. Changes were made to the Medication Guide for consistency. The following changes were made to the product labeling.

The Indication and Usage section was update as follows:
PegIntron®, as part of a combination regimen, is indicated for the treatment of Chronic Hepatitis C in patients with compensated liver disease.

PegIntron in combination with REBETOL (ribavirin) and an approved Hepatitis C Virus (HCV) NS3/4A protease inhibitor is indicated in adult patients (18 years of age and older) with HCV genotype 1 infection (see the Package Insert of the specific HCV NS3/4A protease inhibitor for further information).

PegIntron in combination with REBETOL is indicated in patients with genotypes other than 1, pediatric patients (3-17 years of age), or in patients with genotype 1 infection where use of an HCV NS3/4A protease inhibitor is not warranted based on tolerability, contraindications or other clinical factors.

The Dosage and Administration section, PegIntron Combination Therapy and Discontinuation of Dosing subsections were updated as follows:

DOSAGE AND ADMINISTRATION

2.1 PegIntron Combination Therapy

Adults

The recommended dose of PegIntron is 1.5 mcg/kg/week. The volume of PegIntron to be injected depends on the strength of PegIntron and patient’s body weight (see Table 1).

should be taken with food. REBETOL should not be used in patients with creatinine clearance less than 50 mL/min.

See the Package Insert of the specific HCV NS3/4A protease inhibitor for information regarding dosing regimen and administration of the protease inhibitor in combination with PegIntron and ribavirin.

Duration of Treatment – Treatment with PegIntron/REBETOL of Interferon Alpha-naïve Patients

The treatment duration for patients with genotype 1 is 48 weeks. Discontinuation of therapy should be considered in patients who do not achieve at least a 2 log10 drop or loss of HCV-RNA at 12 weeks, or if HCV-RNA remains detectable after 24 weeks of therapy. Patients with genotype 2 and 3 should be treated for 24 weeks.

Duration of Treatment – Retreatment with PegIntron/REBETOL of Prior Treatment Failures

For patients with genotype 1 infection, PegIntron and REBETOL without an HCV NS3/4A protease inhibitor should only be used if there are contraindications, significant intolerance or other clinical factors that would not warrant use of an HCV NS3/4A protease inhibitor. The treatment duration for patients who previously failed therapy is 48 weeks, regardless of HCV genotype. Re-treated patients who fail to achieve undetectable HCV-RNA at Week 12 of therapy, or whose HCV-RNA remains detectable after 24 weeks of therapy, are highly unlikely to achieve SVR and discontinuation of therapy should be considered

2.4 Discontinuation of Dosing

Adults

See the Package Insert of the specific HCV NS3/4A protease inhibitor for information regarding discontinuation of dosing based on treatment futility.

In HCV genotype 1, interferon-alfa-naïve patients receiving PegIntron, alone or in combination with REBETOL, discontinuation of therapy is recommended if there is not at least a 2 log10 drop or loss of HCV-RNA at 12 weeks of therapy, or if HCV-RNA levels remain detectable after 24 weeks of therapy. Regardless of genotype, previously treated patients who have detectable HCV-RNA at Week 12 or 24, are highly unlikely to achieve SVR and discontinuation of therapy is recommended.

Warning and Precaution section was revised as follows:

Neuropsychiatric Events

Life-threatening or fatal neuropsychiatric events, including suicide, suicidal and homicidal ideation, depression, relapse of drug addiction/overdose, and aggressive behavior sometimes directed towards others have occurred in patients with and without a previous psychiatric disorder during PegIntron treatment and follow-up. Psychoses, hallucinations, bipolar disorders, and mania have been observed in patients treated with interferon alpha.

PegIntron should be used with caution in patients with a history of psychiatric disorders. Treatment with interferons may be associated with exacerbated symptoms of psychiatric disorders in patients with co-occurring psychiatric and substance use disorders. If treatment with interferons is initiated in patients with prior history or existence of psychiatric condition or with a history of substance use disorders, treatment considerations should include the need for drug screening and periodic health evaluation, including psychiatric symptom monitoring. Early intervention for re-emergence or development of neuropsychiatric symptoms and substance use is recommended.

Patients should be advised to report immediately any symptoms of depression or suicidal ideation to their prescribing physicians. Physicians should monitor all patients for evidence of depression and other psychiatric symptoms. If patients develop psychiatric problems, including clinical depression, it is recommended that the patients be carefully monitored during treatment and in the 6-month follow-up period. If psychiatric symptoms persist or worsen, or suicidal ideation or aggressive behavior towards others is identified, it is recommended that treatment with PegIntron be discontinued, and the patient followed, with psychiatric intervention as appropriate. In severe cases, PegIntron should be stopped immediately and psychiatric intervention instituted. Cases of encephalopathy have been observed in some patients, usually elderly, treated at higher doses of PegIntron.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration