June 27, 2013

Nigeria partners MSD, FSRC to battle hepatitis C

Thursday, 27 June 2013 00:00 By Tony Nwanne

AHEAD the World Hepatitis Day which comes up in July 28, international medical firms has beginning to focus more on Africa, most especially Nigeria, to continually create awareness and to also support Nigeria in eradicating the deadly disease in the country.

The firms, Focus Scientific Research Center (FSRC), a physician-led team of researchers, in association with the program sponsor MSD, a global healthcare leader, and a range of collaborators both regional and international, are currently working on an initiative in Nigeria to create awareness about hepatitis with the main focus on HCV.

The stakeholders, who arrived Lagos, Nigeria, last week to brainstorm on programs ahead the World Hepatitis Day, titled “Hepatitis in Africa - Call for Action”, intends to raise disease awareness among the relevant stakeholders in the region, strengthen the existing structures on ground to making sure that the disease is brought to the nearest minimal.

Speaking at the event, the Regional Director Market Access Hospital and Specialty Care, Vivian Mendonca, MSD, noted that the objectives of the program includes engaging and building a relationship with scientific leaders, patient representatives and ministry of health officials from each country to form a regional expert group, and developing national and regional activity plans.

According to Mendonca, “the initiative intends to lay the foundation for the development of country-specific activity roadmaps with the involvement of local stakeholders for effective management of HCV. We want to continually raise the awareness on the burden of Hepatitis C in sub-Sahara Africa among stakeholders”.

While the stakeholders in the health industry brainstormed against the deadly disease, it tends to engage and build a relationship among scientific leaders, patient representatives and ministry of health officials from the participating countries to develop national and regional activity plans.

During the event medical experts will forge a way to combat against HCV ranging from clinicians, physician body representatives, patient groups and policy makers were converging to take a unified call for a plan of action towards hepatitis policy formation to battle Hepatitis C.

Meanwhile, among the participating countries were Angola, Botswana, Burkina Faso, Cameroon, Cote d’Ivoire, Democratic Republic of Congo, Ethiopia, Gabon, Ghana, Kenya, Rwanda, Senegal, Tanzania and Uganda, while Nigeria played the host.

In the same vein, the Chairman, Medical Advisory Committee, Dr. Jesse Otegbayo, who commended the efforts of the two firms added that the World Hepatitis Day by the World Health Organization is mandated to create health awareness days ahead to herald the growing international awareness of hepatitis as a global health care issue. “This realization is one that cannot come too soon, as several aspects of hepatitis characterize it as one of the most serious infectious disease challenges facing public health care today.”

Amongst the viral hepatitis concerns is the hepatitis C virus (HCV). This brings unique challenges like an acute phase that is generally asymptomatic and under-diagnosed; a chronic phase with a long latency period before development of life threatening, difficult to treat complications; genetic polymorphism and the lack of a vaccine. Globally over 185 million people are believed to be afflicted with HCV. In Africa alone, the WHO estimates that the prevalence is 5.3 per cent.

Focus Scientific Research Center (FSRC) of phamax AG is a physician led group of researchers who believe that healthcare issues in high growth economies can only be effectively solved through a combined effort between private, public and academic sectors.

Today’s MSD, known as Merck in the United States and Canada, is a global healthcare leader working to help the world be well. MSD demonstrates her commitments to increasing access to healthcare through far-reaching policies, programs and partnerships.

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Melatonin Fights Liver Cancer According to New Studies

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Maximizing melatonin production in humans is possible by blocking blue light for a few hours before bedtime by wearing amber eyeglasses according to Richard L. Hansler PhD of Photonic Developments LLC. This may be of benefit in avoiding or treating liver cancer.

University Heights, OH (PRWEB) June 27, 2013

A new paper from Thailand (1) shows that melatonin improves the outcome when liver cancer is induced in hamsters. A new study (2) from Spain found that melatonin blocked the processes that control the development of new blood vessels needed for the liver cancer to grow. These studies help explain the 1999 study (3) from France that found that exposing rats to continuous light greatly increased the fraction of rats who developed liver cancer when given a carcinogen compared to those raised in normal 12 hours light 12 hous dark. Continuous light prevents the production of melatonin. This also may explain why the odds are about double of getting colon cancer, prostate cancer, rectal cancer, and pancreatic cancer for men working night shift according to a new paper (4) from Canada. Liver cancer was not included in this study. Working nights reduces the production of melatonin due to exposure to light.

In 2005, physicists at John Carroll University developed light bulbs that don’t produce blue light and amber eyeglasses that eliminate blue light. In 2001, it had been shown that it is primarily the blue rays in ordinary white light that suppress the production of melatonin--the sleep promoting, cancer fighting hormone. These products are available at http://www.lowbluelights.com along with filters for TV and computer screens including iPads and iPhones. Thousands of people have bought these products with a guarantee of money back if they don’t help. About 90% find they help them sleep. Possibly reducing the risk of cancer comes as a free bonus. Contact Dr. Richard L. Hansler at rhansler(at)jcu(dot)edu or call 216-397-1657

(1)
Pineal Res. 2013 May 22. doi: 10.1111/jpi.12068. [Epub ahead of print]
Melatonin inhibits cholangiocarcinoma and reduces liver injury in Opisthorchis viverrini-infected and N-nitrosodimethylamine-treated hamsters.
Umawadee L, Porntip P, Patcharee B, Chawalit P, Aroonsri P, Johns Nutjaree P, Lakhanawan C, Kitti I, Somchai P.

(2)
Br J Cancer. 2013 Jun 11. doi: 10.1038/bjc.2013.285. [Epub ahead of print]
Inhibition of VEGF expression through blockade of Hif1α and STAT3 signalling mediates the anti-angiogenic effect of melatonin in HepG2 liver cancer cells.
Carbajo-Pescador S, Ordoñez R, Benet M, Jover R, García-Palomo A, Mauriz JL, González-Gallego J.

(3)
Life Sci. 1999;64(26):2523-34.
The tumor promoting effect of constant light exposure on diethylnitrosamine-induced hepatocarcinogenesis in rats.
van den Heiligenberg S, Deprés-Brummer P, Barbason H, Claustrat B, Reynes M, Lévi F.

(4)
Am J Epidemiol. 2012 Nov 1;176(9):751-9. doi: 10.1093/aje/kws318. Epub 2012 Oct 3.
Night work and the risk of cancer among men.
Parent MÉ, El-Zein M, Rousseau MC, Pintos J, Siemiatycki J.

Source

Red Door Communications - World Hepatitis Day 2012

Promotional Feature

prweek.com, Thursday, 27 June 2013, 1:56pm

0_0_460_http___offlinehbpl_hbpl_co_uk_News_ORP_85C0FCBB-F09C-1B96-4C5D2A841DDEF9ED

500 million people globally live with either chronic hepatitis B or C.  Whilst that’s higher than the prevalence of HIV or any cancer, the disease is hugely underfunded, with thousands remaining undiagnosed. On a personal level, the disease is too often ignored and shrouded in stigma.

World Hepatitis Day (WHD) takes place on July 28th and is one of four days recognised by the World Health Organisation, aiming to raise awareness of the disease amongst a global community.

The World Hepatitis Alliance wanted a campaign that could be taken up by 100 local groups, was scalable to their needs, and meaningful in all contexts.

By raising awareness among the public the Alliance wanted to prevent new infections and deliver real improvements in health outcomes for people with hepatitis B and C.

The Alliance also wanted to widen access to treatment and lessen the stigma around viral hepatitis by highlighting the prevalence and indiscriminate nature of the disease. Above all the campaign needed to inspire action: know it, confront it, and get tested.

Any potential pitfalls you needed to take into account?

The previous year’s campaign ‘Am I number 12?’ successfully engaged 81 groups around the world, but there was potential to engage more groups to ensure unified action.

In addition, with an average of 3,402 visitors per month to the Alliance website during the previous year’s campaign, the challenge was also set to engage with more audiences online than ever before and look at ways to target audiences in developing countries such as Africa, where viral hepatitis is extremely prevalent and access to the internet is limited.

OK and what was your grand plan to tackle this?

Red Door Communications developed a campaign that sought pro-active engagement and directly communicated the stark reality of hepatitis; with the strap-line - `it’s closer than you think’.

Ten hard-hitting posters were developed communicating the impact of the disease and practical toolkits to implement a local campaign. All were developed in seven languages and distributed to the Alliance’s 193 member countries.

Community engagement was key - so we designed a Guinness World Record attempt for ‘the most number of individuals performing the gestures of "See No Evil, Hear No Evil, Speak No Evil" in a 24 hour period’. These actions were based on the proverb known as the three wise monkeys who cover their eyes, ears and mouth to avoid uncomfortable truths.

This created a striking visual of the denial in which hepatitis is shrouded. To achieve the record, 25 people at ten different locations needed to perform the actions. The event was supported by a Twitter campaign and Facebook app.

A pilot SMS campaign to drive people to get tested was developed with mobile network providers in Ghana, Kenya and South Africa.

Sounds good - What outcome did all this have on your client’s business?

107 patient groups participated in the campaign compared to 81 from the previous year. Traffic to the Alliance website increased by 14.6% compared with 10% in the same period in 2011.

The Twitter campaign asked people to tweet photos of themselves performing the ‘three wise monkeys’ poses.  These were posted to #seehearspeakno and automatically uploaded into an online gallery linked to the World Hepatitis Alliance website, Twitter feed and Facebook page.

Automatic replies were sent to each tweet to thank users and to let them know about their nearest Guinness World Record venue to drive attendance. 1.7 million tweets were posted and measured through the hashtag. 12,588 people participated in the Guiness World Record in 42 locations around the world.

The SMS text-blasting campaign reached 1.45 million people and a staggering 24.5% of people in South Africa texted back to receive more information.

Impressive - Any gems of wisdom you learned from working on this that you’d like to pass on?

Twitter was a great way to engage people with the live Guinness World Record attempt and even received spontaneous celebrity endorsement from famous names such as Sadie Frost, Boy George, and Fat Boy Slim who posted photos to help raise the profile of the campaign.

Building an auto-tweet system was a very effective way of communicating essential public health information. Every time a tweet included a mention of the hashtag, a response was sent back to the user to thank them for getting involved and to provide additional information about the wider World Hepatitis Day campaign.

Establishing partnerships with Mobile Network Operators in Ghana, Kenya and South Africa allowed dissemination of important SMS messages to millions of people in areas where a greater health need exists.

Source

Provided by Healio

Pungpapong S. Liver Transpl. 2013;19:690-700.

June 27, 2013

Liver transplant recipients with hepatitis C experienced moderate early response rates but frequent side effects from triple therapy with antivirals in a recent study.

Researchers evaluated 60 liver transplant recipients with recurrent HCV genotype 1 and significant fibrosis who underwent treatment with pegylated interferon alfa-2a and ribavirin (PEG/RBV) and either telaprevir (TVR) (n=35) or boceprevir (BOC) (n=25), with a minimum follow-up of 12 weeks (mean follow-up, 35 weeks). Most patients were successfully placed on immunosuppressive therapy with cyclosporine before treatment initiation, including 33 TVR patients and 23 BOC patients.

The TVR cohort was assigned 12 weeks of TVR and PEG/RBV followed by PEG/RBV alone for 36 weeks, and those in the BOC group received 4 weeks of lead-in with PEG/RBV followed by 44 weeks of PEG/RBV with BOC.

Undetectable HCV RNA levels were observed in 86% of TVR recipients (mean, 6 weeks), compared with 48% of BOC patients (mean, 11 weeks). After 24 weeks of treatment, undetectable RNA without viral breakthrough had occurred in 67% of the TVR group and 45% of the BOC group in intention-to-treat analysis. Upon completion of follow-up, undetectable RNA remained in 27 TVR cases and 11 BOC recipients.

One patient in each group died during therapy. Cytopenias were common in both groups, and all participants required either hematological growth factor administration or dose reductions of peginterferon and/or ribavirin. Biopsy-proven acute rejection occurred in two TVR patients and none of the BOC recipients during treatment. Infectious complications occurred in six TVR cases but were treated and resolved without interruption.

“Our study has produced some important insights into the management of immunosuppression while patients are on these medications and into the frequency and severity of adverse events, as well as early virological response data,” the researchers wrote. “We have demonstrated that TVR- or BOC-containing antiviral protocols can be used after transplantation and result in moderately successful early virological responses, but these regimens are associated with important toxicities that mitigate their potential benefit.”

Source

June 26, 2013

The War On Drugs Kills: Support, Don't Punish

Sonal Mehta

Director for Programmes and Policy at India HIV/AIDS Alliance

Posted: 06/26/2013 2:02 pm

For more than 40 years, the international community has waged a misguided war against drug use that has done little more than make illegal drugs a multi-billion dollar global industry and contribute to the deaths of literally millions of drug users. Simply put, the war on drugs kills people who use drugs.

On June 26 each year, the United Nations marks the International Day Against Drug Abuse and Illicit Trafficking. This year, we are making it a day against the abuse of drug users by marking the start of the Support Don't Punish campaign to encourage governments to end the war on drugs that fuels the HIV, tuberculosis and hepatitis epidemics, violates human rights and fails to actually tackle the world's drug problem.

What is it about drugs and drug use that has led to this almost universal disapproval? India is a country of over a billion people, a good number of whom have used drugs in some form at some point in their lives. Are they all criminals? Our government certainly thinks so, as do most of the world's governments. Some even consider drug use a criminal offense punishable by death.

Some drug use has always been part of our social and religious culture but it has only been in the last hundred years or so that we have seen the steady tightening of controls on drugs and drug use. The price of this war however is not simply the cost of enforcement and incarceration.

Globally, the HIV and hepatitis C epidemics are fuelled by the criminalization of people who use drugs. Of the 16 million people who inject drugs worldwide, around three million are living with HIV and two thirds are living with hepatitis C. Even though one third of all HIV infections outside of sub-Saharan Africa are among people who inject drugs and even though the evidence of this is quite clear, the necessary funding for specialist prevention services has not followed.

While HIV prevalence in people who inject drugs is 24 times that of the general population in India, less than 3% of the $820 million invested by the Global Fund here in HIV programming so far supports them. While our friends at the Global Fund understand the value of such investments, it's often difficult for countries to get the political support needed to address HIV risk in the context of drug use due to its criminalization. This dynamic fuels a vicious cycle of neglect.

Criminalization undermines the effectiveness of the HIV response. In India and elsewhere, we need to scale up evidence‐based HIV prevention measures for people who inject drugs. The Support Don't Punish campaign calls for the removal of legal sanctions on low-level drug offenses and for the scale-up of scientifically proven health interventions, including a package of "harm reduction" services fully endorsed by the World Health Organisation, UNAIDS, and the United Nations Office on Drugs and Crime. This includes interventions to prevent the sharing of injecting equipment like needle and syringe exchange and effective programmes for those with drug dependency problems, such as opioid substitution therapy.

Rather than demonizing people who use drugs, we should humanize them. Rather than jailing them, we should get them the treatment they need. Rather than punishing them, we must support them. We need to end the war on drugs and make our priority the wellbeing of people who use drugs, their families and communities.

Source

Lure, variety of designer drugs is alarming, U.N. agency says

By Fredrik Dahl

VIENNA | Wed Jun 26, 2013 4:13am EDT

VIENNA (Reuters) - A sharp rise in the variety of legal "designer drugs" with names that entice young people into thinking they pose no risk is alarming from a public health standpoint, the United Nations drugs agency said on Wednesday.

The number of new psychoactive substances - marketed as "designer drugs" and "legal highs" - as reported by member states jumped by more than 50 percent in less than three years to 251 by mid-2012, the U.N. Office on Drugs and Crime said.

"This is an alarming drug problem - but the drugs are legal," it said. "Sold openly, including via the Internet, NPS (new psychoactive substances), which have not been tested for safety, can be far more dangerous than traditional drugs."

Names including "spice", "meow-meow" and "bath salts" mislead young people into believing they are indulging in low-risk fun, UNODC said.

But "the adverse effects and addictive potential of most of these uncontrolled substances are at best poorly understood", the agency said in an annual survey.

Use of such substances among youth in the United States appears to be more than twice as widespread as in the 27-nation European Union, where the United Kingdom, Poland and France have the most users, it said.

New psychoactive substances can be made by slightly modifying the molecular structure of controlled drugs, making a new drug with similar effects which can elude national and international bans.

They are "proliferating at an unprecedented rate and posing unforeseen public health challenges," said the report that examines production, trafficking and consumption trends.

"The international drug control system is floundering, for the first time, under the speed and creativity of the phenomenon" of this type of substances, the UNODC report said.

HEROIN, COCAINE USE SEEMS ON WANE

Overall, global drug consumption has remained stable, the report said, referring to the number of drug users with dependence or drug-use disorders. In 2011, the number of drug-related deaths was estimated at 211,000.

"While the use of traditional drugs, such as heroin and cocaine, seems to be declining in some parts of the world, prescription drug abuse and new psychoactive substance abuse is growing," it said.

Heroin use in Europe and that of cocaine in the United States appear to be falling while the cocaine market is expanding in South America and the emerging economies in Asia.

The U.N. agency's 2013 World Drug Report also said revised data showed that the prevalence of people injecting drugs who are also infected with the human immunodeficiency virus that causes AIDS was sharply lower than previously estimated.

In 2011, about 1.6 million people between the ages of 15 and 64 who injected drugs were living with HIV, a 46 percent decline since estimates three years earlier. The overall number of people using needles to take drugs was also lower.

The reduced figures are "in large part a result of the availability of more reliable information on HIV prevalence among people who inject drugs", the report said.

Criminals have been quick to tap into the lucrative market of new psychoactive substances while the law lags behind, the U.N. office said. Africa is becoming a target for the trafficking and production of illicit substances, it added.

"East and West Africa seems to be gaining in prominence with regard to routes for maritime trafficking," the report said. Seizures of heroin have risen sharply in Africa since 2009, especially in East Africa, where they increased almost tenfold.

(Editing by Michael Roddy)

Source

Provided by NATAP

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Clinical Gastroenterology and Hepatology June 2013
Article in Press

HCV Care in VA Debated - (06/24/13)

Kee Chan, PhD1,2,3, Mai Ngan Lai, MD4, Erik J. Groessl, PhD4,5, Amresh D. Hanchate, PhD3,6, John B. Wong, MD 7, Jack A. Clark, PhD 3,6, Steven M. Asch, MD MPH8, Allen L. Gifford, MD3,6, and Samuel B. Ho, MD 4,5

1. Department of Health Sciences, College of Health and Rehabilitation Sciences: Sargent College, Boston University, Boston, MA
2. Department of Epidemiology, School of Public Health, Boston University, Boston, MA
3. VA HIV/Hepatitis Quality Enhancement Research Initiative, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA
4. VA San Diego Healthcare System, San Diego, CA
5. University of California, San Diego, San Diego, CA
6. Departments of Health Policy and Management, and Medicine, Boston University, Boston, MA
7. Division of Clinical Decision Making, Informatics, and Telemedicine, Tufts Medical Center, Boston, MA
8. HRS&D Center of Excellence and Research Service, VA Palo Alto Healthcare System, Palo Alto, CA

"In conclusion, our model indicates the upfront costs required for treatment with Boc/PR or Tel/PR are high; however the offsetting benefits of extending quality of life and lower costs due to liver-related morbidity indicate that these therapies have very acceptable incremental cost-effectiveness ratios compared to previous therapies in this managed care health care system. Further efforts to expand access to DAA therapy are warranted. In our study, we evaluated cost effectiveness of DAA treatment strategies in a defined managed care population with pharmaceutical pricing based on large group negotiated prices. In the future, integrated care systems may be more common with the evolution of the Affordable Care Act and similar heath care reforms38, and drug pricing advantages will play an important role in determining overall cost effectiveness of new medications. In addition, our data is more relevant to health care systems in other countries with similar large group negotiated prices.

Cost-effectiveness ratios are one very important, but not sufficient, factor for making health policy decisions. Other factors such as system adaptability, budgetary issues, and patient preferences should also be considered in addition to our findings. This model will continue to be of use to evaluate future DAA therapies for HCV treatment, which may demonstrate increased efficacy albeit with significant costs."

Abstract
Background and Aim

The Veterans Health Administration (VHA) is the largest single provider of care for hepatitis C virus (HCV) infection in the US. We analyzed the cost-effectiveness of treatment with the HCV protease inhibitors boceprevir and telaprevir in a defined managed care population of 102,851 patients with untreated chronic genotype 1 infection.

Methods

We used a decision-analytic Markov model to examine 4 strategies: standard dual-therapy with pegylated interferon-alfa and ribavirin (PR), the combination of boceprevir and PR triple therapy, the combination of telaprevir and PR, or no antiviral treatment; sensitivity analysis was performed. Sources of data included published rates of disease progression, the census bureau, and VHA pharmacy and hospitalization cost databases.

Results

The estimated costs for treating each patient were $8000 for PR, $31,300 for boceprevier and PR, and $41,700 for telaprevir and PR. Assuming VHA treatment rates of 22% and optimal rates of sustained viral response, PR, boceprevir and PR, and telaprevir and PR would reduce relative liver-related deaths by 5.2%, 10.9%, and 11.5%, respectively. Increasing treatment rates to 50% would reduce liver-related deaths by 12%, 24.7%, and 26.1%, respectively. The incremental cost-effectiveness ratios were $29,184/quality of adjusted-life years (QALY) for boceprevir and PR and $44,247/QALY for telaprevir and PR vs only PR. With the current 22% treatment rate, total system-wide costs to adopt boceprevir and PR or telaprevir and PR would range from $708 million to $943 million.

Conclusions

Despite substantial upfront costs of treating HCV-infected patients in the VHA with PR, or telaprevir and PR, each regimen improves quality of life and extends life expectancy, by reducing liver-related morbidity and mortality, and should be cost effective. Further efforts to expand access to direct-acting antiviral therapy are warranted.

EXCERPTS

RESULTS

Compared to no treatment, use of standard PR therapy in the patient population at the treatment rate of 22% previously achieved among VA patients initiated on antiviral therapy between 2000-20081, 19 will decrease overall liver-related mortality by 5.0% (Table 2 and Figure 2). In contrast, treatment with DAA triple therapies at this same treatment rate, assuming the highest expected SVR rates (Boc/PR 54 % and Tel/PR 57%), will result in a 10.4 to 11.0% reduction in liver related death, respectively. If a treatment rates with PR, Boc/PR or Tel/PR can be increased to 50% of patients, the long-term reduction liver-related deaths will be 11.4%, 23.7% and 25.0%, respectively.

Cost and cost-effectiveness of antiviral treatments

With the previously achieved inital treatment rate of 22 %, total system-wide costs to adopt Boc/PR or Tel/PR would be $708 million and $943 million, respectively. Increasing treatment rates to 50% would result in the total cost of antiviral therapies PR, Boc/PR and Tel/PR treatment to be $411 million, $1,610 million and $2,144 million, respectively (Figure 3). Without antiviral treatment, the expected total cost of care for hepatitis C-related liver disease is $3,729 million. Compared with no treatment using PR at a 50% treatment rate results in overall cost savings of $30 million over the VHA cohort lifetime. In contrast, using Boc/PR or Tel/PR at a 50% treatment rate results in net cost expenditures of $692 million or $1,175 million, respectively.

The estimated cost and effectiveness (QALY) for the average treatment-naïve genotype 1 VHA patient and the incremental cost effectiveness ratio of DAA triple therapies compared with no therapy and PR therapy are given in Table 3A. Assuming the higher estimated SVR rates, the ICER for BocPR vs. PR = $29,184/QALY gained and TelPR vs. PR = $44,247/QALY gained.

Erythropoetin use was considered optional in the Boc licensing trial and not used in Tel licensing trials, and no SVR data is available for patients treated with TelPR when erythropoietin is used. Table 3B demonstrates the changes in ICER for DAA and PR therapies if potential costs of erythropoietin are included, which is common in clinical practice, although not universal.

For comparison purposes, the corresponding ICERs calculated using the average wholesale prices for Ribavirin, Peginterferon alfa, Boceprevir and Telaprevir are listed in Supplemental Table 6. The cost effectiveness for the four treatment strategies based on patient age and fibrosis stage are listed in Supplemental Table 7, and indicate that treating subgroups with younger age and more advanced fibrosis stage will be more cost-effective. As of 2010 there were approximately 21,466 genotype 1 patients that failed previous interferon treatment in the VHA. There is little data available concerning treatment of prior PR treatment failures in VHA populations, therefore we have used data from published phase III trials to make preliminary estimates related to incremental cost effectiveness ratios of DAA re-treatment in this patient population (Technical Appendix and Supplemental Table 8) 14, 15, 32

DISCUSSION

Our model projects cost-effectiveness analysis of the new DAAs therapy in the veteran population. Our simulated cohort of 102,851 treatment-naïve US veteran patients with HCV genotype 1 infection had more than 2-fold reduction in liver related death when they were treated with either Boc/PR or Tel/PR strategies compared to treatment with PR alone. When we used VHA contract FSS pricing, the incremental cost effectiveness ratio (ICER) of Boc/PR and Tel/PR compared with PR are $29,184/QALY gained and $44,247/QALY gained, respectively. The ICER of Boc/PR and Tel/PR compared to no treatment are $15,027/QALY gained and $24,467/QALY gained, respectively. For patients in their 40's and 50's with early fibrosis stage 1 and 2, the ICERs for DAA treatments compared with PR are within the oft cited $50,000/QALY gained threshold for consideration of acceptable ICERs for medical interventions. Our results indicate that these therapies are cost-effective for the majority of US veteran patients.

Other recent studies have showed similar cost-effectiveness results using wholesale pricing of the new DAA therapy. Liu et al. used average wholesale pricing for DAA therapy of $1100 per week 33. They projected the ICER of triple therapy vs. dual therapy would be $102,600 for patients with mild fibrosis and $51,000 for patients with advanced fibrosis, which is considerably higher than our projected cost effectiveness as would be expected given their higher pharmaceutical costs. Strategies to improve the ICERs of HCV antiviral treatments in the community setting may include selecting patients (such as those with advanced fibrosis) who would be more likely to benefit from therapy. In addition, they evaluated the use of the strategy of IL28 genotyping to guide therapy, with IL28 CC genotypes receiving PR therapy first. IL28-guided triple therapy treatment strategy results in reduced ICER for triple therapy treatment, although reductions in lifetime decompensated cirrhosis and HCC obtained with this strategy were only approximately 83% of those achieved with universal triple therapy. Recent data has demonstrated that IL28 CC patients treated with Tel/PR for 12 weeks achieve a 100% SVR rate compared with 64% SVR for these patients treated with PR for 48 weeks34. These data appear to mitigate the benefits of an IL28-guided strategy and lessen the likelihood that this would be an acceptable clinical alternative, yet further efforts to select patients most likely to benefit would be warranted under these scenarios. Further comparisons and limitations of our study are listed in the Technical Appendix.

We accounted for uncertainties regarding DAA treatment by estimating a range of possible SVR rates based on SVR rates attained in the VHA population with dual therapy pegylated interferon alfa and ribavirin. A recent meta-analysis by Cooper et al. compared SVR rates of BocPR and TelPR based on all data from phase II and phase III trials using a network meta-analysis and indirect comparisons to relative risk for SVR, and resulted in similar results as our analysis using phase III trial data35. For estimating duration of therapy with DAA treatments we used data from registration trials to calculate the percentage of patients with early treatment discontinuation and the percentage eligible to receive shorter durations of therapy. Because data from the Boceprevir registration trial was reported for Non-black and Black populations separately, we adjusted the treatment duration estimates for the known Non-black and Black patient distribution in VHA HCV patients, and therefore this data may be more accurate than the estimated treatment durations obtained from the Telaprevir registration trial.

A critical question for health care systems is the percentage of patients that are able to receive current antiviral therapies. Our data reflects the optimistic treatment rate of 50%, with the potential consequence of a 24-25% reduction in liver-related deaths. Such treatment rates in a VHA population may be attained with the use of integrated care protocols, which have surpassed 40% of VHA patients with pre-existing risk factors for psychiatric and substance use conditions in a recent study36, 37. Future interferon-free regimens are likely necessary for maximizing the number of HCV patients that can receive antiviral therapy.

In conclusion, our model indicates the upfront costs required for treatment with Boc/PR or Tel/PR are high; however the offsetting benefits of extending quality of life and lower costs due to liver-related morbidity indicate that these therapies have very acceptable incremental cost-effectiveness ratios compared to previous therapies in this managed care health care system. Further efforts to expand access to DAA therapy are warranted. In our study, we evaluated cost effectiveness of DAA treatment strategies in a defined managed care population with pharmaceutical pricing based on large group negotiated prices. In the future, integrated care systems may be more common with the evolution of the Affordable Care Act and similar heath care reforms38, and drug pricing advantages will play an important role in determining overall cost effectiveness of new medications. In addition, our data is more relevant to health care systems in other countries with similar large group negotiated prices.

Cost-effectiveness ratios are one very important, but not sufficient, factor for making health policy decisions. Other factors such as system adaptability, budgetary issues, and patient preferences should also be considered in addition to our findings. This model will continue to be of use to evaluate future DAA therapies for HCV treatment, which may demonstrate increased efficacy albeit with significant costs.

Source

Drug-Induced Liver Injury Is On the Rise

Provided by the American Gastroenterological Association

Bethesda, MD (June 26, 2013) — More people are being affected by drug-induced liver injury (DILI) than ever before, according to a new study in Gastroenterology, the official journal of the American Gastroenterological Association. This type of liver injury results from the use of certain prescription and over-the-counter medications, as well as dietary supplements, and is among the more challenging forms of liver disease due to its difficulty to predict, diagnose and manage.

Investigators conducted a population-based study in Iceland uncovering 19.1 cases of drug-induced liver injury per 100,000 inhabitants, per year. These results are significantly higher than the last population-based study of this kind, conducted in France from 1997-2000, which reported 13.9 cases per 100,000 inhabitants, per year.

The most commonly implicated drugs were amoxicillin-clavulante (penicillin used to fight bacteria), azathioprine (an immunosuppressive drug used in organ transplantation and autoimmune diseases) and infliximab (also used to treat autoimmune disease).

“Drug-induced liver injury is not a single, uncommon disease of the general population, but rather a series of rare diseases that occur only in persons who take specific medications,” said Einar S. Björnsson, lead study author from the department of internal medicine, section of gastroenterology and hepatology, National University Hospital, Reykjavik, Iceland, and faculty of medicine at the University of Iceland. “Our study identified which medications put patients most at risk for developing liver diseases. With this information, physicians can better monitor and manage patients who are prescribed potentially liver-injuring drugs.”

The study also showed that drug-induced liver injury was caused by a single prescription medication in 75 percent of cases, by dietary supplements in 16 percent and by multiple agents in 9 percent. Further, the incidence was similar in women and men, but increased with age; not surprising since the need for medication also increases with age.

Jaundice and other symptoms highly suggestive of liver injury, such as itching, nausea, abdominal discomfort and lethargy, were present in the majority of patients. Most patients had a favorable outcome after receiving care.

For more, watch Dr. Björnsson discuss his research in a Gastroenterology video abstract.

About the AGA Institute

The American Gastroenterological Association is the trusted voice of the GI community. Founded in 1897, the AGA has grown to include 17,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. The AGA Institute administers the practice, research and educational programs of the organization. www.gastro.org.

About Gastroenterology 

Gastroenterology, the official journal of the AGA Institute, is the most prominent scientific journal in the specialty and is in the top 1 percent of indexed medical journals internationally. The journal publishes clinical and basic science studies of all aspects of the digestive system, including the liver and pancreas, as well as nutrition. The journal is abstracted and indexed in Biological Abstracts, Current Awareness in Biological Sciences, Chemical Abstracts, Current Contents, Excerpta Medica, Index Medicus, Nutrition Abstracts and Science Citation Index. For more information, visit www.gastrojournal.org.

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Source

Meta-analysis linked NAFLD, vitamin D deficiency

Provided by Healio

Eliades M. Aliment Pharmacol Ther. 2013;doi:10.1111/apt.12377.

June 26, 2013

Vitamin D deficiency may be linked to the development of nonalcoholic fatty liver disease, according to a recent study.

Researchers performed a systematic review of 17 case-control and cross-sectional studies, assessing the association between nonalcoholic fatty liver disease (NAFLD) and serum levels of 25-hydroxy vitamin D (25[OH]D). Included studies were selected from PubMed and EMBASE databases and published before April 22, 2013, evaluated vitamin D levels among cases and controls, and were based in North America (six studies), Asia (four studies) and Europe or Israel (seven studies).

Most studies indicated that vitamin D deficiency was more prevalent among patients with NAFLD than controls. This association lost statistical significance after adjustment for confounders in two studies, and two studies indicated an inverse association between NAFLD, as indicated independently by ALT and vitamin D levels.

Investigators also conducted a pooled analysis including 11 studies, with nine assessing continuous vitamin D levels in 4,855 patients and 7,939 controls, and nine assessing categorical vitamin D in 5,202 patients and 8,520 controls.

Analysis of continuous vitamin D indicated that those with NAFLD had average 25(OH)D levels 0.36 ng/mL lower than controls (P<.01). Assessment of categorical vitamin D indicated that patients with NAFLD were 26% more likely than controls to be vitamin D-deficient (OR=1.26; 95% CI, 1.17-1.35). Deficiency was more prevalent and more severe among Western participants with NAFLD than Eastern patients. Results were not impacted by the exclusion of individual studies, and no evidence of publication bias was observed (P=.32).

“We have demonstrated that vitamin D deficiency is prevalent in NAFLD subjects, suggesting that vitamin D may play a role in the development of the disease,” the researchers concluded. “The anti-inflammatory and immune-modulatory properties of vitamin D provide plausible mechanisms by which vitamin D may impact on disease progression and severity in NAFLD.

“Future research should focus on investigating prospectively the association between vitamin D and NAFLD, as well as on randomized controlled trials of vitamin D supplementation in NAFLD subjects.”

Source

June 20, 2013

Atif Zaman, MD, MPH reviewing Hoshida Y et al. Gastroenterology 2013 May.

Profiling a 186-gene signature from needle-biopsy specimens could improve targeting of intensive surveillance to the highest-risk patients.

Hepatitis C virus (HCV)–related cirrhosis is a leading cause of liver-related morbidity and mortality. Identifying prognostic biomarkers of long-term outcomes might allow clinicians to risk-stratify their patients with cirrhosis and target high-risk patients for closer, more-intensive monitoring. In the current study, investigators assessed whether a 186-gene signature from liver tissue can predict death, progression of cirrhosis, or hepatocellular carcinoma (HCC) in HCV-infected patients with cirrhosis.

Researchers performed whole-genome gene expression profiling on archived liver biopsy tissue of 216 HCV-infected patients with Child-Pugh Class A cirrhosis (identified only by histology). The patients had been enrolled in a long-term, cohort study between 1985 and 1998 (N Engl J Med 1991; 325:675). During median follow-up of 10 years, 66 patients died (31%; 28 from HCC, 20 from liver failure, and 15 from non-liver–related causes), 71 (34%) developed hepatic decompensation, 66 (31%) progressed to Child-Pugh class B or C, 65 (30%) developed HCC (annual incidence, 2.9%), and 12 patients underwent liver transplantation.

Using the gene expression signature, patients were categorized by prognosis: poor (25%); intermediate (47%), or good (28%). In multivariate analysis, having a poor-prognosis signature was significantly associated with increased risk for death (P=0.004), liver disease progression (P<0.001), and HCC development (P=0.009). In the poor-, intermediate-, and good-prognosis groups, 10-year survival rates were 63%, 74%, and 85%, respectively, and annual HCC incidence rates were 5.8%, 2.2%, and 1.5%.

Comment

This study has significant clinical implications. First, such prognostic data will allow clinicians to advise patients with hepatitis C virus and early cirrhosis on their long-term prognoses. Second, these data will enable clinicians and public health programs to more appropriately target intensive surveillance practices to high-risk patients. Finally, genome-wide profiling can seemingly be performed on needle-biopsy specimens, thus allowing these important data to be gathered during routine clinical care. Once this 186-gene signature is further validated, it will become an important clinical tool.

Disclosures for Atif Zaman, MD, MPH at time of publication Speaker&#8217;s bureau Bristol-Myers Squibb; Genentech; Gilead; Kadmon; Merck; Salix; Vertex

Citation(s):

Hoshida Y et al. Prognostic gene expression signature for patients with hepatitis C–related early-stage cirrhosis. Gastroenterology 2013 May; 144:1024. (http://dx.doi.org/10.1053/j.gastro.2013.01.021)

PubMed abstract (Free)

Source

June 25, 2013

Liver disease: ‘50% of rural population hepatitis C positive’

568272-Liver-1372202922-944-640x480

By Imran Rana

Published: June 26, 2013

FAISALABAD: More than half of the rural population of Faisalabad is suffering from hepatitis C, field surveys conducted by the Liver Foundation Trust Faisalabad in June have concluded.

The trust- set up in 2005 under a private-public partnership- runs a liver centre and a mobile health care unit that visits a village each everyday in the region. It now plans to extend its capacity with a Rs100 million investment to deal with the emergency situation. The centre runs with help from philanthropists, who pay for two to 10 patients each.

Field reports show that the percentage of people suffering from hepatitis is between 50 and 70.

In the Muhammadwala village, where 223 patients were tested in the second week of June, 65 per cent were diagnosed with hepatitis C and four per cent with hepatitis B. In a village visited last week, the hepatitis C ratio was 69 per cent.

Doctors at the centre say patients lack awareness about how to protect themselves against the disease. The mobile health units reach out to liver patients at their doorsteps for creating awareness and treatment.

Sheikh Ashfaq Ahmad, the trust’s founder trustee, said trust was vaccinating hepatitis B patients in the rural areas free of cost.

He said the daily expense of the unit was Rs300,000. Visiting villages cost Rs9 million a month. The money, he said, came from philanthropists. Overseas Pakistanis in the UK and the USA also contribute for the hospital, he added.

He said the land for the centre had been provided by the district headquarters hospital. The management had spent Rs30 million on purchase of the equipment for the centre, he added.

Ahmad said the trust has been asking the businessmen in other cities to open similar centres as treatment of hepatitis C was very expensive.

Talking about the expansion plan, he said, it was designed to cater to the needs of the city where one-fourth of the population was suffering from the disease. He said the ratio was fast increasing.

Dilbur Hafeez, a patient at the liver centre, told The Express Tribune that he had been under treatment at the centre for several years. He said when he was first diagnosed with hepatitis C, he didn’t know he would live this long since he could not afford the treatment. “The hospital has not charged a single penny from my treatment,” he said.

Published in The Express Tribune, June 26th, 2013.

Source

PR-Logo-Newswire

PRESS RELEASE

June 25, 2013, 1:04 p.m. EDT

BETHESDA, Md., June 25, 2013 /PRNewswire via COMTEX/ -- The American College of Gastroenterology (ACG) praises the U.S. Preventive Services Task Force (USPSTF) for updating the hepatitis C virus (HCV) screening recommendations for all adults born between 1945 to 1965, the "boomer" generation. HCV is the most common chronic blood-borne disease in the United States and is a leading cause of complications from chronic liver disease.

The USPSTF members concluded that "the benefit of screening for HCV infection in persons in the birth cohort is likely similar to the benefit of screening in persons at higher risk for infection." A similar screening was recommended by the Centers for Disease Control and Prevention in 2012.

Gastroenterologists treat patients with liver disease, and, along with their liver specialist colleagues in hepatology, are on the front line treating patients with chronic viral hepatitis. "The American College of Gastroenterology recognizes the clinical challenges and realities of screening and treating chronic hepatitis C in community settings and is pleased that more undiagnosed patients can start getting the medical care they need upon diagnosis," said ACG President Ronald J. Vender, MD, FACG.

There is significant clinical evidence that, based on age alone, screening among asymptomatic adults can result in better outcomes by earlier treatment. New treatments for hepatitis C are more effective than ever in curing the infection, and may halt progression to cirrhosis, liver failure, liver cancer and death.

About Hepatitis CIn the United States, Hepatitis C virus (HCV) is the most common chronic blood-borne infection, the most common cause of chronic liver disease contributing to progressive liver fibrosis, cirrhosis and liver cancer, and is the most frequent cause for liver transplantation. Hepatitis C is spread primarily by contact with blood and blood products. The use of injection illicit drugs is the most common mode of disease transmission including those people who injected illicit drugs only one time many years ago.

People who received blood transfusions, transfusion of blood products or organ donations prior to 1992, when sensitive tests for HCV were introduced for blood screening, are at risk for hepatitis C infection, as are persons who received clotting factors prior to 1987. Other persons at risk for hepatitis C include long-term kidney dialysis patients, people with tattoos and body piercing other than pierced ears, health care workers after exposures (i.e., needle stick or splashes to the eye) from the blood of an infected person while on the job, infants born to HCV-infected mothers, people with high-risk sexual behavior, multiple partners and sexually transmitted diseases, people who snort cocaine using shared equipment, and people who have shared toothbrushes, razors and other personal items with a family member who is HCV-infected.

About the American College of GastroenterologyFounded in 1932, the American College of Gastroenterology (ACG) is an organization with an international membership of more than 12,000 individuals from 80 countries. The College is committed to serving the clinically oriented digestive disease specialist through its emphasis on scholarly practice, teaching and research. The mission of the College is to serve the evolving needs of physicians in the delivery of high quality, scientifically sound, humanistic, ethical, and cost-effective health care to gastroenterology patients. www.gi.org

SOURCE American College of Gastroenterology

Source

Clinical Gastroenterology and Hepatology

Article in Press

Lei Yu, Chihiro Morishima, George N. Ioannou,

published online 28 May 2013.
Uncorrected Proof

Abstract

Background & Aims

Little is known about whether dietary cholesterol affects disease progression in patients with chronic hepatitis C virus infection.

Methods

We analyzed data from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial, which included patients with advanced fibrosis and compensated cirrhosis. Cholesterol intake was determined for 608 participants on the basis of responses to food frequency questionnaires, administered at baseline and 1.8 years later. We investigated whether cholesterol intake was associated with clinical progression (death, variceal bleeding, encephalopathy, ascites, peritonitis, Child–Turcotte–Pugh score ≥7, or hepatocellular carcinoma) or histologic progression of disease (an increase in Ishak fibrosis score of 2 or more points in a second liver biopsy compared with the first).

Results

After adjustments for age, sex, race, presence of cirrhosis, body mass index, treatment with peginterferon, lifetime alcohol consumption, smoking, health status, and coffee and macronutrient intake, each higher quartile of cholesterol intake was associated with a 46% increase in the risk of clinical or histologic progression (adjusted hazard ratio [AHR], 1.46; 95% confidence interval [CI], 1.13–1.87; P for the trend = .004). Compared with patients in the lowest quartile of cholesterol intake (32–152 mg/day), those in the 3rd (224–310 mg/day; AHR, 2.83; 95% CI, 1.45–5.51) and 4th quartiles (>310 mg/day; AHR, 2.74; 95% CI, 1.22–6.16) had significantly increased risk of disease progression.

Conclusions

On the basis of analysis of data from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial, higher dietary cholesterol intake is associated with higher risk of disease progression in HCV-infected patients with advanced fibrosis or compensated cirrhosis.

Keywords: Diet, Cholesterol, Hepatitis C, Cirrhosis

Abbreviations used in this paper: AHR, adjusted hazard ratio, BMI, body mass index, CI, confidence interval, CTP, Child–Turcotte–Pugh, FFQ, food frequency questionnaire, HALT-C trial, Hepatitis C Antiviral Long-term Treatment Against Cirrhosis trial, HCC, hepatocellular carcinoma, HCV, hepatitis C virus, MTP, microsomal triglyceride transfer protein, TLR, toll-like receptor

Source

213588

New Recommendations Advocate Testing for Both At-Risk Individuals and All Individuals Born Between 1945 and 1965

June 25, 2013 08:00 | Source: OraSure Technologies, Inc.

BETHLEHEM, Pa., June 25, 2013 (GLOBE NEWSWIRE) -- OraSure Technologies, Inc. (Nasdaq:OSUR) announced today its support for the new recommendations issued today by the U.S. Preventive Services Task Force (USPSTF), giving both hepatitis C (HCV) screening for at-risk individuals and age-cohort screening a 'B' grade. Under the Affordable Care Act, preventive services that have received an 'A' or 'B' grade from the USPSTF must be covered by insurance policies without cost-sharing and be part of the essential health benefits for those individuals eligible for Medicare.

The new recommendations, entitled "Screening for Hepatitis C Virus Infection in Adults: U.S. Preventive Services Task Force Recommendation Statement," are a significant expansion of the USPSTF's previous recommendation of screening for HCV. This new recommendation is in response to the higher prevalence of HCV infection in Baby Boomers (those born between 1945 and 1965), approximately 80 million individuals. The Centers for Disease Control and Prevention (CDC) estimates that one out of every 30 Baby Boomers is living with hepatitis C infection. The USPSTF is recommending that all Baby Boomers be tested for hepatitis C at least once.

According to the CDC, the hepatitis C virus infection is the most common chronic blood-borne infection in the United States. Up to 75 percent of people with hepatitis C are unaware of their infection. Hepatitis C is the leading cause of liver cancer and liver transplants in the United States. If left undetected and untreated, the total medical costs for patients with HCV are expected to nearly triple over the next 20 years – from $30 billion to $85 billion according to the Millman Report entitled "Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease."

"We applaud the new U.S. Preventive Services Task Force recommendations, which will help to make hepatitis C screening much more accessible as a regular part of medical care," said Douglas A. Michels, President and Chief Executive Officer of OraSure Technologies. "As a result of the recommendations, we believe that over time more individuals will get tested and learn their hepatitis C status, and we expect that our OraQuick® Rapid HCV test will enable individuals presumed to be infected to be referred immediately for follow-up care."

The OraQuick® HCV Rapid Antibody Test is the first and only FDA-approved, CLIA-waived rapid, point-of-care test for the detection of antibodies to the hepatitis C virus. OraQuick® HCV results are available in 20 minutes, which can help increase the delivery of test results, allowing early diagnosis and linkage to care, treatment and prevention services, particularly for those at risk for hepatitis C.

The USPSTF is an independent group of national experts in prevention and evidence-based medicine that works to improve the health of all Americans by making evidence-based recommendations about clinical preventive services such as screenings, counseling services, and preventive medications. USPSTF recommendations have formed the basis of the clinical standards for many professional societies, health organizations, and medical quality review groups.

About OraSure Technologies

OraSure Technologies is a leader in the development, manufacture and distribution of oral fluid diagnostic and collection devices and other technologies designed to detect or diagnose critical medical conditions. Its innovative products include rapid tests for the detection of antibodies to HIV and HCV at the point of care and testing solutions for detecting various drugs of abuse. In July 2012, the Company received approval from the U.S. Food and Drug Administration for the Company's OraQuick® In-Home HIV Test for sale directly to consumers in the over-the-counter (OTC) market - making it the first and only rapid OTC HIV test approved in the U.S. In addition, the Company is a leading provider of oral fluid sample collection, stabilization and preparation products for molecular diagnostic applications. OraSure's portfolio of products is sold globally to various clinical laboratories, hospitals, clinics, community-based organizations and other public health organizations, research and academic institutions, distributors, government agencies, physicians' offices, and commercial and industrial entities. The Company's products enable healthcare providers to deliver critical information to patients, empowering them to make decisions to improve and protect their health.

For more information on OraSure Technologies, please visit www.orasure.com.

Media Contact:
Jennifer Moritz
Zer0 to 5ive for OraSure Technologies
917-748-4006


Source

FDA approves human feasibility study of device for treatment of HCV

Provided by Healio

June 25, 2013

The FDA has approved an investigational device exemption for a human feasibility study of a medical device for treating patients with hepatitis C, according to a press release.

The Aethlon Hemopurifier (Aethlon Medical) is intended for use in combination with interferon-based therapy or antiviral treatments, to improve early viral kinetic response without introducing additional drug toxicity. The device includes a plasma membrane containing immobilized affinity lectin Galanthus nivalis agglutinin, and allows extracorporeal therapeutic delivery through instruments currently available in medical facilities. According to the release, the Hemopurifier would benefit patients who experience viral rebound and require treatment discontinuation, as well as in those for whom standard or antiviral therapy is contraindicated.

Planned testing for the device will include the enrollment of 10 patients with end-stage renal disease (ESRD) and HCV infection. Participants will have received no pharmaceutical HCV therapy within the previous 30 days or longer. After a control phase of three dialysis treatments over 1 week, patients will subsequently receive Hemopurifier therapy during six dialysis sessions across 2 weeks. Incidence of adverse events will be compared between the control and Hemopurifier phases, and change to viral load during treatment will be assessed.

Prior studies outside of the United States indicated that Hemopurifier use was well tolerated among treatment-naive, HIV/HCV coinfected patients with ESRD when added to standard dialysis, decreasing viral loads from both diseases by an average of more than 50% per treatment. Additional studies of patients with HCV and without ESRD, in which three Hemopurifier treatments were administered in combination with interferon-based therapy, led to undetectable HCV viral loads within as few as 7 days among participants with HCV genotype 1.

“Aethlon Medical has been laying the groundwork necessary to implement the now approved clinical trial protocol for several years,” Rod Kenley, company president, said in the release. “While there is still some work to be done, today the biggest hurdle has been cleared, and we are anxious to make rapid progress toward commercialization.”

Source

Also See: Aethlon Medical Announces FDA Approval of IDE to Treat Hepatitis C (HCV) Patients

AETHLON MEDICAL HEMOPURIFIER

SAN DIEGO, June 25, 2013 /PRNewswire/ -- Aethlon Medical, Inc. (OTCQB: AEMD), announced today that the United States Food and Drug Administration (FDA) has approved an Investigational Device Exemption (IDE) that allows the Company to initiate human feasibility studies of the Aethlon Hemopurifier® in the United States. The Hemopurifier® is a first-in-class medical device that targets the rapid elimination of life-threatening infectious disease and cancer glycopathogens from circulation.

(Photo: http://photos.prnewswire.com/prnh/20090325/LA88762LOGO-b)

Under the feasibility study protocol, Aethlon will enroll ten end stage renal disease (ESRD) patients who are infected with the Hepatitis C virus (HCV) to demonstrate the safety of Hemopurifier therapy. Successful completion of the feasibility study will set the stage for Aethlon to conduct pivotal studies required for market clearance to treat HCV and potentially other disease conditions.

"Obtaining FDA's permission to initiate human studies has been our most important objective for several years," stated Jim Joyce, Chairman and CEO of Aethlon Medical. "I salute the perseverance of our dedicated Aethlon team, their families, and loyal shareholders whose support allowed us to endure the challenges of navigating through FDA. We plan to reward your faith with clinical execution and progression toward a marketable therapy in the United States."

Specific to the treatment of HCV, the Hemopurifier is uniquely positioned as an adjuvant to be incorporated with either interferon-based standard of care (SOC) or emerging all-antiviral drug regimens without adding drug toxicity.  In addition to augmenting the early viral kinetic response to SOC, the Hemopurifier is a candidate solution for viral rebound patients who traditionally are forced to discontinue therapy at the point HCV establishes resistance to drug regimens. Additionally, the Hemopurifier addresses the large population of HCV-infected ESRD patients for which SOC and emerging all-antiviral strategies may be contraindicated or not yet cleared.  According to the World Health Organization (WHO), HCV is a blood-borne pathogen that affects upwards of 170 million persons, or 2-3% of the world's population. It is a leading cause of cirrhosis and liver transplantation.

The FDA approved Hemopurifier therapy feasibility study calls for a single-site enrollment of ten HCV-infected end-stage renal disease (ESRD) patients who have not received any pharmaceutical therapy for their HCV infection for at least 30 days.  The protocol consists of a control phase which consists of three consecutive standard dialysis treatments during week one followed by the inclusion of the Hemopurifier during a total of six dialysis sessions conducted during weeks two and three. The rate of adverse events observed during the Hemopurifier therapy phase will be compared to the rate experienced during the control phase. Per-treatment changes of viral load will be observed through quantitative PCR analysis. Additionally, Aethlon may also choose to quantitate HCV viral copies captured within the Hemopurifier during each treatment session.

In studies previously conducted in India, Hemopurifier therapy was demonstrated to be well tolerated in treatment naïve HIV and HCV-infected ESRD patients when included during normally scheduled four-hour dialysis sessions. In these studies, average per treatment viral load reductions were observed to exceed 50% in both disease conditions.  In follow-on studies of non-ESRD individuals infected with HCV, a three-treatment protocol of Hemopurifier therapy in combination with interferon-based standard of care (SOC) resulted in undetectable HCV in as little as seven days in hardest to treat genotype-1 patients.  The studies also documented the ability of the Hemopurifier to capture as many as 300 billion HCV copies during a single six-hour treatment.

"Aethlon Medical has been laying the groundwork necessary to implement the now approved clinical trial protocol for several years" said Rod Kenley, Aethlon's President. "We are finally able to move forward with our contract research and clinical partners in finalizing all of the activities that can now take place prior to initiating treatment of the first patient.  While there is still some work to be done, today the biggest hurdle has been cleared and we are anxious to make rapid progress towards commercialization."

The feasibility study protocol was originally designed as a human safety challenge and model for addressing drug and vaccine resistant bioterror and emerging pandemic threats such as the Middle East Respiratory Syndrome (MERS) now spreading overseas.  In vitro studies conducted by leading government and non-government researchers have demonstrated that the Hemopurifier is able to capture a broad-spectrum of some of world's deadliest viral pathogens.  These include: Dengue hemorrhagic fever (DHF), Ebola hemorrhagic fever (EHF), Lassa hemorrhagic fever (LHF), H5N1 avian influenza (Bird Flu), H1N1 swine flu virus, the reconstructed 1918 influenza virus (r1918), West Nile virus (WNV) and Vaccinia and Monkeypox (MPV), which serve as models for human smallpox infection.  Human efficacy studies are not permissible against high-threat bioterror and pandemic threats.

The Hemopurifier is also being tested for its ability to capture glycopathogen targets that initiate or enhance the progression of sepsis through a contract with the Defense Advanced Research Projects Agency (DARPA). Sepsis is a life-threatening illness triggered by an overwhelming infection of the bloodstream. Globally, there are 18 million cases of diagnosed sepsis per year and the incidence is rising at 8 to 10% annually. 

In cancer, the Hemopurifier has been discovered to capture tumor-derived exosomes underlying several forms of cancer.  Tumor-derived exosomes have recently emerged to be a vital therapeutic target in cancer care. These microvesicular particles suppress the immune response in cancer patients through apoptosis of immune cells and their quantity in circulation correlates directly with disease progression. Beyond possessing immunosuppressive properties, tumor-derived exosomes facilitate tumor growth, metastasis, and the development of drug resistance.  By addressing this unmet medical need, the Hemopurifier is positioned as an adjunct to improve established cancer treatment regimens. In vitro studies to date have also documented that the Hemopurifier captures exosomes underlying lymphoma, melanoma, ovarian, and breast cancer.

In design, the Aethlon Hemopurifier consists of the affinity lectin Galanthus nivalis agglutinin (GNA) immobilized in the outer-capillary space of advanced plasma membrane technology. The design allows for extracorporeal therapeutic delivery to occur on standard CRRT and dialysis instruments already located in hospitals and clinics worldwide. The mechanism of the Hemopurifier to rapidly eliminate a broad-spectrum disease targets is based on GNA's ability to selectively bind unique high mannose signatures that are abundant on the surface of cancer-secreted exosomes and glycoproteins that reside on the outer membrane of infectious viral pathogens.

The Company will continue to update shareholders, constituents and potential study participants as feasibility study milestones are achieved, including naming a principal investigator, initiation of patient enrollment and the beginning of treatments with the Aethlon Hemopurifier.

About Aethlon Medical
Aethlon Medical creates innovative medical devices that address unmet medical needs in cancer, infectious disease, and other life-threatening conditions. Our Aethlon ADAPT™ System is a revenue-stage technology platform that provides the basis for a new class of devices the rapid, yet selective removal of disease promoting particles from the entire circulatory system.  At present, The Aethlon ADAPT product pipeline includes the Aethlon Hemopurifier to address infectious disease and cancer, and a medical device being developed under a 5-year contract with DARPA to reduce the incidence of sepsis in combat-injured soldiers.  For more information, please visit www.aethlonmedical.com.

Certain statements herein may be forward-looking and involve risks and uncertainties.  Such forward-looking statements involve assumptions, known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of Aethlon Medical, Inc. to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. Such potential risks and uncertainties include, without limitation, that the FDA will not approve the initiation of the Company's future clinical programs or provide market clearance of the Company's products, future human studies whether revenue or non-revenue generating from either compassionate use or non-compassionate use of the Aethlon ADAPT™ system or the Aethlon Hemopurifier® as an adjunct therapy to improve patient responsiveness to established cancer or hepatitis C therapies or sepsis therapies or as a standalone cancer or hepatitis C therapy or standalone sepsis therapy, the approval of the Company's technologies or products as a treatment against pandemic threats, the Company's ability to raise capital when needed, the Company's ability to complete the development of its planned products, the Company's ability to manufacture its products either internally or through outside companies and provide its services, the impact of government regulations, patent protection on the Company's proprietary technology, product liability exposure, uncertainty of market acceptance, competition, technological change, and other risk factors. In such instances, actual results could differ materially as a result of a variety of factors, including the risks associated with the effect of changing economic conditions and other risk factors detailed in the Company's Securities and Exchange Commission filings. The Company undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise.

Contacts:
James A. Joyce
Chairman and CEO
858.459.7800 x301
jj@aethlonmedical.com

Jim Frakes
Chief Financial Officer
858.459.7800 x300
jfrakes@aethlonmedical.com

Marc Robins
877.276.2467
mr@aethlonmedical.com

SOURCE Aethlon Medical, Inc.

RELATED LINKS
http://www.aethlonmedical.com

Source

June 27 is National HIV Testing Day

Provided by Infection Control Today

Posted Yesterday

The Centers for Disease Control and Prevention (CDC) recommends human immunodeficiency virus (HIV) testing for everyone at least once as a part of routine healthcare, and for high-risk groups more often.

This year marks the 19th annual National HIV Testing Day, a time to promote one of the best tools for HIV prevention. Too many people don’t know they have HIV; more than 1 million people are living with HIV in the United States, but 1 in 5 don’t know they are infected.

In April 2013, the U.S. Preventive Services Task Force (USPSTF) released HIV testing recommendations that everyone aged 15 to 65 should be screened for HIV infection; teens younger than age 15 and adults older than 65 also should be screened if they are at increased risk for HIV infection; and all pregnant women, including women in labor who do not know if they are infected with HIV, should be screened for HIV infection. CDC recommends an HIV test once a year for people at increased risk—such as gay and bisexual men, people who inject drugs, or people with multiple sex partners. CDC data suggests that sexually active gay and bisexual men might benefit from more frequent testing (e.g., every 3 to 6 months) Regular testing allows people who have HIV to know their status, get life-saving treatment and care, and prevent HIV transmission to others.
It’s easy to get tested. Ask your doctor for a test, or find a nearby testing site through National HIV and STD Testing Resources. Home test kits are also available. Two FDA-approved tests are available online or from drugstores: a rapid testing kit that provides results in 20 minutes using a swab of oral fluid from your gums, and a kit that involves collecting a finger stick blood sample and sending it to a licensed laboratory, then calling in later for results. In both cases, testing is anonymous, and the manufacturer provides confidential counseling and referral to care.

When you know your status, you can take care of yourself. If you find out that you are infected with HIV (if you test positive), you can seek medical care and get treatment, which helps people with HIV live longer, healthier lives and also lowers the chances of passing HIV to others.

If you don’t have HIV (if you test negative), take steps to stay negative. Remember that if you have unprotected sex or share needles for drug use after your test, you need to get tested again to make sure you are still HIV-negative. Your HIV test result “expires” every time you have risky sex or share needles or related works.

Knowing your HIV status is empowering. When you know your status, you can take care of yourself.

The CDC continues to work with federal, state, and local partners to expand routine HIV testing—not just on National HIV Testing Day but all year long. In 2010, CDC implemented new phases of its successful Expanded Testing Initiative, funding 30 health departments to focus on increasing HIV testing among African Americans and Latinos as well as gay and bisexual men and injection drug users of all races and ethnicities. The men who have sex with men (MSM) Testing Initiative will identify MSM with HIV who were previously unaware of their infection and link them to HIV medical care.

CDC’s Act Against AIDS (AAA) campaigns work to further expand HIV testing, raise awareness about HIV and AIDS among all Americans, and reduce the risk of infection among the hardest-hit populations.
- Reasons/Razones, the newest AAA campaign, promotes HIV testing among gay and bisexual Latino men.
- Let’s Stop HIV Together, a general-awareness AAA campaign to reduce stigma, urges everyone to “get the facts, get tested, and get involved.”
- Testing Makes Us Stronger encourages African American gay and bisexual men to get tested for HIV.
- Take Charge. Take the Test. encourages African American women to get tested for HIV.

On this National HIV Testing Day and throughout the year, people can:

- Get tested for HIV. Ask your doctor for a test, check National HIV and STD Testing Resources for a nearby testing site, call 1-800-CDC-INFO, text your ZIP code to “KNOW IT” (566948), or use one of the home testing kits.

- Get tested once a year or more often if you have multiple sex partners, inject drugs, or are a man who has sex with other men.

- Lower your risk for getting HIV by having sex with only one partner whom you know is not infected, or using a condom every time you have anal, vaginal or oral sex.

- If you have HIV, get medical care as soon as possible to stay healthier longer and to keep from passing the virus to others.

Healthcare providers can:
- Offer patients HIV tests as a routine part of their healthcare.

- Test women for HIV each time they are pregnant.

- Connect people at high risk for HIV to services that help them lower their risk and prevent them from getting infected.

- Make sure people who have HIV get treatment and the services they need to stay healthy and lower their risk of passing the virus to others.

Download materials for healthcare providers from CDC’s Act Against AIDS website.

State and local health departments can:

- Coordinate National HIV Testing Day awareness and testing events to help prevent the spread of HIV and build a local network that responds year-round to the epidemic.

- Create programs and adopt policies to get people at high risk tested early and often. Make sure that those who have a positive test get care quickly.

- Provide services such as medical care, social services, and programs shown to change behavior and lower risk to people at risk for HIV and those living with HIV.

- Promote and use national referral systems for places to get tested, such as National HIV and STD Testing Resources.

- Use CDC’s Act Against AIDS materials to promote HIV testing in target populations.

A Twitter chat with CDC director Thomas Frieden will take place on June 27, 2013, from 2 p.m. to 3 p.m.. ET. Use #CDCchat.

Source: CDC

Source

Annals of Internal Medicine

Clinical Guidelines | 25 June 2013

Virginia A. Moyer, MD, MPH, on behalf of the U.S. Preventive Services Task Force*

[+-] Article and Author Information

Ann Intern Med. Published online 25 June 2013 doi:10.7326/0003-4819-159-5-201309030-00672

Abstract

Description: Update of the 2004 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for and treatment of hepatitis C virus (HCV) infection in asymptomatic adults.

Methods: The Agency for Healthcare Research and Quality commissioned 2 systematic reviews on screening for and treatment of HCV infection in asymptomatic adults, focusing on evidence gaps identified in the previous USPSTF recommendation and new studies published since 2004. The evidence on screening for HCV in pregnant women was also considered.

Population: This recommendation applies to all asymptomatic adults without known liver disease or functional abnormalities.

Recommendation: The USPSTF recommends screening for HCV infection in persons at high risk for infection. The USPSTF also recommends offering 1-time screening for HCV infection to adults born between 1945 and 1965. (B recommendation)

The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms.

It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.

The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.

Summary of Recommendation and Evidence

The USPSTF recommends screening for hepatitis C virus (HCV) infection in persons at high risk for infection. The USPSTF also recommends offering 1-time screening for HCV infection to adults born between 1945 and 1965. (B recommendation)

See the Clinical Considerations for more information on risk factors for HCV infection.

See the Figure for a summary of the recommendation and suggestions for clinical practice.

Appendix Table 1 describes the USPSTF grades, and Appendix Table 2 describes the USPSTF classification of levels of certainty about net benefit.

Rationale

Importance

Hepatitis C virus is the most common chronic bloodborne pathogen in the United States and a leading cause of complications from chronic liver disease. The prevalence of the anti-HCV antibody in the United States is approximately 1.6% in noninstitutionalized persons. According to data from 1999 to 2008, about three fourths of patients in the United States living with HCV infection were born between 1945 and 1965, with a peak prevalence of 4.3% in persons aged 40 to 49 years from 1999 to 2002 (12). The most important risk factor for HCV infection is past or current injection drug use, with most studies reporting a prevalence of 50% or more. The incidence of HCV infection was more than 200 000 cases per year in the 1980s but decreased to 25 000 cases per year by 2001. According to the Centers for Disease Control and Prevention (CDC), there were an estimated 16 000 new cases of HCV infection in 2009 and an estimated 15 000 deaths in 2007. Hepatitis C–related end-stage liver disease is the most common indication for liver transplants among U.S. adults, accounting for more than 30% of cases. Studies suggest that about one half of the recently observed 3-fold increase in incidence of hepatocellular carcinoma is related to acquisition of HCV infection 2 to 4 decades earlier (1).

Detection

The USPSTF found adequate evidence that anti–HCV antibody testing followed by confirmatory polymerase chain reaction testing accurately detects chronic HCV infection.

In screening strategies targeting persons with risk factors for HCV infection (such as past or present injection drug use, sex with an injection drug user, or blood transfusion before 1992), anti–HCV antibody testing is associated with high sensitivity (>90%) and small numbers needed to screen to identify 1 case of HCV infection (<20 persons) (1). Anti–HCV antibody testing remains highly accurate in low-prevalence populations, although the numbers needed to screen to detect 1 case of HCV infection are higher.

The USPSTF also found adequate evidence that various noninvasive tests have good to very good diagnostic accuracy in diagnosing fibrosis or cirrhosis (3).

Benefits of Detection and Early Intervention

The USPSTF found no direct evidence on the benefit of screening for HCV infection in asymptomatic adults in reducing morbidity and mortality. However, the USPSTF found adequate evidence that antiviral regimens result in sustained virologic response (SVR) and improved clinical outcomes.

The USPSTF found inadequate evidence that counseling or immunization of patients with HCV infection against other infections improves health outcomes, reduces transmission of HCV, or changes high-risk behaviors. The USPSTF found inadequate evidence that knowledge of positive status for HCV infection reduces high-risk behaviors. The USPSTF also found inadequate evidence that labor management and breastfeeding strategies in HCV-positive women are effective at reducing risk for mother-to-child transmission.

Given the accuracy of the screening test and the availability of effective interventions for HCV infection, the USPSTF concludes that screening is of moderate benefit for populations at high risk for infection. The USPSTF concludes that 1-time screening in all adults in the United States born between 1945 and 1965 is also of moderate benefit.

Harms of Detection and Early Intervention

The USPSTF found limited evidence on the harms of screening for HCV. Potential harms of screening include anxiety, patient labeling, and feelings of stigmatization.

The USPSTF found adequate evidence on the harms associated with the diagnostic evaluation used to guide treatment decisions (liver biopsy). These harms include bleeding, infection, and severe pain in approximately 1% of persons who had a liver biopsy and death in less than 0.2%. However, the use of liver biopsy to guide treatment decisions is declining, and noninvasive tests have sufficient accuracy to diagnose fibrosis and cirrhosis. Thus, the absolute risk to persons who currently receive a diagnosis of HCV infection and subsequent treatment is probably declining.

The USPSTF found adequate evidence that antiviral therapy regimens are associated with a high rate of harms, such as fatigue, headache, flu-like symptoms, hematologic events, and rash. However, antiviral therapy is given for a defined duration, serious adverse events are uncommon, and adverse events are self-limited and typically resolve after treatment is discontinued. The USPSTF found adequate evidence that these harms of treatment are small.

USPSTF Assessment

The USPSTF concludes with moderate certainty that screening for HCV infection in adults at increased risk for infection and 1-time screening in adults in the 1945–1965 birth cohort has moderate net benefit.

Clinical Considerations

Patient Population Under Consideration

This recommendation applies to all asymptomatic adults without known liver disease or functional abnormalities.

Assessment of Risk

The most important risk factor for HCV infection is past or current injection drug use. Another established risk factor for HCV infection is receipt of a blood transfusion before 1992. Because of the implementation of screening programs for donated blood, blood transfusions are no longer an important source of HCV infection. In contrast, 60% of new HCV infections occur in persons who report injection drug use within the past 6 months (1).

Additional risk factors include long-term hemodialysis, being born to an HCV-infected mother, incarceration, intranasal drug use, getting an unregulated tattoo, and other percutaneous exposures (such as in health care workers or from having surgery before the implementation of universal precautions). Evidence on tattoos and other percutaneous exposures as risk factors for HCV infection is limited. The relative importance of these additional risk factors may differ on the basis of geographic location and other factors (1).

Large population-based studies report an independent association between high-risk sexual behaviors (multiple sex partners, unprotected sex, or sex with an HCV-infected person or injection drug user) and HCV infection. However, HCV seems to be inefficiently transmitted through sexual contact, and observed associations may have been confounded by other high-risk behaviors.

In 1998, the highest prevalence rates of the anti-HCV antibody occurred in persons with significant direct percutaneous exposures, such as injection drug users and persons with hemophilia (60% to 90%); persons with less significant percutaneous exposures involving smaller amounts of blood, such as patients receiving hemodialysis (10% to 30%), had more moderate prevalence rates. Persons engaging in high-risk sexual behaviors (1% to 10%); recipients of blood transfusions (6%); and persons with infrequent percutaneous exposures, such as health care workers (1% to 2%), had the lowest prevalence rates (45).

Among patients with abnormal results on liver function tests (measurement of aspartate aminotransferase, alanine aminotransferase, or bilirubin) who were tested for reasons other than HCV screening, finding the cause of the abnormality often includes testing for HCV infection and is considered case finding rather than screening; therefore, it is outside the scope of this recommendation.

In 2010, the overall incidence rate of acute HCV infection was 0.3 cases per 100 000 persons and varied by race or ethnicity. The incidence rate for acute hepatitis C was lowest among persons of Asian or Pacific Islander descent and highest among American Indians and Alaskan natives. Blacks had the highest mortality rates from HCV, at 6.5 to 7.8 deaths per 100 000 persons, according to data from 2004 to 2008 (6).

Birth-Cohort Screening

Persons born between 1945 and 1965 are more likely to be diagnosed with HCV infection, possibly because they received blood transfusions before the introduction of screening in 1992 or have a history of other risk factors for exposure decades earlier (2). Many persons with chronic HCV infection are unaware of their condition. A risk-based approach may miss detection of a substantial proportion of HCV-infected persons in the birth cohort because of a lack of patient disclosure or knowledge about prior risk status. As a result, 1-time screening for HCV infection in the birth cohort may identify infected patients at earlier stages of disease who could benefit from treatment before developing complications from liver damage.

The USPSTF concluded that the benefit of screening for HCV infection in persons in the birth cohort is probably similar to that in persons at higher risk for infection. Birth-cohort screening is probably less efficient than risk-based screening, meaning more persons will need to be screened to identify 1 patient with HCV infection. Nevertheless, the overall number of Americans who will probably benefit from birth-cohort screening is greater than the number who will benefit from risk-based screening.

The USPSTF recognizes that increased screening and the resulting increased diagnoses and treatment could result in increased overall harms because not all treated persons will benefit from treatment, including those who will never develop signs or symptoms of disease (overdiagnosis). The USPSTF weighed this potential harm against the potential harm of undertreatment attributable to underdiagnosis. It is hoped that future research will reduce overtreatment by clarifying which persons are most likely to benefit from early diagnosis and treatment. However, given that persons in the birth cohort have been living with HCV infection for 20 or more years, the potential benefit of screening and early treatment will probably be at its highest now and in the near future before becoming smaller. After weighing the competing harms of overtreatment and underdiagnosis, the USPSTF recommends 1-time screening for this cohort.

Screening Tests

Anti–HCV antibody testing followed by polymerase chain reaction testing for viremia is accurate for identifying patients with chronic HCV infection. Various noninvasive tests with good diagnostic accuracy are possible alternatives to liver biopsy for diagnosing fibrosis or cirrhosis.

Screening Intervals

Persons in the birth cohort and those who are at risk because of potential exposure before universal blood screening and are not otherwise at increased risk need only be screened once. Persons with continued risk for HCV infection (injection drug users) should be screened periodically. The USPSTF found no evidence about how often screening should occur in persons who continue to be at risk for new HCV infection.

Screening Implementation

The USPSTF believes that screening should be voluntary and undertaken only with the patient's knowledge and understanding that HCV testing is planned. Patients should be informed orally or in writing that HCV testing will be performed unless they decline (opt-out screening). The USPSTF further believes that before HCV screening, patients should receive an explanation of HCV infection, how it can (and cannot) be acquired, the meaning of positive and negative test results, and the benefits and harms of treatment. Patients should also be offered the opportunity to ask questions and to decline testing.

Treatment

The purpose of antiviral treatment regimens is to prevent long-term health complications of chronic HCV infection (such as cirrhosis, liver failure, and hepatocellular carcinoma).

The combination of pegylated interferon (α2a or α2b) and ribavirin is the standard treatment for HCV infection. In 2011, the U.S. Food and Drug Administration approved the protease inhibitors boceprevir and telaprevir for the treatment of HCV genotype 1 infection (the predominant genotype in the United States). Trials have found increased SVR rates in patients with HCV genotype 1 infection who received triple therapy consisting of pegylated interferon, ribavirin, and boceprevir or telaprevir compared with dual therapy consisting of pegylated interferon and ribavirin. Evidence is lacking on the comparative effects of current antiviral treatments on long-term clinical outcomes. Regimens with protease inhibitors are usually of shorter duration than dual therapy (24 or 28 weeks vs. 48 weeks). Triple therapy with protease inhibitors is associated with an increased risk for hematologic events (such as anemia; neutropenia; and thrombocytopenia, particularly with boceprevir) and rash (telaprevir) compared with dual therapy. These adverse events are self-limited and typically resolve after the discontinuation of treatment (7).

Other Considerations

Research Needs and Gaps

As treatment of HCV continues to evolve, more research is needed to understand which persons benefit the most from treatment and when treatment should begin in asymptomatic persons. Research is needed on the outcomes of treatment in screen-detected patients and on treatment decisions guided by “noninvasive” assessment of cirrhosis and fibrosis because these patients may differ from those enrolled in treatment trials or described in prospective cohort studies. In addition, research should focus on the long-term harms associated with antiviral regimens. Other areas of needed research include frequency of testing in high-risk populations; demonstrating individual or public health benefits from counseling, immunizations, and behavioral changes after an HCV diagnosis in asymptomatic patients; the effect of antiviral treatments on quality of life; and the comparative effectiveness of antiviral treatments in patients with various medical and psychological comorbid conditions.

Discussion

Burden of Disease

Hepatitis C is the most common chronic bloodborne pathogen in the United States. The prevalence of the anti-HCV antibody in the United States is approximately 1.6% (1).

An estimated 78% of persons who test positive for the anti-HCV antibody have detectable levels of HCV in the blood (viremia), reflecting chronic infection. Persons who have HCV and undetectable viremia are considered “cured,” as demonstrated by the absence of serum HCV RNA (1).

The prevalence of chronic HCV infection peaked in 2001 at 3.6 million persons. According to data from 1999 to 2008, three fourths of patients in the United States living with HCV infection were born between 1945 and 1965, with a peak prevalence of 4.3% in persons aged 40 to 49 years. The incidence of HCV infection was more than 200 000 cases per year during the 1980s but decreased to 25 000 cases per year by 2001. In 2009, the CDC estimated that there were 16 000 new cases of HCV infection (12).

Hepatitis C virus infection is the leading cause of complications from chronic liver disease, and HCV-related end-stage liver disease is the most common indication for liver transplants among U.S. adults. It is estimated that the total number of patients with cirrhosis will peak at 1 million in 2020; however, rates of hepatic decompensation and liver cancer are expected to increase for another 10 to 13 years because of the lengthy lag time between infection and development of cirrhosis and other complications. An estimated 15 000 deaths from HCV infection occurred in 2007 (1).

Scope of Review

The Agency for Healthcare Research and Quality commissioned 2 systematic reviews (1, 7) to update the 2004 USPSTF recommendation on screening for and treatment of HCV infection in asymptomatic adults (8). These reviews focused on evidence gaps identified in the previous USPSTF recommendation and new studies published since 2004. They also examined the evidence on screening for HCV in pregnant women.

Accuracy of Screening Tests

The USPSTF previously found that screening with later-generation enzyme immunoassay and confirmatory recombinant immunoblot assay accurately detects the anti-HCV antibody (8). In the current review, the USPSTF considered the evidence on the diagnostic accuracy of various noninvasive confirmatory tests to diagnose cirrhosis or advanced fibrosis in patients with HCV infection (1). The USPSTF found more than 100 studies (including 8 of good quality) that compared various noninvasive laboratory-based diagnostic tests with liver biopsy as the reference standard. Sensitivity and specificity varied depending on the cutoff used to define a positive test result. Several of the blood indices were associated with an area under the receiver-operating characteristic curve of 0.75 to 0.86 for fibrosis and 0.80 to 0.91 for cirrhosis (considered good to very good values for diagnostic accuracy) (1).

One study evaluated clinical outcomes associated with different strategies to evaluate patients with HCV infection for treatment. A retrospective cohort study of 156 HCV-positive patients who received interferon and ribavirin therapy found no difference in SVR rates between patients who did not have biopsy before treatment compared with matched patients who did have biopsy (41% vs. 44%; P = 0.87). About three quarters of the patients who did not have biopsy declined the procedure, and about one quarter had contraindications. The study was not designed or powered to evaluate longer-term clinical outcomes and did not report harms associated with biopsy (1, 9).

Clinical practice is moving toward less routine use of biopsy before antiviral treatment. No studies reported current estimates of the proportion of patients who have biopsy before treatment. Although such practice patterns will undoubtedly reduce harms associated with liver biopsy, how this will affect the number of patients considered eligible for treatment and the long-term clinical effectiveness and harms of treatment of these persons is not yet clear.

Effectiveness of Early Detection and Treatment

There is no direct evidence of the benefit of screening for HCV infection in asymptomatic adults in reducing morbidity or mortality. No randomized trials have compared clinical outcomes between persons screened and those not screened for HCV infection.

Various screening strategies have been proposed; however, no randomized trials or observational studies have compared clinical outcomes of different approaches to screening for HCV. Five studies compared screening approaches to determine the relative yield of the different strategies. Targeted screening strategies in high-risk persons were associated with high sensitivity (>90%) and small numbers needed to screen to identify 1 case of HCV infection (<20 persons). The studies used various criteria for targeted screening, but all included current or past injection drug use, sex with an injection drug user, and receipt of blood transfusion before 1992. Narrow screening strategies (such as those targeting only injection drug use) had low numbers needed to screen but missed up to two thirds of infected patients. None of the studies used the birth-cohort screening approach. The studies were retrospective and had methodological issues that limit the overall ability to compare screening strategies (1).

The USPSTF examined the evidence on benefits from counseling, immunizations, and behavioral changes after a diagnosis of HCV infection. No studies evaluated effects of counseling or immunizations on health outcomes or transmission risk. One randomized trial found that a self-management program in patients with HCV infection was associated with small increases in vitality scores on the 36-Item Short Form Health Survey compared with the use of educational materials after 6 weeks, but there were no effects on other quality-of-life measures (10).

Three retrospective studies showed reduced alcohol use after a diagnosis of HCV infection, but 2 prospective studies found no association between sustainable behavior change (alcohol or injection drug use) and knowledge of diagnosis. Two cross-sectional studies had conflicting results (1).

Evidence is limited on effective counseling methods to decrease high-risk behaviors. Two randomized trials reported mixed results on the effects of behavioral-based counseling interventions compared with simple educational interventions. A before–after study of HCV-infected patients who were heavy drinkers found that a counseling intervention was associated with a greater than 50% reduction in alcohol use (1).

Sustained virologic response is the intermediate outcome used to measure treatment efficacy in clinical trials and is the basis for U.S. Food and Drug Administration drug approval. It is defined as a decrease in HCV RNA to undetectable levels 24 weeks after antiviral treatment and is associated with a sustained loss of detectable viremia.

Sustained virologic response rate is the principal outcome used to assess the benefit of antiviral regimens because of a lack of direct evidence on long-term clinical outcomes. Two trials of boceprevir and 3 trials of telaprevir with pegylated interferon (α2a or α2b) and ribavirin found that these regimens were more effective in increasing SVR rates than dual therapy with pegylated interferon (α2a or α2b) and ribavirin. Sustained virologic response rates ranged from 60% to 92% (genotype 1) with triple therapy regimens compared with 42% to 52% (genotype 1) with dual therapy (7).

The link between SVR and clinical outcomes has been evaluated in many studies. The largest was a cohort study of 16 864 patients from the U.S. Department of Veterans Affairs that adjusted for several confounders (demographic factors, comorbid conditions, laboratory characteristics, and treatment characteristics). This fair-quality study showed a decrease in the risk for all-cause mortality compared with no SVR across patient groups stratified by genotype. Hazard ratios (HRs) were 0.71 (95% CI, 0.60 to 0.86), 0.62 (CI, 0.44 to 0.87), and 0.51 (CI, 0.35 to 0.75) for genotypes 1, 2, and 3, respectively (11). Another recently published cohort study of 530 patients from 5 hospitals in Europe and Canada that adjusted for confounding also found a positive association between SVR and reduced risk for all-cause mortality (HR, 0.26 [CI, 0.14 to 0.49]). The study also found reduced risk for liver-related mortality or transplants (HR, 0.06 [CI, 0.02 to 0.19]), with a median follow-up of 8.4 years. All patients had advanced fibrosis or cirrhosis (12). Eighteen other primarily smaller cohort studies (n = 102 to 2698) found that SVR was associated with decreased risk for all-cause mortality and hepatic complications related to chronic HCV infection, including studies of populations with baseline cirrhosis. The smaller cohort studies had methodological limitations. For example, only 5 studies evaluated important confounders (age, sex, genotype, viral load, and fibrosis); 4 studies reported patients who were excluded or lost to follow-up. In addition, 10 of the 18 studies were conducted in Asia, where the incidence of hepatocellular carcinoma in patients with chronic HCV infection is higher than in the United States, possibly limiting applicability. Hazard ratios in the 18 cohort studies also indicated an association between achievement of SVR and improvement in clinical outcomes, but these studies reported stronger estimates than the U.S. Department of Veterans Affairs cohort study (7). A recently published meta-analysis of pooled observational studies (13), most of which were included in the USPSTF review, examined the association between SVR and hepatocellular carcinoma. Overall, the review's conclusions on the association between SVR and decreased risk for hepatocellular carcinoma were consistent with the USPSTF review. The pooled adjusted HR estimates for hepatocellular carcinoma were 0.24 (CI, 0.18 to 0.31) in the general HCV population and 0.23 (CI, 0.16 to 0.35) in patients with advanced fibrosis or cirrhosis.

A recent meta-analysis of 8 randomized, controlled trials comparing antiviral therapy (interferon or pegylated interferon, alone or with ribavirin) versus placebo or no intervention showed a reduction in hepatocellular carcinoma (risk ratio, 0.53 [CI, 0.34 to 0.81]), with a more pronounced effect in virologic responders than in nonresponders. Although the trials examined older regimens, the USPSTF concluded that the benefits from newer, more effective antiviral regimens may be greater (14).

Antiviral therapy is contraindicated in pregnancy because of its potential teratogenic effects. Although evidence is limited, no labor management intervention has been clearly shown to decrease risk for mother-to-child transmission of HCV infection. Breastfeeding does not seem to be associated with increased risk for mother-to-child transmission (1).

The USPSTF also reviewed a modeling study that informed the CDC's 2012 recommendation on screening for HCV and reported large estimated reductions in HCV-related mortality with a birth-cohort approach versus risk-based screening (15). These estimates assumed a lifetime rate of progression to cirrhosis in untreated patients with HCV infection of 54% and a mortality rate from HCV infection of 22%. However, longitudinal studies with up to 20 years of follow-up report cirrhosis in 10% to 20% of HCV-infected patients, and the longest study reported HCV-related mortality in 5.9% of patients after 45 years. In addition, estimates of clinical benefit in the modeling study assumed that risk for cirrhosis and other complications of HCV infection in patients achieving SVR after antiviral therapy reverted to that of uninfected persons (5). These assumptions relate to important uncertainties about the natural history of HCV infection. If progression to cirrhosis or mortality was lower than assumed, the benefit from screening and treatment would also be lower. A recent modeling study by Liu and colleagues (16) evaluated risk factor–guided and birth-cohort screening strategies. Model assumptions seemed conservative and consistent with available data on the natural history of HCV and effectiveness of antiviral treatment. The study concluded that birth-cohort screening provides nearly twice the benefit of risk-based screening.

Harms of Screening and Treatment

Potential harms associated with screening for HCV infection include anxiety, labeling, and effect on relationships, but evidence on these harms is limited. Five studies of patients diagnosed with HCV infection suggest potential negative psychological and social effects, but the sample sizes were small and the studies had methodological flaws, such as lack of an unscreened comparison group (1).

In addition to the potential harms of screening, there are harms related to the diagnostic evaluation of patients who test positive for the anti-HCV antibody. In a study of 2740 patients with chronic HCV infection and an Ishak fibrosis score of 3 or higher (no uncompensated cirrhosis) who had liver biopsy, serious adverse events occurred in 1.1% of patients, including 0.6% who had serious bleeding and 0.3% who had severe pain (1). No deaths were reported. In 5 large intervention series published since 2004, the mortality rate was less than 0.2% and serious complications were found in 0.3% to 1.0% of more than 62 000 patients who had liver biopsy (1). Because of the availability of various noninvasive tests that have good diagnostic accuracy, liver biopsy will probably occur less frequently.

Harms are associated with the medications used to treat HCV. The most common adverse effects of antiviral regimens are fatigue, headache, and other flu-like symptoms, which occurred in as many as one half of patients in some trials. Triple therapy with protease inhibitors was associated with increased risk for hematologic events (anemia; neutropenia; and thrombocytopenia, particularly with boceprevir) and rash (telaprevir) compared with dual therapy. Although treatment-related adverse effects were common, the few serious adverse events reported in the trials were generally self-limited and typically resolved after the discontinuation of treatment (7).

Estimate of Magnitude of Net Benefit

The USPSTF concludes with moderate certainty that there is a linkage between SVR and clinical outcomes (hepatocellular carcinoma and mortality) and that the overall net benefit of screening is moderate. The evidence supporting this linkage includes consistent associations between achieving SVR and improved clinical outcomes, with most studies reporting large effect sizes, as well as evidence from studies that controlled for several confounders and found an early mortality reduction among patients with all viral genotypes who achieved SVR and are probably similar to patients detected and eligible for treatment through U.S. screening programs. In addition, evidence showed that antiviral treatment results in improved clinical outcomes. A new modeling study showed that birth-cohort screening provided nearly twice the benefit of risk-based screening.

Given the decreasing use of liver biopsy before antiviral treatment and evidence that antiviral therapy regimens have small harms, the USPSTF concludes that the net benefit of screening for HCV infection in high-risk populations with a high prevalence (injection drug users) is moderate. Populations at very high risk have a larger overall benefit from screening because of the higher prevalence of infection and greater potential for treatment benefits. Although the birth cohort has a lower prevalence of infection, the small harms of screening are outweighed by the larger benefit of receiving treatment that can prevent liver-related morbidity and mortality. Therefore, the USPSTF concludes with moderate certainty that the net benefit of 1-time screening in adults born between 1945 and 1965 is moderate.

How Does Evidence Fit With Biological Understanding?

Chronic HCV infection is defined by the presence of HCV RNA in the blood for at least 6 months after acute infection. Chronic infection occurs in 78% of infected patients; however, the ability to accurately determine which infected patients will develop cirrhosis and which will not is limited. Many patients with chronic infection do not develop histologic evidence of liver disease or have mild liver disease, whereas others progress to cirrhosis, end-stage liver disease, or hepatocellular carcinoma. Cohort studies show that approximately 7% to 24% of persons will develop cirrhosis after 20 years of infection, with possible acceleration of cirrhosis after infection for 20 years, and up to 5% will die of liver-related complications (1). Evidence is limited on the longer-term natural history of chronic HCV infection.

Sustained virologic response is associated with the absence of detectable serum HCV RNA, improved histologic changes, and normalization of liver aminotransferase levels. It is considered to reflect resolution of HCV infection.

Preparation of the Draft Recommendation Statement

In July 2012, after deliberation of the evidence, the USPSTF preliminarily voted for a B grade for screening for HCV in high-risk persons and a C grade for the birth cohort. In preparing the draft recommendation statement, the USPSTF considered the quality of evidence obtained from observational data, whether results from the cohort studies reflected a “screened population,” and whether SVR is a sufficient proxy for long-term treatment response. These limitations of the evidence led the USPSTF to conclude with moderate certainty that the magnitude of the net benefit was at least small for the birth cohort. The different recommendations for high-risk versus birth-cohort screening reflected differences in the prevalence of HCV infection in the populations and the USPSTF's certainty about net benefit.

A draft version of the recommendation statement was posted for public comment on the USPSTF Web site from 27 November to 24 December 2012. Since then, new evidence has been published by van der Meer and colleagues (12), Morgan and colleagues (13), Kimer and colleagues (14), and Liu and colleagues (16) and reviewed by the USPSTF. The positive association between SVR and mortality (all-cause or liver-related) reported in the cohort study by van der Meer and colleagues strengthened the USPSTF's confidence in the linkage of SVR and clinical outcomes. A meta-analysis of cohort studies by Morgan and colleagues showed findings consistent with those of the USPSTF's evidence review (13). Kimer and colleagues provided new evidence that antiviral treatment was associated with better clinical outcomes than placebo or no intervention, and the modeling study by Liu and colleagues showed that birth-cohort screening provided nearly twice the clinical benefit of risk-based screening.

The USPSTF also considered that risk-based screening does not work well in identifying persons who are at increased risk for HCV infection. The USPSTF recognized that increased screening and diagnoses could lead to increased harms because not all persons will benefit from treatment. The USPSTF assessed the potential harm of overdiagnosis and determined that the harms were small given the reduced use of liver biopsy, the limited duration of antiviral therapy, and the reversibility of adverse effects with discontinuation and therapy and were balanced by the larger benefit of treatment for infected persons in the birth cohort. The new studies provided evidence that the magnitude of the net benefit in the birth cohort is moderate, not small.

Response to Public Comments

A draft version of this recommendation statement was posted for public comment on the USPSTF Web site from 27 November to 24 December 2012. Some comments requested clarification about risk factors. Others addressed the costs of screening in the birth cohort and how HCV treatment may be inaccessible to persons without health insurance coverage. Many comments noted that risk-based screening would be a burden to clinical providers, is viewed as less effective, and may be a low priority for clinicians who see asymptomatic patients. Many comments disagreed with the USPSTF's assessment of the benefits and harms of screening for HCV in the birth cohort compared with high-risk persons.

In response to these comments, the USPSTF distinguished between established risk factors and less established risk factors in the Clinical Considerations section and added language about populations that are at risk. The USPSTF does not make recommendations on insurance coverage or assess or consider financial costs. The USPSTF also clarified how risk-based screening approaches may miss infected persons.

After the public comment period, the USPSTF considered new evidence that was published since its initial deliberation—specifically, studies by Kimer and colleagues (14), van der Meer and colleagues (12), Liu and colleagues (16), and Morgan and colleagues (13). After reviewing this new evidence, the USPSTF determined that the new studies support a moderate magnitude of net benefit for the birth cohort as well as for high-risk persons.

Update of the Previous USPSTF Recommendation

In 2004, the USPSTF recommended against screening for HCV infection in adults not at increased risk for infection (D recommendation) and found insufficient evidence to recommend for or against screening in adults at high risk (I statement). The D recommendation for average-risk persons was based on a low prevalence of HCV infection, the natural history of chronic HCV infection, a lack of direct evidence showing that screening or antiviral treatments improve important health outcomes, and the potential harms of screening. The USPSTF found insufficient evidence on the effects of screening or antiviral regimens on clinical outcomes and the link between improved intermediate and clinical outcomes to determine the balance of benefits and harms of screening (8).

For this update, the USPSTF reviewed the indirect chain of evidence that showed the benefits of screening through improvement of the intermediate outcome of SVR after triple-regimen antiviral treatments and reductions in all-cause and liver-related mortality and hepatocellular carcinoma. The USPSTF examined the evidence and accepted with moderate certainty the association between SVR after antiviral treatments and improved clinical outcomes. The USPSTF also found adequate evidence that antiviral treatment results in improved clinical outcomes (reduction in hepatocellular carcinoma). In addition, a recent modeling study with more conservative assumptions showed that birth-cohort screening provided nearly twice the benefit of risk-based screening.

In reviewing the prevalence data on high-risk groups and the potential for reduced transmission, the USPSTF concluded that screening in high-risk persons (prevalence ≥50%) and the birth cohort (prevalence of about 3% to 4%) would result in a moderate net benefit. With regard to harms, the use of liver biopsy is decreasing and the few serious adverse events reported in the trials were self-limited and typically ended after treatment discontinuation.

On the basis of the evidence, the USPSTF changed its previous recommendations to a grade B recommendation for screening for HCV infection in persons at high risk for infection and 1-time screening for HCV infection in the 1945–1965 birth cohort.

Recommendations of Others

The American Association for the Study of Liver Diseases (17), the Infectious Diseases Society of America (18), and the American College of Gastroenterology (19) recommend screening in higher-risk patients. The CDC now recommends screening in high-risk patients and age cohort–based screening for HCV in all persons born between 1945 and 1965 (5). Previous recommendations on screening for hepatitis C by the American Academy of Family Physicians, which is currently updating its recommendations, have been consistent with those of the USPSTF (20).

Appendices

Appendix: U.S. Preventive Services Task Force

Members of the U.S. Preventive Services Task Force at the time this recommendation was finalized† are Virginia A. Moyer, MD, MPH, Chair (American Board of Pediatrics, Chapel Hill, North Carolina); Michael L. LeFevre, MD, MSPH, Co-Vice Chair (University of Missouri School of Medicine, Columbia, Missouri); Albert L. Siu, MD, MSPH, Co-Vice Chair (Mount Sinai School of Medicine, New York, and James J. Peters Veterans Affairs Medical Center, Bronx, New York); Linda Ciofu Baumann, PhD, RN (University of Wisconsin, Madison, Wisconsin); Kirsten Bibbins-Domingo, PhD, MD (University of California, San Francisco, San Francisco, California); Susan J. Curry, PhD (University of Iowa College of Public Health, Iowa City, Iowa); Mark Ebell, MD, MS (University of Georgia, Athens, Georgia); Glenn Flores, MD (University of Texas Southwestern, Dallas, Texas); Francisco A.R. García, MD, MPH (Pima County Department of Health, Tucson, Arizona); Adelita Gonzales Cantu, RN, PhD (University of Texas Health Science Center, San Antonio, Texas); David C. Grossman, MD, MPH (Group Health Cooperative, Seattle, Washington); Jessica Herzstein, MD, MPH (Air Products, Allentown, Pennsylvania); Wanda K. Nicholson, MD, MPH, MBA (University of North Carolina School of Medicine, Chapel Hill, North Carolina); Douglas K. Owens, MD, MS (Veteran Affairs Palo Alto Health Care System, Palo Alto, and Stanford University, Stanford, California); William R. Phillips, MD, MPH (University of Washington, Seattle, Washington); and Michael P. Pignone, MD, MPH (University of North Carolina, Chapel Hill, North Carolina). Timothy Wilt, MD, MPH, a former USPSTF member, also contributed to the development of this recommendation.

† For a list of current Task Force members, go to www.uspreventiveservicestaskforce.org/members.htm.

References

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12 van der Meer AJ, Veldt BJ, Feld JJ, Wedemeyer H, Dufour JF, Lammert F, et al.  Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012;308:2584-93. [PMID: 23268517]

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16 Liu S, Cipriano LE, Holodniy M, Goldhaber-Fiebert JD.  Cost-effectiveness analysis of risk-factor guided and birth-cohort screening for chronic hepatitis C infection in the United States. PLoS One. 2013;8:e58975. [PMID: 23533595]

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20 American Academy of Family Physicians.  Clinical Preventive Services: Hepatitis. Leawood, KS: American Academy of Family Physicians; 2004. Accessed at www.aafp.org/online/en/home/clinical/exam/hepatitis.html on 24 May 2013.

Source

Also See: Expanded Hepatitis C Virus Screening Recommendations Promote Opportunities for Care and Cure