New Direct-Acting Antivirals Promising for Hepatitis C Treatment

Provided by HCPLive

By Debra Wood, RN | May 20, 2013

Antiviral hepatitis C drugs on the horizon could spur more people to accept treatment and improve patient outcomes, Andrew J. Muir, MD, MHS, associate professor of medicine and clinical director of hepatology at Duke University in Durham, NC, reported at Digestive Disease Week 2013, held May 18-21, 2013, in Orlando, Fla.

“It’s a great time in hepatitis C and for telling patients the great things that are going to come to help them,” Muir said.

According to Muir, approximately 3.2 million people have hepatitis C, and about half of the cases have been detected while one third have been referred to care. Only 5 percent to 6 percent of patients have been successfully treated, Muir said.

“I hope the new drugs and response rates will bring people out,” Muir said. “We need to be proactive to make that happen.”

The Centers for Disease Control and Prevention has recommended screening baby boomers for hepatitis C, but the U.S. Preventive Services Task Force has been less enthusiastic, issuing a Grade B recommendation for people at risk and a Grade C recommendation for people at average risk who were born between 1945 and 1965.

Muir indicated the field has been held back by the inability to prove treatment has saved lives. However, more recent studies have shown reductions in liver-related mortality and transplants.

“There is proof that effective treatment leads to improved clinical outcomes,” Muir said, later adding that “sustained virologic response rates show we can cure most people.”

But Muir noted there are still issues with side effects and treatment duration, which is currently 24 to 48 weeks. Muir called the infection rate found in the CUPIC (Compassionate Use of Protease Inhibitors in Cirrhotics) trial concerning, as more than half of the patients who had compensated cirrhosis and were taking the three drug regimen of pegylated interferon/ribavrin and telaprevir or boceprevir experienced a serious adverse event.

“The infection often began a cascade that led to their demise,” Muir said. He continues to use the therapies but indicated he has changed how he counsels patients to avoid scaring them off. Also, the U.S. Food and Drug Administration (FDA) has added a black box warning to telaprevir related to patients dying after a progressive rash and systemic symptoms.

The OPTIMIZE trial assessed whether a twice-daily regimen of telaprevir was as effective as a thrice-daily regimen when both are administered with pegylated interferon/ribavrin, and it found a similar outcome. Muir called twice-daily dosing a “reasonable option” for patients challenged by the thrice-daily regimen, though he cautioned that the FDA has not yet approved it.

Reporting on three new drugs — simeprevir, faldoprevir, and sofusbuvir — Muir noted, “We are starting to get more drugs demonstrating nice potency.” Clinical trials are also under way on interferon-free regimens. Since many patients continue to hold off on starting treatment because they are waiting for new options, Muir recommended educating them about liver wellness. For patients with significant liver disease, he suggested clinicians discuss benefits and risks and document the session.

With more treatment options in the pipeline, Muir called it an “amazingly wonderful time to be a physician in a liver clinic,” because patients have options and most who receive treatment can live well for years.

“Bottom line: Interferon-free treatments are at hand and just around the corner,” moderator Adrian M. Di Bisceglie, MD, FACP, FACP, Bander chair of internal medicine and chief of hepatology at the Saint Louis University School of Medicine, in Missouri, said after the session. He expects approvals for some uses as soon as the end of the year.

“When we have that, it will transform how we think about the treatment of hepatitis C,” Di Gisceglie added. “An easy, one- to two-drug treatment regimen — that’s what we are looking forward to.”

Source

Primary efficacy and safety findings from phase III study of Simeprevir in treatment-experienced patients demonstrate sustained virologic response

21-May-13 Stockholm, Sweden — Medivir AB (OMX: MVIR) reports that its partner Janssen R&D Ireland (Janssen) today announced primary efficacy and safety results from the global phase III PROMISE study. Results demonstrated that use of the investigational protease inhibitor simeprevir (TMC435) led to sustained virologic response 12 weeks after the end of treatment (SVR12) in 79 percent of treatment-experienced genotype 1 chronic hepatitis C adult patients with compensated liver disease, including all stages of liver fibrosis. Simeprevir was administered once daily with pegylated interferon and ribavirin.

In the study, 37 percent of patients receiving pegylated interferon and ribavirin (placebo) alone achieved SVR12. In the simeprevir arm, on-treatment failure rates were 3 percent and relapse rates were 19 percent, compared to 27 percent and 48 percent in the placebo arm. All patients had previously relapsed following pegylated interferon-based therapy.

The data were presented today as a late breaker oral presentation at Digestive Disease Week 2013 in Orlando, Florida based on abstract number 869b, “Simeprevir (TMC435) With Peginterferon/Ribavirin for Treatment of Chronic HCV Genotype 1 Infection in Patients Who Relapsed After Previous Interferon-Based Therapy: Results From PROMISE, a Phase III Trial.”

“We are very pleased with these data from this phase III study in relapsers. The data demonstrate high cure rates in these treatment-experienced patients. Together with the very good safety profile and the fact that a large proportion of the patients were eligible to end all treatments in a shorter time frame as compared to current standard of care, should provide new hope for large patient groups with this disease”, said Charlotte Edenius, EVP Research and Development, Medivir AB.

Study design
In PROMISE, patients were randomized to receive simeprevir or placebo for 12 weeks plus pegylated interferon and ribavirin for 24 or 48 weeks. In findings related to a secondary endpoint, 93 percent of patients receiving simeprevir were able to shorten therapy with pegylated interferon and ribavirin to 24 weeks as a result of meeting response-guided therapy (RGT) criteria. 83 percent of those patients meeting response-guided therapy criteria to stop treatment at 24 weeks achieved SVR12.

Patients enrolled in PROMISE were stratified by hepatitis C virus (HCV) genotype 1 subtype and IL28B genotype. SVR12 rates among patients treated with simeprevir according to IL28B genotype were 89 percent for the CC allele, 78 percent for the CT allele, and 65 percent for the TT allele, compared to 53 percent for the CC allele, 34 percent for the CT allele and 19 percent for the TT allele in the placebo arm.

Efficacy
Among patients with METAVIR scores F0 to F2, 82 percent of patients treated with simeprevir and 41 percent with placebo achieved SVR12. Among patients with METAVIR scores F3 and F4, 73 percent and 74 percent of patients treated with simeprevir and 20 percent and 26 percent treated with placebo achieved SVR12, respectively. The METAVIR score is used to quantify the degree of inflammation and fibrosis of the liver and patients are scored on a five-point scale.

Safety
The most common adverse events seen in patients receiving simeprevir in PROMISE were fatigue (32 percent versus 42 percent for placebo), headache (32 percent versus 36 percent for placebo) and influenza-like illness (30 percent versus 20 percent for placebo). In the simeprevir arm, rash (19 percent versus 14 percent for placebo), itching (24 percent versus 17 percent for placebo), neutropenia (15 percent versus 17 percent for placebo), anemia (11 percent versus 6 percent for placebo), increased bilirubin (6 percent versus 2 percent for placebo), and photosensitivity conditions (4 percent versus none for placebo) were also observed. One patient in the simeprevir arm and no patients in the placebo arm discontinued treatment due to an adverse event.

For more information please contact:
Rein Piir, EVP Corporate Affairs & IR
Mobile: +46 708 537 292

About PROMISE
PROMISE is a global, phase III, randomized, double-blind, placebo-controlled clinical trial assessing the efficacy, safety and tolerability of simeprevir plus pegylated interferon and ribavirin versus pegylated interferon and ribavirin alone in adult patients with genotype 1 chronic hepatitis C with compensated liver disease, including all stages of liver fibrosis, who relapsed after previous interferon-based therapy.

In the PROMISE trial, 393 patients were randomized to receive one 150 mg capsule of simeprevir or placebo once daily plus pegylated interferon and ribavirin for 12 weeks, followed by pegylated interferon and ribavirin alone for either 12 or 36 weeks based on response-guided therapy criteria. Patients in the simeprevir arm were considered to have met response-guided therapy criteria if their HCV RNA levels were

About Simeprevir
Simeprevir is an investigational NS3/4A protease inhibitor jointly developed by Medivir AB and Janssen R&D Ireland for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including all stages of liver fibrosis. Simeprevir works by blocking the protease enzyme that enables the hepatitis C virus to replicate in host cells. New drug applications were recently submitted for simeprevir in Japan and the United States for the treatment of genotype 1 hepatitis C, and a Marketing Authorisation Application was submitted to the European Medicines Agency seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C. The U.S. FDA has granted Priority Review to the New Drug Application. Janssen Pharmaceutical K.K. also recently announced the submission of a new drug application for simeprevir in Japan for the treatment of genotype 1 hepatitis C.

Global phase III studies of simeprevir include PROMISE in adult patients who have relapsed after prior interferon-based treatment, QUEST-1 and QUEST-2 in treatment-naïve adult patients, and ATTAIN in prior null-responder adult patients. In parallel to these trials, phase III studies for simeprevir are ongoing in treatment-naïve and treatment-experienced HIV-HCV co-infected patients and HCV genotype 4 patients.

Simeprevir is also being studied in phase II interferon-free trials with and without ribavirin in combination with:

· Janssen’s non-nucleoside inhibitor TMC647055 and ritonavir in treatment-naïve genotype 1a and 1b HCV patients;
· Gilead Sciences, Inc.’s nucleotide inhibitor sofosbuvir (GS-7977) in treatment-naïve and previous null-responder genotype 1 HCV patients; and
· Bristol-Myers Squibb's NS5A replication complex inhibitor daclatasvir in treatment-naive and previous null-responder genotype 1 HCV patients.

In addition, Janssen Pharmaceuticals, Inc. has entered into a non-exclusive collaboration with Vertex Pharmaceuticals to evaluate in a phase II study the safety and efficacy of an all-oral regimen of simeprevir and Vertex’s investigational nucleotide analogue polymerase inhibitor VX-135 for the treatment of HCV. As a first step, Janssen Pharmaceuticals, Inc. is conducting a drug-drug interaction (DDI) study with simeprevir and VX-135.

Janssen Pharmaceuticals, Inc. also has plans to initiate a phase II trial of an investigational interferon-free regimen with simeprevir, TMC647055 and Idenix’s IDX719, a once-daily, pan-genotypic NS5A inhibitor, with and without ribavirin.

For additional information about simeprevir clinical trials, please visit www.clinicaltrials.gov

About Hepatitis C
Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease and liver transplants, is a rapidly evolving treatment area with a clear need for innovative treatments. Approximately 150 million people are infected with hepatitis C worldwide, and about 350,000 people per year die from the disease. When left untreated, hepatitis C can cause significant damage to the liver including cirrhosis. Additionally, hepatitis C may increase the risk of developing complications from cirrhosis, which may include liver failure.

About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir, a novel protease inhibitor in late phase III clinical development for hepatitis C that is being developed in collaboration with Janssen R&D Ireland. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

For more information about Medivir AB, please visit the Company’s website: www.medivir.com
Medivir is a collaborative and agile pharmaceutical company with an R&D focus on infectious diseases and a leading position in hepatitis C. We are passionate and uncompromising in our mission to develop and commercialize innovative pharmaceuticals that improve people’s lives.
(http://www.medivir.com)

SVR associated with lower risk for diabetes in HCV

Provided by Healio

May 20, 2013

ORLANDO, Fla. — Patients with hepatitis C who achieve a sustained virologic response after treatment have a lower risk of developing type 2 diabetes, according to research presented here at Digestive Disease Week.

“There are intrahepatic factors and extrahepatic factors that link diabetes and HCV,” Sarah Hyder, MD, a gastroenterology fellow at Brown University, told Infectious Disease News. “Considering this link, we postulated that successful treatment of HCV could decrease the risk for new-onset diabetes in these patients.”

Hyder and colleagues used data from the Veterans Affairs Clinical Case Registry to identify patients with HCV, without pre-existing diabetes, who initiated antiviral treatment between 1998 and 2007. They evaluated the incidence of diabetes among patients who achieved sustained virologic response (SVR) and those who did not clear the infection.

Among the 27,636 patients, 7,617 (27.5%) achieved SVR and 15,243 (55.8%) did not. After a median follow-up of 5 years, 831 of the responders (11%) developed diabetes, and 2,428 of the non-responders (16%) developed diabetes. After controlling for known diabetes risk factors, SVR was independently associated with decreased incidence of new-onset diabetes (HR=0.77; 95% CI, 0.71-0.84). In addition, increasing age, non-white race, hypertension and cirrhosis were associated with an increased risk for new-onset diabetes.

“There are a lot of patients who don’t achieve SVR, either because they can’t tolerate treatment and discontinue, or because they have a resistant genotype of HCV,” Hyder said. “Hopefully, in the era of non-interferon based regimens, patients will be able to tolerate therapy better, and we’ll hopefully see an increased clearance rate and a decreased risk for HCV-associated diabetes. Successful treatment of HCV will provide significant benefits to health outcomes beyond liver-related morbidity and mortality.”

For more information:

Hyder S. #608. Presented at: Digestive Disease Week; May 18-21, 2013; Orlando, Fla.

Disclosure: Hyder reports no relevant financial disclosures.

Source

Nosocomial infections common in patients with cirrhosis

Provided by Healio

May 20, 2013

ORLANDO, Fla. — Most infections among patients with cirrhosis were nosocomial or health care-associated infections, according to study findings presented here at Digestive Disease Week. In addition, use of proton pump inhibitors was an independent predictor of these infections.

“Hospital-acquired and health care-associated infections are considered common in cirrhosis, but population-based data on the occurrence of these infections and their potential impact on outcome are limited,” Konstantina Sargenti, MD, of the department of gastroenterology at Skåne University Hospital in Sweden, said during a presentation. “Acute kidney injury and systemic inflammatory response syndrome indicate poor prognosis in cirrhosis, but it is unclear if they are more common in the presence of these infections.”

Sargenti and colleagues conducted a retrospective study that included all patients diagnosed with liver cirrhosis from 2000 to 2010, in an area with a population of approximately 250,000. They reviewed the patients’ medical records for information on infections, proton pump inhibitor use, acute kidney injury and systemic inflammatory response syndrome, and followed the patients until death, transplantation or the end of 2011.

Among the 344 patients with liver cirrhosis, 122 patients developed 230 bacterial infections: 66 were community-acquired (29%), 119 were health care-associated (51%) and 45 were nosocomial (20%). The most common infections were urinary tract infections (26%), spontaneous bacterial peritonitis (19%), pneumonia (16%) and spontaneous bacteremia (16%).

The researchers found that proton pump inhibitor use (OR=2.07; 95% CI, 1.05-4.06) and decompensated patient status (OR=1.78; 95% CI, 0.57-5.56) were related to nosocomial and health care-associated infections. These infections were not associated with inpatient mortality or systemic inflammatory response syndrome.

“Nosocomial infections appeared to have an impact on outcome as they were related to the occurrence of acute kidney injury and a prolonged length of hospital stay compared to health care-associated or community-acquired infections,” Sargenti said.

For more information:

Sargenti K. #515. Presented at: Digestive Disease Week; May 18-21, 2013; Orlando, Fla.

Disclosure: Sargenti reports no relevant financial disclosures.

Source

Fewer Kids Die While Waiting for New Organs

By Kathleen Struck, Senior Editor, MedPage Today

Published: May 20, 2013

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

• Fewer children died waiting for organ transplants in the past decade after policy changes to the national organ allocation system.
• Note that recipients of pediatic organ donation after circulatory determination of death increased, while recipients of pediatric donation after neurologic determination of death decreased over the study period.

Fewer children died waiting for organ transplants in the past decade after policy changes to the national organ allocation system, researchers stated.

The number of children dying before they could receive a transplant dramatically decreased from 262 to 110 as pediatric transplants increased from 2001 to 2010, stated Jennifer Workman, MD, of the University of Utah School of Medicine in Salt Lake City and colleagues, in Pediatrics.

The authors attributed major policy shifts for liver and kidney transplant protocols to the increase in transplants to children 17 and younger. Those organs compose the greatest percentage of solid-organ transplants in children, they noted.

Changes under the United Network for Organ Sharing (UNOS) allowed for increased transplantation from circulatory death donors while transplants from brain death donors decreased. UNOS is the private, non-profit organization that manages the nation's organ transplant system under the federal government, according to it website.

In fact, recipients of pediatric donation after circulatory determination of death (DCDD) increased by 174% (50 to 137), while recipients of pediatric donation after neurologic determination of death (DNDD) decreased by 13% (2,992 to 2,614), Workman and colleagues stated.

"The increased use of DCDD kidneys and livers for transplantation into children may be one method to increase the number of pediatric transplants," wrote Heung Bae Kim, MD, and Craig Lillehei, MD, of Harvard Medical School and Boston Children's Hospital in an accompanying commentary.

However, "efforts to pursue living donation as the primary option for kidney transplantation in children" should not be ignored, Kim and Killehei wrote.

Other changes included policies affecting pediatric liver transplants, a liver disease end-stage scoring system, and, regional sharing of pediatric liver donors.

"Our analysis suggests that these liver allocation changes improved access to transplantation for children with liver failure and support earlier reports which investigated the effect of the model for end-stage liver disease/pediatric end-stage liver disease scoring systems on pediatric liver transplantation," they wrote.

The authors obtained data from the Organ Procurement and Transplantation Network for U.S. organ recipients and donors from 2001 to 2010. Data were stratified by age, organ, and DCDD, and transplant wait-list removals due to death.

The criteria for donors for pediatric kidney transplants was expanded, giving pediatric recipients priority to kidney donors younger than 35. Pediatric kidney transplants increased an average 61 per year, the authors wrote.

"The kidney shortage remains an enormous problem for the transplant community, and allocation strategy changes to maximize donor kidney utilization are currently being assessed," they wrote.

The authors noted that adult recipients far outnumber child recipients, while adult donors are more numerous than child donors.

The innovative techniques of split, live donor, and reduced liver grafts have increased the number of donations to transplants and decreased waiting times, the authors wrote, although data are conflicting about outcomes.

Interestingly, when a liver is split for size and first offered to a child, the other half typically goes to an adult recipient. However, if a liver is first offered to an adult, no regulations require that the adult be asked to split the liver with a child.

"To increase the availability of split livers from organs offered primarily to adults, adult transplant teams need to place greater importance on this option," the authors said.

In the time period the authors assessed, 14,221 children received organ transplants from deceased donors. The transplant universe was broken down as:

• Pediatric organ transplants increased from 1,170 to 1,475, peaking at 1,628 in 2009
• Pediatric recipients increased 799 to 971
• Pediatric donor organs used for transplantation decreased from 3,042 to 2,751
• Pediatric donors decreased from 987 to 841
• Pediatric transplant donors to adult recipients decreased 2,243 to 1,780

The majority of pediatric donor organs are still transplanted into adults, specially DCDD organs that are used almost exclusively for adult recipients.

"Although it is true that pediatric donation (both DCDD and DNDD) does not always directly benefit other children, improving the overall process of donation and increasing organ recovery allows for more pediatric transplants and fewer pediatric wait-list deaths," the authors wrote.

The study had some limitations. The data were not indexed for population growth and some of the increased rates of donation and transplantation seen in the study years could be attributed to an increase in the overall population. Also, the database identifies donor organs allocated, not individual donors. Organs from a single donor can be used in up to eight individuals, the authors pointed out.

Finally, "during the study period, advances in the medical management of patients have evolved, allowing some of these children to improve and either delay or not require transplantation," they said.

Workman reported no conflicts of interest. Co-authors reported relationships with the Organ Donation and Transplantation Alliance and Up To Date. The authors reported no external funding.

Kim and Lillehei have served on the Board of the New England Organ Bank and several committees within UNOS. They reported no external funding.

Primary source: Pediatrics
Source reference:
Workman J, et al "Pediatric Organ Donation and Transplantation" Pediatrics 2013; DOI: 10.1542/peds.2012-3992.

Additional source: Pediatrics
Source reference:
Kim H, Lillehei C "Organ Donation for Children: The Road Ahead" Pediatrics 2013; DOI: 10.1542/peds.2013-1005.

Source

Clinical Pointers on Rapid Home-Use HIV Testing

CDC Expert Commentary

Philip J. Peters, MD

May 20, 2013

On July 3, 2012, the US Food and Drug Administration approved the OraQuick® In-Home HIV Test, a rapid home-use HIV test kit that can be purchased over the counter and online. The kit provides a test result in 20-40 minutes and allows patients to conduct a self-test in their own home. The kit, which tests a sample of fluid from the mouth, is approved for sale in stores and online to anyone age 17 years and older.

Given the availability of a home-use HIV test, should primary care clinicians advise their patients to use this test, and in what situations is it expected to be most useful?

The Centers for Disease Control and Prevention (CDC) recommends HIV screening for all persons aged 13-64 years, regardless of risk, in healthcare settings where the prevalence of undiagnosed HIV is ≥ 0.1% or the yield of screening is at least 1 new HIV infection identified per 1000 persons screened.^[1]

Annual HIV testing is recommended for those at high risk for HIV infection. The best approach for patients is to go to a physician and get tested as part of regular medical care, which is what the CDC recommends. Home-use self-testing is not a substitute for getting tested by a healthcare provider. Primary care clinicians should continue to encourage their patients to get tested for HIV.

Some patients might be reluctant or reticent to test for HIV with their provider or prefer the convenience of HIV testing at home.^[2] Having access to a home-use, over-the-counter HIV test could lead to increased HIV testing and earlier HIV diagnoses among people who are not currently getting tested for HIV. If so, it will be an important advance.

Some patients at high risk for HIV infection may benefit from frequent (every 3-6 months) HIV testing. For these patients, home-use self-testing might be convenient.

How should physicians counsel patients who use the home-use HIV test?

It is important for patients to read and follow the test instructions carefully. Performing the test incorrectly can result in an invalid (uninterpretable) test result. In a clinical study, 1% of people who took the test did not get an interpretable test result.^[3] A 24/7 support center toll-free number is provided with the test instructions in case there are any questions about how to perform the test correctly. Patients should be aware that in a clinical study, the home-use HIV test did not detect every HIV infection. Among people determined to have HIV infection, approximately 1 in 12 had a negative home-use HIV test result (8% rate of false negative results),^[3] so patients should be counseled that a negative home-use HIV test result does not completely rule out HIV infection. Compared with a blood test performed by a healthcare provider, there is a trade-off for the convenience of self-testing oral fluid at home.

Patients should also be aware that this test does not detect recent HIV infection. This test detects antibodies against HIV approximately 3 months after infection occurred. Patients who are concerned about very recent HIV exposure should discuss this with their healthcare provider to determine whether medication to prevent HIV infection (eg, antiretroviral postexposure prophylaxis for HIV exposures within 72 hours) or diagnostic tests for early HIV infection (eg, a fourth-generation combination HIV antigen/antibody test or an HIV RNA test) are indicated.

Is additional HIV testing recommended for patients who report a positive home-use HIV test result?

Like any rapid test, a positive or reactive home-use, over-the-counter HIV test is a preliminary positive result that needs to be confirmed with additional testing. HIV testing always involves at least 2 tests. Patients who report a positive home-use HIV test should be counseled that they have a preliminary positive test result and must have blood drawn and sent to a laboratory for HIV testing to determine whether HIV infection is truly present or whether the test result is a false positive. (In clinical studies, only 1 false positive result occurred in 4903 tests on HIV-negative people.^[3]) Patients with a confirmed positive HIV test result should be immediately referred for HIV medical care.

Given the high rate of false negative results, when should a clinician consider retesting a patient who reports a negative home-use HIV test result?

Self-testing for HIV at home is not intended as a substitute for going to a healthcare provider and getting tested. Patients who are concerned that they might have been exposed to HIV should be offered an HIV test even if they report a negative home-use test result. The clinical trials showed that the home-use HIV test was positive in 92% of persons who were infected. This is not as accurate as a blood test performed by a healthcare provider. Also, the home-use HIV test does not detect recent HIV infection (less than 3 months after exposure). Some laboratory tests (fourth-generation combination antigen/antibody tests or HIV RNA tests) can detect HIV as soon as 10-14 days after infection. Patients who might have been exposed to HIV very recently (that is, within 72 hours) also should be evaluated for possible use of postexposure prophylaxis with antiretroviral drugs. In addition, patients with ongoing potential exposures to HIV infection should be retested at least annually. Some patients, such as sexually active men who have sex with men, might benefit from testing as often as every 3-6 months. Therefore, the decision to repeat HIV testing should be based on the patient's specific circumstances.

How should clinicians advise partners of high-risk individuals about taking the home-use HIV test?

Partners of people at high risk for HIV infection are an important group to test for HIV infection. Clinicians with patients at high risk for HIV infection should encourage them to discuss HIV testing with their partners and urge their partners to be tested for HIV infection as well. Ideally, these partners could come to your office and receive HIV testing as part of their medical care. Further information on finding an HIV testing site is also available online. Some partners, however, may be reluctant or reticent to test for HIV because of perceived stigma or other reasons. In addition, some couples may prefer to test together, and HIV testing at home offers a convenient way to do that. Patients should be reminded that self-testing for HIV at home does not detect recent HIV infection (less than 3 months after exposure). Because individuals with recent HIV infection are at especially high risk for transmitting HIV infection to their partners, a negative home-use HIV test should not be used to make decisions about behaviors, such as having unprotected sex, that might place them at risk for HIV.

Web Resources

For information on CDC's HIV screening recommendations in healthcare settings: http://www.cdc.gov/actagainstaids/hssc/index.html

For general information on HIV testing: http://www.hivtest.org/

For general information on HIV infection: http://www.cdc.gov/hiv/default.htm

Philip J. Peters, MD, DTM&H, is a Medical Officer with the Division of HIV/AIDS Prevention, US Centers for Disease Control and Prevention, in Atlanta, Georgia. Dr. Peters is the activity leader for HIV testing in the Division of HIV/AIDS Prevention's Epidemiology Branch. He is responsible for conducting epidemiologic and biomedical research activities to evaluate acute HIV infection and important HIV-related coinfections such as Staphylococcus aureus, influenza, and hepatitis B virus. Dr. Peters received his medical degree from Cornell University Medical College. He completed his clinical training in internal medicine at Massachusetts General Hospital and his clinical training in infectious diseases at Emory University. He began his career at the CDC in 2006 when he joined as an Epidemic Intelligence Service Officer. His professional interests include improving HIV diagnosis in the clinical setting.

References

Source

Recent Advances in the Treatment of Chronic Hepatitis C Threaten to Leave Some Parts of the World Behind

Journal of Viral Hepatitis

What About Us?

Recent Advances in the Treatment of Chronic Hepatitis C Threaten to Leave Some Parts of the World Behind

F. Ahmed

J Viral Hepat. 2013;20(5):367-368.

Directly acting antiviral (DAA) agents are currently revolutionizing the treatment of chronic hepatitis C infection. The first generation of these agents have significant limitations including cost issues that are of particular concern in the developing world and a lack of efficacy in genotype 3 patients. Both of these concerns are of particular relevance in Pakistan.

One cannot attend any major international liver conference over the past 1 year and not be struck by the vast array of new directly acting antiviral (DAA) agents currently in the pipeline. Telaprevir and boceprevir have already been licensed for use in Western countries. Although these and other agents will revolutionize the treatment of chronic hepatitis C, these advances threaten to leave some parts of the world, the developing world in particular, and a large proportion of the world's hepatitis C burden, behind.

Pakistan is a case in point. Recent epidemiological data suggest that 4.9% of the Pakistani populace is chronically infected with hepatitis C.^[1] With an overall population estimated at 180 million, this translates into approximately 9 million hepatitis C patients. On a positive note, >65% of these infections are genotype 3. But many patients struggle to pay for the 6-month course of standard interferon-based therapy; some having to sell their jewellery, homes and livestock to do so. The fivefold price difference between standard and pegylated interferon is an insurmountable hurdle for many patients here, where health insurance does not exist and where the average person makes $650 per year. Owing to cost considerations and comparable efficacy, the Pakistan Society of Gastroenterology recommends that the first-line therapy for these genotype 3 patients be standard interferon and ribavirin. A genotype 3 predominance, however, may also have a downside given that recent studies have suggested the genotype 3 is associated with accelerated fibrosis progression.^[2] This is particularly consequential in a developing country, like Pakistan, where no liver transplantation program exists and where most cirrhotics lack the resources to travel abroad for liver transplant.

Where will these new DAA agents fit into the picture here? The minority of patients who have genotype 1 and those with genotype 3 who do not respond to conventional therapy could be considered candidates for newer therapies. However, given that patients here often struggle to pay for interferon-based therapy, the ability to pay for a third additional agent seems unlikely at best. Even if money was not an issue, in Pakistan, at least, the applicability of the first generation of direct-acting antiviral agents that have hit the market would be limited at best. In contrast to their spectacular results in hepatitis genotype 1 patients, telaprevir and boceprivir have limited activity against genotype 3.^[3] It is still unclear whether other agents in development will have the same genotype barriers seen with telaprevir and boceprevir. Preliminary data suggest good activity against genotype 3 of nucleoside polymerase inhibitors and cyclophilin inhibitors, but not non-nucleoside polymerase inhibitors.^[4]

Are there lessons to be learnt here? First of all, it highlights the need in Pakistan and other parts of the developing world to focus on prevention. If we cannot afford to treat these infections, perhaps the wiser approach is to try and prevent them from occurring in the first place. The vast majority of hepatitis C infections in Pakistan occur because of unsafe injections.^[5] This phenomenon has also been recognized in other parts of the developing world.^[6] We need to do a better job in maximizing the outcomes from the existing interferon and ribavirin regimen. Finally, hepatologists in developing countries need to do a better job of leveraging their hepatitis C patient volumes into clinical trials and perhaps drug development that is more relevant to their unique clinical scenarios.

A scenario may develop where hepatitis C is largely eradicated from the developing world but exits in large pockets in developing countries. Given current patterns of human migration, however, increasing numbers of these hepatitis C patients could be projected to arrive on the shores of Europe and North America.^[7] Chronic hepatitis C is a truly global problem and needs to be addressed as such. Furthermore, if the treatment of hepatitis C evolves into a multidrug antiviral combination^[8] similar to that for HIV, it is not difficult to foresee struggles over patents and intellectual property rights analogous to those that occurred in Sub-Saharan Africa in the 1990s and the early part of this decade over HIV drugs.

From my perspective, sitting in my office in Karachi, Pakistan, the new directly acting antiviral agents represent an exciting leap forward in the field of hepatitis C virology but are not obviously clinically relevant to my practice. Issues relating to cost, access and applicability will affect hepatologists in the developing world, in particular, in the coming years. Further advances in this field need to take into account the global hepatitis C burden. Perhaps most importantly, a greater emphasis on prevention is needed. My colleagues and I need to do a better job of marketing our 9 million Pakistani hepatitis C patients to make them more attractive to drug companies involved in new drug development and international aid donors, as do hepatologists in other parts of the developing world. For now, I will have to be content with marvelling at the science behind these new discoveries and envy those hepatologists who have access to new tools in the fight against this global menace.

References

1. Mohsin M, Qureshi H. The first prevalence report on hepatitis B and C in Pakistan. Pak J Gasroenterol 2011; 25(1): 5–7.

2. Bochud PY, Cai T, Overbeck K et al. Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C. J Hepatol 2009; 51: 655– 666.

3. Foster GR, Hézode C, Bronowicki JP et al. Telaprevir alone or with peginterferon and ribavirin reduces HCV RNA in patients with chronic genotype 2 but not 3 infections. Gastroenterology 2011; 141(3): 881–889.

4. Soriano V, Peters MG, Zeuzem S. New therapies for hepatitis C virus infection. Clin Infect Dis 2009; 48: 313–320.

5. Jafri W, Subhan A. Hepatitis C in Pakistan: magnitude, genotype, disease characteristics and therapeutic response. Trop Gastroenterol 2008; 29(4): 194–201.

6. Saleh DA, Shedl FM, AL-Kamary SS et al. Incidence and risk factors for community acquired hepatitis C infection from birth to 5 years of age in rural Egyptian children. Trans R Soc Trop Med Hyg 2010; 104: 357–363.

7. Ahmed F, Foster GR. Global hepatitis, migration and its impact on western healthcare. Gut 2010; 59(8): 1009–1011.

8. Gane EJ, Roberts SK, Stedman CAM et al. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomized, double-blind, placebo-controlled, dose-escalation trial. Lancet 2010; 376: 1467–1475.

Source

Pharmaceutical advances offer new options for health outcomes

Public release date: 20-May-2013

Contact: Aimee Frank
newsroom@gastro.org
407-685-4030
Digestive Disease Week

Research presented at DDW® 2013 feature new drugs for IBS, hepatitis C

Orlando, FL (May 20, 2013) — Research presented at Digestive Disease Week® (DDW) explores pharmaceutical advances for treating irritable bowel syndrome with diarrhea (IBS-D) and hepatitis C.

An international study holds promising results for patients suffering from IBS-D. In the phase II study, researchers found that the drug ibodutant significantly improved symptoms in more than 50 percent of the individuals treated.

"While there's been a lot of progress in medicines for IBS with constipation, we haven't seen the same in IBS with diarrhea," said Jan Tack, MD, professor and director of the division of gastroenterology and internal medicine at Leuven University in Belgium. "Up to this point, we haven't been able to provide a pharmaceutical option for this patient group that successfully manages the pain associated with the condition."

IBS is an extremely common condition, affecting an estimated 10 percent of adults. Funded by Menarini, the double-blind, multinational study recruited 559 patients with IBS-D who were randomized and treated with 1, 3 or 10 mg of ibodutant or a placebo. Patients took an oral tablet once daily for eight consecutive weeks. Researchers found that 10 mg was the most effective dose and that it worked best for females.

"These are exciting findings that could bring a lot of relief to many patients," said Dr. Tack said. "We're looking forward to moving into phase III to confirm our findings with a much larger sample of patients."

New therapy for patients with hepatitis C examined

New research suggests that an investigational therapy for patients with hepatitis C can achieve high response rates in a wide range of patients, even those who respond poorly to current treatments. The study examined the safety and efficacy of interferon-free regimens, including three direct-acting antiviral drugs with and without ribavirin, for 12 or 24 weeks, in patients with chronic hepatitis C who were either treatment-naïve or had previously failed standard treatment with peginterferon and ribavirin.

In the phase II study, researchers found that the treatment regimens achieved high sustained virologic response (SVR) rates, an efficacy measure of a hepatitis C treatment, in non-cirrhotic patients with HCV genotype-1 (GT 1). SVR was achieved by 98.7 percent of treatment-naïve patients and 93.3 percent of prior nonresponders after 12 weeks of treatment with three direct-acting agents with ribavirin.

"Hepatitis C genotype 1 is the most common type of hepatitis in the U.S., and many of these patients are still quite difficult to treat with current interferon-based therapies," said Frederick Nunes, MD, clinical associate professor of medicine at Penn Medicine. "This includes specific populations such as African Americans and patients with high body mass or pre-diabetes. These results suggest that highly effective regimens like this one may overcome that difficulty, without the need for interferon."

###

Assigning 247 patients to 12- or 24-week regimens, researchers found that four weeks after treatment, SVR rates were high regardless of patient characteristics previously associated with poorer response to interferon therapy. Funded by AbbVie (formerly Abbott), the study's results hold particular significance for patients who are older, black, Hispanic or have a higher body mass index.

Dr. Tack will present data from the study "Efficacy of ibodutant, a selective antagonist of neurokinin 2 receptors, in irritable bowel syndrome with diarrhoea (IBS-D): the results of a double-blind, randomised, placebo-controlled, parallel-group phase II study (The IRIS-2)," abstract 520, on Monday, May 20, at 8 a.m. ET in Room 300 of the Orange County Convention Center.

Dr. Nunes will present data from the study "Interferon-free Regimens of ABT-450/r, ABT-267, ABT-333, and Ribavirin Achieve High Sustained Virologic Response 4 Weeks Post-Treatment (SVR4 ) Rates in Patients With Chronic HCV Genotype 1 Regardless of Race, Ethnicity, or Other Baseline Characteristics" abstract 514, on Monday, May 20, at 8 a.m. ET in Room 203AB of the Orange County Convention Center.

Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place May 18 to 21, 2013, at the Orange County Convention Center, Orlando, FL. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. More information can be found at http://www.ddw.org.

Follow us on Twitter @DDWMeeting; hashtag #DDW13. Become a fan of DDW on Facebook.

Source

Help on Wheels for Philly's Public Health 'Time Bomb,' Hepatitis C

Provided by Philadelphia City Paper

Neal Santos

TEST DRIVES: At a recent free mobile screening, (from left) Ta-Wanda Preston and Gladys Thomas tend to Danielle Parks.

Posted: Thu, May. 16, 2013, 12:00 AM

An innovative mobile lab brings testing to highest risk neighborhoods.

Samantha Melamed

City Paper

Stepping out of the high-tech medical lab on wheels and into a sunny afternoon in the projects, McHale Colman, 28, doesn’t seem to notice that he has experienced something revolutionary.

“Anytime I see these buses, I try to come get tested and get it out of the way,” he says with a shrug. “I jump on it: It’s private, I don’t got to go nowhere, I’m in the ’hood.”

After all, free mobile screening programs have become common sights in neighborhoods like this one — Bartram’s Village in Southwest Philly — as public-health organizations try to capture poor residents who tend not to access regular primary care.

But the lab that Colman visited is unique: It’s the first in Philadelphia — and possibly the first in the nation — to pair rapid HIV testing with rapid hepatitis C testing, follow-up confirmatory testing and immediate connections to care. The program, called Do One Thing, is spearheaded by Amy Nunn, a medical researcher at Brown University. It rolled out with HIV tests last summer and added hepatitis C in December, targeting hot spots in Southwest Philly zip codes where the rates of HIV infection are among the highest in Philly — in fact, higher than in some countries in Africa. (Risk is increased due to factors like intravenous drug use or unregulated tattooing, such as in prison or at “tattoo parties.”) The van is out three days a week, sending outreach workers knocking on doors, handing out flyers and explaining those alarming statistics, working toward a goal of testing 12,000 area residents.

It’s an aggressive approach to a disease that Philly Health Commissioner Donald Schwarz recently called a “time bomb” — particularly if Gov. Tom Corbett doesn’t agree to Medicaid expansion in Pennsylvania. “There will be a very large number of people in Philadelphia who will require diagnosis and treatment for hepatitis C. We have been trying to do something about this epidemic that is invisible for the moment,” Schwarz told City Council recently. Hepatitis C is about five times more prevalent than HIV nationwide, but infected people can remain asymptomatic for years, often to be diagnosed only after severe liver damage, including cancer or cirrhosis, has occurred.

Now, with an aging baby boomer population expected to manifest hepatitis C in record numbers over the coming decade, public-health officials are worried. “This could be really costly to the health-care system, in terms of liver transplants, or you’ll have a lot of people potentially dying,” says Philly viral hepatitis prevention coordinator Alex Shirreffs. “There’s definitely a concern that if we don’t start paying attention to hepatitis C, we’re going to be catching people too late.”

But experts are also hopeful. The past few years have been a time of extraordinary progress in the diagnosis and treatment of hepatitis C, bringing the creation of a rapid test, new Centers for Disease Control (CDC) screening guidelines and radically improved treatment regimens that have doubled cure rates among the hardest-to-treat patients. Here in Philly, Do One Thing is just one of several public-health innovations around hepatitis C, including an unprecedented viral-surveillance initiative, a planned public-awareness campaign and a behind-the-scenes effort to educate doctors about new standards of care.

As of now, though, there’s still very little money to go around — not for treatment and not even for screenings. So, for example, while the rapid test was hailed as a major advancement when it was released in 2011, “unfortunately, because the [federal] government didn’t provide a lot of funding for governments to deliver rapid tests, it didn’t … get many done,” says Shirreffs.

In Philly, at least, all that could change, says Drexel professor Dr. Stacey Trooskin, who leads the hepatitis-C component of Do One Thing and, with Shirreffs, co-chairs the year-old, so-far-unfunded coalition Hepatitis C Allies of Philadelphia (HEP CAP). “We’re really focused on trying to put Philadelphia on the map as a city that is facing hepatitis C head on, and trying to address it as the public-health issue that it is.”

To that end, Do One Thing isn’t the only program pushing hep-C screenings: Philadelphia Health Management Corp., for one, is running a pilot effort funded by the CDC. But there’s hope that Do One Thing’s model — which brings testing to the most affected neighborhoods — just might launch a national movement.

Still, to get a program like this up and running means facing numerous regulatory and technical hurdles. In Nunn’s case, those included identifying a lab that could process confirmatory blood tests — a challenge because blood has to be analyzed within six hours of being drawn, and the van keeps late-night and Saturday hours. But the tests are necessary because one in five people who initially test positive do not have chronic infections.

Then there was the problem of connecting those who test positive to care — which can be hard when phone numbers are disconnected or housing is unstable. That’s why the same-day tests results are so important, Nunn says: Otherwise, “You lose a lot of patients to follow-up.” And, finally, there’s what Nunn calls “the real bugaboo”: paying for treatment. Hepatitis C is increasingly curable, but a 12-week course of Incivek, one of the newer drugs, is priced at a jaw-dropping $49,200.

So far, most of the people who’ve been diagnosed on the Do One Thing van have either had insurance or been Medicaid eligible — linkage-to-care coordinators can help them apply — and they’ve all been connected to care. Some people who know they’re positive come in for testing anyway, Nunn says, and get linked to care again. Up to now, Do One Thing has administered 3,000 HIV tests (about 1.3 percent positive) and 550 hepatitis C tests (5.5 percent positive).

The CDC has shown interest in the Do One Thing approach, Nunn says. The federal public-health agency is now two years into its own hepatitis C action plan, which among other things designated age-based screening guidelines. The CDC suggests people aged 47 to 67 get tested; previously, tests were based on risk factors alone.

Epidemiologists considered that change a victory — but in some cases an empty one. Today, Trooskin says, “Primary-care providers are just not testing.” Even the city’s own health centers, which offer risk-based screening, don’t routinely follow the CDC guidelines.

“There’s a lot of misconceptions among primary-care providers about what treatment is available and who’s eligible for it. A lot of primary-care providers aren’t aware that hepatitis C is curable, and they certainly aren’t aware of the rapidly evolving treatment paradigm,” Trooskin says, noting that several experimental treatments offer hope for a 90 percent cure rate. “To get that message out to primary-care providers is really important. Even if [patients are] not treatment candidates today, they may be in a year or two.”

HEP CAP has been getting experts to visit primary-care practices beginning this month and provide education on the guidelines, treatment and referral options.

But more targeted efforts remain elusive, since, as Trooskin puts it, “What we know about the epidemiology of hepatitis C is really the tip of the iceberg.” That could soon change, since Philly was one of seven cities nationwide to receive a federal viral-hepatitis-surveillance grant to study the city’s epidemic. “This idea of a neighborhood-based approach, going out into the community and linking individuals to care, is really going to be the next frontier when it comes to finding individuals that are [hepatitis C] positive but are not currently in care or are unaware of their infection,” Trooskin says. “I don’t think we can just wait for folks to come into the doctor’s office. We need to be out in the community.”

Source

EASL 2013: New Wave of Hepatitis C Treatments On the Way

May 13, 2013, by Liz Highleyman

Studies presented at the EASL International Liver Congress, held April 24–28 in Amsterdam, confirm the expectation that a new generation of safer and more effective therapies for hepatitis C will be available within the next few years. These include both better add-ons to interferon and the first interferon-free combinations of direct-acting antivirals (DAAs).

An estimated three million people in the U.S. have hepatitis C, but most do not know they’re infected. The CDC this week reiterated its recommendation that all “baby boomers” born between 1945 and 1965 get a test for HCV antibodies and, if positive, a viral load test to determine if they’re still infected. “You may not remember what you did in the 60s and 70s, but your liver does,” said CDC director Thomas Frieden.

Testing is crucial because chronic HCV infection can lead to cirrhosis, liver cancer, and death. Now is a good time because better hepatitis C treatments that can stop liver disease progression are on the way.

Interferon Add-Ons

The current standard of care adds one of the first approved DAAs—boceprevir (Victrelis) or telaprevir (Incivek)—to pegylated interferon and ribavirin. Triple therapy works better than interferon/ribavirin alone, but comes with added side effects.

Some people with advanced liver disease cannot wait for better options, but data presented at the EASL meeting show that these regimens carry a high risk of serious complications for patients with cirrhosis and liver transplant recipients.

For people who can wait a bit longer, several studies showed promising outcomes when adding more effective and better-tolerated second-generation DAAs to interferon-based therapy:

• Daclatasvir (HCV NS5A inhibitor)
• Faldaprevir (HCV protease inhibitor)
• MK-5172 (HCV protease inhibitor)
• Simeprevir (HCV protease inhibitor)
• Sofosbuvir (nucleotide analog HCV polymerase inhibitor)
• Vaniprevir (HCV protease inhibitor)

These new drugs produced cure rates in the 80% to 90% range even for difficult-to-treat patients. They can often shorten treatment to three to six months (down from six months to a year) and generally do not cause more side effects than interferon and ribavirin alone. (For more detailed coverage of this study and others presented at EASL 2013, visit HIVandHepatitis.com.)

“DAAs are ready for prime time,” EASL Secretary General Mark Thursz said at an April 24 press conference kicking off the congress.

The first new DAAs are expected to become available by late 2013 or early 2014, initially for use with interferon. Simeprevir and sofosbuvir were submitted for FDA approval in March and April, with a review timeline of six months.

“Interferon is not dead yet,” Thursz emphasized. “Twelve weeks of an interferon triple regimen is tolerable for a large number of patients…and it may be better than waiting another year for a suitable all-oral regimen.”

Interferon-Free Combos

People with early or stable liver disease may be able to wait for all-oral regimens that eliminate interferon, which can cause flu-like symptoms and depression. Some combos also dispense with ribavirin, which can cause anemia.

All-oral regimens have gotten the lion’s share of attention at recent conferences (including the Conference on Retroviruses and Opportunistic Infections in March). While several interferon-free regimens continue to look good, enthusiasm at EASL was somewhat tempered by setbacks among difficult-to-treat patients.

A quad regimen containing DAAs developed by AbbVie (formerly Abbott)—HCV protease inhibitor ABT450 boosted with ritonavir + NS5A inhibitor ABT-267 + non-nucleoside polymerase inhibitor ABT-333 + ribavirin—cured 96% of treatment-naive patients with HCV genotype 1 and 93% of prior interferon non-responders treated for 12 weeks in the Aviator study.

This combo is especially promising because it worked for more than 90% of previously untreated or treatment-experienced patients, people with harder-to-treat HCV subtype 1a or easier-to-treat 1b, and those with mild or moderate liver fibrosis, though people with cirrhosis—who have the poorest response—were excluded.

AbbVie announced this week that the FDA has given this regimen a “breakthrough therapy” designation, intended to speed development and review of promising drugs for serious or life-threatening conditions.

Gilead’s sofosbuvir/ribavirin 12-week dual regimen previously demonstrated 100% sustained virological response (SVR) for previously untreated people with HCV genotypes 2 or 3 and no liver cirrhosis. SVR at 12 or 24 weeks after completing treatment (known as SVR12 and SVR24) is considered a cure.

But researchers at EASL reported lower cure rates in the larger treatment-naive FISSION and treatment-experienced FUSION trials, in which 20%–30% of participants had cirrhosis. SVR12 rates were 67% using a 12-week regimen in FISSION, and 50% with a 12-week regimen or 73% with a 16-week regimen in FUSION.

The major surprise was that people with genotype 2 and genotype 3—usually considered together as a single “easier-to-treat” category compared with genotype 1—responded differently.

Among those with genotype 2, SVR rates were excellent: 97% in FISSION and 86%–94% in FUSION. People with genotype 3 did not fare as well, with cure rates of 56% and 30%–62%—no better than pegylated interferon/ribavirin. The difference was even more pronounced among people with cirrhosis, with cure rates falling as low as 34% in FISSION and 19% in FUSION.

Presenter Edward Gane from Auckland City Hospital suggested that genotypes 2 and 3 should no longer be lumped together, as genotype 3 is “behaving as a harder-to-treat virus.”

Turning to genotype 1, further results from the ELECTRON trial confirmed that sofosbuvir/ribavirin alone is not adequate for such patients. Adding the NS5A inhibitor ledipasvir, however, raised the cure rate to 100% for both treatment-naives and prior null responders.

Gilead announced last week that a coformulation of sofosbuvir/ledipasvir without ribavirin for eight or 12 weeks led to 95%–100% sustained response at four or eight weeks post-treatment—promising, but too soon to declare a cure.

Study findings reported in 2012 showed that sofosbuvir plus Bristol-Myers Squibb’s NS5A inhibitor daclatasvir cured 100% of treatment-naive genotype 1 patients. Gilead decided not to pursue this combination in Phase 3 trials in favor of its own ledipasvir, but some smaller studies have gone forward.

Mark Sulkowski from Johns Hopkins University reported that sofosbuvir plus daclatasvir cured all previously treated genotype 1 patients who did not respond to interferon-based triple therapy using boceprevir or telaprevir, providing some of the first data on “rescue therapy” after failure of the current standard-of-care.

Finally, a three-drug DAA combo containing daclatasvir, the HCV protease inhibitor asunaprevir, and the non-nucleoside polymerase inhibitor BMS-791325, taken for 12 or 24 weeks, cured 88%–94% of previously untreated genotype 1 patients without cirrhosis, with treatment “failures” mostly due to missing data rather than viral breakthrough or relapse.

Taken together, these findings add to the evidence that effective and well-tolerated DAA therapy will be able to cure most people with chronic hepatitis C within the coming years.

“If a patient has early stage [liver disease], lots of physicians are recommending their patients wait” for all-oral regimens, Thursz summarized. For those with more advanced disease, “treating with the standard of care is probably the way to go”—unless they have very advanced disease, in which case they have “significant risk of dying from septic complications” if treated with current triple therapy.

Liz Highleyman (liz (at) hivandhepatitis.com) is a freelance medical writer and editor-in-chief of HIVandHepatitis.com.

Selected Sources

AbbVie. AbbVie’s Investigational HCV Regimen Receives Breakthrough Therapy Designation from the U.S. Food and Drug Administration. Press release. May 6, 2013.

Bristol-Myers Squibb. High Rates of SVR Demonstrated in Phase II Study with Investigational Triple DAA Regimen of Daclatasvir, Asunaprevir and BMS-791325 in Treatment-Naive Patients with Genotype 1 Chronic Hepatitis C Infection. Press release. April 23, 2013.

Everson, G. and others. Interim analysis of an interferon (IFN)- and ribavirin (RBV)-free regimen of daclatasvir (DCV), asunaprevir (ASV), and BMS-791325 in treatment-naive, hepatitis C virus genotype 1-infected patients. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24–28, 2013. Abstract 1423.

Ferenci, P. and others. Faldaprevir plus pegylated interferon alfa-2A and ribavirin in chronic HCV genotype-1 treatment-naive patients: final results from STARTVerso1, a randomised double blind placebo-controlled phase III trial. Abstract 1416.

Fontaine, H. and others. SVR12 rates and safety of triple therapy including telaprevir or boceprevir in 221 cirrhotic non responders treated in the French Early Access Program (ANRS CO20-CUPIC). EASL 2013. Abstract 60.

Gane, E. and others. Phase 3 randomized controlled trial of all-oral treatment with sofosbuvir+ribavirin for 12 weeks compared to 24 weeks of peg+ribavirin in treatment-naive GT2/3 HCV-infected patients (FISSION). EASL 2013. Abstract 5.

Gane, E. and others. All-oral sofosbuvir-based 12-week regimens for the treatment of chronic HCV infection: the ELECTRON study. EASL 2013. Abstract 14.

Gilead Sciences. Gilead reports interim data from Phase 2 LONESTAR study. Press release. May 2, 2013.

Jacobson, I. and others. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. New England Journal of Medicine. April 23, 2013 (Epub ahead of print).

Jacobson, I. and others. Treatment with sofosbuvir+ribavirin for 12 weeks achieves SVR12 of 78% in GT2/3 interferon-ineligible, -intolerant, or -unwilling patients: results of the phase 3 POSITRON trial. EASL 2013. Abstract 61.

Jacobson, I. and others. Simeprevir (TMC435) with peginterferon/ribavirin for treatment of chronic HCV genotype 1 infection in treatment-naïve patients: results from QUEST-1 a phase III trial. EASL 2013. Abstract 1425.

Kowdley, K. and others. Safety and efficacy of interferon-free regimens of ABT-450/r, ABT-267 and ABT-33 +/- ribavirin in patients with chronic genotype 1 infection: results from the Aviator study. EASL 2013. Abstract 3.

Lawitz, E. and others. Sofosbuvir for previously untreated chronic hepatitis C infection. New England Journal of Medicine. April 23, 2013 (Epub ahead of print).

Lawitz, E. and others. Sofosbuvir + peginterferon + ribavirin for 12 weeks achieves 90% SVR12 in genotype 1, 4, 5, or 6 HCV infected patients: the NEUTRINO study. EASL 2013. Abstract 1411.

Manns, M. and others. High sustained viral response at 12- and 24-week follow-up of MK-5172 with pegylated interferon alfa-2b and ribavirin (PR) in HCV genotype 1 treatment-naive non-cirrhotic patient. EASL 2013. Abstract 66.

Manns, M. and others. Simeprevir (TMC435) with peginterferon/ribavirin for treatment of chronic HCV genotype 1 infection in treatment-naive patients: results from QUEST-2 a phase III trial. EASL 2013. Abstract 1413.

Nelson, D. and others. All oral therapy with sofosbuvir+ribavirin for 12 or 16 weeks in treatment experienced GT2/3 HCV-infected patients: results of the phase 3 FUSION trial. EASL 2013. Abstract 6.

Rutter, K. and others. Safety of triple therapy with telaprevir or boceprevir in hepatitis C patients with advanced liver disease – predictive factors for sepsis. EASL 2013. Abstract 65.

Sulkowski, M. and others. Sustained virologic response with daclatasvir plus sofosbuvir +/-± ribavirin (RBV) in chronic HCV genotype (GT) 1-infected patients who previously failed telaprevir (TVR) or boceprevir (BOC). EASL 2013. Abstract 1417.

Verna, E. and others. A multicenter study of protease inhibitor-triple therapy in HCV-infected liver transplant recipients: report from the CRUSH-C group EASL 2013. Abstract 23.

Source

Hepatitis C in the USA and Europe: two problems, one solution

The Lancet, Volume 381, Issue 9879, Page 1688, 18 May 2013

doi:10.1016/S0140-6736(13)61059-4 Cite or Link Using DOI

Original Text

The Lancet

Nearly half of Americans who test positive for hepatitis C virus (HCV) infection with an initial antibody test do not receive the follow-up RNA testing that is necessary to show whether they have recovered or have an ongoing infection. If left untreated, ongoing infection could lead to serious liver disease and death. This worrying finding comes from a new study by the US Centers for Disease Control and Prevention (CDC). In about 20% of cases, the body clears HCV infection unaided, but most people need treatment—typically pegylated interferon and ribavirin. About 3 million Americans are thought to have hepatitis C, but because the disorder can be asymptomatic for years, only a quarter know that they are infected. In Europe, an estimated 9 million people are infected, but only half have been diagnosed.

The CDC study examined surveillance data from eight US sites for 2005—11. Another key finding was that most new cases—67% of those with ongoing infection—were in people who were born between 1945 and 1965 (so-called baby-boomers). The CDC now recommends that all baby boomers receive routine HCV testing.

In Europe, the heterogeneity of the population means that although baby boomers might still have a role, other groups are more at risk. Many of these groups—including injecting drug users, dialysis patients, sex workers, prison inmates, and migrants from endemic regions such as sub-Saharan Africa and the Middle East—are already on the edges of society, and strong advocacy is needed to ensure that they receive appropriate diagnosis and care. France and Germany have HCV screening programmes that target many of these groups, but a Europe-wide approach will be needed if control is to be achieved.

Promising new drugs are in the pipeline, with some, such as sofosbuvir, achieving sustained virological responses in 90% of patients when combined with interferon alfa and ribavirin in phase 2 trials. Substantial decreases in HCV infection are within reach, but only if governments worldwide act together to implement policies and provide funding for effective screening, follow-up, and treatment.

Source

Combination Therapy With Telaprevir for Chronic Hepatitis C Virus Genotype 1 Infection in Patients With HIV: A Randomized Trial

Original Research | 17 May 2013

Mark S. Sulkowski, MD; Kenneth E. Sherman, MD, PhD; Douglas T. Dieterich, MD; Mohammad Bsharat, PhD; Lisa Mahnke, MD, PhD; Jürgen K. Rockstroh, MD; Shahin Gharakhanian, MD, DPH; Scott McCallister, MD; Joshua Henshaw, PhD; Pierre-Marie Girard, MD, PhD; Bambang Adiwijaya, PhD; Varun Garg, PhD; Raymond A. Rubin, MD; Nathalie Adda, MD; and Vincent Soriano, MD, PhD

[+-] Article and Author Information

Ann Intern Med. Published online 17 May 2013 doi:10.7326/0003-4819-159-2-201307160-00654

Background: Telaprevir (TVR) plus peginterferon-α2a (PEG-IFN-α2a) and ribavirin substantially increases treatment efficacy for genotype 1 chronic hepatitis C virus (HCV) infection versus PEG-IFN-α2a–ribavirin alone. Its safety and efficacy in patients with HCV and HIV-1 are unknown.

Objective: To assess the safety and efficacy of TVR plus PEG-IFN-α2a–ribavirin in patients with genotype 1 HCV and HIV-1 and evaluate pharmacokinetics of TVR and antiretrovirals during coadministration.

Design: Phase 2a, randomized, double-blind, placebo-controlled study. (ClinicalTrials.gov: NCT00983853)

Setting: 16 international multicenter sites.

Patients: 62 patients with HCV genotype 1 and HIV-1 who were HCV treatment–naive and taking 0 or 1 of 2 antiretroviral regimens were randomly assigned to TVR plus PEG-IFN-α2a–ribavirin or placebo plus PEG-IFN-α2a–ribavirin for 12 weeks, plus 36 weeks of PEG-IFN-α2a–ribavirin.

Measurements: HCV RNA concentrations.

Results: Pruritus, headache, nausea, rash, and dizziness were higher with TVR plus PEG-IFN-α2a–ribavirin during the first 12 weeks. Serious adverse events occurred in 5% (2 in 38) of those receiving TVR plus PEG-IFN-α2a–ribavirin and 0% (0 in 22) of those receiving placebo plus PEG-IFN-α2a–ribavirin; the same number in both groups discontinued treatment due to adverse events. Sustained virologic response occurred in 74% (28 in 38) of patients receiving TVR plus PEG-IFN-α2a–ribavirin and 45% (10 in 22) of patients receiving placebo plus PEG-IFN-α2a–ribavirin. Rapid HCV suppression was seen with TVR plus PEG-IFN-α2a–ribavirin (68% [26 in 38 patients] vs. 0% [0 in 22 patients] undetectable HCV RNA levels by week 4). Two patients had on-treatment HCV breakthrough with TVR-resistant variants. Patients treated with antiretroviral drugs had no HIV breakthroughs; antiretroviral exposure was not substantially modified by TVR.

Limitation: Small sample size and appreciable dropout rate.

Conclusion: In patients with HCV and HIV-1, more adverse events occurred with TVR versus placebo plus PEG-IFN-α2a–ribavirin; these were similar in nature and severity to those in patients with HCV treated with TVR. With or without concomitant antiretrovirals, sustained virologic response rates were higher in patients treated with TVR versus placebo plus PEG-IFN-α2a–ribavirin.

Primary Funding Source: Vertex Pharmaceuticals and Janssen Pharmaceuticals

Source

HCV patients with late viral breakthrough have similar characteristics

Provided by Healio

May 19, 2013

ORLANDO, Fla. — Viral breakthrough during the interferon/ribavirin phase of hepatitis C triple therapy was associated with genotype 1a and advanced liver fibrosis, similar to findings in previous clinical trials, according to study data presented here at Digestive Disease Week.

“We’ve noticed that there are patients who were experiencing viral breakthrough later in treatment,” Kali Zhou, MD, a resident in the department of medicine at the University of California, Los Angeles, told Infectious Disease News. “We did see later viral breakthrough in clinical trials, but we haven’t evaluated whether the characteristics of our breakthrough patients were similar to those who broke through in clinical trials.”

Zhou and colleagues conducted a retrospective analysis that included 55 patients who were treated from June 2011 to June 2012 and evaluated characteristics of patients who experienced viral breakthrough. Patients were treated with either boceprevir (Victrelis, Merck) or telaprevir (Incivek, Vertex).

Nine patients had viral breakthrough and all of those received telaprevir. Eight of those patients broke through during the interferon/ribavirin phase of treatment, with a mean time to breakthrough of 21.3 weeks. Six patients had genotype 1a, and six of the patients had stage 3-4 fibrosis on liver biopsy. Six patients were prior null responders and one was a prior relapse. Resistance patterns were detected in six of eight patients who underwent resistance testing, and the six patients also had cross-resistance to boceprevir.

“Right now, the recommended frequency of testing viral load is weeks 4, 12, 24 and 48 for patients receiving telaprevir, and one more test at week 8 for patients receiving boceprevir,” Zhou said. “Because most of the patients broke through after week 12, patients at high risk should probably have viral load testing monthly.”

Zhou K. #Sa1040. Characteristics of Viral Breakthrough With Direct Acting Agents for Chronic Hepatitis C Treatment in Clinical Practice. Presented at: Digestive Disease Week; May 18-21, 2013; Orlando, Fla.

Disclosure: Zhou reports no relevant financial disclosures.

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HBV may increase risk for non-Hodgkin lymphoma

Provided by Healio

May 18, 2013

ORLANDO, Fla. — Infection with hepatitis B virus may be a risk factor for non-Hodgkin lymphoma, according to data presented here at Digestive Disease Week 2013.

Researchers from the Marshfield Clinic in Wisconsin conducted a meta-analysis that included 19 case-control studies performed throughout the world. The analysis included a total of 13,947 cases and 1,559,448 controls. In nine of the studies, the controls were non-lymphoma cancer/hospital patients; eight studies incorporated healthy controls, and two studies included both types of controls. In most of the studies (17), patients were diagnosed with hepatitis B by detection of HBsAg, while hepatitis B was self-reported in the remaining two studies. All incidences of non-Hodgkin lymphoma (NHL) were diagnosed with histopathology.

Among the patients with NHL, 1,205 had hepatitis B infection and among the controls, there were 40,592 cases of infection. The risk of hepatitis B was higher for patients with NHL compared with controls (OR=2.53; 95% CI, 2.10-3.03). Significant heterogeneity was not observed across the evaluated studies.

The increased risk of hepatitis B infection was present in both developing and developed countries in subgroup analysis. There was also no difference in risk among controls based in the hospital- and population-based controls.

For more information:

Kanth R. #Sa1020. Presented at: Digestive Disease Week; May 18-21, 2013; Orlando.

Disclosure: The researchers report no relevant financial disclosures.

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HCV prevalence higher among Asian-Americans

Provided by Healio

May 19, 2013

ORLANDO, Fla. — There was a higher prevalence of hepatitis C infection among Asian-Americans than among non-Asians who received care at a free community clinic, researchers reported at Digestive Disease Week.

“Among non-Asians, the prevalence of HCV was similar to what was seen in NHANES data,” Mindie Nguyen, MD, associate professor of medicine at Stanford University, told Infectious Disease News. “Worldwide, a large amount of the HCV burden is in Asia, and we lacked data on whether Asian-Americans have a higher HCV prevalence that is similar to that in their countries of origin. We found that the prevalence of HCV among Asian-Americans was similar to the reported prevalence in many parts of Asia and Southeast Asia.”

Nguyen and colleagues conducted a cross-sectional study that included patients who were seen from July 2011 to October 2012 at a free community primary care clinic, where HCV screening is recommended for all patients seeking routine care. The researchers collected clinical and risk factor data by reviewing medical records.

Of the 691 consecutive patients seen during the timeframe, 436 were screened for HCV with antibody testing. Fourteen of the patients had a positive antibody test and of those 11 were Asian, which resulted in an HCV prevalence of 4.5% for Asians (95% CI, 1.9-7.1), compared with a prevalence of 1.6% for non-Asians (95% CI, 0.21-3.3).

Of the three non-Asians with HCV, two had a history of illicit drug use. Among the Asian patients, one had a history of illicit drug use and one had a history of blood transfusion. The HCV risk factors for four patients were unknown. The remaining five Asians had only a history of prior surgery and uncertain risk factors. In addition, most of the Asians with HCV were foreign-born.

“A large majority of the Asian patients with positive HCV antibodies did not have any of the well-known risk factors for HCV infection,” Nguyen said. “Given the high prevalence, screening for HCV should be done for foreign-born Asian-Americans coming from endemic areas, as hepatitis B virus screening is currently recommended by the CDC for those coming from areas with an HBV prevalence of 2% or higher.”

Lin O. #Sa1069. High Prevalence of Hepatitis C Virus Infection (HCV) in Asian Americans in a Community Primary Care Clinic. Presented at: Digestive Disease Week; May 18-21, 2013; Orlando, Fla.

Disclosure: Nguyen reports financial relationships with Bristol-Myers Squibb, Gilead, Onyx, Novartis, Vertex, Dynavax Technologies and Hoffman-LaRoche.

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Patients with Medicaid less likely to receive HCV treatment

Provided by Healio

May 18, 2013

ORLANDO — Although diagnosed hepatitis C infection was more common among people with Medicaid insurance, the treatment rates were lower compared with people who had commercial insurance, research presented here at Digestive Disease Week suggests.

“These results were pretty much what we expected,” Jenny Griffith, PharmD, senior manager of clinical epidemiology at AbbVie, told Infectious Disease News. “We knew that people who have Medicaid insurance are typically sicker, and we expected to find the same thing in HCV. The one thing that was unexpected was that the rate of diagnosed HCV was double in the Medicaid group. One hypothesis for this is that people with Medicaid typically have a lower socioeconomic status, and according to NHANES data, there is a higher prevalence of HCV among those with a lower socioeconomic status.”

Griffith and colleagues conducted a retrospective analysis that included approximately 28 million commercial beneficiaries from Jan. 2000 to Dec. 2009 and 3.2 million Medicaid beneficiaries from July 1999 to June 2009. They evaluated the prevalence of HCV and treatment estimates, as well as comorbidities and possible contraindications to treatment.

The 10-year prevalence of HCV was 302 per 100,000 among people with commercial insurance and 663 per 100,000 among people with Medicaid. The prevalence of treatment, however, was 26.5% among patients with commercial insurance and 19.5% among Medicaid beneficiaries. Those with Medicaid had higher rates of most evaluated comorbidities, including drug abuse, ascites, COPD, depression, autoimmune disease and pregnancy. More patients on Medicaid also had possible contraindications to treatment with ribavirin and/or interferon.

“The take-home message is that if you have someone who has Medicaid insurance, they are more than likely to be sicker and have more comorbidities that will make it more difficult to treat them,” Griffith said. “The development of interferon-free treatment may increase eligibility for treatment and hopefully eliminate this gap.”

For more information:

Griffith J. #Sa1066. Presented at: Digestive Disease Week; May 18-21, 2013; Orlando.

Disclosure: Griffith is an employee of AbbVie.

Source

Fatty Liver Predicts Heart Risk Independent of Other Factors

Daniel M. Keller, PhD

May 16, 2013

AMSTERDAM, the Netherlands — In subjects at high risk for cardiovascular events, there is an increased prevalence of nonalcoholic fatty liver disease, and that prevalence correlates with predictors of atherosclerosis, according to a large cohort study.

We found that fatty liver disease independently predicts early atherosclerosis and 10-year risk for cardiovascular disease, beyond the traditional risk factors, said Raluca Pais, MD, from the Université Pierre et Marie Curie in Paris, France.

Dr. Pais presented the study results here at the International Liver Congress 2013.

The study cohort consisted of subjects with at least 2 cardiovascular risk factors, including dyslipidemia, hypertension, diabetes, high fasting glucose, obesity, and smoking. Subjects had no previous cardiovascular events, no known causes of chronic liver disease other than fatty liver disease, and alcohol intake was 50 g/day or less.

Of the 5685 study subjects, 2073 (36.5%) had fatty liver disease.

About half the study subjects were men, mean age was 55 years, and mean body mass index was 26.4 kg/m². Mean carotid intima-media thickness on ultrasound was 0.62 mm, and 26% had at least 1 carotid plaque. Mean Framingham risk score was 10.6.

Mean fatty liver index score was 45. This score is calculated on the basis of body mass index, waist circumference, triglyceride level, and gamma-glutamyl transferase level, and a score of 60 or more is a marker of hepatic steatosis.

Subjects with a fatty liver index score above 60 had a higher body mass index than those with a lower score, and higher levels of alanine transaminase, aspartate transaminase, and gamma-glutamyl transferase (P < .001 for all). They also had greater carotid intima-media thickness (0.64 vs 0.61 mm; P < .001) and higher 10-year Framingham risk scores (14.7 vs 8.3; P < .001).

The prevalence of carotid plaques was higher in subjects with fatty liver disease than in those without (29% vs 25%; P < .001).

The interaction between fatty liver index score and the presence of carotid plaques was age dependent.

For subjects 50 years and older, the prevalence of plaques was higher in those with a fatty liver index score above 60 than in those with a lower score (36% vs 32%; P = .01). For younger subjects, there was no significant difference (10% vs 12%). The index was independently associated with the Framingham risk score (P < .001).

On multivariate analysis, fatty liver index score was independently correlated with carotid intima-media thickness (P < .001) and carotid plaques (P = .01), independent of age, cholesterol level, or the presence of diabetes or hypertension.

Better Than Traditional Risk Predictors?

This study suggests that fatty liver disease is a heterogeneous entity requiring a multidisciplinary approach and modified screening strategies, Dr. Pais concluded.

Is the fatty liver index any better than traditional risk predictors for coronary heart disease?

"These data will have to be duplicated before you can really answer that question with certainty. But this is exactly what these authors were trying to show — that you can use this test in your daily practice, Jean-François Dufour, MD, told Medscape Medical News. Dr. Dufour, who is professor of hepatology at the University of Bern in Switzerland, was not involved in the study.

"Although patients with nonalcoholic fatty liver disease have long been known to suffer from excess cardiovascular disease," Dr. Dufour noted, "it was unclear whether this was mediated through a higher risk for earlier atherosclerotic lesions. This study shows that nonalcoholic fatty liver disease is an independent predictor of cardiovascular risk."

The authors have disclosed no relevant financial relationships. Dr. Dufour is an investigator with the Fatty Liver: Inhibition of Progression Consortium.

International Liver Congress 2013: 48th Annual Meeting of the European Association for the Study of the Liver (EASL). Abstract 1356. Presented April 26, 2013.

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Summary from EASL 2013 for Hepatitis C - New HCV DAAs on their way soon: what do the phase III studies tell us?

Provided by NATAP

Jürgen K. Rockstroh M.D., Professor of Medicine
University of Bonn, Germany

Correspondence:
Prof. Dr. J.K. Rockstroh
Department of Medicine I
University of Bonn
Sigmund-Freud-Str. 25
53105 Bonn
Germany

Introduction

Ever since the first DAA based triple therapy for HCV became available treatment paradigms for HCV therapy have subsequently changed significantly and promise cure of HCV infection in around two thirds of treatment naïve HCV-genotype-1 infected patients undergoing triple therapy. Nevertheless, with more widespread use of boceprevir and telaprevir based triple therapy the current challenges of HCV therapy have become quite evident: Adherence issues due to high pill burden and food requirements with tablet intake, high rate of adverse events particularly in patients with more advanced liver disease, multiple drug-drug interactions and finally also significantly lower response rates in more challenging patient populations (cirrhosis, previous null-response to dual therapy, post-transplant treatment etc.). So not so surprisingly after an initial euphoria to offer triple therapy to HCV patients who had waited a long time for more efficacious HCV treatment options, many physicians and patients likewise now seem to wait for easier to take and potentially better tolerated and at best even interferon free new treatment options in the near future. At this year's EASL in Amsterdam with over 9600 delegates the phase III study results for the two "second wave HCV protease inhibitors" faldaprevir and simeprevir each in combination with pegylated interferon (PEG-IFN) and ribavirin (RBV) for HCV genotype 1 patients were presented as well as the phase III findings for the polymerase inhibitor sofosbuvir again in combination with PEG-IFN/RBV for treatment of genotypes 1,4,5 and 6. In addition phase III results of the first interferon free combination of sofosbuvir with ribavirin for treatment of genotype 2 and 3 were presented. As these new drugs have been or are about to be filed for licensing it can be expected that at least for the US, approval of these new HCV drugs can be expected 2013/2014. Therefore, with most likely less than a year ahead before these new drugs hit the market the question who to treat now and in whom to wait for improved HCV treatment options has become even more pertinent.

But clearly there is an even more promising future behind these new HCV agents, suggesting interferon free regimens will become available even in more difficult to treat patient populations and for all genotypes in the upcoming years. Again several studies which were presented at EASL allowed a glimpse into this highly promising future. Nevertheless, issues around the potential cost of the HCV drugs to come as well as the question which prediction factors allow us to decide which patient needs how many DAAs and what kind of combination suits which type of patient remain unanswered to the very day. Indeed the high number of compounds and combinations makes it increasingly difficult to follow all studies. Also 100% sustained virological response rates in easy to treat naïve HCV patients with early fibrosis stages and an IL28b CC genotype as well as a 1b infection cannot be automatically transferred to more challenging patient populations. In summary, the HCV field is moving fast and new HCV compounds promising simpler treatment regimens with increased tolerability and shortened treatment durations can be expected soon. In addition first interferon-free treatment approach for genotype 2 and 3 will be available shortly. A successful interferon-free HCV treatment strategy for all patients however, still has not yet arrived.

Why treat hepatitis C?

In consideration of the high costs of HCV therapy many countries in Europe have restricted the use of HCV protease inhibitor based triple therapy to more advanced fibrosis stages. Therefore, it is important that studies look at the impact of HCV therapy on survival in HCV infected individuals in order to demonstrate the benefits of HCV therapy and ultimately demonstrate cost-effectiveness of these treatment approaches. Interesting data in this context was presented at the EASL conference from a retrospective cohort study using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) (1). Within this study the predictors of mortality among US HCV infected veterans were evaluated. Overall they were able to compare an impressive number of 195,585 HCV Patients with 202,739 non-HCV infected veterans. The all-cause mortality rate among Veterans with HCV infection was much higher with 43.9 (43.4-44.3) per 1000 person-years (PY) than in Veterans without HCV infection (all-cause mortality was 24.0 (23.7-24.4) per 1000 PY). The table 1 shows the relevant predictors found to impact mortality. Among Veterans with HCV infection, decompensated liver disease, anemia, cancer, chronic kidney disease and COPD were the strongest predictors of higher risk of mortality, while HCV treatment was associated with over 50% reduction in mortality in this group. These findings once again underline the importance of HCV therapy to significantly lower risk of mortality in HCV infected individuals.

Continue to full article here ….