HCV Weekend Reading - News and Views: Recent Approval Holds Promise for Genotype 3, but Hurdles Anticipated

August Updates

Featuring HCV research, news and views

Hi everyone, hope you are all enjoying the weekend! We have a few August updates from; Healio, HCV Advocate, Dr. Joe Galati, and a handful of wonderful bloggers, enjoy.

Just Published

We begin with the August print edition of "HCV Next" published  today online at "Healio."

"HCV Next" offers information on a range of topics, which include diagnosis, new combination therapies, side effects, drug/drug interaction, guidelines, fatty liver disease and more.

Table of Contents
5 QUESTIONS
A Conversation with Mitchell Shiffman, MD

COVER STORY
Forgotten History:The Hunt for Undiagnosed Patients with HCV

EDITORIAL
Recent Approval Holds Promise for Genotype 3, but Hurdles Anticipated

IN THE JOURNALS
Study Suggests Less Than 1% of Acute HCV Cases Reported to the CDC

Study Shows low SVR Among Veterans on Sofosbuvir-Based Regimens

Study Shows Medicaid Restrictions for Sofosbuvir Create Barriers for Care

Alisporivir Plus Ribavirin Yields High Response Rates for HCV Genotype 3

Combination Regimen Yields High SVR in Former Injection Drug Users

FDA Showcases Clinical Trial Design, Regulation for HCV

Experts: Needle Exchange Programs Prevent Outbreaks Among IDUs

SPECIAL SERIES
Continuum of Care: HCV and the ID Clinician

TREND WATCH
TURQUOISE-III: Treatment Yields 100% SVR12 for HCV Genotype 1b

California Could Spend Nearly $5 Billion on HCV Drugs Over Next Year

Newsletter

HCV Advocate Mid-Month Newsletter
Aug 15
In this month’s column of HCV Drugs I discuss the exciting news about the Food and Drug Administration (FDA) approval of AbbVie’s and BMS’s HCV medications, the study results from AbbVie’s once-a-day combination to treat genotype 1b, and the acceptance by the FDA of Merck’s new drug application for grazoprevir and elbasvir and the decision date.

HCV Advocate Fact Sheets
Genotype 3: Daklinza plus Sofosbuvir 

Genotype 4: TECHNIVIE plus Ribavirin 

Liver Night - On Your Health First

Latest News on Hepatitis C Cures
by DR. JOE GALATI on 08/16/2015
For tonight’s broadcast of Your Health First, Dr. Rashid Khan joins me to discuss the latest news on fatty liver disease, and the new therapies for hepatitis C, which results in a cure rate of over 95% of the cases. 

Podcast At CMAJ

CMAJ Blogs

CMAJ Blogs hosts the Medical Student Humanities Blog, as well as blogs by CMAJ editors and guest bloggers.

Social determinants of hepatitis C
Dr. Tyndall draws attention to the fact that although new treatments for hepatitis C virus are much more effective, we must not forget to address the social drivers of the disease, especially amongst people who inject drugs. IV drug users, both current and past, make up the majority in the second wave of HCV infection.



Source

Podcast At HealthLink On Air 

How latest techniques help surgeons fight cancer, other diseases of liver, pancreas, gallbladder
by Jennifer Congel
Obesity and drug abuse can lead to fatty liver and hepatitis C, which are major factors for developing liver cancer, according to Ajay Jain, MD, associate chief of hepatobiliary and pancreatic surgery at Upstate. Jain, who specializes in cancer surgery, describes the latest procedures – often minimally invasive and robotically assisted — to treat cancers and other diseases of the liver, pancreas, gallbladder and bile ducts. He also reviews promising new research on early detection of pancreatic cancer.
Listen here...

Blog Updates From Around The Web

Hepatitis C, Marijuana, and the Liver

By Lucinda K. Porter, RN

Regular readers have probably figured out that my notions are liberal-leaning. I believe in medical coverage for everyone, including hepatitis C treatment for anyone who wants it. I advocate treatment for active drug users, prisoners, and people with no liver damage. I believe that health is a right, not a privilege. I also believe that spending our healthcare dollars is a wise investment in society and helps to increase productivity.

Hepatitis C and Your Kidneys

By Lucinda K. Porter, RN

A chronic hepatitis C diagnosis often spurs us to educate ourselves about the liver. Few of us think about our kidneys, but we should. People living with hepatitis C have a higher risk of developing kidney failure compared to those without hep C (52.6% vs. 38.4%).

Genotype One: Indian Sofosbuvir and Chinese Daclatasvir

By Greg Jefferys

I have written previously of UK Doctors' fear of prescribing generic Hep C medicine (genericnophobia) and have recently had correspondence with a London GP and a Welsh patient consulting a liver specialist in Wales that sheds some light on the source of this strange psychological condition, genericnophobia, which affects more than 90% of British medical practitioners.

When we make commitments and life gets in the way

By Grace Campbell
Often we make a commitment to something and it all sounds very reasonable, until something unrelated, unexpected and unplanned blows it out of the water.

I Am My Own Personal Trainer for Liver Health

Karen Hoyt

What I really need to do is to hire a professional. But – that’s way out of my price range – for now… so I guess I’ll have to do.

HAVE GUN, WILL TRAVEL–JETGUNS

Well, there you have the particulars. I suspect it is much more than plausible that the jetgun was capable of cross-contamination by any of the above even if no one had flinched and bled. 

PHC Impacts Hepatitis C Surveillance!

Pennsylvania’s Medicaid covers Sofosbuvir if the patient has an F3 or F4 stage of liver fibrosis and demonstrates a record of at least 6 months abstinence from drugs and alcohol.

The Long and Winding Road

**Ricki**

Every time I took my son in to the doctors, I would pretend that it was just a regular checkup, but I knew that eventually, his blood work would probably come back with an elevated liver panel.

My Integrative Strategies for Managing Hepatitis C
By George M. Carter

My HCV genotype is 1A. For many years, it was considered harder to treat, with a lower likelihood of a sustained viral response (SVR) -- which is considered being cured -- when using alpha interferon or, even later, a combination of pegylated interferon and ribavirin. The low likelihood of success, the 48 weeks of injections and the horrific side effects persuaded me to wait. In addition, I was not too concerned since some data I saw suggested that not everyone with HCV goes on to develop cirrhosis.

Anthem sued for denying Hep C drug treatment
By Jason Schossler
From Westlaw Journal Insurance Coverage: Anthem Blue Cross Life & Health Insurance Co. is facing a proposed class-action lawsuit for allegedly refusing to cover the newly approved but expensive hepatitis C treatment Harvoni, which reportedly can cure most cases of the disease within eight to 12 weeks.

A Tale of Two Liver Transplants: Altruistic Compassion for a Compassionate Altruist
By Nathan Sheon
"Talk about your life changing in an instant,” Helen said, remembering her first diagnosis of acute liver failure. The doctor told her family there was nothing more to be done, and she was given two weeks to live.

Preparing for College, Dating and Disclosing Hepatitis B

When my daughter, who has chronic hepatitis B, packed for her freshman year of college, I peppered her with warnings about the need for standard precautions and condoms. I suggested wording for a future conversation where she would disclose her infection and negotiate safe sex with a potential partner.

Of Interest

Nature
Registered clinical trials make positive findings vanish
Chris Woolston
A study showing a fall in positive trial results after the roll-out of clinicaltrials.gov attracted much attention on social media.

Healthy You

Junk Food Disguised as Healthy: Don’t Be Fooled
Dr. Joe Galati
Good nutrition is a requirement for wellness. There is no doubt that good nutrition prevents disease. Most reasonable people seek out foods that are nutritions, and thus support wellness. But, you need to beware that the food marketers are taking advantage of you-big time.

Happy Sunday!

Tina

Hepatitis C patients in England denied lifesaving liver drug

August 16th, 2015
Original Article: The Guardian

Health experts concerned about decision not to extend Daklinza treatment to patients with genotype 3 strain of virus

Summary Source @ http://www.firstwordpharma.com/node/1307411?tsid=1#axzz3izyVxC7p

Hepatitis C patients in England denied lifesaving liver drug

Summary 
The National Institute for Health and Care Excellence (NICE) recommended restricting use of Bristol-Myers Squibb’s Daklinza in England for patients with a particular strain of hepatitis C, even though the therapy is available to patients in Wales, Scotland and Northern Ireland, The Guardian reported.

Last year the European regulator approved Daklinza for use, in conjunction with other drugs, as a treatment for four main strains of hepatitis C genotypes, but NICE has not recommended it for the treatment of patients with the genotype 3 of the disease, which accounts for around 45 percent of all cases in England.

NICE says that prescribing the drug for genotype 3 patients is not cost-effective as a full course of Daklinza can cost up to 48,700 pounds.

Anna Maria Geretti, professor of virology and infectious diseases at the University of Liverpool, said studies had shown that, when used in combination with other drugs, almost 100 percnet of patients taking Daklinza were cured.

Geretti suggested that up to 1000 people in England could benefit from the drug, although Nice is understood to put the figure at nearly 3000.

Bristol-Myers Squibb noted that “Nearly 100,000 patients in the UK are thought to have hepatitis C genotype 3. This group could suffer severe treatment inequality from this decision. BMS will be working closely with Nice to see if a solution can be found, and hope that this decision can be urgently reassessed.”
Source

Newly discovered cells restore liver damage in mice without cancer risk

Newly discovered cells restore liver damage in mice without cancer risk

The liver is unique among organs in its ability to regenerate after being damaged. Exactly how it repairs itself remained a mystery until recently, when researchers supported by the National Institutes of Health discovered a type of cell in mice essential to the process. The researchers also found similar cells in humans.

When healthy liver cells are depleted by long-term exposure to toxic chemicals, the newly discovered cells, known as hybrid hepatocytes, generate new tissue more efficiently than normal liver cells. Importantly, they divide and grow without causing cancer, which tends to be a risk with rapid cell division.

“This is the first time anyone has shown how liver cells safely regenerate,” said William Suk, Ph.D., director of the Superfund Research Program at the National Institute of Environmental Health Sciences (NIEHS), part of NIH.

The researchers studied liver function in mice following long-term exposure to carbon tetrachloride, a chemical commonly associated with Superfund sites. The scientists were able to isolate the hybrid hepatocytes after observing how the tissue regenerated. They then exposed healthy mice to three known cancer-causing pathways and watched the hybrid hepatocytes closely. Liver cancer never originated from these cells.

The research team, led by Michael Karin, Ph.D., distinguished professor of pharmacology and pathology at the University of California, San Diego (UCSD) School of Medicine and a member of the prestigious National Academy of Medicine, conducted the research at the UCSD Superfund Research Center.

“The entire program at UCSD is focused on the effects of toxicants on liver metabolism and functionality,” said Suk.

One of the goals of the Superfund Research Program is to better understand how toxic chemicals affect human health. The liver plays an essential role in this process by helping to remove toxicants from the body.

“Hybrid hepatocytes represent not only the most effective way to repair a diseased liver, but also the safest way to prevent fatal liver failure by cell transplantation,” noted Karin.

The findings appear Aug. 13 in the journal Cell.

Grant Number: P42ES010337

NIEHS supports research to understand the effects of the environment on human health and is part of NIH. For more information on environmental health topics, visit http://www.niehs.nih.gov. Subscribe to one or more of the href="http://www.niehs.nih.gov/news/releases/newslist/index.cfm">NIEHS news lists to stay current on NIEHS news, press releases, grant opportunities, training, events, and publications.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Source

Reference
Font-Burgada J, Shalapour S, Ramaswamy S, Hsueh B, Rossell D, Umemura A, Taniguchi K, Nakagawa H, Valasek MA, Ye L, Kopp JL, Sander M, Carter H, Deisseroth K, Verma IM, Karin M. 2015. Hybrid periportal hepatocytes regenerate the injured liver without giving rise to cancer. Cell 162(4):766-779.

Also See:

Aug 5

Liver stem cell identified in mice

Hepatitis C infection may fuel heart risk

PUBLIC RELEASE: 11-AUG-2015

Hepatitis C infection may fuel heart risk

Results suggest need for vigilant monitoring in those infected with the liver-damaging virus

JOHNS HOPKINS MEDICINE

People infected with the hepatitis C virus are at risk for liver damage, but the results of a new Johns Hopkins study now show the infection may also spell heart trouble.

The findings, described online July 27 in The Journal of Infectious Diseases, emerged from a larger ongoing study of men who have sex with men, many but not all of whom were infected with HIV and followed over time to track risk of infection and disease progression. A subset of the participants had both HIV and hepatitis C, two infections that often occur together.

Even though people infected with HIV are already known to have an elevated risk for heart disease, researchers emphasize their results offer strong evidence that hepatitis C can spark cardiovascular damage independent of HIV.

Specifically, the research found that study participants chronically infected with hepatitis C were more likely to harbor abnormal fat-and-calcium plaques inside their arteries, a condition known as atherosclerosis and a common forerunner of heart attacks and strokes.

"We have strong reason to believe that infection with hepatitis C fuels cardiovascular disease, independent of HIV and sets the stage for subsequent cardiovascular trouble," says study principal investigator Eric Seaberg, Ph.D., assistant professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health. "We believe our findings are relevant to anyone infected with hepatitis C regardless of HIV status."

Investigators emphasize they don't know exactly how infection with the hepatitis C virus precipitates the growth of artery-clogging plaque but that their evidence is strong enough to warrant vigilant monitoring for cardiac symptoms among people infected with the virus.

"People infected with hepatitis C are already followed regularly for signs of liver disease, but our findings suggest clinicians who care for them should also assess their overall cardiac risk profile regularly," says study author Wendy Post, M.D., M.S., professor of medicine at the Johns Hopkins University School of Medicine and a cardiologist at the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease.

Post says that at a minimum patients with hepatitis C would benefit from an annual cardiac evaluation that includes cholesterol and glucose testing, a blood pressure check and assessment of lifestyle habits.

The study involved 994 men 40 to 70 years old without overt heart disease who were followed across several institutions in Baltimore, Washington, D.C., Pittsburgh, Los Angeles and Chicago. Of the 994, 613 were infected with HIV, 70 were infected with both viruses and 17 were only infected with hepatitis C. Participants underwent cardiac CT scans to detect and measure the amount of fat and calcium deposits inside the vessels of their hearts. Those infected with hepatitis C, regardless of HIV status, had, on average, 30 percent more disease-fueling calcified plaque in their arteries, the main driver of heart attack and stroke risk. People infected with either HIV or hepatitis C, on average, had 42 percent more noncalcified fatty buildup, a type of plaque believed to confer the greatest cardiac risk.

In addition, those who had higher levels of circulating hepatitis C virus in their blood were 50 percent more likely to have clogged arteries, compared with men without hepatitis C. Higher virus levels in the blood signal that the infection is not well controlled by drugs or the immune system. Poorly controlled infection, the investigators add, may lead to more inflammation throughout the body, which can fuel blood vessel damage and thus contribute to heart disease.

Treating hepatitis C infection promptly can ward off long-term liver damage, but researchers say their findings now raise another critical question: whether a new class of medications that help 90 percent of patients clear the virus within a few short months could also halt the formation of plaque and reduce cardiac risk in the long run.

More than 2.7 million people in the United States are infected with the hepatitis C virus, according to estimates from the Centers for Disease Control and Prevention.

###

Other Johns Hopkins investigators involved in the study included Rebeccah McKibben, Sabina Haberlen, Todd Brown and Chloe Thio. Investigators from other institutions included Matthew Budoff, Mallory Witt, Lawrence Kingsley and Frank Palella.

The work was by funded by the National Heart, Lung, and Blood Institute under grant number RO1 HL095129, with additional support from the National Center for Advancing Translational Sciences (grant UL1 TR 001079) and the National Institute of Allergy and Infectious Diseases.

Conflict of interest disclosure: Johns Hopkins investigator Todd Brown, M.D., is a consultant for the following pharmaceutical companies: Gilead Sciences, Bristol-Myers Squibb, Merck, Abbvie, EMD Serono and ViiV Healthcare. These relationships are managed by Johns Hopkins in accordance with its policy on interaction with industry.

Johns Hopkins Medicine
Media Relations and Public Affairs

Source

Key Management Decisions in HCV - Case-based Video Presentation Led By Ira M. Jacobson, MD.

Key Management Decisions in HCV

Hello folks, great news, check out this newly released case-based video presentation led by Ira M. Jacobson, MD., over at Clinical Care Options. 

Kick back and watch the good doctor explore the best treatment choice, based on three different case scenarios.

No Questions To Answer

Anyone can view this patient friendly learning activity, no viewer questions, only the audience taking part in the symposium responds.

Topics

Topics include; screening patients, alcohol use, fatigue, diabetes, HCV-related complications, imaging/assessing fibrosis(fibroscan), with a breakdown of HCV regimens used for each case study, including SVR rates. 

After each patient history is presented a short break is taken while the audience responds to the panel question. After the votes are in, or the question is answered, results are discussed, with follow up commentary by Andrew J. Muir, MD and Nancy Reau, MD.

Here is a snapshot of one question:

Learning Objectives

• Integrate the results of clinical studies of approved HCV treatments into current and future patient management strategies
• Implement practical strategies to optimize patient outcomes with HCV therapy
• Apply key insights from clinical trials and/or approved indications on the use of oral therapy for hepatitis C
• Pharmacists will be better able to provide accurate and appropriate counsel as part of the treatment team
• Nurses will be better able to provide appropriate care and counsel for patients and their families

***Free registration is required. 

Begin by clicking on the "Video" link .....

Released: 8/7/2015

A Study of Health-related Quality of Life - Interferon Plus Ribavirin to Interferon- and Ribavirin-free HCV Regimens

The Patient's Journey With Chronic Hepatitis C From Interferon Plus Ribavirin to Interferon- and Ribavirin-free Regimens

A Study of Health-related Quality of Life
How do interferon and ribavirin impact health-related quality of life during treatment for chronic hepatitis C, and are patients better off with different drug therapies?

August 10, 2015
Z. M. Younossi; M. Stepanova; F. Nader; B. Lam; S. Hunt

Aliment Pharmacol Ther. 2015;42(3):286-295. 

Article Source - Medscape

Discussion ONLY

Link To Full Article

• Abstract and Introduction
• Methods
• Results

Discussion
This is the largest analysis of  Health-related Quality of Life (HRQL) in over 3400 CH-C patients who were treated with a variety of anti-HCV regimens in nine phase 3 clinical trials. In this study, we clearly demonstrated a significant improvement of HRQL scores with regimens which were free of IFN, and more recently, regimens which are also free of both IFN and RBV. This significant improvement is in contrast to the substantial decrement seen in HRQL with the previous standard of care for chronic hepatitis C which included interferon and ribavirin and was associated with substantial side effects.^[19–21]

The results of this analysis also document that the physical aspects of HRQL in CH-C patients were primarily predicted by the presence of fatigue, depression, insomnia, and diabetes. Additionally, the strongest predictors of mental health aspects of HRQL were also depression, anxiety, and fatigue, all consistent with prior reports.^[11–18] Although some of these factors may be related to the host, it is possible that some factors, such as fatigue, may be related to HCV viremia and could improve after viral eradication. Indeed, viral eradication 12 weeks after treatment cessation was observed together with improvement in a number of HRQL domain scores which was especially prominent for the vitality domain.

In multivariate analysis, we showed that receiving a regimen that contained both IFN and RBV was the strongest negative predictor of HRQL during treatment, while IFN- and RBV-free (LDV/SOF) was the only regimen independently associated with HRQL improvement during treatment. Furthermore, LDV/SOF remained the only independent predictor of HRQL improvement after achieving SVR-12. We also have shown that the negative effect of IFN does lessen with longer follow-up in patients who cleared HCV infection. In fact, this is the first study which demonstrates that by 24 weeks after treatment cessation, post-treatment HRQL improvement after virologic clearance is manifested regardless of the regimen. Nevertheless, it is still possible that patients who receive interferon may have longer lasting effect which can be picked up by more in-depth neuropsychiatric testing. These potential changes were not detectable by SF-36 instrument.

To the study limitations, we could not strictly assess the magnitude of the impact of SVR to HRQL after treatment cessation due to short follow-up and small number of non-responders. Furthermore, limiting assessment to 24 weeks post-treatment limited the potential long-term implications of viral clearance. Also, some important and difficult to treat HCV subpopulations, such as patients with renal failure, decompensated cirrhosis or liver transplants, were not enrolled. Furthermore, the original clinical trials used in this study were not designed to be comparable, so adjustments were made to account for the bias in the study cohort, thus, introducing uncertainty. Additionally, a number of socio-economic and clinical factors which may also affect HRQL, including but not limited to the level of education, income, residence, marital status, social support, the route of HCV transmission, duration of the infection, family history of major comorbidities, etc., were not available so could not be adjusted for. Finally, none of the original trials were pragmatic, i.e. conducted in real-life, routine practice conditions, while efficacy observed in explanatory clinical trials may not necessarily translate into similarly high effectiveness in real life so the degree of generalisability of our results remain unclear.

In conclusion, the use of the new IFN-free and RBV-free regimens results in substantial improvement in patients' HRQL scores during and after treatment. These HRQL data, when considered together with the excellent efficacy and safety profile of these regimens, provides a more comprehensive picture of the true impact these new treatments have on patients' lives.

Medscape

Tx Options for HCV GT 1 or 4 Non-responders

Tx Options for HCV GT 1 or 4 Non-responders

Posted on August 9, 2015

New study shows that genotype 1- or 4-infected non-responders, including patients with cirrhosis, achieve high SVR12 rates on the 24 week, quad treatment regimen of daclatasvir plus asunaprevir and peginterferon/ribavirin. The combination was well tolerated and no additional safety and tolerability concerns were observed compared with peginterferon/ribavirin regimens. A combination of Direct Acting Antivirals (DAAs) and peginterferon/ribavirin may provide a viable treatment option for those patients who experience virologic failure on all-oral, DAA regimens.

Some of the more difficult chronically-infected HCV patients to treat are those with a prior null or partial response to peginterferon/ribavirin therapy. Daclatasvir is a potent, pan-genotypic inhibitor of the HCV NS5A protein with activity against genotypes 1 to 6 in vitro.

Asunaprevir is an NS3 protease inhibitor with activity against genotypes 1 and 4. Positive results of HALLMARK-QUAD, a global, single-arm, open-label, phase 3 study evaluating the efficacy and safety of daclatasvir plus asunaprevir combined with peginterferon/ribavirin in patients (≥18 years) infected with HCV genotype 1 or 4 who were null or partial responders to peginterferon alfa-2a or -2b plus ribavirin (Study AI447029; ClinicalTrials.gov number NCT01573351), were recently published in Journal of Hepatology (Jensen D, et al. J Hepatol. 2015 Jul;63(1):30-7).

• Patients received daclatasvir 60 mg once-daily, asunaprevir 100 mg softgel capsule twice-daily and 180 μg peginterferon alfa-2a weekly and twice-daily ribavirin dosed according to bodyweight (<75 kg, 1000 mg daily; ≥75 kg, 1200 mg daily) for 24 weeks and were subsequently followed for 24 weeks post-treatment
• Null response to peginterferon/ribavirin was defined as a <2 log10 decline in HCV RNA after ≥12 weeks of therapy, or a <1 log10 decline after ≥4 weeks of therapy
• Partial responders had achieved a ≥2 log10 decline, but never achieved undetectable HCV-RNA after ≥12 weeks of peginterferon/ribavirin therapy, or became undetectable and subsequently had detectable HCV-RNA on-treatment
• Patients with compensated cirrhosis were eligible but were capped at a maximum of 25% of the treated population

Of the 496 patients who were screened for the study, 354 with HCV genotype 1, and 44 with HCV genotype 4 treated between May 2012 and December 2013. The majority of patients (379/398; 95.2%) completed the 24- week treatment period.

• The majority of patients were male (68.6%) and white (76.4%) with a median age of 52.7 years
• Approximately two-thirds of the study population were null responders and as expected, a high proportion had a non- CC IL28B genotype
• Overall, 23.4% of patients enrolled in the study had compensated cirrhosis; 45.5% of genotype 4-infected patients had compensated cirrhosis compared with 20.6% of genotype 1-infected patients

Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated rapid early antiviral activity among genotype 1- and 4-infected patients. SVR12 rates of 92.9% (329/354) were achieved in genotype 1-infected patients. Among genotype 4-infected patients, the SVR12 rate was 97.7% (43/44).

• One patient had a missing post-treatment week 12 HCV-RNA value, but subsequently achieved SVR24, yielding a 100% SVR rate in genotype 4-infected patients. Study authors noted that this supports the ongoing development of the all-oral triple DAA regimen of daclatasvir and asunaprevir plus beclabuvir (BMS-791325), which has achieved high SVR rates in both genotype 1 (89–94%) and genotype 4 (100%) patients (Everson GT, et al. Gastroenterology. 2014;146:420-429. Hassanein T, et al. J Hepatol. 2014;60(suppl1):S472). Other potential treatment options in development for this population include the combination of ABT-450/ritonavir plus ombitasvir, which achieved high SVR rates in a small cohort of 50 genotype 4-infected null and partial responders (Hezode C, et al. J Hepatol. 2014;60(suppl1):S24).
• SVR12 rate 94.9% in genotype 1-infected patients who achieved RVR (82.5% [292/354]), compared with 83.1% among those who did not achieve RVR
• A large number of cirrhotic null and partial responders were treated in this study (23%). Daclatasvir plus asunaprevir and peginterferon/ribavirin resulted in high SVR12 rates in both cirrhotic (90.4%; 66/73) and non-cirrhotic genotype 1 patients (93.6%; 263/281).
• Baseline factors previously associated with a suboptimal response to peginterferon/ribavirin-based regimens, such as sex, age, body mass index, and baseline HCV-RNA did not appear to affect response, as SVR12 rates were high across all groups
• SVR12 rates were slightly lower among the small number of black patients (87.9%; 29/33) compared with white patients (92.6%; 251/271)
• SVR12 was higher among patients infected with subtype 1b (98.9%; 176/178) compared with subtype 1a (86.9%; 153/176)

Virological failure was observed infrequently among genotype 1-infected patients: 3.1% (11/354) experienced virological breakthrough, 0.6% (2/354) had detectable HCV-RNA at the end of treatment, and 2.4% (8/337) experienced relapse post-treatment.

• Three patients with baseline asunaprevir resistance polymorphisms did experience virological breakthrough. Multiple linked resistance variants were present in two of these patients, which are unusual in protease inhibitor-naive patients, suggesting these patients may have been previously exposed to protease inhibitor-based therapy, but this could not be verified after further investigation.
• No association between the presence of baseline daclatasvir resistance polymorphisms and virological failure was observed
• No genotype 4-infected patients experienced virological failure

Daclatasvir plus asunaprevir and peginterferon/ribavirin was well tolerated in this patient population. The most frequent AEs and laboratory abnormalities observed during treatment were those typically associated with peginterferon/ribavirin therapy.

• AEs occurring at a frequency >20% were fatigue, headache, pruritus, asthenia, influenza-like illness, insomnia, and rash
• Serious AEs were reported in 5.5% (22/398) of patients during treatment, with nine events considered by the investigator to be related to study therapy: anemia, anemia/dehydration, encephalopathy, pneumonia, traumatic ulcer, lymphadenopathy, sepsis, hepatic enzymes increased, and dry skin in one patient each
• No clinically relevant differences in hepatic laboratory abnormalities or AEs were noted between patients with or without cirrhosis
• Grade 3/4 ALT and aspartate aminotransferase (AST) elevations occurred in 3.0% and 3.3% of patients, respectively.

Infrequent viral breakthrough and relapse, combined with a low rate of AE-related discontinuations, led to a high number of patients completing treatment in this study, compared with historical peginterferon/ribavirin-based studies.

• Discontinuations due to AEs occurred in 4.5% (18/398) of patients; the most frequent events leading to discontinuation were rash, malaise, neutropenia, and vertigo, occurring in two patients each

Study authors noted that future therapeutic options for patients with a partial or null response to peginterferon/ribavirin are likely to focus on all-oral regimens such as daclatasvir in combination with other DAAs including asunaprevir and sofosbuvir, and simeprevir plus sofosbuvir, which are well tolerated and provide SVR rates comparable to those observed in this study. However, study authors also note that a combination of DAAs and peginterferon/ribavirin may provide a viable treatment option for those patients who experience virologic failure on all-oral regimens.

Source - http://hepcblog.amjmed.com/hep-c-treatment/tx-options-for-hcv-gt-1-or-4-non-responders/

Cirrhosis and decompensation are common among people with chronic hepatitis C

Cirrhosis and decompensation are common among people with chronic hepatitis C
Liz Highleyman
Produced in collaboration with hivandhepatitis.com

More than one-quarter of people with chronic hepatitis C at Kaiser-Permanente developed liver cirrhosis over 12 years and 40% of these experienced decompensation – higher rates than expected, according to a presentation at the recent Digestive Disease Week 2015 meeting in Washington, DC. The study also found that cirrhosis and decompensation were associated with comorbid conditions, supporting the idea of hepatitis C as a systemic disease.

Over years or decades, chronic hepatitis C virus (HCV) infection can lead to serious liver disease including advanced fibrosis, cirrhosis, liver cancer, decompensated liver failure and the need for a liver transplant. People with decompensation – which occurs when the liver can no longer carry out its vital functions – may develop ascites (abdominal fluid accumulation), bleeding varices (enlarged veins) in the oesophagus or stomach and hepatic encephalopathy (brain impairment).

Continue reading...