Showing posts with label AASLD 2012-63rd Annual Meeting. Show all posts
Showing posts with label AASLD 2012-63rd Annual Meeting. Show all posts

Saturday, March 9, 2013

AASLD oral presentations from "Hepatitis C Treatment in Special Populations"

AASLD 2012-63rd Annual Meeting

AASLD is pleased to announce the availability of the newly webcasted presentations from the AASLD Hepatitis C Treatment in Special Populations Conference on LiverLearning®: The Official eLearning Portal of AASLD.

AASLD - Liver Learning
If you haven't yet explored the "Liver Learning" section available @ the AASLD website you're missing out on meeting webcasts, video podcasts, abstracts and more. The presentations can be viewed on your computer, Android Smartphones or Tablets.

To access presentations through "TALKS on the GO", please visit or download it through the Apple App Store or Google Play store for Android Smartphones and Tablets by searching for: "Talks on the Go" (Please note you must include the quotation marks)
To access oral presentations from "Hepatitis C Treatment in Special Populations":
1) Go to:
2) Register or Click "Sign In" on the top right corner
3) Enter your username and password
4) Click on the "Events" tab and start browsing!

*Free registration required

Newly Webcasted Presentations
Session 1: Current State of the Art Therapy by Gentoype
 Stuart C. Gordon
Genotype 1, Naive

(Podcast available)
 Eugene R. Schiff
Genotype 1, Treatment-Experienced

(PowerPoint shared by the speaker; Podcast available)
 Alessandra Mangia Genotype 2/3: Naïve/Treatment Experienced

(PowerPoint shared by the speaker; Podcast available)
 Norah Terrault
Genotype 4-6: Naïve/Treatment Experienced

(Podcast available)
 Panel Discussion
Panel Discussion

(Podcast available)
Session 2: Special Populations as Designated by FDA
 Maureen M. Jonas

(Podcast available)
 Norbert Brau
HIV/HCV Coinfection

(PowerPoint shared by the speaker; Podcast available)
 Geoffrey M. Dusheiko
Bleeding Disorders

(PowerPoint shared by the speaker; Podcast available)
 Marina Berenguer
Liver Transplant Recipients

(Podcast available)
 Fred Poordad
IDUs, Including Methadone/Partial Agonists: Counterpoint

(Podcast available)
 Diana Sylvestre
IDUs, Including Methadone/Partial Agonists: Point

(Podcast available)
 Panel Discussion
Panel Discussion

(Podcast available)
Session 3: Treating in the Face of Comorbidities
 Stephen Harrison
Coexistent Liver Diseases (NAFLD, HBV, Autoimmune)

(PowerPoint shared by the speaker; Podcast available)
 Michael W. Fried
Renal Insufficiency/Hemodialysis

(Podcast available)
 Glenn Treisman

(PowerPoint shared by the speaker; Podcast available)
Session 4: Treating Patients with Hepatitis C to Prevent Related Diseases
 Marina Berenguer
Cryoglobulinemia - MPGN, Neuropathy, Vasculitis, Arthritis

(PowerPoint shared by the speaker; Podcast available)
 Jordan Feld
Lymphoma and Other Lymphorproliferative Malignancies

(PowerPoint shared by the speaker; Podcast available)
 Francesco Negro

(PowerPoint shared by the speaker; Podcast available)
 Hashem B. El-Serag
HCC/ Cholangiocarcinoma

(PowerPoint shared by the speaker; Podcast available)
 Panel Discussion
Panel Discussion

(Podcast available)
Session 5: Potpourri of Special Groups
 Jordan Feld
Acute Hepatitis

(PowerPoint shared by the speaker; Podcast available)
 Michael R. Lucey

(Podcast available)
 Geoffrey M. Dusheiko
Elderly: Counterpoint

(PowerPoint shared by the speaker; Podcast available)
 Eugene R. Schiff
Elderly: Point

(PowerPoint shared by the speaker; Podcast available)
 W Ray Kim
Towards Cost-effective Care in Special Populations

(PowerPoint shared by the speaker; Podcast available)
 Panel Discussion
Panel Discussion

(Podcast available)
Session 6: Towards the Elimination of Special Populations
 Michael W. Fried
What's New with IFN-Based Therapies

(Podcast available)
 Fred Poordad
What's New with DAA Combo Therapies

(Podcast available)
 Jeffrey Murray
Expanded Access to Special Populations: Panel Discussion

(PowerPoint shared by the speaker; Podcast available)
 Stuart C. Gordon Introduction - Expanded Access to Special Populations: Panel Discussion

(Podcast available)
 Nisha K. Gupta
Expanded Access to Special Populations: Panel Discussion

(Podcast available)

Thursday, February 14, 2013

Real-World Use of HCV DAAs Differs From Clinical Trials

Articles from the February issue of Gastroenterology & Endoscopy News are now online. Click here to see all of the stories from the February issue. Click below to read:

Souped-Up IFN Could Improve HCV Treatment
Studies Point to Advent of IFN-Free Regimens for Hepatitis C Infection

Real-World Use of HCV DAAs Differs From Clinical Trials

by Kate O'Rourke
Boston—Discontinuation rates with boceprevir (Victrelis, Merck & Co.) and telaprevir (Incivek, Vertex Pharmaceuticals) are much higher in the real-world setting than in the clinical trials that led to the drugs’ approvals. This news comes from two studies presented at The Liver Meeting, the annual meeting of the American Association for the Study of Liver Diseases.

Researchers say that treatment rates are low because of the complexity of treatment with the direct-acting antivirals (DAA) and concerns about side effects, even at experienced centers. The FDA approved boceprevir and telaprevir for the treatment of patients with hepatitis C virus (HCV) genotype 1 infection in combination with pegylated interferon and ribavirin in 2011.
Fasiha Kanwal, MD, MSHS, associate professor at Baylor College of Medicine, in Houston, who was not involved with the study, said she was not surprised by the high discontinuation rates of these two agents.

“With the addition of the new DAAs, the probability of cure is much higher (approximately 70% in clinical trials) and the duration of treatment may be half as long for some patients, but the side effect burden is significantly greater than the previous standard,” Dr. Kanwal said. “Moreover, participants in the DAA registration trials were generally much healthier than most HCV patients in routine practice, who often have physical or mental comorbidities that may complicate treatment. The fact that rates of treatment-related adverse events and resulting discontinuations are higher in these community-based patients is therefore not surprising.”

High Discontinuation Rates
In one of the studies presented at The Liver Meeting, researchers reviewed the medical charts of all adult HCV patients being treated with DAA triple regimens over a one-year period at the University of Texas Southwestern Medical Center, in Dallas, and a referral center at the University of Miami Health System, in Florida (abstract 133). All patients had at least 12 weeks of follow-up. Researchers excluded patients who were post-transplant, receiving dialysis or co-infected with HIV.

Of the 454 patients at the two centers, only 19% began triple therapy. Reasons for treatment deferral included early disease stage (19%), comorbidities (18%) and advanced liver disease (13%). The overall discontinuation rate of the triple therapy was 21% before week 12. This discontinuation rate was higher than that seen in the trials that led to the telaprevir approval, with the ADVANCE trial showing a 10% discontinuation rate and REALIZE showing a 13% discontinuation rate (Jacobson IM et al. N Engl J Med 2011;364:2405-2416; Zeuzem S et al. N Engl J Med 2011;364:2417-2428). This rate is also higher than the rates seen in the trials that led to boceprevir’s approval, which was roughly 2% in the Sprint-2 trial and 8% and 12% in the two boceprevir arms in the RESPOND-2 trial (Poordad F et al. N Engl J Med 2011;364:1195-1206; Bacon BR et al. N Engl J Med 2011;364:1207-1217).

In a second study, researchers reviewed the records of HCV patients treated with telaprevir-based triple therapy at Mount Sinai Medical Center and Montefiore Medical Center, both in New York City (abstract 1755). Patients had at least 12 weeks of follow-up. Of 157 patients who initiated the triple therapy, 32% discontinued telaprevir prematurely and 21% discontinued treatment due to adverse events. Discontinuation rates were similar in patients with stage F0-F2 and F3-F4 fibrosis. Discontinuation due to adverse events was almost 10% greater than the REALIZE trial that led to telaprevir’s approval (21% vs. 13%; P=0.01).

Dr. Kanwal said that DAAs are effective, and treatment response in clinical practice has been approximately twice as high as seen with pegylated interferon and ribavirin alone.
“Given this, I believe that the message for the clinicians is that these new agents [boceprevir and telaprevir] hold promise, particularly for patients with more advanced fibrosis or cirrhosis, where watchful waiting may not be appropriate. For patients with less advanced fibrosis, waiting for other ‘in-the-pipeline’ antivirals may be a reasonable alternative,” Dr. Kanwal said.
“Treatment decisions in this new era of DAAs may need to be informed with not only the scientific knowledge base of the treating clinician, but also patients’ perceptions of outcome expectancies, risks and benefits associated with the available options and subsequent preferences for treatment,” she added.

Drug–Drug Interactions Overlooked
In another study (abstract 136), researchers found that in the real world, HCV patients frequently use drugs that have the potential to interact with boceprevir and telaprevir. This study was presented at The Liver Meeting by Christina Mayer, PharmD, a postdoctoral research associate at the University of North Carolina at Chapel Hill’s Eshelman School of Pharmacy. Investigators identified adults with chronic HCV infection in a large commercial claims database; drugs with the potential to interact with boceprevir or telaprevir were identified using
Of the 20 most frequently filled prescriptions by 71,584 patients, six had potential for a drug–drug interaction and four had clear indications. For example, 17% of patients were using zolpidem, 14.3% were using tramadol and 11.8% were using alprazolam, all of which have interactions with both boceprevir and telaprevir. Other frequently used drugs that interact with these two DAAs included amlodipine (10.2%), escitalopram (8.1%) and bupropion (7.2%).

Drs. Kanwal and Mayer reported no relevant conflicts of interest.

Tuesday, February 12, 2013

Potential IFN-Free Regimens For HCV


Potential IFN-Free Regimens For HCV
New Treatment Strategies Could Bring ‘Many More Cures’
by Kate O'Rourke
imageBoston—Enthusiasm is growing for the various interferon (IFN)-free therapies on the horizon for patients with hepatitis C virus (HCV) infection. At the recent annual meeting of the American Association for the Study of Liver Diseases (AASLD), The Liver Meeting 2012, four of the six late-breaking abstracts and a slew of other studies discussed new oral regimens that can be used to achieve high rates of sustained virologic response (SVR) in a variety of HCV patient cohorts, including null responders.
“We can see a light at the end of the tunnel,” said Guadalupe Garcia-Tsao, MD, professor of medicine at Yale University, New Haven, Conn., and chief of the section of digestive diseases at the Connecticut Veterans Affairs Healthcare System, West Haven, referring to a future that includes IFN-free regimens for the treatment of HCV infection. “It is going to come to a point where we are going to have a lot of options.”

Dr. Garcia-Tsao, who also is president of the AASLD, thinks that some doctors may choose to “warehouse” or delay treating some patients with HCV infection in anticipation of an IFN-free regimen soon becoming available.

“It depends on where the patient stands in the natural history of the disease,” she explained. “If you are very early in the fibrotic process, and we think we are going to get more effective oral drugs in the next two or three years, would you wait or would you want to go ahead with current therapies?” It requires a big discussion, she said, and ... doctors need to find out what each patient’s priorities are.
Following are highlights from some of the trials of IFN-free therapies presented at the AASLD meeting.

Kris Kowdley, MD, director of research and director of the Liver Center of Excellence at the Digestive Disease Institute, Virginia Mason Medical Center, Seattle, discussed the AVIATOR trial.
The trial tested eight-, 12- and 24-week regimens of a combination of ribavirin plus three direct-acting antiviral agents (DAAs) being developed by Abbott Laboratories: ABT-450, ABT-267 and ABT-333. ABT-450, an NS3/4A protease inhibitor, is coadministered with ritonavir (ABT-450/r) in a once-daily dose. ABT-267, an NS5A inhibitor, also is a once-daily therapy. ABT-333, a non-nucleoside polymerase inhibitor, is used twice daily.

In exploratory studies, combinations containing ABT-450/r have achieved SVR rates greater than 90% in HCV genotype (GT) 1–infected patients. In the current study, researchers set out to identify the optimal drug combination for HCV GT1–infected patients who were either treatment-naive or null responders to previous treatment with peginterferon and ribavirin. To be eligible, participants could not have cirrhosis or HIV infection. Seven arms of the study, which included 571 patients, were evaluated for different drug combinations and regimen durations, up to 24 weeks. Dr. Kowdley presented results of the eight- and 12-week regimens, which included 448 patients.

“Regardless of treatment assignment, very high rates of SVR at week 12 were reached across all categories, both in the treatment-naive and null responders, but in particular, the group receiving three DAAs and ribavirin showed the highest SVR rates,” said Dr. Kowdley, who is clinical professor of medicine at the University of Washington in Seattle. SVR rates at week 12 were 97.5% in the treatment-naive group and 93.3% in null responders. Relapses primarily occurred in patients who received eight weeks of therapy compared with those who received 12 weeks.

Ninety-six percent of HCV GT1a–infected treatment-naive patients and 89% of HCV GT1a–infected null responders achieved SVR at week 12.

“High SVR12 rates were observed across all interleukin-28B [IL28B] genotypes,” Dr. Kowdley noted.

No serious adverse events (AEs) were observed, and only two of the 448 patients discontinued treatment due to an AE attributed to the study drug.

“The most commonly reported AEs were fatigue, headache, insomnia and nausea, which were reported infrequently,” Dr. Kowdley said. An 8% rate of fatigue was identified in one group, but all other AEs were observed at rates of 4% or lower. “The only laboratory irregularity that occurred with any frequency was an elevation of total bilirubin, occurring in 6.7% of treatment-naive patients and in 12.2% of null responders.”

The researchers said they will be moving the combination of ABT-450/r, ABT-267 and ABT-333 forward in Phase III trials, but ABT-450/r and ABT-267 will be coformulated into one tablet. The regimen will be tested with and without ribavirin.

The ELECTRON trial evaluated sofosbuvir (Gilead Sciences), an NS5B inhibitor, as a backbone of antiviral therapy in patients with HCV GT1-3 infection, for treatment-naive patients and patients who previously had been treated (abstract 229). Various drug combinations have been used in the trial, which has 11 arms so far.

Researchers announced that 100% of 25 patients with HCV GT1 infection who were treatment-naive achieved an SVR at week 4 using a combination of sofosbuvir, GS-5885 (Gilead) and ribavirin. HCV genotype or IL28B genotype did not affect sofosbuvir’s performance. AEs were generally mild: 48% of patients experienced at least two AEs, including anemia (20%), headache (4%) and depression (8%).

“In HCV genotype 1 infection, sofosbuvir plus GS-5885 plus ribavirin [taken] for 12 weeks appears to be a safe and effective regimen for treatment-naive patients,” said Edward Gane, MD, deputy director of the New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, who reported the results of the study.

Sound-C2 Trial
The SOUND-C2 trial tested a combination of two drugs developed by Boehringer Ingelheim, faldaprevir and BI 207127—with or without ribavirin, in treatment-naive patients with HCV GTI infection (abstract 84). Faldaprevir is a NS3/4A protease inhibitor, and BI207127 is a non-nucleoside NS5B inhibitor.

The study, which included 362 patients (33 with cirrhosis), had five arms, testing different dosing schemes and different treatment durations, from 16 to 40 weeks. The 28-week regimen, using a twice-daily dosing scheme performed the best, resulting in a 69% SVR overall at week 12 and an 85% SVR at week 12 in HCV GT1b patients. Patients with cirrhosis achieved an SVR of 67%.
The most common AEs were asthenia, pruritus, rash, photosensitivity, jaundice, nausea, vomiting, diarrhea and transient indirect hyperbilirubinemia. Overall, 36% of patients experienced AEs: 12% were considered severe, and 8% led to discontinuation of treatment. The company is launching a Phase III trial to further test this IFN-free drug regimen.

Ribavirin-Free Regimens
Mark Sulkowski, MD, medical director of the Viral Hepatitis Center in the Divisions of Infectious Diseases and Gastroenterology & Hepatology at Johns Hopkins School of Medicine, Baltimore, presented results of a study that tested an all-oral combination of daclatasvir (Bristol-Myers Squibb), an NS5A inhibitor, and sofosbuvir, with or without ribavirin (abstract LBA2). The combination—tested in treatment-naive patients—was given for 24 weeks to patients infected with HCV GT1a, GT1b, GT2 or GT3, and for 12 weeks to patients with HCV GT1a or GT1b. All patients were noncirrhotic

Researchers randomized 44 patients with HCV GT2/3 to one of three treatment groups: daclatasvir 60 mg daily plus sofosbuvir 400 mg daily with or without ribavirin for 24 weeks, or sofosbuvir daily for seven days and then daclatasvir daily plus sofosbuvir daily for a total treatment time of 24 weeks. Researchers also randomized 44 patients with HCV GT1a/1b to receive sofosbuvir every day for seven days and then daclatasvir and sofosbuvir daily for a total of 24 weeks, or daclatasvir plus sofosbuvir daily, with or without ribavirin, for 24 weeks. During a second stage of the study, 82 patients with HCV GT1a or GT1b were randomized to receive 12 weeks of daclatasvir plus sofosbuvir with or without ribavirin.

Overall, more than 93% of patients with HCV GT1, GT2 or GT3 achieved an SVR with the drug combinations. Among the 44 patients with HCV GT2 or GT3 infection, 93% achieved an SVR at week 24, with one patient having a confirmed relapse. Among the 126 patients with HCV GT1 infection, 96% of those who had reached the 12 weeks post-treatment stage had an SVR at week 12; this included three patients who did not have an SVR at week 4. The SVR rate at week 24 in this group was 98%. The drug combination was well tolerated.

“Virologic response did not vary according to IL28B genotype, viral subtype or with the administration of ribavirin,” Dr. Sulkowski said. “Up until very recently, ribavirin has played a critical role in hepatitis C treatment regimens. It was surprising and also encouraging that this combination—daclatasvir, an NS5A inhibitor, plus sofosbuvir, a nucleotide analog—may not require ribavirin.”

Gregory Everson, MD, director of the section of hepatology at the University of Colorado Denver, in Aurora, presented results from a Phase IIa open-label study of AI443-014 (abstract LBA3), which tested a 12-week regimen of three drugs developed by Bristol-Myer Squibb: daclatasvir, asunaprevir and BMS-791325. The four-armed study included treatment-naive, noncirrhotic patients with HCV GT1 infection. Results were presented only for the two arms of the study that included BMS-791325 75 mg plus daclatasvir and asunaprevir. One group of patients was treated for 12 weeks (n=16) and the other was treated for 24 weeks (n=16). Patients (mean age, 48 years) had a high viral load and 75% were infected with HCV GT1a. (The other two study arms received 150 mg of the investigational agent.)

In the group receiving treatment for 24 weeks, researchers only had complete data for SVR at week 4 (94%). Two patients assigned to this arm discontinued treatment before completing the 24-week phase: One patient, who withdrew consent at week 9 of treatment, was lost to follow-up (HCV RNA was undetectable at week 8), and the other patient, who stopped treatment at week 14 due to poor venous access, achieved SVR at week 4. In the group that received 12 weeks of treatment, SVR was 94% at weeks 4 and 12. Two patients assigned to this arm discontinued treatment before completing the full 12-week phase: One patient stopped treatment at week 11 but still achieved SVR at week 12, and the other completed the 12 weeks of treatment but failed to return for post-treatment follow-up (HCV RNA was undetectable at end of treatment). These high rates for SVR were achieved despite the more difficult-to-treat characteristics of HCV GT1a infection and non-CC IL28B genotypes of the patients. Although four patients in the study discontinued treatment prematurely, there were no discontinuations because of AEs.

“The regimen was generally well tolerated. There was no viral breakthrough and no post-treatment relapse to date,” Dr. Everson said. “Some of these patients have been followed now for 24 weeks, and with available data to date, we have not yet seen relapse. Further investigation of this regimen in the treatment of hepatitis C is warranted.”

The trial is being extended into other populations, including null responders, treatment-experienced patients and patients with more advanced fibrosis.

Dr. Everson cautioned, however, that the current results come from a small number of select patients.

Difficult-to-Treat Populations
Anu Osinusi, MD, MPH, of SAIC-Frederick Inc./National Institutes of Health (NIH), Bethesda, Md., presented the interim results of the NIH SPARE (Selective bladder Preservation Against Radical Excision) trial.

The two-part trial tested six months of treatment with sofosbuvir in combination with ribavirin in patients with treatment-naive HCV GT1. In the first phase, 10 patients with stage 0 to 2 fibrosis received sofosbuvir and a weight-based dose of ribavirin 1,000 to 1,200 mg per day. In the second phase, 50 patients with all stages of fibrosis, including Child Pugh Class A, were randomized to receive either weight-based or low-dose ribavirin (600 mg) daily.

Eighty-three percent of the study population was black, largely overweight, and had the less favorable IL28B CT/TT genotype. A majority of patients had a high HCV viral load and GT1a infection.

The investigators found that 77% of patients who received weight-based ribavirin had an SVR at week 4, and 56% of those who received low-dose ribavirin had an at week 4.
“There were no safety signals or drug-related discontinuations in this study,” Dr. Osinusi said.

Many More Cures
“It was not long ago that nearly all hepatologists felt that IFN would always be a mainstay of HCV therapy,” Dr. Everson observed. “The current experience is proving that bias to be wrong: Clearly IFN-free treatment is not only possible but highly effective. IFN-free treatment represents a real breakthrough for patients: a high likelihood for SVR; few, if any, side effects; shorter duration of treatment; and newer formulations combining two or more antivirals into a single tablet that will improve compliance to the treatment regimen. Simply speaking, these advances should translate into many more cures.”

Drs. Garcia-Tsao and Osinusi reported no conflicts of interest. Dr. Kowdley has received grants/research support from and serves on the advisory board of Abbott Laboratories. Dr. Gane has served on committees and review panels for Boehringer Ingelheim, Gilead Sciences, Jannsen Cilag, Novartis, Pharmasset, Roche and Vertex Pharmaceuticals. Dr. Sulkowski has served as a consultant for Abbott Laboratories, BIPI, Bristol Myers-Squibb, Gilead Sciences, Janssen, Merck & Co., Novartis, Roche/Genentech and Vertex Pharmaceuticals; he has received grants/research support from Abbott Laboratories, BIPI, Gilead Sciences, Janssen, Merck & Co., Roche/Genentech and Vertex Pharmaceuticals; and he has served on advisory committees and review panels for Pfizer. Dr. Everson has received grants/research support from Abbott Laboratories, Bristol-Myers Squibb, Conatus, GlobeImmune, GlaxoSmithKline, Pfizer, Pharmasset, PSC Partners, Roche/Genentech, Schering Plough, Tibotec, Vertex Pharmaceuticals and ZymoGenetics; he has served on advisory committees and review panels for Hep C Connection and Roche/Genentech Merck; he has served as a consultant for Abbott Laboratories and Roche/Genentech; and he has served as a board member for HepQuant LLC and PSC Partners.

Friday, January 25, 2013

TGIF HCV Rewind: Ribavirin induced anemia and New interferon speeds HCV virologic responses

Hello folks,
Its a cold snowy day here in Michigan, hope its warmer in your part of the world

Welcome to HCV rewind, a weekly digest of news, research and a look at today's headlines.

Interferon Free

Published recently online at Medscape, is a look into the therapeutic options beyond interferon for the treatment of hepatitis C, presented by Catherine AM Stedman.

Current Prospects for Interferon-free Treatment of Hepatitis C in 2012
Published Jan 22 2013  in Journal of Gastroenterology and Hepatology

Numerous other DAAs are in clinical development, and phases 2 and 3 trials are evaluating interferon-free combination DAA therapy.

Interferon-free sustained virologic responses have now been achieved with combinations of asunaprevir and daclatasvir; sofosbuvir and ribavirin; sofosbuvir and daclatasvir; faldaprevir and BI207127; ABT-450, ritonovir and ABT-333; ABT-450, ritonovir and ABT-072; miracitabine, danoprevir and ritonavir; and alisporivir and ribavirin.

Some drugs are genotype-specific in their activity, whereas others are pan-genotypic, and differential responses for the genotype 1 subtypes 1a and 1b have emerged with many DAA combinations. Viral breakthrough and resistance are important considerations for future trial design. The prospect of interferon-free combination DAA therapy for hepatitis C virus is now finally becoming a reality.

Continue reading at Medscape or here on the blog.

Updates Telaprevir

Futility rules defined for telaprevir-based HCV therapy
Therapy with telaprevir, peginterferon, and ribavirin should be stopped in both treatment-naive and treatment-experienced patients with hepatitis C virus infection if HCV RNA levels are greater than 1,000 IU/mL at week 4 or 12 of treatment, according to new futility rules developed using phase II and III trial data.
The rules are important for preventing needless drug exposure and to minimize the development of drug-resistant variants in patients with little or no chance of achieving sustained virologic response, reported Dr. Nathalie Adda of Vertex Pharmaceuticals Inc., Cambridge, Mass., and her colleagues.
Continue reading @ GI and HEPATOLOGY News

Pegylated interferon and ribavirin

Reported by Reuters; About one in six of the estimated 5 million U.S. patients with chronic hepatitis C (HCV) has a contraindication to standard treatment with pegylated interferon and ribavirin, researchers say.

The study published online January 7 in Alimentary Pharmacology & Therapeutics included 45,690 hepatitis C patients diagnosed between 2004 and 2009, a reported 7,903 or 17.3% were found to have contraindications to therapy. Notably the majority -  6,928, (87.6%) had only one contraindication.

The most common contraindications were bipolar disorders (6.5%), anemia (5.9%), and pregnancy (1.9%). The study concluded, "Clinical assessment of contraindications as relative and/or modifiable should be considered and used to determine if patients could benefit from current pegylated-interferon–containing triple therapy or future pegylated-interferon– or ribavirin-free regimens.

"Dr. Andrew H. Talal from the State University of New York, Buffalo, told Reuters Health by email. "The fact that the majority of the contraindications are reversible or readily treatable was another surprising aspect."

This study was funded in part by Genentech Inc. and F. Hoffmann-La Roche Ltd; some of the authors are employees of Genentech.

Read the article here, or the full text published in Alimentary Pharmacology & Therapeutics.

In Todays News - Treatment response improved neurocognitive function in patients with chronic HCV

Patients with chronic HCV who responded to treatment with pegylated interferon and ribavirin experienced a subsequent improvement to neurocognitive performance in a recent study.

Continue reading....

Hepatitis C In Elderly Patients

Commentary: efficacy and safety of ribavirin plus pegylated interferon-alpha in geriatric patients with chronic hepatitis C

The study of Hu et al. from Taiwan adds evidence on the safety and efficacy of treatment with pegylated interferon-alpha plus ribavirin (PR) in elderly patients with chronic hepatitis C virus (HCV) infection.......

Possibly the development of new all oral HCV therapies with direct-acting antivirals will become the standard of care in the difficult to treat HCV patients, including the elderly.

Read more here.....
Research - Hepatitis C Genotypes

New Ways to Study HCV, Genotypes 3 and 4
Posted on January 21, 2013
by Kristine Novak, PhD, Science Editor
Researchers can now study replication of Hepatitis C virus genotypes 3 and 4 in cultured cells, described in 2 articles in the January issue of Gastroenterology. These new tools will improve our understanding of how they cause liver disease, and could lead to new treatments.
There are 6 major HCV genotypes. Genotypes 1 and 2 are the most prevalent in North America, Europe, and Japan, and are the most highly studied. However, other genotypes have specific characteristics. Genotype 3a infection can cause hepatic steatosis, and is more resistant to treatment with telaprevir and boceprevir. Genotype 4 is prevalent in the Middle East and many African countries, and is becoming more common in central and northern Europe; it accounts for 93% of HCV infections in Egypt, and 5%–15% of infections in several European countries....
Continue reading....

Today From Medscape
IL28B Polymorphisms Predict Response to Therapy Among Chronic Hepatitis C Patients With HCV Genotype 4

Discussion Only
View full text @ Medscape

This study confirms that SNP near IL28B strongly predicts virological response to therapy among chronic hepatitis C with HCV-4. Although HCV-4 was initially branded as a 'difficult-to-treat' genotype, recent data, especially from Egypt, where HCV-4 represents >90% of HCV infections,[14] have suggested SVR rates between 43 and 70%, that is, intermediate between those reported for HCV-1 and HCV-2 or HCV-3.[14]

Major factors influencing response are Egyptian origin, absence of advanced fibrosis and insulin resistance – measured as homoeostasis model assessment of insulin resistance or homoeostasis model assessment of insulin resistance (HOMA-IR).[15]

As multivariate analyses have shown that polymorphisms near IL28B are the strongest predictors of response to therapy among HCV-1, and much less so in HCV-2 and -3,[3–7] the interest of studying these genetic variants as predictors of response in HCV-4 is obvious. The amount of available data is, however, limited and often gathered on ethnically heterogeneous populations of patients. Three series reported patients monoinfected with HCV: one analysed 102 cases from Austria (97% from Egypt),[8] another on 103 patients from Milan, Italy (68% from Egypt)[9] and a third on 82 patients from different ethnic groups (51% Egyptians, 34% Europeans and 13.4% Sub-Saharan Africans).[10] These studies identified several baseline predictors of SVR in HCV-4: female sex,[9]rs12979860 CC genotype,[8–10] Egyptian ethnicity,[9] low stages of liver fibrosis[8,9] or low viral load.[8,10]

In two additional studies on small series of patients (n = 13 and n = 23, respectively) coinfected with HCV and HIV[11,12] suggest that both viremia and low stages of fibrosis predicted response independently of IL28B SNP, although in the larger study patients with HCV-1 and HCV-4 were pooled together, rendering the analysis difficult. Our present study, the largest to date on patients of homogeneous ancestry (all from Middle East), confirms the strong predictive value of IL28B genotypes on SVR, and, indeed, predictors of SVR were similar to those previously reported, with the exception of SNP at marker rs12979860 being replaced by rs8099917. In our series, in fact, both the absence of advanced fibrosis and polymorphisms near IL28B were independent predictors of SVR, confirming that algorithms of treatment for HCV-4 should include at least these two variables.

Additional prospective analyses are warranted to ascertain whether on-treatment variables should also be considered, for example, to tailor therapy duration in patients with rapid virological response (RVR). In general, in HCV-monoinfected patients with HCV-4, IL28B polymorphisms do not seem to predict SVR in patients who have achieved RVR.[8,9] However, IL28B genotype may be included in treatment algorithms to tailor therapy among patients who have failed to achieve RVR.[9] In the study from Milan,[9] HCV-4 non-RVR patients with CT/TT genotypes at marker rs12979860 had SVR rates as low as 23%, compared with 75% reached by patients with the CC genotype. These Authors stated that lack of RVR in patients with unfavourable IL28B genotypes should not be considered as a univocal stopping rule; however, premature therapy termination should be considered in cases with severe treatment side effects, poor motivation or severe comorbidities.[9] In our study, we could not collect data on RVR.

Thus, also given the small sample size of studies conducted so far, additional prospective studies are warranted to assess the predictive value of IL28B polymorphisms on the virological response to therapy among HCV-4, possibly assessing the impact of liver fibrosis stage, HOMA-IR score and on-treatment viral response relative to IL28B genotypes.

Thus, IL28B polymorphisms are strong predictors of virological response also in chronic hepatitis C with HCV-4, confirming previous reports[8–12] and extending data on spontaneous eradication.[15] Interestingly, IL28B SNP do not seem to predict viral response to therapy among patients with HCV-5 from the same genetic ancestry as the present study.[16] Whether these polymorphisms may be used to tailor therapy duration in patients with HCV-4 remains to be determined by larger prospective studies.

Free registration required, full text available here

Do HCV Patients Still Need A Liver Biospy In 2013?

Over at CCO the age old debate lives on rather hepatitis C patients still need a liver biopsy for assessing liver damage, in the article one physician is satisfied with today's non-invasive methods, Mark S. Sulkowski MD writes; "With interferon-free, all-oral therapies on the near-term horizon, I am increasingly comfortable relying on patient history, physical exam, routine laboratory tests, and liver imaging as well as noninvasive serum markers to obtain a picture of liver health.." 

View all links to the article here,  along with a review of imaging technology developed by Mayo to detect liver fibrosis called Magnetic Resonance Elastography, or MRE. 

2013-Guide to Clinical Trials for People with Hepatitis C

This month  TAG published an insightful second edition guide to hepatitis C clinical trials, written by Tracy Swan and Matt Sharp.

Of Interest
A Study of TMC435 in Combination With PSI-7977 (GS7977) in Chronic Hepatitis C Genotype 1-Infected Prior Null Responders To Peginterferon/Ribavirin Therapy or HCV Treatment-Naive Patients

Hepatitis C - 8 Clinical Trials For: Sofosbuvir (GS-7977)

Hepatocellular carcinoma (HCC)

This week in an analysis of HALT-C data, investigating the surveillance of liver cancer in academic centers published by the American Journal of Gastroenterology, reported only 20% of hepatocellular carcinoma (HCC), was found at a very early stage.

The primary goal of the HALT-C Trial was to determine if ongoing therapy with pegylated interferon monotherapy could suppress the Hepatitis C virus and slow disease progression, including the development of liver cancer in patients who were not able to achieve SVR using pegylated interferon and ribavirin.

Full text is available here

Liver Cirrhosis

When the Spleen Gets Tough, the Varices Get Going

Published in Gastroenterology - Volume 144, Issue 1, January 2013
In this era of personalized medicine, it is necessary to stratify different risk groups among patients with cirrhosis. As recently proposed, a revised staging of cirrhosis should start with its main classification of compensated and decompensated cirrhosis, 2 separate entities with different prognostic significance.  Decompensated cirrhosis is defined by the presence of complications that are mostly secondary to portal hypertension: Ascites, variceal hemorrhage, and/or hepatic encephalopathy. Compensated cirrhosis would in turn be composed of 2 substages: Without varices or with varices. These 2 substages of compensated cirrhosis also have different prognostic significance; patients without varices have a significantly better survival than those with varices....
Full text available here...

Liver Cirrhosis - Poor Sleep, Depression and Anxiety

Published January 22 2013 online at BMC Gastroenterology;

Studies have shown psychological distress in patients with cirrhosis, yet no studies have evaluated the laboratory and physiologic correlates of psychological symptoms in cirrhosis. This study therefore measured both biochemistry data and heart rate variability HRV analysis, and aimed to identify the physiologic correlates of depression, anxiety, and poor sleep in cirrhosis. The found; increased serum AST and abnormal autonomic nervous activities by HRV analysis were associated with psychological distress in cirrhosis. Because AST is an important mediator of inflammatory process, further research is needed to delineate the role of inflammation in the cirrhosis comorbid with depression.

Download PDF here

Of Interest - Hepatitis C and Sleep

by Lucinda Porter, RN
Being tired is a common hepatitis C symptom. However, before blaming fatigue on hepatitis C, rule out other causes, including sleep disorders. There are many types of sleep disorders, and one of the worst is insomnia.
Continue reading... 
Big Pharma

BMS-986094 Lawsuit

We heard more on the lawsuit involving 15 patients who were tragically hurt - one died- during the company-sponsored clinical trials of the hepatitis C drug BMS-986094. On Thursday The Wall Street Journal reported that Bristol-Myers Squibb agreed to pay $80 million to 15 patients who were harmed during the clinical trials.

Read the story @ WSJ 

HCV Transmission - The Tattoo

Reuters Reports - Hepatitis C linked to ink
(Reuters Health) - Researchers are hoping that people will do some research about where to get a tattoo, after a study found a link between body art and hepatitis C.The new study found that people with the virus were almost four times more likely to report having a tattoo, even when other major risk factors were taken into account, co-author Dr. Fritz Francois of New York University Langone Medical Center told Reuters Health. 
Although the study could not prove a direct cause and effect, "Tattooing in and of itself may pose a risk for this disease that can lay dormant for many, many years," Francois said.
The abstract is available here, the article here.

Related @
If tattoos came with ‘fine print’ warnings…
Hepatitis C risk increases for anyone who gets one or more tattoos.
Read more.

HCV Transmission In A Clinical Setting

A Second New York hospital warns of potential HIV, hepatitis C or hepatitis B infection
A second western New York hospital is notifying patients that they may have been exposed to HIV, hepatitis B or hepatitis C through the improper sharing of insulin pens, hospital officials said Thursday. 
Olean General Hospital was mailing letters to 1,915 patients who received insulin at the hospital from November 2009 through last week, advising them to call to arrange for blood testing. The risk of infection is very low, hospital officials said, but they wanted patients to be aware of the possibility. 
Hospital officials said the action follows an internal review conducted after the Veterans Affairs hospital in Buffalo discovered more than 700 patients may have been exposed to blood-borne pathogens over a two-year period when multi-use pens intended for use by a single patient may have been used on more than one person. 
“Interviews with nursing staff indicated that the practice of using one patient’s insulin pen for other patients may have occurred on some patients,” said Timothy Finan, president and chief executive of Upper Allegheny Health System, the parent company of the Olean hospital
 Continue reading......

Liver Health - Don’t Double Up on Acetaminophen

You have flu symptoms, so you've been getting some relief for the past two days by taking a cough and flu medicine every few hours. Late in the day, you have a headache and you think about grabbing a couple of acetaminophen tablets to treat the pain.

Stop right there.

What you may not realize is that more than 600 medications, both prescription and over-the-counter (OTC), contain the active ingredient acetaminophen to help relieve pain and reduce fever. Taken carefully and correctly, these medicines can be safe and effective. But taking too much acetaminophen can lead to severe liver damage.

Acetaminophen is a common medication for relieving mild to moderate pain from headaches, muscle aches, menstrual periods, colds and sore throats, toothaches, backaches and to reduce fever. It is also used in combination medicines, which have more than one active ingredient to treat more than one symptom.

'Tis Cold and Flu Season

The National Institutes of Health (NIH) says that Americans catch one billion colds per year and as many as 20% of Americans get the flu. Moreover, 7 in 10 Americans use OTC medicines to treat cold, cough and flu symptoms.

Fathia Gibril, M.D., M.HSc., a supervisory medical officer at the Food and Drug Administration (FDA), explains that consumers looking for relief from a cold or the flu may not know that acetaminophen comes in combination with many other medications used to treat those symptoms. "So if you're taking more than one medicine at a time," she says, "you may be putting yourself at risk for liver damage."

Symptoms of acetaminophen overdose may take many days to appear, and even when they become apparent, they may mimic flu or cold symptoms. The current maximum recommended adult dose of acetaminophen is 4,000 milligrams per day, To avoid exceeding that dose:
  • don't take more than one OTC product containing acetaminophen,
  • don't take a prescription and an OTC product containing acetaminophen, and
  • don't exceed the recommended dose on any product containing acetaminophen.
"When you're at the store deciding which product to buy, check the 'Drug Facts' label of OTC cold, cough and flu products before using two or more products at the same time," Gibril says. If you’re still not sure which to buy, ask the pharmacist for advice.

FDA has an online list of brand names of products containing acetaminophen8.
Rely on Health Care Experts

Acetaminophen is used in many commonly prescribed medications in combination with pain relievers such as codeine, oxycodone and hydrocodone. As of January 2011, FDA reported that overdoses from prescription medicines containing acetaminophen accounted for nearly half of all cases of acetaminophen-related liver injury in the U.S. When your health care professionals prescribe a drug, be sure to ask if it contains this active ingredient, and also to inform them of all other medicines (prescription and OTC) and supplements you take.

Even if you still have fever or pain, it's important not to take more than directed on the prescription or package label, notes FDA supervisory medical officer Sharon Hertz, M.D. But be careful, the word "acetaminophen" is not always spelled out in full on the container's prescription label. Abbreviations such as APAP, Acetaminoph, Acetaminop, Acetamin, or Acetam may be used instead.

When buying OTC products, Hertz suggests you make it a habit of telling the pharmacist what other medications and supplements you’re taking and asking if taking acetaminophen in addition is safe.

When the medicine is intended for children, the "Directions" section of the Drug Facts label tells you if the medicine is right for your child and how much to give. If a dose for your child's weight or age is not listed on the label and you can't tell how much to give, ask your pharmacist or doctor what to do.

If you're planning to use a medication containing acetaminophen, you should tell your health care professional if you have or have ever have had liver disease.

Acetaminophen and alcohol may not be a good mix, either, Hertz says. If you drink three or more alcoholic drinks a day, be sure to talk to your health care professional before you use a medicine containing acetaminophen.

This article appears on FDA's Consumer Updates page9, which features the latest on all FDA-regulated products.
January 24, 2013

Related - Hepatitis C and Tylenol

Written by Lucinda Porter, RN
The most common question I am asked by hepatitis C patients, “Is Tylenol (acetaminophen or paracetamol as it is called in other countries) safe for the liver? The answer is, “Yes, if taken as directed.”
Read the full article @

Liver Health - Binge Drinking

Binge drinking will exacerbate liver injury, especially if comorbid conditions such as obesity, Hepatitis C, or HIV infection exist.
Alcoholic liver disease (ALD) is characterized by a fatty liver, hepatitis, fibrosis, and cirrhosis. Binge drinking is on the rise worldwide, and is particularly common in the U.S. A review of studies addressing the effects of binge drinking on the liver underscores the complex interactions among various immune, signaling pathways, epigenetic, and metabolic responses of the liver to binge drinking.  
"Therefore, people should not binge drink, especially on an empty stomach, and if they are chronic heavy drinkers, binge drinking will exacerbate liver injury, especially if comorbid conditions such as obesity, Hepatitis C, or HIV infection exist."
Continue reading....

Heavy Alcohol Use Increases Liver Cancer Risk for People with Hepatitis B
Hepatitis B patients with liver cirrhosis who consumed large amounts of alcohol were more likely to develop hepatocellular carcinoma than people who drank less, according to a report in the December 6, 2012, online edition of the Journal of Hepatology .
Read more @ HIV and Hepatitis

In Todays News -  Liver Health


FDA: Significant Liver Injury Associated With Use of Tolvaptan

ROCKVILLE, Md -- January 25, 2013 -- The US Food and Drug Administration (FDA) and Otsuka pharmaceuticals are notifying healthcare professionals of significant liver injury associated with the use of tolvaptan (Samsca).

In a double-blind, 3-year, placebo-controlled trial in about 1,400 patients with autosomal dominant polycystic kidney disease (ADPKD) and its open-label extension trial, 3 patients treated with the drug developed significant increases in serum alanine aminotransferase (ALT) with concomitant, clinically significant increases in serum total bilirubin.

In the trials the maximum daily dose of tolvaptan administered (90 mg in the morning and 30 mg in the afternoon) was higher than the maximum 60 mg daily dose approved for the treatment of hyponatremia.

Most of the liver enzyme abnormalities were observed during the first 18 months of therapy. Following discontinuation of treatment, all 3 patients improved.

An external panel of liver experts assessed these 3 cases as being either probably or highly likely to be caused by tolvaptan.

These findings indicate that tolvaptan has the potential to cause irreversible and potentially fatal liver injury.

These data are not adequate to exclude the possibility that patients receiving tolvaptan for its indicated use of clinically significant hypervolemic and euvolemic hyponatremia are at a potential increased risk for irreversible and potentially fatal liver injury.

Tolvaptan is a selective vasopressin V2-receptor antagonist indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia. Tolvaptan is not approved for the treatment of ADPKD.

Recommendations for Healthcare Professionals:

· Healthcare providers should perform liver tests promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.

· If hepatic injury is suspected, tolvaptan should be promptly discontinued, appropriate treatment should be instituted, and investigations should be performed to determine probable cause.

· Tolvaptan should not be re-initiated in patients unless the cause for the observed liver injury is definitively established to be unrelated to treatment with Samsca.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of this product to the FDA's MedWatch Safety Information and Adverse Event Reporting

· Complete and submit the report Online:

Forms or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

SOURCE: US Food and Drug Administration

Published Today - In The Current Issue Of GI & Hepatology News

AASLD - Ribavirin induced anemia
IMNG Medical News BOSTON

Cirrhotic patients have similar hepatitis C virus SVRs when treated with either ribavirin dose reduction or erythropoietin

 Anemia developed significantly more often among patients with hepatitis C virus infection and compensated cirrhosis than among noncirrhotic patients during triple therapy in a randomized, open-label trial of treatment-naive patients, but in most instances the anemia was effectively treated.

In an anemia management subanalysis of a study comparing sustained virologic response (SVR) rates in cirrhotic and noncirrhotic patients treated with boceprevir (Victrelis), pegylated interferon alfa-2b (Peg-Intron), and ribavirin (RBV), 57% of patients with cirrhosis and anemia treated with a ribavirin dose reduction had an SVR, compared with 64% of those treated with erythropoietin.

Among noncirrhotic patients with anemia, the respective SVR rates were 73% and 72%. None of the differences between those treated with a RBV dose reduction or erythropoietin was significant in cirrhotic and noncirrhotic patients, Dr. Eric J. Lawitz, AGAF, reported at the annual meeting of the American Association for the Study of Liver Diseases. ª

Sustained viral responses are comparable in cirrhotic patients when anemia is managed by ribavirin dose reduction or erythropoietin,º said Dr. Lawitz, medical director and principal investigator at Alamo Medical Research in San Antonio.

He also noted that ribavirin dose reductions should be the initial strategy for managing anemia, followed, if necessary, by erythropoietin. In the trial, 687 treatment-naive patients with hepatitis C virus (HCV) infections were treated for 4 weeks with pegylated interferon (PEG-IFN) alfa-2b and RBV, then 24 or 44 weeks of boceprevir added in.

Baseline hemoglobin (Hb) levels ranged from 12 g/dL to 15 g/dL for women, and from 13 g/dL to 15 g/dL for men. Patients with Hb approaching 10 g/dL or less (tested from baseline through week 48) were randomized to either ribavirin dose reduction (249 patients) in 200-mg increments (first increment of 400 mg for initial 1,400-mg daily doses) at the investigators' discretion, or to erythropoietin (251 patients) at 40,000 U/week, modifiable to 20,000 U/week or 60,000 U/week at the investigator's discretion.

The remaining patients received anemia prophylaxis but were not randomized. If the Hb level dropped to 8.5 g/dL, patients could receive the other treatment as a secondary intervention, and patients with Hb 7.5 g/dL were discontinued from all study drugs.

Primary efficacy measures for all patients (cirrhotic and noncirrhotic) in each anemia strategy group were identical, with 82% having an end-oftreatment response, 71% having an SVR, and 10% experiencing relapse. Among cirrhotic vs. noncirrhotic patients, rates were 68% vs. 76% for end-of-treatment response , 55% vs. 64% for SVR, and 18% vs. 11% for relapse. Patients with cirrhosis were significantly more likely to require a secondary anemia intervention (44% vs. 26%, P = .009).

Among noncirrhotic patients (but not cirrhotic patients), a secondary anemia intervention was associated with a greater likelihood of SVR (80% vs. 70% for only one intervention, P = .05).

Serious adverse events occurred in 20% of cirrhotic patients and 12% of noncirrhotic patients, but only one study death occurred. The noncirrhotic patient died of a cardiac arrest, which was considered to be unrelated to therapy.

Treatment-emergent adverse events occurred in 3% of patients with cirrhosis and 2% of those without cirrhosis. Drug discontinuation for adverse events occurred in 17% of cirrhotic patients, and 16% of noncirrhotic patients, according to Dr. Lawitz.

Cirrhotic patients were more likely to have Hb concentrations ranging from 6.5 to 8.0 g/dL than were noncirrhotic patients, but no patient in either group had an Hb concentration below 6.5 g/dL.

Neutrophil counts in the range of 500-749/mm3 occurred in 24% of cirrhotic patients and 27% of noncirrhotic patients, and counts below 500/mm3 were seen in 20% and 12%. Platelet counts from 25,000 to 49,999/mm3 occurred in 22% of cirrhotic patients and 2% of noncirrhotic patients.

Counts below 25,000/mm3 were seen in 3% vs. less than 1%, respectively. Transfusion rates were similar between the groups.

AASLD - New interferon speeds HCV virologic responses
Medical News BOSTON

 Call it interferon 3.0. An investigational form of the immunomodulator, known as interferon- lambda, appeared to be effective against chronic hepatitis C virus infections, but had fewer side effects than interferon alfa, in two separate clinical trials.

In a phase IIb study, ribavirin plus pegylated interferon-lambda-1a (IFNL/ RBV) was comparable in efficacy to ribavirin plus pegylated interferon alfa-2a (PEG-IFN/RBV) in treatment- naive patients with hepatitis C (HCV) genotype 1 or 4 viral infections, Dr. Andrew J. Muir reported at the annual meeting of the American Association for the Study of Liver Diseases.

The improved tolerability, together with a faster time to virologic response, supports the further assessment of lambda-based, directacting antiviral combination regimens in patients chronically infected with HCV genotypes 1 or 4,º said Dr. Muir, clinical director of hepatology in the department of medicine at Duke University Medical Center, Durham, N.C.

In a separate small study also presented at the meeting, IFN-L/RBV, combined with a direct-acting antiviral agent, yielded high rates of sustained virologic response (SVR) in Japanese patients with HCV genotype 1b infections, said Dr. Namiki Izumi of Musashino Red Cross Hospital in Tokyo. IFN-L is a type III interferon with strong antiviral activity but a restricted receptor distribution that is reputed to give the drug a better tolerability profile than the alfa interferons currently in widespread clinical use.

Comparing New and Old IFNs
In the EMERGE phase IIb study, Dr. Muir and his colleagues randomized 527 noncirrhotic, treatment-naive adults with HCV genotypes 1-4 on a 1:1:1:1 basis to either PEG-IFN 180 mcg weekly plus daily ribavirin or IFN-L at dose levels of 120, 180, or 240 mcg weekly plus daily ribavirin.

Because of safety issues, patients with genotypes 1 and 4 assigned to receive the 240-mcg dose of IFN-L had their dose reduced to 180 mcg at study week 12, and this dose level was subsequently chosen for phase III trials.

Dr. Muir reported results through 72 weeks of follow-up for 407 patients with genotypes 1 or 4 treated for 48 weeks. Approximately 60% of patients in each of the four treatment arms completed treatment and follow-up. IFN-L at the 180-mcg dose was associated with significantly more rapid virologic responses at week 4 (RVR4 14.7% vs. 5.8%) and complete early virologic responses at week 12 (55.9% vs. 36.9%) than was PEG-IFN (P less than .05 for each comparison).

However, there were no significant differences in response rates at either the end of treatment or in SVR24 at last follow-up, and relapse rates were similar between the groups.

Adverse events of any grade were similar among the groups, except for lower percentages of myalgia (5.9% for IFN-L vs. 33.0% for PEG-IFN), pyrexia (7.8% vs. 33%, respectively), chills (3.9% vs. 21.4%), and arthralgia (5.9% vs. 20.4%). Treatment-emergent liver abnormalities included alanine aminotransferase (ALT) 5 to 10 times the upper limit of normal in 2.9% of patients on IFN-L, compared with 4.9% for those on PEG-IFN.

In contrast, total bilirubin levels 2.6 to 5 times the upper limit of normal were seen in 5% vs. 3.9%, respectively. In both the 120-mcg and 180- mcg IFN-L groups and the PEG-IFN group, 1% of patients required dose reductions due to liver-related lab abnormalities. In all, 2.9% of patients of IFN-L discontinued the drug for liver abnormalities, compared with 1.9% for PEG-IFN.

High SVR With Lambda and Direct- Acting Antivirals
In the D-LITE study, Dr. Izumi and her colleagues compared IFN-L/RBV in combination with either daclatasvir, an investigational viral NS5A replication complex inhibitor, or asunaprevir, an investigational NS3 protease inhibitor, with each group including a placebo for the alternate direct-acting antiviral agent. (For example, patients receiving IFN-L/RBV and daclatasvir also received an asunaprevir placebo.)

In addition, the trial contained a substudy arm with patients assigned to PEG-IFN/RBV with daclatasvir and asunaprevir placebos; Dr. Izumi reported only on the IFN-L arms. All patients in the IFN-L groups were treated for 24 weeks, at which point those patients who did not have a protocol-defined response (PDR) were given an additional 24 weeks of treatment.

A PDR was defined as an HCV RNA level at week 4 below the lower limit of quantification (less than 25 IU/mL) and undetectable HCV RNA at 12 weeks.

In the daclatasvir group, eight of eight patients had a PDR, compared with five of six in the asunaprevir arm. The single patient without a response in the latter arm discontinued therapy for an adverse event during week 3.

All eight patients in the daclatasvir arm and the five remaining patients in the asunaprevir arm had week 4 and week 12 sustained virologic responses (SVR4 and SVR12).

Grade 3 or 4 adverse events occurred in one of eight patients on daclatasvir, and in four of five on asunaprevir.

There were no grade 3 or 4 lab abnormalities among patients on daclatasvir. In the asunaprevir group, there was one case of hemoglobin abnormalities, three with elevated ALT, four with elevated aspartate aminotransferase, and one with elevated total bilirubin.

The authors concluded that the combination of IFN-L/RBV and daclatasvir had the best safety profile, and that the data support further investigation of the combination in patients with HCV genotype 1b.

Both the EMERGE IIb and DLITE studies were supported by Bristol-Myers Squibb.
Dr. Muir reported receiving grant and research support and serving on advisory committees or review panels for the company.
Dr. Izumi reported receiving speaking and teaching fees from the company.

AASLD - Triple therapy has poor safety in cirrhotic hepatitis C
Medical News BOSTON

 In patients with chronic hepatitis C virus infections and compensated cirrhosis, a combination of a direct-acting antiviral agent, pegylated interferon, and ribavirin produced high on-treatment virologic response rates, but at the cost of significantly increased toxicities in an interim analysis of a French multicenter trial.

Although the efficacy of direct-acting antiviral regimens involving the protease inhibitors telaprevir (Incivek) and boceprevir (Victrelis) combined with pegylated interferonalfa-2a or -2b in combination with ribavirin (PEG-IFN/RBV) in cirrhotic nonresponders to prior therapy was good, their safety was ª poor,º said Dr. Christophe Hézode of Hôpital Henri Mondor, Créteil, France.

Virologic response at 16 weeks in a per-protocol analysis was 92% with telaprevir and 77% with boceprevir. However, there were increased rates of serious adverse events and more difficult-to-manage anemia than in phase III trials for telaprevir and boceprevir, which included only a few patients with cirrhosis, Dr. Hézode said at the annual meeting of the American Association for the Study of Liver Diseases.

In treatment-experienced cirrhotic patients with platelet counts of 100,000/mm3 or serum albumin levels below 35 g/L, clinicians should treat on a case-by-case basis because of the high risk for severe complications, Dr. Hézode said. Cirrhotic experienced patients without predictors of severe complications should be treated, but carefully monitored, he added.

Dr. Hézode and his coauthors in the French Cohort of Therapeutic Failure and Resistances in Patients Treated With a Protease Inhibitor(telaprevir or boceprevir), Pegylated Interferon, and Ribavirin (CUPIC) trial studied two cohorts of patients with chronic hepatitis C virus (HCV) infections, and compensated cirrhosis (Child Pugh class A) who had relapsed or had only a partial response to prior therapy, with partial response defined as at least a 2 log10 decline in HCV RNA but failure to clear virus by week 24.

He presented data on 497 patients who had completed 16 weeks of therapy on one of two regimens. In one cohort, 292 patients received 12 weeks of telaprevir 750 mg every 8 hours, and PEG-IFN alfa-2a (Pegasys) 180 mcg/wk with ribavirin 1,000-1,200 mg/day, followed by PEG-IFN/RBV through 48 weeks. In the second cohort, patients received a 4-week initiation phase with PEG-IFN alfa-2b (PegIntron) and ribavirin, followed by 44 weeks of boceprevir 800 mg every 8 hours, PEG-IFN 1.5 mcg/kg per wk, and ribavirin 800-1,400 mg/day.

At week 16, 45% of patients on telaprevir had had at least one serious adverse event, with 14.7% ending therapy because of a serious side effect. In all, 22.6% discontinued therapy, and there were five deaths: from septicemia, septic shock, pneumopathy, endocarditis, and bleeding esophageal varices.

Other complications in this group included grade 3or 4 infections in 6.5%, grade 3 or 4 hepatic decompensation in 2%, grade 3/4 asthenia in 5.5%, and renal failure in 1.7%.

Hematologic adverse events included anemia of grade 2 or greater in 30.4%, erythropoietin use in 53.8%, blood transfusion in 16.1%, and ribavirin dose reduction in 13%.

In addition, 2.7% of patients had grade 3 or 4 neutropenia, and 1.7% had grade 3 or 4 thrombocytopenia. In the boceprevir group, 32.7% had at least one serious adverse event, 26.3% discontinued prematurely, and 7.3% discontinued because of serious events.

The cause of one death was pneumopathy. Grade 3 or 4 adverse events involved infections in 2.4%, hepatic decompensation in 2.9%, and asthenia in 5.8%.

Hematologic events included grade 2 or greater anemia in 27.8%, erythropoietin use in 46.3%, blood transfusion in 6.3%, and ribavirin dose reduction in 10.7%.

Grade 3 or 4 neutropenia was seen in 4.4%, and grade 3 or 4 thrombocytopenia in 5.4%.

Two patients (1%) in this cohort received thrombopoietin.

In a multivariate analysis, significant baseline predictors of severe complications (death, severe infection, hepatic decompensation) included platelet counts of 100,000/mm3 or lower (odds ratio, 3.11; P = .0098) and a serum albumin level below 35 g/L (OR, 6.33; P less than .0001).

The Current Issue Of GI & Hepatology News
(VOL. 7 NO. 1 JANUARY 2013): Download PDF Or View Interactive Version

GI & Hepatology News is the official newspaper of the AGA Institute and provides the gastroenterologist with timely and relevant news and commentary about clinical developments and about the impact of health-care policy.

The newspaper is led by an internationally renowned board of editors.

Personal HCV Experiences

An Interview with Alan Franciscus of the Hepatitis C Support Project (Part 1)
There is a very good argument to be made that Alan Franciscus is the most significant trailblazer in his work for hepatitis C awareness and advocacy movement in the United States. Since the existence of hepatitis C as a distinct virus was not even proven until 1989, the movement has been in existence for only about twenty odd years, and it has been far from a powerful entity in terms of public awareness and reach. In fact, a good deal of what has been accomplished has been accomplished by Alan Franciscus. And the man doesn’t even have a Wikipedia page.
Read the interview at Hepatitis Connect 


Christopher Kennedy Lawford who unknowingly contracted hepatitis C during his years of drug use, also wrote Healing Hepatitis C in 2009, here is his video.

In The News - Christopher Kennedy Lawford brings his story of recovery and redemption to Pasadena

By Carl Kozlowski 01/23/2013
Growing up in a world of showbiz and political privilege as the son of movie star Peter Lawford and the nephew of President John F. Kennedy, Christopher Kennedy Lawford couldn’t have imagined that alcohol and drug addiction would eventually cost him his share of the family fortune and very nearly his life.