Monday, October 14, 2013

Monday Hepatitis C News: Sofosbuvir, Faldaprevir, Liver Disease and Second Opinions

Hello Folks,
Welcome to a new week of HCV news and research. If you missed it over the weekend an editorial on several new DAA agents currently in late stages of development was posted on the website, simeprevir and sofosbuvir were included.

Dr. Galati a leading authority on liver transplantation, liver disease and gastroenterology last week launched an interesting concept for patients with HCV or liver disease seeking a second opinion. Liver Specialists of Texas, Dr. Galati’s practice located in Huston, Texas is offering a 30 minute consultation via the Internet using an innovative software program.

Through Videoconferencing liver patients who can not travel to Huston are able to review and ask questions about past consultations, including abnormal liver tests, fatty liver, or biopsies.

Liver Specialists of Texas is one of America’s largest private liver services. Galati also produces and hosts Your Health First, a weekly one-hour radio program.

Videoconferencing - Huston, Texas

Second Opinion in Hepatitis: Videoconferencing Between Houston and the World
by Dr. Joe Galati on 10/07/2013

Each week, I receive dozens of e-mails from followers of our social media sites (Twitter, YouTube, FaceBook, Your Health First, and Liver Specialists of Texas) seeking assistance regarding some form of liver disease they are suffering from, or one of their relatives. I usually respond back with some direction they should head in, or ask if they are available to travel to Houston for a face-to-face evaluation.

As technology improves, the availability of videoconferencing has never been easier. Working with Houston based software developers, there is now the opportunity to participate in a second opinion program with experts in liver disease in our practice. Because there is such variability in everyone’s home or work connectivity to the internet, we plan on supplying you with the needed technology to connect.

The savings of not having to travel to Houston, hotel and food charges, lost wages, and time, makes this an economically sensible alternative.

Second opinions in all aspects of liver disease will be available, including abnormal liver tests, fatty liver disease, hepatitis C, hepatitis B, cirrhosis, liver cancer, alcohol related liver disease, liver transplant, hemochromatosis, and autoimmune disease of the liver. The cost for this service will be based on a minimum of a 30 minute consultation, allowing for additional time at 15 minute increments. Medical records, x-ray reports and films, biopsies, and past consultations will be reviewed.

Feedback on this program is important to us. Please let us know what you think.

For additional information, contact Dee at (713) 634-5103.

Here we go with today's news and headlines, enjoy your day! 

New HCV Drugs 

Effectiveness of New Hepatitis C Treatments Featured at ACG Annual Scientific Meeting Rapid Evolution of Medical Research Advancing Hepatitis C Treatment

San Diego, CA (October 14, 2013) – Data on new treatment options and combinations of therapies to treat chronic viral hepatitis C infection were presented at the 78th Annual Scientific Meeting of the American College of Gastroenterology in San Diego in a scientific session dedicated to liver disease. Three research teams reported on trials of several experimental treatments, including interferon-free drug combinations and direct acting antiviral agents effective against genotypes 2 and 3 of the Hepatitis C virus, as well as new agents which have the potential to shorten the duration of therapy.

“These studies highlight how rapidly medical research is advancing in hepatitis C,” said Kris V. Kowdley, M.D., FACG, director of the Liver Center of Excellence in the Digestive Disease Institute at Virginia Mason Medical Center, and Clinical Professor of Medicine at the University of Washington in Seattle. “The new wave of direct-acting oral agents has the potential to transform therapy for patients living with hepatitis C, both in terms of their safety and efficacy profiles, but also in terms of the possibility of reducing the duration of, or completely eliminating the need for, interferon injections.”

Faldaprevir STARTVerso1 Trial: Up to 89 Percent of Patients Eligible to Stop Treatment at 24 Weeks

Final results of the STARTVerso1 Phase 3 trial of faldaprevir plus pegylated interferon and ribavirin in chronic hepatitis C infection in treatment-naïve patients infected with genotype1 were presented by Christophe Moreno, M.D., Ph.D. of the Hôpital Universitaire Erasme in Brussels, Belgium and colleagues. This randomized, double-blind, placebo-controlled trial assessed the efficacy and safety of faldaprevir, an investigational protease inhibitor.

Treatment-naïve patients with chronic hepatitis C genotype 1 were randomized to receive 24 weeks of pegylated interferon and ribavirin with faldaprevir placebo (arm 1); or faldaprevir 120 mg for 12 or 24 weeks (response guided; arm 2); or faldaprevir 240 mgs for 12 weeks (arm 3). Patients in arms 2 and 3 also received pegylated interferon and ribavirin for 24 weeks. Patients with early treatment success (ETS) at week 8 in Arms 2 and 3 stopped all treatment at week 24. Early treatment success was defined in the protocol as virus at week 4 below limit of quantification [BLQ] and at week 8 below limit of detection.

The investigators reported that in previously untreated patients with genotype-1 hepatitis C virus (HCV) who received once-daily faldaprevir plus PegIFN/RBV, 79 percent and 80 percent in the 120mg and 240mg arms, respectively, achieved viral cure when measured 12 weeks after treatment was completed (SVR12). This is compared with 52 percent of patients receiving PegIFN/RBV plus placebo (p<0.0001).

Anemia, rash and gastrointestinal issues were the most common Grade 2-4 adverse events in placebo, faldaprevir 120mg and faldaprevir 240mg arms, respectively. In total, up to 89 percent of patients treated with faldaprevir were eligible to stop all treatment at week 24. The study was supported by a grant from Boehringer Ingelheim.

“In the STARTVerso™1 study, faldaprevir has shown efficacy in achieving viral cure for treatment-naïve patients with HCV, with the potential for a shorter treatment duration. These results are particularly promising, as the study evaluated genotype 1a and 1b HCV patients, including difficult to treat patients such as those with liver cirrhosis,” commented Dr. Moreno.

Sofosbuvir with Ribavirin and Pegylated Interferon Shortens Treatment for HCV Genotype 1

Kris V. Kowdley, M.D., FACG reported results of four multi-center randomized trials of combination therapies of sofosbuvir for patients with chronic hepatitis C.

“Among genotype 1 patients receiving sofosbuvir plus ribavirin and pegylated interferon, the sustained viral response rate was 91 percent at 12 weeks after end of treatment,” commented Dr. Kowdley, highlighting findings from the NEUTRINO study, one of four trials of sofosbuvir reported by Dr. Kowdley and his colleagues.

The four studies reported included the NEUTRINO trial, in which treatment- naïve patients with genotype 1,4, 5 and 6 received 12 weeks of sofosbuvir and pegylated interferon plus ribavirin; FISSION in which treatment-naïve patients with genotype 2 or 3 were randomized to receive either 12 weeks of sofosbuvir plus ribavirin or 24 weeks of pegylated interferon plus ribavirin; POSITRON in which interferon-ineligble, -intolerant or –unwilling genotype 2 or 3 patients were randomized to receive 12 weeks of sofosbuvir plus ribavirin or placebo; and FUSION in which treatment-experienced genotype 2 or 3 patients were randomized to receive 12 or 16 weeks of sofosbuvir and ribavirin.

In the FISSION, POSITRON and FUSION trials, patients with genotype 2 infection had rates of sustained viral response at 12 weeks after the end of treatment (97 percent VR-12 FISSION; 93 percent SVR-12 POSITRON and 86 percent SVR-12 FUSION) that were higher than those patients with genotype 3 (56 percent SVR-12 FISSION; 61 percent SVR-12 POSITRON; and 30 percent SVR-12 FUSION).

Researchers concluded that previously treated patients with genotype 3 hepatitis C infection may benefit from extending treatment to 16 weeks. Currently, no direct-acting antiviral agents have yet been approved for patients with genotype 2 or 3 Hepatitis C infection. This work was supported by a grant from Gilead Sciences Inc.

“The sofosbuvir results seen in these four pivotal studies represent a significant advance in hepatitis C treatment,” said Dr. Kowdley. “First, they indicate that we should be able to shorten therapy for many patients to just 12 weeks. Second, for the first time we have Phase 3 evidence that we can do away with debilitating interferon injections for some patients. Sofosbuvir has the potential to usher in a new era of simple, tablet-based treatment for hepatitis C that boosts cure rates and is much easier for patients to take and to tolerate.”

Results of the Aviator Study of an Interferon-Free Regimen for Hepatitis C

Dr. Kowdley was also the lead author on a study on the safety and efficacy of interferon-free regimens for hepatitis C patients with genotype 1 using a combination of three experimental direct-acting anti-viral agents (DAA) ABT-450/r, ABT-267, and ABT-333 with or without ribavirin. This trial, known as Aviator, treated 247 subjects in the 12 and 24 week arms of three DAA plus ribavirin.

Overall, the sustained viral response at 12 weeks post treatment was 98.7 percent in treatment naïve patients and 93.3 percent in null responders (those patients with hepatitis C virus who failed to respond to prior therapy with other drugs). “Comparable responses were seen with 12 and 24 weeks of treatment, supporting selection of a 12-week duration of therapy in these populations. Consistently high SVR rates were achieved in naïve and prior null responder patients with a three direct acting anti-viral agent regimen, across HCV subtype, IL28B genotype baseline HCV-RNA or severity of fibrosis,” concluded Dr. Kowdley. The design, study conduct, analysis and financial support of this clinical trial were provided by Abbvie.

According to Dr. Kowdley, "The high sustained viral response rates across patient types in the Aviator study were very encouraging. This study, one of the largest phase 2 trials of interferon-free therapy for HCV, was designed to identify the most effective regimens for treating HCV genotype 1 infection. It is noteworthy that the trial included a large number of prior interferon null responders, a population that typically has a poorer response to treatment than treatment-naïve patients. Aviator was the first trial to show that a highly active interferon-free regimen could achieve high SVR rates in null responders. The fact that a well-tolerated 12-week regimen of 3 DAA+ribavirin showed consistently high SVR rates regardless of baseline predictors of poor response suggest that it could be an effective treatment even in difficult-to-treat patients."

About Hepatitis C Virus
Hepatitis C is a liver disease affecting as many as 170 million people worldwide. The virus is primarily spread through direct contact with the blood of an infected person. Hepatitis C infection increases the risk of chronic liver disease, cirrhosis, liver cancer and death. Of the six main genotypes of hepatitis C, genotypes 1, 2 and 3 are the most widespread. Genotype 1 is the most common genotype in the United States and the most difficult to treat with interferon-based therapies. Patients with genotypes 2 and 3 are more likely than individuals with genotype 1 to respond to therapy with pegylated interferon or the combination of pegylated interferon and ribavirin. To learn more, visit the ACG Patient Resource Center on Hepatitis C.

About the American College of Gastroenterology
Founded in 1932, the American College of Gastroenterology (ACG) is an organization with an international membership of more than 12,000 individuals from 80 countries. The College's vision is to be the pre-eminent professional organization that champions the evolving needs of clinicians in the delivery of high quality, evidence-based, and compassionate health care to gastroenterology patients. The mission of the College is to advance world-class care for patients with gastrointestinal disorders through excellence, innovation and advocacy in the areas of scientific investigation, education, prevention and treatment. View releases on research breaking at the ACG meeting and follow ACG on Twitter and share your live updates #acg2013. 

Treatment of chronic HCV genotype 1 infection with telaprevir: a Bayesian mixed treatment comparison of fixed-length and response-guided treatment regimens in treatment-naive and --experienced patients

Armin D Goralczyk, Silke Cameron and Ahmad Amanzada

BMC Gastroenterology 2013, 13:148 doi:10.1186/1471-230X-13-148 Published: 14 October 2013

Abstract (provisional)
Telaprevir (TVR) has been approved for response-guided-therapy (RGT) of chronic hepatitis C (HCV) genotype-1-infection in treatment-naive and --experienced patients. In RGT-regimens patients that did not achieve extended rapid-virological-response (eRVR) within the first 4--12 weeks undergo treatment for 48-weeks, whereas in fixed-length-treatment (FLT) patients are treated for a fixed-duration regardless of their RVR.

This systematic review and Bayesian mixed-treatment-comparison (MTC) aimed to compare the efficacy and safety of standard-therapy with pegylated-interferon-alpha/ribavirin (Peg-IFN-alpha/RBV (48 weeks), group A), FLT with TVR, Peg-IFN-alpha/RBV for 12 weeks with a long (+36 weeks, group B) or short (+12 weeks, group C) tail of Peg-IFN-alpha/RBV treatment, and RGT with 12 weeks of TVR, Peg-IFN-alpha/RBV followed by 12 weeks of Peg-IFN-alpha/RBV (group D) or no therapy (group E).

We identified seven randomized controlled trials including 3505 patients. Compared to standard-treatment (group A), treatment-naive patients allocated to groups B, C, and D were significantly more likely to achieve sustained-virological-response (SVR, odds ratios (OR): B vs. A 3.5 (credibility interval [CrI] 2.2-5.4), C vs. A 3.0 (CrI 1.8-4.9), D vs. A 3.4 (CrI 2.5-4.6)). Treatment-experienced patients achieved increased SVR rates when they were treated in group B (OR: 8.2 (CrI 5.0-13.5)), C (OR 7.0 (CrI 3.9-12.8)), or simulated group D (OR 8.2 (CrI 4.3-15.3)). Patients treated with short RGT (simulated group E) did also have a significant improvement when they were treatment-experienced (simulated OR 3.6 (CrI 1.6-8.2)), whereas the effect was not significant in treatment-naive patients (OR E vs. A 1.6 (CrI 0.9-2.7)).

Long FLT and RGT regimens are useful treatment options for HCV-genotype-1 in both treatment-naive and -experienced patients. A short 24-weeks FLT regimen does not seem to be inferior and should further be evaluated in clinical trials to reduce side effects and costs of treatment.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production. 


If You Are Newly Diagnosed with Hepatitis C or Feeling Afraid Because of It
by Lucinda Porter on October 14, 2013
You are not alone. You may feel alone, scared, confused, angry, numb, or shattered. A hepatitis C diagnosis changes everything, at least at first. You may wonder how you got hepatitis C. Perhaps you know how you got it, and if it is because of choices you made earlier in your life, you may be kicking yourself right now. Please don’t do that. The past is past, and kicking yourself when you are down is cruel, unnecessary, and it won’t help anything........


Hepatitis C Trust says strategy urgent as related liver disease on the rise
Only 3% of people with hepatitis C are treated each year, yet government is dragging its heels on strategy, says trust

There are 160,000 people living with the hepatitis C virus in England and yet half of those do not know it, said the Hepatitis C Trust. They are at risk of developing a disease which could destroy their liver and cause their death. Only 3% of people receive treatment each year......

Liver Cancer 

World J Gastroenterol. 2013 Oct 7;19(37):6127-6130.
Strategy for improving survival and reducing recurrence of HCV-related hepatocellular carcinoma.
Toru Ishikawa, Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata 950-1104, Japan.

View - Free full text

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related death in the world. With advances in imaging diagnostics, accompanied by better understanding of high-risk patients, HCC is now frequently detected at an early stage; however, the prognosis remains poor. The recurrence rate after treatment of HCC is higher than that associated with cancers of other organs. This may be because of the high incidence of intrahepatic distant recurrence and multicentric recurrence, especially with hepatitis C virus (HCV)-related hepatocellular carcinoma. The Barcelona Clinic Liver Cancer (BCLC) classification has recently emerged as the standard classification system for the clinical management of patients with HCC. According to the BCLC staging system, curative therapies (resection, transplantation, transcatheter arterial chemoembolization, percutaneous ethanol injection therapy, percutaneous microwave coagulation therapy and percutaneous radiofrequency ablation) can improve survival in HCC patients diagnosed at an early stage and offer a potential long-term cure. However, treatment strategies for recurrent disease are not mentioned in the BCLC classsification. The strategy for recurrence may differ according to the recurrence pattern, i.e., intrahepatic distant recurrence vs multicentric recurrence. In this article, we review recurrent HCC and the therapeutic strategies for reducing recurrent HCC, especially HCV-related HCC.

Arterial chemotherapy, Hepatitis C virus, Hepatocellular carcinoma, Interferon, Intrahepatic distant recurrence, Multicentric recurrence 
Free full text 


 Scars! Some people will pay for scarification as an alternative to tattoos

Blair McLean shows off his scarification which is similar to tattooing but instead you burn your skin to create scar tissue as a work of art in Toronto on Thursday, Oct. 3, 2013. The procedure, known as scarification, is a form of extreme and permanent body modification that is offered in many tattoo and piercing stores across the country and is gaining popularity.

ByErica Lenti 
TORONTO - When Holly Mosienko decided to cover up an unsightly scar on her leg, she strayed away from typical solutions, like plastic surgery or makeup. Instead, she opted for more scarring — this time, in the shape of a tribal dragon. 

The procedure, known as scarification, is a form of extreme and permanent body modification that is offered in many tattoo and piercing stores across the country and is gaining popularity.
It involves a process in which one's skin is cut, etched, burned or branded into a design to create a inkless tattoo-like scar. Though it is not as widely practised as tattooing or piercing, it has been around for just as long. 

"Branding and cutting is not all that different from tattooing," said Mosienko, 51, who runs a piercing store in Peterborough, Ont. 

"It's popular. I'd say it's even more interesting than getting a tattoo." 

Mosienko says she chose scarification for practical reasons. A lover of body art, she knew covering up her scar — caused by surgery — with a tattoo would be too painful, the constant pressure of a needle over scar tissue would be unbearable. Rather, she chose to have the design etched into her skin. 

The entire process — from sketching the design on her leg to the actual cutting — took about an hour. 

Mosienko's artist, 45-year-old Blair McLean of New Tribe Tattoos and Piercings in Toronto, says there are many misconceptions about the practice. 

He says scarification often hurts less than a tattoo; in fact, all forms of scarification occur on the same level of the skin as tattoos: on the dermis, far above fatty tissues and muscle matter. 

The practice is illegal in some countries such as the United Kingdom and several U.S. states. Most recently, the practice was banned in Arkansas, though that bill was overturned after public outcry against the decision. Winnipeg declared the practice illegal in 2008. 

A spokesman for the Ontario Ministry of Health and Long-Term Care says there can be severe health risks that result from having these procedures. 

"Because certain body modification practices break intact skin and mucus membranes through cutting, burning and piercing, there is an increase in the risk of scarring, hemorrhaging and psychological trauma as well as exposure and infection with blood borne pathogens, such as hepatitis B, hepatitis C and HIV," David Jensen said. 

In Toronto, the public health board monitors tattoo and piercing parlours through regular inspections, though officials say they have yet to come across the practice of scarification, which is considered a "personal service." 

"We inspect (the practice) as part of the Personal Service Settings program. We would follow the same Infectious Prevention and Control principles as any other invasive service," said agency spokesman Kris Scheuer. 

"Toronto Public Health does inspect a number of places for control and to stop the spread of infection," she added. 

McLean, who has practised scarification for decades in Canada and around the world, including Tokyo, London and New York, says prohibition poses more health risks to the public.
"It sends people into the underground to practice on their friends," he says. "That increases the risk for infection or problems." 

Scarification was not always an alternative practice: It has roots in tribal culture, in which members would brand themselves as a rite of passage to either their tribes or the gods. But with the body modification movement of the '80s came a resurgence in scarification, during which fraternity brothers would brand their house letters on their body to symbolize eternal membership.
While it is historically a symbolic practice, McLean says those opting for scarification today typically do it for aesthetic reasons or to gain status. 

"In the past, fraternity brothers didn't care what the scar looked like," McLean said. "It was about brotherhood." 

"Today, (clients) seem to be vainer." 

For clients who are "in it for the right reasons," McLean says the decision to be scarified runs deeper than plain aesthetics. 

"Some people don't want ink or foreign pigments in their body, like from tattoos," he said. "With scarification, the design is from your body only." 

Others, he adds, want an intense, euphoric experience, making the body art all the more important.
"At the end of the day, it's not just about me getting paid," McLean said. "I want it to be mean a lot, to be special."
The Canadian Press    

Health Tip: Stay Safe at the Nail Salon
Published: October 14, 2013 7:21 AM @ HealthDay
 -- Nancyann Rella

Whether you live in a big city or small town, you'll probably find no shortage of nail salons. But before you treat yourself to a manicure or pedicure, find out if health and sanitation guidelines are being met.

Dirty instruments and poor sanitation at some nail salons can put women at risk for diseases such as athlete's foot and hepatitis B and C.

St. Mary's Hospital Medical Center in Green Bay, Wisc., advises taking these precautions:

  • Make sure your salon has an up-to-date operating license.
  • Don't shave your legs the night before or the day of a salon footbath. Scrapes and nicks can make you more susceptible to infection.
  • Check that nail instruments are properly sanitized. Heat sterilization is best. Even better: Bring your own nail tools.
  • Wash your hands before a manicure and ask your manicurist to do the same.
  • Insist on fresh soapy water for hand or foot soaking.
  • Ask the manicurist to push back cuticles instead of cutting them.
Copyright © 2013 HealthDay. All rights reserved. 

Celebrity Diagnosis 

Did Yo-Yo Dieting Cause Tom Hanks' Diabetes?
Just "like a box of chocolates. You never know what you're gonna get" when you have Tom Hanks as a guest on your show.

So David Letterman found out when he was talking to Hanks about his upcoming movie, Captain Phillips.When complementing Hanks on his svelter figure, Hanks said:
I went to the doctor, and he said, 'You know those high blood sugar numbers you've been dealing with since you were 36? Well, you've graduated! You've got Type 2 diabetes, young man.'

Hanks went on to say that it is a "controllable" condition and that he is working to "maintain the temple."
Tom Hanks is one of those actors who is well known for the dramatic, voluntary weight gains and losses he has undergone for a number of his film roles:

  • Hanks gained 30 pounds to play baseball coach Jimmy Dugan in 1992's "A League of Their Own." 
  • He lost 55 pounds playing a FedEx employee on an abandoned island after a plane crash in "Castaway."
  • He won his first Academy Award for Best Actor in the 1993 film  "Philadelphia" for which he lost 26 pounds to play a lawyer with AIDS.

A number of media outlets are questioning whether Hanks' diabetes was caused by this degree of weight fluctuation. But Hanks doesn't think that's the main reason. Speaking at a press conference for Captain Phillips on Wednesday, he said:

"Gaining and losing of weight may have had something to do with this because you eat so much bad food and you don't get any exercise when you're heavy."
"But I think I was genetically inclined to get it and I think it actually and goes back to a lifestyle I've been leading ever since I was 7 years old, as opposed to 36."

Weight cycling, also known as yo-yo dieting, is a term  coined by Kelly D. Brownell at Yale University to describe a process whereby the dieter is initially successful in the pursuit of weight loss but is unsuccessful in maintaining the loss long-term and begins to gain the weight back. The dieter then seeks to lose the regained weight, and the cycle begins again.

What is the evidence regarding weight fluctuation and Type 2 diabetes?

As is often the case in topics such as this, the evidence is mixed.

A study by in the American Journal of Epidemiology looked at the association between weight patterns during middle age and the incidence of type 2 diabetes using a subset (n = 1,476) of the Framingham Heart Study original cohort. They conclude that although being overweight or obese was associated with higher rates of diabetes, weight cycling was not associated with a higher incidence of diabetes.  In other words, weight itself was a more important factor than changes in weight.

Furthermore, Stevens et. al, concluded, based on epidemiological evidence, that weight cycling does not lead to an increased risk of mortality.

It has been shown that accumulation of proinflammatory immune cells in adipose tissue contributes to the development of obesity-associated disorders.Emily Anderson, Alyssa Hasty, and their colleagues at Vanderbilt University alternated mice between high- and low-fat diets. They were trying to determine whether weight cycling altered the numbers of immune cells, inflammation, and insulin resistance in adipose tissue. They found that adipose tissue in mice who had been weight cycled do show an amplified T-cell response compared with mice that lost weight without cycling. Weight cycling also impaired systemic glucose tolerance and AT insulin sensitivity.

But there is some good news:Anne McTiernan, at the Fred Hutchinson Cancer Research Center, found that "a history of weight cycling does not impede successful participation in lifestyle interventions or alter the benefits of diet and/or exercise on body composition and metabolic outcomes."

No comments:

Post a Comment