3-Drug Therapy Deemed Effective Hepatitis C Treatment

An investigational combination of 3 interferon-free drugs has proven effective at treating hepatitis C virus (HCV) in a recent trial. The study, published in the Journal of the American Medical Association, examined a 12-week dose of daclatasvir, asunaprevir, and beclabuvir in patients with HCV-related liver cirrhosis. None of the 3 medications has yet been approved for use in the United States, although daclatasvir is currently under review by the FDA.

The researchers found that the combination cleared HCV in 93% of trial participants who had not been previously treated, as well as in 87% of those with past failed therapies. However, the addition of a fourth drug, ribavirin, increased the cure rate of patients with past failed therapies to 93%, comparable to that of patients who were receiving treatment for the first time.

“The development of interferon-free treatments has been a tremendous step forward in the standard of care,” said lead author Andrew Muir, MD, MHS, in a press release. “These drugs are highly effective and well tolerated by patients at all stages of liver disease.”

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Image of the Week: Gamification Approach Educates Delegates at World Hepatitis Summit

Earlier this month, MCI worked with the World Health Organization (WHO), the Scottish Government and the World Hepatitis Alliance to deliver the first ever World Hepatitis Summit in Glasgow, Scotland.

A key objective for the three-day programme was to help attendees – a mix of government officials, healthcare professionals and patient representatives – realise how to form a national plan should an outbreak of hepatitis happen.

MCI’s creative team knew that engaging the audience through an immersive experience would be more effective than simply presenting facts and figures, so created an experiential session that inspired attendees to think on their feet and gain practical skills in terms of assessing the level of threat to their countries and preparing a National Plan for Hepatitis.

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Benitec Initiates a Fourth Site in Hepatitis C Clinical Trial

SYDNEY, Sept. 16, 2015 /PRNewswire/ -- Benitec Biopharma Limited (NASDAQ: BNTC; NASDAQ: BNTCW; ASX: BLT) a clinical-stage biotechnology company developing innovative therapeutics based on its gene-silencing technology, DNA-directed RNA interference (ddRNAi), is pleased to announce it has initiated a new site for its ongoing Phase 1/2a TT-034 trial at the Methodist Health System Clinical Research Institute in Dallas, Texas.  The site has commenced pre-screening hepatitis C patients and is led by principal investigator Dr. Parvez Mantry, a gastroenterologist and hepatologist.

This brings the total number of trial sites to four, with Benitec already having established sites at the Duke Clinical Research Institute, the University of California San Diego and the Texas Liver Institute.

Benitec CEO and Managing Director Dr. Peter French said, "We are pleased to welcome a fourth site to join our first-in-man trial of TT-034, an innovative therapeutic based on Benitec's gene silencing technology, ddRNAi. The addition of this site reflects the growing interest from the medical community in Benitec's potentially transformational approach to treating and curing hepatitis C. Recruitment and dosing for the trial is proceeding well."

More detail on the TT-034 trial:  TT-034 is a ddRNAi-based therapeutic, designed to treat and potentially cure hepatitis C (HCV) with a single administration. TT-034 targets the hepatitis C viral RNA at three separate, highly conserved sites. As such it acts as a "triple therapy" even though it is a monotherapy, and minimises the ability of the virus to mutate and escape the therapy. Once it reaches the liver cells it enters the nucleus and produces three separate short hairpin RNAs continuously for the lifetime of the cell. Thus it has the potential to not only treat the existing HCV infection but to guard against reinfection for months to years without the need to re-treat. It has been extensively tested in pre-clinical in vivo studies and no adverse effects were seen at any therapeutic dose.  However, as it is regulated as a gene therapy, the trial design is to primarily ensure that treatment with TT-034 is safe, hence the gradual dose escalation.

Read complete press release here: http://www.prnewswire.com/news-releases/benitec-initiates-a-fourth-site-in-hepatitis-c-clinical-trial-300143931.html

Medical Office Responsible For Transmitting Hepatitis C To Patients Can Reopen

SANTA BARBARA, Calif. -The Santa Barbara medical office of Dr. Allen Thomashefsky may reopen after it was shut down for unsafe injection practices.

The Public Health Department for Santa Barbara County released the following statement:
"Santa Barbara County Health Officer, Charity Dean, MD, MPH, has rescinded the Health Officer Order closing the medical office of Dr. Allen Thomashefsky. This action follows a number of measures that have been implemented to assure infection control practices are maintained at the medical office.

Genetic testing of Dr. Thomashefsky's former patients revealed at least four people who had procedures at his office the same day tested positive for Hepatitis C. A fifth may have contracted the deadly disease prior to treatment.

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Hepatitis C in Children

—Alan Franciscus, Editor-in-Chief

It is estimated that Hepatitis C (HCV) occurs in about 0.15% of 6-11 year-olds and 0.4% of 12-19 year-olds.  It is estimated that there are 23,000 to 46,000 children in the US with HCV.1  The actual number of children with HCV is unknown because children are not routinely tested for it.

Prior to 1992, the most common transmission route for HCV in children was through blood transfusion, blood products, and organ transplantation.  Now that blood products and organs are screened for hepatitis C the most frequent transmission of hepatitis C in infants is mother-to-child transmission.  The second most common transmission route in children and teenagers is in those who share equipment to inject drugs (needles, cookers, cotton, water, etc.)

Transmission of HCV from an HCV-infected mother-to-infant occurs about 6% of the time.  It can occur up to 10% of the time if a mother is coinfected with HIV and hepatitis C.  Also, a high viral load increases the risk of mother-to-infant transmission.   Unfortunately, there are no effective strategies or drugs to prevent the transmission of HCV from mother to child.  

When a baby is born to an HCV-infected mother, the child will acquire the mother’s HCV antibodies. For this reason, the child will not be tested for HCV antibodies for 18 months.  This is the period that it takes for the baby’s body to clear out the mother’s antibodies.
An HCV RNA or viral load test can be given as early as one month.  It might be too early since the HCV RNA, or viral load fluctuates during the acute infection phase.  Also, babies have a high rate of natural clearance.  Most medical providers prefer to wait out the 18-month period to test for HCV antibodies and the confirmatory HCV RNA (viral load test).

Table 1.  Children for whom screening is recommended.

• Children and adolescents with unexplained elevated aminotransferasesChildren at risk for vertically acquired HCV
• Children from regions with high prevalence of HCV (adoptees, refugees, immigrants)
• Children and adolescents with HIV
• Children or adolescents who are victims of sexual assault
• Adolescents with multiple sexual partners
• Adolescents who are or were intravenous drug users, even if only once in the past
• Children or adolescents who have ever been on dialysis
• Sexual partner of HCV-infected person
• Children or adolescent who have received needle stick (needles, piercing or tattooing)*

Source:  Mack CL1, Gonzalez-Peralta RP, Gupta N, et al. NASPGHAN practice guidelines:
Diagnosis and management of hepatitis C infection in infants, children, and adolescents Pediatric Gastroenterol, Nutr 2012;54:838-855

Baker R. Viral Hepatitis. In: Pohl JF, editor. Pediatric Gastroenterology. Baton Rougue, FL: CRC Press: 2014.  pp 313-327

*I read this recommendation with interest because we know that receiving a tattoo or piercing in a commercial parlor is safe.  .

Chronic Infection
Approximately 75% of infants who are acutely infected with hepatitis C will continue to chronic infection.  In children, the rate of disease progression is slow.  There is, however, a small percentage (estimated at less than 2%) of children in whom there is a rapid rate of disease progression that could lead to fibrosis and cirrhosis.

Watch, Wait and Protect
A baby born to an HCV-infected mother should receive the hepatitis A and hepatitis B vaccines to protect the child from becoming infected with another liver disease.  As well the baby and child should receive other immunizations to protect the health of the child.

Hepatitis C is not spread by casual contact and infected children should not be restricted from attending daycare or school.  Children should be taught that they should not share toothbrushes, nail clippers, razors or any other items that have the potential to transmit hepatitis C.

Any drug, herb or supplement that the child is given should be screened to make sure that it is liver safe.  When the child is older, a discussion should take place about sex, drugs, and alcohol.

Most importantly, a child should be medically monitored on a regular basis.

When to Tell a Child
Telling a child that they have hepatitis C can be one of the most difficult decisions a parent can ever make.  The timing is the most important decision.  The best advice is never to lie to a child.  We have an excellent fact sheet that can provide plenty of advice to parents.  http://hcvadvocate.org/hepatitis/factsheets_pdf/TellChild_HCV.pdf

Treatment
As stated above most children have a slowly progressive disease.  For the small percentage that have severe fibrosis or cirrhosis, immediate treatment may be needed.   The decision to treat or not is never easy and in children it is even more difficult.  Some questions that are important to consider include:

• Can treatment be postponed until the interferon-free therapies are available?
• Is there an interferon-free clinical trial that your child can enroll in?
• Are you and your child ready to take on interferon treatment and the side effects?
• The new medications are very expensive—there is always the possibility that your insurance company may not cover the new medications.

Current treatment of pegylated interferon plus ribavirin is approved for children who are three years and older with compensated cirrhosis.

Again, most children have slowly progressive disease, and it takes decades before serious liver disease develops.  By this time, children will age to adults and be eligible for interferon- and ribavirin-free therapies that approach 100% effectiveness.

The Future
Hepatitis C infections are on the rise.  The so-called Second Epidemic of hepatitis C is affecting females equally as males.  As a result, there will be many women of child-bearing age that will become pregnant and have children who may also have hepatitis C.

For the first time, there is an opportunity to prevent mother-to-child transmission. Direct-acting antiviral medications without ribavirin that are pregnancy category B.

Pregnancy Category B: In humans, there are no well-controlled studies. However, in animal studies, pregnant animals received the medicine, and the babies did not show any problems related to the medicine.

However, there have not been any clinical studies using the interferon- and ribavirin-free medications in pregnant women.  As a result, studies are needed to evaluate the safety and effectiveness of these new drugs for the mother and the infant.

1American Liver Foundation
Source:  Hepatitis C in Children in Times of Changes, Robert D. Baker and Susan S. Baker Walters Kluwer Health, Inc.

Women Living with HIV Face Higher Rates of Cancer Diagnosis: Study

Vancouver, BC [September 15, 2015] Due to the introduction of modern highly active antiretroviral therapy (HAART), people living with HIV are now much less likely to develop AIDS-related cancers, which were characteristic of the epidemic in the 1980s. However, a new study published in HIV Medicine shows women living with HIV still have a higher likelihood of being diagnosed with certain cancers, when compared with the general population.

While rates of AIDS-defining malignancies may be decreasing over time, there has been an observed increase in non-AIDS defining malignancies among women living with HIV compared to the general population. This trend primarily involves cancers with underlying infectious causes such as human papillomavirus (HPV) and hepatitis.

“This research suggests chronic inflammation, immune-suppression, aging and viral infections may be contributing to the cancer risk,” said Dr. Robert Hogg, Senior Research Scientist at the BC Centre for Excellence in HIV/AIDS (BC-CfE) and Professor at Simon Fraser University. Dr. Hogg is the thesis supervisor for Kate Salters, the study’s main author. “The study highlights the importance of ongoing access to HIV care and cancer screening practices that are specific to the risks facing women living with HIV. With sustained treatment, women with HIV are now able to live longer, healthier lives – making it increasingly important to address emerging health needs.”

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Big Questions about Hepatitis C 

Answers to some common questions about hepatitis C and its treatment. 

—Lucinda K. Porter, RN

Do you lay awake pondering questions about hepatitis C? If so, you probably need some answers so you can sleep better. This month, I answer some common questions I hear from patients. 

I just finished hepatitis C treatment. My final hepatitis C viral (HCV) load test result was “not detected.” I was hoping that my viral load would be “negative” rather than “not detected.” My doctor was happy with the result. What does this mean?

Undetected (or nondetected) means that hepatitis C is gone, and presumably all gone. The confusion over this test is because viral load tests don’t measure down to zero. Viral load tests vary. For instance, the Abbott RealTime HCV assay (assay is a fancy word for a test that determines and counts the ingredients of something) measures down to 12 IU/mL in a 0.5 mL sample of blood. This means that if you have 12 IU/ml of hepatitis C (HCV RNA) in your blood, the test can measure it. If you have less than 12, the test can’t measure it. In some cases, the test may not even see the virus.

Each test has its own detection range, some 

lower than others. The main thing is this: 

“Not detected” = negative for hepatitis C

“Detected” or an actual number of how much 

HCV RNA you have = positive for hepatitis C

If you are concerned that you may have some residual HCV swimming around in your body, that will someday become a full-blown infection, rest assured, as this is quite unlikely. Hep C replicates a trillion times a day, so “not detected” might as well be zero. It is extremely unlikely that a small amount of HCV will remain alive in your body without having replicated to much higher amounts. In fact, viral load tends to replicate at much higher numbers when treatment fails.

My HCV load was nondetectable and my doctor says I am cured. How do I know for sure that the virus won’t come back?

Doctors have been treating hepatitis C for more than two decades. In the beginning, only a small percentage of patients responded to treatment. We weren’t sure these patients were permanently cured, so the term sustained viral response (SVR) was used. Over time, we learned that a sustained viral response (SVR) equals a cure, and that once gone, hepatitis C does not return unless there is exposure to a new infection. The rare exception to this is when a patient has cryoglobulinemia or a rare immune condition.  I’ve worked in this field for 18 years, have crossed paths with thousands of patients, and have never known anyone who had an SVR but the virus came back, except for those who were reinfected or had an error in their testing procedure.

So, are you saying that if I am cured, I can get hep C again?

Yes. The chance of a hepatitis C reinfection with hepatitis C is low, but it is not impossible. Risk of reinfection is higher if you are HIV positive or use injection drugs. 

In a poster presented this year at CROI in Seattle, Andrew Hill and colleagues analyzed data from 11,071 patients in 66 studies. (Five-Year Risk of Late Relapse or Reinfection with Hepatitis C after Sustained Virologic Response: Meta-analysis of 49 Studies in 8534 Patients) They found:

•HCV mono-infected persons with low risk of exposure to the virus had a 1.14% reinfection rate 

•HCV mono-infected persons who injected drugs or prisoners had a 13.22% reinfection rate 

•HIV/HCV co-infected persons had a 21.72% reinfection rate

•All of the patients reviewed were treated with the dual regimen of pegylated interferon and ribavirin. 

The best way to avoid reinfection is to reduce risky behaviors that may expose you to hepatitis C. Never share needles or syringes. Do not share injection or inhaled drugs or equipment associated with it. Avoid blood-to-blood contact with others. Use condoms if you are sexually active with a new partner or with a partner who has used injection drugs.

If hepatitis C can live on a surface for up to 63 days, then shouldn’t I change my toothbrush (razor, cuticle scissors) during treatment, particularly when I am nondetectable. I don’t want to reinfect myself.

I haven’t seen a single study on this. There is probably no chance of reinfecting yourself with your own virus, particularly while you are taking antiviral medication. Also, the chances of hepatitis C being viable on a toothbrush, razor, or other personal instrument are extremely slim. Add to this the low reinfection rate, and I’d say the chances of self-reinfection are slim to none. 

However, I had hepatitis C once, and I know full well that sometimes we just don’t care what science says. It won’t hurt you to be overly cautious, and if you want to change these items, then go ahead. Rather than throw away perfectly good personal care items, you can store them for a few months and then use them later. You can also clean them with one part bleach to ten parts water.   

I just finished HCV treatment, but my viral load was detectable at week 8 and 12.  Does this mean my chances of being cured are low?

No. In the old days, back when treatment was long and used interferon, there were clear milestones that helped us know what our chances were of permanently clearing hepatitis C. Now with new direct-acting antivirals (DAAs), things have changed. Research by the NIH Clinical Center showed that low levels of HCV RNA at the end of treatment are not predictive of treatment response among patients with hepatitis C virus treated with interferon-free regimens. (Clinical Infectious Diseases, March 2, 2015).  Harvoni was used in this study, but the trend is likely to apply to all treatments using HCV DAAs. 

For years I thought I had genotype 1a, but a recent genotype test revealed I have 1b. How did this happen? 

It may be that you have more than one genotype at the same time. When this occurs, often the genotype test shows whichever genotype is more predominate, and sometimes the genotype can switch. 

Having more than one HCV genotype is not rare, with studies placing it in the 5 to 10% range. There are various ways a person could have more than one hepatitis C genotype: 

•Dual infection –This occurs when a person is infected with more than one hep C genotype at the same time. Hemophiliacs who received clotting factors, which are derived from thousands of sources, were at risk for dual infections. 

•Co-infection – This happens when someone is exposed from two different sources of hep C within a short time span, and acquires hep C from a second source before the first infection is established.

•Superinfection – Someone whose hepatitis C infection is established, and then they are infected with another genotype. 

There is also something called HCV recombination. In this situation, a person may be co-infected with more than one HCV genotype, and the viruses exchange genetic material. 

If I have more than one genotype, how do I know which treatment is best for me? 

If only one genotype shows up on the test, your doctor will treat you based on that genotype. If more than one genotype is apparent, then likely your doctor will recommend a regimen based on the harder to treat genotype. 

  

Will the Giants win the series this year? 

I admit, no one has ever asked me this, but they should. Lying awake worrying about hep C makes no sense, especially when there are more important issues to lose sleep over, such as whether the Giants will win the series again. 

QUOTE:

Sustained Viral Response (SVR) equals a cure, and that once gone, hepatitis C does not return unless there is exposure to a new infection. 

Lucinda K. Porter, RN, is a long-time contributor to the HCV Advocate and author of 

Free from Hepatitis C and Hepatitis C One Step at a Time. Her blog is www.LucindaPorterRN.com