Findings about WWII-Era Spread of Hepatitis C Could Inform Future Prevention Efforts

The breakneck pace of clinical research means that, by necessity, there is little time to assess the past. But research published earlier this year in the Journal of Virology on the origins of the Hepatitis C virus (HCV) shows that such examination is not a morbid trip down memory lane, but rather can deliver key insights into current prevention efforts.   

The study, from researchers at the University of Glasgow, dates the beginnings of HCV to the 1940s and says it most likely arrived through the mass treatment of soldiers in field hospitals across the country during WWII. Under circumstances of war, hastily organized and overwhelmed care units meant that HCV was easily spread easily between soldiers as their injuries were treated.   

Using statistical analysis to examine the transmission dynamics, the researchers say, can help provide a basis for identifying HCV transmission hotspots. They posit that a more comprehensive understanding of exactly how hepatitis C virus is transmitted during times of significant spread could facilitate public health initiatives to reduce the prevalence of HCV in people who contract it through intravenous drug use.

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Article: Hepatitis B Virus Reactivation During Successful Treatment of Hepatitis C Virus with Sofosbuvir and Simeprevi

This article is being re-posted from a previous newsletter.  I have been hearing from patients who have been inquiring about treatment with a DAA and who are also co-infected with chronic hepatitis B.  People co-infected with HCV and HBV should make their medical providers aware that their chronic hepatitis B should be monitored on a regular basis.  The article below recommends that people being treated with a DAA should be monitored every 2 weeks.  -Alan

Snapshots - Alan Franciscus

Article:  Hepatitis B Virus Reactivation During Successful Treatment of Hepatitis C Virus with Sofosbuvir and Simeprevir—J. M. Collins et. Al
  Source:  Clinical Infectious Diseases Advance Access

Results and Conclusions: This was a case report of two individuals with hepatitis C. 

The first case was a 55 yo man who was coinfected with hepatitis B and hepatitis C genotype 1a.  He had been previously treated with pegylated interferon plus ribavirin but did not achieve a cure.  He was started on sofosbuvir and simeprevir.  After week 4 he was HCV undetectable, but at week 7 he started to have severe liver symptoms (AST of 1792 IU/L, ALT of 1495 IU/L, total bilirubin of 12.2 mg/dl and INR of 1.96) and his hepatitis B viral load rose to 22 million.  His other tests (antinuclear antibody, ferritin, a-fetoprotein, etc.) were also abnormal.

The HCV treatment was discontinued, and hepatitis B treatment (tenofovir/emtricitabine) was started and the hepatitis B viral load subsequently decreased to less than 20 IU/mL.  The hepatitis B treatment was continued for ongoing hepatitis B suppression.

The second case was a 57 yo man with HCV genotype 1a.  He had been treated for HCV with pegylated interferon plus ribavirin but had not been cured. He was positive for the hepatitis B virus, but the hepatitis B viral load was below the level of detection (20 IU/mL).  He was started on HCV treatment—sofosbuvir and simeprevir and his HCV and hepatitis B viral loads were monitored every two weeks.  After two weeks, his HCV viral load was undetectable and his hepatitis B viral load increased to 353 IU/mL.  After four weeks of HCV treatment, HCV was still undetectable, but the hepatitis B viral load increased to 11,255 IU/mL.  The liver function tests were normal, and there were no other signs of liver disease.  The patient remained on sofosbuvir/simeprevir treatment.  Tenofovir was added to the HCV treatment regime to treat hepatitis B. 

The Bottom Line:  The reactivation of HBV in people who were coinfected with HBV and HCV was rare in the days of pegylated interferon based therapies.  This was most likely because PEG works against HBV whereas the new HCV direct acting antivirals do not have antiviral properties that will suppress hepatitis B while treating HCV.   

Editorial Comment:  A couple of important points:

• Everyone with hepatitis C should be tested for hepatitis B (and A), and if not previously infected should be vaccinated.
• People who are chronically infected with HBV and HCV who are being treated with the direct-acting antiviral medications (Harvoni or Viekira Pak) and monitored very closely—every two weeks as listed in the second study—for HBV flares and treated for chronic HBV as needed. 

THE FIVE Clinical Trials – What Patients Need To Know —By Alan Franciscus

THE FIVE: Clinical Trials – What Patients Need To Know
—By Alan Franciscus

In this month’s The Five column, I will provide a simple overview of clinical trials, the pluses and minuses of participating in a clinical study and information about how to find clinical trials your area. I hope this article will help our readers who are interested in participating in a clinical trial to make an educated decision. '

1.  Phases of Clinical Trials – Clinical trials begin with pre-clinical studies conducted in test tubes or animals.  If the results are positive the drugs can move through different phases—1 through 3—and a possibly 4th phase.  A brief recap of the 4 phases is listed below

• Phase 1 studies usually include healthy people, but can include persons with the particular disorder that the study drug is being tested to treat.  The primary reason for phase 1 studies is to establish the safety of the study drug.  Another important part of a phase 1 study is to find the dose that combines the highest effectiveness with the lowest rate of side effects.  (generally 20 to 80 people are recruited for phase 1 trials),    

• Phase 2 only includes people who have the disorder or disease that the investigational drug is being tested in to find the efficacy—also called effectiveness.  In some phase 2 studies the study drug may be compared to a current drug approved by the Food and Drug Administration (FDA) or a placebo drug (sugar pill).  Additional safety and side effect information is also  obtained.  (generally 100 to 300 people are recruited for phase 2 studies), 

• Phase 3 is similar to phase 2 clinical trials but have a larger patient population.  They also compare the study drug to other medicines to treat the same disorder or disease—usually the current standard of care drugs—and in different patient populations.  Since the patient population is much larger the effectiveness, side effect information and other information obtained is more realistic data compared to the information obtained in phase 1 and 2 studies.  (up to 1,000 or more people).

The pharmaceutical company will compile and review the phase 3 data and apply to the FDA for New Drug Application (NDA).  After a period of review and if appropriate the FDA will approve the medication for a particular patient population.  The FDA will also issue a package label

• Phase 4 is post-marketing studies.  These are studies that the FDA may require as part of the FDA approval process.  Phase 4 studies gather more information about the safety, effectiveness, and/or the use of the approved medication in certain patient populations

2.  Types of Studies – In clinical studies there are various types of studies including:

• Randomization means that some patients will receive the study drug and some will receive the drug that it is being compared against (an FDA approved drug) or a placebo (sugar pill), 

• Open-label means that everyone will receive the study drug,

• Prospective these are studies that look ahead look for certain outcomes.  These are studies that recruit patients to find out if the drugs in development work.

• Informed Consent – To participate in a clinical study, a document called ‘informed consent’ is filled out.  The subject/patient is required to read, understand and sign the document.  A copy is given to the subject/patient.   A study nurse is assigned to each study. It is the nurse’s responsibilities that every patient in the study understands the benefits and risks of the study.  The informed consent form should be written in language (6th grade and lower) that is simple, and easy to understand.  The sentences should be short, and non-technical. The person who is entering into a clinical trial should be encouraged to ask questions and understand every aspect of the clinical trial.  

Listed below is some general information that should be included in an informed consent form.

• The nature of the study,

• Why the candidates are being recruited for this study,

• What risks, benefits and alternatives are associated with the research, and

• What rights the subjects/patients have as research subjects.

4. Questions Patients Should Ask – If you are thinking of enrolling in a clinical trial, there are many questions you should ask yourself in order to make an informed choice:

• Do you think the study drug may be better than the current standard-of-care medications that have been approved by the FDA?  If so, why?

• What is the current phase of the trial (phase 1, 2, 3 or 4)?  

• Have you considered the possible side effects and the safety profile of the trial drugs 

• Is it too early in the clinical trial development that it may pose too many risks?

• Are your willing to take the possible risks, and side effects?

• What are the potential benefits?  

• Is the cost of the study tests covered?

• Is it an open-label study—that is, does everyone receive the study drug?

• Is it a randomized study?  If so, if you do not get the study drug are you offered the study drug at the end of the study?

• Who will be in charge of the patient care?

• Can you wait until the study drugs are FDA approved?

Note:  Remember you can drop out of a clinical trial any time you want.

5. Next Steps

There are many questions to think about before entering into a clinical trial.  Some people would like to further the knowledge about a particular disease and treatment that will help their community.  Others may want to receive medical care and treatment.  Medical care and treatment may be particularly important for many people who do not have insurance or for those who have been denied coverage.  Still others who have been treated but have not been cured may seek treatment and care through clinical trials.  All of these reasons are valid and clinical trials are a good way to explore HCV treatment and care.  However, as with any HCV treatment you do not want to rush into any decision.  It is always good to do your research and work with your medical provider to make the best possible medical decision that is the best decision for you.

Ask your medical provider and/or gastroenterologist/hepatologist about clinical trials in your area.  Many medical hospitals also conduct clinical trials.

The best website that I have found is www.clinicaltrials.govhttps://www.clinicaltrials.gov/.

Type in ‘HCV’ and away you go…

For more information:  Making sense of Hepatitis C Research and Medical Literature
http://hcvadvocate.org/hepatitis/factsheets_pdf/Making_Sense.pdfhttp://hcvadvocate.org/hepatitis/factsheets_pdf/Making_Sense.pdf

Gilead Submits New Drug Application to U.S. Food and Drug Administration for Fixed-Dose Combination of Sofosbuvir/Velpatasvir for Treatment of All Six Genotypes of Hepatitis C

FOSTER CITY, Calif.–(BUSINESS WIRE)–Gilead Sciences, Inc. (Nasdaq:GILD) today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for an investigational, once-daily fixed-dose combination of the nucleotide analog polymerase inhibitor sofosbuvir (SOF), approved as Sovaldi® in December 2013, and velpatasvir (VEL), an investigational pan-genotypic NS5A inhibitor, for the treatment of chronic genotype 1-6 hepatitis C virus (HCV) infection. The NDA is supported by clinical studies exploring the use of 12 weeks of SOF/VEL for patients with genotype 1-6 HCV infection, including patients with compensated cirrhosis and 12 weeks of SOF/VEL with ribavirin for patients with decompensated cirrhosis.

“As the first fixed-dose combination of two pan-genotypic, direct-acting antivirals, SOF/VEL represents an important step forward in the treatment of patients with hepatitis C,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer at Gilead. “Genotype 1 is the most prevalent form of HCV in the United States, but worldwide, more than half of people living with HCV are infected with other genotypes. SOF/VEL complements our current HCV portfolio of Sovaldi and Harvoni, offering high cure rates and the potential to simplify treatment and eliminate the need for HCV genotype testing.”

The FDA has assigned SOF/VEL a Breakthrough Therapy designation, which is granted to investigational medicines that may offer major advances in treatment over existing options. The NDA for SOF/VEL is supported by data from four Phase 3 ASTRAL trials, which evaluated the fixed-dose combination in hepatitis C genotypes 1-6. Of the 1,035 patients treated with SOF/VEL for 12 weeks in the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,015 (98 percent) achieved the primary efficacy endpoint of SVR12. The ASTRAL-4 study randomized 267 patients with decompensated cirrhosis (Child-Pugh class B) to receive 12 weeks of SOF/VEL with or without ribavirin (RBV), or 24 weeks of SOF/VEL. Those who received SOF/VEL plus RBV for 12 weeks achieved an SVR12 rate of 94 percent,while those who received SOF/VEL for 12 weeks and 24 weeks achieved SVR12 rates of 83 percent and 86 percent, respectively.

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Hepatitis C: behind new wonder drugs lies a terrible dilemma

There are 160m carriers of the hepatitis C virus across the world. Combined with the hepatitis B virus, which has 240m carriers, this causes 1.4m deaths every year.

Yet there are grounds for optimism around hepatitis C. Numerous pharmaceutical companies have recently brought to market new sets of “direct-acting antiviral” medicines to combat the infection. These have been shown to permanently clear the hepatitis C virus in 90% of patients in only a few short weeks, and with negligible adverse effects. It is not an overstatement to say that these antivirals have the potential to do for hepatitis C what oral vaccination did for polio.

But there is a fly in the ointment. The new drugs are unaffordable. Take the UK as an example, where around 214,000 people live with hepatitis C. Going by the indicated list price of £35,000 per treatment course, it would cost around £7.5 billion to treat every infected person. Even the staunchest hepatitis advocate would concede that since that approaches the entire NHS annual drug budget, treating everyone is not feasible in the short term.

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Open Enrollment for Obamacare and Medicare —By Jacques Chambers

Open Enrollment for Obamacare and Medicare
—By Jacques Chambers

Medicare Open Enrollment starts October 15, 2015 and ends December 7, 2015.
All changes made during this time are effective January 1, 2016.

Affordable Care Act Open Enrollment runs from November 1, 2015 through January 31, 2016.
The effective date will be based on when the changes are requested;

• If made on or before 12/15/2015 – Changes effective on January 1, 2016
• If made 12/16/2015 through 01/15/2016 – Changes effective on February 1, 2016
• If made 01/16/2016 through 01/31/2016 – Changes effective on March 1, 2016 

Employer-Provided Benefit Programs also frequently provide an Open Enrollment Period for employees, allowing them to make changes in their employee benefits choices. Although employers can select other times of the year, most employers who offer one have their Open Enrollment in November and/or December for a January 1, 2016 effective date.

Medicare

Medicare beneficiaries have the opportunity to switch their coverage from any to any of several choices:

Original Fee For Service Medicare – Parts A and B of original Medicare are the same for everyone; however, each beneficiary can elect the prescription drug plan in which to enroll. The best way to do this is to compare plans using your own current prescriptions, since your medications may have changed and plan formularies and prices also change.

There is a program on line at www.medicare.gov that allows you to enter your medications, which pharmacy your prefer, and where you live; it will then show you what each plan would cost you out of your pocket based on your medications.  Click on “Find Health and Drug Plans” and follow from there. I recommend the “General Search” rather than the personal one; it is much quicker and just as accurate. If you are on particularly expensive medications, once you find a drug plan, you should confirm the coverage and what you will pay directly with the insurance company as errors sometimes occur.

Even if your current Drug Plan has been serving you well, it is still advisable to run the program. The plans for 2016 are already up on the website.

For persons who are not comfortable with computers, Medicare’s toll-free number (800-MEDICARE) will do the same calculation.  However, I recommend you find a friend or relative who will do it for you on a computer because the results are too long and involved for a telephone operator to spend much time reviewing the options based on your specific needs.  

Medicare Supplement (also called Medigap) Plans – This open enrollment period does NOT apply to the Medigap Plans sold to people with Original Medicare to “fill the coverage gaps” left by Medicare Parts A & B.  To find out when you can purchase them, go to www.medicare.gov and search for “When Can I Buy a Medigap Policy”. It will list the Open Enrollment opportunities for them. They may also be purchased at other times, but the insurance company may require proof of good health.

Medicare Advantage Plans – These are plans offered by insurance companies and health service providers and are an alternative to Fee-for-Service Medicare.  Many of these plans are run by Health Maintenance Organizations (HMOs), but there are also Preferred Provider Organization Plans (PPOs), Exclusive Provider Organizations (EPOs), Special Needs Programs, and Private Fee-For-Service plans, although all types are not available in all areas. All Medicare Advantage Plans must offer all of regular Medicare’s benefits and may add more.  Some plans may also charge an additional premium, usually relatively small.  These plans frequently include the prescription drug coverage in their plan so you don’t have the additional task of finding a Part D drug plan.

During this Open Enrollment Period, persons may switch from one Medicare Advantage Plan to another or move back to or away from Fee-For Service Medicare.

NOTE: If you move from a Medicare Advantage Plan to Original Fee-for-Service Medicare, you have until February 14, 2016 to enroll in a Part D Drug Plan.


Affordable Care Act (Obamacare)
Persons enrolled in coverage, as well as those who have not yet joined, have the opportunity to enroll into or change health plans under the Affordable Care Act.

Many plans are making changes in coverage as well as cost, so I do recommend you go to your state’s health exchange, or to www.healthcare.gov for people in those states that do no operate their own exchange, and search to see if there is better coverage for you.

Since most of these plans use network providers, you should confirm directly with the insurance company that the doctors and hospitals you prefer are part of the network. Also, make sure your medications are on the plan’s formulary.

Employer Provided Benefit Plans 
Employers offering an Open Enrollment period for their employees will publish (or offer online) an Open Enrollment Guide that spells out each employee’s current benefits plus the available options, opportunities, and costs that may be chosen during this period. For persons dealing with a serious medical condition like HCV, it can be an opportunity to alter benefits and, in some cases, actually increase benefits since these programs usually offer more than just health insurance.

Life Insurance. Persons dealing with HBV/HCV are generally unable to purchase life insurance in the individual market. An employer may give all employees a base benefit from $10,000 to $50,000, and a few will allow employees to purchase additional coverage. If your employer offers supplemental life insurance above what he or she offers; see if there is an amount you can purchase that will not require evidence of good health. If it is available, it is an excellent way for an otherwise “uninsurable” person to obtain additional life insurance.

Long Term Disability.  Less common, but still occasionally available, is the opportunity to increase the benefit of your LTD plan.  Some employers will provide a basic benefit for LTD, such as 50% or 60% of your monthly earnings, and allow employees to purchase an additional 10% or 15% to raise the benefit they would receive in the event of disability.

Some employers may allow you to add this benefit if you did not elect it originally. Again, it is important to read your Open Enrollment material to see if your employer offers this and if proof of good health is required.

Revising LTD Premium Payment. One additional possibility to explore is the payment of LTD premiums. Some employers will allow you to have the premium they pay for your LTD coverage added to your W-2 making the premiums taxable rather than receiving it as a tax-free gift. If this is possible you may want to jump at the chance, the reason being tax-free disability benefits should you become disabled.

If you pay for the LTD coverage with money that is taxed as income, then the benefits you receive if you become disabled will be income tax free, substantially increasing the spendable dollars you would receive as a disability benefit. The rule is the IRS will tax either the premium paying for the coverage or the disability benefits being paid out, but not both.

Health Related Benefits.  Many employers, especially larger ones, offer a variety of health, dental, and vision plans from which employees can choose.  At Open Enrollment, you have the opportunity to change your coverage from one plan to another regardless of your medical condition, and sometimes have the opportunity to make choices within your plan, such as increase or decrease the size of the deductible.

For someone dealing with HCV, this can be an important choice, especially if this is the first Open Enrollment since diagnosis.  There is no one type of health plan that is best for everyone. There are two main kinds of plans that employers offer most often:

Preferred Provider Organization (PPO) – These plans provide some coverage for all physicians, but pay more if you choose a physician that has contracted with the insurance company, a Participating Provider.  This plan will give you the greatest flexibility in medical providers; however, it will often cost you more out of pocket for both your portion of the monthly premium as well as the plan co-pays and co-insurance.

Health Maintenance Organizations (HMO) – These plans usually offer the lowest out-of-pocket expenses, but limit your choice of physician. Coverage is only provided when using one of their contracting doctors and hospitals.  Also, a Primary Care Physician (also called a Gatekeeper) oversees all your medical care and must refer you to a specialist before the HMO will cover the specialist’s charge.

Exclusive Provider Organization (EPO) – These plans are exactly like an HMO except, there is no Gatekeeper physician. You decide if you need to see a specialist and make the appointment directly.

Which plan is better for you will depend on which doctors you wish to retain and what HMOs or PPO plans they are part of, as well as the cost to you.

National Chocolate Day

Dark Chocolate has some positive health affects.  There is some literature that shows that eating a piece of a quarter size piece of dark chocolate can be healthy.  But remember just one piece!  

In appreciation of National Chocolate Day - Indulge in that one small piece of chocolate!