Hep B Blog

Monthly Archives: November 2016

Hepatitis B Prevention, Hepatitis B Treatment, Living with Hepatitis B

Family Getting Together for The Holidays? Time to Talk Hepatitis B and Your Family’s Health History

Image courtesy of Apolonia at FreeDigitalPhotos.net.
Image courtesy of Apolonia at FreeDigitalPhotos.net.

By Christine Kukka

When we have chronic hepatitis B, knowing our family medical history can give us an inside edge to fight this infection.

Hepatitis B is an infection that often runs in families. Knowing how our parents, grandparents and aunts/uncles responded to this liver disease can give us insider information about our own genetic prospects with hepatitis B.

Experts estimate that more than half of us worldwide became infected at birth. Our mothers may have been infected with hepatitis B. Immunization, which can prevent infection if administered within 12 hours of birth, was not available to us as newborns, nor to our mothers or grandmothers.

So if we suspect or know our parents have or had hepatitis B, it’s important to find out if our aunts and uncles or grandparents were also infected and had signs of liver damage. Did anyone get liver cancer or die from liver-related problems? Or, did our relatives live long lives due to strong genes, healthy lifestyle choices, and avoiding smoking and alcohol?

Knowing how our genetic predecessors handled this infection gives clues about:

  • How often we should be screened for liver cancer? We should be screened earlier and more often if we have a family history of cancer.
  • How soon should we start treatment? If our predecessors had liver damage at a young age, perhaps we should start treatment sooner rather than wait and endure long periods of liver damage and high viral loads.
  • How effective are our family’s genes in fighting this infection? Did many family members with hepatitis B have liver damage or cancer, or did they have relatively long and healthy lives?
  • What effect did the hepatitis B virus’ strain or genotype play? Depending on the HBV genotype that infects us, we may have different experiences with hepatitis B. We may we develop the hepatitis B “e” antibody earlier if we have certain HBV genotypes. Knowing our relatives’ health history gives us some insight into this.
  • What effect does gender play? Did women experience liver damage or did it only happen to men? The female hormone estrogen is believed to confer some protection against hepatitis B. It may be that men in your family are at highest risk of liver damage and need more frequent monitoring and earlier treatment.
Image courtesy of jk1991 at FreeDigitalPhotos.net.
Image courtesy of jk1991 at FreeDigitalPhotos.net.

There are other factors besides genes that affect a multi-generational experience of hepatitis B. Did our grandparent who developed liver cancer suffer poor nutrition for extended periods in their country of origin that weakened their immune system? Did the uncle who had cirrhosis also smoke, drink or suffer exposure to chemicals at work? Could a grandparent who died of liver disease eat moldy rice or corn that contained aflatoxin, which severely damages the liver?

Taken together, all of these factors give us clues to medical conditions that may run in our families, and this knowledge isn’t limited to just hepatitis B. By identifying family patterns of medical problems such as diabetes, heart disease, high blood pressure or breast cancers, healthcare providers can determine if we and our children are at increased risk of a particular condition.

Because knowing your family’s health history is such a powerful tool, the Surgeon General created a free website to help everyone create a portrait of their family’s health at My Family Health Portrait.

After completing the questions, the website creates a personalized “family health tree” that can be saved to a home computer. From there, families may update the information any time. The tool can be shared with other family members, who can add their health information to the portrait. It’s also important to share this portrait with your doctor.

The Surgeon General has declared Thanksgiving to be National Family Health History Day. But whenever your family gathers for a holiday, ask about their medical history. It just might save your life.

Hepatitis B Treatment

Global Researchers Brainstorm Solutions in the Search for a Cure for Hepatitis B

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Timothy Block, cofounder and president of the Hepatitis B Foundation and the Baruch Blumberg Institute, discussed reducing hepatitis B surface antigen production as a strategy to stop chronic hepatitis B infection at the workshop.
Timothy Block, cofounder and president of the Hepatitis B Foundation and the Baruch Blumberg Institute, discussed reducing hepatitis B surface antigen production as a strategy to stop chronic hepatitis B infection at the workshop.

By Christine Kukka

Liver specialists, virologists and immunologists from around the world met at the 3rd International Workshop on a Hepatitis B Cure in Toronto last week to share their advances and brainstorm solutions to the challenges they face as they hunt for a cure for the liver infection that affects 240 million worldwide.
Eradicating hepatitis B virus (HBV) infection is no easy task. HBV is a far more complicated and resilient virus than hepatitis C, and scientists predict a cure will require a careful orchestration of drugs and immune-enhancing treatments that could:
  • Eliminate HBV antigens—especially the hepatitis B surface antigen (HBsAg). This viral protein appears able to “exhaust” or disable the immune system’s T cells so they’re unable to effectively fight the infection.
  • Find a vulnerability in the HBV replication cycle that can be exploited to keep the virus from entering liver cells and inserting its genetic material (cccDNA) required for viral reproduction.
  • Enhance or “wake up” the exhausted T cells, after HBsAg is reduced or eliminated, so the immune system can successfully eradicate the HBV-infected liver cells.

As researchers learn more about why HBV is so successful at evading the immune system and hijacking liver cells for viral production, they are also realizing how much they don’t know and what tools they lack to identify if and when they find successful treatment strategies. Here are some of the challenges the researchers addressed during the day-long brainstorming session.

Panelists (left to right) Jordan Feld of the Toronto Western Hospital Liver Center, Stephen Urban, head of Translational Virology at Heidelberg University Hospital, Harry Janssen, head of the Toronto Centre for Liver Disease, and Marion Peters, chief of hepatology research at the University of California at San Francisco, were among the speakers at the 3rd International Workshop on Hepatitis B Cure.
Panelists (left to right) Jordan Feld of the Toronto Western Hospital Liver Center, Stephen Urban, head of Translational Virology at Heidelberg University Hospital, Harry Janssen, head of the Toronto Centre for Liver Disease, and Marion Peters, chief of hepatology research at the University of California at San Francisco, were among the speakers at the 3rd International Workshop on Hepatitis B Cure.

What will a cure look like? Can scientists ever expect to totally eradicate HBV from the liver? Even when healthy adults are able to clear HBV following an acute infection, small reservoirs of the virus remain – similar to chicken pox that causes shingles later in life when the immune system can no longer hold it in check. Should researchers instead set their sights on a cure that duplicates what Mother Nature now achieves following an acute infection, which simply eradicates most of the virus and greatly reduces the risk of liver damage.

Do researchers currently have the right tools to identify when a treatment works? Nearly all hepatitis B lab tests used today evolved from blood bank tests designed to identify HBV-infected donated blood. As a result, lab tests produce a “positive” or “negative” measurements for the presence of antigens and antibodies, but nothing more nuanced. Labs measure the amount of HBV DNA (viral load) in a patient, but rarely measure HBsAg even though patients can have an undetectable viral load and still have lots of HBsAg circulating in their bodies.
But figuring out when a treatment is able to reduce HBsAg or other antigens may be critical to a cure. Several research initiatives are working to reduce HBsAg, which is produced in great quantities and is believed to prevent the immune system from actively attacking the infection. But right now, most lab tests in the U.S. don’t measure how much HBsAg a patient has in their bloodstream.
“We don’t have great assays (lab tests) for measuring treatment responses (to current or new drugs),” said workshop panelist Jordan Feld, a clinical scientists and researcher from the Toronto Western Hospital Liver Center.
“Maybe we don’t have the right endpoints to measure how effective treatment is,” said Marion Peters, chief of hepatology research at the University of California at San Francisco. “A treatment might be having an effect, but we don’t know what to measure so we don’t know it.”
A lost research opportunity with TAF clinical trials? On Nov. 10, the U.S. Food and Drug Administration (FDA) approved TAF, a new, lower-dose formulation of tenofovir that channels the antiviral more effectively to infected liver cells while reducing the drug’s impact on kidney function and bone loss. Because TAF’s clinical trials focused primarily on comparing the reformulated drug’s impact on viral load, ALT (liver health) and side effects, researchers did not conduct liver biopsies on TAF clinical trial participants.
While lower-dose TAF was found to work as well as tenofovir in slowing viral replication, it did something that researchers didn’t expect. During one clinical trial, 50 percent of patients treated with TAF achieved normal ALT levels–indicating no liver damage– compared to only 32 percent of patients treated with tenofovir.
Why was TAF so effective on liver cells? Was it able to remove some of the cccDNA or prevent HBV from replicating in liver cells in a way that tenofovir could not? “There seems to be a correlation, but because they didn’t have that possible endpoint in mind, they didn’t think to perform liver biopsies, which would have answered some of those questions,” Dr. Peters commented.
“We need to go beyond commercially-available tests so we can see with better sensitivity whether TAF or another drug would actually be more efficient and see what the effect is within the liver,” observed Fabien Zoulim, MD, PhD, associate director of the Liver Department at the Hôtel Dieu hospital in Lyon (France) and scientific director of the INSERM Unit 871.
How to eliminate HBV-infected liver cells without damaging the liver: In chronic hepatitis B, a large percentage of liver cells are infected. Some treatments in development, such as those using small interfering RNAs technology, target HBV antigens including HBsAg and quickly reduce their numbers. Using a combination treatment of antivirals to reduce viral load and RNAii technology to eradicate HBsAg, the immune system can swing into action and attack the infected liver cells. But how do you pace this “attack” so the liver is not severely damaged and the patient’s health threatened?
If only a small percentage of infected liver cells are killed during treatment, others will survive and continue to churn out virus. Kill too few infected liver cells and continual re-treatment is required. Kill too many liver cells and a patient could die from liver failure.
Flares are inevitable when the immune system is attacking infected liver cells – such as during an acute hepatitis B infection — but can this clearance be controlled without harming the patient?
The day before the workshop, the FDA ordered Arrowhead Pharmaceuticals to stop its Phase II human trials of its ARC 520 drug that uses RNAii to eradicate HBsAg after reports of deaths in animals that had been given high doses of the drug. The doses were much higher than were administered to humans in the Phase II clinical trial, which was evaluating the reduction of HBsAg after intravenous administration of ARC-520 in combination with entecavir or tenofovir. Panelists noted that this potential cure may still have promise, but the treatment dose must be examined and monitored carefully.
Takeaway:
The workshop presentations highlighted the inevitable setbacks and advances that scientists make in the search for a cure. But optimism remained. Never have so many researchers been working from so many directions to find the synergistic solution that will one day reduce HBsAg, stop HBV from reproducing and spur T cells to attack infected liver cells.
One panelist suggested in the next five years, researchers should be able to develop ways to reduce viral load while enhancing the immune system’s T cell response to eradicate a hepatitis B infection. Around the world, 240 million people living with hepatitis B are waiting anxiously.
 
The Hepatitis B Foundation was a partner of the workshop. For more information about the workshop and researchers’ presentations, please click here.

Hepatitis B Advocacy, Hepatitis B Treatment, Liver Cancer

Shop Carefully for Lowest-Cost Hepatitis B Drugs When Signing Up for Medicare by Dec 7

Image courtesy of Witthaya Phonsawat at FreeDigitalPhotos.net
Image courtesy of Witthaya Phonsawat at FreeDigitalPhotos.net

By Christine Kukka

With the cost of healthcare and prescription drugs soaring, it’s important for people age 65 and older who live with hepatitis B to shop for Medicare coverage carefully before they sign up by Dec. 7, especially if they need costly antivirals and frequent lab tests.

As we age, our immune system weakens and loses its ability to suppress our hepatitis B infection. We may notice a gradual rise in our viral load (HBV DNA) and/or our liver enzymes (ALT/SGPT), which indicate liver damage.

We may also experience other medical conditions, such as cancer or arthritis that require immune-suppressing drugs that unfortunately enable our hepatitis B to reactivate. To lower our viral load and reduce the risk of liver damage, we’ll need antivirals, and they’re not cheap. Medicare recipients must shop carefully for the most affordable plan. Here are the three key Medicare coverage areas:

Part A is free. It covers most of hospital and nursing home care, however you still pay for some deductibles and copays. For example, if you go to a hospital for a liver biopsy, you will pay a portion of that cost if you only have Part A.

Part B covers doctor visits and lab tests, and it costs about $150 a month and increases based on your income. There is a deductible of $166 a year and you pay a 20 percent copay for many services. Instead of selecting Part B, you may instead choose a private or employer-sponsored Medicare advantage plan.

Part D covers your drug costs and it’s optional, but if you’re on antivirals, interferon or other medications, it important that you have drug coverage under this or a Medicare Advantage plan (such as HMOs or PPOs) that cover all Medicare benefits including drugs. If you have a low income, you may be eligible for assistance to help pay for your Part D plan.

Image courtesy of Ambro at FreeDigitalPhotos.net
Image courtesy of Ambro at FreeDigitalPhotos.net

It is critical that you shop around before selecting a drug plan. Just like the Affordable Care Act’s Health Exchange, there will be fewer drug programs available to you to choose from this fall. You also need to make sure your plan:

  • Has your specialist or primary care doctor and lab in its network, and
  • Offers the lowest copay for the drugs you need.

When you shop for a Medicare Part D drug plan: You select from plans based on where you live and what drugs you take. For example, if you’re shopping for a drug plan to cover tenofovir (Viread), plan prices can vary by more than $1,000 a year. Comparison shopping is critical!

To find a plan, go to Medicare Plan Finder and enter your zip code and select the drugs you expect to take during 2017. It’s a good idea to sit down with someone who can help you during your search or call a Medicare representative at 1-800-633-4227 (1-800-MEDICARE) as you search online.

The drug plans have different pricing tiers for prescription drugs, a simple generic antibiotic can be less expensive Tier 1 or 2 drug, while a brand name drug like tenofovir can be a more costly Tier 4 or 5 drug.  Without Part D drug coverage, a year’s supply of tenofovir could cost about $12,880 a year. Before you select a plan, here are some suggestions:

Check the fine print: Make a list of all of your medications and check how much each plan reimburses for each. Search for any “hidden extras” you’ll have to pay if you’re using a brand name or specialty drug. Some plans have separate, high copays for brand-name and specialty drugs, which can include hepatitis B drugs.

If you need a brand-name maintenance drug (like tenofovir) that isn’t available as a generic yet, you may want to focus only on plans that have the lowest co-pay for that drug. Your other drug needs may be less expensive, generic cholesterol- or blood pressuring-lowering medication.

Consider both the monthly premium and the copay. You must consider both costs when searching for the best plan.

Does the plan require you to use a specific pharmacy? An increasing number of plans require you to use a preferred pharmacy, or even a mail-order option. Factor in convenience and your premium and copay.

Can you get discounts because of your income? You may be eligible to get all or part of your Medicare premiums, deductibles or co-payments covered if you have limited income and resources. Individuals with incomes less than $17,820 and assets less than $13,640, and couples with incomes less than $24,030 and assets less than $27,250, qualify for subsidies. You also may qualify, even if your income is higher, if you support other family members who live with you. Call Social Security at 800-772-1213 for information.

The good news: The dreaded “doughnut hole” or the gap during which you must pay a higher percentage of your drug costs, continues to shrink next year and will be completely phased out in 2020.

Even if you’re happy with what you had last year, do your research: Kaiser Foundation research found only 10 percent of Medicare enrollees switched plans between 2007 and 2014. Those who switched on average saved about $16 a month just on premiums. It pays to shop around.

Like your doctor? Make sure he/she is in your provider networks: Advantage plans can shuffle their provider and hospital networks each year. And their provider lists may not be included in Medicare’s online Plan Finder or the basic plan documents.

Contact your plan and ask for their 2017 provider directory before making a decision. Check if specialty facilities like university-based teaching medical centers are included. Or, call your physician and ask if they will be in the plan you’re considering — and, if not, where they’re going. And be aware: While doctors can leave a plan in the middle of a year, you typically can’t.

Hepatitis B Advocacy, Hepatitis B Treatment

Hepatitis B Foundation Expert Timothy Block Predicts Transformational New Therapies for Hepatitis B

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Hepatitis B Foundation President Timothy Block
Hepatitis B Foundation President Timothy Block

By Christine Kukka

For more than 25 years, Timothy Block, Ph.D,, has worked tirelessly to find a cure for hepatitis B, promoting research, writing papers, mentoring students and collaborating with experts around the world to find a cure for the 240 million people living with this deadly liver disease.

Today, the cofounder and president of the Hepatitis B Foundation, the Baruch S. Blumberg Institute and the Pennsylvania Biotechnology Center, is optimistic and believes there are new therapies in sight for those living with chronic hepatitis B.

An unprecedented number of researchers are scrutinizing every stage of the hepatitis B virus (HBV) replication cycle to find its vulnerabilities and develop drugs to permanently disable it. The cure Block wants would completely eradicate the infection so no one would ever wake up worrying about the risk of liver damage or cancer to themselves or a loved one.

This global, active march towards a cure is in stark contrast to 1991 when Block began his solitary quest, after a friend’s devastating hepatitis B infection made him rethink his career and start focusing on the liver disease that infects more than one in three people worldwide.

Twenty-five years ago, the only available treatment was conventional interferon, which was largely ineffective. The first antiviral, lamivudine, appeared shortly thereafter. It would be one of several to emerge from HIV’s drug arsenal. Since then, more antivirals designed to disrupt HBV’s replication process have been developed that target the polymerase—the essential enzyme needed for HBV replication.

“But they are not cures,” Block explained during a recent webinar. “They’re good at reducing viral load (HBV DNA), but they don’t get rid of the virus, and considerable viral DNA and  hepatitis B surface antigen (HBsAg) remain in liver cells.” Nor do current antivirals get rid of the HBV chromosome called cccDNA that embed in liver cells and stubbornly remain, ready to churn out more virus if a person stops taking antiviral drugs, or if their immune system weakens due to advancing age or another illness.

There are other roadblocks that make hepatitis B far harder to cure than hepatitis C. HBV generates massive amounts of HBsAg that appear to overwhelm the immune system’s B cells, whose job is to produce antibodies to eradicate HBV’s antigens. When newborns or young children are infected, these B-cells become paralyzed or “exhausted” by the flood of HBsAg engulfing them and they don’t generate the antibodies needed to fight infection. In contrast, when healthy adults are infected, these B-cells act quickly and aggressively to eradicate HBsAg within six months.

“Now for the first time, we’re looking beyond the polymerase to find more targets that are essential for HBV replication,” Block explained. HIV researchers have already done this and have identified more than 30 different “targets” in the HIV replication process. Hepatitis B researchers are also expanding their target range.

There are now new drugs in development, some have even reached Phase II clinical trials, that target new HBV reproductive terrain. They employ a variety of strategies ranging from immune system enhancers to molecular weapons designed to halt cccDNA integration into liver cells.

“If you can suppress cccDNA, the game would be over,” Block said, “but cccDNA is small, tough target. It’s so small compared to other material, that it’s almost impossible to distinguish from other molecules.” However, biologicals that are able to “inhibit” or block cccDNA from entering a liver cell could stop the virus from hijacking and reproducing in liver cells. Here are some types of drug strategies currently in development that could lead to a cure:

Restructured versions of tenofovir: There are two new tenofovir “prodrug” compounds, called TAF and CMX 157, that are more effective at reaching liver cells and impeding HBV replication. TAF is now in Phase III clinical trials and is expected to reach the U.S. Food and Drug Administration (FDA) this month (November 2016).

Molecular agents that target and disable HBV replication:

  • A new agent, called the CRISPR/Cas9 system, may be able to operate on a molecular level to search out and destroy HBV cccDNA molecules.
  • One of the more advanced molecular strategies, already in Phase II trials, is a “silencing” RNA process. This approach uses RNAi gene silencers to target and destroy HBV RNA to prevent viral reproduction. “CccDNA remains,” Block explained, “but all of its gene products it needs are choked.”

Entry inhibitors: Some of these drugs resemble HBsAg, but they work as decoys to prevent the virus from entering or binding to the liver cell. One is in Phase II clinical trial.

Capsid inhibitors: This approach interferes with the viral DNA’s ability to connect or glue together during the replication process. Several of these drugs are in Phase II clinical trials.

HBsAg inhibition and eradication: “There are 1 million more HBsAg as the actual virus,” Block observed. “Why are there so many? What is it doing in the blood? Why is it able to exhaust our B-cells?” Because HBsAg appears to hold a key in stopping infection, researchers are working to develop a way to eradicate HBsAg. Two of these HBsAg eradicator products are in Phase II trials.

Adaptive and innate host defense: This approach involves a two-step strategy, first reducing viral load to undetectable levels by helping liver cells become “in-hospitable” hosts to HBV’s reproductive efforts, and then introducing a vaccine or some other immune enhancer that can break the B-cell exhaustion cycle while firing up immune cells to aggressively fight and eradicate the infection. There are several of these drugs in Phase I and II clinical trials.

Block told his webinar audience that ideally one of these drugs would emerge as a single, simple cure. “But every infectious disease today, such as hepatitis C and HIV, is almost always treated with a combination of drugs. We might see two direct-acting antivirals and maybe a third drug that work as an immune system activator.”

When asked which patients would get first access to a new cure, Block predicted that people with high viral loads and liver damage would be treated first based on medical need. “As drugs get safer, I hope we will  treat people in the immune tolerant phase (with high viral load but no signs of liver damage yet), before they begin to have signs of liver damage.”

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Baruch S. Blumberg Institute