Research at the HBF’s Baruch S. Blumberg Institute

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Hepatitis C is now declared curable. Hepatitis B is still not, despite having been discovered nearly 50 years ago. An interview with Dr. Timothy Block of  the Hepatitis B Foundation and the Baruch S. Blumberg Institute. The future does look bright…

Perhaps this should not be a surprise, thinks Timothy Block, PhD, president and co-founder of the Hepatitis B Foundation (HBF) and its research arm, the Baruch S. Blumberg Institute. According to Block,there are two main reasons for the “cure deficit” between hepatitis B and C — funding and physiology.

He points out that commercial and federal investment in hepatitis C have been far greater than in hepatitis B. And that has clearly paid off in terms of finding a hepatitis C cure. “You get what you pay for,” he observes.

Physiologically, hepatitis B also presents unique challenges not found with hepatitis C — most notably cccDNA (or covalently closed circular DNA), the “mini- chromosome” produced by the hepatitis B virus. The cccDNA persists in the nucleus of the liver cell, where it can hide amidst the host’s own chromosomes, apparently out of reach of the cell’s own defense systems.

Acting like “an indestructible template,” cccDNA continues to produce virus particles throughout the life of the infected liver cell, even in people being treated with antiviral agents.

Hepatitis C, on the other hand, doesn’t enter the cell’s nucleus, so it’s possible to cure a person by stopping this virus from replicating long enough for the liver cells to regenerate.

But remember that people who have been “cured” of hepatitis C can still get re-infected,” Block cautions. The hepatitis C drugs apparently do not trigger an immune response that protects against re-infection.

In contrast, some people can be cured of hepatitis B, either naturally or through drug therapy. These individuals do seem to have long-term protective immunity. “And that’s what we are aiming for,” he declares.

Why We Need a Cure for Hepatitis B 

It can be argued that the approved antiviral agents are very successful in keeping the virus under control. So do we really need a cure? Definitely yes, Block replies emphatically.

Current antiviral drugs are effective, but need to be taken lifelong and are recommended for use in only about half of the infected population. And even after 10 years of use, the antivirals reduce HBV-related diseases by only about 50 to 60 percent. The drugs can also lead to the development of resistant hepatitis B strains (drug resistance).

For those who benefit from treatment, the antiviral drugs have been transformational and prove that medical intervention can be effective. However, there are millions who do not benefit and are still left vulnerable.

Clearly, new approaches to a “functional cure” are needed, which Block defines as “returning the risk of death due to hepatitis B to the level of someone who has a resolved infection.” And the person should not need to take any drugs to stay at this low-risk level.

Targeted Strategy for a Cure

The HBF/Blumberg Institute scientists, with their research partners from Drexel University College of Medicine, both located in the HBF’s Pennsylvania Biotechnology Center, are developing two types of therapies: direct-acting antivirals and innate host defense activators. The first type inhibits virus-host interactions and viral gene products; the second recruits the host’s immune system to attack and eliminate cccDNA and infected liver cells.

For each of these approaches, the researchers have identified key steps to target in the hepatitis B infection cycle, from virus entry into the liver cell, to cccDNA replication, to formation of virus particles.

For many of these steps, “Our scientists have developed assays that can be used to screen for new drugs. We are a recognized leader in designing and developing these assays and, for a time, had the only cccDNA- dependent cell lines,” notes Block. Almost 100 different cell lines for assays have been developed that can be used to screen for drugs that activate the innate host defense pathways.

For drug screening, cell lines are incubated with potential drug candidates from the Foundation’s own library of almost 90,000 compounds and the natural products collection that it received as a donation from Merck & Co. in 2011.

The strategic goal is to discover new drugs that complement existing therapies, but also enable the immune system to provide long-lasting antiviral protection, even when the person is no longer on drug therapy.

Several compounds in development already show some effectiveness in animal models. “We have a capsid inhibitor, a pregenomic RNA capsid inhibitor (JT Guo), an HBsAg inhibitor (A Cuconati), a cccDNA repressor (H Guo, A Cuconati, JT Guo), and an activator of innate host defense pathways (J Chang and JT Guo),” Block reports.

He is particularly excited about their stimulator of interferon genes (STING) agonist, which was very effective in mouse models. The research group is now working on a human STING agonist, although an appropriate assay for this compound still needs to be developed.

What the Future Holds 

“The Hepatitis B Foundation and its Blumberg Institute have contributed
to some of the most important work in studying the phases of the virus lifecycle that has led to the currently available drugs. Our researchers continue to be at the forefront in developing a promising pipeline for hepatitis B drug discovery,” says Block.

“I am absolutely confident that a cure is possible” he asserts. “After all, enough people with hepatitis B resolve their infections, either medically or spontaneously — even some people with chronic infections. So we know it’s possible.”

 

 

WHO’s New HBV Guidelines to Help Combat Africa’s Growing Hepatitis B Crisis

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The World Health Organization (WHO) will release their first management guidelines for hepatitis B virus (HBV) by the end of 2014. For the first time, the guidelines will be geared towards resource-constrained countries, where the disease burden is high but resources are lacking. The new guidelines will be particularly welcome in African nations, where the incidence of viral hepatitis is increasing.

The overall scope of the World Health Organization’s new management guidelines for hepatitis B will include prevention, screening, and treatment of chronic hepatitis B and will be geared towards resource-constrained countries. Thus, WHO’s guidelines will be valuable for countries where the disease burden is high but resources are lacking.

The WHO Global Hepatitis Programme established a Guideline Development Group of external experts in 2013, which includes Hepatitis B Foundation (HBF) executive director Joan Block, and is co-chaired by Dr. Brian McMahon, who also serves on the HBF Scientific and Medical Advisory Board.

The new WHO guidelines will be particularly welcome news to African nations, where the incidence of viral hepatitis is increasing.

According to the WHO Global Hepatitis Survey 2013, the prevalence of chronic hepatitis B virus (HBV) infection on the African continent is up to 8% of the general population, and 75% of the population may have had prior exposure to the virus.

Yet, only two of the African member states that responded to the WHO Survey have a written national strategy to prevent and control viral hepatitis.

In Ghana, where the incidence of viral hepatitis is increasing, the sero-prevalence rate is high among blood donors (6.7%), pregnant women (6.5%) and school
aged children (15.6%), according to Mr. Theobald Owusu-Ansah, president of the Theobald Hepatitis B Foundation and the Hepatitis B Coalition in Ghana.

Compounding the lack of public health plans and national investment are factors common in many low-resource countries: limited awareness of hepatitis B among the public and providers, poor access to care, expensive therapies, and few liver specialists.

Global agencies are beginning to recognize the urgency of the situation. In addition to the WHO, the World Health Assembly is taking steps to combat the growing crisis. The Assembly adopted a second resolution on viral hepatitis in May 2014 that advises governments on how to prioritize and coordinate public health efforts.

But governments cannot tackle these problems alone, Mr. Owusu-Ansah believes. He urges governments to partner with commercial and nonprofit organizations to mobilize much-needed expertise and resources.

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HBV Journal Review – December 2014

ChrisKHBF is pleased to connect our blog readers to Christine Kukka’s monthly HBV Journal Review that she writes for the HBV Advocate. The journal presents the
 latest in hepatitis B research, treatment, and prevention from recent academic and medical journals. This month, the following topics are explored:

  • Twenty-five Percent of HBV-Infected Women Have Liver “Flares” after Childbirth
  • Experts: Do Not Treat Patients in the Immune-Tolerant Stage of Infection
  • Entecavir and Tenofovir Equally Effective in HBeAg-positive Patients and Cirrhotics
  • Tenofovir Effective in Patients with Adefovir- and Lamivudine-Resistance
  • Adding Interferon to Ongoing Antiviral Treatment Effective in HBeAg-positive Patients
  • Antivirals Improve Survival Among Hepatitis B Patients
  • Interferon Effective in HBeAg-negative Patients, Early HBsAg Declines Predict Success
  • Study Finds Asian Immigrants, Especially Chinese, at High Risk of Hepatitis B
  • Immunization Continues to Protect Against Hepatitis B Decades Later
  • Doctors Fail to Vaccinate Hepatitis Patients Against Other Hepatitis Infections
  • Study Confirms HBV Patients Have Higher Kidney Disease Rates

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Fighting the Doom and Gloom: It Takes a Team

universal-health-care-medical-teamPeople generally think liver cancer is non-treatable and non-curable. But that perception needs to change. Diagnosis and treatment of liver cancer have improved so much in the past 20 years that it can be cured if caught early and managed by an experienced health care team. Liver Cancer Connects “Fighting the Doom and Gloom” series explains how the right treatment plan  and teamwork offer the best chances for a cure.  Continue reading

AASLD 2014 Liver Meeting – HBV Coverage

Unknown-5Get HBV Advocate’s Christine Kukka’s take on the top HBV related, published reports from the AASLD Liver Meeting as she provides her Top Ten List! 

 

Top Ten Reports from the 65th Annual Liver Meeting
By Christine M. Kukka, HBV Advocate 

Hepatitis B experts from around the world met at the 65th annual American Association for the Study of Liver Diseases (AASLD) conference in Washington D.C. this week to share the latest in hepatitis B treatment and research.

  1.  Which combination of antivirals and interferon works best against hepatitis B
  2. Tenofovir continues to excel with no signs of drug resistance after eight years
  3. Tenofovir treatment is safe over an entire pregnancy for both mother and child
  4. Tenofovir and entecavir combination successful against drug-resistant HBV
  5. Who remains at risk for hepatitis B in the U.S.?
  6. Antivirals appear to lower liver cancer risk
  7. But antivirals don’t reduce cancer risk in older patients with cirrhosis
  8. How long do patients have to keep taking antivirals after they lose HBeAg and achieve undetectable viral load?
  9. Liver cancer risk remains, even after HBsAg clearance in older, male patients
  10. Experts say treatment is needed when ALT levels are only moderately elevated

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