The World Health Organization has designated July 28 as World Hepatitis Day, a day to work for global change to eliminate viral hepatitis and the suffering, death and discrimination that accompanies hepatitis B and C by 2030.
From Asia to North America, on this day people around the world raise awareness about viral hepatitis and advocate for better access to treatment and prevention programs and more effective government action. Why? Because 4,000 deaths a day from viral hepatitis is 4,000 deaths too many.
This action is critical, because for too long global leaders have made hepatitis a low priority. Viral hepatitis is a silent disease that causes no symptoms until it’s too late, and many believed the hepatitis B vaccine would simply make the infection go away.
Instead, global health organizations focused on other diseases such as HIV/AIDS, tuberculosis and malaria. HIV especially benefited from unprecedented efforts and donated resources to enable diagnosis and prevention of transmission and to provide treatment at low cost.
Today, we need the same effort and resources to eradicate viral hepatitis, which kill an estimated 1.4 million each year – more people die from hepatitis annually than from HIV/AIDS and tuberculosis combined. For example, between 5 to 20 percent of the 1 billion people living in Sub-Saharan Africa have chronic hepatitis B Despite this prevalence, there are no widespread screening, education or prevention programs in Africa. The majority of people lucky enough to get screened and diagnosed for hepatitis B are often blood donors, because there are no public health clinics that provide screening for viral hepatitis.
In Asia and Africa, even when pregnant women are diagnosed with hepatitis B, their newborns are often not given that critical, first vaccine dose within 12 hours of birth that would break the mother-to-child hepatitis B infection cycle. The birth dose of the hepatitis B vaccine is either too costly or simply unavailable. Perinatal infection, though preventable, continues to be a major source of chronic infection worldwide. Continue reading "World Hepatitis Day: Because 4,000 Deaths a Day Is 4,000 Too Many"→
How far are we from finding a cure for hepatitis B? We are close, said Timothy Block, PhD, president and co-founder of the Hepatitis B Foundation and its research arm, the Baruch S. Blumberg Institute. He points out that hepatitis C, once thought to be incurable, is today cured with new combination treatments.
Image courtesy of suphakit73 at FreeDigitalPhotos.net.
Experts believe a cure for hepatitis B will also soon be developed. And the need for a cure has never been greater, with more than 240 million people worldwide living with chronic hepatitis B, causing 1 million deaths per year from related liver failure and liver cancer.
“Treatments are available,” explained Block, “but we have become a little too comfortable with the medications that are currently approved for use.” While these drugs are effective, interferon has many side effects and daily antivirals require lifelong use. These drugs work in only half of the infected population and reduce death rates by only about 40 to 70 percent.
What will a cure look like?
The available antivirals are similar and combining them offers no advantage. They have limited effectiveness against cccDNA, the seemingly indestructible “mini-chromosome” of the hepatitis B virus that continues to produce virus particles in infected liver cells, even in people being treated. A cure, therefore, would have to destroy or silence cccDNA and provide long-term immunity. Because one-drug treatments can lead to drug resistance, a cure would almost certainly involve combination therapy, similar to hepatitis C. Continue reading "Is a Cure for Hepatitis B Coming? Experts Say Yes"→
This year’s HEP DART conference brought together liver specialists and researchers from around the world to review and brainstorm about the latest research to find a cure for hepatitis B.
Biopharmaceutical companies presented data that showed their cutting-edge treatments, which use micro-RNAs and other innovative approaches to reduce the virus, appear promising. Much of this research, however, is in early, pre-clinical stages and focuses on laboratory-grown liver cells or laboratory animals, though a few are in Phase I and Phase II trials.
Joan Block, co-founder and executive director of the Hepatitis B Foundation, reported the following news in hepatitis B research from the conference, which was held in Hawaii from Dec. 6-10.
HepDart 2015 marks the 20th anniversary of this conference, and about 600 attendees from 20 countries attended. In opening remarks, Dr. Patrick Marcellin of France noted that the cure for hepatitis C is a huge medical breakthrough, now, he noted we are faced with finding a cure for hepatitis B.
This year’s HepDart meeting included nearly two days devoted to hepatitis B drug development—which shows the new momentum around finding a cure hepatitis B by the scientific community. During previous HepDart meetings, there was almost no discussion about new hepatitis B treatment. But this year, there are more than five companies presenting new hepatitis B drug findings, Block reported.
Researchers at the conference continued to lament the lack of resources spent to research and develop a cure for hepatitis B. They noted the U.S. government has spent $17.5 billion treating HIV. A fraction of that has been spent on finding cures for hepatitis B and C, which infects up to 6 million Americans.
Despite the lack of financial investment in finding a cure, Joan Block reports that the consensus at the conference is that a cure is indeed possible. Despite barriers to achieving a cure because of the complexity of the hepatitis B virus, “the feeling is that there are many targets in the life cycle of the virus and that a combination of a direct-acting antiviral along with an immunomodulator (to boost the immune system) will be the most likely route to success,” she reported.
In the short term, experts may be looking at a “functional” cure. For example, some of the new experimental drugs appear to increase the chances of clearing the hepatitis B surface antigen (HBsAg) with a finite duration of treatment. “Although this wouldn’t take care of (lingering) cccDNA or viral integration into liver cells, it would be a significant advance in treatment,” she said.
Day 2 of HepDart focused on targets within the virus, new therapies and possible cures. Experts explored whether any of the new drugs could produce a functional cure (similar to a resolved hepatitis B infection with loss of surface antigen) versus producing a complete cure that totally eradicates the virus from the liver (including cccDNA). Loss of cccDNA is referred to as the holy grail of the HBV cure.
“The parsing of the word ‘cure’ is frustrating to patient advocates,” she reported, “but the feeling is that the hepatitis B virus life cycle is very complex so an incremental or functional approach might be most feasible.
“Everyone wants a complete cure, including the scientists working on hepatitis B,” she noted, “however, a functional cure might be the most realistic goal in the next 10 years.”
A functional cure means patients will have to take one of the new drugs for only a limited period of time–compared to the current long-term reliance on antivirals that patients take in order to keep their viral loads down and prevent liver damage.
The downside of a functional cure is the potential for reactivation if a person, later in life, needs to take immune-suppressing drugs, such as chemotherapy, to fight cancer. However, this can be managed with antivirals if necessary. This is a similar situation to those who spontaneously recover from an infection.
To underscore the complexity of finding a cure, the image below shows the different targets in the hepatitis B virus life cycle that companies are examining to find a cure.
There are many promising targets that are being pursued by scientists in academia, NIH, biotech companies and the Hepatitis B Foundation. At this point, the small interfering RNA (siRNA) technology is most advanced. However there are compounds in the pipeline for each category (see below), which is very exciting. Please refer to the Hepatitis B Foundation’s Drug Watch Page for complete list of drugs in development.
“The research work continues,” Joan Block reported, “and there is reason for optimism.”
Dr. Marion Peters – HepDart 2015
The Hepatitis B Foundation president, Dr. Tim Block chaired a special session at HepDART to discuss what new endpoints will be needed to evaluate the efficacy of the new drugs coming down the pipeline. This will include immunological, virologic, and clinical endpoints for both a functional cure and complete cure. The clinical endpoint goals might differ based on the phase (immune tolerant, immune active and inactive phase) the patient is in at the time of treatment with these newer agents.
HBF president, Dr. Tim Block
Late breaking update from HepDART!
Arrowhead’s hepatitis B surface antigen (HBsAg)-lowering drug (ARC 520) looks promising according to the company’s presentation at HepDart. A single injection of the siRNA first in class type drug lowered HBsAg 10-fold in hepatitis B “e” antigen (HBeAg) positive people. The study was small (a few individuals) but impressive.
Arrowhead’s ARC 520 may also be telling us something about chronic HBeAg-positive hepatitis B versus HBeAg-negative hepatitis B. They suggest that the amount of HBsAg in the blood of people with HBeAg-negative hepatitis B may come from “integrated” hepatitis B in the liver, not from “cccDNA.” This has profound implications for treatment.
Novira’s oral drug is a first-in-class capisd inhibitor and was able to lower HBV DNA levels by as much as 100-fold in the small number of people in the initial human trial, according to their presentation at HepDart. Novira was recently acquired by the pharma giant J&J.
“Excitement is really building as the first new hepatitis B drugs come into the clinic,” said Joan Block.
Image courtesy of David Castillo Dominici at FreeDigitalPhotos.net
October is Liver Cancer Awareness Month. It may be a sleeper of a event when compared to other health campaigns, but for us who live with viral hepatitis, it’s an uncomfortable but critical reminder of the importance of monitoring our liver health to prevent cancer.
Viral hepatitis, especially B and C, are viral infections that can cause liver cancer (also called hepatocellular carcinoma or HCC.) Researchers are still studying why some people are more prone to liver cancer, but we who live with chronic hepatitis B or C have a 25 to 40 percent lifetime risk of developing liver cancer. The infection, which hijacks our liver cells to manufacture more virus, causes inflammation, scarring and even cancer as the liver cells grow out of control.
The North and South Americas group builds relationships to eradicate viral hepatitis.
The mood was euphoric. It was a love fest, actually. Last week, more than 600 policy makers, public health experts, and representatives from non-governmental organizations and patient advocacy groups from 80 countries were invited to participate in the first World Hepatitis Summit in Scotland hosted by the World Hepatitis Alliance in partnership with the World Health Organization (WHO). The Hepatitis B Foundation was pleased to be invited and to speak during the pre-summit meeting as well.
Image courtesy of Witthaya Phonsawat at FreeDigitalPhotos.net
Around the world, older adults bear the greatest burden of hepatitis B. Born before the childhood vaccination became available, about 4.7 percent of U.S. adults over age 50 have been infected and their chronic hepatitis B rate is nearly two-fold higher than in younger adults.
The 50-plus generation has lived with with chronic hepatitis B for decades, and over time their risk of liver damage, cirrhosis, and cancer has steadily increased. That is why it is very important that older adults living with this infection see their physicians regularly and have tests for liver damage and cancer performed as needed. Continue reading "Growing Older with Hepatitis B: Why Testing for Liver Damage Still Matters"→
By Joan M. Block, RN, BSN
Executive Director and Co-Founder, Hepatitis B Foundation
Tuesday, July 28, is World Hepatitis Day, which commemorates the birthday of Dr. Baruch S. Blumberg, who won the Nobel Prize in Medicine for identifying the hepatitis B virus and developing a vaccine to prevent it. This year also marks the 50th anniversary of the discovery of the hepatitis B virus – a discovery that has literally saved hundreds of millions of lives. Continue reading "Celebrate World Hepatitis Day By Making Hepatitis B History"→
Image courtesy of stockimages at FreeDigitalPhotos.net.
This summer, students living with hepatitis B face a task that can be as stressful as SATs, entrance exams or writing college essays – completing their colleges’ health forms.
Some colleges and graduate schools require no medical information while others expect you to document in detail your allergies, immunizations, medical history and even undergo TB testing.
The good news is colleges want to make sure all students are vaccinated against hepatitis B, the bad news is the requirement can force students to disclose their hepatitis B infection. Here are some important things parents and students should know when filling out college health forms.
No school can deny you admission or treat you differently because you have hepatitis B. The Americans with Disabilities Act (ADA) prohibits discrimination based on disabilities, and that includes hepatitis B.
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 hepatitisCcure. “You get what you pay for,” he observes.
Physiologically,hepatitisB also presents unique challenges not found with hepatitisC — 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,” cccDNAcontinues 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 BiotechnologyCenter, 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 to try and find new therapeutic drugs for future hepatitis B treatment. 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.
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.”
By Christine Kukka
For example, between 5 to 20 percent of the 1 billion people living in Sub-Saharan Africa have chronic hepatitis B Despite this prevalence, there are no widespread screening, education or prevention programs in Africa. The majority of people lucky enough to get screened and diagnosed for hepatitis B are often blood donors, because there are no public health clinics that provide screening for viral hepatitis.
