Hep B Blog

Tag Archives: Research

Is a Cure for Hepatitis B Coming? Experts Say Yes

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.
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"

Can People with HBeAg-Negative Hepatitis B Ever Stop Taking Antivirals?

Image courtesy of rakratchada torsap, at FreeDigitalPhotos.net.
Image courtesy of rakratchada torsap, at FreeDigitalPhotos.net.

Medical guidelines suggest that individuals with HBeAg-negative hepatitis B with signs of liver damage face an “indefinite” or even lifetime commitment to taking daily antiviral pills.

In this week’s blog, we explore when—if ever—individuals with hard-to-treat HBeAg-negative hepatitis B can ever stop taking antivirals.

First of all, what is HBeAg-negative hepatitis B? Many people infected with hepatitis B at birth and who remain infected into their 40s, 50s or 60s, develop HBeAg-negative hepatitis B. Researchers believe that over time the virus mutates to evade the immune system. Though individuals may have lost the hepatitis B “e” antigen (HBeAg) and developed the “e” antibody, this mutated virus develops the ability to keep replicating despite the loss of HBeAg. And this mutated virus is capable of putting people at higher risk of liver damage.

Generally, doctors recommend treatment to HBeAg-negative patients when their viral load exceeds 2,000 IU/ML and their ALT liver enzyme levels, which rise when liver cells are damaged, are even moderately elevated. (Normal ALT levels are less than 30 for men and 19 for women.)

The most common antiviral treatments are either entecavir (Baraclude) or tenofovir (Viread). These two are considered the most powerful at quickly reducing viral load (HBV DNA) and have a very low risk of causing drug resistance, which is critical considering the long-term treatment required by HBeAg-negative patients.

But can individuals with HBeAg-negative hepatitis B ever stop treatment? Antivirals are expensive, without insurance tenofovir costs about $1,000 a month and generic entecavir costs about $407 in the U.S. Additionally, long-term antiviral treatment can cause bone loss.

Late last year, hepatitis B experts with the American Association for the Study of Liver Disease (AASLD) tackled this question and reviewed recent studies that followed HBeAg-negative hepatitis B patients who stopped antivirals. They found that even when these patients enjoyed two years of undetectable viral load and normal ALT levels during treatment, when they stopped only half of them were able to maintain a low viral low (below 2,000 IU/mL) and normal ALT levels.

The risk of dangerous “flares” after stopping treatment, “requires careful weighing of potential for harm and benefit,” the experts wrote. This is important because many HBeAg-negative patients are older and more vulnerable to liver damage and cancer.

In their new recommendations, AASLD experts make clear their findings are “conditional” and the quality of evidence found in the studies they reviewed is “low.” However, this is what they tentatively recommend:

  • Stopping treatment, “may be considered in persons who have (lost) the hepatitis B surface antigen (HBsAg). However, there is currently insufficient evidence to definitively guide treatment decisions for such persons.”
  • And, anyone who stops antiviral therapy should be monitored every three months for at least one year to see if their viral load rebounds or if they have signs of liver damage, including ALT flares.

Given the knowledge-gap about the long-term health consequences of HBeAg-negative hepatitis B, more research with longer durations of monitoring are needed, experts recommended. “Alternative treatment strategies for patients on long-term antiviral therapy, such as adding or switching to (pegylated interferon), warrant further study,” they concluded.

 

There’s Hope for a Hepatitis B Cure at the HEP DART 2015 Conference

IMG_1387This 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.

IMG_1423

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
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
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.

New Hepatitis B Treatment Guidelines Revealed at AASLD 2015 Conference

IMG_1369

The American Association for the Study of Liver Disease (AASLD), the organization that defines how doctors should treat hepatitis B and other liver ailments, unveiled new hepatitis B treatment guidelines this week at its annual conference in San Francisco.

The new guidelines are published here.  Patients should review them and discuss any updates that address their individual conditions with their physicians. Continue reading "New Hepatitis B Treatment Guidelines Revealed at AASLD 2015 Conference"

HBV Journal Review – June 2015

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:

  • HBV Liver Cancer Requires Aggressive Treatment from the Start
  • Experts: Treat Cirrhotic Patients, Even if Viral Load Is Low
  • Some Patients Can Safely Stop Antiviral After Four Years
  • Tenofovir Safe and Effective in Pregnant Women with Drug Resistance
  • Researchers Discover Why Children Become Chronically Infected
  • Expert Recommends Treatment for Mental Confusion from Cirrhosis
  • Antivirals Increase Survival After Liver Cancer Treatment
  • HBV Patients with Diabetes Have a Higher Risk of Liver Cancer
  • Long-term Antiviral Use Increases Hip Fracture Rates Slightly
  • Second Vaccine Series May Be Needed for Children with Celiac Disease
  • Researchers Find HBV B Strain in Cuba Did Not Come from Africa

Continue reading "HBV Journal Review – June 2015"

Clinical Trials Webinar -What YOU need to know!

Why do we have clinical trials? What is involved with clinical trial participation? How do I find a trial that’s right for me? Find out by listening to this webinar from Liver Cancer Connect, a dedicated program of the Hepatitis B Foundation. Presenters Jill McNair of the Center for Information & Study on Clinical Research Participation, and Katelyn Levy, BS, clinical research coordinator at Johns Hopkins Suburban Hospital, explain what clinical trials are and answer frequently asked questions about participating in a trial.

Continue reading "Clinical Trials Webinar -What YOU need to know!"

HBV Journal Review – May 2015

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:

  • New Treatments Targeting Hepatitis B Start Clinical Trials Soon
  • Experts Urge Doctors to Screen Pregnant Women for Both Hepatitis B and High Viral Loads
  • Using Antivirals Early in a Pregnancy Reduces Infection of Newborns
  • Some Pregnant Women in U.S. Still Not Getting Screened for HBV and STIs
  • High Viral Loads in Men Increase the Amount of HBV DNA in Their Sperm
  • Despite Vaccine, Rural States See Rise in Hepatitis B Due to Heroin Use
  • More Than Half of Young Drug Users Are Not Vaccinated Against Hepatitis A and B
  • Shorter Vaccination Schedule Works to Prevent Infection Among Drug Users
  • Generic Entecavir Could Treat All Patients Worldwide for $36 a Year
  • Reformulated Tenofovir Appears Better at Fighting Infection in Liver Cells
  • Another Report Calls for Doctors to Screen All Patients for HBV Before Starting Chemotherapy
  • Study Confirms Aflatoxins Increase Liver Cancer in Hepatitis B Patients

Continue reading "HBV Journal Review – May 2015"

HBV Journal Review April 2015

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:

  • Half of Patients with HBV Genotype C Will Lose HBsAg
  • Five-year Study Shows Tenofovir Dramatically Improves Cirrhosis
  • Tenofovir Also Effective Against Adefovir and Multi-drug Resistance
  • Tenofovir Is Effective in Pregnant Women Who Have Resistance to Other Drugs
  • Estimates of Liver Cirrhosis in the U.S. Jump 50%
  • Taking Antivirals for Three Years After Undetectable Viral Load Reduces Relapse Risk
  • Study Finds Antivirals Can Replace Costly HBIG after Liver Transplant Surgery
  • Hospitalized Hepatitis B Patients Have Higher Death Rates and Longer Stays Than Hepatitis C Patients
  • Small Study Finds Psoriasis Treatment May Not Reactivate Hepatitis B
  • Emulsion Made from Ginkgo Leaves Shows Promise Against Hepatitis B
  • Experimental Treatment Boosts the Immune System and Slows Viral Replication
  • HIV-HBV Coinfected Patients Have High Rates of Hip Fractures

Continue reading "HBV Journal Review April 2015"

HBV Journal Review February 2015

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:

  • Quality of Care for Women with Hepatitis B Varies Dramatically Across U.S.
  • One-third of HBeAg-negative Women Experience “Flares” After Childbirth
  • Immunizing Newborns Is an Effective Tool in Preventing Cancer
  • Experts Warn: Don’t Delay Treatment in Patients with HBV Genotype C
  • Antivirals Help Patients with Cirrhosis, If Started Early Enough
  • Entecavir Effective at Clearing HBV’s cccDNA from Liver Cells
  • Older Age and a Weakened Immune System Can Cause HBV to Reactivate
  • Survey Shows Doctors Fail to Adequately Screen for Liver Cancer
  • Innovative Venues Increase Hepatitis B Screening Among Asian-Americans
  • Study Finds Waste Collectors at High Risk of Hepatitis B
  • Study Comparing Four Antivirals Finds All Appear Effective

Continue reading "HBV Journal Review February 2015"

The Drug Discovery Process

It takes talent, dedication, lots of  time, and a sizable investment to bring a safe and effective drug to market. The Drug Discovery Process YouTube video, compliments of PhRMAPress, introduces the long and arduous drug process from the identification of a compound in the lab, though clinical trials and the FDA approval process. It may sound simple, but this process may take up to 1,000 people, 12-15 years and up to 1.3 to 1.6 billion dollars to put a new drug in the hands of the patient.

Consider this process when following the progress of  hepatitis B drugs on the Hepatitis B Foundation Drug Watch page.  Compounds could remain in various stages for years. Note that the “preclinical” phase represents the drugs that are still in the lab and not yet ready for human clinical trials.

The Hepatitis B Foundation also maintains a webpage with the latest hepatitis B related clinical trials. Contact information is provided for each trial for those wishing to volunteer to participate.  Volunteers must meet the criteria for participation in a trial.

The future looks bright for a functional cure for hepatitis B. It may take a few more years to get the drug into the hands of the patient, but each step of the process is crucial in order to produce a drug that is both effective and safe.