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October is Liver Cancer Awareness Month! What’s the Hep B Connection?

Liver Cancer Ribbon

According to the World Health Organization (WHO), liver cancer is the second most common cancer in the world, leading to 788,000 annual deaths worldwide. Most liver cancer cases occur in developing countries. More than 80 percent of these cancers are found in sub-Saharan Africa and Eastern Asia where more than 20 of every 100,000 people will suffer and die from liver cancer. However, liver cancer is alarmingly on the rise in developed countries, as well. In a recent study, researchers from The American Cancer Society found that liver cancer is the fastest-growing cause of cancer deaths in the United States. Only 20 percent of people diagnosed with liver cancer survive beyond five years, and the number of deaths have doubled since the mid-1980s, and they are expected to continue to rise.

Why is liver cancer growing in most of the world? There are many risk factors for liver cancer, but chronic hepatitis B accounts for up to 60% of liver cancer and is the most common risk factor for this type of cancer. People who are chronically infected with hepatitis B are 100 times more likely to develop liver cancer compared to those who are not. The hepatitis B virus attacks the liver directly and repeatedly over time. This can lead to liver damage and scarring of the liver (or cirrhosis); which greatly increases the risk of liver cancer.

Sometimes, people with hepatitis B can develop liver cancer even when they do not have cirrhosis. There are a number of complicating factors which can  increase the risk of liver cancer including traits specific to the virus and the person and their health status, which should be discussed with a liver specialist to determine when you should initiate screening.

Forms

How many years have you had hepatitis B? The longer you’re infected, the higher your risk of liver cancer.

What is your gender? Men are considered at higher risk of liver cancer and may be screened starting at an earlier age because they may be more likely to smoke, drink alcohol, have more “active” hepatitis, and higher iron stores—all of which increase cancer risk. Estrogen is believed to protect pre-menopausal women against liver cancer.

Have you had a high viral load (HBV DNA) after age 30? Having a viral load exceeding 2,000 international units per milliliter (IU/mL) is associated with a higher risk of liver cancer even if you have no other signs of liver damage.

Do you have a family history of liver cancer? If an immediate family member has had liver cancer, this greatly increases your risk.

Are you overweight, or have you been diagnosed recently with type 2 diabetes? A fatty liver and/or diabetes increase your risk of liver damage and cancer dramatically when you’re also infected with hepatitis B.

Do you have hepatitis B virus genotype C or core/precore viral mutations? Originating in Asia, this hepatitis B strain is associated with loss of the hepatitis B e antigen (HBeAg) later in life. That means you may have had a high viral load and liver damage for a longer period than people with genotypes who clear HBeAg at a younger age. Having core or precore mutations in your HBV also increase liver cancer risk.

If you are living with chronic hepatitis B and are concerned about liver cancer, there are steps you can take. Working with a good health care provider to manage your hepatitis B is important, as is having a healthy lifestyle. Talk to you doctor about your risk, and about getting screened for liver cancer at least annually – early detection saves lives!

To commemorate Liver Cancer Awareness Month this October, help us spread the word about the link between hepatitis B and liver cancer! You can also join our Twitter Chat on Thursday, October 12th at 2:00pm – along with our partners CDC Division of Viral Hepatitis, and the National Alliance of State and Territorial Aids Directors (NASTAD). To join the chat, use the hashtag #liverchat. For more information, visit our blog post.

Remember to talk to your doctor about the risk factors for liver cancer, and if you have hepatitis B, ask to get screened for liver cancer. For more information about liver cancer visit the Liver Cancer Connect website.

Newly Diagnosed with Hepatitis B? How Did I Get this? Learning the HBV Basics, Transmission – Part I

If you have just been diagnosed with hepatitis B virus (HBV) then you need to understand how HBV is transmitted. This is the case whether you are acutely or chronically infected.  You must understand you are infectious at this time and can transmit the virus to others.

How is hepatitis B transmitted? Hepatitis B is transmitted through blood and infected body fluids. This can happen through direct blood-to-blood contact, unprotected sex, unsterile needles and unsterile medical or dental equipment, and from an infected mother to her baby.  For kids, pediatric experts report that the fluid that oozes from cuts and open sores is also highly infectious. HBV can also be transmitted inadvertently by the sharing of personal items such as razors, toothbrushes, nail clippers, and other personal items that may have trace amounts of blood on them.

HBV is not transmitted casually by sneezing or coughing, shaking hands or sharing or preparing a meal. In fact it is not contracted during most of life’s daily activities. Hugging or even kissing won’t cause infection unless there are bleeding gums or open sores during the exchange. It’s really all about trace amounts of infected blood, though the virus is in other bodily fluids in lower concentrations.  For example, it’s not about the saliva on the toothbrush that is a big concern, but rather the potential for trace amounts of blood that could be exchanged with a shared toothbrush.

How did I get this? If you have been diagnosed with hepatitis B virus you are likely racking your brain trying to figure out how you could have gotten HBV. Some can immediately track their likely exposure to a recent event, or perhaps a time period in their life where they were more likely to have been exposed. They may fit into an at-risk category for hepatitis B due to lifestyle choices, country of origin, frequent travel and exposure in endemic areas of the world, high risk employment, or unsafe blood or medical or dental procedures without adequate infection control. (Sadly, this is common in many parts of our world, but accidents can happen anywhere).

Since HBV is a silent infection there can be years before it is detected.  Many individuals born in endemic parts of the globe find out later in life that they are hepatitis B positive, even though they have likely had HBV since birth or early-childhood. Children are especially vulnerable to chronic HBV. 90% of babies and up to 50% of young children infected with HBV will remain chronic, and most will have no symptoms.  Often it remains undetected until it is caught in routine blood work or later in life when there may be liver disease progression. In Asia, vertical transmission from mother to child is very common; whereas in Africa, horizontal transmission at a young age is often the culprit.

Although not casually transmitted, there are inadvertent opportunities for exposure to hepatitis B. If you are from an area where HBV is very common, then the odds of exposure, transmission, and infection will be higher. If you do, or have participated in high-risk activities at some point in your life, you are also at greater risk. People are often quick to point out that they have never injected drugs or participated in more obvious high-risk activities, but let’s face it – multiple sex partners? Certainly sexual experimentation in college or early adulthood is not that unique. Things happen, people change, or sometimes they don’t. This isn’t a time for judging, it’s a reflection of what happened yesterday or 20 years ago that may have exposed you to HBV and resulted in infection.  That being said, unless it happened just recently and you can definitively identify your exposure, I would advise that you let it go and move forward. I spent a number of years wondering about the details of my daughter’s infection, but ultimately, it really doesn’t matter.

Time to move forward.

The next step – preventing transmission to others, Part II

A Capitol Celebration: US Leaders in Hepatitis B Celebrate World Hepatitis Day

Hep B United (HBU), a coalition established by the Hepatitis B Foundation (HBF) and the Association of Asian Pacific Community Health Organizations (AAPCHO), held its fifth annual Hep B United Summit from July 26th to 28th in Washington D.C. The summit was held to promote screening and prevention strategies and advocate for a cure to further HBU’s mission to eliminate hepatitis B in the United States.

The summit is the largest gathering of hepatitis B leaders from around the country including public health agencies, national non-profit organizations, community coalitions, and individuals and family members affected by hep B. Catherine Freeland, MPH, Public Health Manager of HBF, said, “The summit is like a family reunion.” It’s an opportunity for HBU members to convene, share best strategies, and celebrate their wins over the past five years. The partnerships within HBU ensures that best practices and resources are shared as well. “Once we have a cure, we are committed to making sure chronically infected Americans get it,” Chari Cohen, DrPH, MPH, co-chair of HBU mentioned during the summit. Over the past year, HBU screened 22,556, educated 52,194, and reached over 6 million people with in-language hepatitis B messaging! That’s a win for sure!

As a part of the summit, HBU partners visited Capitol Hill to discuss with federal legislators the need to support hepatitis B and liver cancer research, education, screening, and treatment programs. A Congressional reception was also held to highlight the “#justB: Real People Sharing their Stories of Hepatitis B” storytelling campaign, which increases awareness of hepatitis B through personal stories. There were also meeting sessions focusing on capacity building, sustaining local hepatitis B coalitions, and best ways to utilize resources like the “Know Hepatitis B” campaign from the CDC and Hep B United and the #justB campaign. The Hep B United Summit is a way to celebrate World Hepatitis Day, which is on July 28th every year. Partners celebrated and raised awareness for World Hepatitis Day around Capitol Hill with a scavenger hunt!

At the Summit, HBU and its CDC partners presented five community leaders with the 2017 Hep B Champion Awards in recognition of their outstanding commitment to eliminating hepatitis B and liver cancer in their communities:

 Cathy Phan, the Health Initiatives Project Manager at HOPE Clinic in Houston, Texas, is recognized for her dedication to reducing health disparities, advocating for access to health care and health equity for underserved populations. Cathy brings unique perspectives, best practices and creative, innovative ideas from the local community clinics to the national level.

Vivian Huang, MD, MPH, the Director of Adult Immunization and Emergency Preparedness for the New York City Department of Health and Mental Hygiene and the medical director for the NYC Department of Health Immunization Clinic is recognized for her commitment to reducing the burden of vaccine-preventable diseases locally and globally including hepatitis B and liver cancer. Dr. Huang is a strong, tireless advocate for hepatitis B prevention, education, and treatment and health equity through health department engagement.

Hong Liu, PhD, the Executive Director of the Midwest Asian Health Association in Chicago, Illinois, is recognized for her innovative approaches to educating the public on hepatitis B and her willingness to share her best practices and experiences with others working in the field. This year, Dr. Liu’s leadership has led her organization to educating over 1,337 individuals in Chicago’s Chinatown district and screening close to 300 individuals for hepatitis B.

Dan-Tam Phan-Hoang, MSc., is program manager of HBI-Minnesota, a Minneapolis, Minnesota-based non-profit that she helped start in 2015. Dan-Tam is recognized for her leadership in Minneapolis, building strong collaborations with community leaders, healthcare providers, funders, and government agencies to address hepatitis B throughout the state and successfully establishing a hepatitis B outreach and prevention program for high-risk communities in the Twin Cities.

The National Task Force on Hepatitis B for AAPI, is a national organization that brings together scientists, health professionals, non-profit organizations, and concerned citizens in a concerted effort to eliminate the transmission of hepatitis B and to decrease health disparities among those chronically infected. The Task Force is recognized for increasing physicians’ awareness about hepatitis B and launching a new health care provider program, bringing together public health and health care professionals in regional meetings around the country. The Health Education for Liver Providers (H.E.L.P.) Training Program is designed to provide health care providers and their medical team core medical knowledge of hepatitis B and hepatitis C.

Read the summit press release here.

More pictures of the summit can be found on HBU’s Facebook album, Storify, and e-newsletter.

To read about the Hep B United 2016 Summit from last year, click here.

Join Us for a Twitter Interview! Meet Our Storytellers and Learn Their Hepatitis B Stories

#justB-Twittervu-blogThe Hepatitis B Foundation is proud to launch its storytelling campaign, sharing the stories of people living with and affected by hepatitis B. Join the Twitter interview at 2 p.m. (EST), Tuesday, May 16, hosted by the Hepatitis B Foundation and StoryCenter.

We will introduce three of our storytellers and their stories. Join the Twitter interview with the hashtag #justB and hear the poignant stories of real people living with hep B.

We will be introducing Jason, Bunmi and Maureen K. Jason, was in a difficult place in his life with addiction and depression when he learned of his hepatitis B and sought treatment. Bunmi, originally from Nigeria, talks about the loss of her father to hepatitis B- related liver cancer and the unwillingness of her family to talk about his disease. Maureen’s hepatitis B journey began with the adoption of her daughter, and the struggle with disclosure with family and friends. These brave storytellers are ready to put an end to the silence surrounding hepatitis B.

Below are the topics scheduled for discussion during the Twitter interview. How can you contribute to the conversation? Please support Jason, Bunmi and Maureen K. as they disclose their hepatitis B stories on social media. Consider sharing parts of your hep B story or pose a question. Join the conversation with the hashtag #justB.

T1. Tell us about hepatitis B, the storytelling campaign and what the foundation hopes to achieve for those affected by hepatitis B.
T2. What makes hepatitis B different from other diseases, and how do these stories highlight the challenges associated with hepatitis B?
T3. We’d like to open it up to our storytellers. Please tell us about your story, and what makes hepatitis B different from other diseases.
T4. How has hepatitis B affected your life?
T5. What made you decide to share your hepatitis B story? Were you concerned with the stigma associated with hepatitis B?
T6. Describe your experience meeting with others impacted by hepatitis B.
T7. If there is one message you would like to get across to others about coping with #hepatitis B, what would it be?
T8: What would you tell others that are struggling with whether or not they should share their hepatitis B story?

Co-hosts and special guest handles include:

Be sure to watch Jason, Bunmi and MaureenK‘s stories.

Are you just getting started with Twitter and want to know how to join the conversation?  Type #justB in the search box of the Twitter application and click on the “latest option” to follow the twitter view.

#justB in search box

 

 

 

 

 

 

 

You can prepare any questions or tweets you might have for the above participants in advance, or you can also tweet on the fly, re-tweet, or Like a tweet from the chat.

The topics are labeled T1, T2, etc. so please respond/answer specific topic by using A1, A2, etc. in front of your tweets. Remember to include the #justB hashtag, which is not case sensitive, in all of your tweets.

Looking forward to sharing the stories of our guests on the Twitter view. Please welcome them by joining the conversation!

Newly Diagnosed with Hepatitis B? Acute or Chronic? Learning the Hep B Basics

Image courtesy of dream designs at FreeDigitalPhotos.net
Image courtesy of dream designs at FreeDigitalPhotos.net

If you’ve just been diagnosed with hepatitis B after a routine blood test or following a blood donation, you may be feeling overwhelmed with information about this complicated infection and references to acute or chronic hepatitis B.

Here is an explanation of these two terms and what happens when you’re first infected with the hepatitis B virus (HBV). Hepatitis B is transmitted through blood and body fluids. It can be spread during unprotected sex, unsafe medical procedures, exposure to blood that enters your body through a cut,  or by sharing personal items such as body jewelry or toothbrushes. Most commonly it is spread during childbirth when the mother is infected.

What is a chronic infection? When we’re infected as newborns or young children, our immature immune systems don’t notice or fight the virus and it travels to our liver and begins reproducing. With no opposition from our immune systems, a hepatitis B infection can continue for years. When a hepatitis B infection lasts longer than six months, it is considered a chronic or long-term infection. Most people with chronic hepatitis B were infected at birth or during early childhood. Immunization with the hepatitis B vaccine and hepatitis B immune globulin (HBIG), if available, within 12 to 24 hours of birth can break this mother-to-child infection cycle, but the birth vaccine dose and often HBIG is not always available around the world.

What is an acute infection? When we’re infected with HBV as healthy adults, about 90 percent of us are able to get rid of the infection within six months. It can take up to six months for our immune systems to generate antibodies and eradicate the infection in our liver. This short-term infection is called acute hepatitis B.

To determine if you have an acute or chronic infection, you must be tested for hepatitis B over a six-month period. The specific test that indicates if you are infected is the hepatitis B surface antigen (HBsAg) test. This antigen covers the surface of the virus and usually there are lots of HBsAg in your blood when you’re infected. If you test positive for HBsAg for longer than six months, it means you have a chronic hepatitis B infection.

But, if you no longer test positive (or “reactive”) for HBsAg after six months and you develop hepatitis B surface antibodies (HBsAb), then you have cleared hepatitis B after an “acute” infection. There are some additional blood tests that your doctor may order to get a better understanding of your infection, but not everyone has access to these tests. Some tests are rather expensive and they may still need to be repeated over time in order to confirm the diagnosis. Please be patient. The good news is that hepatitis B is not typically an emergency.

Here is more good news. If you are a healthy adult and are newly or acutely infected, know that your chances are good that the hepatitis B infection will go away on its own. It is rare that you require medication to get rid of the virus, your immune system does that for you.  A person with a new hepatitis B infection may not have any symptoms, or they may not be very notable. For example, you might feel more tired. About 70 percent of people newly-infected with hepatitis B never experience symptoms.

But, some people experience severe symptoms like jaundice (yellowing skin or eyes), severe nausea or vomiting, or a bloated stomach (unrelated to your weight), and they need to see a doctor immediately. If you have a new or acute infection, even these drastic symptoms may not necessarily mean that you need any form of treatment, but you will need to be monitored with additional tests to make sure your liver is safe.

If you can’t confirm you were infected as a child, you will need to wait the six months to find out if you cleared your infection. Please be patient and do not panic, but remember you do need to take precautions during this time to make sure you don’t spread the infection to others. Practice safe sex (use a condom), and don’t share personal items that may have trace amounts of blood on them.

Also, you can suggest that your family members get screened for hepatitis B and vaccinated if needed. If you were infected at birth, there is a chance that your siblings may also be infected. Sexual partners and close household members should also be tested. There may be a nine-week period right after infection when they may not test positive for HBsAg even if they have been infected.

Diagnosed With Chronic Hepatitis B? What Does Your HBV DNA Test Tell You?

Image courtesy of Praisaeng, at FreeDigitalPhotos.net.
Image courtesy of Praisaeng, at FreeDigitalPhotos.net.

If you have been diagnosed with chronic hepatitis B, your doctor has probably run several blood tests that show if the infection is harming your liver and identify what stage of infection you are in. Doctors consider all of these results when deciding if you need treatment and how often you should be monitored.

In this blog, we’ll examine how one of the tests — the HBV DNA or viral load test –can give you a snapshot into your hepatitis B infection and your health. The HBV DNA test  is performed on a blood sample using a Polymerase Chain Reaction (PCR) technique that rapidly generates HBV DNA fragments so they can be measured. Today, viral load is usually measured using international units per milliliter (IU/mL). However, in the past it was measured in copies per milliliter (copies/mL), and in some regions and labs, it is still used.

If you ever need to convert copies into international units, there are about 5.6 copies in one international unit, so 5,000 copies/mL equals about 893 IU/mL. Remember to keep copies of your lab information on file so you can track your status. An Excel spreadsheet works great.

The sensitivity of HBV DNA tests may vary with each lab so it’s a good idea to always use the same lab for your test. Labs usually measure down to about 300 IU/mL. Below that threshold, the viral load is considered “undetectable” – something all of us with chronic hepatitis B wants to hear.

How HBV DNA results are presented mathematically on your lab report can be confusing. Because the amount of virus in the blood may be very high – in the millions or billions – the result may be displayed as an exponent or a log, rather than a whole number. If this is confusing to you, please take a look at this explanation on the math.

What does viral load say about what stage of hepatitis B you are in? Your viral load also varies over time, depending on your age and “stage” of infection.

Children and adults in the “immune tolerant” stage can have viral loads in the millions or even billions. It sounds scary, but it’s not unusual. Your viral load can remain very high for decades until your immune system begins attacking the infection. Most children and young adults who test positive for the hepatitis B “e” antigen (HBeAg) generally have high viral loads, generally doctors don’t treat patients in this stage. Once their immune systems get rid of HBeAg and generate “e” antibodies (HBeAb), their viral loads begin to decline.

Adults with undetectable or low viral loads and no signs of liver damage are in an “inactive” stage. Adults with normal ALT (SGPT) levels, which indicate no current liver damage, and undetectable or viral loads less than 2,000 IU/mL generally do not require treatment.

People in the “active” stage with elevated viral loads and signs of liver damage need treatment. Many people in their 40s, 50s or 60s, develop HBeAg-negative hepatitis B. Though individuals may have lost HBeAg, the virus has mutated over time and is able to keep replicating, putting these older patients at risk of liver damage. Doctors recommend antiviral treatment if these patients’ viral load exceeds 2,000 IU/ML and their ALT levels are elevated.

Why is it important to measure HBV DNA during treatment? When daily antiviral pills (either tenofovir or entecavir) are prescribed, doctors measure your HBV DNA to see if the drug is working to reduce your viral load. Antivirals work by meddling with the viral DNA so the virus cannot reproduce effectively. Doctors measure your viral load to make sure the antiviral is working.

Why is measuring viral load important if you’re pregnant? Today, all pregnant women are screened for hepatitis B, and experts also want their viral loads to be measured. When pregnant women have high viral loads—exceeding 200,000 IU/mL—medical guidelines recommend antiviral therapy during their third trimester of pregnancy to reduce their risk of infecting their newborns. Babies born to HBV-infected women can become infected even if they are immunized at birth and treated with HBIG (hepatitis B antibodies) if their mothers have high viral loads.

It is important to remember that a viral load test provides you with important information, but it must be considered in relation to your other HBV and liver function tests results to determine if treatment is needed at all, or if you are responding favorably to current treatment. Although an undetectable or low viral load is good news, it does not necessarily guarantee that you have not, or will not experience liver damage. Hepatitis B is a tricky virus. Talk to your liver specialist about all of your test results.

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"

The Fifty Shades of “Gray” of Hepatitis B Transmission – Part 1

1716136dfa105e7f9bdf96de16e31742All pun and a little fun is intended with this title, but the “adult” version of hepatitis B transmission is a serious concern. There are “shades of gray” when it comes to hepatitis B transmission and the degree of risk with sexual activity. Continue reading "The Fifty Shades of “Gray” of Hepatitis B Transmission – Part 1"

Research at the HBF’s Baruch S. Blumberg Institute

hbvvirus

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.”

 

 

Perspective on the Liver Biopsy – “The Gold Standard”

carey_william_original

Have you noticed fewer patients living with chronic HBV seem to get liver biopsies to assess liver damage?  Here is a perspective on the Liver Biopsy, known as the “gold standard”, by William Carey, MD, Division of Gastroenterology and Hepatology of the Cleveland Clinic.

Published in Healio , July 14, 2014 

Liver biopsy is referred to as the “gold standard” in assessing both the activity and degree of fibrosis in many chronic liver diseases including hepatitis B. It is not likely to retain this lofty status much longer. Liver biopsy has several important drawbacks. Among them are cost, risk for complications, need for additional health care resources, patient and physician aversion to the procedure, inadequate specimen size and the lack of specific findings.

Liver biopsy adds between $2,500 to $3,500 to the cost of an evaluation (even higher for transvenous liver biopsy). Approximately 20% of patients will experience significant pain following percutaneous liver biopsy. More severe complications include pneumothorax, major bleeding, inadvertent biopsy of the kidney or colon, and perforation of the gallbladder. Death, most often due to uncontrolled bleeding, may occur in up to 1 in 1,000 biopsies. Underappreciated is the risk of no-representative sampling, either because of the small size of biopsy specimen or patchy distribution of fibrosis.

Noninvasive measures to assess hepatic fibrosis have been around for a generation and are increasingly used as a substitute for liver biopsy. The 2014 medley of noninvasive estimates of hepatic fibrosis includes FibroTest/FibroSure, APRI, FIB-4, other serum based test combinations, and elastography (either ultrasound- or MRI-based). Noninvasive tests have potential both for determination of current liver damage and for monitoring disease progression. They can be done at a fraction of the cost of a liver biopsy. Salkic and colleagues have reported the results of an exquisitely performed meta-analysis of peer reviewed published reports and confirmed the value of FibroTest/FibroSure in hepatitis B — mainly in excluding the diagnosis of cirrhosis. The findings of this review are restricted to hepatitis B, but others have shown similar findings in hepatitis C and alcoholic liver disease.

While there is growing consensus that noninvasive markers provide valuable information, allowing the clinician to make important decisions about treatment, screening for varices and hepatocellular carcinoma, it is essential to understand limitations of FibroTest, including distortions in results in individuals with Gilbert’s syndrome and in those with hemolysis. This study reiterates the relative insensitivity of noninvasive tests in discriminating between lesser degrees of fibrosis (F0, F1, and F2).

Data are accumulating to suggest noninvasive markers (combining a noninvasive test plus ultrasound-based elastrography, for example) are powerful tools in assessing natural history of individuals with many chronic liver diseases including hepatitis B, providing indices of disease activity, progression and fibrosis regression after treatment. Convenience, lower cost, and ease of repeated measurements over time favor widespread acceptance of these tools in clinical practice.