Hep B Blog

Category Archives: Hepatitis Delta (HDV)

Where is Hepatitis D? High Prevalence of Hepatitis B/D Coinfection in Central Africa

ResearchWhile hepatitis B is known to be highly endemic to sub-Saharan Africa and is estimated to affect 5-20% of the general population, the burden of hepatitis D, a dangerous coinfection of hepatitis B, has largely been left undescribed. Since the virus’s discovery 40 years ago, Africa has faced structural barriers that have contributed to the ongoing prevalence of the virus in this region. Widespread instability, under-resourced health systems, and poor surveillance have contributed to inadequate research and a lack of understanding about the health burden of hepatitis D on hepatitis B patients, particularly in Central Africa.

New data, however, reveals pockets of hepatitis B/D coinfection in this region, particularly in countries such as Cameroon, Central African Republic and Gabon. In a recently published study of nearly 2,000 hepatitis B infected blood samples from 2010-2016 in Cameroon, 46.7% tested positive for hepatitis D antibodies, a marker of past or current hepatitis D coinfection. Another study of 233 chronic hepatitis B carriers from 2008-2009 found a 17.6% positivity for hepatitis D antibodies. Other small studies from the Central African Republic have revealed 68.2% prevalence in hepatitis B patients, 50% coinfection in liver cancer patients and an 18.8% coinfection in hepatitis B infected pregnant women. Not only are new studies revealing evidence that there are groups at higher risk for hepatitis D, but a 2008 study on 124 community members in Gabon found 66% of them had markers for hepatitis D, proving this virus can also be circulating in the general population. Globally, hepatitis D is thought to affect about 5-10% of hepatitis B patients, making Central Africa an area of extremely high prevalence.

A diagnosis with hepatitis B and D can increase the risk for cirrhosis and liver cancer by nearly three times, and with only one available treatment, the future for coinfected patients if often uncertain. Although hepatitis B and D can be safely prevented by completing the hepatitis B vaccine series, which is available in many countries throughout Africa, the birth dose of the hepatitis B vaccine is often not given within the recommended 24 hours of birth. Lack of awareness, availability, and high cost mean many infants will not begin the vaccine series until 6 weeks of age, creating a window for exposure to hepatitis B. Greater than 95% of babies infected with hepatitis B will go on to develop chronic hepatitis B infections, leaving them susceptible to a future hepatitis D infection. Spread the same way as hepatitis B, through direct contact with infected blood and sexual fluids, hepatitis D can be contracted through unsterile medical and dental equipment and procedures, blood transfusions, shared razors and unprotected sex. Although the severity of disease varies greatly by hepatitis D genotype, coinfection always requires expert management by a knowledgeable liver specialist, which are often difficult to find.

As an increasing number of studies continue to describe the widespread endemicity of hepatitis B/D coinfection and its public health burden, researchers and the Hepatitis Delta International Network are calling on the World Health Organization (WHO) to declare hepatitis D a “threat” in this region in order to promote increased priority and awareness. Addressing hepatitis B/D coinfection prevention and management will be complex and require a multi-pronged approach through methods such as government prioritization, increased funding for health systems, hepatitis B vaccination awareness programs, birth dose prioritization, better sterilization techniques in hospitals, clinics, and barbers, and public awareness of the disease.

For more information about hepatitis B/D coinfection and the Hepatitis Delta Connect program, please visit www.hepdconnect.org or email us at connect@hepdconnect.org. Hepatitis Delta Connect seeks to provide information, resources and support for hepatitis B/D patients and their families through its website, social media, fact sheets, webinars and hepatitis D liver specialist directory.

Karen and Dave’s Story

One Couple’s Journey through Hepatitis B, Hepatitis D and Liver Cancer

“Dave knew he had hepatitis B for decades, but honestly, no one ever seemed concerned. His liver
enzymes were slightly elevated, so the doctor told him to just watch what he ate and drank. He didn’t
even insist on bi-yearly blood tests!

In 2016, Dave was scheduled for a routine colonoscopy. Because he’d been looking pale and sickly
around that time, I suggested they do a blood test first at his family doctor. His numbers were off the
chart. They sent us back for the colonoscopy and added an endoscopy too. They found four varices
(enlarged veins in the esophagus that can indicate serious liver disease). How did this happen?

This was when I started to get angry. The gastroenterologist called us in to discuss the results. He asked
if Dave knew he had hepatitis B. Dave said yes, knowing his drug use in his teens and early twenties was
likely the source. Dave never felt shame about it at all, and just accepted it as a path he took, and
thankfully came out of. After that conversation, the doctor slammed his chart shut and pushed it across
the desk. He said that Dave’s liver was so badly damaged that there was nothing he could do and to
‘come back in a year’. When we asked about his options for treatment for the varices and his hepatitis B,
he actually told me that no one would treat the varices unless they were bleeding! He also told us that
hepatitis B antivirals would “make things worse”. That didn’t make sense. We asked about a transplant.
He said there was ‘no way’ anyone would give him a new liver. He didn’t even let us know that there
were actual liver clinics for this very purpose. He sent Dave away to die, really.

Many months later, with much perseverance, we made it to Stanford, where he was immediately put on
entecavir to treat his hepatitis B and to hopefully relieve some of his liver damage. That doctor alerted
us that he should also be tested for hepatitis D, a coinfection of hepatitis B. “It won’t be good if you have
it.” He did.

Due to changes in our health insurance, we were sent to continue at the University of California San
Francisco Liver Center…they were our saving grace. They treated the varices right away and put him on
other medications to help his failing systems. His hepatitis B viral load was now undetectable, with
hepatitis D being the biggest concern. Dave tried interferon to treat the hepatitis D, but with no luck. His
only chance was a transplant, but even though he was doing poorly, his test results didn’t qualify him to
get on the transplant list right away. He had lots of ER visits – 210 office visits in 2017 alone. It was a
whirlwind. Dave hadn’t even driven in 2 ½ years. It was an enormous stress on me, too.

Dave developed liver cancer but wasn’t in good enough shape to go through treatment. As he got sicker,
he eventually qualified for two different                  
liver transplant waiting lists. Finally, on
Thanksgiving night 2017, we got the call
that a healthy liver was available, and we
took it.
Caregiving is a very tough road. Especially
when your person also has encephalopathy,
caused by years of liver damage – and Dave
had it really bad. The encephalopathy
caused mood swings, short-term memory
loss, hand tremors, low appetite. He could
be down-right nasty. At that time, we were
doing the 4 ½ hour drive to San Francisco
once or twice a week. It was stressful for
both of us – and he was really unaware of
the stress that was put on me. Between
driving, taking out the garbage, bills, our
construction business…you name it, I did it
all.

The first 3-4 months out of the transplant, people were telling him all that had gone on. Much to my
frustration, he didn’t believe any of it! Now, over 6 months post-transplant, little things are coming back
to him. I showed him about 2 dozen pictures of him during his journey, and he was shocked! He said he
thought he was fooling everyone into thinking he was well.

The hardest part of this journey was seeing Dave so sick at times. I spent a lot of time in my closet
crying. It was hard on our adult girls too, to see their dad so weak and disoriented. I had a lot of support
through our girls though, and my family, which made a world of a difference. My sister is also a retired
nurse, and she accompanied us to most of our visits. She was a helpful adviser, since his medications
always needed tweaking, and we were often on long calls with our care team, health insurance
company, and pharmacies.

The good we took away is his health! He still doesn’t feel it’s real. We went through so much, and are so
grateful to be on the other side.

Things I’ve learned:
• Get on a Facebook forum for liver transplant patients…they are a great resource and a wealth of
information from other patients.
• Take a third person with you to doctor visits and procedures. At times, I was so consumed with
my concern for Dave, it was easy for me to forget some of the things we discussed. My sister
would take notes, and we would review them after.
• Always get a second opinion if you don’t have a good feeling about your doctor. You will all
become a team, and it’s important to have a team you can trust.
• Get on the transplant list at multiple hospitals, their criteria for transplant varies!
• Have willing family members and friends get tested to see if they are donor matches. Usually the
recipient’s insurance will pay for the testing and survey if they are a match. My sister-in-law and
I were both tested but were not a match.
• Ask about organ swap programs. Apparently, my kidneys were in perfect health. My
hepatologist had me apply to the kidney donor program, in hopes that I may be able to donate
my kidney in exchange for a piece of someone’s liver for Dave.
• Dave was put on depression and anxiety medication early in the process. He was initially very
resistant, mostly because of the stigma. His doctors finally convinced him it would be very
helpful for his general mood…it was!
• I had to make several phone calls to his team without his knowing. Encephalopathy really makes
you confused, and in Dave’s case, grumpy. I asked the doctor to push for the depression and
anxiety medications, which she did. Also, he wouldn’t exercise or take short walks before
surgery, which she had asked him to, to better prepare for surgery. I made the phone call, and
at the next visit, she set him up with a Fitbit! It helped that the ‘suggestions’ came from his
doctor and not me!
• After the transplant, I was so surprised he wasn’t more ‘thankful’ …that he wasn’t in awe of
what we had all gone through for HIM! I got angry with him. I made a private call to our new
post-transplant team. She said depression right after is very common. The patient feels
overwhelmed, and sometimes not very thankful. It’s kind of a way to deny they were in trouble,
to deny that they needed help. That fits my man to a tee!
• I would strongly suggest lots of patience after the transplant. I wish our team would have told
me the possible mental-state Dave might be in. Don’t force them to be thankful. Don’t play the
‘remember when’ game, “remember when I drove you to the ER in the middle of the night?
Remember when they told us you had cancer? Remember when I tried to be your donor?”
Because a lot of it he doesn’t remember.
• Take pictures along the way, but don’t show them until at least 6 months out. I showed Dave
pictures right away, and they didn’t resonate. I just showed him them the other night…and he
was floored! He really ‘got it’. He’s been looking at things differently lately: he’s calmer and
more loving.
• I wish I had kept a journal. The ups and downs of this journey were sometimes excruciating, and
Dave wasn’t ‘present’ to understand it. Hire cleaning help if needed. Get family and friends to
take the patient to lesser important appointments. Don’t let household things pile up on you. Fix
the gutter. Repair the screen. Hire a gardener for a few hours. Ask family to set things up for
you. It’s amazing how in two years without Dave to physically help around the house, things
started to go south pretty quickly! Luckily, I dug in and kept up.

Quite the journey for sure. I feel blessed to be on this side of health!”

– Karen

Hepatitis D: Coinfection vs. Superinfection

Hepatitis D is an aggressive form of hepatitis that can only exist alongside hepatitis B. This means that all hepatitis B patients are at risk for hepatitis D, but so are people who have not received the hepatitis B vaccination series.

If contracted, 70-90% of people with chronic hepatitis B will go on to also develop a chronic hepatitis D infection – called a “superinfection”. Approximately 70% of these cases will progress to cirrhosis (liver scarring), compared to 15-30% of those infected only with the hepatitis B virus.

Due to the likelihood of liver complications, hepatitis B patients should be aware of potential exposures to hepatitis D. The virus is spread the same way as hepatitis B, through direct blood-to-blood contact and unprotected sex with an infected person. It is important to be aware that blood contact could also occur by exposure to unsafe blood transfusions, unsterile medical or dental equipment, and the sharing of razors or toothbrushes with an infected person due to the possibility of infected blood entering the body.

People who are not infected with hepatitis B may be at risk for “coinfection”, when someone contracts hepatitis B and D simultaneously during one exposure. In these cases, greater than 90% of adults will clear both infections and develop protective antibodies. While a co-infection generally resolves spontaneously after about 6 months, it can sometimes result in a life-threatening or fatal liver failure.

The good news is that the hepatitis B vaccine series can prevent both viruses in people who are not already infected. Once completed, the vaccine can provide a lifetime of protection!

For more information about hepatitis B/D coinfection, please visit www.hepdconnect.org or email us at connect@hepdconnect.org.

What New Treatments Are on the Horizon for Hepatitis B/D Coinfected Patients?

Although there are highly effective treatments available to manage hepatitis B, there are few available treatments for hepatitis D, and none are U.S. Food and Drug Administration (FDA) approved. Hepatitis D is the most severe form of viral hepatitis, and coinfection can accelerate liver damage and cause cirrhosis or liver cancer in as little as 5 years for some patients. Currently there is no approved drug for acute or chronic hepatitis B/D coinfection, but in trials pegylated interferon alpha has shown to be somewhat effective. By stimulating the body’s immune system, around 25-30% of patients are able to suppress their hepatitis D viral load with weekly injections over 48 weeks. Emerging research is showing higher rates of effectiveness with prolonged interferon treatment beyond one year, but it can be difficult for patients to continue due to the physical and mental toll of interferon on the body. Antiviral medications that are proven effective against hepatitis B are sometimes prescribed along with interferon therapy for patients with a high hepatitis B viral load, but these have no effect on hepatitis D. It is urgent that more treatment options be developed for the millions of hepatitis B/D patients that are eagerly awaiting them.

The good news is that with renewed scientific interest, research and funding, eight new drugs are currently in development that offer hope for more treatment options in the coming years. Two drugs have even been granted special designations by the FDA and one by European Medicines Agency (EMA), paving the way for increased resources and funding for development. Due to recent advancements, the future looks hopeful, and within a few years it is likely there will be more treatment options available. Below is a chart that provides more information on these new drugs and their current clinical trial status.

Pegylated Interferon Lambda

Pegylated-interferon-lambda (PEG-IFN-λ) is a well-characterized, late-stage, first in class, type III interferon that stimulates cell-mediated immune responses that are critical for the development of host protection during viral infections. This drug has now been granted “Orphan Drug Designation” by the FDA, fast-tracking the development process.

Myrcludex B

This drug is an “entry inhibitor” that prevents the virus from entering into hepatocytes (liver cells) and has shown activity against the hepatitis B virus. It may also stop the development of a hepatitis D infection. A recent study showed promise for Myrcludex B when combined with PEG-INF in reducing hepatitis D viral levels. It has been granted PRIME Eligibility by the European Medicines Agency, a status that promotes support in development of drugs that serve an unmet medical need.

Ezetimibe

Currently used to lower cholesterol in the blood, Ezetimibe is being studied for effectiveness against hepatitis D. Ezetimibe possesses pharmacophore features to stop NTCP, the receptor required for hepatitis B and hepatitis D hepatocyte entry.

Lonafarnib

This drug works by targeting the protein assembly process, preventing the production of new virus particles. In a current clinical trial, Lonafarnib combined with Ritonavir has shown promise in reducing hepatitis D viral levels, and the FDA has granted it fast-track status since this class of drugs have been developed for the treatment of cancers and have been shown to be safe.

Rep 2139

This compound is known as a “Nucleic acid-based Amphipathic Polymer” (NAP) which prevents the release of hepatitis B surface antigen (HBsAg) from infected liver cells and is being evaluated for hepatitis D virus in combination with pegylated interferon (PEG IFN).

GI-18000

GI-18000 Tarmogen is being studied for its effectiveness in causing a T cell immune response against cells infected with Hepatitis D and thereby improving outcomes. The strategy is to identify molecular targets that distinguish diseased cells from normal cells and activate the immune system to selectively target and eliminate only the diseased cells.

ALN-HDV

This approach is being used for both the hepatitis B and hepatitis D virus to “silence” the viral RNA with compounds that interfere with and cause the destruction of the viral genome (e.g. stop replication of the virus).

As clinical trials progress, sites may open across the world that are enrolling hepatitis D patients. Keep checking here for an up-to-date list of all current clinical trials.

Click here for more information about the phases of the clinical trial process.

For more information about hepatitis B/D coinfection, please visit www.hepdconnect.org or email us at connect@hepdconnect.org.

I Have Hepatitis B. Could I Also Be Infected with Hepatitis Delta?

Hepatitis delta, or hepatitis D, is an aggressive form of hepatitis that can only infect someone who is also infected with hepatitis B.

People can become infected with hepatitis B and hepatitis D from the same exposure, or people who are already infected with hepatitis B can later be infected with hepatitis D. Coinfection can promote more rapid progression to cirrhosis and liver cancer than being infected with hepatitis B alone and will require an altered treatment and management plan. Being aware could save your life!

Hepatitis D can be spread similarly to hepatitis B, through exposure to blood or bodily fluids of an infected person. People with hepatitis B are likely to develop a chronic hepatitis delta coinfection if they are exposed to the virus, making it important for you and your doctor to be aware of the signs of a coinfection.

Cues to suspect a coinfection:

  • You have chronic hepatitis B but are not responding to antiviral treatment, or you have signs of liver damage even though your viral load is low (HBV DNA below 2,000 IU/mL)

Note: Fatty liver disease (caused by obesity) and liver damage from alcohol or environmental toxins should be ruled out as causes of liver damage before testing for hepatitis D.

It is also important for hepatitis B patients who originate from Sub-Saharan Africa, China, Russia, the Middle East, Mongolia, Romania, Georgia, Turkey, Pakistan and the Amazonian River Basin to be tested for hepatitis D, where it is more common. Most of the time, patients do not have any signs or symptoms to let them know they are coinfected, so a simple blood test is the only way to know for sure! Talk to your liver specialist about testing at your next appointment.

Hepatitis Delta Connect is a dedicated program of the Hepatitis B Foundation aimed to provide information and support for those affected by hepatitis D. Please visit our website, www.hepdconnect.org for more information and follow us on Facebook, Twitter and Instagram to stay up to date on the latest hepatitis D news! If you are a patient or provider and have questions or concerns, please email us at connect@hepdconnect.org.

Check out our previous posts about hepatitis D here, here, and here.