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HBV Journal Review – January 2014

HBF 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: Continue reading "HBV Journal Review – January 2014"

HBV Journal Review – July 2013

HBF 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:

*Experts Describe When to Treat Pregnant Women with Antivirals
Does pregnancy worsen hepatitis B?
When should pregnant women be treated?
Which antivirals are safe to use during pregnancy?
What if women have elevated ALTs before becoming pregnant and have never         been treated?
What about women with normal ALTs and high viral loads?
Is it safe to use antivirals during the entire pregnancy?
Monitoring recommendations after delivery
Can a woman taking antivirals breastfeed?
* Half of Patients Treated Long-Term with Tenofovir Lose HBeAg
*Even Patients with High Viral Load Lose HBeAg with Tenofovir
*New Type of Interferon Effective in Phase 2 Hepatitis B Trial
*Majority of Hepatitis B Patients Have Vitamin D Deficiency
*But Patients with Healthy Vitamin D Levels Are More Likely to Clear HBsAg
*Activists Develop a National Plan to Eradicate Hepatitis B in the U.S.
*New Guidelines Urge Britain’s Doctors to Improve Hepatitis B Care
*Measuring HBsAg Levels May Identify Fibrosis and Avoid Liver Biopsies
*HBsAg Levels May Also Predict Cancer Risk in HBeAg-negative Patients

HBV Journal Review


July 1, 2013, Vol 10, no 7
by Christine M. Kukka

Experts Describe When to Treat Pregnant Women with Antivirals
Two U.S. hepatitis B experts have crafted guidelines for doctors to use when deciding when to treat pregnant women infected with the hepatitis B virus (HBV) with antivirals in order to safeguard the women’s health and prevent infection of newborns.

More than half of new hepatitis B infections result from mother-to-child (vertical) transmission and despite immediate immunization and administration of HBIG (hepatitis antibodies), about 30% of infants born to women with high viral loads become infected. Additionally, women who want to become pregnant may already be treated with antivirals because of liver damage.  There is little medical guidance on whether treatment is safe over the entire pregnancy.

Does pregnancy worsen hepatitis B? Generally it does not unless the woman has cirrhosis (severe liver scarring.) Studies show a pregnant woman’s viral load generally does not increase over a pregnancy, but after the baby is born and the woman’s hormone levels change (akin to a sudden decline in steroids), some women experience a “flare” and their alanine transaminase (ALT) levels may increase due to moderate liver cell damage. Because of these flares, doctors must monitor new mothers carefully for several weeks after childbirth.

When should pregnant women be treated? Starting in the second or third trimester of pregnancy, antiviral treatment is recommended when women have high viral loads—exceeding 1 million copies per milliliter or 200,000 international units per milliliter. However, if women are already receiving antiviral treatment when they become pregnant, treatment should probably continue over the pregnancy to prevent worsening liver disease.

Which antivirals are safe to use during pregnancy? The experts recommend tenofovir (Viread) in the event the woman continues to need antiviral treatment because this drug has a very low rate of drug resistance, or telbivudine (Tyzeka). Both have been shown to be safe and cause no birth defects when used in pregnant women infected with HIV or HBV.

Continue reading about this and additional studies…


High HBV Viral Load Tied to Low Serum Vitamin D Levels

An interesting study published in Healio Hepatology:  “High HBV viral load tied to low serum vitamin D levels” discusses the relationship between the HBV viral load and vitamin D levels. In fact is shows seasonal fluctuations of HBV viral load associated with vitamin D levels. Vitamin D has been on the radar for years, but this interesting correlation between HBV virus flucuations and vitamin D levels warrants additional research to investigate how adequate vitamin D levels can positively impact treatment for those living with chronic HBV. Please refer to earlier blogs, Hepatitis B and Vitamin D and Got HBV? Adding Vitamin D to Your Diet for additional information.  As always, please talk to your doctor and have your serum vitamin D levels checked before making any drastic changes to your diet or supplements you may be taking. Don’t forget that vitamin D is the sunshine vitamin, so be sure to keep in mind the impact of the seasons on your levels. 

Patients with chronic hepatitis B who also were vitamin D deficient had significantly higher HBV DNA levels than patients with adequate vitamin D concentrations in a recent study.

In a retrospective study, researchers measured the serum levels of 25-hydroxyvitamin D (25OHD) in 203 treatment-naive patients with chronic hepatitis B seen between January 2009 and December 2012. Patients with 25OHD levels less than10 ng/mL were considered severely deficient, levels below 20 ng/mL were considered deficient, and levels of 20 ng/mL or greater were considered adequate. Patients’ samples were collected upon initial presentation, except 29 participants whose samples were taken at antiviral therapy initiation.

The mean 25OHD concentration for the cohort was 14.4 ng/mL. Forty-seven percent of participants were considered 25OHD deficient; 34% were severely deficient. 25OHD levels were similar between Caucasians (14.38 ng/mL) and non-Caucasians (14.59 ng/mL) (P=.7).

An inverse correlation was observed between levels of HBV DNA and 25OHD (P=.0003). Multivariate analysis indicated that HBV DNA was strongly predictive of low 25OHD levels (P=.000048), and vice versa (P=.0013). Patients with HBV DNA levels less than 2,000 IU/mL had 25OHD concentrations of 17 ng/mL; those with 2,000 IU/mL or higher had concentrations of 11 ng/mL (P<.00001 for difference). Participants who tested positive for hepatitis B e antigen (HBeAg; n=26) had significantly lower 25OHD levels than HBeAg-negative participants (P=.0013); this association was significant only under univariate analysis.

Investigators also noted fluctuations in HBV DNA and 25OHD levels according to season. Significantly lower HBV DNA levels were observed among samples taken during spring or summer than in autumn or winter (P=.01).

“The present study demonstrates a profound association between higher levels of HBV replication and low [25OHD] serum levels in chronic hepatitis B patients,” the researchers wrote. “At least in patients without advanced liver disease … HBV DNA viral load appears to be the strongest determinant of low [25OHD] serum levels. … Future studies to evaluate a therapeutic value of vitamin D and its analogs in HBV infection may be justified.”

Diagnosed With Chronic Hepatitis B? What Stage – HBeAg-Positive Chronic Infection / Immune Tolerant?

Do you know the stage or phase of your chronic hepatitis B infection? Quite often people may refer to themselves as “hepatitis B carriers”. This statement by itself does not really say anything about your chronic hepatitis B infection except that you are someone who tests positive for hepatitis B, and that you are HBsAg positive.  The names of the stages or phases of HBV have changed a bit over the years, but they reflect the natural history of the virus. It is important for your doctor to determine if you are in the immune tolerant, immune active or clearance phase, the inactive carrier phase, have developed HBe negative chronic hepatitis B, or if you are in an HBsAg negative phase. It may take a few months or even half a year to accurately determine the phase, and then your doctor can talk to you about possible treatment options and whether or not treatment would benefit you at this time.  Remember, hepatitis B is typically not an emergency, so try to relax with the process knowing you may not have immediate answers.

If you are acutely infected, you also follow the natural course of the virus in a matter of months (clearance of an acute HBV infection within 6 months is considered an acute hepatitis B  infection). However, at the end of 6 months, those acutely infected will have a resolved infection, and will no longer be HBsAg+. If you are chronically infected, you will pass through many of these phases too, but unfortunately you will likely never get to an HBsAg negative or resolved phase.  The journey from phase to phase is different for each person and the time it takes to move through these phases varies along with the amount of liver damage that occurs. The importance of a good liver specialist or knowledgeable doctor  cannot be over emphasized. These stages and phases may seem simple to understand, but not everything is black and white, and the gray between phases, time between phases, lab and other diagnostic data collected, varies with each patient. The importance of being actively involved in your hepatitis B care can also not be overstated. Tracking your lab data over time and putting it into an excel spreadsheet or graphing the data may help you understand what is happening with the virus and may even be helpful for your doctor, so don’t forget to request copies of all lab results. You are more in control than you think. Get involved with your care!

Once you have confirmed that you have chronic hep B, you need further testing to determine your HBeAg status. Those with chronic hepatitis B  are either HBeAg positive or negative. If you are HBeAg positive, you have a higher hepatitis B viral load/HBV DNA and are more infectious to others. People who are HBeAg positive are either in the immune tolerant stage or the immune clearance stage. Additional labs will clarify this for your doctor.

If you are in the immune tolerant stage, you are HBeAg positive and have a high viral load. You will have normal or very mildly elevated ALT (SGPT) levels and mild or no inflammation or damage to the liver. This is very common with chronically infected young children who may have viral loads in the millions or even billions. During this time the virus is actively replicating in the liver, but the immune system has not recognized the virus so it is not trying to kill the infected liver cells. It is not the replication of the virus that kills liver cells, causing liver damage, but it is the response of your immune system killing these infected liver cells.  So, during the immune tolerant phase the virus is happily replicating, completely unchecked by the immune system, which accounts for the high viral load and lack of liver damage during this time. People in the immune tolerant phase may remain in this phase for a couple of years, or it may be decades.  Treatment is not typically recommended during this phase.  Certainly for those that have been in this phase for decades, treatment is something that may be recommended by your liver specialist.

What happens when you move into the HBeAg-positive chronic hepatitis /Immune Reactive / Immune clearance  phase? Read more. 

Diagnosed with Chronic Hepatitis B? What do the HBe Blood Tests Mean?

Your liver specialist has informed you that you have a chronic hepatitis B infection, and that he wants to run additional blood work so he can learn more about your HBV. Some of this blood work may need to be repeated over a period of time, but over the next 6 months or so, your doctor will determine whether or not you are a good candidate for treatment.  Regardless, he will definitely want to continue monitoring. Remember, treatment is important, but rarely an emergency, so be patient.

Now you need additional lab work to determine your HBe status, which will tell you whether or not you are HBeAg and HBeAb (anti-HBe) negative or positive. This reveals a great deal about your HBV such as whether or not the virus is replicating, and how infectious you are to others.

At this point, it is helpful to have a little background on antigens and antibodies.  An antigen is a foreign substance in your body that evokes an immune response. This may include viruses, bacteria or other environmental agents such as pollen or a chemical. In this case, it is the HBV e antigen. Your previous hepatitis B panel tested for the surface antigen, or HBsAg.

Antibodies are produced as a result of an immune system response to antigens. These antigen/antibody pairings are unique. An antibody response can be generated as a result of an immune response to an actual infection, or as a result of vaccination.  An uninfected person vaccinated against hepatitis B will generate an immune response, or surface antibody (HBsAb, or anti-HBs) to the HBV vaccine.

The hepatitis e antigen, or HBeAg, is a marker of an actively replicating HBV virus infection. Those with a positive HBeAg have active replication in their liver cells, more of the virus circulating in their blood, and as a result, they are more infectious, with a higher likelihood of transmitting HBV to others.  Most often, when a person is HBeAg positive, they tend to be HBeAb negative and vice-versa. This active, replicating phase may go on for weeks, as in the case of an acute infection, or for years, or even decades in those chronically infected.

Eventually most move into a non-replicative stage. During this time, e antigen (HBeAg) is no longer in the blood, and the anti-HBe antibody (HBeAb) is generated and appears in blood work. This HBeAg serconversion, or loss of HBeAg and the gaining of the antibody, HBeAb, can happen due to treatment, or spontaneously without treatment. Entering this stage is typically a good thing, and is often a goal of treatment.  However, monitoring by your liver specialist bi-annually or at least annually is essential, even if you have had an HBeAg serconversion years ago and are considered in the non-replicative phase.

HBV is complicated, and sometimes you may relapse. In other words, you may seroconvert losing HBeAg and gaining the HBeAb antibody, but it may not be durable, and you may have an HBeAg reversion to an actively replicating stage where you are once again HBeAg positive and HBeAb negative.  Years ago they called it “flip-flopping”.  This possibility is one of many reasons why regular monitoring by your liver specialist is so important.

The other possibility is the development of HBe-negative hepatitis B, which is the result of hepatitis B mutations. These precore or core promoter mutations replicate without generating the HBe antigen. However, they are actively generating the virus, though typically not at the levels of those with HBeAg positive HBV.  Once again, it is critical to continue regular monitoring by your liver specialist, so you are sure you have not begun active generation of HBe negative mutations.

Additional blood work ordered by your liver specialist will further clarify your HBeAg and over-all HBV status, and whether or not treatment may benefit you.

More next time…

Reflections from Hep B Free Phildelphia’s HBV Screening Event – CHOP site

Last week ended with an exciting city-wide hepatitis B screening event in downtown Philadelphia.  This event was sponsored by the Hepatitis B Foundation and Hep B Free Philly as part of the Hep B Free Philadelphia campaign. Hospitals included Hahnemann University Hospital, Thomas Jefferson University, Children’s Hospital of Philadelphia (CHOP), and Albert Einstein Medical Center.  Naturally each site was a little different and had their unique challenges. Throughout the four sights there were Hepatitis B Foundation and Hep B Free Philly volunteers, and 100 college-student volunteers. Student volunteers were a mix of pre-med and medical students, public health students, tutors in Chinese, Vietnamese, Korean, Spanish and French, and students interested in doing community out-reach. Twenty community –based organizations were also involved in order to reach out to high risk communities throughout the city of Philadelphia.  During this event, 200 at-risk participants were screened for hepatitis B. Those participants that do not have HBV will be invited to receive their free HBV vaccine.  This info will arrive in the mail with their test results.  Those with HBV will be provided with a linkage to care.

I thoroughly enjoyed my participation at the CHOP location. Although I was not involved in the planning and set-up process, it was clear that the logistics involved in making this multi-screening event come to fruition was extensive.  Testing sites needed to be secured. Community out-reach needed to be done long in advance in order to reach out to high risk communities. Supplies were purchased and carted (via a red-wagon at the CHOP site!) to the various sites. Phlebotomists were hired for the day. Student volunteers were organized. At CHOP, our French translators were essential in making the screening event work.  It was great to see the students take an active part in the event. Some went off campus and distributed flyers. Others manned the give-away desk.  A number of volunteers helped patients with paper work and translations, while a number of students directed and maintained the flow of traffic from one station to the next.  All volunteers worked to make the operation run smoothly.

During the CHOP screening event, participants received their paper-work and went into the auditorium and answered screening questions, signed consent forms, and filled out their self-addressed envelope for their test-results.  Paper work was reviewed by volunteers for signatures and accuracy, and appropriate labels were placed on paper work and tubes by Chari and Jessie – a very tedious process. One small tube of blood was drawn by highly qualified phlebotomists.  Since we were at CHOP, our expertise included pediatric phlebotomists and smaller, pediatric tubes, and tiny needles for kids.  From experience I can tell you this is a real bonus! We did not have many small children screened at our site, but we were happy to accommodate those little ones that were screened.  Each child also got a sticker, a band-aid and a coloring book and crayons following their screening or the screening of their parents.  Water and crackers were available for all that were screened, and each family got a “B A Hero” tote bag.

Following the blood draw, participants were invited back into the auditorium to learn more about hepatitis B, whether it was to address specific questions or in small or larger group presentations.  This is where I spent most of my time.  The majority of participants screened at CHOP were African immigrants. Most were French speaking, so the need for a French translator was essential to our outreach mission.

In the past I have enjoyed providing HBV training in China, but this is my first time working with the African Immigrant population.  It’s always a pleasure to work with different ethnic communities.  In Philadelphia, the prevalence numbers of those with HBV are between 8% and 13% in the African Immigrant community, so getting the HBV basics across is very important in this community. One man was quite empowered by what he learned and asked if he could take some of our HBV information sheets home so he could distribute them to friends and neighbors. We also had a religious leader come for screening at the very end of the event. Hopefully he will bring his message back to his faith community, and it will encourage others to be screened at another time. It doesn’t get any better than that!

Personally, I found the screening event a very rewarding experience. Hep B Free Philadelphia is committed to continutedl outreach and screening in the Philadelphia area for those that missed last week’s event and would like to be screened. Please check it out if you are local and interested in volunteering.  If you’re not local, you might find a Hep B Free organization in your own city.  Get involved!  B A Hero! Save lives! Stop Hepatitis B!

Visit: www.bfreephilly.org

Check out: Reflections from the 10/22 Screening  Event at Thomas Jefferson University

B A Hero…Free Hepatitis B Sreening Day!

Hep B Free Philadelphia is putting on a city-wide “B A Hero” free hepatitis B screening day on Saturday October 22, 2011. Free hepatitis B screenings will be available at the following hospital sites:

  • Jefferson – Focusing on the Chinese community and will be a bi-lingual event
  • Einstein – Focusing on the Cambodian community and others, and will be a bilingual event
  • Children’s Hospital of Philadelphia (CHOP) – Focusing on the African community and the screening of entire families, including kids.  Event is bi-lingual (French/Haitian Creole)
  • Drexel – Focusing on the Chinese and Korean communities.  Event will likely be tri-lingual.

Please join us.

B sure and B tested

All screening and education is Free!  Fun give-aways for everyone screened!

 All test results are private and will be mailed to the individual.

 

Hepatitis B and Vitamin D

Vitamin D is essential for everyone, but how might vitamin D help those living with HBV? Vitamin D is especially important for children and older adults, as it aids in the body’s absorption and regulation of calcium and phosphorus, which helps form and maintain healthy bones and teeth.  Vitamin D is also a potent immune modulator, and aids in the prevention of hypertension, and cancer. Vitamin D levels appear to play a critical role in type I and type II diabetes, glucose intolerance, and metabolic disorders.  Studies have also shown a link between low vitamin D levels and NAFLD (Non-alcoholic fatty liver disease), independent of metabolic syndrome, diabetes, or insulin-resistance profile (for those without HBV). The lower the vitamin D level, the higher the risk for NAFLD, or fatty liver disease.  The liver plays such an integral part in digestion, regulation, storage, and removal of toxins – the list goes on.  You can’t live without it!  As a result, it seems logical that healthy levels of vitamin D would benefit those living with HBV, if adequate vitamin D levels help reduce the risk of NAFLD, metabolic syndrome, etc.

Vitamin D is a potent immune modulator.  It has been on the radar for the prevention and treatment of infectious diseases for years. If you are being treated for HBV, you may want to discuss the potential benefits of adding vitamin D to your current therapy.  It has been shown to benefit hepatitis C patients undergoing treatment.  There is currently a clinical trial in Israel looking into the possible benefits of adding vitamin D supplementation to hepatitis B patients undergoing Peginterferon, or treatment with nucleotide analogs.

While researching this blog, I ran across a couple references that mention Fanconi’s Syndrome and vitamin D.  This is interesting since Fanconi’s Syndrome may be acquired as a result of HBV treatment with tenofovir.  Fanconi’s Syndrome and supplementation with vitamin D is also mentioned on the Mayo Clinic site.  The problem is there are no studies that definitively discuss the benefits of vitamin D supplementation for those living with HBV.  I am no doctor, but there seems to be a connection between vitamin D and good liver health.

Start by talking to your doctor or liver specialist about the pros and cons of considering additional vitamin D in your diet. Request that your vitamin D levels be tested so you get a snapshot of your current levels. I had my girls’ levels checked.  They were adequate, but I regretted having them tested during the summer break when they are outside more often. I wonder how this reflects on their levels in the winter when they are rarely outside?  Food for thought.

The 25-hydroxyvitamin D (25(OH) D) blood test is used to measure serum levels of vitamin D. Normal serum levels, indicated by the Institute of Medicine (NIH), are 50 nmol/L (20 ng/mL) or greater.  Low levels are under 30 nmol/L (12 ng/mL).  See detailed charts for age specific requirements. There are all kinds of reasons for inadequate levels of vitamin D, so it is important to follow up with your doctor if your results are out of the normal range.  You may require additional testing.

It is important to maintain a balance and use common sense when considering supplementing your diet with Vitamin D.  Vitamin D is essential, but too much of a good thing can be dangerous to your health. Be sure to keep your doctor in the loop – especially if you are currently undergoing HBV treatment.

Check out Thursday’s blog for those looking for vitamin D details and sources.

Do You Have Hepatitis B?

Have you been told you may be infected with  hepatitis B?  Did you get a letter following a blood donation, or receive lab results indicating infection?  It’s important you relax, educate yourself, and don’t let the news scare you.  The next step is to determine if you are infected, and if so, do you have an acute or chronic infection.

You’ll want to talk with your doctor, and have a hepatitis B blood panel run.  It is essential that you do not ignore the possibility of infection.  That being said, it’s equally important that you not panic.

When you get your lab results, ask your doctor to explain them to you.  It’s possible that you are not infected, but if you are, then you will need follow-up testing.  Be sure to ask for copies of your labs for your own records.  The test results are initially confusing, so you will want to refer back to the hard-copy results.

It is important to determine if you have an acute or chronic infection, but this may take some time.  If you were infected with HBV as an adult, there is a good chance you are acutely infected.  Fortunately, 90% of infected adults resolve the virus on their own. Recently infected adults may have flu-like symptoms, fatigue, yellowing of the eyes, or they may have no symptoms at all.  The answer is in the lab work.  Your doctor may run an HBc-IgM test, which will tell you if the infection is newly acquired. If it is a new infection, you will be monitored for the next one to six months to see if the HBV infection clears, and to ensure you are safe.  During this time, you are infectious to others, so it is important to practice standard precautions and ensure household members are vaccinated.  It is important to eat properly, rest, and avoid alcohol and tobacco. Talk to your doctor about the use of prescription and OTC drugs.  Hopefully your body will be able to mount an appropriate immune response, and you will be able to rid yourself of the virus.  If you remain surface antigen positive (HBsAg+) for more than six months you will be considered chronically infected.

Ten percent of those infected with HBV as an adult, will not clear the virus, and will become chronically infected.  Another group of adults that may just be learning of their Hepatitis B status, are those that acquired HBV at birth.  HBV infected mothers may unknowingly transmit HBV to babies.  Transmission can be prevented with vaccination at birth, but in many countries where HBV is endemic, a cycle of HBV transmission may exist where vaccination has not been available, and the virus is passed unknowingly from one generation to the next. Unfortunately, 90% of those infected at birth are chronically infected, even though it may not be determined until adulthood.  HBV is usually an uncomplaining disease, so it may be picked up accidently with blood-work , or when liver disease progresses due to decades of chronic infection.

Keep in mind that being vaccinated against hepatitis B will not protect you against the virus if you were infected with HBV prior to vaccination.  This can be confusing since most people are not screened prior to vaccination, and is  especially pertinent in high risk groups where the likelihood of mother to child transmission is greater.

The Hepatitis B Foundation has a step-by-step, comprehensive, yet-easy-to-understand tutorial that leads you through the process of determining your hepatitis B status, specific test results, and practical advice for coping with your HBV diagnosis.