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Hepatitis B Diagnosis & Monitoring, Hepatitis B Treatment

HBV Journal Review – June 2013

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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:

• U.S. Doctors Failing to Treat Patients Who Need Treatment
• Doctors Say Poor Training and Limited Resources Contribute to
Substandard Care • More Proof—Many Patients with Slightly Elevated ALTs
Have Fibrosis • Tenofovir Reduces Viral Load in HBeAg-Positive Patients
Faster than Entecavir • Researchers Find Tenofovir Does Not Damage
Kidneys • Tenofovir and Entecavir Highly Effective—If Taken as
Prescribed • Family History of Liver Cancer Boosts Cancer Risk to 15.8%
Among HBV-Infected • Vitamin D Deficiencies Found in People with High
Viral Loads • More Evidence Shows Breastfeeding Does Not Transmit HBV
Infection • Cesareans Do Not Reduce Mother-to-Child HBV Infection
• 2% of HBV Genotype D Adults Lose HBsAg Annually

HBV Journal Review

June 1, 2013, Vol 10, no 6
by Christine M. Kukka

U.S. Doctors Failing to Treat Patients Who Need Treatment
Fewer than 50% of patients infected with the hepatitis B virus (HBV) who need treatment get antivirals or interferon from their primary care doctors and fewer than 70% of patients who go to university liver clinics get appropriate treatment, according to research presented at the Digestive Disease Week medical conference held in Orlando in May.

Stanford University researchers conducted a real-life study to see what percentage of 1,976 hepatitis B patients treated in various clinical settings over four years received treatment. They used current medical guidelines when evaluating whether patients received appropriate treatment.

Continue reading about this and additional studies…

 

 

 

 

 

 

 

 

 

 

Hepatitis B Advocacy, Hepatitis B Prevention, Liver Cancer, Living with Hepatitis B

The Hepatitis B Foundation Participates in Liver Capitol Hill Day, 2013 – A Personal Reflection

Yesterday the Hepatitis B Foundation participated in the American Association for the Study of Liver Diseases (AASLD) annual “Liver Capitol Hill Day” visits. This is a great opportunity to get in front of state Senators and Congressmen in order to make requests known to them. It is also an opportunity to educate. As a constituent, your state representatives are interested in what you have to say. The “Asks” for the day were to support funding for liver related research, prevention strategies, and support of liver patient access to quality medical care.  Specifically, we were asking for NIH funding growth, rather than the 20% cut over the last decade, along with support of government agencies such as the CDC Division of Viral Hepatitis, and the delivery of health care systems and payment policies for patients living with liver diseases.  Prevention is also critical with specific asks for new, one-time hepatitis C testing and screening for hepatitis B for at-risk patients. As we are all aware, budgets are tight and we will all soon feel the effects of the Sequester. Research programs may no longer be funded, or severely cut, public health agencies and programs will be cut, and patients who are currently receiving medical assistance will suffer. For treated patients with HBV, it is essential nothing interrupts the daily antiviral use, and of course HBV and liver cancer prevention through screening, vaccination and surveillance is both necessary and cost effective in the long run.

Due to the Sequester, the day started in a panic for many Hill visitors. I was fortunate to arrive early – a good thing since I waited in a long security line for 45 minutes that wrapped around the building. As Maryland residents, Dave Li and I met with staff from both Senator Ben Cardin’s (D) and Senator Barbara Mikulski’s (D) offices.  Senator Mikulski was recently appointed the Chairperson of the U.S. Senate Appropriations Committee. This means she will have a great deal of influence on budget and spending decisions. We were told that due to the Sequester, the Continuing Resolution (CR) will remain in place for the remainder of the 2013, but Senator Mikulski is optimistic that the FY14 and future funding for the NIH, specifically, will be maintained. As a Maryland Senator, this is extremely important to Sen. Mikulski on many fronts. Senator Cardin has been making visits to agencies in MD, including the NIH, and researchers are frustrated they are unable to do their work.  Both Senator Cardin and Senator Mikulski support federal agencies (such as the CDC, Division of Viral Hepatitis, Public Health Agency etc.) and initiatives that provide care and services to meet the health care needs of Marylanders.  Fortunately this supports the Health and U.S. Health and Human Services (HHS) Viral Hepatitis Action Plan initiatives, since both Senators are supportive of prevention and surveillance initiatives.  Dave and I walked out of our Senate meeting feeling pretty good.

Unfortunately, the outlook was not so optimistic on the House side. We visited staffers from Congressman Chris Van Hollen and Congressman Elijah Cummings offices. Although they are working on budgets, they are meeting with opposition and resigned to deep cuts in their supported programs.  Congressman Cumming’s staffer was pleased to hear an optimistic viewpoint from Mikulski’s office.  Although clearly mixed signals from our House and Senate meetings, we can only hope that Congress will eventually work together and move forward with continued funding of agencies and programs that support those living with liver disease.

Please remember that your state Senators and Representatives have been voted to serve YOU. It is imperative that your voice be heard. If you don’t let them know what is important to you, important programs and agencies will be drastically cut.  You do not need to be a political machine to participate. Don’t know your Representative?   Find your Rep. on-line by putting in your zip code or state to learn who you need to contact. Find your Senator, Governor and Congressmen here. Call the Capitol switchboard’s toll free number at 1-888-876-6242 , or send an email  or letter with your asks, and your personal stories. Be sure your message is clear and concise, and personalize it if you can. You can visit your Representative or Senator when you are visiting Washington, D. C., or in the local, state office. Let your voice be heard – especially during this very difficult time.

Hepatitis B Diagnosis & Monitoring, Living with Hepatitis B

HBsAg Levels Linked with Fibrosis in HBeAg-Positive Patients

Below is a publication from “Healio Hepatology, February 21, 2013 – HbsAg Levels Linked with Fibrosis in HBeAg-Positive Patients” , showing the correlation between HBsAg and HBV DNV virus levels and the risk of moderate to severe fibrosis in HBeAg positive patients.

Patients with hepatitis B who tested positive for hepatitis B e antigen were at increased risk for moderate-to-severe fibrosis with lower levels of hepatitis B surface antigen in a recent study.

Researchers evaluated serum samples and liver biopsy results from 406 treatment-naive patients with chronic hepatitis B. HBV genotype and hepatitis B e antigen (HBeAg) status were recorded along with levels of HBV DNA and hepatitis B surface antigen (HBsAg).

HBeAg-positive patients (n=101) had a higher mean fibrosis stage than HBeAg-negative patients (1.86 ± 1.18 vs. 1.40 ± 0.99; P<.001) and had greater levels of HBV DNA (7.06 ± 1.71 vs. 4.12 ± 1.67)and HBsAg (4.24 ± 0.9 vs. 3.53 ± 0.92) (P<.0001 for both). Investigators observed strong correlations between HBV DNA and HBsAg levels (r=0.44; P<.0001) and between fibrosis severity and HBsAg levels (r=0.43; P<.0001) among HBeAg-positive patients, but not among HBeAg-negative participants.

HBeAg-positive patients with moderate-to-severe fibrosis had lower HBsAg (3.84 ± 1.01 vs. 4.63 ± 0.58; P<.0001)and HBV DNA levels (6.47 ± 1.81 vs. 7.62 ± 1.40; P<.001) than those with mild or no fibrosis. HBeAg-positive patients with genotypes B, D or E had significantly higher HBsAg levels than HBeAg-negative patients, along with higher HBV DNA levels regardless of genotype.

Modeling analysis established an HBsAg cutoff of 3.85 log IU/mL-1 with a theoretical sensitivity of 100%, specificity of 86% and NPV of 100% for predicting moderate-to-severe fibrosis among HBeAg-positive patients with genotypes B or C. Investigators noted that the small cohort size used to establish this cutoff requires further validation to be clinically useful.

“To our knowledge, the current study is only the second to associate an HBsAg cutoff with the prediction of fibrosis severity in CHB patients,” the researchers wrote. “It will be of considerable interest to see whether the serum HBsAg and HBV DNA levels in the patients infected with different genotypes are significantly different from the mean values of the overall HBeAg-positive group, and if they will require the development of genotype-specific cutoffs, or whether a single cutoff is applicable to all HBV genotypes.”

Disclosure: See the study for a full list of relevant disclosures.

Liver Cancer, Living with Hepatitis B

Aspirin Use Associated With Lower Risk of Developing Hepatocellular Carcinoma and Dying of Chronic Liver Disease

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HBF welcomes special guest bloggers, Vikrant V. Sahasrabuddhe, M.B.B.S., M.P.H., Dr.P.H and Katherine A. McGlynn, Ph.D, M.P.H. both researchers at the National Cancer Institute of the NIH, and study authors of the recent Journal of the National Cancer Institute publication.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer.  New cases of HCC and deaths related to HCC have been increasing in the United States since the 1980s.  Most cases of HCC occur in individuals with chronic liver disease (CLD).  CLD is caused by chronic inflammation related to viral infection, excess alcohol consumption or other causes.  While HCC is relatively rare in the U.S., occurring in fewer than 10 per 100,000 persons per year, CLD is more common.  Unfortunately, CLD is among the top 10 causes of death in adults between the ages of 45 and 75 years.

In a new study from the National Cancer Institute, researchers investigated whether reduction of inflammation, through the use of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, could reduce the risk of developing HCC or death due to CLD. The study was published in the Journal of the National Cancer Institute on November 28, 2012.

The researchers studied a cohort of over 300,000 men and women between the ages of 50 and  71 years who were enrolled in the NIH-AARP Diet and Health Study.  Aspirin and non-aspirin NSAID (for example Advil, Motrin) use was compared among persons who developed HCC or died from CLD and those who did not develop these outcomes.  In all, 250 study participants developed HCC and 428 died from CLD.  Almost three-fourths of the participants reported using aspirin and approximately one-half reported using non-aspirin NSAIDs.

The study found that participants who reported taking aspirin were 41% less likely to develop HCC, and 45% less likely to die from CLD than those who did not take aspirin. Use of non-aspirin NSAIDS did not reduce the risk of developing HCC, but did reduce the risk of dying from CLD by 26%. The researchers note that additional studies will be required to confirm these findings.

While this study will not lead to any immediate changes in clinical practice, it raises interesting new questions on the role of inflammation in risk for HCC.  Although the researchers took into consideration the effect of alcohol intake (a major risk factor for HCC) as well as smoking and body mass index, the study had no information on hepatitis B virus (HBV) or hepatitis C virus (HCV) status of the study participants.  In addition, NSAID use was only measured for the past 12 months, and the study had no information on the indication, duration or dose.  To partially overcome such limitations, results were analyzed after excluding participants who reported hypertension or cardiovascular disease at the beginning of the study. Those individuals might be taking a low-dose aspirin for a longer duration for the prevention of cardiovascular disease. The results were similar after excluding these participants, which suggests that the main results are likely valid regardless of the indication, duration or dose of aspirin.

The study is the largest population-based study to date to assess development of HCC and risk of death due to CLD in relation to NSAID use.  HCC and CLD involve chronic, long-term inflammatory changes in liver cells, which are caused by enzymes such as cyclooxygenases (COX).  One of the primary ways that NSAIDs modulate the risk of chronic inflammation is by stopping or inhibiting the action of COX enzymes; thus inflammatory changes that contribute to the development of CLD and HCC are reduced.  It is also speculated that aspirin may have other anti-inflammatory mechanisms.  NCI researchers are investigating these hypotheses through basic and translational research studies, as well as assessing the risk of developing HCC and dying of CLD in association with NSAID intake in other epidemiologic studies.

The full study is by:

Vikrant V. Sahasrabuddhe, Munira Z. Gunja, Barry I. Graubard, Britton Trabert, Lauren M. Schwartz, Yikyung Park, Albert R. Hollenbeck, Neal D. Freedman and Katherine A. McGlynn. Nonsteroidal Anti-inflammatory Drug Use, Chronic Liver Disease, and Hepatocellular Carcinoma. J Natl Cancer Inst (2012). Published online at: doi: 10.1093/jnci/djs452

Editorial Comments by W. Thomas London, HBF Senior Medical Advisor

In previous blogs I reported that several drugs commonly used to treat or prevent diseases or conditions other than liver cancer or chronic liver disease may also prevent these serious liver diseases.  These included propranolol used to reduce pressure in the portal vein; metformin used to treat diabetes; and statins for the lowering of cholesterol and reducing the risk of heart disease.

The above report adds aspirin to this list, but people with chronic hepatitis B or C should not begin taking aspirin immediately.  Aspirin may cause serious bleeding that is sometimes fatal.  In order for blood to clot, platelets (cell fragments in blood) must clump.  One of aspirin’s actions is to prevent platelets from aggregating (clumping). This action may be the main reason that regular aspirin may prevent heart attacks. Patients with CLD are already at risk of developing serious bleeding.  The take home message is that patients with chronic hepatitis B or C should consult their doctor before taking aspirin or any other drug.

About the blog authors:

Vikrant Sahasrabuddhe,M.B.B.S., M.P.H., Dr.P.H.

Associate Investigator in the Hormonal and Reproductive Epidemiology Branch and is currently detailed to the NCI from the faculty at Vanderbilt University School of Medicine.

Katherine A. McGlynn, Ph.D., M.P.H.

Deputy Chief, Hormonal and Reproductive Epidemiology Branch 

 

Hepatitis B Diagnosis & Monitoring, Hepatitis B Treatment, Living with Hepatitis B

Hepatitis B and Vitamin D

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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.

Hepatitis B Diagnosis & Monitoring, Hepatitis B Treatment, Living with Hepatitis B

The Hepatitis B Foundation’s Hepatitis B Clinical Trials Page

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Did you check out Tuesday’s Hep B Blog, “Participating in HBV Clinical Trials” for those living with Hepatitis B?  It’s time to have a more in-depth look at the HBV  trial entries that are updated monthly on The Hepatitis B Foundation’s (HBF’s) Hepatitis B Clinical Trials web page. Roughly 350 trials out of the 112,278 clinical trials maintained by ClinicalTrials.gov pertain to HBV related studies.  The ClinicalTrials.gov site is a registry of trials that located in 175 different countries.  Changes to ClinicalTrials.gov are an ongoing process.

Each month the HBF’s Hepatitis B Clinical Trials web page is updated based on a thorough review of clinicalTrials.gov registry.   Trials that are new and are recruiting are added.  Completed trials are deleted, and modifications are made based on the “last updated date” of the each trial entry. All identified trials are active and currently recruiting patients. Modifications may include anything from additional site locations added to the trial, to new contact information, or even a change in protocol.  A few international trials are in an unknown state, but remain on our page until we hear word if the trial is completed, or no longer recruiting patients.  If you are local and interested, it is worth pursing to get the current status.

The page is divided into U.S. trials, International trials, Co-Infection trials, Pediatric trials, HBV & Liver Transplantation, HBV & Liver Cancer, and HBV Reactivation and Lymphoma. Some of these categories are more recent and were added to address other areas for those living with HBV.

Recently HBF has made an effort to include trials, within the country of origin for the trial, that not only treat HBV, but also monitor patients.  These long term studies may use new, experimental techniques to monitor HBV patients, or those at high risk for HCC.  There are also opportunities to participate in long-term studies that monitor patients and look for common factors, trends etc. among those living with HBV.  It’s another opportunity to meet with  cutting-edge liver specialists, and possibly even contribute by helping researchers determine factors that may cause HBV disease to activate, or worsen, or hopefully improve.

So have a seat at your computer and review HBF’s Hepatitis B Clinical Trials web page, or go to the individual section that interests you.  The trials listed contain the original title, the purpose, or basic description of the trial.  Due to logistics, the trial site is very important, which is why all entries contain the countries included in the site unless they are too great to list. Then they are listed as “international“. Contact information is also maintained and updated, with a link to email and phone contact info.  Most importantly is the NCT number (NCT followed by an 8 digit identifier), or ClinicalTrials identifier, which is how all trials are referenced in the ClinicalTrials.gov registry. By clicking on the NCT#, you will be linked to the trial of interest directly within ClinicalTrials.gov, where you can investigate the details of the trial and see if it is of interest, and whether or not you meet the criterion for participation.

Give it some thought and think about whether an HBV clinical trial is an option for you.  Discuss your ideas with your liver specialist, and confer with others in HBV support groups that may have experience with a drug, or past clinical trial experience.  Feel free to contact HBF with any questions you might have regarding clinical trials.

If you think of a way to make our clinical trials page more user-friendly, or trial categories that might be missing, be sure to leave a comment and let me know.  And if you happen to find an HBV trial that is recruiting, but is not listed, please be sure to let us know. HBF is here to help!

Hepatitis B Diagnosis & Monitoring, Hepatitis B Treatment, Living with Hepatitis B

Participating in HBV Clinical Trials

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Have you considered participating in hepatitis B clinical trial?   A clinical trial can be a great opportunity to take advantage of the latest advancements in HBV treatment and monitoring, typically without expense to the patient.  It can open doors and provide an opportunity to interact with liver specialists on the leading edge of treating HBV.  There are numerous clinical trials for hepatitis B offered all around the world, from adult to pediatric patient populations.

There are three testing phases that drugs go through before they are approved for use for by the FDA.  A fourth phase examines long-term use.  This is a rigorous process, costs hundreds of millions of dollars and takes 12-15 years before a drug is finally approved. Check out the animated Drug Discovery Time Line to get a better appreciation for the process.

A major advantage of participating in a clinical trial is that expensive treating medications, clinical monitoring, and lab work are typically provided without expense to the patient, and the patient is monitored throughout the process by experienced, participating liver specialists.

The next thing to consider is whether or not you are eligible for a particular trial.  There are various inclusion/exclusion criterion.  Some trials or studies are looking for patients that are treatment naïve, (patients who have not taken medications for HBV) while others are looking for patients that are treatment experienced, (patients who have taken particular medications for HBV) but may have failed on one treatment protocol, and might need “rescue therapy,” such as an antiviral to replace a previous antiviral where a resistance to the drug has occurred based on a viral mutation.  It varies with trial.

Other studies may be looking for candidates based on HBe status (positive or negative), degree of liver damage, or ALT or HBV DNA levels over a particular time period. You must first qualify before you consider participation in a trial or study, so be sure to check the qualifying criterion, and discuss with your doctor.

Naturally, each candidate will need to weigh the risks versus the benefits of receiving an experimental drug. Discuss the pros and cons with your doctor. Do you really need treatment for your HBV at this time? What are the possible short and long term side effects? Do you think you can manage them? You know your body best. What about the logistics?  Is there a need for frequent lab work?  Does it need to be done on site, or can blood be drawn at a local lab?  What happens when the trial is complete?  This is especially important when considering antivirals. Will you need to remain on the medication when the trial is complete?  Will you be financially responsible, and if so can you afford it?  Will participating in a trial exclude you from future trials?  What about resistance and cross resistance to future drugs? These are a few of the questions for which you need to think long and hard, and of course discuss them with your liver doctor and the participating specialist.

It also doesn’t hurt to ask other patients on HBV internet support groups.  You might well find someone with personal experience with the drug, keeping in mind that everyone responds somewhat uniquely to the same drug therapy. I have found these forums extremely helpful when considering a new drug.

The Hepatitis B Foundation is committed to maintaining monthly, updated clinical trial data available to friends living with HBV on our website.  We do much of the up-front work for you by sorting through the hundreds of trials available via clinicalTrials.gov, a registry of clinical trials.  We divide the data into unique treating situations that might benefit various patients, such as clinical trials for patients that live in the U.S. or internationally,  pediatrics, coinfected, candidates for liver transplantation, patients struggling with HBV related hepatocellular carcinoma, and HBV reactivation and lymphoma.  Most trials relate to the treatment of HBV, while some are observational studies, long term studies where patients are monitored over time.  Some relate back to treatment studies – durability of treatment or long term effects, while others study patients with HBV, and identifying factors that may cause the disease to activate or worsen, and are monitored via annual or bi-annual blood work and annual visits.  It varies with the trial.

So if you have HBV, consider your status. If you are a candidate for treatment, consider existing, approved treatments vs. participation in an HBV clinical trial. It’s up to you and your doctor to determine if a clinical trial is a good fit.

 

Hepatitis B Advocacy

The Hepatitis B Community Loses Cherished Friend and Advocate

It is with great sadness and heavy hearts that we notify the hepatitis B community of the passing of Dr. Baruch S. Blumberg.  Dr. Blumberg died suddenly on Tuesday, April 5, 2011.  His discovery of the hepatitis B virus and invention of the first vaccine against hepatitis B, which resulted in the Nobel Prize for medicine in 1976, have been among the most important in the history of science and medicine.  In addition to serving as Senior Advisor to the President of Fox Chase Cancer Center, Dr. Blumberg co-founded the Hepatitis B Foundation and served the Foundation as a Trustee Distinguished Scholar.  His ongoing acts of support to the Foundation will always be remembered and admired.

“It has been one of the greatest professional privileges of my life to have known and to have worked with Dr. Blumberg.  He was a wonderful mentor to me, and to all of us at the Hepatitis B Foundation, who had the honor of knowing him.  His curiosity and enormous intellect was always so motivational.  He made it clear to all of us at the Foundation, how one life can do so much to benefit the world.  Nothing will be the same without him, but so much has changed because of him.  He will always be an example and inspiration for us all.” –  Dr. Timothy Block, President of the Hepatitis B Foundation

Please join us in remembering our dear friend, colleague, advocate and champion of the hepatitis B cause, Dr. Blumberg.  Our thoughts and prayers are with the Blumberg family.

Baruch S. Blumberg

1925-2011

 

 

Baruch S. Blumberg Institute