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The majority of people infected with hepatitis B lead healthy and normal lives. However, a small number of people may develop liver disease that will dramatically affect their quality of life and their ability to work on a short-term or long-term basis.
They may not be able to work for several weeks because of side effects from pegylated interferon treatment, or progressive liver damage could make it impossible to work and support themselves and their families even after treatment.
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By Christine Kukka
To prevent liver damage and cirrhosis and reduce the risk of liver cancer–especially in older patients who’ve had hepatitis B for decades–doctors often prescribe long-term antiviral treatment. But some antivirals cause minor bone loss, which poses a problem for older patients with osteoporosis.
According to experts, the risk of bone loss from long-term antiviral treatment is low, and in fact some antivirals do not cause any bone loss at all. But if you are starting antivirals at an older age, or if you have been on antivirals long-term, experts recommend you monitor your potassium and vitamin D levels and regularly test for bone loss in the hip area so you know if you are experiencing bone loss and need a calcium or vitamin D supplement. Continue reading "Taking Antivirals Long-Term for Hepatitis B? Should You Worry About Bone Loss?"→
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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 use the same lab for your test. Labs usually measure down to less than 200 IU/mL. Below the threshold, the viral load is considered “undetectable” – something everyone 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. You may need to convert these numbers to fully understand them.
What does viral load say about what stage of the virus you are in? Your viral load also varies over time depending on the “stage” of hepatitis B infection. That is why regular monitoring is so important.
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 virus. Most children and young adults who test positive for the hepatitis B “e” antigen (HBeAg) generally have high viral loads, though doctors typically 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 and liver enzymes (ALT/AST) normalize.
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 usually indicate no current liver inflammation, and undetectable or viral loads less than 2,000 IU/mL generally do not require treatment. However, it is important to confirm with your doctor that there is no evidence of advanced liver disease. This phase may be lifelong, decades, or not long at all. That is why monitoring in this inactive phase remains important.
People in the “active” stage with elevated viral loads and signs of liver damage need treatment. These may be people that are HBeAg positive and unable to seroconvert and lose HBeAg and gain the antibody without experiencing significant liver damage. There may be a pattern of SGPT/ALT elevation that cycles up and down over time without mounting an adequate immune response to seroconvert. This can be dangerous, causing liver damage, which is why regular monitoring is key. You want to give your immune system the opportunity to try to mount an immune response and seroconvert but not at the expense of extensive liver damage. That’s why a knowledgeable doctor is so important!
Many people in their 40s, 50s or 60s, develop HBeAg-negative hepatitis B, though this may occur in younger individuals as well. Although individuals may have seroconverted and lost HBeAg (HBeAg negative/HBeAb positive), the virus is able to mutate allowing it to keep replicating, putting these patients at risk of liver damage. They may see the viral load start to creep up along with SGPT/ALT. Eventually they may require treatment with antivirals based on clinical guidelines doctors follow to manage their patients. Once again, monitoring is key!
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.
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Medical guidelines suggest that individuals with HBeAg-negative hepatitis B with signs of liver damage face an “indefinite” or even lifetime commitment to taking daily antiviral pills.
In this week’s blog, we explore when—if ever—individuals with hard-to-treat HBeAg-negative hepatitis B can ever stop taking antivirals.
First of all, what is HBeAg-negative hepatitis B? Many people infected with hepatitis B at birth and who remain infected into their 40s, 50s or 60s, develop HBeAg-negative hepatitis B. Researchers believe that over time the virus mutates to evade the immune system. Though individuals may have lost the hepatitis B “e” antigen (HBeAg) and developed the “e” antibody, this mutated virus develops the ability to keep replicating despite the loss of HBeAg. And this mutated virus is capable of putting people at higher risk of liver damage.
Generally, doctors recommend treatment to HBeAg-negative patients when their viral load exceeds 2,000 IU/ML and their ALT liver enzyme levels, which rise when liver cells are damaged, are even moderately elevated. (Normal ALT levels are less than 30 for men and 19 for women.)
The most common antiviral treatments are either entecavir (Baraclude) or tenofovir (Viread). These two are considered the most powerful at quickly reducing viral load (HBV DNA) and have a very low risk of causing drug resistance, which is critical considering the long-term treatment required by HBeAg-negative patients.
But can individuals with HBeAg-negative hepatitis B ever stop treatment? Antivirals are expensive, without insurance tenofovir costs about $1,000 a month and generic entecavir costs about $407 in the U.S. Additionally, long-term antiviral treatment can cause bone loss.
Late last year, hepatitis B experts with the American Association for the Study of Liver Disease (AASLD) tackled this question and reviewed recent studies that followed HBeAg-negative hepatitis B patients who stopped antivirals. They found that even when these patients enjoyed two years of undetectable viral load and normal ALT levels during treatment, when they stopped only half of them were able to maintain a low viral low (below 2,000 IU/mL) and normal ALT levels.
The risk of dangerous “flares” after stopping treatment, “requires careful weighing of potential for harm and benefit,” the experts wrote. This is important because many HBeAg-negative patients are older and more vulnerable to liver damage and cancer.
In their new recommendations, AASLD experts make clear their findings are “conditional” and the quality of evidence found in the studies they reviewed is “low.” However, this is what they tentatively recommend:
Stopping treatment, “may be considered in persons who have (lost) the hepatitis B surface antigen (HBsAg). However, there is currently insufficient evidence to definitively guide treatment decisions for such persons.”
And, anyone who stops antiviral therapy should be monitored every three months for at least one year to see if their viral load rebounds or if they have signs of liver damage, including ALT flares.
Given the knowledge-gap about the long-term health consequences of HBeAg-negative hepatitis B, more research with longer durations of monitoring are needed, experts recommended. “Alternative treatment strategies for patients on long-term antiviral therapy, such as adding or switching to (pegylated interferon), warrant further study,” they concluded.
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Eighteen years ago, doctors started treating hepatitis B patients with antivirals and today liver specialists have a wealth of knowledge about how these drugs stop the virus from replicating and reduce viral load. But one thing they’re still not certain about is when patients can safely stop taking their daily antiviral pill.
In this week’s blog, we’ll explore when experts think it’s safe for patients, who have lost the hepatitis B “e” antigen (HBeAg) during antiviral treatment, to stop . Next week, we’ll look at when it’s safe for patients who were already HBeAg-negative when they began antiviral treatment to stop.
Today, doctors prescribe one of two antivirals—either entecavir (Baraclude) or tenofovir (Viread). Among the antivirals developed since 1998, these two are considered the most powerful in quickly reducing viral load (HBV DNA) and they carry the lowest risk of drug resistance. Doctors usually prescribe antivirals when our viral load is elevated and we have sign of liver damage–indicated by elevated liver enzymes (ALT or SGPT).
Antivirals quickly knock down viral load, which in turn is believed to lower our risk of liver damage and cancer. But antivirals work for only as long as we take them. When we stop, the virus usually reactivates although this is very rarely fatal or results in a liver transplant. Studies show that at least 78 percent of people who stop antivirals have an increase in viral load, 44 percent have a rise in ALT levels indicating liver damage, and among those who lose HBeAg during treatment, at least 9 percent experienced a return of HBeAg.
But what about individuals who take antivirals for long periods and enjoyed years of undetectable viral load, no signs of liver damage, loss of HBeAg, and development of the “e” antibody? Can they stop? After all, antivirals are expensive. Without insurance, a month’s supply of tenofovir costs about $1,000 and generic entecavir costs about $407 in the U.S., not to mention possible side effects such as bone loss or reduced kidney function with tenofovir..
Late last year, hepatitis B experts from the American Association for the Study of Liver Disease (AASLD) tackled this question and reviewed recent studies that followed patients who stopped antivirals after losing HBeAg. They found no clear answers and made clear their recommendations were “conditional” because the quality of evidence found in the studies was “low.” But here is what they recommend for patients who lost HBeAg during antiviral treatment and now have normal ALT levels:
Experts “suggest” that adults who don’t have cirrhosis (severe liver scarring) who lost HBeAg and developed “e” antibodies may stop treatment after a minimum of 12 months of normal ALT levels and undetectable viral load.
However, they recommend a longer “consolidation” treatment period might be better to reduce patients’ risk of relapse and a return of HBeAg after treatment stops. They suggested that an alternative approach would be to stay on antivirals until patients lose the hepatitis B surface antigen (HBsAg).
Decisions about how long to stay on antivirals require careful consideration of health risks and benefits, they wrote, including risks of relapse, liver damage, and liver cancer. Other considerations include the cost of treatment, the risk of developing drug resistance if people stop antivirals intermittently, and other side effects.
Anyone who stops taking antivirals, they advise, should be monitored frequently – at least every three months — for at least one year for liver damage and resurgence of viral load. Anyone with cirrhosis should continue treatment indefinitely because of their high risk of liver cancer.
For now, the message appears to error on the side of caution and continue on antivirals until you have cleared HBsAg for a prolonged period of time. Clearly this decision is one you must discuss carefully with your doctor.
In next week’s blog, we examine how long people who were HBeAg-negative when they started antivirals should remain on treatment.
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If antiviral medications almost always lower viral loads, why don’t doctors treat young adults with high viral loads with this daily pill? After all, don’t high viral loads lead to liver damage and even liver cancer?
This is one of the most common questions posed to the Hepatitis B Foundation, and at first glance the decision not to treat a high viral load with antivirals seems counter-intuitive or plain wrong. If antivirals reduce the number of hepatitis B virus (HBV) in the body, won’t that give the immune system an opportunity to clear out the remaining residual HBV?
Unfortunately, it doesn’t work that way. It’s complicated, as are many aspect of hepatitis B.
It’s common for young adults (up to age 30) who live with hepatitis B to be in the “immune tolerant” stage of infection with extremely high viral load (HBV DNA) but with no signs of liver damage.
When we’re born to mothers infected with hepatitis B, unless we’re immunized at birth 90 percent of us become infected from exposure to infectious blood and body fluids during delivery. And when infants are infected, their immature immune systems don’t recognize the virus. The young immune system misses the “red flag” signature on this hepatitis B virus and “tolerates” the infection instead of attacking it.
In contrast, when we’re infected as healthy adults, our immune systems immediately detect and identify hepatitis B as a viral invader and aggressively attacks the virus and any infected liver cells. In adults, it generally can take up to six months for the immune system to eradicate the virus. When we’re infected as children, it can take up to three or even four decades for our immune systems to notice the virus and shift into “immune active” battle mode.
Until the immune systems notice the virus and begins to fight the infection, children and young adults remain in the “immune tolerant” stage, with sky high viral loads that can reach 1 billion international units per milliliter (IU/mL). Unencumbered by an immune system that’s on the offense, the virus hijacks liver cells to replicate and churn out more virus.
Because the immune system isn’t attacking and damaging the infected liver cells, liver tests (ALT or SGPT) results show no signs of damage and usually remain in the normal range (30 or less for men and 19 or less for women). And until our immune systems wake up and launches its attack, doctors say there is no reason to try to lower the viral load in these young adults because even when antivirals lower viral load, the immune system stays dormant and doesn’t go on the offensive.
Experts recently re-examined whether this hands-off approach was still valid and reviewed more than a dozen studies that examined whether antiviral treatment benefited immune-tolerant adults.
At the November 2015 AASLD Liver Conference, researchers reported, “There are no studies demonstrating that antiviral therapy is beneficial in reducing rates of liver cancer, cirrhosis, and liver-related death in persons with immune-tolerant chronic hepatitis B.”
Following their instruction to “first do no harm,” the experts recommended, “Given the lack of evidence of benefit to those with (high viral load and normal ALT levels), the potential harms of finite (or longer) antiviral therapy, including cost, antiviral drug side effects, and development of resistance, outweigh benefits.”
Let’s explore their rationale:
Antivirals work for only as long as you take them. Once started because of liver damage, patients can be on them for many years, and when patients go off antivirals, they often experience a “flare” with a sudden increase in viral load and ALT levels that can be dangerous.
The leading antivirals, including tenofovir (Viread) and entecavir (Baraclude), are not cheap, especially tenofovir which is not yet available in a generic formula.
And antivirals have side effects, which can include bone loss, impact on kidney function, and a risk of developing drug resistance.
So, if treatment will not yield good results, why put young adults through the cost and medical risk? In fact, experts don’t even treat immune-tolerant patients who have family members with hepatitis B-related liver cancer.
The experts did make clear that all immune-tolerant patients should have their ALT levels and viral load checked at least every six months so doctors could monitor their infection.
Still, this is challenging to hear when we are living with hepatitis B or just recently diagnosed with a chronic infection. We want to do something to fight the infection. But without an active immune system as a strategic partner in our fight against hepatitis B, we must be patient and let go of a quick-fix hope, as much as we all want a magic pill to cure our infection.
So in the interim, until our immune systems wake up and starting fighting the virus in our bodies, we do what we can to protect our health, including eating healthy foods, avoiding alcohol and cigarettes, and getting monitored every six months. It may not feel like it’s enough, but for now it’s all we can do.
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In 2015, doctors continued to unlock the mysteries of hepatitis B and uncovered promising new treatments. Armed with new information, here are 10 things we can do in 2016 to safeguard our health and help prevent the spread of hepatitis B.
Get monitored regularly. No one likes a blood draw or to be reminded they have hepatitis B, but it’s important that you’re tested annually or more often if you have a high viral load and/or signs of liver damage. There’s no cure yet, but there are effective treatment options with more in the pipeline. So be brave, protect your health, and go to the lab for a blood test.
If you’ve been prescribed an antiviral, don’t forget to take it. Taking a pill every day is tedious and it’s tempting to skip it, but failing to take your daily antiviral reduces its effectiveness and can lead to drug resistance. The hepatitis B virus is a master at mutating to escape whatever is attacking it. Forgetting to take your daily pill can lead to an uptick in your viral load and liver damage. Stay strong, take your daily pill, and keep that virus undetectable.
Face it, antivirals are a long-term commitment. Until a cure is developed, antivirals—either tenofovir (Viread) or entecavir (Baraclude)—are the best treatment to quickly reduce both viral load (HBV DNA) and liver damage. But they work for only as long as we take them, and once we start, we are usually committed to years of treatment. Quitting antivirals before we’ve achieved undetectable viral load and lost the hepatitis B surface antigen (HBsAg) often results in a resurgence of both viral load and liver damage. Antivirals are a long-term treatment that help prolong our lives.
Demand to be screened for liver cancer. Some experts say current medical guidelines that recommend when we should be screened for liver cancer don’t go far enough to protect us. So take charge of your health and ask for a liver cancer screen, which includes a semi-annual blood test and an ultrasound. Hepatitis B-infected Asian men (or of Asian descent) over age 40 years and Asian women over age 50 years, patients with a family history of liver cancer, patients with cirrhosis, and Africans over the age of 20 should all be screened. Think you’re not at risk for cancer because you take antivirals? Think again. Antivirals help reduce liver damage, but if you’ve had cirrhosis or are older, the risk of liver cancer remains.
If someone promises a new cure or treatment that sounds too good to be true….it probably is. In our search to be rid of hepatitis B, we may be tempted to yield to clever marketing and try a supplement that promises to cure us. But first, do your homework and practice precaution. To check out an herbal supplement, visit the National Center for Complementary and Integrative Health’s website to see what scientific evidence exists for a supplement and talk to your doctor. There is no magic bullet that will cure hepatitis B. Experts hope to find one soon, but for now be patient and stay skeptical. If you want to safeguard your health, eat healthy foods and avoid alcohol and cigarettes.
Experts say a cure is coming … so stay informed about new drug developments and clinical trials. There is lots happening on the research front. To find out what drugs are in the development pipeline, visit the Hepatitis B Foundation’s Drug Watch page for the latest news. You can also find out if you qualify for a clinical trial. Expensive blood work, treatment medications, and doctor’s visits are usually free-of-charge for those accepted into a study. The foundation features a list of hepatitis B-related clinical trials that are recruiting patients in the U.S. and around the world at its Clinical Trials page. You could become part of the cure.
Pregnant with hepatitis B? Get your viral load tested and ask your doctor about antivirals. In November, the American Association for the Study of Liver Disease (AASLD) for the first time recommended that pregnant women with viral loads (HBV DNA) higher than 200,000 IU/mL (or 1 million copies/mL) receive an antiviral (either tenofovir or telbivudine) starting at their 28th week of pregnancy. The antivirals won’t hurt you or your baby and will reduce the risk that your baby will be infected with hepatitis B to nearly zero, as long as your baby gets the first dose of the hepatitis B vaccine and a dose of HBIG (hepatitis B antibodies) within 12 hours of birth.
Fight discrimination against hepatitis B and know your rights. Hepatitis B should never be a barrier to the education or job you want. Sadly, ignorance and stigma remains in the U.S. and abroad. It depends on us, our friends, and our family, to stand up and fight for our civil rights. We can’t back down. If we don’t fight, who will?
Practice safe sex and never re-use needles. Today, in some areas of the U.S., hepatitis B is increasing—even though a safe and effective vaccine exists. Unfortunately, not everyone is immunized and the infection is still getting transmitted sexually. In the midst of America’s heroin epidemic, it’s also spreading when syringes are re-used and shared. Do you want to end hepatitis B? Make sure your friends and family members know how to prevent sexually-transmitted infections (even if those conversations are challenging, their lives may depend on it) and support needle exchange programs in your region and state. Countless studies show that when needle exchange programs are available, HIV, hepatitis B and C rates decline! It saves lives and healthcare dollars!
Be brave, disclose, and get your friends, family, and lovers screened for hepatitis B and vaccinated. Yes, it will be one of the hardest conversations you will ever have, but if you are infected with hepatitis B, you need to disclose your infection to people who may be at risk. If you just discovered you have chronic hepatitis B, which you may have contracted at birth, you need to tell your siblings and your mother and get them screened and immunized if needed. Dating someone, and about to take the next step? You need to disclose ahead of time and give them information and choices. It builds trust and it’s the right thing to do. You would want the same for yourself.
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Early detection of cancer saves lives. Whether it’s breast, liver, or skin cancer, when it’s found and treated early, our survival improves markedly.
But here’s the rub. We intellectually know that early detection works, but performing those self-breast exams or getting screened for liver cancer carries a huge risk – what if something is found?
Every trip to the doctor or lab reminds us of our mortality, especially when we have hepatitis B. We have to take that risk and acknowledge our mortality, even when the healthcare system doesn’t make it easy.
A few months ago, the Hepatitis B Foundation assembled national experts to discuss how well the system worked to identify and treat liver cancer, which is now one of the top causes of cancer deaths. Worldwide, today hepatitis B causes 45 percent of liver cancers.
Their findings, published in the April 2015 issue of the Journal of the National Cancer Institute, paint a dismal picture of a healthcare system that often fails us, our family members, and our friends who live with hepatitis B and are at risk of liver cancer. Not only are providers failing to screen a large percentage of at-risk patients, when they find liver cancer, their treatment is often inadequate and inconsistent across clinics.
Who should be screened for liver cancer? Hepatitis B-infected Asian men (or of Asian descent) over age 40 years and Asian women over age 50 years, patients with a family history of liver cancer, patients with cirrhosis, and Africans over the age of 20 should all be screened.
What is the screening? A semi-annual ultrasound and blood tests to detect liver cancer are recommended, but this approach is only 70 to 80 percent effective in identifying liver cancers. This means 20 to 30 percent of people at risk of cancer won’t get diagnosed. And there are other problems.
A recent, large study of 5,000 insured hepatitis B patients in the U.S. who did not have cirrhosis found that only 6.7 percent of them had been screened properly, based on recommendations, over the four-year study. And these are the patients with insurance who have good access to healthcare. Liver cancer screening among uninsured people is downright abysmal, and usually performed only after liver cancer has progressed to an inoperable and untreatable stage.
About 60 percent received partial screens and 34 percent had not been screened at all. Those least likely to be screened lived in rural areas (where doctors had little hepatitis B expertise and were unfamiliar with current guidelines) or were coinfected with HIV.
While ultrasound exams are affordable, relatively easy to perform and widely available, the success of this screen depends entirely on the operator’s skill and experience. If the operator is having a bad day or is not trained in identifying liver cancers, small nodules or tumors can remain unnoticed, at a time when they’re in the early, treatable stage.
And then there’s obesity. Especially in the U.S., many patients with viral hepatitis and/or fatty liver-related cancer are overweight, and obesity reduces the accuracy of ultrasounds.
The advantages of blood tests is they are widely available, relatively affordable, and generally require only a blood sample. The disadvantages is they are not highly accurate, especially when tumors are small (and still treatable). The most well-studied and commonly-used blood test is the alpha fetoprotein (AFP) test, but it is so unreliable that current guidelines says that an ultrasound must be used with it.
You might think with so much stacked against early detection of liver cancer, why bother? Because we owe it to ourselves and our families and friends.
Even when faced with an imperfect healthcare system, we need to overcome our fears, find out our risk factors, and ask for screening even when our doctors fail to recommend it.
The study, Hepatitis-Associated Liver Cancer: Gaps and Opportunities to Improve Care, was written by experts from the Hepatitis B Foundation and its Baruch S. Blumberg Institute, the Alaska Native Tribal Health Consortium’s Liver Disease and Hepatitis Program, Drexel University’s School of Public Health, the Fox Chase Cancer Center, and the University of Toronto.
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When we have chronic hepatitis B, knowing our family medical history can give us an inside edge to fight this infection.
Hepatitis B is an infection that often runs in families, and knowing how our parents or grandparents handled this liver disease can give us insider information about our own genetic prospects with hepatitis B.
The American Association for the Study of Liver Disease (AASLD), the organization that defines how doctors should treat hepatitis B and other liver ailments, unveiled new hepatitis B treatment guidelines this week at its annual conference in San Francisco.
