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Why Won’t Doctors Treat Young Adults with High Viral Load and No Signs of Liver Damage?

Image courtesy of Graur Razvan Ionut at FreeDigitalPhotos.net.
Image courtesy of Graur Razvan Ionut at FreeDigitalPhotos.net.

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.

 

 

Diagnosed With Chronic Hepatitis B? What State – 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 HBV 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 HBV, 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, HBV 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 HBV infection). However, at the end of 4-6 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 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.

Once you have confirmed that you have chronic HBV, you need further testing to determine your HBeAg status. Those with chronic HBV are either HBeAg positive or negative. If you are HBeAg positive, you have a higher HBV viral load 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, but this trend seems to be changing even with children. (The idea is to prevent integration of the HBV cccDNA into the host DNA.) 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 immune clearance phase? Read more.