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Reactivation with Hepatitis B: Understanding Risk Factors and Prevention Strategies

Understanding the hepatitis B virus and the panel of blood tests needed to determine infection or immunity can be a stressful and challenging task. In simplest terms, “hepatitis” means liver inflammation and the hepatitis B virus can ultimately cause liver inflammation. The liver is an important organ in the human body and responsible for the removal of toxins and regulation of digestion (learn more about the function of the liver here). The hepatitis B virus can infect and disrupt critical functions of the liver in supporting your overall health. 

How the hepatitis B virus works 

In the case of the hepatitis B virus, the host is the liver cell. As the virus makes more copies of itself, the liver may become damaged, and sometimes it is unable to carry out its essential tasks to regulate metabolism, nutrients, and digestion. It is best to prevent hepatitis B infections when we can – and since antibodies are the best defense against the virus, the hepatitis B vaccine can be used to signals the body to make antibodies to fight the virus. The hepatitis B vaccine provides lifelong protection from the virus. However, this is only possible before infection with the virus. If somebody is already infected with the virus, antiviral therapy is used to control the virus and prevent liver damage – antiviral medications disrupt the life cycle of the virus by disabling viral receptors from binding to liver cells. 

Blood test panel to diagnose hepatitis B: 

The only way to tell someone’s hepatitis B status is through a panel of blood tests – the tests are all done at one time, and only one small tube of blood is needed. These tests are not included in routine testing, so it is important to ask your doctor to test you for hepatitis B or try to find a free screening event near you (http://www.hepbunited.org/). The panel consists of the following tests to determine your hepatitis B status: 

  1. HBsAg: 
    • This tests for the hepatitis B surface antigen in someone’s blood. The surface antigen is the protein that surrounds the virus and protects it from attack by the host. A positive surface antigen test indicates that the virus is present in the body. A “positive” or “reactive” result for HBsAg indicates that someone is infected with hepatitis B and can transmit the virus to others.  
  1. HBsAb 
    • This tests for the hepatitis B surface antibody in someone’s blood. The surface antibodies are produced by the immune system and can fight off the virus by attaching to the surface antigen protein. This test can detect the presence of these antibodies. Ideally this test will be ordered quantitatively (numerically). A “positive” surface antibody test (meaning numbers reading >10 IU/mL) means that a person has protection against the hepatitis B virus (either by vaccine or from a past exposure).  
  1. HBcAb (total) 
    • This is known as the hepatitis B core antibody test. The core antibody is produced by the immune system after infection with the virus. This test indicates an existing or past infection of the hepatitis B virus.  

 

To learn more about interpreting your test results, click here. 

Important things to know about Hepatitis B Core Antibody (HBcAb) 

Someone who has markers of past infection, particularly hepatitis B core antibody, can be at risk for hepatitis B reactivation. Reactivation can be triggered by immunosuppressive therapies and cause significant life-threatening challenges. If you test HBcAb+, please talk to your doctor about what that means, and make sure you notify all future health care providers. 

How is reactivation with HBV defined? 

Reactivation is defined as the sudden increase or reappearance of HBV (hepatitis B virus) DNA. When the virus invades the cell, it forms a covalently closed circular DNA (cccDNA) in the nucleus of infected cells referred to as hepatocytes. Because cccDNA is resistant to antiviral treatments, it is never removed from the cells. Therefore, even after recovery from a past infection, the cccDNA is present and may reactivate. It is not clearly understood why this may happen, but certain factors may increase the risk for reactivation.  

To learn more about the core, click here. 

What puts one at risk for reactivation? 

  1. Virologic factors such as high baseline HBV DNA, hepatitis B envelope antigen positivity (HBeAg), and chronic hepatitis B infection that persists for more than 6 months.
    • Detectable HBV DNA levels and detectable levels of HBsAG can increase the risk for HBRr (reactivation) 
    • Testing positive for HBeAg also increases the risk for reactivation 
  2. Co-infection with other viruses such as hepatitis C or hepatitis Delta 
  3. Older age 
  4. Male sex 
  5. Cirrhosis 
  6. An underlying condition requiring immunosuppressive therapies (rheumatoid arthritis, lymphoma, or solid tumors) 
    • Certain medications can increase the likelihood of reactivation by more than 10%.  
    • B-cell depleting agents such as rituximab, ofatumumab, doxorubicin, epirubicin, moderate or high-dose corticosteroid therapy lasting more than 4 weeks. 

How to prevent reactivation of hepatitis B 

Hepatitis B reactivation is a serious condition that can lead to health complications, Reactivation is avoidable if at-risk individuals are identified through screening. Current guidelines recommend that individuals at the highest risk (those receiving B-cell depleting therapies and cytotoxic regimens) should receive antiviral therapies as prophylaxis before beginning immunosuppressive therapy. These antiviral therapies should also be continued well beyond stopping the immunosuppressive therapies. Be sure to talk to your doctor to be sure you are not at risk for reactivation.  

References 

Hepatitis b virus reactivation: Risk factors and current management strategies.

Reactivation of hepatitis B virus: A review of Clinical Guidelines.

https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/cld.883

https://www.hepb.org/prevention-and-diagnosis/diagnosis/understanding-your-test-results/

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

Learn Which Cancer, Arthritis or Asthma Drugs Can Reactivate Hepatitis B – Even If You’ve Cleared the Infection

Courtesy of Pixabay.
Courtesy of Pixabay.

By Christine Kukka

Drugs that suppress your immune system in order to treat cancers, rheumatoid arthritis, psoriasis, COPD and asthma can cause a life-threatening reactivation of your hepatitis B.

This dangerous viral rebound can occur if you are currently infected or even if you cleared the infection and now test negative for the hepatitis B surface antigen (HBsAg) and positive for the surface antibody (HBsAb).

These drugs weaken the immune system, which allows your infection to rebound with a vengeance, spiking your viral load and causing life-threatening liver damage within weeks of starting chemotherapy or high-dose steroids.

What’s behind this reactivation risk? Think herpes or chicken pox (shingles). You might get rid of the infections and the ugly blisters, but small amounts of virus remain and as we age and our immune systems weaken, they can reappear.

The hepatitis B virus (HBV) behaves similarly. When we lose HBsAg and/or develop surface antibodies, there are still small amounts of HBV lurking in our bodies. When we’re healthy, our immune systems effectively contain these trace amounts of virus, but old age, another serious medical condition or immune-suppressing drugs allow hepatitis B to reactivate.

Today, medical guidelines require doctors to test everyone they plan to treat with any immune-suppressing drugs for the hepatitis B core antibody (HBcAb) so they know who has been infected with hepatitis B. If a patient tests positive, doctors must run more tests to determine what risk the new drug will pose. When a patient is at risk of reactivation, doctors will simultaneously treat them with antivirals (either tenofovir or entecavir) and continue antiviral treatment for six more months after the immune-suppressing therapy ends to prevent reactivation.

U.S. CDC.
U.S. CDC.

This mandatory testing is important because some people don’t know they should tell their doctors about their past infection, and many don’t know they’re infected. Here is what happened to one person who contacted the Hepatitis B Foundation after her doctor failed to test her for hepatitis B:

“I recently had my first dose of chemotherapy and I did not mention (to) my oncologist that I was a carrier of hepatitis B, (because) I knew that it was not active. Then, after a week of chemo, I was really sick and got a high temperature. Then, my blood test came back (indicating) that my hepatitis B was reactivated. My liver doctor gave me medicine (an antiviral) to take to deactivate the virus.”

Her oncologist immediately stopped chemotherapy and monitored her HBV DNA (viral load) and liver enzymes (ALT/SGPT) to make sure the antiviral lowered her viral load before restarting chemotherapy. This example shows why it’s important to tell all doctors, including specialists, about a current or resolved hepatitis B infection. No one wants to be battling cancer and a reactivated hepatitis B infection at the same time.

According to experts, about 4.3 percent of people who have cleared hepatitis B will experience a reactivation when treated with immune-suppressing drugs.

Which drugs reactivate hepatitis B? Below is a summary of drugs that can reactivate your hepatitis B and require monitoring and preventive use of antivirals to reduce reactivation risk, according to American Gastroenterological Association (AGA) guidelines:

High-risk Drugs:

More than 10 percent of people with current or resolved hepatitis B infections will experience a dangerous reactivation if treated with:

  • Rituximab for non-Hodgkins lymphoma, or
  • Ofatumumab for chronic lymphocytic leukemia

Anyone with a current infection (HBsAg positive) treated with the following is also at high risk of reactivation:

  • Anthracycline derivatives (such as doxorubicin, epirubicin) used to treat cancers, including breast or bladder cancer, Kaposi’s sarcoma, lymphoma or acute lymphocytic leukemia, or,
  • Moderate-doses of prednisone/corticosteroids (10 to 20 mg daily) or high doses (more than 20 mg daily or equivalent) for four or more weeks. This steroid is used to treat inflammatory diseases including asthma, COPD, rheumatic disorders, ulcerative colitis, Crohn’s disease, MS, tuberculosis, shingles side effects, lupus, poison oak and tuberculosis among others.

Moderate-risk Drugs:

 Anyone with a resolved or current infection treated with the following drugs is at moderate risk of reactivation:

  • Tumor necrosis factor alpha inhibitors, such as etanercept, adalimumab, certolizumab, infliximab, for arthritis, inflammatory bowel disease, psoriasis and asthma;
  • Other cytokine or integrin inhibitors (such as abatacept, ustekinumab, natalizumab, vedolizumab), or
  • Tyrosine kinase inhibitors (such as imatinib, nilotinib)

 Also with a current infection treated is at moderate risk if treated with:

  • Low-dose (less than 10 mg prednisone daily or equivalent) corticosteroids for four or more weeks.

Also, anyone with a resolved infection treated with:

  • Moderate-dose (10—20 mg prednisone daily or equivalent) or high-dose (more than 20 mg prednisone daily or equivalent), or
  • Corticosteroids daily for four or more weeks, or anyone treated with anthracycline derivatives (eg, doxorubicin, epirubicin).

Low-risk Drugs:

Drugs that reactivate hepatitis B in fewer than 1 percent of patients include:

Current or previously-infected people treated with:

  • Traditional immunosuppressive drugs such as azathioprine, 6-mercaptopurine or methotrexate, or
  • Intra-articular corticosteroids
  • Any dose of oral corticosteroids daily for a week or less.

Previously-infected patients treated with:

  • Low-dose (less than 10 mg prednisone or equivalent) corticosteroids for four weeks or longer.

To see the entire list of immune-suppressing drugs, read the AGA guidelines.

Hepatitis B reactivation following successful hepatitis C treatment: New antivirals (such as Harvoni), used to cure hepatitis C do not suppress the immune system, but they leave coinfected people at risk of HBV reactivation once the dominant hepatitis C virus disappears. Coinfected patients need to be monitored carefully and treated with antivirals if their HBV rebounds.

Baruch S. Blumberg Institute