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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.

Got HBV? What is Your Skin Trying to Tell You?

The liver is the largest solid organ in the body, and your skin is the largest organ.  It only makes sense that the skin may be a window into what is going on inside your body and your liver.  The problem is trying to figure out what your skin is trying to tell you!

The most common skin manifestation associated with “hepatitis” is the yellowing of the skin (jaundice) and the sclera, or white part of the eye.  Jaundice  may be associated with a newly acquired or acute hepatitis B infection.  It certainly gets your attention and gets you to the door of your doctor, which is a good thing.  However, keep in mind that HBV is often asymptomatic, with few or no obvious symptoms, and jaundice is a more severe symptom of an acute HBV infection. Jaundice may also occur in those with advanced liver disease, and a decompensated liver. Jaundice is due to an accumulation of bilirubin, a yellow pigment, in the blood and tissues.  Your liver is responsible for controlling the levels of bilirubin.  If your liver is having problems performing basic, yet essential functions, yellow skin, eyes, dark urine, and itching (pruritus) may all be due to an inability to filter excess bilirubin.  Please see your doctor immediately if you experience jaundice of the skin or eyes.

It is also not uncommon for those with more advanced liver disease such as cirrhosis to have palmar erythema, which presents like red palms –especially around the base of the thumb and little finger.  Keep in mind that there may be other reasons for experiencing red palms, such as high blood pressure, pregnancy, or elevated estrogen levels. Talk to your doctor if you have concerns.

Spider nevi or spider angioma are another indicator of more serious liver disease. These are not to be confused with spider veins. It is also important to note that 10-15% of healthy adults and children have spider nevi, with no underlying disease. They range in size from 0.5 to 1 cm in diameter, with a dark center, radiating out to fine, red lines. When the center is depressed with the finger, the radiating lines disappear, and then re-appear, when the finger is lifted. Spider nevi may be caused by an increased level of estrogen in the body.  Naturally these may also appear during pregnancy, and in women using oral contraceptives. Following pregnancy and the discontinuation of contraceptives, the spider angiomas will disappear on their own. Like so many basic, but essential functions, the liver is responsible for breaking down and removing excess estrogen. Spider nevi associated with liver disease tend to be large in number and appear on the upper part of the body, face, and neck – especially on the backs of the hands and arms. Once again, it is a good idea to point out these out to your doctor.

Gianotti-Crosti Syndrome is a rash associated with HBV and EBV (Epstein Barr Virus). This rash almost always occurs in children, with 90% of kids under the age of four. The rash may last from two to eight weeks. Basically, it’s just a response to a virus, and nothing to worry about – just an indicator. Kids often have a rash for one reason or another.  If the rash is excessively itchy, talk to your pediatrician about using a topical steroid. Every parent of a child with HBV is convinced their child has some sort of HBV associated rash. (Speaking from experience…) Even the pediatric liver specialist was unsure, so she got a consult with a pediatric dermatologist.  The rash was unrelated to HBV.

Wondering about your finger nails?  There’s a condition called Terry’s Nails which is present in many of those with cirrhosis. The nail appears mostly white, similar to the appearance of “ground glass”, and possibly with a little pink strip at the top of the nail bed.  This is due to a decrease in blood flow to the nail bed and an increase in connective tissue.  Remember that your doctor will not be able to see any of this if you wear nail polish to your appointment.

How about your basic rash that is associated with hepatitis B?  Rashes are most often associated with acute hepatitis B infections, although a recurring rash may occur in those chronically infected.  Talk to people living with HBV and they’ll tell you they have occasional rashes and annoying itching, even if their doctor may tell them they do not.  Could be totally unrelated, or it could be erythematous papular lesions, or palpable purpura.  In other words, your basic red or purplish, raised, bumpy rash. It’s not easy to find specific information linking your basic rash to HBV, but when you consider how the skin is a window to your general health, it makes sense that you may see skin manifestations that reflect your immune system response to your HBV infection as it cycles through various stages, phases and flares.

If you are living with HBV, you know the importance of monitoring your HBV status and your liver health.  Annual, bi-annual, or the schedule recommended to you by your liver specialist, will keep you on top of what is going on with your HBV and any associated liver disease.  However, it is good to take notice of any changes in the skin and nails as the liver is a non-complaining organ.  Sometimes we have to look for evidence that something is going on. That being said, I feel the need to rush to a mirror and check myself out after having researched and written this blog.  The skin may be a window to our general health, but it is not always easy to figure out what it’s trying to tell us. If you have any questions, don’t try to self-diagnose. Talk to your doctor and bring any of your concerns to his attention.

Living With HBV and Drinking Coffee

The pros and cons of drinking coffee have been wildly debated for years.  However, for those with Hepatitis B and other liver diseases, the addition of a couple of cups of coffee per day to slow down the progression of liver disease, along with decreasing the risk of diabetes and heart disease just makes sense.

Dr. Melissa Palmer was a guest speaker at a previous Hepatitis B Foundation patient conference. The information from her presentation had all sorts of nutritional nuggets for those with HBV (Check out Dr. Palmer on podcast if you would like to have a listen!) She stated, based on studies, that coffee and caffeine intake has been associated with improvements in liver ALT and AST levels.  There also seems to be a correlation between increased coffee consumption and warding off cirrhosis and HCC.

Just recently there are was an article that discussed the benefits of coffee for those patients with HCV, undergoing treatment with pegylated interferon (PEG) and ribavirin therapy.  It claimed that drinking three or more cups of coffee a day not only reduced some of the difficult side-effects associated with treatment of PEG, but it also increased the treatment success.  However, like so many of these coffee studies, it was a small study and had to be adjusted for other factors.

We all know that HBV and HCV are very different viral infections, but you have to wonder if any of the benefits of coffee that is seen in those being treated for HCV can be extrapolated to include those with HBV being treated with Pegylated interferon or antivirals.  Dr. Palmer did mention that coffee did seem to have a greater impact on those with hepatitis C, although I have no idea why.

Regardless, if you’re living with HBV, you have to think about the pros and cons of adding coffee to your daily list.  Since all studies seem to show an increased number of cups of coffee having a more positive impact on preventing liver disease progression, or warding off cirrhosis or potentially reducing PEG side effects or benefiting treatment, you have to consider just how much caffeine you can take.  It does not appear that caffeine is the only factor involved, but rather the coffee bean itself and associated antioxidant features.  This seems to be the case because tea, despite all of its benefits, does not appear to have the same protective effect on the liver.

What about decaffeinated coffee?  I kept looking to see if it was specifically referenced, but I haven’t seen it. However, during the decaffeinating process, much of the bean is lost, and it may be treated with a chemical solvent, both which might nix the positive benefits.  If you’re going to give decaffeinated coffee a try, consider a coffee with a more natural decaffeinating process. Personally, I’d have a tough time balancing the jitters and racing heart rate associated with drinking more than a cup or two of high-test coffee a day, but we’re all individuals.  If you can drink coffee and sleep well at night, it seems like it can’t hurt your liver health to add a few cups to your daily regimen.