HBV Reactivation: How Biologics and Chemotherapy Trigger Liver Danger - And How to Prevent It

12 Jan 2026 | Health | by Brian Halstead

When you're undergoing treatment for cancer or an autoimmune disease, the last thing you think about is your liver. But if you’ve ever had hepatitis B - even if you didn’t know it - your treatment could trigger a silent, life-threatening explosion in your liver. This is HBV reactivation, and it’s more common than most doctors and patients realize.

What Exactly Is HBV Reactivation?

Hepatitis B virus (HBV) can hide in your body for years after an infection, even if you feel fine and your liver tests look normal. It’s not active. It’s dormant. But when powerful drugs like chemotherapy or biologics weaken your immune system, that virus wakes up. It starts multiplying again. Your liver gets attacked. Your ALT and AST levels spike. You develop jaundice. You could go into liver failure - or die.

This isn’t rare. In people who are HBsAg-positive (meaning they still carry the virus), reactivation rates can hit 73% with drugs like rituximab. Even in those who cleared the virus long ago (HBsAg-negative but anti-HBc-positive), the risk isn’t zero. For some treatments, it’s 18%.

The process happens in three stages. First, the immune system gets suppressed - the virus starts copying itself. Then, the immune system tries to fight back, causing massive liver inflammation. Finally, the inflammation fades - but by then, the damage may already be irreversible.

Which Treatments Are Most Dangerous?

Not all immunosuppressive drugs are created equal. Some are like lighting a match near gasoline. Others are barely a spark.

• High-risk (38-81% reactivation): Anti-CD20 drugs like rituximab and ofatumumab. These wipe out B-cells, which are critical for keeping HBV in check. In lymphoma patients, up to 73% reactivate without prophylaxis. Stem cell transplants - especially allogeneic - carry an 81% risk. Anthracycline chemotherapy (used for breast cancer and lymphomas) also tops the danger list.
• Intermediate-risk (1-10% reactivation): Conventional chemo without steroids (20-50% in carriers), TNF-alpha inhibitors like infliximab (3-8%), and tyrosine kinase inhibitors like ibrutinib. Even TACE, a procedure for liver cancer, has a 17-34% reactivation rate - far higher than most assume.
• Low-risk (<1%): Most non-TNF biologics and targeted therapies like hormone blockers or PARP inhibitors.

But here’s the twist: checkpoint inhibitors - newer cancer drugs like pembrolizumab - are a wildcard. In HBsAg-positive patients not on antivirals, 21% reactivated. These drugs don’t suppress immunity - they rev it up. That means reactivation can look like drug-induced hepatitis. Mistake the two, and you give steroids instead of antivirals. That’s deadly.

Who’s at Risk? The Hidden Carriers

Most people who reactivate HBV never knew they were infected. That’s the problem.

In high-prevalence areas like Asia or sub-Saharan Africa, HBV is common. But even in the UK, where prevalence is under 0.5%, there are tens of thousands of silent carriers. They’re the ones who tested positive for anti-HBc (a marker of past infection) but never got tested for HBsAg. They think they’re safe. They’re not.

Studies show:

• HBsAg-positive patients: 20-81% risk of reactivation, depending on the drug.
• HBsAg-negative / anti-HBc-positive patients: 1-18% risk. Higher with high-dose chemo or stem cell transplants.
• Patients with resolved HBV: 3% risk with standard chemo, but up to 18% with intense regimens.

The bottom line? If you’ve ever had hepatitis B - even decades ago - you’re at risk. And if you’re from a region where HBV is common, your risk is higher even if you think you’re clean.

Screening: The One Thing That Saves Lives

The fix is simple: screen everyone before starting immunosuppressive therapy.

You need two blood tests:

• HBsAg - tells you if the virus is currently active.
• anti-HBc - tells you if you’ve ever been infected.

If HBsAg is positive, you’re at high risk. Start antivirals before treatment. If HBsAg is negative but anti-HBc is positive, you’re at lower but real risk. For high-intensity therapies, you still need prophylaxis. For low-risk treatments, monitor closely.

The American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) both say: screen everyone. No exceptions. The cost of testing is less than $20. The cost of a reactivation episode? Up to $150,000 in hospital bills. And some patients don’t survive.

A 2018 study of 1,245 patients found that those on prophylaxis had only a 3.2% reactivation rate. Those without? 48.7%. That’s a 93% reduction.

Prophylaxis: What Drugs Work?

Two antivirals are the gold standard: tenofovir and entecavir.

• Start them at least one week before immunosuppression begins.
• Keep them going for at least 6-12 months after treatment ends. For high-risk drugs like rituximab or stem cell transplants, go for 12 months. For others, 6 months is often enough.

Lamivudine used to be common. But resistance is high. It’s outdated. Tenofovir and entecavir are more powerful, have no resistance in most cases, and are safe for long-term use.

The biggest mistake? Waiting until liver enzymes rise. By then, it’s too late. Prophylaxis is preventive. It’s not a rescue.

Why Isn’t Everyone Getting Screened?

You’d think this would be routine by now. But it’s not.

A 2020 survey found only 58% of community oncologists follow screening guidelines. In academic centers? 89%. Why the gap?

• Doctors don’t know the guidelines.
• They assume patients are low-risk because they’re from the UK.
• There’s no automated alert in the electronic health record.
• Patients are seen by multiple specialists - no one takes responsibility.

A case report from 2019 tells the story: a 52-year-old man with lymphoma got rituximab. Never screened. Died of liver failure two weeks later. His family sued. The hospital settled. He didn’t need to die.

Some institutions have fixed this. UCSF added automated EHR alerts. If a patient is scheduled for chemo and hasn’t been screened, the system blocks the order until testing is done. Reactivation rates dropped from 12.3% to 1.7% in five years.

The Future: Faster Tests, Smarter Systems

Point-of-care HBV tests are coming. The OraQuick HBV rapid test, expected to get FDA approval in late 2023, could give results in 20 minutes - right in the oncologist’s office. No waiting. No missed appointments.

Companies like Tempus Labs are now embedding HBV status into genomic cancer profiles. If you’re getting a tumor DNA test, your HBV status pops up too. No one slips through.

The biggest win? A 2022 study in the New England Journal of Medicine showed that six months of antiviral prophylaxis is enough for most patients. That cuts costs, reduces side effects, and makes compliance easier.

What You Should Do Now

If you’re about to start:

• Chemotherapy
• Biologics like rituximab, infliximab, or ibrutinib
• Stem cell transplant
• Checkpoint inhibitors
• TACE or other liver-directed cancer therapies

Ask your doctor: “Have I been screened for hepatitis B?” If they say no - insist. If they say yes - ask for the results. Don’t assume.

If you’re a clinician: Make screening mandatory. Build it into your workflow. Use alerts. Train your staff. This isn’t optional. It’s standard of care.

FAQ

What Happens If You Skip Screening?

You might get lucky. Or you might end up in the ICU.

HBV reactivation is one of the most preventable causes of liver death in modern medicine. It’s not a mystery. We know who’s at risk. We know how to test. We know how to treat. The only thing missing is consistent action.

This isn’t about complex science. It’s about basic care. Screen. Treat. Monitor. Repeat.

If you’re getting immunosuppressive therapy, don’t wait for your doctor to bring it up. Ask. Demand. Protect your liver. Your life depends on it.