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

Every year, thousands of people undergoing cancer treatment or taking powerful immune drugs for autoimmune diseases face a hidden threat: their own dormant hepatitis B virus waking up and attacking their liver. This isn’t rare. It’s predictable. And it’s preventable - if you know what to look for.

What Exactly Is HBV Reactivation?

HBV reactivation happens when a virus that’s been sleeping in your liver for years suddenly starts multiplying again. This isn’t a new infection. It’s the same virus you’ve carried since childhood - maybe without ever knowing it. People with past or chronic hepatitis B infection often show no symptoms. But when their immune system gets shut down by chemotherapy, biologics, or steroids, the virus takes advantage.

The result? A sudden spike in liver enzymes, jaundice, severe fatigue, and sometimes liver failure. In the worst cases, it’s fatal. Studies show 5-10% of people who experience full-blown reactivation die from it. That’s not a side effect. That’s a preventable medical emergency.

Who’s at Risk? It’s Not Just What You Think

Not everyone with hepatitis B is at equal risk. Your danger level depends on two key blood tests: HBsAg and anti-HBc.

• HBsAg-positive: You have active, chronic hepatitis B. Your risk of reactivation is 20% to 81%, depending on the drug. If you’re getting rituximab for lymphoma? Your risk jumps to nearly 70%.
• HBsAg-negative, anti-HBc-positive: You cleared the virus years ago. Your body still carries traces. This group is often overlooked. But if you’re on high-dose chemo or a stem cell transplant, your reactivation risk is still 1% to 18%. In some cases, it’s higher than people think.
• Both negative: You’ve never had HBV. No risk. No screening needed.

Here’s the catch: many people don’t know their status. In countries with low HBV rates, doctors assume it’s rare. But in the U.S., 1 in 12 Asian Americans, 1 in 20 African immigrants, and 1 in 50 overall have past or chronic infection. Screening isn’t optional - it’s essential.

Which Drugs Are Most Dangerous?

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

High-risk drugs (reactivation risk >10%):

• Rituximab, ofatumumab (anti-CD20 biologics): Used for lymphoma, rheumatoid arthritis. Reactivation risk: 38-73% in HBsAg-positive patients.
• Anthracycline chemo (like doxorubicin): Common in breast cancer and lymphoma. Risk: 25-40%.
• Stem cell transplants: Autologous? 66% risk. Allogeneic? 81% risk. Most reactivations happen in the first year.
• Transarterial chemoembolization (TACE): Used for liver cancer. Reactivation risk: 17-34% - higher than most assume.
• Checkpoint inhibitors (like pembrolizumab): Newer cancer immunotherapies. Risk: 21% in HBsAg-positive patients not on antivirals.

Medium-risk drugs (1-10%):

• Standard chemo without steroids
• TNF-alpha inhibitors (like adalimumab for arthritis)
• Ibrutinib (for leukemia and lymphoma)

Low-risk drugs (<1%):

• Non-TNF biologics (like abatacept)
• Most targeted therapies (like imatinib)
• Low-dose steroids

Don’t assume low risk just because it’s not chemo. Even drugs for arthritis can wake up your virus.

How to Prevent It: Screening and Prophylaxis

The fix is simple: screen everyone before starting immunosuppressive therapy. That means two blood tests - HBsAg and anti-HBc - done at least two weeks before treatment begins.

If you’re HBsAg-positive, you need antiviral prophylaxis. Start it at least one week before your first dose of chemo or biologic. The two most effective drugs are:

• Tenofovir (Viread, Tenvir)
• Entecavir (Baraclude)

These drugs suppress the virus so well that reactivation drops from nearly 50% to under 5%. One study of 1,245 patients found that those on prophylaxis had only a 3.2% reactivation rate. Those without it? 48.7%.

How long do you stay on it? For high-risk drugs like rituximab or stem cell transplants, continue for 6 to 12 months after treatment ends. For checkpoint inhibitors, 6 months may be enough - new data suggests you don’t always need a full year.

For HBsAg-negative, anti-HBc-positive patients? Guidelines are less clear. Some experts recommend prophylaxis only for very high-risk therapies like stem cell transplants. Others suggest it for all. The safest approach? Talk to a liver specialist.

Why Do So Many People Still Get Hurt?

Here’s the uncomfortable truth: most cases of HBV reactivation are avoidable. But they keep happening.

A 2020 survey found only 58% of community oncologists follow screening guidelines. In academic centers? 89%. That gap isn’t about knowledge - it’s about systems. One patient in a case report died after rituximab because no one checked his HBV status. He was 52. He had no symptoms before. He had no warning.

Why does this happen?

• Doctors assume HBV is rare in their patient population.
• Screening isn’t built into the electronic health record.
• Patients are seen by multiple specialists - no one takes responsibility.
• There’s a false belief that if the patient “feels fine,” they’re not at risk.

At UCSF, they fixed this by adding automatic alerts in their EHR. If a patient is flagged for chemo or biologics, the system pops up: “HBV screening required.” Result? Reactivation rates dropped from 12.3% to 1.7% in just five years.

What About the Cost? Is Screening Worth It?

Some argue screening is overkill, especially in low-prevalence areas. But the math doesn’t lie.

Screening costs about $20-$40 per person. Treating a single case of severe reactivation? $50,000 to $150,000. Add ICU stays, liver transplants, lost work time - and the real cost is higher.

Dr. Anna S. Lok, a leading hepatologist, calls antiviral prophylaxis “one of the most cost-effective interventions in modern medicine.” The number needed to treat to prevent one reactivation? Just three. That means for every three people screened and treated, you prevent one life-threatening event.

And the legal risk? In malpractice claims, HBV reactivation makes up 12% of infectious complications in oncology. Hospitals are getting sued for this. It’s not a question of if - it’s a question of when.

What’s Next? The Future of Prevention

Technology is catching up. In late 2023, the FDA is expected to approve the OraQuick HBV rapid test - a finger-prick test that gives results in 20 minutes. Imagine screening in a clinic, not a lab.

Companies like Tempus Labs are now integrating HBV status into genomic cancer profiles. If you’re getting a tumor DNA test, your HBV status comes with it. That’s precision medicine in action.

But tech won’t fix this alone. The real solution is culture change. Every oncologist, rheumatologist, and surgeon needs to treat HBV screening like a pre-op blood test - non-negotiable, automatic, routine.

The tools are here. The guidelines are clear. The evidence is overwhelming. The only thing missing is consistent action.

What Should You Do?

If you’re about to start chemotherapy, a biologic, or any immune-suppressing treatment:

1. Ask your doctor: “Have you checked my HBV status?”
2. If they say no - insist. Request HBsAg and anti-HBc tests.
3. If you test positive for HBsAg, ask for tenofovir or entecavir before treatment starts.
4. If you’re anti-HBc-positive, ask if you need prophylaxis based on your treatment.
5. Don’t stop antivirals early. Follow your doctor’s timeline - even if you feel fine.

If you’re a healthcare provider:

1. Make HBV screening part of your pre-treatment checklist.
2. Use your EHR to build automated alerts.
3. Refer anti-HBc-positive patients to hepatology if they’re on high-risk therapy.
4. Don’t wait for a tragedy to change your practice.

HBV reactivation isn’t a mystery. It’s a missed opportunity. And every case that happens today is one that could have been stopped yesterday.