The Double Whammy: Febrile Neutropenia and a Hidden Virus in Cancer Treatment

Hey There, Let’s Talk About the Tough Stuff

Dealing with cancer is incredibly challenging, and the treatments, while necessary, can bring their own set of hurdles. We often talk about chemotherapy and its side effects, and one of the big ones we always watch out for is something called febrile neutropenia (FN). It sounds complicated, but basically, it means your white blood cell count, specifically neutrophils, drops really low because of the chemo, and you get a fever. It’s a serious situation because those neutrophils are your body’s little soldiers fighting off infection, and when they’re down, you’re really vulnerable.

FN is an emergency, no doubt about it. If we don’t jump on it fast with antibiotics, things can go south quickly – we’re talking sepsis, longer hospital stays, and even worse outcomes. It happens because chemo drugs are tough; they can’t always tell the difference between fast-growing cancer cells and other fast-growing cells, like those in your bone marrow that make white blood cells. So, the count drops, and a fever might be the only sign that an infection is brewing because your body can’t mount a full inflammatory response.

Standard practice? Hit it hard and fast with broad-spectrum antibiotics, especially for high-risk patients where the low count might stick around for a while. But sometimes, even when we do everything right for the FN, other unexpected guests show up.

The Patient’s Journey Begins

Let me tell you about a specific case that really highlights this. We had a 46-year-old gentleman diagnosed with rectal cancer. Not only was the primary tumor there, but the cancer had already spread to his liver and lungs – what we call synchronous metastasis. This meant he needed pretty aggressive treatment.

He started on a regimen of chemotherapy and targeted therapy – a combination called FOLFOXIRI plus bevacizumab. He went through ten cycles, and initially, things seemed to be going reasonably well, with signs that the treatment was working on the primary tumor.

The First Hurdle: Febrile Neutropenia Strikes

After those ten cycles, routine blood tests showed a significant problem: grade 4 bone marrow suppression. That’s the most severe level, meaning his blood cell counts were critically low. This sent him straight to the hospital.

Just two days after getting admitted, the expected happened: he developed a high fever, peaking at 39.5 °C. With his neutrophil count already low (below the threshold for neutropenia), the diagnosis was clear: chemotherapy-induced febrile neutropenia. We immediately started him on empirical broad-spectrum antibiotics, which is the absolute must-do in this situation to prevent serious infection from taking hold.

We also gave him medications to help his bone marrow recover and provided nutritional support. We were doing everything by the book to manage the FN and support his body.

A Lingering Mystery: Liver Troubles Appear

Here’s where the story takes a bit of a turn. Even as his white blood cell counts started to recover, the fever didn’t completely disappear. More concerningly, his liver enzyme levels – the aminotransferases and bilirubin – which were already a bit elevated on admission, continued to climb significantly. This was puzzling.

We were tracking potential sources of infection. Sputum cultures showed a resistant bacteria, but blood cultures were negative. CT scans showed some minor issues like gallbladder stones and a small amount of fluid, but nothing that screamed “this is causing severe liver damage and persistent fever.” We even checked for bile duct blockages, which can cause bilirubin to rise, but imaging confirmed there was no obstruction.

So, we had a patient who was immunocompromised from chemo, had FN that was starting to resolve on paper, but still had fever and worsening liver numbers that didn’t quite fit the picture of a typical bacterial infection or even just drug-induced liver injury (DILI), which is a common suspect with chemotherapy.

Unmasking the Culprit: Hepatitis E Enters the Scene

When you’re dealing with an immunocompromised patient and you’ve ruled out the usual suspects for fever and liver problems, you have to start thinking outside the box. Elevated liver enzymes in someone on chemo could be DILI, sure, but it could also be infections that a healthy person might shrug off, but hit hard when your immune system is down.

Because the liver numbers kept climbing and the fever persisted without a clear bacterial source, we decided to look deeper. We sent blood samples for next-generation sequencing (NGS), a fancy test that can identify genetic material from all sorts of pathogens.

And guess what? About two weeks after he was admitted, the NGS results came back suggesting Hepatitis E virus (HEV). We confirmed this with a standard blood test looking for HEV IgM antibodies, which signal a recent infection. Turns out, there was a sneaky little virus hiding in the background, complicating everything.

HEV is a virus that often causes a mild, self-limiting illness in healthy people, sometimes without even causing jaundice. But in folks with weakened immune systems, like those undergoing chemotherapy, it can behave very differently. It can cause more severe or prolonged hepatitis, and its symptoms, like elevated liver enzymes and sometimes fever, can easily be mistaken for other issues, including DILI. This case really hammered home the point: when you see liver problems in an immunocompromised patient, especially if DILI is suspected, you must consider and rule out HEV infection.

The clinical picture aligned with severe hepatitis, and his bilirubin levels were high enough to indicate liver failure was a concern.

The Road to Recovery and Beyond

Once HEV was diagnosed, the focus shifted. For acute HEV infection, especially in immunocompromised patients, the treatment is primarily supportive. Unlike some other viruses, HEV often clears on its own, even in this group, though it can take longer. Ribavirin is an option for severe or persistent cases, but often, supporting the patient through the acute phase is key.

Thankfully, after the diagnosis and continued supportive care, his condition began to improve. His body temperature returned to normal within a couple of days of the HEV diagnosis becoming clear, and his liver enzyme levels started their slow descent back towards normal. His bilirubin peaked a few days later but then also began to normalize.

He was discharged after a 30-day hospitalization, in a stable condition. We followed up a month later, and his liver function tests were back within the normal range. This was a great relief, as it meant the acute HEV infection had resolved.

Of course, the cancer treatment needed to continue. He resumed chemotherapy once his liver function recovered. Over the next several months, he underwent surgeries to remove the primary rectal tumor and most of the lung metastases. The liver lesions also largely regressed with continued treatment. He’s now been on treatment for over 14 months and is in a state of “near no evidence of disease,” receiving maintenance therapy.

What We Learned From This Case

This patient’s journey is a powerful reminder for anyone involved in cancer care:

• Febrile Neutropenia is serious: Always treat FN as an emergency and start empirical broad-spectrum antibiotics immediately.
• Think beyond the obvious: In immunocompromised patients, especially those with complex presentations like persistent fever and liver issues after initial FN management, don’t stop looking for causes.
• HEV is a sneaky culprit: Hepatitis E infection can mimic other conditions, particularly drug-induced liver injury (DILI), in patients with weakened immune systems.
• Test for HEV: If an immunocompromised patient on chemotherapy develops elevated liver enzymes, especially with predominant aminotransferase elevation, make sure to test for HEV infection. NGS or specific antibody tests are crucial diagnostic tools.
• Supportive care is vital: Early diagnosis and comprehensive supportive treatment are key to managing acute HEV in this vulnerable population, improving outcomes and reducing the duration of illness.

It just goes to show that even when you’re focused on fighting a big battle like cancer, you have to be vigilant for unexpected challenges, like a quiet virus that can cause significant problems when the body’s defenses are down. This case highlights the importance of a broad differential diagnosis and using advanced tools like NGS when the clinical picture is unclear.

Source: Springer