A Lifesaving Drug or a "Poison"? A New Study Reveals Potential Viral Risks in the Treatment of Cystic Fibrosis Patients

Introduction

For patients with Cystic Fibrosis (CF), pancreatic enzyme replacement therapy (PERT), a drug made from porcine pancreatic extract, is crucial for maintaining their life and health. However, a recent study from the University of Calgary, Canada (published in "Gut" journal, ) dropped a bombshell: this widely used drug may be contaminated with Hepatitis E virus (HEV) and could lead to chronic hepatitis in CF patients who have undergone lung transplantation. This finding not only reveals a previously unknown route of infection but also poses a severe challenge to the drug safety of tens of thousands of patients worldwide who rely on such drugs.

Background: When a Rare Disease Meets an "Unusual" Virus

To understand the importance of this study, we first need to understand two key players: Cystic Fibrosis (CF) and Hepatitis E virus (HEV).

• Cystic Fibrosis (CF): This is the most common fatal genetic disease affecting Caucasians. It causes abnormally thick secretions (such as sweat, mucus) in multiple organs of the body (especially the lungs and digestive system), leading to recurrent lung infections and digestive problems. Approximately 90% of CF patients have "pancreatic insufficiency" and cannot secrete digestive enzymes normally to break down food. To absorb nutrients, they must take pancreatic enzyme replacement therapy (PERT) drugs for life. The active ingredients of these drugs are extracted from pig pancreases, and patients need to take a large number of capsules daily (the study median shows about 8760 capsules per person per year).

• Hepatitis E virus (HEV): This is a virus primarily transmitted through the fecal-oral route, often causing outbreaks due to contaminated water sources in areas with poor sanitation. However, in developed countries, HEV is mainly a "zoonotic disease," usually associated with consuming undercooked pork or wild game. For most people with healthy immune systems, HEV infection is usually an acute, self-limiting hepatitis that resolves quickly. But the story is completely different in immunocompromised individuals. Since its first discovery in organ transplant patients in 2008, doctors have gradually realized that for patients who need to take immunosuppressants long-term due to organ transplantation, HEV can "lurk" and cause chronic hepatitis, which can rapidly progress to cirrhosis and even liver failure, threatening life.

The starting point of this study was the unexpected discovery by researchers at their CF center of several cases of chronic hepatitis E in CF patients who had undergone lung transplantation. This raised their alarm: why was this rare infection concentrated in this particular patient population?

Key Findings: A Surprising "Bridge" Connecting Patients and Viruses

The research team launched a meticulous investigation, and their findings were shocking:

1. CF Patients Have a Significantly Higher Risk of HEV Infection: The study found that both transplanted and non-transplanted CF patients had an HEV seroprevalence (i.e., the proportion who had been infected with the virus) as high as approximately 20%, which is four times the Canadian national average and twice that of the population tested for HEV due to suspected liver disease in that province. This indicates that the CF patient population appears to face a higher risk of HEV exposure.

2. Chronic Infection Only Occurs in Transplant Patients: Although the risk of exposure was generally high, only CF patients who had undergone lung transplantation and were taking immunosuppressants (3 cases in total) developed chronic HEV infection. This confirms that immunosuppression is a key factor for HEV to transition from acute to chronic.

3. The "Culprit" Points Directly to the Lifesaving Drug PERT: The researchers put forward a bold hypothesis: since HEV is a porcine-derived virus, and the PERT capsules that CF patients take daily are also derived from pigs, could PERT be the source of infection? To verify this, they collected 11 different formulations of PERT capsules from all manufacturers in Canada from pharmacies and patients for testing. The results showed that up to 44% of the PERT capsules tested positive for Hepatitis E virus genetic material (RNA).

4. Genetic Sequencing Confirms the Link: More convincing evidence came from genetic sequencing. By comparing the genetic sequences of the virus in patients and in PERT capsules, researchers found that their sequences were highly similar and both homologous to HEV strains in local Canadian pig populations. This provides strong molecular biological evidence for the hypothesis that "PERT is the source of infection."

Research Methods (Brief)

Researchers screened all post-lung transplant CF patients (29 individuals) and some non-transplanted CF patients (83 individuals) at a regional CF center for HEV serology and viral RNA. They compared the infection rate of CF patients with that of the general population. A crucial step was that they independently purchased various commercially available PERT capsules and used precise molecular biological techniques (RT-qPCR and digital PCR) to detect the presence of HEV viral RNA, and performed phylogenetic analysis of positive samples with viral sequences from patients to trace the origin of the virus.

Limitations and Warnings

Although the findings of this study are significant, the authors also frankly admitted some limitations. Firstly, this was a study conducted at a single regional center, with a relatively small sample size. Secondly, although viral RNA was detected in PERT capsules, this does not equate to the definite presence of infectious live virus. Viral RNA may just be "fragments of dead virus." Therefore, it cannot be 100% confirmed that taking PERT will lead to HEV infection; although the link between the two is close, causality still needs further experimental confirmation.

Application Prospects and Future Directions

This study sounds an alarm for clinical practice and future scientific research:

• Implications for Clinical Practice: For patients receiving PERT treatment, especially those who are also immunocompromised (e.g., after organ transplantation), if unexplained liver function abnormalities occur, doctors should be highly vigilant about the possibility of HEV infection and conduct relevant tests.

• Challenges for Drug Safety: The study results strongly call for drug regulatory agencies and manufacturers to re-examine the production processes and safety standards of porcine-derived medical products (such as PERT). Is it necessary to introduce virus inactivation steps? How to ensure that these life-saving drugs themselves do not become new health threats? These are urgent problems to be solved.

• Driving Future Research: This study opens Pandora's box. Future research needs to cover a wider population of CF patients to confirm the generality of this phenomenon. At the same time, experiments must be conducted to verify whether HEV in PERT capsules is infectious and to determine the viral dose required for infection.

Summary

This groundbreaking work by Canadian scientists is the first to link a life-saving routine drug with a potentially fatal viral infection, particularly in the vulnerable population of cystic fibrosis patients. It acts as a "whistleblower," reminding us that we must re-evaluate the safety of animal-derived medical products, especially their use in immunocompromised patient populations. Although the conclusions still need to be strengthened by more research, this finding undoubtedly provides crucial clues for protecting patient safety and improving drug regulation, and may change the treatment and lives of tens of thousands of patients in the future.