Hepatitis E virus infection linked to PERT in CF lung transplant
Transplant recipients in study showed chronic infection
Chronic infection with the hepatitis E virus (HEV) may be linked to pig-derived pancreatic enzyme replacement therapy (PERT) in people with cystic fibrosis (CF) who underwent lung transplants, a study found.
CF patients in general had disproportionately higher rates of antibodies against HEV, regardless of transplant status, and chronic HEV infection was found solely in CF transplant recipients.
The source of HEV appeared to be PERT, with almost half of PERT capsules testing positive for HEV genetic material.
“This study warrants a re-analysis of PERT safety as an agent with potential for zoonotic [animal sourced] infection risk — especially in profoundly immunosuppressed population, such as CF lung transplant recipients,” the scientists wrote.
The study, “Porcine-derived pancreatic enzyme replacement therapy may be linked to chronic hepatitis E virus infection in cystic fibrosis lung transplant recipients,” was published in Gut.
Chronic HEV infection rare
Chronic HEV infection, which causes hepatitis, or inflammation of the liver, is rare. That’s especially true in high-income countries, where exposure has been linked to the consumption of pork products. Among heavily immunosuppressed populations, HEV can cause chronic hepatitis that ultimately may progress to liver failure.
A team led by scientists at the University of Calgary identified three cases of chronic HEV infection in patients at their CF center. These were the second, third, and fourth cases of such an infection ever described in Canada.
The researchers sought to investigate the prevalence of HEV in a group of CF patients who had undergone lung transplants. “We hypothesised that this apparent cluster of HEV chronic disease observed in [CF patients] was the result of disproportionate HEV exposure risk,” they wrote.
All 29 CF transplanted patients were screened for antibodies against HEV (seropositivity), and six (20.7%) tested positive. Three (10.3%) also tested positive for HEV RNA, a sign of chronic HEV infection.
More than three years after transplant, the risk of HEV seropositivity was 2.5 times higher than less than three years post-transplant. Still, the type and amounts of transfused blood products (whole blood, platelets, plasma) did not differ between groups at the time of transplant. HEV seropositivity was also not associated with the amount of PERT used or other patient characteristics, including age and sex.
Among CF patients who didn’t undergo lung transplant, 16 of 83 (19.3%) tested positive for anti-HEV antibodies, but none was positive for HEV RNA, indicating the likelihood of HEV seropositivity was similar, regardless of transplant status.
Nearly all CF patients (92%), either transplanted or non-transplanted, were pancreatic insufficient, but the total number of PERT treatments did not differ based on transplant status.
Across non-CF populations investigated for hepatitis, 115 (10.7%) residents of Alberta, Canada, were seropositive for HEV. Thirteen (11.3%) were single-organ transplant recipients, with the most prevalent being liver followed by kidney. Despite CF patients at the clinic comprising only 0.0056% of Alberta’s population, all cases of chronic HEV hepatitis occurred in CF patients.
Overall, CF patients had a twofold higher seropositivity risk, which was four times higher than the Canadian average.
When PERT capsules containing digestive pancreatic enzymes typically derived from pigs were tested, almost half (44%) were positive for HEV RNA. The virus’s genetic material was detected in PERT samples from all four Health Canada-approved manufacturers, with rates ranging from 27% to 58%.
Population analysis of the viruses showed three different HEV strains in the three patients with chronic HEV. CF-associated chronic HEV cases and PERT analysis showed RNA sequences similar to Canadian swine strains and other Canadian human HEV RNA sequences, “suggesting a potential iatrogenic mechanism of infection,” the researchers noted. An iatrogenic infection disease results from diagnostic and therapeutic procedures.
“Here, we describe the first cases series of chronic HEV infection identified in Alberta (and Canada) — all in [CF patients] post-transplant,” the scientists concluded. “Screening for HEV infections in [CF patients] post-transplant and establishing the seroprevalence of HEV in other cohorts of [CF patients] are urgently required.”
About the Author
