Viral infections present a significant complication in organ transplant patients. So-called posttransplant immunosuppression, where the suppressed immune system is unable to respond to infection, is primarily associated with the transmission or reactivation of herpesviruses (e.g. CMV, EBV) and polyomaviruses, which contribute significantly to increased morbidity and, in some cases, mortality as well as to increased costs related to treatment of these complications. While the role of herpesviruses in patients with impaired immunity has long been known, polyomaviruses represent a relatively unexplored area of posttransplant complications.
One of the most widespread polyomaviruses is the BK virus, which can be found in 80% of the population. The virus most commonly resides in renal epithelial cells, the urinary tract, or in circulating leucocytes. In people with a healthy immune system, the virus does not manifest symptoms and does not present a serious clinical complication. In patients with compromised immunity, however, the virus may be reactivated, leading to its excretion in urine or even development of nephropathy, a serious kidney disease afflicting 5–10% of kidney transplant patients. As yet, there is no treatment for the disease; boosting the immune system remains the only option, but it increases the risk of rejection of the transplanted organ.
Viral hepatitis presents another serious complication for posttransplant patients, namely hepatitis B, C, and E infections. While hepatitis C is now curable thanks to direct-acting antiviral drugs, hepatitis B is still an incurable disease, with the virus remaining in the nuclei of liver cells for life. Suppression of the immune system can result in reactivation of the virus and development of infection with a very severe course. Likewise, hepatitis E can have a severe chronic course in posttransplant patients and quickly lead to cirrhosis of the liver. There is still no registered drug for this disease either.
Viral myocarditis is also a relatively common disease. Its clinical presentation can range from a nearly symptom-free course to severe symptoms, such as life-threatening heart failure or long-term worsening of myocardial function. There are practically no specific therapy options available; nevertheless, for many patients, effective treatment can considerably mitigate the acute course of the disease and improve long-term prognosis.
What we’re working on
The goal of the collaboration between IKEM, IOCB, and IPHYS is the development of an effective antiviral therapy for use in a wide spectrum of patients, including those either awaiting organ transplantation or already recovering from it.