Liver Transplants for Hep C: A Surprising Finding

By Sondra Forsyth

An international team of researchers was surprised to find that in some hepatitis C patients who receive liver transplants, genes that target the hepatitis C virus (HCV) as part of the innate immune system actually enable the patients to tolerate a foreign organ without taking immunosuppressant medication. The study was published in July 2014 in Science Translational Medicine.

Over 150 million people throughout the world suffer from chronic infection with the HCV, which causes massive damage to the liver. Advanced liver diseases often necessitate liver transplants. For the study, lead scientist Dr. Felix Bohne at Technische Universitaet Muenchen in Munich, Germany and colleagues at King’s College London and the University Hospital Clínic de Barcelona set out to gain a better understanding of the mechanisms that enable the body’s own immune system to tolerate the new organ despite the HCV infection. They were also looking for factors that could act as biomarkers for tolerance in the patients.

A release from the university in Munich quotes Dr. Bohne as saying, “If tolerance could be reliably predicted based on certain markers, many patients could stop taking immunosuppressants after a certain period of time.” The release i that patients must take these strong drugs after transplants. The medications suppress the immune system so that the body does not identify the new organ as foreign and reject it. For patients with hepatitis C, this is a particular burden because they need a stable immune system after the transplant to control their chronic HCV infection.

During the study, the patients stopped taking the immunosuppressants. They were observed for twelve months to see which of them could tolerate the new organ without the drugs, and which of them did not. The scientists took liver and blood samples from the patients prior to and after the cessation of the drugs. Detailed immunological tests on these patient samples were carried out under the leadership of Prof. Ulrike Protzer of the “Immunmonitoring Platform” at the Institute of Virology. The scientists compared the patients with each other and looked for any differences that arose in tolerant patients only.

The scientists struck gold: A certain group of genes was very active only in the livers of tolerant patients. The genes in question belonged to the type I interferon system, which targets viruses like HCV as part of the innate immune system. As the results showed, an anti-viral mechanism does actually enable the patients to better tolerate a foreign organ.

Ulrike Protzer provides a possible explanation for this: “When the interferon system is constantly activated as is the case in some chronically-infected patients, it downregulates other immune reactions in order to protect the body. This state could act like a natural immunosuppressant and reduce the rejection of the organ.”

In addition to the genes of the type I interferon system, a second factor was considered as a possible marker. This was discovered by the researchers in a previous study on liver recipients who did not have a HCV infection. Patients were very likely to be tolerant if they had a certain ratio of two different subgroups of immune cells in their blood. This ratio was also a reliable predictor of tolerance in the new study involving HCV patients.

Dr. Tanja Bauer and Carolina Russo from the Immunmonitoring Platform at the Helmholtz Zentrum München were also involved in the study as cooperation partners. Felix Bohne was awarded a DFG (German Research Foundation) grant for his research work.