Discovery of Crucial Window of Opportunity for Antiviral Treatment of Acute Hepatitis C

16 January 2012
As part of an international collaboration, scientists of the University Medical Center Hamburg-Eppendorf (UKE) have now shown that in patients with an acute hepatitis C infection, an immune response mediated by T helper cells is always present at the beginning of the infection. Until now researchers had assumed that such a response of the immune system only existed in patients with spontaneous healing. Moreover, the scientists found that these virus-specific T helper cells disappear relatively quickly in a chronic course of hepatitis C infection. Timely antiviral treatment during the acute phase can prevent the loss of these T helper cells. These findings open up new approaches in the fight against chronic hepatitis C infection.
Over 70 percent of all hepatitis C infections are chronic. The immune system is primed to fight off the virus already in the acute phase in only few cases of infection. In spontaneous healing, a strong immune response, mediated by T helper cells, is always detectable. Until now it was not clear why in patients with a chronic infection, no hepatitis C virus (HCV)-specific T helper cells could be detected in the blood. To solve this enigma, Julian Schulze zur Wiesch, MD, (1st Medical Clinic, UKE) collaborated with the lab of Professor Georg Lauer at Massachusetts General Hospital, Harvard Medical School, Boston, and analyzed the T helper cells in the blood of a large group of patients who had an acute hepatitis C infection but different clinical courses of the disease. Schulze zur Wiesch heads a subproject of the Collaborative Research Centre 841 (CRC 841) “Liver Inflammation: Infection, Immune Regulation and Consequences.”
Timely treatment stops T-cell loss
Using a new, very sensitive method called MHC class II tetramer technology, the researchers found HCV-specific T helper cells in all of the examined persons in early stages of infection. In chronic courses of the disease, however these immune cells very soon showed functional defects and finally disappeared entirely. The functional defects of the T helper cells were partially reversible if an immune messenger substance, interleukin 2 (IL-2) was added at an early stage to isolated cells in culture. Even in the patients, early antiviral treatment started in the first six months after the infection could prevent the complete loss of the HCV-specific T helper cells. “The next step will be to exactly understand the causes of the functional defects of these cells,” Schulze zur Wiesch explained. In his opinion, the findings of the research suggest that antiviral treatment should be initiated early in acute HCV-infected persons. According to him, further clinical trials are needed to confirm this observation.
Preventing the disease from becoming chronic
The findings, published in the latest issue of the renowned Journal of Experimental Medicine, are an important step forward in finding an approach to prevent the HCV infection from becoming chronic. A chronic HCV infection can have grave consequences – e.g. a liver cirrhosis or even liver cancer. Around 50,000 people in Germany suffer from a chronic hepatitis C disease; worldwide circa 170 million people are affected. In contrast to hepatitis A and B, no vaccination exists as yet against the hepatitis C virus. Despite new developments in recent months, antiviral treatment of chronic HCV infection remains complex and has many side effects.