Hepatitis C: Lazy Genes heal better

22. July 2008

New results provided by researchers from Basel/Switzerland give new hope to physicians: The diagnostic identification of the activation status of the body's own interferon system in liver biopsies enable prognoses about the chances of success of therapy and applied antiviral drugs. The discovery of the researchers: The more active the genes, the lower the chances.

As yet the regular every day’s prognoses are little inspiring: Only half of the patients with chronic Hepatitis C can be healed with the standard interferon therapy applied today. Up to now the “why” puzzled physicians. The work of researchers at the University Hospital Basel and the Friedrich Miescher Institute brings some light into the dark now. A total of 16 patients underwent a liver biopsy four hours after the first injection of the interferon pegIFNalpha. “This removal of tissue enabled the researchers to study the molecular effect of pegIFNalpha directly in the liver”, informs the Basel university right after publication of the study in the “Proceedings of the National Academy of Sciences“, and: “The analysis of the organ samples shows that in many patients the target genes which are supposed to get stimulated by the interferons are already activated”.

Unwelcome consequence of this effect unknown until now: Against all expectations an effect worth mentioning of pegIFNalpha in the liver cells failed to appear. In addition further therapy did not show any impact on the virus – and the healing of the patient remained wishful thinking.

The realization is what counts

But those patients not showing any activation of the body’s own interferon system display a “strong effect of pegIFNalpha with an induction of hundreds of target genes”, as Basel reports. In other words: The used drugs only worked with this group of patients.

But why the body’s own interferon system is activated in nearly half of the patients and the effect of the used drugs is switched off, is totally unknown. Yet unanswered is also the question why the activated interferon system cannot eliminate the infection with the Hepatitis C virus. What counts though is the inversion and the observation that an inactive interferon system obviously could make the therapy a success.

Co-infection is a worldwide problem

The PNAS-publication might not just keep hepatologists busy but also physicians with HIV positive patients might be interested in the results. Because more than three years ago, the European commission had authorized the combination of the active ingredient Peginterferon alfa-2a [40 kD] and Ribavirin for treatment of chronic Hepatitis C (HCV infection) for clinically stabilized patients with simultaneous HIV infection. The authorization followed only one month after a positive official statement regarding the combination therapy of the according drug thus advancing it to the first Hepatitis C drug indicated for HIV-HCV-co-infected patients in Europe since.

Admittedly the vigor of the admission board is not a coincidence: The so-called co-infection has developed into a serious public health concern, 30 percent of all HIV positive patients worldwide are infected with HVC as well. The authorization in 2005 followed an according EMEA authorization for the therapy of Hepatitis C patients with continuously “normal” liver enzyme values as well as several authorizations for the drug for Hepatitis B in various countries.

The odds are in our favor

But even without any connection to HIV therapy, the results from Basel have farreaching consequences: Because the chronic infection with Hepatitis C virus is one of the most frequent liver diseases worldwide. In Germany about 400,000 to 500,000 people are infected with the virus. The disease is considered extremely dangerous since it can cause cirrhosis of the liver and liver cancer. Up to now physicians count on a combination of certain interferons (pegyliated interferon alpha, “pegIFNalpha”) and the antiviral substance – a therapy that takes up to 12 months – and only half of the patients can be considered as healed afterwards. However, should treatment guidelines be adjusted to the latest findings in the PNAS-publications, the future balance might look completely different: After only one month, the treatment of the predominant number of patients without activation of the body’s own interferon system lead to “an elimination of the virus”. And exactly that – the physicians rejoice – means that the majority of those patients could be healed.

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