At least 2 independent studies, one done from our center and another from Canada, have shown that HHV-6 viremia may be associated with a more severe recurrence of HCV after liver transplantation. Both studies showed that HHV-6 viremia did not impact on the overall rate of recurrence, but was associated with earlier recurrence and higher fibrosis score. And this effect was independent of other known risk factors that can influence the severity of HCV: CMV infection, intensity of immunosuppression, HCV genotype, and concurrent alcohol use.
The study from Toronto was also able to correlate the peak viral load of HHV-6 with a more severe recurrence. Why might that be so? Why is HHV-6 leading to a more severe recurrence of HCV? The likely plausibility is that TNF plays a role. HHV-6 is known to be a promoter of TNF, and TNF increasingly has been found to play an important role in the pathogenesis of HCV; higher TNF levels have been associated with greater fibrosis scores and poor response to interferon in patients who have HCV.Antiviral Therapy of HHV-6
How do the antivirals affect HHV-6? I've listed the commonly used or available antiviral agents as well as the dosages for these drugs, the IC50 of these agents for HHV-6, and the serum level that is achievable by the particular dose of the antiviral agent. Acyclovir is not likely to be very effective against HHV-6; the attainable serum level with this dose is 4 micromolar and IC50 is much higher. Valacyclovir has serum levels that are much better than acyclovir but the drug is likely not going to be efficacious.
On the other hand, ganciclovir as well as foscarnet can achieve serum levels with the dosages listed that can render them effective against HHV-6.
Does effective therapy influence outcome? There are very few data correlating the efficacy of viral regimens with clinical outcome but it is clear that there is perhaps an effect. This is a study that we published a couple of years ago (2000) looking at antiviral therapy in patients with HHV-6 encephalitis. We were able to show that with receipt of ganciclovir or foscarnet for 7 days (in other words, patients who didn't die very quickly and were able to receive some duration of effective therapy), patients were more likely to do well compared with patients who were either diagnosed too late in the course of the disease and therefore did not receive therapy, or received therapy for a very brief period of time.
