A group of physicians from Hannover Medical School in Hannover, Germany, have reported that high intrahepatic HHV-6 virus loads are associated with decreased graft survival after diagnosis of graft hepatitis. Interestingly, elevated levels of CMV and EBV were not correlated with a reduction in graft survival time.
However, although the detection of HHV-6 DNA in liver tissue biopsies was associated with decreased graft survival, other methods of HHV-6 detection were less reliable in predicting poor outcome. For instance, the detection of HHV-6 IgM antibodies was not significantly correlated with any clinical outcome. Furthermore, although the detection of HHV-6 DNA in blood samples was associated with significantly shorter survival in Kaplan Meier Analysis, it was not found to be significantly associated with decreased graft survival. These findings support the findings of other groups as well, and suggest that because HHV-6 is such a low copy number virus and can “smolder” actively in the tissues, blood testing may be misleading; the most useful tool for the proper detection and diagnosis of HHV-6 infection continues to be the evaluation of tissue biopsy.
In their study, samples from 173 liver transplant patients who presented with an episode of graft hepatitis—a liver complication which features the increase of liver enzymes, among other things—were retrospectively analyzed for the presence of potential etiological agents associated with reduced graft survival, defined as the time between initial transplantation and re-transplantation and/or death. Samples such as tissue biopsy, serum, and whole blood—when available—from each patient were evaluated for the presence of EBV, CMV (both known to cause complications among liver transplant patients) and HHV-6.
HHV-6 was detected in 58% of liver biopsies, and high intrahepatic HHV-6 DNA levels (defined as the 75th percentile; >11.27 copies/1000 cells) were significantly associated with decreased graft survival following diagnosis of graft hepatitis. Low levels of intrahepatic HHV-6 DNA, which indicate latent viral infection, were not associated with decreased graft survival. Furthermore, although elevated viral loads of both CMV and EBV were observed in some tissues, these values did not correlate with decreased graft survival.
This important publication suggests that HHV-6 may be a significant contributor to liver dysfunction, particularly in the liver transplant population, and merits further elucidation. It also calls attention to the more broadly controversial issue of proper testing for HHV-6 infection, suggesting yet again that tissue biopsy may be the only way to identify a subset of patients who may benefit from anti-HHV-6 therapy.