Multiplex Qpcr Facilitates Identification Of Betaherpesviruses In Patients With Acute Liver Failure Of Unknown Etiology

Abstract Background: The etiology of acute liver failure (ALF) is often unknown and reported to be associated with herpesviruses in a number of cases. In this study, we examined for betaherpesviruses infections in patients with ALF of unknown etiology using a multiplex qPCR to Betaherpesviruses subfamily. Methods: Liver and serum samples from 27 patients with ALF of unknown etiology were analyzed with the aid of multiplex qPCR to identify betaherpesviruses. All positive samples were sequenced to confirm herpes infection and liver enzyme levels evaluated. Results: Betaherpesviruses infection was effectively detected using multiplex qPCR. Seven (26%), two (7%) and three (11%) cases were positive for HHV-6, HHV-7 and HCMV, respectively. Two cases of dual infection (HHV-7/HHV-6 and HHV-7/HCMV) were additionally identified. Interestingly, HHV-7 was only detected in the presence of other betaherpesviruses. Sequencing information confirmed betaherpesviruses infection. High hepatic enzyme levels and INR values>1.4 were determined in all betaherpesvirus-positive patients. Conclusions: Multiplex qPCR facilitated efficient quantification, indicating that differentiation between betaherpesviruses is possible with the sole use of real-time PCR. Liver and serum samples were positive for some betaherpesviruses, suggesting an association with ALF. Coinfection of HHV-7 with HHV-6 or HCMV was additionally detected, suggesting that the precursor betaherpesviruses infection can trigger HHV-7 infection. Based on these results, we propose that ALF patients should be screened for the presence of betaherpesviruses.