Abstract
BackgroundThe 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.MethodsLiver explant 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.ResultsBetaherpesviruses infection was effectively detected using multiplex qPCR. Six (22%) HHV-6, one (3%) HCMV and two (7%) dual infections (one with HHV-7/HHV-6, and the other with HHV-7/ HCMV). Interestingly, HHV-7 was only detected in the presence of other betaherpesviruses. Sequencing information confirmed betaherpesviruses infection. High hepatic enzyme levels and INR values> 1.5 were determined in all betaherpesvirus-positive patients.ConclusionsMultiplex qPCR facilitated efficient quantification, indicating that differentiation between betaherpesviruses is possible with the sole use of real-time PCR. Liver explant and serum samples were positive for some betaherpesviruses, and coinfection of HHV-7 with HHV-6 and HCMV was additionally detected. Based on these results, we propose that ALF patients should be screened for the presence of betaherpesviruses.
Highlights
The etiology of acute liver failure (ALF) is often unknown and reported to be associated with herpesviruses in a number of cases
Inclusion criteria demanded the development of coagulopathy [i.e. prothrombin time activity (PTA) > 15 s or international normalized ratio (INR) > 1.5] and hepatic encephalopathy within 8 weeks of jaundice onset in the absence of preexisting liver disease
Nine (33%) patients with ALF from previously unrecognized viral pathogens were positive for betaherpesviruses, six (22%) human herpesvirus 6 (HHV-6), one (3%) human cytomegalovirus (HCMV) and two (7%) dual infections
Summary
The etiology of acute liver failure (ALF) is often unknown and reported to be associated with herpesviruses in a number of cases. We examined for betaherpesviruses infections in patients with ALF of unknown etiology using a multiplex qPCR to Betaherpesviruses subfamily. Acute liver failure (ALF) is a condition whereby healthy liver deteriorates rapidly, resulting in jaundice, encephalopathy and coagulopathy. Previous studies have reported the presence of viruses of the family Herpesviridae in cases of ALF, including the betaherpesviruses. Primary HCMV and/or HHV-6A/B infections can cause mild and self-limiting hepatitis in immunocompetent patients. In immunocompromised cases, in particular, organ transplant recipients, HCMV infection is associated with increased morbidity [7]. Primary infection with HHV-6 is a frequent cause of ALF, necessitating antiviral therapy during early post-transplantation procedures. A number of studies have disclosed the presence of HHV-6
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