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The Long-Term Outcomes of Patients Transplanted Due to Acute Liver Failure With Hepatic Human Herpesvirus-6 Infection

https://doi.org/10.1016/j.transproceed.2013.01.091Get rights and content

Abstract

Human herpesvirus (HHV)-6, comprised of HHV-6A and HHV-6B, belongs to the betaherpesviruses that infect 95%–100% of humans. Primary infection, known as exanthema subitum, occurs in early childhood. Reactivations of latent HHV-6, mostly HHV-6B, are common after liver transplantation. The vast majority of them are asymptomatic; in a minority of cases, the virus may infect the liver transplant, causing graft dysfunction or hepatitis. An association between hepatic HHV-6 infection and indeterminate acute liver failure (ALF) has been shown, but the causality is not clear because of the ubiquitous nature of HHV-6. We have previously observed HHV-6B antigens in the explanted livers of most patients (80%, n = 32) transplanted with ALF of unknown cause, whereas it was not observed among those with ALF of known cause. After transplantation, half of the patients with pretransplant HHV-6 infection (9/18) developed recurrences. The aim of this study was to investigate their long-term course (9–14 years). Half of the patients with pretransplant HHV-6 developed recurrences. Two also showed cytomegalovirus (CMV) hepatitis, whereas none of the other patients demonstrated intrahepatic CMV. During the 9 years or more of follow-up, 1 graft and 2 patients were lost in both groups (HHV-6 recurrence/HHV-6-negative patients). The reasons for graft loss were hepatic arterial thrombosis and portal venous thrombosis. In addition 2 patients died in the HHV-6 recurrence group, one because of rethrombosis of hepatic artery (day 460) and one with a functioning transplant (4.5 years after transplantation). In the control group 1 patient died at 1.5 years and 1 at 10 years after liver transplantation because of pneumonia. HHV-6 relapse was common in ALF patients after transplantation. However, HHV-6 did not cause liver failure and had no significant long-term effect on survival.

Section snippets

Methods

We have previously found HHV-6B antigens in the explanted livers of most patients (80%, n = 32) with unknown ALF, whereas, the opposite was observed in ALF patients with known cause.14 After transplantation, half of the patients with previous pretransplant HHV-6 infection (9/18) develop recurrences, whereas no post-transplant HHV-6 infection of the liver graft was seen among those without pre-transplant HHV-6.16 The aim of this study was to investigate the long-term (9–14 years) courses of

Results

Half of the patients (9/18) with pretransplant HHV-6 developed a relapse of intrahepatic HHV-6 infection. Two of the HHV-6 recurrence patients also had CMV hepatitis, whereas none of the other patients demonstrated intrahepatic CMV.

During the follow-up of 9 years or more, 1 graft and 2 patients were lost in both HHV-6 recurrence and HHV-6-negative groups. The reasons for graft loss were hepatic arterial thrombosis (patient 9) or portal venous thrombosis (patient 23). In addition, 2 patients

Discussion

An association has been established between HHV-6 and indeterminate ALF.12, 13, 14, 15, 16 However, in our material HHV-6 relapse did not cause liver dysfunction, and failed to exert a significant long-term effect on survival. The actual pathogenic role of HHV-6 in ALF remains suggestive only, as viral reactivation could alternatively be induced by an unknown factor, which leads to ALF with HHV-6 entering the scene after the onset of liver failure. However, HHV-6 infection may impact

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This work was supported by the grants from the Sigrid Juselius Foundation (to K.H. and I.L.) and the Helsinki University Central Hospital Funds (EVO) (to I.L.).

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