Human herpesvirus 6 (HHV-6) was first isolated from patients with the acquired immunodeficiency syndrome or lymphoproliferative diseases and was named human B lymphotropic virus [1]. HHV-6 has been identified as the etiologic agent of exanthema subitum in infants [2] and an acute febrile illness in young children [3]. Most people are seropositive for HHV-6 by the age of three years [4]. HHV-6 also produces latent or chronic infections [5] and is occasionally reactivated in immunocompromised hosts [1,6]. Furthermore, HHV-6 has been implicated in several diseases in immunocompetent adults, including Kikuchi's lymphadenitis [7] and an infectious mononucleosis-like syndrome that is negative for Epstein-Barr virus and cytomegalovirus [8]. We describe the immunopathological and clinical features of a severe acute hepatitis in a 18-year-old woman that was probably caused by a primary infection with HHV-6.

Our data indicate that HHV-6 was the cause of our patient's acute illness. Serologic studies excluded the possibility of active infection by HCV, HBV or other human herpesviruses such CMV and EBV. The presence of HHV-6 IgM antibodies shortly after the onset of liver disease and positive ANA titres suggest that HHV6 or an autoimmune disease may also be involved in the pathogenesis. HHV-6 is a CD4 lymphotropic virus isolated from T-cells cultures derived from the blood of subjects HIV+ [1]. Infection by HHV6 is rapidly controlled by the host immune response, and the virus established a state of latency. Primary infection occurs mostly in early childhood and only rarely in adults, in whom the prevalence of anti-HHV6 IgG is more than 90% [3]. Symptomatic infection is characterized by fever, skin rash (exanthema subitum), sometimes associated with mild respiratory illness, leukopenia and atypical lymphocytosis [3,10]. Recovery is usually rapid and benign, although a more severe course with meningitis, encephalitis, myocarditis or hepatitis, variable from mild hepatitis to fulminant liver failure, has been described [3]. HHV6 has also been associated with interstitial pneumonia and encephalitis in immunocompromised patients. [11] We assume that HHV-6 caused the initial clinical manifestations but an humoral virus-triggered autoimmune reaction, indicated by the positive ANA titre, responding to immunosuppression induced hepatic damage. Manifestations of autoimmune hepatitis have been described repeatedly after infection with hepatitis A, B and C as well as with herpes viruses, namely HSV1, EBV and HHV6 [12,13].

Autoantibodies may be triggered by a virus specific mechanism to evade immune responses called 'molecular mimicry', when domains on viral proteins closely resembling human self-epitopes are generated [14,15]. Thus, we believe that in addition to causing exanthem subitum in infants and a febrile illness in children, HHV-6 type B can cause an acute and potentially fulminant hepatitis in adults with an autoimmune pathogenetic mechanism.

The authors declare that they have no competing interests.

PGjr acquisited data and made analysis and interpretation of data, PC assessed ultrasonographic examination, RC assessed liver biopsy, PG analized tissue molecular test and helped to draft the manuscript. All authors read and approved the final manuscript. Informed written consent was received from the patient for publication of the manuscript.