A Rare Case of Acute Liver Failure in an Infant: Unmasking the Hidden Threat of HHV-6 — A Case Report and Review of the Literature

Introduction: Pediatric acute liver failure (PALF) is a rare condition characterized by abrupt hepatocellular injury resulting in severe hepatic impairment. Recently, there have been increasing reports of children with liver failure of unknown etiology and HHV-6 detected in their blood or tissue samples, raising the idea that HHV-6 could be the primary cause of acute liver failure (ALF) and hepatitis. This case highlights the importance of considering viral etiologies, including HHV-6, in pediatric patients with ALF. Case Presentation: We present the case of a 7-month-old girl with a two-day history of fever, diarrhea, and agitation. Initial investigations suggested viral gastroenteritis; however, she later developed abdominal distention and palpable hepatomegaly. Laboratory findings revealed markedly elevated liver enzymes and coagulopathy that did not respond to vitamin K, consistent with ALF. Comprehensive testing excluded common causes of PALF, such as drug- or toxin-induced liver injury, autoimmune hepatitis, hemophagocytic lymphohistiocytosis, metabolic and genetic disorders, cardiovascular conditions, hematological malignancies, and various viral etiologies, including SARS-CoV-2, influenza A and B, hepatitis A-E, adenovirus, Epstein-Barr virus, parvovirus B19, cytomegalovirus, and Human herpesviruses type 7. HHV-6 testing via blood qPCR was positive, strongly implicating it as the causative agent of ALF. The presence of Pseudo-Pelger-Huet cells on the peripheral blood smear added further support to the diagnosis. Despite intensive management, the patient developed severe complications and ultimately succumbed to the illness. Postmortem examination confirmed ALF, and the detection of HHV-6 in liver tissue reinforced its association with the condition. Conclusions: In conclusion, given the undetermined etiology of over 40% of cases of PALF and the high mortality rates among them, it is imperative to conduct viral screening protocols in cases of liver failure of unknown etiology. We strongly advise pediatricians to implement viral screening protocols with particular consideration for HHV-6 when facing liver failure of unknown etiology. Moreover, we highly encourage further research to clarify associations between HHV-6 and hepatic complications, mechanisms by which HHV-6 can lead to liver failure, and establish treatment indications and protocols.