Etiology and management of fulminant hepatic failure

Abstract

Fulminant hepatic failure (FHF) remains a rare but devastating disease. Viruses and drug-induced hepatotoxicity are the most common causes of the syndrome, but the relevance of each differs depending on the geographic area. In a large proportion of patients no cause for FHF can be identified. Good intensive care is critical for patient survival. Orthotopic liver transplantation (OLT) remains a definitive therapeutic option. Prognostic indices have helped to optimize patient selection and timing for performance of OLT. However, the accuracy of these prognostic indices decreases when they are applied to different populations, probably because of regional differences in etiology and peculiar native host factors. More accurate prognostic criteria and new therapeutic alternatives to OLT are required.

Altered Expression of Zonula Occludens-2 Precedes Increased Blood–Brain Barrier Permeability in a Murine Model of Fulminant Hepatic Failure

“…Patients in early stages of FHF may recover spontaneously. However, during stages III and IV (comatose stages), when encephalopathy and brain edema occur, the disease takes a rapidly progressive and lethal course [1][2][3]. Brain edema in FHF results from compromised blood-brain barrier (BBB) permeability, leading to increased extravasation of water and other small molecules into the brain [2,3].…”

Lack of Chemokine Receptor CCR5 Promotes Murine Fulminant Liver Failure by Preventing the Apoptosis of Activated CD1d-Restricted NKT Cells

“…The incidence of FLF has increased in the last decade accounting for Ͼ2000 deaths annually in the United States alone (2) and represents the reason for 11 and 30% of all liver transplants in Europe and the United States, respectively (1)(2)(3). FLF is a clinical syndrome that is characterized by the sudden onset of severe acute hepatitis with associated symptoms, including jaundice and hepatic encephalopathy in a patient with no previous history of liver disease (2,3). Viruses, drugs (such as acetaminophen), and toxins have all been identified as trigger factors of FLF (2, 3); however, in many patients (ϳ20%), the etiology of FLF remains unknown (1).…”

“…Viruses, drugs (such as acetaminophen), and toxins have all been identified as trigger factors of FLF (2, 3); however, in many patients (ϳ20%), the etiology of FLF remains unknown (1). Although complex events are likely involved in the pathogenesis of FLF, current theories suggests that regardless of the etiology of FLF, an uncontrolled systemic activation of the immune system as an early initiating event (1)(2)(3). Despite today's advanced medical management, the factors leading to the development of systemic immune activation and ultimately FLF are poorly understood.…”

Point-of-care continuous13C-methacetin breath test improves decision making in acute liver disease: Results of a pilot clinical trial

“…Current predictors of survival in patients with FHF are far from optimal [12,13] . Thus, it is often problematic to make decisions concerning medical treatment and time of transplantation based on clinical and laboratory assessments [14][15][16] . A therapeutic dilemma arises from the need to provide expedient transplants to patients with a failing liver while avoiding unnecessary transplantations in patients that are likely to recover spontaneously [17][18][19] .…”