Clinical PotpourriAcute liver failure: An up-to-date approach☆,☆☆
Introduction
Acute liver failure (ALF) is a rare condition characterized by new and rapidly evolving hepatic dysfunction associated with neurologic dysfunction and coagulopathy. It is more frequent in young individuals and its etiologies vary geographically, with impact on both clinical course and outcomes. Throughout the last decades, ALF outcomes have been improving in the context of the optimized overall management. However, its present morbidity and mortality remain high in patients fulfilling poor prognostic criteria and without emergent liver transplantation (LT).
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Definition and epidemiology
Acute liver failure definition has evolved throughout the time and presently includes the following features: international normalized ratio (INR) at least 1.5, neurologic dysfunction with any degree of hepatic encephalopathy (HE), no preexisting cirrhosis, and disease course of 26 weeks or less [1]. Exceptions to this definition may be patients with acute presentations of Wilson disease, autoimmune hepatitis, or vertically transmitted hepatitis B if by the time of the new hepatic insult, they
Pathophysiology and clinical manifestations
In ALF, the liver insult results in extensive death of hepatocytes with activation of the innate immune system responses (Kupffer cells and circulating monocytes) causing a large production of inflammatory mediators. The “spill-over” of these inflammatory mediators into the circulation ultimately leads to the systemic disturbances and clinical manifestations of ALF [12]. An overwhelming systemic inflammatory response syndrome (SIRS) is associated with the several organ failures that may ensue.
General management
The initial management of acute liver injury (hepatitis) or ALF is supportive with the objective to optimize conditions for the liver to regenerate and prevent and treat as early as possible complications [17]. Although most patients with acute liver injury may be managed in a regular ward, patients with ALF should be referred to the ICU, ideally one in a center capable of providing emergent LT, as soon as possible as they may deteriorate quickly [1].
The initial diagnostic approach should be
Intensive care management
Acute liver failure may lead to several organ failures; therefore, ICU admission should be considered as early as possible, especially when HE is being difficult to control in a regular ward or coagulopathy is progressing. In this context, supporting organ failures follows the rules of general ICU patients but with some specificities, which deserve to be emphasized.
Liver transplantation
Liver transplantation is the only definitive treatment for patients with ALF. Overall survival after LT has been reported to be lower for patients with ALF in comparison to patients with cirrhosis until 1 year after transplant, but it tends to be similar from then on [68]. In fact, most deaths after LT for patients with ALF occur from infection during the first 3 postoperative months [4]. Nevertheless, survival after LT for ALF has been improving throughout the last decades, with 21-day
Conclusions
Acute liver failure diagnostic and therapeutic strategies have evolved throughout the time and that has been associated with improved outcomes. New advances in basic and clinical research may potentiate even more such outcomes. Despite this, these patients' early referral to an LT center, ICU timely treatment, and a comprehensive multidisciplinary strategy in risk stratification and selection for LT will continue to be fundamental steps for a successful approach.
References (77)
- et al.
Acute liver failure
Lancet
(2010) - et al.
Lessons from look-back in acute liver failure? A single centre experience of 3300 patients
J Hepatol
(2013) - et al.
Modulation of monocyte/macrophage function: a therapeutic strategy in the treatment of acute liver failure
J Hepatol
(2014) - et al.
The importance of immune dysfunction in determining outcome in acute liver failure
J Hepatol
(2008) - et al.
Acute liver failure: a curable disease by 2024?
J Hepatol
(2015) - et al.
Choice of fluid in acute illness: what should be given? An international consensus
Br J Anaesth
(2014) - et al.
ESPEN guidelines on enteral nutrition: liver disease
Clin Nutr
(2006) - et al.
Lactulose therapy in acute liver failure
J Hepatol
(2002) - et al.
Efficacy of l-ornithine l-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study
Gastroenterology
(2009) - et al.
Minimal effects of acute liver injury/acute liver failure on hemostasis as assessed by thromboelastography
J Hepatol
(2012)