Elsevier

The Lancet

Volume 376, Issue 9736, 17–23 July 2010, Pages 190-201
The Lancet

Seminar
Acute liver failure

https://doi.org/10.1016/S0140-6736(10)60274-7Get rights and content

Summary

Acute liver failure is a rare disorder with high mortality and resource cost. In the developing world, viral causes predominate, with hepatitis E infection recognised as a common cause in many countries. In the USA and much of western Europe, the incidence of virally induced disease has declined substantially in the past few years, with most cases now arising from drug-induced liver injury, often from paracetamol. However, a large proportion of cases are of unknown origin. Acute liver failure can be associated with rapidly progressive multiorgan failure and devastating complications; however, outcomes have been improved by use of emergency liver transplantation. An evidence base for practice is emerging for supportive care, and a better understanding of the pathophysiology of the disorder, especially in relation to hepatic encephalopathy, will probably soon lead to further improvements in survival rates.

Introduction

Acute liver failure is the clinical manifestation of sudden and severe hepatic injury and arises from many causes. After abrupt loss of hepatic metabolic and immunological function, it leads to hepatic encephalopathy, coagulopathy, and, in many cases, progressive multiorgan failure (panel 1). Although uncommon, this critical illness occurs mostly in young adults and is associated with high mortality and resource cost. In many countries it is the most frequent indication for emergency liver transplantation.

In the past 10 years, there have been major changes in the understanding of the cause and pathogenesis of the disease, and an evidence base for treatment has evolved. In this Seminar, we summarise these changes, present approaches to management, and suggest future developments.

Section snippets

Definitions

The term fulminant hepatic failure was first used11 in 1970 to describe a potentially reversible disorder that was the result of severe liver injury, with an onset of encephalopathy within 8 weeks of symptom appearance and in the absence of pre-existing liver disease. The key elements of this definition remain relevant, although classifications have changed to recognise that prognosis and complications vary in relation to the rate of evolution of illness.

The terminology developed by O'Grady and

Incidence

Acute liver failure is rare. Reports from the developed world suggest an overall incidence of between one and six cases per million people every year.16, 17, 18 Data for other regions are sparse, although rates are probably high in locations where infective hepatitis is common and medical therapies that interrupt progression of hepatic injury and development of extrahepatic organ dysfunction are not readily available.

Viral infections

The main causal agents for the hepatic injury that triggers the onset of liver failure show wide geographical variation, and depend on the prevalent hepatotropic virus infections and patterns of drug use (table 2).13, 27, 28 In the developing world, viral causes predominate, with infection by hepatitis A, B, and E viruses accounting for most cases. By contrast, acute viral infection is an uncommon cause in the USA and much of western Europe, where drug-induced liver injury predominates.

Principles of care

Acute liver failure leads to a unique combination of often rapidly progressive, severe multiorgan failure with unpredictable complications, and necessitates urgent decision making about use of the only effective treatment for those with advanced disease: emergency liver transplantation. However, the general principles of care are straightforward. Standard intensive care is delivered with additional specific measures aimed at identification and removal or amelioration of the insult that caused

Future directions

A range of extracorporeal supportive devices has been advocated to replace liver function in patients with acute liver failure, either to stabilise the patient before transplantation, or to improve native liver regeneration. Despite many uncontrolled case series and individual randomised trials,151, 152, 153 conclusive evidence of benefit to patients has not been reported. There are no published data to support the use of either biological or non-biological systems as sole treatment when

Search strategy and selection criteria

We searched Medline with the terms “acute liver failure” and “fulminant hepatic failure” between 1997 and 2009. We also reviewed reference lists of publications we identified and selected those most relevant to practice. We have not attempted to give a comprehensive review of all features of acute liver failure, but have focused on areas in which there have been substantial advances in understanding of the disorder and in which there have been major new developments in treatment.

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