Research ArticleLessons from look-back in acute liver failure? A single centre experience of 3300 patients
Introduction
Acute liver failure (ALF) combines the clinical features of an acute severe insult to a previously normal liver, with the development of progressive hepatic encephalopathy (HE), coagulopathy, jaundice, and the potential to rapidly progress to multi-organ failure [1], [2], [3]. In those with severe HE, progression to cerebral oedema (CE) and intracranial hypertension (ICH) is a feared outcome, often with fatal consequences [4], [5]. ALF is rare, with an incidence in the developed world of probably fewer than 5 cases per million population per year [6], [7].
This disease rarity, severity and phenotypic heterogeneity combine, to result in a uniquely challenging illness, particularly in relation to its study and the development of effective treatments. Few specific interventions have been tested in controlled trials, with most supportive interventions and decision-making strategies evolving from analysis of natural history data with extrapolation from other critical illnesses [1], [8], [9].
Even with these limitations, the last four decades have seen major changes in approach to the care of patients with ALF. The most visible impact has come from emergency liver transplantation (ELT) with less tangible improvements from complex intensive care. The profile of ALF has also changed over time, influenced by public health initiatives reducing the incidence of acute viral hepatitis and by some restrictions of the availability of hepatotoxic medication – exemplified by the restriction of sales of paracetamol (acetaminophen) in the United Kingdom (UK) [10].
Since its opening in 1973, the Liver Intensive Therapy Unit (LITU) within the Institute of Liver Studies, Kings College Hospital, has maintained a specific interest in the care of patients with ALF. Operating as a high-volume centre for the care of patients with liver disease, it has developed a multi-disciplinary approach to care of these patients and as such has a unique opportunity to evaluate the evolution of care and changes in the nature and outcome of the illness over time. In this study, we analysed data of the 3305 patients with acute liver disease admitted to the LITU over the period 1973–2008, seeking to evaluate and quantify the effects of intensive care support and the introduction and refinement of ELT. We sought also to delineate the changes in disease etiology and severity that had occurred over time, and how these related to the clinical complications and outcomes observed.
Section snippets
Patients and dataset
The analysis is based on all patients aged ⩾16 years admitted to the LITU between 1973 and 2008, with a diagnosis of acute liver injury (ALI) or ALF. Inclusion criteria for ALI included: (1) an INR of ⩾1.5; (2) absence of a previous history and clinical/radiologic findings of liver disease; and (3) illness ⩽26 weeks of duration. Those who had or developed overt encephalopathy (HE grade ⩾2) [11] at any time during their hospital stay were classified as having ALF [12]. Transfer to the LITU was
Etiology
During the study period, a total of 3305 patients fulfilling ALI/ALF inclusion criteria were admitted to LITU. Median age was 33 (24–44) years and 1968 (59.5%) were female; 2163 (65.4%) had paracetamol and 1142 (34.6%) non-paracetamol etiologies. Overall, 2095 (63.6%) had on admission or subsequently developed overt HE (ALF), 840 with non-paracetamol and 1255 with paracetamol etiologies. As compared to those with ALI, patients with ALF of both etiologic groups were older and had evidence of
Discussion
Most modern definitions of ALF seek to quantify the interval between symptom onset and development of encephalopathy, and in some, the severity of liver injury by degree of coagulopathy. However, no consensus exists on the severity of either coagulopathy or encephalopathy that marks the transition from liver injury to frank failure [19]. For the purposes of this study and with a restricted dataset, we adopted the pragmatic approach of simply classifying patients on the basis of the presence or
Conflict of interest
The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
Acknowledgements
We thank Professors Roopen Arya (Department of Haematology) and Roy Sherwood (Department of Clinical Chemistry) at Kings College Hospital, London for their comments in relation to changes in laboratory technique.
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