Research Article
Lessons from look-back in acute liver failure? A single centre experience of 3300 patients

https://doi.org/10.1016/j.jhep.2013.02.010Get rights and content

Background & Aims

Acute liver failure (ALF) is a rapidly progressive critical illness with high mortality. Complex intensive care unit (ICU) protocols and emergency liver transplantation (ELT) are now often available, but rarity and severity of illness have limited its study and evidence-base for care. We reviewed patients treated over a 35-year period at a specialist high-volume ICU, quantifying changes in disease aetiology, severity and evolution of ICU support and ELT use and outcome.

Methods

Review of adult patients admitted during the period 1973–2008, with acute liver dysfunction and coagulopathy with overt hepatic encephalopathy (ALF) and those without (acute liver injury; ALI).

Results

3305 patients fulfilled inclusion criteria, 2095 with ALF. Overall hospital survival increased from 30% in 1973–78 to 76% in 2004–08; in ALF from 17% to 62% (both p <0.0001). In ALF patients treated without ELT, survival rose from 17% to 48% (p <0.0001); in those undergoing ELT (n = 387) from 56% in 1984–88 to 86% in 2004–08 (p <0.01). Coincident with drug sales-restriction, paracetamol-related admissions fell significantly. Viral admissions fell from 56% to 17% of non-paracetamol cases (p <0.0001). Admission markers of liver injury severity fell significantly and the proportion of patients with intracranial hypertension (ICH) fell from 76% in 1984–88 to 20% in 2004–08 (p <0.0001). In those with ICH, mortality fell from 95% to 55% (p <0.0001).

Conclusions

The nature and outcome of ALF have transformed over 35 years, with major improvements in survival and a fall in prevalence of cerebral oedema and ICH, likely consequent upon earlier illness recognition, improved ICU care, and use of ELT.

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.

References (37)

  • A.T. Blei

    Medical therapy of brain edema in fulminant hepatic failure

    Hepatology

    (2000)
  • J. Vaquero et al.

    Infection and the progression of hepatic encephalopathy in acute liver failure

    Gastroenterology

    (2003)
  • P. Ichai et al.

    Etiology and prognosis of fulminant hepatitis in adults

    Liver Transpl

    (2008)
  • W. Bernal et al.

    Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure

    Hepatology

    (2007)
  • A. Escorsell et al.

    Spanish Group for the Study of Acute Liver F. Acute liver failure in Spain: analysis of 267 cases

    Liver Transpl

    (2007)
  • W.A. Bower et al.

    Population-based surveillance for acute liver failure

    Am J Gastroenterol

    (2007)
  • W. Bernal et al.

    Intensive care management of acute liver failure

    Semin Liver Dis

    (2008)
  • R.T. Stravitz et al.

    Intensive care of patients with acute liver failure: recommendations of the US. Acute Liver Failure Study Group

    Crit Care Med

    (2007)
  • Cited by (309)

    • Managing a Prospective Liver Transplant Recipient on the Waiting List

      2024, Journal of Clinical and Experimental Hepatology
    • Acute liver failure in low-income and middle-income countries

      2023, The Lancet Gastroenterology and Hepatology
    View all citing articles on Scopus
    View full text