ArticlesAcute liver failure: redefining the syndromes
Abstract
Existing definitions of clinical syndromes in acute liver failure do not accurately reflect important differences in clinical features and prognosis. Based on a large series of patients with acute liver failure treated at King's College Hospital, London between 1972 and 1985, we propose a new terminology. Hyperacute liver failure is our suggested term for cases in which encephalopathy occurs within 7 days of the onset of jaundice; this group includes the sizeable cohort likely to survive with medical management despite the high incidence of cerebral oedema. We suggest the term acute liver failure for cases with an interval of between 8 and 28 days from jaundice to encephalopathy; they also have a high incidence of cerebral oedema, but have a much poorer prognosis without liver transplantation. The term subacute liver failure is suggested to describe cases with encephalopathy that occurs within 5 to 12 weeks of the onset of jaundice; these patients are characterised by a low incidence of cerebral oedema, but have a poor prognosis. Adoption of this terminology should help in the management of these patients, in addition to standardising the structure and interpretation of controlled trials of therapies.
References (9)
- Jg O'Grady et al.
Early indicators of prognosis in fulminant hepatic failure
Gastroenterology
(1989) - B. Lucke et al.
Fulminant form of epidemic hepatitis
Am J Pathol
(1946) - C. Trey et al.
The management of fulminant hepatic failure
- J. Bernuau et al.
Fulminant and subfulminant liver failure: definitions and causes
Semin Liver Dis
(1986)
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In total, 305 patients underwent CRRT while 1137 patients did not receive CRRT. CRRT was associated with improved overall survival [risk ratio (RR) 0.83, 95% confidence interval (CI) 0.70–0.99, p-value 0.04, I2 = 50%] and improved TFS (RR 0.65, 95% CI 0.49–0.85, p-value 0.002, I2 = 25%). There was a trend towards higher mortality with no CRRT (RR 1.24, 95% CI 0.84–1.81, p-value 0.28, I2 = 37%). Ammonia clearance data was unable to be pooled and was not analyzable.
Use of CRRT in ALF patients is associated with improved overall and transplant-free survival compared to no CRRT.
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2023, Clinics in Liver DiseaseAcute liver failure: updates in pathogenesis and management
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Current vision on diagnosis and comprehensive care in hepatic encephalopathy
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The first clinical guidelines on hepatic encephalopathy were published in 2009. Almost 14 years since that first publication, numerous advances in the field of diagnosis, treatment, and special condition care have been made. Therefore, as an initiative of the Asociación Mexicana de Gastroenterología A.C., we present a current view of those aspects. The manuscript described herein was formulated by 24 experts that participated in six working groups, analyzing, discussing, and summarizing the following topics: Definition of hepatic encephalopathy; recommended classifications; epidemiologic panorama, worldwide and in Mexico; diagnostic tools; conditions that merit a differential diagnosis; treatment; and primary and secondary prophylaxis. Likewise, these guidelines emphasize the management of certain special conditions, such as hepatic encephalopathy in acute liver failure and acute-on-chronic liver failure, as well as specific care in patients with hepatic encephalopathy, such as the use of medications and types of sedation, describing those that are permitted or recommended, and those that are not.