Acute Liver Failure - It's Just a Matter of Cell Death

Abstract

Background: Acute liver failure (ALF) is characterized by a sudden loss of hepatic function due to hepatocyte cell death and dysfunction in previously healthy individuals. The clinical presentation of ALF is associated with coagulopathy (international normalized ratio ≥1.5) and hepatic encephalopathy, although the latter may be less pronounced. Without appropriate and timely intensive care or liver transplantation (LTx), ALF will result in multi-organ failure and death. Various causes may induce ALF, with acetaminophen (APAP) intoxication and acute hepatitis B infection as most common causes in industrialized countries. While conventional terminology discerns acute, acute-on-chronic and acute-on cirrhosis liver failure, some chronic liver diseases (i.e. autoimmune hepatitis (AIH), Wilson's disease) can remain undiagnosed until an initial presentation as ALF. Key Messages: Upon definite diagnosis of ALF, the underlying cause must be identified, since etiology affects prognosis and clinical management. Individual prognosis should be evaluated with one of various available scoring systems. Most widely used are Model for End-Stage Liver Disease, the King's College Criteria and the Clichy criteria. Other markers, that is, cell death markers, lactate or thyroid status, may improve diagnostic accuracy of classic scores, though routine use of these is not yet established. Etiology-specific treatment under intensive care should be performed, if possible (APAP and amanita intoxication, acute viral hepatitides and AIH). LTx is the only curative option for other causes, unknown reasons of ALF or when etiology-specific therapy fails. In ambiguous cases, that is, suspected drug induced ALF or AIH, co-infection with hepatitis E virus should be tested, as this might be more common than it is currently supposed to be. Conclusions: Despite major improvements in clinical management of ALF patients, a significant proportion of ALF cases remains without clear identification of the underlying cause or unrecognized multiple causes. In depth analyzes of ambiguous ALF cases is warranted to further improve clinical management.

Low transferrin and high ferritin concentrations are associated with worse outcome in acute liver failure

“…Acute liver failure is a life‐threatening event with high mortality and immediate intensive care measures are necessary for patient survival . Developing prognostic scores to assess the probability of survival with and without transplantation is of great interest, since some patients recover without liver transplantation while for others transplantation is the only hope for survival.…”

“…Many scores have been developed (e.g. MELD and KCC) to address this issue, most of them with good sensitivity but unsatisfactory specificity . Improvement of prognostic scores with better specificity is necessary to gain a higher prognostic value.…”

“…Various scoring systems have been proposed to evaluate the prognosis of patients with ALF, most of them with good sensitivity but unsatisfactory specificity. Novel scores have been proposed a few times, but to date with no confirmation in large independent studies and clinical application …”

How to Define Acute Liver Failure Patients with Pre-Existing Liver Disease without Signs of Cirrhosis

“…Acute liver failure (ALF) is the final common result of severe hepatocyte injury [1]. ALF itself is one of the most dangerous complications in hepatology, with a high rate of mortality [2,3] and immediate requirement of intensive care [1].…”

“…ALF itself is one of the most dangerous complications in hepatology, with a high rate of mortality [2,3] and immediate requirement of intensive care [1]. When patients are admitted with the diagnosis of ALF to a tertiary care or liver transplant center, a thorough examination is necessary to identify the underlying cause of ALF and the severity of the situation [4].…”