Liver failure—future challenges and remaining questions

Abstract

This review compiles the current state of controversial aspects of liver failure and outlines future challenges. The definition of acute liver failure (ALF) is widely accepted and implies no previous liver injury whereas the term "acute-on-chronic liver failure" remains contested. We will promote a concept, in which we differentiate three types of liver failure: ALF, acute-on-chronic liver failure (AOCLF) and acuteon-liver-cirrhosis (AOCi). The mechanistical insights into the coagulation system in patients with hepatic insufficiency have increased fundamentally in the past 10 years. Therefore, we follow now the concept of the so-called rebalanced hemostasis. This lower-level equilibrium arises from the fact that most coagulation factors and inhibitors are synthesized within the liver. We will demonstrate the advantage of viscoelastic test methods, which can assess the coagulation situation in patients with liver insufficiency much more precisely than conventional global coagulation tests. The therapeutic option of emergency liver transplantation (ELT) has significantly improved the prognosis of patients with ALF. However, limiting factors such as shortage of organs increase more and more the need for reliable prognostic markers. Due to a better understanding of the regenerative process during ALF new survival markers and prognostic tools have been emerging on the horizon in the last decade. Therefore, we will describe the current state of research in this field.

Loss of liver function in chronic liver disease: An identity crisis

“…Deterioration and loss of hepatic functions is a hallmark of severe acute injury and chronic damage to the organ [78,79]. In the clinic, the scores most commonly used to predict patients' outcome, the Child-Turcotte-Pugh (CTP) and the Model of End-Stage Liver Disease (MELD) scores, include the serum levels and the activity of proteins produced by hepatocytes such as albumin and coagulation factors, as well as bilirubin concentration, which are indicative of liver biosynthetic and secretory functions [78].…”

The impact of COVID-19 on liver injury in various age

“…Patients who make severe acute liver injury in the absence of preexisting chronic liver disease, usually indicate noteworthy liver dysfunction marked with coagulopathy, which is described as an international normalized ratio ≥ 1.5 and is classically defined as acute liver failure (ALF) when any degree of hepatic encephalopathy (HE) is existing[ 15 ]. The ALF types include: (1) Hyperacute: < 7 d; (2) Acute: 7–28 d, and (3) Subacute: 28 d to 6 mo, depending on latency between the beginning of signs and development of encephalopathy and coagulopathy[ 16 , 17 ].…”

Hepatische Enzephalopathie Teil 1: Definitionen, Pathogenese und Diagnostik

“…Auch wenn der Ammoniak eine große Bedeutung in der Pathogenese der Typ-C-HE hat, korreliert der Serum-Ammoniakspiegel nicht immer mit dem Schweregrad oder der Prognose der Erkrankung [4,7,13,28]. Die Bestimmung des Ammoniaks ist zur Therapieüberwachung nicht geeignet [1,29].…”