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.

Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) have emerged as leading causes of chronic liver diseases worldwide. ALD and NAFLD share several pathophysiological patterns as well as histological features, while clinically, they are distinguished by the amount of alcohol consumed daily. However, NAFLD coexists with moderate alcohol consumption in a growing proportion of the population. Here, we investigated the effects of moderate alcohol consumption on liver injury, lipid metabolism, and gut microbiota in 30 NAFLD-patients. We anonymously assessed drinking habits, applying the AUDIT- and CAGE-questionnaires and compared subgroups of abstainers vs. low to harmful alcohol consumers (AUDIT) and Cage 0–1 vs. Cage 2–4. Patients who did not drink any alcohol had lower levels of γGT, ALT, triglycerides, and total cholesterol. While the abundance of Bacteroidaceae, Bifidobacteriaceae, Streptococcaceae, and Ruminococcaceae was higher in the low to harmful alcohol drinking cohort, the abundance of Rikenellaceae was higher in the abstainers. Our study suggests that even moderate alcohol consumption has an impact on the liver and lipid metabolism, as well as on the composition of gut microbiota.

<b><i>Background:</i></b> In current general practice, elevated serum concentrations of liver enzymes are still regarded as an indicator of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). In this study, we analyzed if an adjustment of the upper limit of normal (ULN) for serum liver enzymes can improve their diagnostic accuracy. <b><i>Methods:</i></b> Data from 363 morbidly obese patients (42.5 ± 10.3 years old; mean BMI: 52 ± 8.5 kg/m²), who underwent bariatric surgery, was retrospectively analyzed. NAFL and NASH were defined histologically according to non-alcoholic fatty liver activity score (NAS) and according to steatosis activity fibrosis (SAF) score for 2 separate analyses, respectively. <b><i>Results:</i></b> In 121 women (45%) and 45 men (46%), elevated values for at least one serum parameter (ALT, AST, γGT) were present. The serum concentrations of ALT (<i>p</i> &#x3c; 0.0001), AST (<i>p</i> &#x3c; 0.0001) and γGT (<i>p</i> = 0.0023) differed significantly between NAFL and NASH, irrespective of the applied histological classification method. Concentrations of all 3 serum parameters correlated significantly positively with the NAS and the SAF score, with correlation coefficients between 0.33 (ALT/NAS) and 0.40 (γGT/SAF). The area under the curves to separate NAFL and NASH by liver enzymes achieved a maximum of 0.70 (ALT applied to NAS-based classification). For 95% specificity, the ULN for ALT would be 47.5 U/L; for 95% sensitivity, the ULN for ALT would be 17.5 U/L, resulting in 62% uncategorized patients. <b><i>Conclusion:</i></b> ALT, AST, and γGT are unsuitable for non-invasive screening or diagnosis of NAFL or NASH. Utilizing liver enzymes as an indicator for NAFLD or NASH should generally be questioned.