Alcohol use disorder is a leading cause of morbidity and mortality [
1] and refers to impaired control over alcohol use, leading to physiological dependency and tolerance with psychological, social and physical consequences. While the alcohol consumption in Austria was below average in 2010, Austrians had the highest largest rate of chronic liver disease and liver cirrhosis in Europe in 2017 [
2]. Prevalence of alcohol use disorders and dependence was roughly 15% in Austria in 2014 [
3,
4], proving a tremendous burden of disease and socioeconomic costs. Examination of different indicators of alcohol consumption and its possible health effects in Austria suggest that alcohol consumption behaviour is becoming more moderate, thus, decreasing the negative effects associated with alcohol [
5].
Contemporary psychiatric research suggests that developmental and neurobiological pathways are related to the dopamine system, oxytocin system and the glucocorticoid system in alcohol use disorder [
6]. The pathways leading to alcohol addiction are complex and multidimensional including dysregulation of molecular and gene expression, altered brain sensitivities to reward- and stress-related cues and behavioural patterns that include risk taking, social isolation or especially stress dysregulation [
6]. The pathophysiology of alcohol dependency is not only a dysregulation of neuronal function; it can be understood as a systemic disease with alterations induced by various metabolic stresses. Alcohol consumption increases circulating levels of fibroblast growth factor (FGF) 21 in humans and mice [
7]. FGF proteins are classified into endocrine- and paracrine/autocrine-regulated energy and are involved in a wide variety of biological metabolic processes. FGF 21 with a half-life of 0.7–1.1 h is expressed in liver, white adipose tissue, brown adipose tissue and pancreas and seems to influence drinking and eating preferences. FGF21 as a neurotropic hormone acts on the nervous system by suppressing the intake of alcohol. This provides evidence for a feedback liver–brain endocrine pathway that limits alcohol consumption [
7]. The effects of FGF21 on the central nervous system (CNS) are associated with decreased dopamine, a key neurotransmitter used in reward pathways [
8]. The family of fibroblast growth factors (FGFs) consists of 22 members; these proteins function as signalling molecules with endocrine or paracrine function and influence for example energy and mineral metabolism, tissue repair and organogenesis in early development [
9]. FGF21 is a key regulating protein in energy metabolism; it is highly active in liver, white adipose and brown adipose tissue and the pancreas [
10]. Its function is regulated by β‑Klotho, a cofactor necessary for the receptor binding of FGF21 in target organs that is expressed in several of these tissues. In addition to the expression of β‑Klotho in the CNS, FGF21 can cross the blood–brain barrier [
11]. FGF21 administration reduces sweet and alcohol preference in mice, requires the FGF21 coreceptor β‑Klotho in the central nervous system and correlates with reductions in dopamine concentrations in the nucleus accumbens [
8]. FGF21 also increases insulin sensitivity and leads to a decline of plasma glucose, triglycerides, insulin and glucagon [
12]. In mice, supraphysiological levels of FGF21 lead to a reduced intake of alcohol, which is most likely due to changes in drinking behaviour rather than in ethanol metabolism [
8]. Among its central actions, FGF21 induces corticotropin-releasing factor, suppresses arginine vasopressin expression in the hypothalamus and leads to reductions in dopamine concentrations in the nucleus accumbens [
13]. Chronic alcohol consumption stimulates dopamine release from the major terminal area of the mesolimbic dopamine system, the nucleus accumbens [
14]. Chronic alcohol consumption is associated with functional alterations of this important part of the brain reward system [
14]. This leads to the question whether there is a liver–brain reward system.
To better understand the relation of FGF21 and alcohol intake in humans, we measured FGF21 levels in patients with alcoholic liver cirrhosis (ALC), in patients with nonalcoholic liver cirrhosis (NALC) and healthy persons to correlate their present alcohol consumption.