Introduction An imbalance between the acetylation and deacetylation of histone proteins regulated by histone deacetylases (HDACs) has been shown in different types of cancer including hepatocellular carcinoma (HCC). HDAC inhibition appears as promising therapeutic strategy for HCC. However, mostly unspecific HDAC inhibitiors have been applied and the knowledge about the expression and role of individual HDACs in HCC is very limited.

Fibrosis is characterized by accumulation of extracellular matrix and is highly conserved following tissue injury. The regulation of fibroblast growth factor (FGF) signaling is a prerequisite for adequate wound healing in various organs. The FGF family contains 22 proteins that are divided in seven subfamilies and can be classified into paracrine, intracrine and endocrine factors. FGFs signal through tyrosine kinase FGF receptors (FGFRs). Hepatic fibrosis represents a chronic wound healing response and hepatocellular carcinoma (HCC) frequently develops in this “non-healing” wound. Although FGFRs are targets for the treatment of HCC, the expression of FGFs in hepatic fibrosis is still poorly understood.

Hepatocellular carcinoma (HCC) is closely linked to hepatic fibrosis. The activation of hepatic stellate cells (HSC) is the key event of liver fibrosis and activated HSC are major players in hepatocarcinogenesis. Following activation, HSC produce fibroblast growth factors (FGFs) to promote liver regeneration. FGF signaling plays a major role in development, differentiation and wound healing. The FGF family comprises 22 proteins that can be classified into paracrine, intracrine and endocrine factors. FGFs signal through transmembrane tyrosine kinase FGF receptors (FGFRs). Overexpression of FGFRs contributes to HCC development and progression. However, the expression and tumorigenic effects of FGFR-ligands in HCC are largely unknown.

Histone deacetylases (HDACs) comprise in humans currently 18 members divided in 4 classes. Histone deacetylase (HDAC) inhibition (HDACi) is emerging as a promising therapeutic strategy. However, most pharmacological HDACi unselectively block different HDAC classes and their molecular mechanisms of action are only incompletely understood.

Epidemiological and animal studies suggest that (dietary) lipids differ in their potential to drive the development and progression of non-alcoholic fatty liver disease (NAFLD). However, systematic analyses of the effects of different fatty acids (FAs) on hepatocellular steatosis and injury are missing.

Pregnancy-associated plasma protein-A (PAPP-A), a member of the metzincin metalloproteinase superfamily, can enhance local insulin-like growth factor (IGF) bioavailability through proteolytic cleavage of IGF binding proteins. Recently, we have discovered PAPP-A as a tumor promotor in hepatocellular carcinoma applying causal modeling (PLoS Comput Biol. 2015;11(5):e1004293). The IGF-system is known to play a role in hepatic fibrosis, however, the expression and function of PAPP-A in chronic liver disease is unknown.

Background & Aims: Despite a multitude of microbial challenges, knowledge about innate antimicrobial defense of the liver is limited. We systematically investigated expression and regulation of hepatic antibacterial peptides and post-translational modification of human beta defensin-1 (hBD-1).

Pregnancy-associated plasma protein-A (PAPP-A) was firstly discovered as a placental protein present in the circulation of pregnant women. PAPP-A is a metalloproteinase that specifically cleaves insulin-like growth factor (IGF) binding proteins (IGFBPs). It binds tightly to glycosaminoglycans present on the cell surface and thus functions as a growth-promoting enzyme, releasing bioactive IGF in close proximity to the IGF receptor. Recently, we have discovered PAPP-A as a tumor promotor in hepatocellular carcinoma applying causal modeling (PLoS Comput Biol. 2015;11(5):e1004293). Although the IGF-system is known to play a critical role in liver fibrosis, no further information existed regarding the expression and function of PAPP-A in chronic liver disease.

Einleitung: Patienten mit permanentem endständigen Ileostoma (PEI) stellen eine besondere Risikogruppe für eingeschränkte Lebensqualität (LQ) dar.

Hepatocellular carcinoma (HCC) is a refractory malignancy with a high mortality and increasing worldwide incidence rates, including the United States and central Europe. In this study, we demonstrate that a specific inhibitor of signal transducer and activator of transcription 3 (STAT3), NSC74859, efficiently reduces HCC cell proliferation and can be successfully combined with oncolytic virotherapy using vesicular stomatitis virus (VSV). The potential benefits of this combination treatment are strengthened by the ability of NSC74859 to protect primary hepatocytes and nervous system cells against virus-induced cytotoxicity, with an elevation of the VSV maximum tolerated dose in mice. Hereby we propose a strategy for improving the current regimen for HCC treatment and seek to further explore the molecular mechanisms underlying selective oncolytic specificity of VSV.

Background & Aims: Several clinical studies proposed a strong causative link between the consumption of alcohol and progressive liver disease in obese individuals. However, it is incompletely understood how alcohol and obesity interact and whether the combined pathological effects are additive or synergistic. Here, we aimed to establish an in vitro model for joint effects of alcohol and steatosis in hepatocytes.

The metabolic syndrome and hepatic steatosis are independent risk factors for the progression of hepatocellular carcinoma (HCC). Still, the underlying mechanisms are only incompletely understood.

Einleitung: Das Cholangiokarzinom (CC) hat bei Inoperabilität eine schlechte Prognose. Daher wird bei Resektionen häufig das Limit des Operationsausmaßes erreicht unter Akzeptanz eines hohen Risikos für perioperative Komplikationen und R1-Resektionen. Ziel der Untersuchungen war die Analyse des Risikos für perioperative Komplikationen und R1-Situationen unseres Zentrums.

Preoperative chemotherapy with irinotecan is associated with the development of chemotherapy-associated steatohepatitis (CASH). Epidemiological studies have shown that irinotecan-treated obese patients have a higher risk to develop CASH and subsequent related mortality. However, the underlying mechanisms of these aggravated effects of irinotecan in hepatic steatosis are still unknown.

Alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) are the most frequent conditions leading to elevated liver enzymes and liver cirrhosis, respectively, in the Western world. However, despite strong epidemiological evidence for combined effects on the progression of liver injury, the mutual interaction of the pathophysiological mechanisms is incompletely understood.

Silymarin derived from the milk thistle plant Silybum marianum is composed of six major flavonolignans and is widely used for self-treatment of liver diseases. Widely investigated is Silymarin's protective effect on hepatocytes, and recent studies exhibited anticholestatic properties in experimental models of hepatocellular cholestasis. Furthermore, silymarin extracts (SE) have been shown to exert anti-fibrogenic effects in animal models. However, scant information is available on the direct effect of silymarin on activated hepatic stellate cells (HSC), the key players of hepatic fibrosis.

Hintergrund: Effekt und Wirkmechanismus von H2S im Jejunum und Kolon der Ratte sowie Veränderungen in der Neurotransmission mit H2S während des postoperativen Ileus (POI) sollten identifizieren werden.

Iso-alpha-acids (IAA), the main bitter acids present in hops, are constituted during wort boiling with hop, thereby providing beer with its typical bitter taste and foam stability. Recent studies showed that IAA exhibit beneficial effects on glucose and lipid levels in diabetic mice and obese subjects with pre-diabetes. Non-alcoholic fatty liver disease (NAFLD) is considered is the hepatic manifestation of the metabolic syndrome and related metabolic disorders. It starts with hepatocellular lipid accumulation, i.e. steatosis, and a significant number of patients also develops hepatocellular damage and inflammation, i.e. non-alcoholic steatohepatitis (NASH) and progressive fibrosis. The activation of hepatic stellate cells (HSCs) is the key event of hepatic fibrosis, since these cells are the cellular source of excessive extracellular matrix deposition in chronic liver disease including NASH.

Despite improvements in liver surgery over the past decades, hemostasis during hepatic resections remains challenging. This multicenter randomized study compares the hemostatic effect of a collagen hemostat vs. a carrier-bound fibrin sealant after hepatic resection.