S2k-Leitlinie nicht alkoholische Fettlebererkrankungen

Roeb, Elke; Steffen, Hans‐Michael; Bantel, Heike; Baumann, Ulrich; Canbay, Ali; Demir, Münevver; Drebber, Uta; Geier, Andreas; Hampe, Jochen; Hellerbrand, Claus; Pathil‐Warth, Anita; Schattenberg, Jörn M.; Schramm, Christoph; Seitz, Helmut K.; Stefan, Norbert; Tacke, Felix; Tannapfel, Andrea; Jansen, Petra Lynen; Bojunga, Joerg

doi:10.1055/s-0035-1553193

Cited by 159 publications

(119 citation statements)

References 160 publications

(178 reference statements)

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“…This is a particular high unmet medical need in non-alcoholic fatty liver disease (NAFLD) encompassing non-alcoholic steatohepatitis (NASH), which can result in end-stage liver disease. Despite the fast growing prevalence of this disease worldwide, no curative therapy exists [4] . Similarly, cirrhosis occurring in the course of alcoholic liver disease cannot be reverted in most cases despite the termination of alcohol consumption [2] .…”

Section: Introductionmentioning

confidence: 99%

Liver Fibrosis: From Pathogenesis to Novel Therapies

Weiskirchen

Tacke²

2016

Dig Dis

131

100

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Chronic liver injury is accompanied by a dysbalanced scarring process, termed fibrosis. This process is mainly driven by chronic inflammation and an altered activity of a multitude of different chemokines and cytokines, resulting in the infiltration by immune cells (especially macrophages) and increase of matrix-expressing cell types. These processes might lead to cirrhosis representing the end-stage of fibrosis. Recent clinical studies comprising patients successfully treated for viral hepatitis showed that liver fibrogenesis and even cirrhosis may be reverted. The hepatic capacity to remodel scar tissue and to revert into a normal liver follows specific mechanistic principles that include the termination of chronic tissue damage, shifting the cellular bias from inflammation to resolution, initiation of myofibroblast apoptosis or senescence and, finally, fibrinolysis of excess scar tissue. The plurality of molecular and cellular triggers involved in initiation, progression and resolution of hepatic fibrogenesis offers an infinite number of therapeutic possibilities. For instance, inflammatory macrophages can be targeted via inhibition of chemokine CCL2 or its receptor CCR2 (e.g., by cenicriviroc) as well as by transfer of restorative macrophage subsets. Another target is galectin-3 that acts at various stages along the continuum from acute to chronic inflammation. Profibrogenic cytokines (e.g., transforming growth factor-β), matricellular proteins (e.g., CCN1/CYR61) or signaling pathways involved in fibrogenesis offer further possible targets. Other options are the application of therapeutic antibodies directed against components involved in biogenesis or remodeling of connective tissue such as lysyl oxidase-like-2 or synthetic bile acids like obeticholic acid that activate the farnesoid X receptor and was antifibrotic in a phase 2 study (FLINT trial). Factors affecting the gut barrier function or the intestinal microbiome further expanded the repertoire of drug targets. In this review, we discuss novel concepts in resolution of hepatic fibrosis and focus on drug targets that might be suitable to trigger resolution of fibrosis.

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Section: Introductionmentioning

confidence: 99%

Liver Fibrosis: From Pathogenesis to Novel Therapies

Weiskirchen

Tacke²

2016

Dig Dis

131

100

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“…To date, liver biopsy represents the only available method that allows discrimination between NAFL and NASH [29]. However, this procedure is invasive and is potentially associated with complications.…”

Section: Diagnosismentioning

confidence: 99%

Fat and Sugar—A Dangerous Duet. A Comparative Review on Metabolic Remodeling in Rodent Models of Nonalcoholic Fatty Liver Disease

et al. 2019

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Nonalcoholic fatty liver disease (NAFLD) is a common disease in Western society and ranges from steatosis to steatohepatitis to end-stage liver disease such as cirrhosis and hepatocellular carcinoma. The molecular mechanisms that are involved in the progression of steatosis to more severe liver damage in patients are not fully understood. A deeper investigation of NAFLD pathogenesis is possible due to the many different animal models developed recently. In this review, we present a comparative overview of the most common dietary NAFLD rodent models with respect to their metabolic phenotype and morphological manifestation. Moreover, we describe similarities and controversies concerning the effect of NAFLD-inducing diets on mitochondria as well as mitochondria-derived oxidative stress in the progression of NAFLD.

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“…Dies sollte nur dann erfolgen, wenn insbesondere bei eine elastographisch erkennbaren Fibrose Zweifel an der Diagnose bestehen [7].…”

Section: (Ausschlussdiagnostik Histologie)unclassified