Etablierte Therapien und neue therapeutische Ansätze bei der alkoholischen Leberkrankung

Abstract

Chronical alcohol abuse causes more than 200 diseases and/or symptoms and among these alcoholic liver disease (ALD) is of special importance since it occurs frequently and may be life-threatening. In Europe alcohol consumption as well as ALD increased as compared to the rest of the world. It has been estimated that in Europe approximately 500 000 people die every year due to ALD. ALD consists of alcoholic fatty liver, alcoholic steatohepatitis (ASH), alcoholic cirrhosis and hepatocellar cancer (HCC ). Alcohol hepatitis (AH) is a clinical feature with jaundice and liver failure and a high mortality. The course of ALD is variable and depends among others, on genetics, gender, the presence of other liver diseases as well as exposure towards toxic substances and drugs. The treatment of ALD mainly consists of alcohol abstinence which may be difficult to achieve in the alcoholic. The results of the therapy improve by cognitive psychotherapy as well as antigraving medication. The treatment of AH with poor prognosis is limited. Although a number of therapeutic approaches in AH have been tried, the present therapy consists of intensive care in association with the administration of steroids, hyperalimentation and possibly the administration of N-acetylcystein. Presently it is discussed whether liver transplantation is an option for these patients. New therapeutic approaches focuses on pathopyhsiologically identified targets in ALD. This includes elimination of endotoxines, cytokines, and chemokines as well as an inhibition oxidative stress. Antigraving substances, such as Nalmafen also may improve liver function since their administration degreases alcohol consumption. In addition, betain to stimulate methyltransfer as well the inhibition of apoptosis have been investigated. Stimulation of liver regeneration by granulozytecolony stimulating factor as well as mesenchymalcell and bone marrow transplantation have shown some positive results. Nevertheless new therapeutic strategies are urgently needed. Especially in AH with its high mortality.

Pathogenesis, Early Diagnosis, and Therapeutic Management of Alcoholic Liver Disease

“…It gives MSCs the ability to migrate through the endothelial cell layer and be attached and retained in ischemic tissue rather than in distal or intact tissues. Although the mechanisms driving this property are not fully understood, damaged tissues may express specific receptors or ligands that promote the transport, adhesion, and infiltration of MSCs to damaged sites, similar to white blood cells [161,162] (Figure 3).…”

“…In addition, MSCs can also express various soluble factors such as nitric oxide (NO), prostaglandin E2 (PGE2), indoleamine 2, 3-dioxygenase (IDO), IL-6, IL-10, and human leukocyte antigens G (HLA-G). These soluble factors regulate the proliferation and function of a variety of immune cells, and they have also been shown to induce regulatory T cells (Treg) [162,165] (Figure 3).…”

Does Hypoxia Cause Carcinogenic Iron Accumulation in Alcoholic Liver Disease (ALD)?

“…Moreover, the novel concept could provide a molecular rationale to better explain recent advances in treating ALD, e.g. with intravenous infusions of antioxidants such as N-acetylcysteine [ 112 ].…”