Pathophysiology and Management of Alcoholic Liver Disease: Update 2016

Abstract

Alcoholic liver disease (ALD) is a leading cause of cirrhosis, liver cancer, and acute and chronic liver failure and as such causes significant morbidity and mortality. While alcohol consumption is slightly decreasing in several European countries, it is rising in others and remains high in many countries around the world. The pathophysiology of ALD is still incompletely understood but relates largely to the direct toxic effects of alcohol and its main intermediate, acetaldehyde. Recently, novel putative mechanisms have been identified in systematic scans covering the entire human genome and raise new hypotheses on previously unknown pathways. The latter also identify host genetic risk factors for significant liver injury, which may help design prognostic risk scores. The diagnosis of ALD is relatively easy with a panel of well-evaluated tests and only rarely requires a liver biopsy. Treatment of ALD is difficult and grounded in abstinence as the pivotal therapeutic goal; once cirrhosis is established, treatment largely resembles that of other etiologies of advanced liver damage. Liver transplantation is a sound option for carefully selected patients with cirrhosis and alcoholic hepatitis because relapse rates are low and prognosis is comparable to other etiologies. Still, many countries are restrictive in allocating donor livers for ALD patients. Overall, few therapeutic options exist for severe ALD. However, there is good evidence of benefit for only corticosteroids in severe alcoholic hepatitis, while most other efforts are of limited efficacy. Considering the immense burden of ALD worldwide, efforts of medical professionals and industry partners to develop targeted therapies in ALF has been disappointingly low.

Fatigue in chronic liver disease: New insights and therapeutic approaches

“…Within this figure, cirrhosis is responsible for 70%‐80% of the directly recorded mortality from alcohol. In addition to its remarkable health impact, this huge disease burden related to ALD has an economic impact of about 125 billion Euros annually in Europe, accounting for 1.3% of the gross domestic product …”

“…In addition to its remarkable health impact, this huge disease burden related to ALD has an economic impact of about 125 billion Euros annually in Europe, accounting for 1.3% of the gross domestic product. 7 The focus of the clinician in CLD is naturally on managing the risk to life associated with progression of the disease to cirrhosis and its associated complications through disease slowing therapy, management of complications and, where necessary, transplantation. It is increasingly being appreciated, however, that CLD can be accompanied by complex symptoms present throughout the disease course which often have a substantial impact on patient quality of life (QOL).…”

Premature mortality due to alcohol-related diseases of the liver in Poland according to voivodships

“…It is estimated that 60--80% of liver cirrhosis cases are caused by excessive consumption of alcohol [10]. Less often, they are caused by other factors, such as hepatotropic viruses, autoimmune diseases, bile stuck in the course of various illnesses, drugs and other toxins [20]. as another example, acute pancreatitis is associated with alcohol consumption in 30-50% of cases [21,22].…”

FXR and TGR5 Agonists Ameliorate Liver Injury, Steatosis, and Inflammation After Binge or Prolonged Alcohol Feeding in Mice

“…However, despite significant advances in understanding ALD pathogenesis, very few treatment options are still available. ( )…”

“…However, despite significant advances in understanding ALD pathogenesis, very few treatment options are still available. (4) Bile acids (BAs) act as signaling molecules, activating two dedicated receptors: farnesoid X receptor (FXR), a member of the nuclear receptor superfamily of transcription factors, and transmembrane G protein-coupled receptor 5 (TGR5). (5) FXR (NR1H4), highly expressed in liver, gut, kidney and adrenal glands, regulates BA synthesis, lipid, glucose and energy homeostasis, as well as inflammation and fibrosis, all of which are important components in the pathogenesis of NASH and ASH.…”