title: Molecular targets in the treatment of alcoholic hepatitis.
abstract: Alcohol related costs to health and society are high. One of the most serious complications of alcohol misuse to the individual is the development of alcoholic hepatitis (AH), a clinical syndrome of jaundice and progressive inflammatory liver injury in patients with a history of recent heavy alcohol use. It has a poor outcome and few existing successful therapies. The use of glucocorticoids in patients with severe AH is still controversial and there remains a group of patients with glucocorticoid-resistant disease. However, as our understanding of the pathogenesis of the condition improves there are opportunities to develop new targeted therapies with specific actions to control liver inflammation without having a detrimental effect on the immune system as a whole. In this article we review the molecular mechanisms of AH concentrating on the activation of the innate and adaptive immune response. We consider existing treatments including glucocorticoids, anti-tumor necrosis factor therapy and pentoxifylline and their limitations. Using our knowledge of the disease pathogenesis we discuss possible novel therapeutic approaches. New targets include pro-inflammatory cytokines such as interleukin (IL)-17, chemokines and their receptors (for example IL-8, CXCL9 and CXCR3) and augmentation of anti-inflammatory molecules such as IL-10 and IL-22. And there is also future potential to consider combination therapy to selectively modulate the immune response and gain control of disease.
authors.affiliation: Department of Liver Medicine, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom.
authors.forename: Ashwin D
authors.initials: AD
authors.lastname: Dhanda
authors.forename: Richard Wl
authors.initials: RW
authors.lastname: Lee
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
authors.forename: C Anne
authors.initials: CA
authors.lastname: McCune
mesh_terms: D000818:Animals; D006519:Hepatitis, Alcoholic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D058990:Molecular Targeted Therapy; D010431:Pentoxifylline / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline
keywords: Alcoholic hepatitis; Chemokine receptors; Interleukins; Pentoxifylline; Tumour necrosis factor-α