Transcriptome Analysis Identifies Fn14, a TNF Superfamily Receptor Member, as a Therapeutic Target in Alcoholic Hepatitis

Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease and occurs in patients with excessive alcohol intake It is characterized by marked hepatocellular damage, steatosis and pericellular fibrosis. Patients with severe AH have a poor short-term prognosis. Unfortunately, current therapies (i.e. corticosteroids and pentoxyphylline) are not effective in many patients and novel targeted therapies are urgently needed. The development of such therapies is hampered by a poor knowledge of the underlying molecular mechanisms. Based on studies from animal models, TNF alfa was proposed to play a pivotal role in the mechanisms of AH. Consequently, drugs interfering TNF alfa were tested in these patients. The results were disappointing due to an increased incidence of severe infections. Unluckily, there are not experimental models that mimic the main findings of AH in humans. To overcome this limitation, translational studies with human samples are required. We previously analyzed samples from patients with biopsy-proven AH. In these previous studies, we identified CXC chemokines as a potential therapeutic target for these patients. We expanded these previous observations by performing a high-throughout transcriptome analysis.

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Affò S, Dominguez M, Lozano JJ, Sancho-Bru P, Rodrigo-Torres D, Morales-Ibanez O, Moreno M, Millán C, Loaeza-del-Castillo A, Altamirano J, García-Pagán JC, Arroyo V, Ginès P, Caballería J, Schwabe RF, Bataller R