Project description: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. Hepatic gene expression profiling was assessed by DNA microarray in patients with Alcoholic hepatitis (n=15) and normal livers (n=7).
Project description:Supporting plasma proteomic data from clinical patients with alcoholic hepatitis in comparison to relevant controls and across treatment time points, baseline, 28/29 days, 12 weeks. Samples were digested with trypsin, labeled with TMT 10-Plex, then analyzed by LC-MS/MS. Data was searched with MS-GF+ using PNNL's DMS Processing pipeline.
Project description:Super enhancer in liver propagates inflammatory signaling by super enhancer-mediatedinducing chemokine expression and is the therapeutic potential of BET inhibition in Alcoholic hepatitis(AH) treatment.
Project description:Corticosteroids are the current standard of care to improve short-term mortality in severe alcoholic hepatitis (AH), although nearly 40% of the patients do not respond and accurate pre-treatment predictors are lacking. We developed 123-gene prognostic score based on molecular and clinical variables before initiation of corticosteroids. Furthermore, The gene signature was implemented in an FDA-approved platform (NanoString), and verified for technical validity and prognostic capability. Here we demonstrated that a Nanostring-based gene expressoin risk classificatoin is useful to predict mortality in patients with severe alcoholic hepatitis who were treated by corticosteroid
Project description:Corticosteroids are the current standard of care to improve short_term mortality in severe alcoholic hepatitis (AH), although nearly 40% of the patients do not respond and accurate pre_treatment predictors are lacking. We developed 123_gene prognostic score based on molecular and clinical variables before initiation of corticosteroids. Furthermore, The gene signature was implemented in an FDA_approved platform (NanoString), and verified for technical validity and prognostic capability. Here we demonstrated that a Nanostring_based gene expressoin risk classificatoin is useful to predict mortality in patients with severe alcoholic hepatitis who were treated by corticosteroid
Project description:Super enhancer in liver propagates inflammatory signaling by super enhancer-mediatedinducing chemokine expression and is the therapeutic potential of BET inhibition in Alcoholic hepatitis(AH) treatment.