The pathobiology of cirrhosis and acute-on-chronic liver failure (ACLF), with an emphasis on alcohol-related liver disease (ARLD)

The pathobiology of cirrhosis and acute-on-chronic liver failure (ACLF), with an emphasis on alcohol-related liver disease (ARLD)

My group studies the pathobiology of cirrhosis and acute-on-chronic liver failure (ACLF), with an emphasis on alcohol-related liver disease (ARLD). We have specific expertise in animal models of liver disease, the study of non-coding RNAs, and the regulation of innate immunity.

We have 3 main projects underway:

1. The role of the IL-1 axis in the pathobiology of ACLF. The IL-1 axis has been shown to be of pivotal importance in determining outcome from cirrhosis and ACLF (Alcaraz-Quiles et al, 2017). The aim of this work is to define the mechanisms of IL-1 signalling in the processes of liver cell death and innate immune activation in ACLF, and identify novel targets for therapy.

2. The role of non-coding RNAs in ACLF. Non-coding RNAs have been demonstrated to regulate innate immune cell phenotype in response to systemic inflammation (Carpenter et al, 2013).  We have identified a novel long non-coding RNA (lncRNA) that regulates innate immune signalling in ACLF. This project is aimed at understanding the mechanism of this process, and developing oligonucleotide therapeutics in this area. 

3. Epigenetics and disease progression in ARLD. Our work has identified an important relationship between pattern of drinking and disease progression in ARLD. We hypothesise this is mediated through epigenetic effects of alcohol. This work is aimed at defining these epigenetic alterations, and their relationship to ARLD disease phenotype. 

Contact Dr Gautam Mehta: gautam.mehta@ucl.ac.uk 

Key collaborators:

Professor Rajiv Jalan, UCL, London, UK; Professor Kevin Moore, UCL, London, UK;  Professor Richard Moreau, INSERM, Paris, France; Professor Schalk van der Merwe, KU Leuven, Belgium.

Key publications:

  1. Bell S, Mehta G, Moore K et al. Ten-year alcohol consumption typologies and trajectories of C-reactive protein, interleukin-6 and interleukin-1 receptor antagonist over the following 12 years: a prospective cohort study. Journal of Internal Medicine. 2017;281:75-85.
  2. Garcia-Martinez R, Andreola F, Mehta G, et al. Immunomodulatory and antioxidant function of albumin stabilises the endothelium and improves survival in a rodent model of chronic liver failure. Journal of Hepatology 2015;62:799-806.
  3. RP Mookerjee, G Mehta, V Balasubramanian, et al. Hepatic Dimethylarginine-Dimethylaminohydrolase1 is Reduced in Cirrhosis and is a Target for Therapy in Portal Hypertension.  Journal of Hepatology 2015;62:325-31.
  4. Mehta G, Mookerjee RP, Sharma V, et al. Systemic Inflammation Is Associated With Increased Intrahepatic Resistance And Mortality In Alcohol-Related Acute-On-Chronic Liver Failure. Liver International 2015;35:724-34.
  5. Mehta G, Gustot T, Mookerjee RP, et al. Inflammation and Portal Hypertension – The Undiscovered Country. Journal of Hepatology 2014;61:155-63.
  6. Mehta G, Jalan R, Mookerjee RP. Cracking the ENCODE: from transcription to therapeutics. Hepatology 2013, 57:2532-5.

Published by: Foundation for Liver Research

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