Research interest

Systemic inflammation plays a crucial role in the progression of liver injury and cirrhosis culminating in liver failure. Acute-on-chronic liver failure (ACLF) is a distinct clinical syndrome with defined clinical, prognostic and pathophysiological characteristics associated with high mortality rates that consumes huge healthcare resources and its treatment is an unmet need.

The approach

I have developed a vibrant clinical practice and laboratory with many novel therapies and established extensive collaborations with key investigators, foundations and industry around the world to study the pathophysiological basis of ACLF.

Main discoveries and innovations

  • Establishment of TIPSS for the treatment of variceal bleeding.
  • Recognition of the importance of inflammation in the development of hepatic encephalopathy.
  • Treatment of acute liver failure patients with uncontrolled intracranial hypertension using hypothermia.
  • First hypothesis that acute on chronic liver failure (ACLF) is a clinically, prognostically and pathophysiologically distinct entity.
  • Development of albumin dialysis as treatment for pruritus and acute on chronic liver failure.
  • First large studies showing benefit of transplant in these patients, lack of equity of access and inadequacy of current allocation programs led to change in policy in UK and Spain already.
  • Identification of DASIMAR, a biomarker for liver failure in phase 2 clinical trials.
  • Development of DIALIVE, a liver dialysis device. Phase 2 clinical trial completed.
  • Role of TLR4 in liver failure. Pre-clinical proof of concept completed.
  • Identification of neutrophil dysfunction biomarker in alcoholic hepatitis.
  • Development of Yaq-001, a novel nanoporous carbon to reduce gut bacterial translocation. Phase 2 clinical trial completed.
  • Discovery of L-ornithine phenylacetate (MNK6105), an ammonia lowering drug to treat hyperammonemia and hepatic encephalopathy. Due to enter phase 3 clinical trails.
  • Development of an alcohol management system using information and communication technology strategy.
  • Pyropoptosis as a novel biomarker and target for therapy in liver failure.
  • Necroptosis is dependent upon the RIPK1 pathway and a target of therapy for liver disease.
  • Heart rare variability as a novel strategy for remote monitoring to predict decompensation in patients with cirrhosis.
  • G-TAK, a novel combinatorial therapy for the prevention and treatment of acute-on-chronic liver failure.

Affiliations

University College London, UK
Professor of Hepatology (2000–present)

Royal Free Hospital, UK
Hepatologist (2000–present)

Journal of Hepatology
Editor-in-Chief (2015–2019)