Gautam Mehta

Gautam Mehta
University College London | UCL · Institute for Liver and Digestive Health

MD PhD

About

102
Publications
19,226
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1,296
Citations
Additional affiliations
January 2012 - December 2013
University College London
Position
  • UCL
January 2010 - present
January 2003 - present

Publications

Publications (102)
Article
Full-text available
SARS-CoV-2 can cause acute respiratory distress and death in some patients1. Although severe COVID-19 disease is linked to exuberant inflammation, how SARS-CoV-2 triggers inflammation is not understood2. Monocytes and macrophages are sentinel cells that sense invasive infection to form inflammasomes that activate caspase-1 and gasdermin D (GSDMD),...
Article
Full-text available
Background and aims: The development of multi-organ injury in cirrhosis is associated with increased intestinal permeability, translocation of gut-derived bacterial products [e.g., lipopolysaccharide (LPS)] into the circulation, and increased non-apoptotic hepatocyte cell death. Pyroptosis is a non-apoptotic, lytic form of cell death mediated by t...
Article
Background and Aim Failure to control oesophago-gastric variceal bleeding (OGVB) and acute-on-chronic liver failure (ACLF) are both important prognostic factors in liver cirrhosis. The aims of this study were to determine whether ACLF and its severity define the risk of death in OGVB and whether insertion of rescue transjugular intrahepatic stent-s...
Article
Full-text available
Objective Acute-on-chronic liver failure (ACLF) is associated with dysfunctional circulating monocytes whereby patients become highly susceptible to bacterial infections. Here, we identify the pathways underlying monocyte dysfunction in ACLF and we investigate whether metabolic rewiring reinstates their phagocytic and inflammatory capacity. Design...
Article
Full-text available
The COVID-19 pandemic is the largest public health challenge in living memory. Patients with underlying liver disease have been disproportionately affected, experiencing high morbidity and mortality. In addition, elevated liver enzymes appear to be a risk factor for disease progression, even in the absence of underlying liver disease. Nevertheless,...
Article
Full-text available
Here, we describe an assay for intestinal permeability in mouse intestinal organoids, although this may also be adapted for other species. Propidium iodide (PI) does not penetrate intact biological membranes and thus cannot enter the lumen of intact organoids. Passage of PI within the lumen can be induced by tight junction disruption or epithelial...
Article
Full-text available
Acute-on-chronic liver failure (ACLF) is characterized predominantly by non-apoptotic forms of hepatocyte cell death. Necroptosis is a form of programmed lytic cell death in which receptor interacting protein kinase (RIPK) 1, RIPK3 and phosphorylated mixed lineage kinase domain-like (pMLKL) are key components. This study was performed to determine...
Article
Full-text available
LINKED CONTENT This article is linked to Thiele et al papers. To view these articles, visit https://doi.org/10.1111/apt.16567 and https://doi.org/10.1111/apt.16672
Article
Full-text available
Effective, low-cost therapeutics are needed to prevent and treat COVID-19. Severe COVID-19 disease is linked to excessive inflammation. Disulfiram is an approved oral drug used to treat alcohol use disorder that is a potent anti-inflammatory agent and an inhibitor of the viral proteases. We investigated the potential effects of disulfiram on SARS-C...
Conference Paper
Full-text available
Background Yaq-001 is a non-absorbable, synthetic carbon with high adsorptive capacity for bacterial products including lipopolysaccharide (LPS) and pro-inflammatory cytokines. Studies in cirrhotic rats showed reduced endotoxemia, improvements in end-organ dysfunction and reduced sensitisation to LPS. The aims of this study were to evaluate the saf...
Article
Albumin is a globular, multifunctional protein that is highly conserved in nature. Alpha‐fetoprotein, Vitamin D and E binding proteins are part of the albumin family and these are produced exclusively in the liver. Albumin is negatively charged and this gives it the oncotic properties it is well known for. More recently, it has become clear that al...
Article
Full-text available
Background Sepsis is common in cirrhosis and is often a result of immune dysregulation. Specific stimuli and pathways of inter‐cellular communications between immune cells in cirrhosis and sepsis are incompletely understood. Immune cell‐derived Extracellular Vesicles (EV) were studied to understand mechanisms of sepsis in cirrhosis. Methods Immune...
Preprint
Full-text available
In the global COVID-19 pandemic, there is a substantial need for effective, low-cost therapeutics. We investigated the potential effects of disulfiram on the incidence and outcomes of COVID-19 in an observational study in a large database of US Veterans Administration clinical records, the VA Corporate Data Warehouse (CDW). The study is motivated b...
Preprint
Full-text available
SARS-CoV-2 causes acute respiratory distress that can progress to multiorgan failure and death in some patients. Although severe COVID-19 disease is linked to exuberant inflammation, how SARS-CoV-2 triggers inflammation is not understood. Monocytes are sentinel blood cells that sense invasive infection to form inflammasomes that activate caspase-1...
Preprint
Full-text available
SARS-CoV-2 causes acute respiratory distress that can progress to multiorgan failure and death in a minority of patients. Although severe COVID-19 disease is linked to exuberant inflammation, how SARS-CoV-2 triggers inflammation is not understood. Monocytes and macrophages are sentinel immune cells in the blood and tissue, respectively, that sense...
Article
Full-text available
Background and AimsPatients with cirrhosis and acute-on-chronic liver failure (ACLF) have immunosuppression, indicated by an increase in circulating immune-deficient monocytes. The aim of this study was to investigate simultaneously the major blood-immune cell subsets in these patients.Material and Methods Blood taken from 67 patients with decompen...
Article
Acute-on-chronic liver failure (ACLF) is a recently recognised and defined syndrome seen in patients with liver cirrhosis and carries a high short-term mortality in excess of 15% at 28 days. ACLF is defined by organ failures (OFs) and is distinct from simple 'acute decompensation' (AD) of cirrhosis. OFs involve the liver, kidney, brain, coagulation...
Article
Full-text available
Objective Systemic inflammation predisposes acutely decompensated (AD) cirrhosis to the development of acute-on-chronic liver failure (ACLF). Supportive treatment can improve AD patients, becoming recompensated. Little is known about the outcome of patients recompensated after AD. We hypothesise that different inflammasome activation is involved in...
Article
Full-text available
Many aspects of the innate immune system have been studied in cirrhosis, and abnormalities have been described supporting both a pro-inflammatory and anti-inflammatory phenotype of myeloid cells. However, the findings of these studies vary by stage of disease and methodology. The recent description of the syndrome of acute-on-chronic liver failure...
Article
Objective: To evaluate the longitudinal relationship between repeated measures of alcohol consumption and risk of developing fatty liver. Patients and methods: This study includes 5407 men and women from a British population-based cohort, the Whitehall II study of civil servants, who self-reported alcohol consumption by questionnaire over approx...
Article
Full-text available
Objective To assess changes in metabolic risk factors and cancer-related growth factors associated with short-term abstinence from alcohol. Design Prospective, observational study. Setting Single tertiary centre. Participants Healthy subjects were recruited based on intention to: (1) abstain from alcohol for 1 month (abstinence group), or (2) co...
Article
Full-text available
Portal hypertension (PH) is a major cause of morbidity and mortality in chronic liver disease. Infection and inflammation play a role in potentiating PH and pro-inflammatory cytokines, including TNF, are associated with severity of PH. In this study, cirrhotic bile duct ligated (BDL) rats with PH were treated with Infliximab (IFX, a monoclonal anti...
Article
Full-text available
Background: Cirrhosis and acute-on-chronic liver failure (ACLF) are associated with systemic inflammation, and caspase-mediated hepatocyte cell death. Emricasan is a novel, pan-caspase inhibitor. Aims of this study were to assess the pharmacokinetics, pharmacodynamics, safety and clinical outcomes of emricasan in acute decompensation (AD) of cirrh...
Article
Full-text available
Background: Moderate alcohol consumption is thought to confer cardiometabolic protective effects. Inflammatory pathways are hypothesized to partly underlie this association. Objectives: The aim of this study was to examine the association between typologies of alcohol consumption and markers of inflammation, and their rate of change over time....
Conference Paper
Portal hypertension is a grave step in the progression of cirrhosis, associated with complications and mortality. The pathobiology of portal hypertension involves fibrosis as well as increased intrahepatic vascular tone. Nitric oxide (NO), synthesized by endothelial nitric oxide synthase (eNOS), is a key regulator of intrahepatic vascular tone. Asy...
Article
Background and aims: Non-selective beta-blockers (NSBBs) have been shown to have deleterious outcomes in patients with refractory ascites, alcoholic hepatitis and spontaneous bacterial peritonitis leading many physicians to stop the drug in these cases. Acute on chronic liver failure (ACLF) is characterized by systemic inflammation and high mortal...
Article
Acute liver failure (ALF) is a rare condition, associated with high mortality and high healthcare cost. Common causes of acute liver injury leading to ALF are viral infection or specific drugs, with significant geographic variation in epidemiology. The most frequent cause of ALF in the UK is paracetamol (acetaminophen) toxicity. Advances in the cri...
Article
Introduction Porto-systemic shunt embolization (PSSe) is an emerging procedure for the treatment of refractory hepatic encephalopathy (HE).1A criteria of MELD <11 was proposed by Laleman et alas a cutodd to predict recurrent HE post embolization. No other significant liver-related complications were noted in this retrospective study. The aim of thi...
Article
Full-text available
Background & aims: Liver failure is characterized by endothelial dysfunction, which results in hemodynamic disturbances leading to renal failure. Albumin infusion improves hemodynamics and prevents renal dysfunction in advance liver failure. These effects are only partly explained by the oncotic properties of albumin. This study was designed to te...
Article
Background & aims: Portal hypertension is characterized by reduced hepatic eNOS activity. Asymmetric-dimethylarginine (ADMA), an eNOS inhibitor, is elevated in cirrhosis and correlates with the severity of portal hypertension. Dimethylarginine dimethylaminohydrolase-1 (DDAH-1) is the key enzyme metabolizing hepatic ADMA. This study characterized D...
Article
Full-text available
Portal hypertension has traditionally been viewed as a progressive process, involving ultrastructural changes including fibrosis, nodule formation and vascular thrombosis, leading to increased intrahepatic resistance to flow. However, it is increasingly recognized that a significant component of this vascular resistance results from a dynamic proce...
Article
The main protagonist of the Emmy award-winning television series 'Breaking Bad', chemistry teacher Walter White, is famously noted for his ambiguous nature as both 'hero' and 'anti-hero'. In a similar vein, the ambiguous influence of microbiota on liver disease has been an active area of discussion in hepatology circles. Various authors have descri...
Conference Paper
Background and Aims: Cirrhosis related portal hypertension causes significant morbidity and mortality. Our previous study in BDL rats showed 5 days of FXR agonist obeticholic acid (OCA) therapy, reduces portal pressure by increasing eNOS activity. This proof of-concept study evaluated short-term OCA treatment to assess tolerance and HVPG response....
Article
Background and AimAcute-on-chronic liver failure (ACLF) is characterized by acute deterioration of cirrhosis, systemic inflammation and multiorgan failure. Inflammation is also key to the pathobiology of portal hypertension. This study aims to define the relationship between systemic and hepatic hemodynamics in patients with ACLF.Methods Sixty-pati...
Article
The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign bioc...
Article
Full-text available
Introduction Portal hypertensive bleeding is a grave complication of cirrhosis. Asymmetric dimethylarginine (ADMA), an endogenous eNOS inhibitor, is elevated in cirrhosis, relates to degree of portal hypertension, and is prognostic in acute-on-chronic liver failure. Dimethylarginine-dimethylaminohydrolase-1 (DDAH-1), a key enzyme metabolising hepat...
Article
Full-text available
The splanchnic and hepatic circulations account for over a quarter of cardiac output and are highly specialized to meet the demands of these complex and complementary organs. The hepatic circulation is fundamental to liver function, and the splanchnic circulation participates in the control of systemic hemodynamics as well as perfusion of the intes...
Article
Gautam Mehta and Bilal Iqbal talk you through changes to the membership of the Royal College of Physicians exam
Chapter
1. Jaundice is a marker of severity of liver disease, as well as a consequence of decompensation. Yellow discolouration is not usually seen until the serum bilirubin is >40μmol/L (twice the upper limit of normal), although the earliest signs of jaundice can be detected in the periphery of the conjunctivae, or in the buccal mucosa. Remember, there a...
Chapter
Interstitial lung disease is a common case for the respiratory section of the MRCP PACES examination. Quite often they are cases of idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) or in the context of systemic (commonly rheumatological) disease. The above cases reflect these common scenarios. To make the diagnosis of interstitial l...
Chapter
As with all neurological patients, you will be more likely to pick up the diagnosis if you take a step back and look at the whole patient. Take some time to assess their facial expressions, speech, tremor, and posture. A common instruction at this station, with the patient seated on a chair is ‘Look at this patient, and examine as appropriate’. Can...
Chapter
• Capacity is at the heart of ethical decision making. Capacity to make choices about healthcare will rarely, if ever, be assessed without the benefit of input from a clinician. Often it is assumed that a psychiatrist should be involved where there are doubts about capacity, but the criteria for assessing capacity are relatively straightforward and...
Book
Volume 2 of a two volume MRCP text, this book includes cases which mimic the style and approach of the MRCP PACES exam. Clinical Medicine for MRCP PACES will equip the candidate attempting the MRCP examination with the skills and knowledge necessary for success, and will also provide an overview of evidence-based medicine for competency-based train...
Chapter
The new Station 5, Integrative Clinical Assessment involves two 10-minute encounters, each known as a ‘Brief Clinical Consultation’. Following an introductory referral, the candidate has 8 minutes to undertake a focused history and examination to solve a clinical problem, answer any questions the patient may have and explain their investigation and...
Chapter
1. Always mention presence/absence of signs of endocarditis in any patient with physical signs of valvular heart disease. More than often, they are absent—but this is an important negative finding. 2. Both a low volume and a slow-rising pulse are signs of severe aortic stenosis. If the patient is in atrial fibrillation (AF), then the pulse usually...
Book
Volume 1 of a two volume MRCP text, this book includes cases which mimic the style and approach of the MRCP PACES exam. Clinical Medicine for MRCP PACES will equip the candidate attempting the MRCP examination with the skills and knowledge necessary for success, and will also provide an overview of evidence-based medicine for competency-based train...
Chapter
Recent years have seen a shift in the perception of communication skills from being considered subjective personal traits, to an objective, evidence-based curriculum of skills and techniques. This development was founded on the recognition that core communication skills are identifiable, can be taught, and form the basis of the majority of professi...