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Sambrotta M.,Institute of Liver Studies | Thompson R.J.,Institute of Liver Studies | Thompson R.J.,Kings College Hospital
Tissue Barriers | Year: 2015

Progressive familial intrahepatic cholestasis is a clinical description of a phenotype, which we now realize has several different genetic aetiologies. The identification of the underlying genetic defects has helped to elucidate important aspects of liver physiology. The latest addition to this family of diseases is tight junction protein 2 (TJP2) deficiency. This protein is also known as zona occludens 2 (ZO-2). The patients, so far presented, all have homozygous, protein-truncating mutations. A complete absence of this protein was demonstrated. These children presented with severe liver disease, some manifesting extrahepatic features. By contrast, embryonic-lethality was seen in ZO-2 knockout mice. This discovery highlights important differences, not just between species, but also between different epithelia in humans. This commentary discusses the recently presented findings, and some of the issues that arise. © 2015, © Taylor & Francis Group, LLC.


Hames A.,Institute of Liver Studies | Matcham F.,Foundation Medicine | Joshi D.,Institute of Liver Studies | Heneghan M.A.,Institute of Liver Studies | And 3 more authors.
Liver Transplantation | Year: 2016

Young people (YP) with chronic illness have higher rates of mental health problems than the general population, with psychosocial complexity associated with nonadherence and poorer health outcomes. This study aimed to describe the prevalence of anxiety and depression in YP after liver transplantation, with autoimmune liver disease and other chronic liver diseases, identify the factors YP attribute their distress to and the relationship between anxiety/depression, and describe YP's beliefs about their illness and treatment. An electronically administered questionnaire battery was given routinely to YP attending an outpatient liver transition clinic; 187 YP participated, of which 17.7% screened positive for anxiety or depression. There were no significant differences between disease groups. This is significantly higher than the prevalence of common mental health problems in the general adolescent population. Patients most frequently attributed their distress to fatigue, sleep difficulties, financial concerns, problems at work/school, worry, and low self-esteem. Higher levels of depression and anxiety were significantly associated with specific illness and treatment beliefs but not with perceived understanding of illness or treatment control. In conclusion, the increased prevalence of mental health problems in YP and the intertwined nature of these with their physical health outcomes provide evidence that holistic care should be delivered as standard for this age group. Liver Transplantation 22 1544–1553 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases


Efe C.,Hacettepe University | Kav T.,Hacettepe University | Aydin C.,Hacettepe University | Cengiz M.,Gazi University | And 8 more authors.
Digestive Diseases and Sciences | Year: 2014

Results: Mean serum 25(OH)D levels were significantly lower in AIH compared to healthy controls (16.8 ± 9.2 vs. 35.7 ± 13.6, p < 0.0001). Low levels of 25(OH)D (<30 µg/L) were independently associated with advance fibrosis and severe interface hepatitis in AIH patients [p = 0.014; odds ratio (OR) 0.12, 95 % confidence interval (CI) 0.02–0.65 and p = 0.020; OR 0.17, 95 % CI 0.04–0.76, respectively]. Severe 25(OH)D deficiency (<10 µg/L) was associated with advance fibrosis, severe interface hepatitis, low platelet counts and sampling time in a univariate analysis. Only interface hepatitis and fibrosis scores were independently associated with 25(OH)D deficiency in a multiple regression analysis (p = 0.005; OR 0.12, 95 % CI 0.03–0.53 and p = 0.022; OR 0.15, 95 % CI 0.03–0.75, respectively). Mean serum 25(OH)D levels were lower in non-responders compared to responders (9.2 ± 4.8 vs. 17.1 ± 9.4, p = 0.015), and 25(OH)D deficiency was more commonly observed in non-responders than the responders (80 vs. 43 %, p = 0.036).Conclusions: Low 25(OH)D levels are associated with advance fibrosis and severe inflammation in AIH. Our study suggests that vitamin D may be a potential biomarker that predicts response to therapy and histological features in AIH.Background and Aim: 25-Hydroxyvitamin D [25(OH)D] has an important role in fibrosis progression and inflammatory response in patients with various etiologies of chronic liver disease. However, its influence on autoimmune hepatitis (AIH) has not been investigated. We evaluated the association of serum 25(OH)D levels with clinical, biochemical and histological features and response to therapy in AIH.Materials and methods: Serum 25(OH)D levels were quantified in 68 therapy naïve AIH patients and 34 healthy controls. © 2014, Springer Science+Business Media New York.


Rajakumar A.,Institute of Liver Disease and Transplantation | Gupta S.,Institute of Liver Disease and Transplantation | Malleeswaran S.,Institute of Liver Disease and Transplantation | Varghese J.,Institute of Liver Disease and Transplantation | And 3 more authors.
Indian Journal of Anaesthesia | Year: 2016

Background and Aims: The perioperative management of patients presenting for simultaneous liver and kidney transplantation (SLKT) is a complex process. We analysed SLKTs performed in our institution to identify preoperative,intraoperative and post-operative challenges encountered in the management. Methods: We retrospectively studied the case records of 12 patients who underwent SLKT between 2009 and 2014 and analysed details of pre-operative evaluation and optimisation, intraoperative anaesthetic management and the implications of use of perioperative continuous renal replacement therapy (CRRT) and the post-operative course of these patients. Results: Of the total 12 cases, 4 were under 16 years of age. The indications for SLKT were primary hyperoxaluria (5), congenital hepatic fibrosis with polycystic kidney disease (2), ethanol-related end-stage liver disease (ESLD) with hepatorenal syndrome type 1 (1). Four patients had ESLD with end-stage renal disease due to other causes. Six recipients received live donor grafts and 6 patients received cadaveric grafts. Seven patients received intraoperative CRRT. Mean duration of surgery was 12.5 h. Cardiac output monitors used were trans-oesophageal echocardiogram (2), pulmonary artery catheter (1) and pulse contour cardiac output monitor (3). There was 1 sepsis-related mortality on 7th post-operative day. Conclusion: A thorough pre-operative evaluation and optimisation, knowledge and anticipation of potential problems, and meticulous intraoperative fluid management guided by appropriate monitoring and use of CRRT when needed can help in achieving successful outcomes. © 2016 Indian Journal of Anaesthesia | Published by Wolters Kluwer - Medknow.


Rajakumar A.,Institute of Liver Disease and Transplantation | Kaliamoorthy I.,Institute of Liver Disease and Transplantation | Reddy M.S.,Institute of Liver Disease and Transplantation | Rela M.,Institute of Liver Disease and Transplantation | Rela M.,Institute of Liver Studies
Indian Journal of Anaesthesia | Year: 2016

Propionic acidemia (PA) is an autosomal recessive disorder of metabolism due to deficiency of the enzyme propionyl-CoA carboxylase (PCC) that converts propionyl-CoA to methylmalonyl-CoA with the help of the cofactor biotin inside the mitochondria. The resultant accumulation of propionyl-CoA causes severe hyperammonaemia and life-threatening metabolic acidosis. Based on the positive outcomes, liver transplantation is now recommended for individuals with recurrent episodes of hyperammonaemia or acidosis that is not adequately controlled with appropriate medical therapies. We report anaesthetic management of two children with PA for liver transplantation at our institution. It is essential for the anaesthesiologist, caring for these individuals to be familiar with the manifestations of the disease, the triggers for decompensation and management of an acute episode. © 2016 Indian Journal of Anaesthesia.


PubMed | Institute of Liver Studies and The Institute of Hepatology
Type: Journal Article | Journal: Results in immunology | Year: 2013

Cirrhotic patients (CPs) are susceptible to spontaneous bacterial peritonitis (SBP). Aim of this study was to examine if this susceptibility was related to peritoneal macrophages (PMs) altered host defence. Absorbance of phagocytosed particles by PMs from CPs was lower than that of control (31.88% vs. 77.2%). Particle opsonisation increased the absorbance to 41% in CPs PMs, and this value remains lower than the control; 77.2%. Respiratory burst (RB) was expressed as fluorescence index values, and these were higher in PMs from CPs than in controls (82 vs. 41, 73 vs. 26 and 71 vs. 26). IFN- made no further increase of RB values in PMs from CPs. CD14 expression was also higher in CPs PMs. IFN- significantly downregulated CD14 expression in both CPs PMs and control. Reduced phagocytosis by predominantly CD14-positive PMs from CPs could be related to intense RB. Findings suggest altered host defence that could contribute to susceptibility to SBP.


Portal A.J.,Institute of Liver Studies | McPhail M.J.W.,Institute of Liver Studies | McPhail M.J.W.,Imperial College London | Bruce M.,Institute of Liver Studies | And 7 more authors.
Liver Transplantation | Year: 2010

Postoperative acute kidney injury (AKI) increases morbidity and mortality after liver transplantation (LT). Novel methods of assessing AKI including cystatin C (CyC) and neutrophil gelatinase-associated lipocalin (NGAL) have been identified as potential markers of AKI. We compare the ability of standard renal markers (serum creatinine [sCr], estimated glomerular filtration rate [eGFR] and intensive therapy unit organ failure scores with CyC and NGAL to predict AKI within the first 48 hours after LT. 95 patients (median age 50 [interquartile range = 41-59], 60% male) underwent LT (25% with acute liver failure). AKI was defined according to the Acute Kidney Injury Network criteria. Severe AKI was classified as ≥stage 2. NGAL (urine [u] and plasma [p]) and CyC concentrations taken immediately after transplantation on admission to the Liver Intensive Care Unit were compared with standard markers of renal function. Predictive ability was assessed using the area under the curve generated by receiver operator characteristic analysis (AUROC) and logistic regression. Day 0 sCr, uNGAL, pNGAL, CyC, and eGFR predicted AKI as did SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) scores. APACHE II and pNGAL were the most powerful predictors of severe AKI (APACHE II AUROC = 0.87 [0.77-0.97], P < 0.001; pNGAL AUROC = 0.87 [0.77-0.92], P < 0.001). Using multivariate logistic regression, APACHE II (odds ratio 1.64/point [95% confidence interval = 1.22-2.21, P = 0.001] and pNGAL [odds ratio = 1.01/ng/mL [95% confidence interval = 1.00-1.02], P = 0.002) retained independent significance. A "renal risk score" using APACHE II > 13 and pNGAL > 258 ng/mL was calculated with a score of ≥1 having a 100% sensitivity and 76% specificity for severe AKI. In conclusion, a combination of NGAL and APACHE II predicts AKI with high sensitivity and specificity after LT. © 2010 American Association for the Study of Liver Diseases.

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