Publications by authors named "Evangelia Fatourou"

15 Publications

  • Page 1 of 1

Prevalence of bleeding and thrombosis in critically ill patients with chronic liver disease.

Thromb Haemost 2021 Oct 12. Epub 2021 Oct 12.

Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom of Great Britain and Northern Ireland.

Introduction: Haemorrhage and venous thromboembolism (VTE) are recognised complications of chronic liver disease (CLD), but their prevalence and risk factors in critically ill patients is uncertain.

Patients And Methods: We studied a retrospective cohort of patients with CLD non-electively admitted to a specialist intensive care unit determining the prevalence and timing of major bleeding and VTE (early, present on admission/diagnosed within 48h; later diagnosed >48h post ICU admission). Associations with baseline clinical and laboratory characteristics, multi-organ failure (MOF), blood product administration and mortality were explored. Odds ratios (OR) and 95% CIs were calculated using logistic regression.

Results: Of 623 patients with median age 52, bleeding (>48 hours after admission) occurred in 87 (14%) patients. Bleeding was associated with greater illness severity and increased mortality. Gastrointestinal bleeding accounted for 72% of events, secondary to portal hypertension in >90%. Procedure-related bleeding was uncommon. VTE occurred in 125 (20%) patients: Early VTE in 80 (13%) and involving the portal vein (PVT) in 85%. Later VTE affected 45 (7.2%) patients. Hepatocellular Carcinoma (HCC) and non-alcoholic liver disease were independently associated with early VTE (OR 2.79, (95% CI 1.5 -5.2) and 2.32, (1.4 -3.9) respectively), and HCC, sepsis and cryoprecipitate use with late VTE (OR 2.45, (1.11-5.43), 2.26 (1.2-4.3) and 2.60 (1.3-5.1).

Conclusion: VTE was prevalent on admission to critical care and less commonly developed later. Bleeding was associated with MOF and increased mortality. Severe MOF was not associated with an increased rate of VTE which was linked with HCC, and specific etiologies of CLD.
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http://dx.doi.org/10.1055/a-1667-7293DOI Listing
October 2021

Pharmacogenetic Testing in an Academic Psychiatric Clinic: A Retrospective Chart Review.

J Pers Med 2021 Sep 8;11(9). Epub 2021 Sep 8.

Department of Psychiatry and Behavioral Neuroscience, Stritch School of Medicine, Loyola University Chicago and Loyola University Medical Center, Maywood, IL 60660, USA.

Pharmacogenomic (PGx) testing is being increasingly recognized by clinicians as an essential tool to guide medication decisions for treatment of psychiatric illnesses. Extensive implementation of PGx testing, however, varies by setting and location. In this retrospective study, we reviewed charts from 592 patients diagnosed with a psychiatric disorder at the Loyola University Medical Center, for whom PGx testing was performed. Information collected included demographics at the time of testing, psychiatric diagnosis, medical and psychiatric history and medications prior and after PGx testing. Of the 592 charts analyzed, the most common primary diagnoses were depression (52%) and anxiety (12%). Prior to PGx testing, 72% of patients were prescribed three or more medications, whereas, after testing, only 44% were prescribed three or more medications included in the test panel ( < 0.0001). The most common clinical consideration on the PGx reports was recommendation to reduce dosages (33%). After PGx testing, the proportion of patients taking incongruent medications decreased from 26% to 19% and that of patients taking congruent medications increased from 74% to 81% ( = 0.006). The results from this retrospective data analysis demonstrated a reduction in polypharmacy and an increase in recommendation-congruent medication prescribing resulting from implementation of PGx testing.
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http://dx.doi.org/10.3390/jpm11090896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470368PMC
September 2021

Leucocyte ratios are biomarkers of mortality in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure.

Aliment Pharmacol Ther 2020 09 19;52(5):855-865. Epub 2020 Jul 19.

Liver Intensive Therapy Unit, Kings College Hospital, King's College, London, UK.

Background: In patients with cirrhosis, progression to acute decompensation (AD) and acute-on-chronic liver failure (ACLF) has been associated with poor prognosis. Differential leucocyte ratios might predict mortality in systemic inflammatory conditions.

Aim: To evaluate differential leucocyte ratios as prognostic biomarkers in patients with cirrhosis.

Methods: Patients with AD and ACLF were recruited from four centres in three countries. Peripheral blood differential leucocytes were measured (three centres using flow cytometry) on hospital admission and at 48 hours. Ratios were correlated to model for end-stage liver disease (MELD), chronic liver failure-sequential organ failure (CLIF-SOFA), suspected/culture-positive bacterial infection and survival.

Results: Nine hundred twenty-six patients (562 (61%) male, median age 55 (25-94) years) were studied. Overall, 350 (37%) did not survive to hospital discharge. Neutrophil-lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR) were elevated in patients with AD and ACLF who died during their hospital stay. On multivariate analysis NLR retained statistical significance independently of CLIF-SOFA or MELD. NLR >30 was associated with an 80% 90-day mortality in patients with ACLF but not AD. On sensitivity analysis for subgroups (alcohol-related liver disease and suspected sepsis), NLR and MLR retained statistically robust accuracy for the prediction of mortality. Significant predictive accuracy was only observed in centres using flow cytometry.

Conclusion: Leucocyte ratios are simple and robust biomarkers of outcome in ACLF, which are comparable to CLIF-SOFA score but dependent on leucocyte quantification method. NLR and MLR may be used as screening tools for mortality prediction in patients with acutely deteriorating cirrhosis.
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http://dx.doi.org/10.1111/apt.15932DOI Listing
September 2020

Management of metabolic syndrome and cardiovascular risk after liver transplantation.

Lancet Gastroenterol Hepatol 2019 09;4(9):731-741

Sheila Sherlock Liver Unit and University College London Institute for Liver and Digestive Health, Royal Free Hospital, London, UK. Electronic address:

Cardiovascular events are the second most prevalent cause of non-hepatic mortality in liver transplant recipients. The incidence of these events is projected to rise because of the growing prevalence of non-alcoholic steatohepatitis as a transplant indication and the ageing population of liver transplant recipients. Recipients with metabolic syndrome are up to four times more likely to have a cardiovascular event than recipients without, therefore prevention and optimal treatment of the components of metabolic syndrome are key in reducing the risk of these events. Although data on the treatment of metabolic comorbidities specifically in liver transplant recipients are scarce, there is detailed guidance from learned societies that mostly mirrors the guidance for patients at increased cardiovascular risk in the general population. In this Review, we discuss the management of the components of metabolic syndrome following liver transplantation and provide practical stepwise guidance. We also emphasise the need for adequately powered studies for the treatment of metabolic comorbidities in liver transplant recipients.
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http://dx.doi.org/10.1016/S2468-1253(19)30181-5DOI Listing
September 2019

Clinical and prognostic associations of liver volume determined by computed tomography in acute liver failure.

Liver Int 2018 09 25;38(9):1592-1601. Epub 2018 Mar 25.

Liver Intensive Therapy Unit, Institute of Liver Studies, Kings College Hospital, London, UK.

Background: Liver volume (LV) can be non-invasively determined from the analysis of computed tomography (CT) images, and in patients with acute liver injury (ALI) or failure (ALF), it can reflect the balance of structural collapse with hepatic regeneration. We examined its relation to cause of liver injury, measures of liver function and histopathological findings, and utility in prediction of complications and mortality.

Methods: Two hundred and seventy-three patients with ALF/ALI admitted to a specialist intensive care unit were studied. One hundred and ninety-nine patients (73%) had non-acetaminophen (NA) aetiologies and 74 (27%) had acetaminophen-induced disease. LV and proportion of predicted LV (PLV%) were determined from admission CT imaging.

Results: LV and PLV% showed marked variation when aetiologic groups were compared (P < .0001), including loss in cases with indeterminate cause (LV 939 cm [IQR 680-1259], PLV% 56% [42-84]) and increase in Budd-Chiari syndrome (1891 cm [1601-2094], 121% [111-131]). Progression to high-grade encephalopathy was more common with smaller LV and PLV. A < 1000 cm threshold identified NA patients who later developed it with 93% (95%CI 83-98) specificity and odds ratio 10.6 (3.3-34.5) at median 5 days prior to onset, and risk of death in those with NA-drug-induced (DILI) or indeterminate disease with 91% (71-99) specificity and 63% (50-75) sensitivity.

Conclusion: In patients with ALF/ALI, LV shows marked variation by the cause of disease, and in prognostic importance. In indeterminate and DILI cases, loss of volume to <1000 cm may indicate irreversible liver injury and regenerative failure and serve as an early clinical predictor for the development of high-grade encephalopathy and death.
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http://dx.doi.org/10.1111/liv.13725DOI Listing
September 2018

Transfusion strategies in patients with cirrhosis: less is more.

Liver Int 2016 Apr;36(4):503-4

UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and UCL, London, UK.

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http://dx.doi.org/10.1111/liv.13056DOI Listing
April 2016

Keratin 19 protein expression is an independent predictor of survival in human hepatocellular carcinoma.

Eur J Gastroenterol Hepatol 2015 Sep;27(9):1094-102

aLaboratory of Histology-Embryology b2nd Department of Internal Medicine c1st Department of Surgery d2nd Department of Surgery e1st Department of Pathology fDepartment of Pathology, Aretaieion Hospital, National & Kapodistrian University of Athens, Athens, Greece gDepartment of Gastroenterology, Chelsea and Westminster Hospital, London hInstitute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK iDepartment of Anesthesiology, Washington University School of Medicine, Saint Louis, Missouri, USA.

Aim: We aimed to assess the clinicopathological relevance and prognostic significance of expression of the hepatic progenitor cell markers keratin 19 (K19), epithelial cell adhesion molecule (EpCAM) and CD117 (c-KIT) in a White series of hepatocellular carcinoma (HCC).

Methods: We evaluated the immunohistochemical expression of K19, EpCAM and CD117 in 89 surgical specimens of HCC from Greek patients (mean age 66.7±11.3 years, male 75.2%) followed up for 39.6±25.3 months.

Results: K19, EpCAM and CD117 expression was detected in tumour cells of 10.11, 15.38 and 3.7% HCCs, respectively. Female sex was correlated with EpCAM immunohistochemical expression (P=0.035), whereas no other significant relationship with clinicopathological parameters was observed. K19 positivity tended to be correlated with microvascular invasion (P=0.054). In univariate analysis, K19 positivity and microvascular invasion were found to be associated with decreased recurrence-free survival (P<0.001 and P=0.004, respectively) and overall survival (P=0.002 and P=0.029, respectively). EpCAM and CD117 positivity was not correlated with patient survival. In multivariate analysis, K19 positivity emerged as an independent predictor of recurrence-free survival (odds ratio=7.84, 95% confidence interval=2.658-22.912, P<0.001) and overall survival (odds ratio=3.845, 95% confidence interval=1.401-10.549, P=0.009).

Conclusion: Our study confirms the prognostic significance of K19 expression in Caucasian patients with HCCs, providing further evidence that it may be used to stratify HCC according to tumour aggressiveness.
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http://dx.doi.org/10.1097/MEG.0000000000000398DOI Listing
September 2015

ART and science in using transarterial chemoembolization for retreating patients with hepatocellular carcinoma.

Hepatobiliary Surg Nutr 2014 Dec;3(6):415-8

1 Liver Unit, St. Mary's Hospital, London, UK ; 2 Sheila Sherlock Liver Unit and UCL Institute of Liver and Digestive Health, Royal Free Hospital, London, UK.

Intermediate stage hepatocellular carcinoma (HCC) comprises of a highly heterogeneous patient population, both in terms of liver function and tumour burden. Transarterial chemoembolization (TACE) is the treatment of choice for this subgroup of patients, provided that liver function is relatively preserved. Not all patients respond to an initial session of TACE, and further session might impair liver function. The ART score consists of an increase of AST >25%, increase of Child-Pugh of one or two points and absence of radiological tumour response and helps identify patients that would not benefit from further TACE sessions. We critically appraise the use of this score, particularly in terms of patient selection and timing of calculation of its variables. Once sufficiently validated, it can become a safe, objective and accurate clinical tool in everyday practice.
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http://dx.doi.org/10.3978/j.issn.2304-3881.2014.07.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4273114PMC
December 2014

Inflammation-based scores do not predict post-transplant recurrence of hepatocellular carcinoma in patients within Milan criteria.

Liver Transpl 2014 Nov;20(11):1327-35

Royal Free Sheila Sherlock Liver Centre and UCL Institute for Liver and Digestive Health, UCL and Royal Free Hospital, London, UK.

Increased preoperative inflammation scores, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and inflammation-based index (IBI) have been related to post-transplant HCC recurrence. We evaluated the association between inflammation-based scores (NLR, PLR, IBI) and post-LT HCC recurrence as well as tumor necrosis after transarterial embolization. 150 consecutive patients who underwent transplantation for HCC within the Milan criteria between 1996 and 2010 were included; data regarding inflammatory markers, patient and tumor characteristics were analyzed. NLR, PLR, and IBI were not significantly associated with post-LT HCC recurrence or worse overall survival. Increased NLR and PLR were associated with complete tumor necrosis in the subset of patients who received preoperative transarterial embolization (P < 0.05). Cox regression analysis revealed that absence of neoadjuvant transarterial therapy (OR = 4.33, 95% CI = 1.28-14.64; P = 0.02) and no fulfillment of the Milan criteria in the explanted liver (OR = 3.34, 95% CI = 1.08-10.35; P = 0.04) were independently associated with post-LT HCC recurrence inflammation-based scores did not predict HCC recurrence post-LT in our group of patients. NLR and PLR were associated with better response to TAE, as this was recorded histologically in the explanted liver. Histological fulfillment of the Milan criteria and absence of neoadjuvant transarterial treatment were significantly associated with post-LT HCC recurrence.
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http://dx.doi.org/10.1002/lt.23969DOI Listing
November 2014

Transarterial chemoembolization and bland embolization for hepatocellular carcinoma.

World J Gastroenterol 2014 Mar;20(12):3069-77

Emmanuel A Tsochatzis, Evangelia Fatourou, James O'Beirne, Andrew K Burroughs, Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute of Liver and Digestive Health, London NW3 2QG, United Kingdom.

Transarterial chemoembolization (TACE) is the first line treatment for patients with intermediate stage hepatocellular carcinoma but is also increasingly being used for patients on the transplant waiting list to prevent further tumor growth. Despite its widespread use, TACE remains an unstandardized procedure, with variation in type and size of embolizing particles, type and dose of chemotherapy and interval between therapies. Existing evidence from randomized controlled trials suggest that bland transarterial embolization (TAE) has the same efficacy with TACE. In the current article, we review the use of TACE and TAE for hepatocellular carcinoma and we focus on the evidence for their use.
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http://dx.doi.org/10.3748/wjg.v20.i12.3069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964379PMC
March 2014

Transarterial embolization as neo-adjuvant therapy pretransplantation in patients with hepatocellular carcinoma.

Liver Int 2013 Jul 26;33(6):944-9. Epub 2013 Mar 26.

The Royal Free Sheila Sherlock Liver Centre and UCL Institute of Liver and Digestive Health, Royal Free Hospital and UCL, London, UK.

Background & Aims: Neo-adjuvant transarterial therapies are commonly used for patients with HCC in the waiting list for liver transplantation (LT) to delay tumour progression, however, their effectiveness is not well-established. We studied the effect of pre-LT transarterial therapies on post-LT HCC recurrence, using the explanted liver histology to assess therapeutic efficacy and the predictors of response to these therapies.

Methods: We included 150 consecutive patients from our prospectively compiled database, listed for liver transplantation using the Milan criteria. Transarterial embolization without chemotherapeutic agents was the transarterial therapy used as standard of care. PVA particles were the embolizing agent of choice.

Results: Sixty-seven (45%) patients had TAE as bridging therapy to liver transplantation, of which 60 were transplanted after 2001. The majority of patients (36, 54%) had partial tumour necrosis after transarterial therapy, whereas 22 (33%) had complete tumour necrosis and 9 (13%) had no necrosis. HCC post-transplant recurrence was independently associated with no neo-adjuvant transarterial therapy (OR 5.395, 95% CI 1.289-22.577; P = 0.021) and the total radiological size of HCC nodules (OR 1.037, 95% CI 1.006-1.069; P = 0.020).

Conclusions: Pre-transplant TAE with the more permanently occluding PVA particles significantly reduces post-transplant HCC recurrence in patients within the Milan criteria.
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http://dx.doi.org/10.1111/liv.12144DOI Listing
July 2013

Liver disease in adult transfusion-dependent beta-thalassaemic patients: investigating the role of iron overload and chronic HCV infection.

Liver Int 2013 Mar;33(3):420-7

2nd Department of Internal Medicine, Hippokration General Hospital, Medical School, University of Athens, Athens, Greece.

Background: Iron overload and hepatitis-C virus (HCV) infection, have been implicated in the evolution of liver disease, in patients with transfusion-dependent beta-thalassaemia major (BTM). However, the impact of these factors in late stages of liver disease in adults with BTM, has not been extensively studied.

Aims: To investigate serum indices of iron overload, HCV infection and liver disease, in a cohort of 211 adult Greek patients with BTM, in relation with the findings from liver biopsies.

Methods: In this cross-sectional study, 211 patients with BTM were enrolled and studied, in relation with HCV infection, ferritin, transaminases, chelation treatment and antiviral treatment. Based on 109 patients biopsied, we correlated liver fibrosis, haemosiderosis and inflammation, with serum indices and HCV status

Results: Among all patients, 74.4% were anti-HCV positive (HCV+). Ferritin was positively correlated with transaminases and negatively correlated with age, while it was not significantly different among HCV+ and HCV- patients. Among the HCV+ patients, 55.4% reported antiviral treatment, while genotype 1 predominated. In a subfraction of 109 patients, in which liver biopsy was performed, 89% were HCV+ and 11% HCV-. Fibrosis was significantly correlated with age (P = 0.046), AST (P = 0.004), ALT (P = 0.044) and inflammation (P < 0.001). Advanced fibrosis was present with even minimal haemosiderosis, independently of ferritin values or HCV history.

Conclusions: These data suggest that in the late stages of liver disease in BTM patients, iron overload may be the critical determinant, since fibrosis is related to the minimal haemosiderosis, independently of HCV history.
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http://dx.doi.org/10.1111/liv.12095DOI Listing
March 2013

Transarterial therapies for hepatocellular carcinoma.

Recent Results Cancer Res 2013 ;190:195-206

The Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, London, NW3 2QG, UK.

Transarterial therapies for hepatocellular carcinoma are considered palliative and should be offered to patients with intermediate stage multinodular disease without extra-hepatic metastases and sufficient liver reserve. They mainly include transarterial chemoembolisation and transarterial embolisation. While transarterial therapy is now a validated treatment for unresectable HCC, there is still a lack of conclusive evidence as to which type and schedule is the optimal procedure. This is mainly due to the lack of standardisation. Combining local therapies or intra-arterial therapies with systemic targeted therapies might prove more effective strategies in the future. In the present article, we review transarterial therapies and critically comment on their indications, complications and outcomes.
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http://dx.doi.org/10.1007/978-3-642-16037-0_13DOI Listing
January 2013

E2F-1 is overexpressed and pro-apoptotic in human hepatocellular carcinoma.

Virchows Arch 2012 May 27;460(5):439-46. Epub 2012 Mar 27.

Laboratory of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, 75 M. Asias str, Goudi, Athens 11527, Greece.

E2F-1 is a transcription factor involved in DNA synthesis and repair, cell proliferation, and apoptosis. Hyposphorylated pRb represses E2F-1 action in early G1 phase, while in late G1, pRb hyperphosphorylation leads to E2F-1 release and activation. In vitro studies have shown that E2F-1 may act either as oncogene or as tumor suppressor gene. We evaluated immunohistochemical expression of E2F-1 protein in chronic viral liver disease and hepatocellular carcinoma (HCC) and correlated this with clinicopathological parameters, cell proliferation, apoptosis, and the expression of E2F-1-regulators, pRb, and phospho-pRb (Ser795). In liver biopsies from 30 patients with chronic viral hepatitis, including 22 with cirrhosis without HCC, and 57 with cirrhosis with HCC, E2F-1 expression was assessed by immunohistochemistry. In chronic hepatitis and cirrhosis, hepatocytes and cholangiocytes demonstrated mild cytoplasmic and/or nuclear membrane E2F-1 immunostaining. In contrast, all HCC (100 %) showed strong nuclear E2F-1 immunostaining, with or without membrane accentuation, while a minority demonstrated additional moderate cytoplasmic immunostaining. Abnormally low pRb and phospho-pRb expression was seen in 70 % and 67.9 % of HCC, respectively. In HCC, nuclear E2F-1 expression was inversely correlated with phospho-pRb expression (p = 0.001) and positively related to tumor apoptotic index (p = 0.025). No significant correlation was found between E2F-1 expression and patient demographics, HCC etiology, tumor grade, pRb, p53 expression, or cell proliferation. In conclusion, we show that the increased expression of E2F-1 protein in human HCC is correlated with enhanced tumor cell apoptosis supporting a pro-apoptotic role of E2F-1 in human HCC.
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http://dx.doi.org/10.1007/s00428-012-1220-4DOI Listing
May 2012

Adaptive immunity in hepatocellular carcinoma: prognostic and therapeutic implications.

Expert Rev Anticancer Ther 2009 Oct;9(10):1499-510

2nd Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital, 114 Vas. Sophias Ave., 115 27 Athens, Greece.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and has a poor prognosis. Host immunity can either protect or promote tumor growth by the predominance and activation of certain subsets of immune cells. It has been established that antigens such as AFP, MAGE, glypican 3 and NY-ESO, which are highly expressed in HCC, are potential targets for T-cell responses. Several studies have come to the conclusion that cytotoxic T-cell infiltration of the tumors is indicative of a better survival, whereas the predominance of suppressor cells is associated with a worse outcome and lower survival rates. Finally, certain therapeutic strategies, including radiofrequency ablation and chemoembolization, can enhance the release and exposure of tumor antigens, which might help to overcome the immune tolerance towards the tumor. Therefore, such immune-stimulating therapeutic interventions in combination with immunotherapy strategies represent a promising future approach for HCC treatment.
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http://dx.doi.org/10.1586/era.09.103DOI Listing
October 2009
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