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New insights into the coagulopathy of liver disease and liver transplantation

World Journal of Gastroenterology 2006年第48期12卷 7725-7736页

作者： M Senzolo P Burra E Cholongitas ak burroughs Gastroenterology Department of Surgical and Gastroenterological Sciences University Hospital of Padua Padua ItalyLiver Transplantation and Hepatobiliary Unit Royal Free Hospital London United Kingdom Gastroenterology Department of Surgical and Gastroenterological Sciences University Hospital of Padua Padua Italy Liver Transplantation and Hepatobiliary Unit Royal Free Hospital London United Kingdom

The liver is an essential player in the pathway of coagulation in both primary and secondary haernostasis. Only yon Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrornbotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore, these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrornbopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haernostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery.

关键词： Coagulation Cirrhosis Liver transplantation

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Veno occlusive disease: Update on clinical management

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World Journal of Gastroenterology 2007年第29期13卷 3918-3924页

作者： M Senzolo G Germani E Cholongitas P Burra ak burroughs Gastroenterology Department of Surgical and Gastroenterological Sciences University Hospital of Padua Padua Italy Liver Transplantation and Hepatobiliary Unit Royal Free Hospital London United Kingdom

Hepatic veno-occlusive disease is a clinical syndrome characterized by hepatomegaly, ascites, weight gain and jaundice, due to sinusoidal congestion which can be caused by alkaloid ingestion, but the most frequent cause is haematopoietic stem cell transplantation （STC） and is also seen after solid organ transplantation. The incidence of veno occlusive disease （VOD） after STC ranges from 0 to 70%, but is decreasing. Survival is good when VOD is a mild form, but when it is severe and associated with an increase of hepatic venous pressure gradient 〉 20 mmHg, and mortality is about 90%. Prevention remains the best therapeutic strategy, by using non-myeloablative conditioning regimens before STC. Prophylactic administration of ursodeoxycholic add, being an antioxidant and antiapoptotic agent, can have some benefit in reducing overall mortality. Defibrotide, which has pro-fibrinolytic and antithrombotic properties, is the most effective therapy; decompression of the sinusoids by a b-ansjugular intrahepatic portosystemic shunt （TIPS） can be tried, especially to treat VOD after liver transplantation and when multiorgan failure （HOF） is not present. Liver transplantation can be the last option, but can not be considered a standard rescue therapy, because usually the concomitant presence of multiorgan failure contraindicates this procedure.

关键词： Veno occlusive disease Defibrotide Transjugular intrahepatic portosystemic shunt Liver transplantation

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RECOMMENDATIONS FOR THE SELECTION,STABILIZATION,AND COMPACTION OF SOIL FOR RAMMED EARTH WALL CONSTRUCTION

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Journal of Green Building 2010年第1期5卷 101-114页

作者： Steve burroughs Associates Pty. Ltd. Macquarie ACT 2614 38 Blackman Crescent Australia

Rammed earth possesses environmental advantages over most other competing construction ***,if it is to be more routinely used in the construction of modern,sustainable buildings,its material properties and produc-tion processes must be properly *** paper proposes practical recommendations for soil selection,stabilizer treatment,and on-site compaction for rammed earth,based on a recent set of 219 stabilization *** pur-pose of the recommendations is to maximize the probability of constructing rammed earth walls that meet or exceed a compressive strength criterion of 2 *** recommendations cover:(1)Quantifying the natural soil properties of linear shrinkage and texture in a staged sequence in order to identify suitable soils to stabilize(and to reject unsuit-able soils);(2)Quantifying the amounts of cement and/or lime to be added to the selected soil according to the values of soil properties measured;and(3)Quantifying the forces involved in on-site compaction of stabilized soil(for both manual and pneumatic ramming),and relating these to laboratory-based test *** the recommenda-tions need to be tested and verified/refined using new data,their initial application to rammed earth construction situations in Australia indicates that they have predictive *** research will also indicate the degree of applicability of the recommendations to the production of compressed earth bricks.

关键词： building materials rammed earth soil stabilization cement lime compressive strength compaction

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Transarterial chemoembolization and bland embolization for hepatocellular carcinoma

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World Journal of Gastroenterology 2014年第12期20卷 3069-3077页

作者： Emmanuel A Tsochatzis Evangelia Fatourou James O'Beirne Tim Meyer Andrew K burroughs Sheila Sherlock Liver Centre Royal Free Hospital and UCL Institute of Liver and Digestive Health Department of Oncology Royal Free Hospital and UCL

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 *** 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 *** evidence from randomized controlled trials suggest that bland transarterial embolization(TAE)has the same efficacy with *** the current article,we review the use of TACE and TAE for hepatocellular carcinoma and we focus on the evidence for their use.

关键词： Cirrhosis Hepatocellular carcinoma Mortality Embolization Transarterial chemoembolization Transarterial embolization Prognosis

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Anti-tumour necrosis factor agent and liver injury:literature review,recommendations for management

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World Journal of Gastroenterology 2014年第46期20卷 17352-17359页

作者： Roberta Elisa Rossi Ioanna Parisi Edward John Despott Andrew Kenneth burroughs James O'Beirne Dario Conte Mark Ian Hamilton Charles Daniel Murray Centre for Gastroenterology Royal Free HospitalLondon NW3 2QGUnited Kingdom Department of Pathophysiology and Organ Transplant Universita’ degli Studi di Milano20122 MilanoItaly Division of Gastroenterology and Endoscopy Fondazione IRCCS Ca' GrandaOspedale Maggiore Policlinico20122 MilanoItaly Sheila Sherlock Liver Centre Royal Free Hospital and Institute of Liver and Digestive HealthLondon NW3 2PFUnited Kingdom

Abnormalities in liver function tests,including transient and self-limiting hypertransaminasemia,cholestatic disease and hepatitis,can develop during treatment with anti-tumour-necrosis-factor(TNF)*** optimal management of liver injury related to antiTNF therapy is still a matter of *** some authors recommend discontinuing treatment in case of both a rise of alanine aminotransferase more than5 times the upper limit of normal,or the occurrence of jaundice,there are no standard guidelines for the management of anti-TNF-related liver *** searches were performed in Pub Med,using the following key words:inflammatory bowel disease(IBD);TNF inhibitors;hypertransaminasemia;drugrelated liver injury;*** to published data,elevation of transaminases in patients with IBD treated with anti-TNF is a common finding,but resolution appears to be the usual ***-TNF agents seem to be safe with a low risk of causing severe drugrelated liver *** to our centre experience,we found that hypertransaminasemia was a common,mainly self-limiting finding in our IBD cohort and was not correlated to infliximab treatment on both univariate and multivariate *** algorithm for the management of liver impairment occurring during antiTNF treatment is also proposed and this highlights the need of a multidisciplinary approach and suggests liver biopsy as a key-point in the management decision in case of severe rise of ***,hepatic injury is generally self-limiting and drug withdrawal seems to be an exception.

关键词： Inflammatory bowel disease Tumour necrosis factor inhibitors Hypertransaminasemia Drug-related liver injury Infliximab

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Can non-invasive measurements aid clinical assessment of volume in patients with cirrhosis?

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World Journal of Hepatology 2013年第8期5卷 433-438页

作者： Andrew Davenport Banwari Argawal Gavin Wright Konstantinos Mantzoukis Rumyana Dimitrova Joseph Davar Panayota Vasianopoulou Andrew K burroughs UCL Center for Nephrology Royal Free Hospital Intensive care Unit Royal Free Hospital Sheila Sherlock centre for hepatic diseases Royal Free Hospital Department of Cardiology Royal Free Hospital

AIM:To evaluate the non-invasive assessments of volume status in patients with ***:Echocardiography and multifrequency bioimpedance analysis measurements and short synacthen tests were made in 20 stable and 25 acutely decompensated patients with ***:Both groups had similar clinical assessments,cortisol response and total body water(TBW),however the ratio of extracellular water(ECW)/TBW was significantly greater in the trunk(0.420±0.004 vs0.404±0.005),and limbs(R leg 0.41±0.003 vs 0.398±0.003,P<0.05,and L leg 0.412±0.003 vs 0.399±0.003)with decompensated cirrhosis compared to stable cirrhotics,P<0.05).Echocardiogram derived right atrial and ventricular filling and end diastolic pressures and presence of increased left ventricular end diastolic volume and diastolic dysfunction were similar in both *** decompensated group had lower systemic blood pressure,mean systolic 101.8±4.3 vs122.4±5.3 and diastolic 58.4±4.1 mmHg vs 68.8±3.1 mmHg respectively,P<0.01,and serum albumin30(27-33)vs 32(31-40.5)g/L,P<***:Decompensated cirrhotics had greater leg and truncal ECW expansion with lower serum albumin levels consistent with intravascular volume depletion and increased vascular permeability.

关键词： Cirrhosis Bioimpedance Echocardiography Extracellular water Ascites Cortisol

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Adipokines levels are associated with the severity of liver disease in patients with alcoholic cirrhosis

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World Journal of Gastroenterology 2015年第10期21卷 3020-3029页

作者： Maria Kalafateli Christos Triantos Emmanuel Tsochatzis Marina Michalaki Efstratios Koutroumpakis Konstantinos Thomopoulos Venetsanea Kyriazopoulou Eleni Jelastopulu Andrew burroughs Chryssoula Lambropoulou-Karatza Vasiliki Nikolopoulou Department of Gastroenterology University Hospital of Patras The Royal Free Sheila Sherlock Liver Centre Royal Free Hospital Department of Endocrinology University Hospital of Patras Department of Public Health Medical SchoolUniversity of Patras Department of Internal Medicine University Hospital of Patras

AIM:To investigate the adipokine levels of leptin,adiponectin,resistin,visfatin,retinol-binding protein 4(RBP4),apelin in alcoholic liver cirrhosis(ALC).METHODS:Forty non-diabetic ALC patients[median age:59 years,males:35(87.5%),Child-Pugh(CP)score:median 7(5-12),CP A/B/C:18/10/12,Model for End-stage Liver Disease(MELD):median 10(6-25),follow-up:median 32.5 mo(10-43)]were prospectively *** serum adipokine levels were estimated in duplicate by *** characteristics were assessed with tetrapolar bioelectrical impedance ***’s rank correlation coefficient was used to assess possible associations with adipokine *** and multivariate Cox regression analysis was used to determine independent predictors for ***:Body mass index:median 25.9(range:20.1-39.3),fat:23.4%(7.6-42.1),fat mass:17.8(5.49-45.4),free fat mass:56.1(39.6-74.4),total body water(TBW):40.6(29.8-58.8).Leptin and visfatin levels were positively associated with fat mass(P<0.001/P=0.027,respectively)and RBP4 with TBW(P=0.025).Median adiponectin levels were significantly higher in CPC compared to CPA(CPA:7.99±14.07,CPB:7.66±3.48,CPC:25.73±26.8,P=0.04),whereas median RBP4 and apelin levels decreased across the spectrum of disease severity(P=0.006/P=0.034,respectively).Following adjustment for fat mass,visfatin and adiponectin levels were significantly increased from CPA to CPC(both P<0.001),whereas an inverse correlation was observed for both RBP4 and apelin(both P<0.001).In the multivariate Cox regression analysis,only MELD had an independent association with overall survival(HR=1.53,95%CI:1.05-2.32;P=0.029).CONCLUSION:Adipokines are associated with deteriorating liver function in a complex manner in patients with alcoholic liver cirrhosis.

关键词： Adipokines Adiponectin Cirrhosis Leptin Resistin

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