Abstract:
BACKGROUND & AIMS:Non-alcoholic fatty liver disease (NAFLD) is characterized by increased risk of cardiovascular events and liver-fibrosis. Both could be explained by a procoagulant-imbalance that was surmised but never directly demonstrated. We investigated 113 patients with varying histological liver damage [steatosis (n=32), steatohepatitis (n=51), metabolic-cirrhosis (n=30)], 54 with alcoholic/viral-cirrhosis and 179 controls. METHODS:Plasma was evaluated for levels of pro- and anti-coagulants, and for thrombin-generation assessed as endogenous-thrombin-potential (ETP) with and without thrombomodulin or Protac® as protein C activators. The procoagulant-imbalance was defined as ETP-ratio (with-to-without thrombomodulin) or as Protac®-induced-coagulation-inhibition (PICI%). High ETP-ratios or low PICI% indicate resistance to thrombomodulin or Protac® and hence a procoagulant-imbalance. RESULTS:ETP-ratio increased from controls [0.57 (0.11-0.89)] to steatosis [0.72 (0.33-0.86)] and metabolic-cirrhosis [0.80 (0.57-0.95)], (p<0.001), the latter being comparable to that for alcoholic/viral-cirrhosis [0.80 (0.57-0.95) vs. 0.80 (0.44-0.96)]. Factor VIII (a potent procoagulant for thrombin-generation) increased from steatosis [99% (71-150)] to metabolic-cirrhosis [157% (64-232)], p<0.001. Protein C (a powerful anticoagulant) decreased from steatosis [103% (77-228)] to metabolic-cirrhosis [77 (17-146)], p<0.001. As a consequence, factor VIII-to-protein C ratio increased from steatosis [0.96 (0.36-1.60)] to metabolic-cirrhosis [2.05 (0.81-12.1)], p<0.001 and was correlated with the ETP-ratio (rho=0.543, p<0.001). Similar results were obtained for PICI%. Patients with procoagulant-imbalance detected as ETP-ratio greater or PICI% lower than the median value of controls tended to have a higher risk of metabolic-syndrome, higher intima-media thickness, fibrosis, steatosis or lobular inflammation, all considered clinical manifestations of NAFLD. CONCLUSION:NAFLD is characterized by a procoagulant-imbalance progressing from the less severe (steatosis) to the most severe form of the disease (metabolic-cirrhosis). This imbalance appears to result from increased factor VIII and reduced protein C and might play a role in the risk of cardiovascular events and liver-fibrosis commonly observed in NAFLD.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Tripodi A,Fracanzani AL,Primignani M,Chantarangkul V,Clerici M,Mannucci PM,Peyvandi F,Bertelli C,Valenti L,Fargion Sdoi
10.1016/j.jhep.2014.03.013subject
Has Abstractpub_date
2014-07-01 00:00:00pages
148-54issue
1eissn
0168-8278issn
1600-0641pii
S0168-8278(14)00159-7journal_volume
61pub_type
杂志文章abstract:BACKGROUND/AIMS:A distinct subgroup of angiotensin II type 1 receptor (AT1R) blockers (ARBs) have been reported to suppress the development of hepatic steatosis. These effects were generally explained by selective peroxisome proliferator-activated receptor (PPAR) gamma modulating properties of ARBs, independent of thei...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.01.018
更新日期:2009-06-01 00:00:00
abstract::The First European Consensus Conference on the Treatment of Chronic Hepatitis B and C in HIV Co-infected Patients aimed to produce recommendations that could be applied across Europe. However, some important differences exist around Europe, in terms of access to treatment and tests for monitoring. This short survey of...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2005.11.034
更新日期:2006-01-01 00:00:00
abstract::Hepatitis viruses are major threats to human health. During the last decade, highly diverse viruses related to human hepatitis viruses were found in animals other than primates. Herein, we describe both surprising conservation and striking differences of the unique biological properties and infection patterns of human...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2018.11.010
更新日期:2019-03-01 00:00:00
abstract:BACKGROUND AND AIMS:Little is known about EBV-associated intrahepatic cholangiocarcinoma (EBVaICC) due to its rarity. We aimed to comprehensively investigate the clinicopathology, tumor immune microenvironment (TIME) and genomic landscape of this entity in southern China. METHODS:We evaluated 303 ICCs using in situ hy...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.10.037
更新日期:2020-11-16 00:00:00
abstract:BACKGROUND & AIMS:Aceruloplasminemia is a rare autosomal recessive neurodegenerative disease associated with brain and liver iron accumulation which typically presents with movement disorders, retinal degeneration, and diabetes mellitus. Ceruloplasmin is a multi-copper ferroxidase that is secreted into plasma and facil...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.04.039
更新日期:2010-12-01 00:00:00
abstract::The term cirrhosis-associated immune dysfunction refers to the main syndromic abnormalities of immune function, immunodeficiency and systemic inflammation that are present in cirrhosis. The course of advanced cirrhosis, regardless of its aetiology, is complicated by cirrhosis-associated immune dysfunction and this con...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2014.08.010
更新日期:2014-12-01 00:00:00
abstract:BACKGROUND/AIMS:To bridge acute liver failure (ALF) patients to orthotopic liver transplantation, several bioartificial liver (BAL) systems have been developed. The bio-component of most BAL systems consists mainly of porcine hepatocytes. Plasma or blood of ALF patients is perfused through the BAL thereby contacting po...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.11.041
更新日期:2005-04-01 00:00:00
abstract:BACKGROUND & AIMS:Treating HCV infection reduces overall mortality and reduces the risk of multiple extrahepatic complications. Whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications is unknown. METHODS:We identified HCV-positive individuals treated for...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.02.022
更新日期:2020-08-01 00:00:00
abstract::Hepatitis B virus (HBV) variants with a stop codon, a mutated translation initiation codon or other mutations in the pre-C region which prevent e-antigen expression are highly prevalent in anti-HBe chronic carriers and can be positively selected from a mixed virus infection. Our laboratories recently described pre-C v...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(91)90083-n
更新日期:1991-11-01 00:00:00
abstract:BACKGROUND & AIMS:Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of stages from simple steatosis to non-alcoholic steatohepatitis (NASH). However, disease pathogenesis remains largely unknown. microRNA (miRNA or miR) expression has recently been reported to be altered in human NASH, and modulated by urs...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.08.008
更新日期:2013-01-01 00:00:00
abstract::We investigated whether regulation of interferon-alpha gene expression could be involved in liver tumor biology and the role, if any, of hepatitis B virus in the regulation of tumor cytokine gene expression. Gene expression was investigated at the transcriptional level using 'in situ' hybridization of cytokine message...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80215-6
更新日期:1993-03-01 00:00:00
abstract:BACKGROUND/AIMS:Suppressor of cytokine signaling (SOCS)-1, a negative feedback regulator of cytokine signaling pathway, also has a tumor suppressor activity, the silencing of its gene by hypermethylation is suggested to contribute to hepatocarcinogenesis. We studied the effect of the core protein of hepatitis C virus (...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.03.028
更新日期:2005-11-01 00:00:00
abstract::The EASL Monothematic Conference on Translational Research in Viral Hepatitis brought together a group of leading scientists and clinicians working on both, basic and clinical aspects of viral hepatitis, thereby building bridges from bench to bedside. This report recapitulates the presentations and discussions at the ...
journal_title:Journal of hepatology
pub_type:
doi:10.1016/j.jhep.2014.05.016
更新日期:2014-09-01 00:00:00
abstract:BACKGROUND & AIMS:High-density lipoprotein cholesterol (HDL-C) levels are reduced in patients with chronic liver disease and inversely correlate with disease severity. During acute conditions such as sepsis, HDL-C levels decrease rapidly and HDL particles undergo profound changes in their composition and function. We a...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.01.026
更新日期:2020-07-01 00:00:00
abstract:BACKGROUND & AIMS:Non alcoholic steatohepatitis (NASH) has no approved pharmacological therapy. Insulin sensitisers such as thiazolidinediones ameliorate insulin resistance and are a potential therapeutic option. We performed a systematic review and meta-analysis of the effect of thiazolidinediones on histological and ...
journal_title:Journal of hepatology
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.jhep.2011.03.016
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND/AIMS:Interferon therapy has been shown to have beneficial effects in chronic hepatitis C, but the optimal duration of treatment has not been clearly defined. The aims of this study were: (a) to perform a detailed histological comparison of the effects of a 6-month and a 12-month treatment using the Knodell s...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0168-8278(96)80286-8
更新日期:1996-12-01 00:00:00
abstract:BACKGROUND/AIMS:Hepatocellular carcinoma recurrence after curative treatment adversely influences clinical outcome. It is important to explore adjuvant therapies. This phase II/stage 1 multi-center, randomized trial investigated the safety, optimal dosage and preliminary efficacy of PI-88, a novel heparanase inhibitor,...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.jhep.2008.12.023
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND & AIMS:Tumor shrinkage has been considered a fundamental surrogate efficacy measure for new cancer treatments. However, in patients treated with sorafenib for advanced hepatocellular carcinoma (HCC), tumor shrinkage rarely accompanies increased survival, thereby questioning the prognostic value of imaging-ba...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.02.016
更新日期:2012-07-01 00:00:00
abstract:BACKGROUND & AIMS:The mechanisms of treatment resistance to interferon (IFN) and ribavirin (Rib) combination therapy for hepatitis C virus (HCV) infection are not known. This study aims to gain insight into these mechanisms by exploring hepatic gene expression before and during treatment. METHODS:Liver biopsy was perf...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.04.036
更新日期:2010-11-01 00:00:00
abstract:BACKGROUND/AIMS:To evaluate the fluctuating course of serum HBV-DNA levels during the natural history of chronic HBV infection in the general population of North-Eastern Greece, in association with liver disease progression. METHODS:Two hundred and sixty-three adults with chronic HBV, median 34 years of age, were rand...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2008.06.009
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND/AIMS:Rats with long-term cholestasis have reduced ketosis of unknown origin. METHODS:Fatty acid metabolism was studied in starved rats with biliary obstruction for 4 weeks (bile duct ligated rats = BDL rats), and 3, 7, 14, 28 and 84 days after reversal of biliary obstruction by Roux-en-Y anastomosis (RY rat...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00248-9
更新日期:2002-11-01 00:00:00
abstract::Evidence is accumulating that there are changes in the expression of antigens on biliary epithelium in early primary biliary cirrhosis and graft rejection. If any of the biliary diseases including rejection are associated with specific alterations in biliary glycoprotein structure, lectin histochemistry could be usefu...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(88)80043-6
更新日期:1988-06-01 00:00:00
abstract::The heart and liver are organs that are closely related in both health and disease. Patients who undergo liver transplantation may suffer from heart disease that is: (a) related to the original cause of the liver disease such as hemochromatosis, (b) related to the liver disease itself, or (c) related to other associat...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2010.11.003
更新日期:2011-04-01 00:00:00
abstract::We previously reported that high-dose ursodeoxycholate (UDC) infusion in rats resulted in extensive glucuronidation of UDC, and speculated that the glucuronidation causes bicarbonate-rich hypercholeresis induced by UDC (Takikawa, H., Sano, N., Narita, T. and Yamanaka, M. Hepatology 1990; 11: 743-749). To test this hyp...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(92)90015-h
更新日期:1992-05-01 00:00:00
abstract::Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries that is predicted to become also the most frequent indication for liver transplantation by 2030. Over the last decade, it has been shown that the clinical burden of NAFLD is not only confined to liver-relat...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2014.12.012
更新日期:2015-04-01 00:00:00
abstract:BACKGROUND/AIMS:Alcoholic cirrhosis is a common indication for liver transplantation. The present study was aimed to assess the influence of superimposed alcoholic hepatitis on the outcome of liver transplantation in patients with alcoholic cirrhosis. METHODS:Survival rates of 68 patients transplanted for alcoholic ci...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00047-8
更新日期:2002-06-01 00:00:00
abstract:BACKGROUND/AIMS:Treatment of hepatorenal syndrome (HRS) is based on vasoconstrictors. Terlipressin is the one with the soundest evidence. Noradrenalin has been suggested as an effective alternative. The current study was aimed at assessing the efficacy and safety of noradrenalin vs terlipressin in patients with HRS. M...
journal_title:Journal of hepatology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jhep.2007.04.010
更新日期:2007-10-01 00:00:00
abstract:BACKGROUND/AIMS:Non-alcoholic fatty liver disease (NAFLD) pathogenesis remains unknown. Due to the emerging role of free cholesterol (FC) in NAFLD, our aim was to examine the correlation between FC accumulation in patients with NAFLD and the expression of enzymes that regulate cholesterol homeostasis. METHODS:Filipin ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2008.12.016
更新日期:2009-04-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatocytes differentiated from human embryonic stem cells (hESCs) have the potential to overcome the shortage of primary hepatocytes for clinical use and drug development. Many strategies for this process have been reported, but the functionality of the resulting cells is incomplete. We hypothesize t...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2016.02.028
更新日期:2016-06-01 00:00:00
abstract::In this Grand Round presentation, the case of a man with decompensated liver disease is described. He subsequently developed a fatal pulmonary embolism, which may not have occurred if he had been prescribed prophylactic anticoagulation to prevent venous thromboembolic disease. The burden of thrombotic disease in those...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2017.01.006
更新日期:2017-06-01 00:00:00