Abstract：
BACKGROUND & AIMS:Hepatic stellate cell activation is a wound-healing response to liver injury. However, continued activation of stellate cells during chronic liver damage causes excessive matrix deposition and the formation of pathological scar tissue leading to fibrosis and ultimately cirrhosis. The importance of sustained stellate cell activation for this pathological process is well recognized, and several signalling pathways that can promote stellate cell activation have been identified, such as the TGFβ-, PDGF-, and LPS-dependent pathways. However, the mechanisms that trigger and drive the early steps in activation are not well understood. METHODS AND RESULTS:We identified the Hippo pathway and its effector YAP as a key pathway that controls stellate cell activation. YAP is a transcriptional co-activator and we found that it drives the earliest changes in gene expression during stellate cell activation. Activation of stellate cells in vivo by CCl4 administration to mice or activation in vitro caused rapid activation of YAP as revealed by its nuclear translocation and by the induction of YAP target genes. YAP was also activated in stellate cells of human fibrotic livers as evidenced by its nuclear localization. Importantly, knockdown of YAP expression or pharmacological inhibition of YAP prevented hepatic stellate cell activation in vitro and pharmacological inhibition of YAP impeded fibrogenesis in mice. CONCLUSIONS:YAP activation is a critical driver of hepatic stellate cell activation and inhibition of YAP presents a novel approach for the treatment of liver fibrosis.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Mannaerts I,Leite SB,Verhulst S,Claerhout S,Eysackers N,Thoen LF,Hoorens A,Reynaert H,Halder G,van Grunsven LAdoi
10.1016/j.jhep.2015.04.011subject
Has Abstractpub_date
2015-09-01 00:00:00pages
679-88issue
3eissn
0168-8278issn
1600-0641pii
S0168-8278(15)00294-9journal_volume
63pub_type
杂志文章abstract：BACKGROUND/AIMS:We have developed a gene therapy strategy based on the observation that insulin-like growth factor I (IGF-I) is necessary for the acquisition and maintenance of the transformed phenotype in hepatocarcinoma. This strategy consists in transfecting the rat hepatoma cell line with an episomal vector express...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/s0168-8278(98)80263-8
更新日期：1998-11-01 00:00:00
abstract：BACKGROUND & AIMS:To evaluate the hypothesis that increasing T cell frequency and activity may provide durable control of hepatitis B virus (HBV), we administered nivolumab, a programmed death receptor 1 (PD-1) inhibitor, with or without GS-4774, an HBV therapeutic vaccine, in virally suppressed patients with HBV e ant...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2019.06.028
更新日期：2019-11-01 00:00:00
abstract：:Eighty-eight dialysis patients were vaccinated with recombinant hepatitis B vaccine prepared in yeast. Fourty-nine patients were immunized 3 times (months 0, 1, 6) intragluteally with 40 micrograms hepatitis B surface antigen (HBsAg) per dose. Only 32 of them (65.3%) showed anti-HBs concentrations above 10 IU/l with a...
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(86)80025-3
更新日期：1986-01-01 00:00:00
abstract：BACKGROUND/AIMS:To evaluate the clinical, biochemical and histological implications of a concomitant HGV infection in "HCV-related" chronic liver disease. METHODS:Eighty-three HCV-RNA positive patients with chronic liver disease were tested for GBV-C/HGV coinfection by heminested PCR. RESULTS:Twenty-two (26.5%) patie...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/s0168-8278(97)80448-5
更新日期：1997-06-01 00:00:00
abstract：BACKGROUND & AIMS:Despite the clinical and genetic significance of macrotrabecular-massive hepatocellular carcinoma (MTM-HCC), its characteristics on imaging have not been described. This study aimed to characterise MTM-HCC on gadoxetic acid-enhanced MRI and to evaluate the diagnostic accuracy and prognostic value of t...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2020.08.013
更新日期：2021-01-01 00:00:00
abstract：:A young female, who had been in excellent health and had used third-generation oral contraceptives, was admitted to hospital because of abdominal pain and ascites. Budd-Chiari syndrome (BCS) was diagnosed by radiographic and histological examination. Tests for myeloproliferative disease, deficiency of coagulation inhi...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/s0168-8278(00)80290-1
更新日期：2000-09-01 00:00:00
abstract：:The reversibility and time course of the adaptive changes in hepatic bile salt transport related to modifications of the bile salt enterohepatic circulation and bile salt pool size have not been previously studied. For this reason a model of reversible interruption of entero-hepatic circulation was characterized in un...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/s0168-8278(05)80182-5
更新日期：1993-08-01 00:00:00
abstract：BACKGROUND:Retrorsine, a naturally occurring pyrrolizidine alkaloid, impairs liver regeneration after partial hepatectomy by mechanisms that are still unclear. AIM:The aim of the study was to clarify the influence of retrorsine on cell cycle progression in the regenerating liver lobes of rats after portal branch ligat...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/s0168-8278(03)00176-4
更新日期：2003-07-01 00:00:00
abstract：:Activities of superoxide dismutase, catalase and glutathione peroxidase were measured in liver biopsy specimens from patients with various liver diseases, including six with chronic persistent hepatitis, nine with chronic active hepatitis, nine with non-alcoholic cirrhosis, eight with alcoholic cirrhosis and eight wit...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/0168-8278(90)90114-7
更新日期：1990-09-01 00:00:00
abstract：BACKGROUND & AIMS:Although the growth suppressing Hippo pathway has been implicated in hepatocellular carcinoma (HCC) pathogenesis, it is unknown at which stage of hepatocarcinogenesis its dysregulation occurs. We investigated in rat and human preneoplastic lesions whether overexpression of the transcriptional co-activ...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2014.06.033
更新日期：2014-11-01 00:00:00
abstract：:The addition of protease inhibitors, boceprevir or telaprevir, to peginterferon+ribavirin (PegIFN/RBV) increases the frequency as well as the severity, and hence, clinical relevance of anemia, which has now become one of the major complications associated with triple therapy. Most significant factors associated with a...
journal_title：Journal of hepatology
pub_type： 杂志文章,评审
doi：10.1016/j.jhep.2013.07.014
更新日期：2013-12-01 00:00:00
abstract：BACKGROUND & AIMS:The accuracy of creatinine-based estimated GFR (eGFR) in assessing the prevalence of chronic kidney disease (CKD) and associated mortality after liver transplantation (LTx) is unknown. Using measured GFR (mGFR) by iothalamate clearance, we determined the prevalence of the entire spectrum of renal dysf...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2014.03.034
更新日期：2014-08-01 00:00:00
abstract：BACKGROUND/AIMS:The number of perisinusoidal myofibroblasts has been shown to be increased in hepatocellular carcinoma, as compared to cirrhosis. This increase might suggest a cooperative relationship between tumour cells and myofibroblasts. To assess this relationship, we undertook: (a) an immunohistochemical study to...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/s0168-8278(98)80186-4
更新日期：1998-07-01 00:00:00
abstract：BACKGROUND/AIMS:Silymarin has protective effects in different experimental conditions, but its efficacy in human liver cirrhosis has not been completely established. Therefore, this study was carried out to determine the effect of silymarin in alcoholics with liver cirrhosis with respect to survival and clinical and la...
journal_title：Journal of hepatology
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1016/s0168-8278(98)80285-7
更新日期：1998-04-01 00:00:00
abstract：:Two groups of patients with HBV DNA-positive chronic active hepatitis B, from 20 French hospitals, separated according to HBe status, were prospectively subjected to a comparative analysis of various epidemiological, clinical, biochemical, serologic and histologic features. There were 61 patients with anti-HBe and 215...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/s0168-8278(05)80352-6
更新日期：1994-05-01 00:00:00
abstract：BACKGROUND & AIMS:Primary non-function and ischaemic cholangiopathy are the most feared complications following donation-after-circulatory-death (DCD) liver transplantation. The aim of this study was to design a new score on risk assessment in liver-transplantation DCD based on donor-and-recipient parameters. METHODS:...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2017.10.034
更新日期：2018-03-01 00:00:00
abstract：:Chronic hepatitis C is now a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma. In March 1997, the National Institutes of Health sponsored a Consensus Development Conference entitled "Management of Hepatitis C". The final statement from the Consensus Panel set forth clear, evidence-based gui...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/s0168-8278(99)80414-0
更新日期：1999-01-01 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:Myeloproliferative neoplasms (MPNs) are the most frequent cause of non-tumoural non-cirrhotic splanchnic vein thrombosis (NC-SVT). Diagnosis of MPN is based on blood cell count alterations, bone marrow histology, and detection of specific gene mutations. Next-generation sequencing (NGS) allows the sim...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2020.06.045
更新日期：2021-01-01 00:00:00
abstract：BACKGROUND & AIMS:In developed countries, hepatitis E is usually associated with travelling to endemic areas, but a growing number of sporadic cases are also seen in patients with no travel history. The aim of this study was to assess the impact and the molecular epidemiology of hepatitis E in Italy. METHODS:Between J...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2010.06.017
更新日期：2011-01-01 00:00:00
abstract：:Chronic cholestatic diseases, whether occurring in infancy, childhood or adulthood, are characterized by defective bile acid transport from the liver to the intestine, which is caused by primary damage to the biliary epithelium in most cases. In this article, approaches to diagnosis and management of the main specific...
journal_title：Journal of hepatology
pub_type： 杂志文章,评审
doi：10.1016/s0168-8278(00)80421-3
更新日期：2000-01-01 00:00:00
abstract：BACKGROUND/AIMS:While combination of peginterferon-alpha (PEG-IFN) and ribavirin (RBV) therapy is the current standard of care for chronic hepatitis C (CHC), only 44-51% of genotype-1 patients achieve a sustained virological response (SVR), and both agents produce treatment-limiting toxicities. In the hepatitis C virus...
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.2007.03.028
更新日期：2007-10-01 00:00:00
abstract：AIM/METHODS:To elucidate the metabolic effect of interferon alpha, the following tests were performed on 14 patients with chronic active hepatitis C before and after interferon therapy (6 million units/day for 2 weeks): (1) oral glucose tolerance tests to measure insulin secretion; (2) euglycemic hyperinsulinemic clamp...
journal_title：Journal of hepatology
pub_type： 临床试验,杂志文章
doi：10.1016/0168-8278(88)80004-7
更新日期：1998-02-01 00:00:00
abstract：:An uncontrolled pilot study of adenine arabinoside monophosphate intramuscularly (ARA-AMP) for 5 days at 10 mg/kg/day and 23 days at 5 mg/kg/day in divided doses, was conducted in 15 consecutive patients known to be HBeAg-positive for a minimum of 12 months. Two patients were lost to follow-up (1 having developed an h...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/s0168-8278(86)80104-0
更新日期：1986-01-01 00:00:00
abstract：BACKGROUND/AIMS:The organic anion transporting polypeptides (OATPs) mediate the uptake of numerous amphipathic compounds into hepatocytes. Our aim was to study the expression and regulation of OATP8 (OATP1B3, SLC21A8/SLCO1B3) and OATP-C (OATP1B1, SLC21A6/SLCO1B1) in hepatocellular carcinomas (HCC). METHODS:RNA and pro...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2003.10.008
更新日期：2004-02-01 00:00:00
abstract：BACKGROUND & AIMS:CD4(+) CD25(+) Foxp3(+) regulatory T cells (Tregs) have a profound ability to control immune responses. We have previously shown that the liver is a major source of peripherally induced Tregs. Here, we investigate the liver cell types and molecular mechanisms responsible for hepatic Treg induction. M...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2014.04.027
更新日期：2014-09-01 00:00:00
abstract：:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and its burden is expected to increase further in the next years. In spite of the advances of classical therapies, such as surgery, transplantation, use of radiofrequency and transarterial embolization, the prognosis of this neoplasm ...
journal_title：Journal of hepatology
pub_type： 杂志文章,评审
doi：10.1016/j.jhep.2013.09.009
更新日期：2014-02-01 00:00:00
abstract：:The coagulation inhibitor protein C was measured in 151 patients with various liver diseases. The protein C level was significantly decreased in patients with alcoholic cirrhosis (n = 73) compared to patients with steatosis (n = 24) (40 +/- 2%) vs. 88 +/- 4%, mean S.E., p less than 0.001). It was also decreased in cas...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/0168-8278(92)90153-g
更新日期：1992-03-01 00:00:00
abstract：BACKGROUND/AIMS:To assess the efficacy and safety of naltrexone for the short and long term treatment of pruritus of cholestasis. METHODS:Twenty patients with pruritus and cholestasis were included. A baseline pruritus score was obtained over 1 week. Patients were then randomized to receive 50 mg/day of naltrexone or ...
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(02)00318-5
更新日期：2002-12-01 00:00:00
abstract：:Data derived from population, case-control, and cohort studies conducted in several Euro-Mediterranean and African countries disclose impressive similarities in the age and modes of hepatitis B virus (HBV) transmission and in the prevalence, duration, and outcome of the four phases of the natural history of chronic in...
journal_title：Journal of hepatology
pub_type： 历史文章,杂志文章,评审
doi：10.1016/j.jhep.2010.12.030
更新日期：2011-07-01 00:00:00
