Abstract：
BACKGROUND & AIMS:Virus-specific T cells capable of controlling HBV and eliminating hepatocellular carcinoma (HCC) expressing HBV antigens are deleted or dysfunctional in patients with chronic HBV or HBV-related HCC. The goal of this study was to determine if T cell receptor (TCR) gene transfer can reconstitute HBV-specific T cell immunity in lymphocytes of chronic HBV patients and investigate whether HCC cells with natural HBV-DNA integration can be recognized by genetically modified T cells. METHODS:We used vector-mediated gene transfer to introduce HLA-A2-restricted, HBV-specific TCRs into T cells of chronic HBV as well as HBV-related HCC patients. RESULTS:The introduced TCRs were expressed on the cell surface, evidenced by Vβ and pentamer staining. TCR transduced T cells produced IFN-γ, TNF-α, IL-2, and lysed HBV infected hepatocyte-like cell lines. Furthermore, HCC cell lines with natural HBV-DNA integration could be recognized by HBV-specific TCR-re-directed T cells. CONCLUSIONS:TCR re-directed HBV-specific T cells generated from PBMC of chronic HBV and HBV-related HCC patients were multifunctional and capable of recognizing HBV-infected cells and HCC tumor cells expressing viral antigens from naturally integrated HBV DNA. These genetically modified T cells could be used to reconstitute virus-specific T cell immunity in chronic HBV patients and target tumors in HBV-related HCC.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Gehring AJ,Xue SA,Ho ZZ,Teoh D,Ruedl C,Chia A,Koh S,Lim SG,Maini MK,Stauss H,Bertoletti Adoi
10.1016/j.jhep.2010.10.025subject
Has Abstractpub_date
2011-07-01 00:00:00pages
103-10issue
1eissn
0168-8278issn
1600-0641pii
S0168-8278(10)01086-Xjournal_volume
55pub_type
杂志文章abstract：BACKGROUND/AIMS:The x gene of hepatitis B virus encodes a transactivating factor of 154 amino acids, termed HBx, which stimulates transcription of multiple viral and cellular genes. The transactivating function is probably associated with a tumorigenic potential of HBx, since x gene sequences, encoding functional HBx, ...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/0168-8278(95)80311-4
更新日期：1995-07-01 00:00:00
abstract：:Interleukin-6 has a variety of biological effects, mainly on the immune system. The regulation of this signal at both the site of production and the site of action is necessary to maintain the organism's homeostasis. In the microenvironment of the hepatic sinusoids, Kupffer cells as resident macrophages are the most p...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/s0168-8278(94)80099-5
更新日期：1994-10-01 00:00:00
abstract：BACKGROUND/AIM:Chronic rejection is an important cause of graft loss following liver transplantation. A number of risk factors for chronic rejection have been identified previously, albeit inconsistently. These include cytomegalovirus infection detected by a number of different techniques, including immunohistochemical...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/s0168-8278(99)80294-3
更新日期：1999-11-01 00:00:00
abstract：BACKGROUND & AIMS:Liver failure is associated with progressive cytotoxic brain oedema (astrocyte swelling), which underlies hepatic encephalopathy (HE). Ammonia and superimposed inflammation are key synergistic factors in HE, but the mechanism(s) involved remain unknown. We aimed to determine whether aquaporin-4 (AQP4)...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2010.02.020
更新日期：2010-07-01 00:00:00
abstract：BACKGROUND/AIMS:Combinations of beta-blockers and vasodilators have been assessed for their ability to lower portal pressure and so prevent variceal haemorrhage. However, reservations have been raised particularly with respect to renal function and perfusion after the use of these medicines in patients with chronic liv...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/s0168-8278(96)80296-0
更新日期：1996-12-01 00:00:00
abstract：BACKGROUND & AIMS:MicroRNAs (miRNAs) have been shown to be involved in many biological processes by affecting their target gene expression. miR-122 has been extensively studied in hepatocarcinogenesis. However, the role of miR-122 in liver fibrosis remains unknown. METHODS:The mRNA expression levels of miR-122, prolyl...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2012.11.011
更新日期：2013-03-01 00:00:00
abstract：BACKGROUND/AIMS:Haematopoietic stem cells (HSC) have previously been shown in some studies to migrate to damaged and diseased liver where a small proportion will engraft. Such cells can promote liver repair in rodent models of liver injury and lead to improved liver function in uncontrolled clinical studies. In order t...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2009.06.021
更新日期：2009-10-01 00:00:00
abstract：BACKGROUND/AIMS:Urinary 3-oxo-delta4 bile acids have been detected in infants who ultimately died of liver disease. We used qualitative and quantitative methods to compare urinary 3-oxo-delta4 bile acids in liver disease, determining their composition and evaluating the prognostic implication in patients of various age...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/0168-8278(88)80014-x
更新日期：1998-02-01 00:00:00
abstract：BACKGROUND/AIMS:Liver allograft is known to protect simultaneously transplanted organs from acute rejection. We have reported that only 6% of combined liver-kidney recipients, versus 32.5% of kidney recipients, develop kidney graft acute rejection. Release of soluble human leukocyte antigen (HLA) molecules by the liver...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/s0168-8278(03)00354-4
更新日期：2003-10-01 00:00:00
abstract：BACKGROUND:Hepatopulmonary syndrome (HPS) has been defined as a clinical triad, including chronic liver disease, gas exchange defects (increased alveolar-arterial PO2 difference irrespective of the presence of arterial hypoxemia), and widespread intrapulmonary vascular dilatations. We determined the incidence and the c...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/s0168-8278(00)00108-2
更新日期：2001-05-01 00:00:00
abstract：BACKGROUND:Individuals who reach the antibody threshold level of 10IU/l against the surface protein of the hepatitis B virus (HBV) after completion of a series of hepatitis B vaccination are considered to be long-term protected against a clinically manifest HBV infection. CASE REPORT:Here we describe an acute hepatiti...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2008.07.040
更新日期：2009-02-01 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:In the sera of infected patients, hepatitis C virus (HCV) particles display heterogeneous forms with low-buoyant densities (<1.08), underscoring their lipidation via association with apoB-containing lipoproteins, which was proposed to occur during assembly or secretion from infected hepatocytes. Howev...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2018.11.033
更新日期：2019-04-01 00:00:00
abstract：BACKGROUND/AIMS:[corrected] Hepatobiliary carcinoma (HBC) has been considered to be a late complication of end-stage primary sclerosing cholangitis (PSC). The incidence of HBC is approximately 20% in PSC patients evaluated for liver transplantation. The diagnosis of HBC is difficult, at least at an early stage and the ...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/s0168-8278(01)00042-3
更新日期：2001-06-01 00:00:00
abstract：BACKGROUND/AIMS:Extrahepatic biliary atresia (EHBA) and chronic progressive intra-hepatic cholestasis (Byler's disease) are two distinct disorders of unknown etiology in the neonate, characterized by profound cholestasis. The aim of the present study was to investigate the inflammatory reaction in liver tissue from pat...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/s0168-8278(97)80253-x
更新日期：1997-04-01 00:00:00
abstract：BACKGROUND & AIMS:Blocking intestinal bile acid (BA) absorption by inhibiting or inactivating the apical sodium-dependent BA transporter (Asbt) classically induces hepatic BA synthesis. In contrast, blocking intestinal BA absorption by inactivating the basolateral BA transporter, organic solute transporter alpha-beta (...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2012.03.025
更新日期：2012-08-01 00:00:00
abstract：BACKGROUND & AIMS:Acetaminophen (APAP)-induced liver injury is the most frequent cause of acute liver failure in the US and many other countries. Metabolism of APAP results in formation of APAP protein adducts (APAP-AD) in hepatocytes and triggers mitochondrial dysfunction and necrosis. However, the mechanisms for how ...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2016.04.025
更新日期：2016-08-01 00:00:00
abstract：BACKGROUND & AIMS:Sepsis is an acute systemic inflammatory response to infection associated with high patient mortality (28-40%). We hypothesized that interleukin (IL)-30, a novel cytokine protecting mice against liver injury resulting from inflammation, would generate a protective effect against systemic inflammation ...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2015.12.020
更新日期：2016-05-01 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
abstract：BACKGROUND & AIMS:miR-224 is up-regulated in human HCCs as compared to both paired peri-tumoral cirrhotic tissues and cirrhotic livers without HCC. Here, we have cloned the miR-224 regulatory region and characterized its transcriptional regulation by the NFκB-dependent inflammatory pathways. METHODS:Mature miRNA expre...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2011.11.017
更新日期：2012-04-01 00:00:00
abstract：:Calcium concentrations in pig livers were serially estimated following ischemia-reperfusion. Ischemia was produced by clamping the hepatic artery and the portal vein for 90 min (Group 1, n = 6) or for 180 min (Group 2, n = 6) during temporary side-to-side portacaval shunt performed before the induction of ischemia. Al...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/s0168-8278(05)80140-0
更新日期：1994-06-01 00:00:00
abstract：BACKGROUND/AIMS:Osteopenia is a common complication in some chronic cholestatic liver diseases. Our aims were to determine the prevalence and severity of bone disease in patients with primary sclerosing cholangitis; and identify risk factors to predict the presence and progression of osteopenia. METHODS:Eighty-one pat...
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(98)80253-5
更新日期：1998-11-01 00:00:00
abstract：BACKGROUND/AIMS:Hepatic stellate cells are pivotal to fibrogenesis in the liver and many potential anti-fibrotic therapeutics are required to act on targets within hepatic stellate cells. The aim of this study was to generate a human antibody fragment to hepatic stellate cells. METHODS:Phage display was used to genera...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2005.01.028
更新日期：2005-06-01 00:00:00
abstract：BACKGROUND/AIMS:Multidrug resistance-associated protein 3 (MRP3) is a carrier-type transport protein belonging to the ABC transporters. It is expressed in normal tissues, and enhanced expression in many cancers has been reported. In this study, we investigated the usefulness of MRP3 as a target antigen in immunotherapy...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2008.05.012
更新日期：2008-12-01 00:00:00
abstract：BACKGROUND & AIMS:Common genetic variation within the IL28 locus has been found to influence the effect of peg-interferon and ribavirin combination therapy against chronic hepatitis C virus (HCV) infection. Expression of IL28 in peripheral blood cells has been reported to be higher in patients with IL28 SNP genotypes a...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2010.09.019
更新日期：2011-06-01 00:00:00
abstract：:This article summarizes the current state of antiviral therapy of hepatitis B with special attention given to areas that remain controversial or poorly defined. Strict adherence to liver association practice guidelines may result in missed opportunities to treat patients with significant underlying liver disease. In p...
journal_title：Journal of hepatology
pub_type： 杂志文章,评审
doi：10.1016/j.jhep.2008.01.011
更新日期：2008-01-01 00:00:00
abstract：:Advances in the management of the pulmonary complications of cystic fibrosis may result in an increasing prevalence of patients with chronic liver disease which may, therefore, become more important in the long-term management of cystic fibrosis patients. However, no simple and reliable test is available for the diagn...
journal_title：Journal of hepatology
pub_type： 临床试验,杂志文章
doi：10.1016/0168-8278(95)80444-7
更新日期：1995-05-01 00:00:00
abstract：:Hepatitis C virus (HCV) infects mononuclear cells and may be responsible, as are other viruses, for immunologic disorders. The immunologic abnormalities observed in HCV infections are usually non-specific (i.e. cryoglobulinemia, immune complex deposits, autoantibodies). The association with cryoglobulinemia is clear a...
journal_title：Journal of hepatology
pub_type： 杂志文章,评审
doi：10.1016/s0168-8278(99)80404-8
更新日期：1999-01-01 00:00:00
abstract：BACKGROUND & AIMS:Because abdominal ultrasonography cannot reliably quantify hepatic steatosis, accurate data on the incidence of non-alcoholic fatty liver disease (NAFLD) are lacking. We aimed to study the population incidence of NAFLD with state-of-the-art non-invasive tests. METHODS:This was a prospective cohort st...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2014.08.041
更新日期：2015-01-01 00:00:00
abstract：BACKGROUND/AIMS:The efficacy of anti-viral therapy for chronic hepatitis B virus (HBV) is lost upon the emergence of resistant virus. Using >500 patient HBV isolates from several entecavir clinical trials, we show that phenotypic susceptibility correlates with genotypic resistance and patient virologic responses. METH...
journal_title：Journal of hepatology
pub_type： 杂志文章
doi：10.1016/j.jhep.2007.12.024
更新日期：2008-06-01 00:00:00
