Abstract:
:The establishment of robust HCV cell culture systems and characterization of the viral life cycle provided the molecular basis for highly innovative, successful years in HCV drug development. With the identification of direct-acting antiviral agents (DAAs), such as NS3/4A protease inhibitors, NS5A replication complex inhibitors, nucleotide and non-nucleoside polymerase inhibitors, as well as host cell targeting agents, novel therapeutic strategies were established and competitively entered clinical testing. The first-in-class NS3/4A protease inhibitors telaprevir and boceprevir, approved in 2011, were recently outpaced by the pan-genotypic nucleotide polymerase inhibitor sofosbuvir that in combination with pegylated interferon and ribavirin, further shortens therapy durations and also offers the first interferon-free HCV treatment option. In the challenging race towards the goal of interferon-free HCV therapies, however, several oral DAA regimens without nucleotide polymerase inhibitors that combine a NS3/4A protease inhibitor, a NS5A inhibitor and/or a non-nucleoside polymerase inhibitor yielded competitive results. Second generation NS3/4A protease and NS5A inhibitors promise an improved genotypic coverage and a high resistance barrier. Results of novel DAA combination therapies without the backbone of a nucleotide polymerase inhibitor, as well as treatment strategies involving host targeting agents are reviewed herein.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Welzel TM,Dultz G,Zeuzem Sdoi
10.1016/j.jhep.2014.08.014subject
Has Abstractpub_date
2014-11-01 00:00:00pages
S98-S107issue
1 Suppleissn
0168-8278issn
1600-0641pii
S0168-8278(14)00554-6journal_volume
61pub_type
杂志文章,评审abstract:BACKGROUND & AIMS:High oxidative stress plays a major role in increasing hepatic vascular resistance in cirrhosis, by facilitating liver fibrosis and by increasing hepatic vascular tone. This study is aimed at investigating whether the use of the novel isoform of recombinant human manganese superoxide dismutase (rMnSOD...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.09.010
更新日期:2013-02-01 00:00:00
abstract::The oesophageal pH was recorded for 3 h after a test-meal in 27 healthy control subjects (group I), 40 patients with alcoholic cirrhosis (group II), and 22 patients with a normal liver and symptoms of gastro-oesophageal reflux (control refluxers). Gastro-oesophageal reflux was observed in 10 of the cirrhotic patients....
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(87)80088-0
更新日期:1987-04-01 00:00:00
abstract:BACKGROUND/AIMS:The aim of this study was to identify human liver proteins that are associated with different stages of liver development. METHODS:We collected liver samples from 14 fetuses between 14 and 41 weeks of development, one child and four adults. Proteins which exhibited consistent and significant variations...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.02.029
更新日期:2009-07-01 00:00:00
abstract:BACKGROUND & AIMS:Insulin resistance, fibrosis and steatosis are established predictors of response to peg-interferon/ribavirin therapy in chronic hepatitis C (CHC). Several host genetic polymorphisms (IL28B, PNPLA3) modify treatment-outcome, the degree of steatosis or fibrosis. The aim of our study was to evaluate the...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.04.036
更新日期:2012-09-01 00:00:00
abstract::Recently reports have indicated that both cimetidine and ranitidine delay cell proliferation in rats following 70% partial hepatectomy and result in an increased mortality following this procedure. The present study was designed to determine whether three H2 blocking agents (cimetidine, ranitidine, famotidine) and a n...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(89)90159-1
更新日期:1989-01-01 00:00:00
abstract::We measured plasma abnormal prothrombin (des-gamma-carboxy prothrombin; DCP) levels in normal subjects and in patients with hepatocellular carcinoma and other various diseases using the enzyme-linked immunosorbent assay developed by Motohara et al. (Pediatr Res 1985; 19: 354-357). Fifty-eight percent of 52 patients wi...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(87)80546-9
更新日期:1987-06-01 00:00:00
abstract:BACKGROUND & AIMS:The therapeutic option for patients with chronic hepatitis delta virus infection (CHD) is limited to interferon alpha with rare curative outcome. Myrcludex B is a first-in-class entry inhibitor inactivating the hepatitis B virus (HBV) and hepatitis D virus (HDV) receptor sodium taurocholate co-transpo...
journal_title:Journal of hepatology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jhep.2016.04.016
更新日期:2016-09-01 00:00:00
abstract:BACKGROUND & AIMS:The prognosis of patients with chronic liver disease is to a great extent determined by the presence and degree of portal hypertension (PHT). Hepatic venous pressure gradient (HVPG) has been shown to be an accurate prognostic index in patients with cirrhosis. Transient elastography is a non-invasive p...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.01.051
更新日期:2011-11-01 00:00:00
abstract::The efficacy of hematin has been evaluated in eight patients with acute intermittent porphyria: six with acute attacks and two with chronic subacute symptoms. Hematin suppressed the chemical signs of porphyria in all patients and the symptoms in those with acute attacks. The clinical response to hematin occurred unifo...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(88)80456-2
更新日期:1988-02-01 00:00:00
abstract:BACKGROUND/AIMS:The major regulatory events leading to cell proliferation occur in the G1 phase of cell cycle, and the deranged expression of G1 cyclins is related to oncogenesis. In this study, we analyzed the aberrant expressions of cyclins D1 and E, and their role in hepatocellular carcinoma. METHODS:We examined pa...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80014-7
更新日期:1998-08-01 00:00:00
abstract:BACKGROUND & AIMS:The liver is a crucial organ at the crossroads of iron and glucose metabolism. The aim of the study was to assess intra-hepatic iron in young patients with non-alcoholic fatty liver disease (NAFLD) and its association with insulin resistance and severity of liver damage. METHODS:Intrahepatic iron con...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.12.007
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND/AIMS:Ascites in patients with cirrhosis is associated with worsening of systemic hemodynamics. Thus, the aim of this study was to investigate the biological activity of ascites on endothelial cells. METHODS:Human umbilical vein endothelial cells (HUVECs) were used to investigate the angiogenic activity of a...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.01.035
更新日期:2005-07-01 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:To review our experience of thrombolytic therapy in patients with acute Budd Chiari syndrome (BCS). METHODS:Records of 10 patients with BCS, treated by thrombolysis over a 12-year period were retrospectively analysed for demographics, clinical presentation/duration, primary disease, thrombolytic regime...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2003.09.028
更新日期:2004-01-01 00:00:00
abstract::Recently antibodies to hepatitis C virus were detected in sera of chronic active hepatitis patients, with anti-smooth muscle autoantibodies or with anti-liver/kidney microsomal type 1 autoantibodies. As the latter were used to differentiate autoimmune chronic active hepatitis from chronic non-A, non-B virus hepatitis,...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80281-8
更新日期:1993-07-01 00:00:00
abstract:BACKGROUND/AIMS:In these studies, we tested the hypothesis that increased lipid intake would exacerbate the severity of nutritional steatohepatitis. METHODS:C57Bl/6J mice were fed methionine-and-choline deficient (MCD) diets containing 20% (high) or 5% (low) fat by weight for 3 weeks and compared to lipid-matched cont...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2008.03.026
更新日期:2008-09-01 00:00:00
abstract:BACKGROUND/AIMS:Liver macrophages play an essential role in necro-inflammatory liver damage which leads to fibrosis and cirrhosis. The aim of the present study was to compare the mediator release and the DNA synthesis of macrophages at an early and at a later stage of liver cirrhosis induced by thioacetamide. METHODS:...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80118-3
更新日期:1997-05-01 00:00:00
abstract:BACKGROUND & AIMS:The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is affected by epigenetic factors as well as by genetic variation. METHODS:We performed targeted-bisulfite sequencing to determine the levels of DNA methylation of 4 CpG islands (CpG99, CpG71, CpG26, and CpG101) in the regulatory regions o...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2015.02.049
更新日期:2015-08-01 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:INTRODUCTION:Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (AD-No ACLF), or with ACLF phenotype (AD-ACLF) defined by organ failure(s). Precipitants may induce AD. This multicenter, prospective, observational PREDICT study (NCT03056612) analyzes and characterizes the pr...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.11.019
更新日期:2020-11-20 00:00:00
abstract::Tissue stress and cell death result in inflammation even in the absence of pathogens. Such sterile inflammation is dependent on a cytosolic complex of proteins inside immune cells termed the inflammasome. This complex converts two groups of extracellular signals into an inflammatory response via activation of caspase-...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.12.017
更新日期:2013-05-01 00:00:00
abstract::The presence of hepatitis B virus DNA (HBV-DNA) in the peripheral blood mononuclear cells (PBMC) of 29 anti-HIV symptomless carriers (eleven HBeAg positive, eleven anti-HBe positive and seven HBsAg negative) and of 40 anti-human immunodeficiency virus (HIV)-negative patients (15 HBeAg positive, 15 anti-HBe positive an...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(90)90050-2
更新日期:1990-03-01 00:00:00
abstract::In a rat model of chronic portal hypertension we studied ethanol-induced gastric mucosal damage and the effects of pretreatment by propranolol and sucralfate. Susceptibility to ethanol was increased in chronic portal hypertensive rats compared with sham-operated rats (55 +/- 8% vs. 25 +/- 4%). Both acute pretreatment ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(87)80568-8
更新日期:1987-10-01 00:00:00
abstract:BACKGROUND & AIM:Alcohol consumption increases intestinal permeability and causes damage to hepatocytes, leading to the release of pathogen- and damage-associated molecular pattern molecules (PAMPs and DAMPs), stimulating hepatic macrophages and activating NF-κB. The resultant inflammation exacerbates alcoholic liver d...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.08.023
更新日期:2017-09-21 00:00:00
abstract:BACKGROUND/AIMS:Patients infected with hepatitis C virus (HCV) genotype 2 or 3 usually respond better to interferon (IFN) treatment than those infected with genotype 1. In this study, we investigated whether the non-structural 5A protein (NS5A) of HCV genotypes 1 and 2 (1b-NS5A and 2a-NS5A, respectively) exerted differ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2008.06.030
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND/AIMS:Vaccination strategies able to induce strong T-cell responses might contribute to eradicate hepatitis C virus (HCV) infection. We previously demonstrated that fusion of an antigen to the extra domain A from fibronectin (EDA) targets the antigen to TLR4-expressing dendritic cells (DC) and improves its im...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.06.005
更新日期:2009-09-01 00:00:00
abstract::The effect of amphotericin B on hepatic microsomal cytochrome P-450 (P-450) concentration was measured in vitro, in vivo and ex vivo in the rat. In vitro, both amphotericin B (0-500 micrograms/ml) and its vehicle, sodium deoxycholate (0-410 micrograms/ml), caused similar dose-dependent decreases of P-450 concentration...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(92)90174-n
更新日期:1992-03-01 00:00:00
abstract:BACKGROUND/AIM:The present in vivo study investigated the impact of a monoclonal antibody directed against the intercellular adhesion molecule-1 (ICAM-1) on initial microvascular reperfusion injury after liver transplantation. METHODS:Orthotopic, syngeneic liver transplantation including arterial reconstruction was pe...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80252-4
更新日期:2000-05-01 00:00:00
abstract:BACKGROUND & AIMS:In patients with cirrhosis and refractory ascites the role of beta-blockers in the development of paracentesis-induced circulatory dysfunction (PICD) is unknown. The aim of this study was to investigate the incidence of PICD before and after discontinuation of beta-blockers in patients with cirrhosis ...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/j.jhep.2011.01.034
更新日期:2011-10-01 00:00:00
abstract::Infection with the hepatitis C virus (HCV) is the major cause of nonA-nonB hepatitis worldwide. Although this virus cannot be cultivated in vitro, several of its key features have been elucidated in the past few years. The viral genome is a positive-sense, single-stranded, 9.6 kb long RNA molecule. The viral genome is...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/s0168-8278(99)80374-2
更新日期:1999-01-01 00:00:00