Abstract:
BACKGROUND & AIMS:There is little information regarding the extent to which difficult to cure patients with advanced liver fibrosis, due to hepatitis C virus genotype-1 (HCV-1) can successfully and safely be treated with triple therapy with telaprevir (TVR), pegylated interferon alpha (P) and ribavirin (R). In the TVR early access program HEP3002 we aimed to explore treatment safety and efficacy, and identify predictors of sustained virological response at week 24 (SVR24). METHODS:1078 patients with bridging fibrosis (n=552) or cirrhosis (n=526) diagnosed by either liver biopsy or non-invasive markers, with compensated bone marrow (neutrophils >1500/mm(3), Hb >12/13 g/dl) and liver function (Albumin >3.3g/dl, Platelets >90,000/ml) received TVR PR for 12 weeks, followed by a PR tail according to label. RESULTS:Overall, 614 (57%) achieved SVR24 by intention-to-treat analysis. The SVR24 rate was 68% in 221 treatment naïve patients (62.8% F4), 72% in 356 prior relapsers (64.4% F4), 55% in 139 partial responders (53.2% F4), and 34% in 294 null responders (28.6% F4). The SVR24 rate to response-guided therapy (24 weeks treatment duration if undetectable viremia at weeks 4 and 12) was 84% in 222 naïve/relapser F3 patients. Independent predictors of response were: (A) F3 (odds ratio (OR)=1.51, 95% CI 1.31-2.00, p=0.005), (B) subtype 1b (OR=1.63, 95% CI 1.18-2.24, p=0.0029), (C) alpha-fetoprotein <10 ng/ml (OR=2.50, 95% CI 1.87-3.36, p<0.0001) and (D) any prior response other than null (OR=3.29, 95% CI 2.40-4.52, p<0.0001). SVR24 rose for patients who had more of these predictive factors: 6/32 (19%) for none, 38/139 (27%) for 1, 129/260 (50%) for 2, 202/329 (61%) for 3, and 194/235 (83%) for 4 factors. Grade 2-4 treatment-related adverse events (AE) were experienced by 719 (67%) patients; 169 (16%) discontinued therapy for AE and 7 (0.6%) died during the PR tail. CONCLUSIONS:Naïve and experienced patients with advanced fibrosis or cirrhosis due to HCV-1 who have compensated bone marrow and liver function, can effectively and safely be treated by TVR triple therapy. Baseline predictors of outcome have been identified to optimize pre-treatment counselling.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Colombo M,Strasser S,Moreno C,Abrao Ferreira P,Urbanek P,Fernández I,Abdurakmonov D,Streinu-Cercel A,Verheyen A,Iraqi W,DeMasi R,Hill A,Lonjon-Domanec I,Wedemeyer Hdoi
10.1016/j.jhep.2014.06.005subject
Has Abstractpub_date
2014-11-01 00:00:00pages
976-83issue
5eissn
0168-8278issn
1600-0641pii
S0168-8278(14)00400-0journal_volume
61pub_type
临床试验,杂志文章,多中心研究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::Human serum albumin (HSA) is one of the most frequent treatments in patients with decompensated cirrhosis. Prevention of paracentesis-induced circulatory dysfunction, prevention of type-1 HRS associated with bacterial infections, and treatment of type-1 hepatorenal syndrome are the main indications. In these indicatio...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2014.04.012
更新日期:2014-08-01 00:00:00
abstract::In a multicentre trial, 82 patients known to be hepatitis B e antigen and hepatitis B virus DNA positive for at least 1 year, with elevated serum alanine aminotransferase levels and chronic liver lesions on biopsy, were randomized to receive either recombinant interferon alfa-2a at a dose of 4.5 million units thrice w...
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:10.1016/0168-8278(90)90179-u
更新日期:1990-01-01 00:00:00
abstract:BACKGROUND & AIMS:Large extracellular vesicles, specifically AnnexinV+ EpCAM+ CD147+ tumour-associated microparticles (taMPs), facilitate the detection of colorectal carcinoma (CRC), non-small cell lung carcinoma (NSCLC) as well as pancreas carcinoma (PaCa). Here we assess the diagnostic value of taMPs for detection an...
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doi:10.1016/j.jhep.2017.02.024
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatitis B virus (HBV) and D virus (HDV) co-infections cause the most severe form of viral hepatitis. HDV induces an innate immune response, but it is unknown how the host cell senses HDV and if this defense affects HDV replication. We aim to characterize interferon (IFN) activation by HDV, identify ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2018.02.021
更新日期:2018-07-01 00:00:00
abstract:BACKGROUND/AIMS:Hepatocellular carcinoma is one of the most malignant tumors in the world. Although a wide range of therapeutic options is available, the efficacy of these methods and the prognosis of hepatocellular carcinoma are still very poor. The nucleoside analogs 2-chlorodeoxyadenosine (Cladribine, 2-CdA) and 2',...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80326-7
更新日期:1998-03-01 00:00:00
abstract:BACKGROUND/AIMS:To compare carotid intima-media thickness (IMT) - an index of early atherosclerosis - among patients with non-alcoholic steatohepatitis (NASH), patients with chronic hepatitis B (HBV) or C (HCV) and control subjects. METHODS:We studied 60 consecutive patients with biopsy-proven NASH, 60 patients with H...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2007.01.021
更新日期:2007-06-01 00:00:00
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pub_type: 杂志文章
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更新日期:2000-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:2017-02-01 00:00:00
abstract:BACKGROUND/AIMS:The natural history of chronic hepatitis C infection during pregnancy has not been clearly established, and thus our aim was to assess serum alanine aminotransferase levels and serum HCV RNA levels during pregnancy. METHODS:Twenty-six pregnant women with chronic hepatitis C were studied. Serum alanine ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80075-6
更新日期:2000-02-01 00:00:00
abstract::In recent years a new concept of the mechanism of hepatic fatty acid uptake has been described. It was shown that this major class of energy yielding substrates enters hepatocytes by a carrier-mediated uptake system. After the dissociation of the fatty acid-albumin complex at the sinusoidal liver cell plasma membrane,...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
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abstract:BACKGROUND/AIMS:The precise mechanism of formation and significance of Mallory bodies (MBs) are poorly understood. The endoplasmic reticulum (ER) is the organelle responsible for proper folding and elimination of unfolded proteins. Therefore, failure of this function increases defective proteins in the cell. METHODS:W...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2007.01.039
更新日期:2007-07-01 00:00:00
abstract:BACKGROUND & AIMS:Histopathology is the gold standard in the diagnosis of liver diseases but may be complicated by sampling error and bleeding. Confocal laser endomicroscopy (CLE) is a novel imaging modality providing in vivo histology. Previous studies using CLE for liver microscopy suffered from limited imaging depth...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.01.039
更新日期:2010-07-01 00:00:00
abstract:BACKGROUND/AIMS:Although 6-thioguanine (6-TG) has been suggested as an effective treatment option for patients with inflammatory bowel disease (IBD), the recent description of its hepatotoxicity has led to the recommendation not to consider this drug. We initiated a multicenter safety study in IBD-patients treated with...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2005.02.051
更新日期:2005-08-01 00:00:00
abstract::MRI has emerged as the most comprehensive non-invasive diagnostic tool for liver diseases. In recent years, the value of MRI in hepatology has been significantly enhanced by a wide range of contrast agents, both clinically available and under development, that add functional information to anatomically detailed morpho...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2020.06.020
更新日期:2020-11-01 00:00:00
abstract:BACKGROUND & AIMS:The approval of all-oral direct-acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) has led to the expansion of therapy to include patients with cirrhosis who have hepatocellular carcinoma (HCC). Data on the use of DAAs in HCV+ patients with HCC is limited. The aim of this stu...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.01.020
更新日期:2017-06-01 00:00:00
abstract:BACKGROUND/AIMS:Previous studies have shown that hepatic natural killer (NK) cells, also called pit cells, have a higher cytotoxicity against certain tumor cells and have a higher expression of the cell adhesion molecule CD11a as compared with blood NK cells. We further investigated the involvement of the adhesion mole...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80170-6
更新日期:1999-07-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1016/s0168-8278(96)80174-7
更新日期:1996-04-01 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:BACKGROUND/AIMS:No study has compared the liver fibrosis progression rates among chronic liver diseases and the risk factors in order to better organize screening strategies. METHODS:A total of 4852 patients were retrospectively studied (chronic hepatitis C (HCV) [n=2313], human immunodeficiency virus (HIV)-HCV co-inf...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00413-0
更新日期:2003-03-01 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:Patients with hepatic encephalopathy show altered motor function, psychomotor slowing and hypokinesia. The underlying mechanisms remain unclear. This work's aims were: (1) to analyse in rats with chronic liver failure due to portacaval shunt (PCS) the neurochemical alterations in the basal ganglia-thala...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.06.019
更新日期:2006-11-01 00:00:00
abstract:BACKGROUND/AIMS:Catabolism is associated with decreased serum concentrations of insulin-like growth factor (IGF)-I and insulin-like growth factor binding protein (IGFBP)-3 associated with elevated IGFBP-3 protease activity and increased concentrations of IGFBP-1 and -4. The effects of the acute phase mediators interleu...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00170-2
更新日期:2001-11-01 00:00:00
abstract::A quantitative immunohistochemical study of Kupffer cells in liver biopsies from alcoholics was carried out. Two markers were compared, lysozyme and an antimacrophage monoclonal antibody EMB/11. The results showed that there is no significant reduction in Kupffer cell numbers in acute and chronic alcoholic liver disea...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(89)90005-6
更新日期:1989-03-01 00:00:00
abstract:BACKGROUND/AIMS:To elucidate the mechanisms of action of interferon (IFN) against hepatitis C virus (HCV), we studied the serum HCV dynamics of free-virions (FV) and immune-complexes (IC) in patients treated with IFN. METHODS:FV and IC were separated by immunoprecipitation using anti-human immunoglobulin and quantifie...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(03)00472-0
更新日期:2003-12-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00243-4
更新日期:2002-02-01 00:00:00
abstract::Hepatitis C infection is common in patients undergoing liver transplantation. Few studies have focused on the prevalence and epidemiology of hepatitis C infection among liver transplant recipients since the implementation of donor screening for antibodies against the hepatitis C virus (anti-HCV). Using reverse transcr...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract:BACKGROUND & AIMS:Simeprevir is an oral hepatitis C virus (HCV) NS3/4A protease inhibitor approved for treatment of chronic HCV infection. Baseline NS3 polymorphisms in all patients and emerging mutations in patients who failed to achieve sustained virologic response (SVR) with simeprevir plus peginterferon/ribavirin (...
journal_title:Journal of hepatology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jhep.2014.11.032
更新日期:2015-05-01 00:00:00
abstract::Since the early 1990's, hepatitis B immune globulin (HBIG) has been central to the prevention of hepatitis B virus (HBV) recurrence after liver transplantation. When used in combination with oral nucleos(t)ide analogues, HBIG prevents reinfection with HBV in ⩾90% of transplant recipients. While HBIG is highly efficaci...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2011.08.026
更新日期:2012-05-01 00:00:00
abstract:BACKGROUND/AIMS:Graft reperfusion in liver transplantation is usually performed by initial portal reperfusion (IPR) and delayed rearterialization. Its influence on graft microcirculation is unknown. This study aimed to assess sinusoidal perfusion in dependence to this reperfusion technique during human living-donor liv...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.04.017
更新日期:2004-08-01 00:00:00