Abstract:
BACKGROUND/AIMS:To analyze the kinetics of the hepatitis C virus and the patterns of resistance to interferon alpha, we assessed HCV RNA levels early during retreatment with high-dose interferon in patients who did not respond to standard treatment. METHODS:Eleven non-responders to previous therapy with 3-6 MU interferon three times a week were retreated with daily 10 MU. Plasma was sampled at days 0, 1, 2, 3, 14 and 28; all samples were prepared within 2 h and stored at -70 degrees C without thawing until analysis. The quantitative HCV RNA level was assessed by the Superquant assay (NGI, USA). The Eurohep reference panel, tested blindly, confirmed the linearity of the assay with a detection limit for genotypes 1 and 3 between 10(2) and 10(3) copies/ml. RESULTS:All patients showed a fall in viral load between week 0 and week 2 (2.6 log, i.e. 99.7%, range 1.3-4.7 log), whereas no fall was detected after week 2. Closer examination in nine patients revealed that all had a dramatic fall in the first 2 days (first day 1.8 log, 0.8-3.5; second day 0.8 log, -0.2-1.3), without any significant fall thereafter. The calculated half-life of viral decay in plasma was 5 (2-8.9) h, corresponding to a clearance of 2.4 (0.2-13.7) x 10(11) virions per day. Sustained responders showed a significantly greater fall in viral load in the first day (3.2 log, 2.8-3.5) than those who did not respond (1.4 log, 0.8-2.1, p=0.001). All three sustained responders had undetectable plasma HCV RNA at day 14. CONCLUSION:In patients without a response to standard interferon, the hepatitis C virus has a high daily turnover rate similar to that reported in naive patients. Our findings suggest that an early clearance of HCV RNA from the circulation is the key to a sustained response, which might be induced in about 25% of these patients by treatment with high (10 MU) daily doses of interferon. These findings have important implications for the concept of treatment of hepatitis C, which should shift its focus from long-term mild treatment towards aggressive therapy aiming at a fast viral disappearance within the first few days.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Bekkering FC,Brouwer JT,Leroux-Roels G,Van Vlierberghe H,Elewaut A,Schalm SWdoi
10.1016/s0168-8278(98)80343-7subject
Has Abstractpub_date
1998-06-01 00:00:00pages
960-4issue
6eissn
0168-8278issn
1600-0641pii
S0168-8278(98)80343-7journal_volume
28pub_type
临床试验,杂志文章abstract:BACKGROUND/AIMS:Some patients chronically infected with the hepatitis C virus (HCV) have persistently normal alanine aminotransferase (ALT) levels while progressive liver damage is observed histologically. In the present study, we compared the rate of proliferation, apoptosis, and necrosis in liver biopsy specimens of ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1034/j.1600-0641.2000.033004640.x
更新日期:2000-10-01 00:00:00
abstract::The Hepatitis Delta Virus (HDV), a defective ribonucleic acid virus dependent on the Hepatitis B Virus (HBV) is a cause of severe liver disease that often leads to cirrhosis and death. Since the HDV finds in the HBV infection a biological niche in which to thrive indefinitely, the major victims of its infection are th...
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)80125-8
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND/AIMS:Interleukin-12 (IL-12), a cytokine with antitumor activity, was examined for the suppressive effect on hepatocellular carcinoma (HCC) in mouse model, and its mechanism of antitumor activity was analyzed. METHODS:Mice implanted with MIH-2 HCC cells were treated with recombinant mouse IL-12 (500 ng/mouse...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.05.018
更新日期:2006-11-01 00:00:00
abstract:BACKGROUND/AIMS:We developed a bioartificial liver (BAL) based on a direct hemoperfusion typed nonwoven fabric bioreactor containing porcine hepatocytes. In this study, the efficacy of our BAL was evaluated with a pig fulminant hepatic failure (FHF) model. METHODS:FHF was induced with intravenous administration of D-g...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.08.006
更新日期:2006-02-01 00:00:00
abstract:BACKGROUND/AIMS:We previously showed that in cultured human myofibroblasts (hMFBs), Oncostatin M (OSM)-stimulated collagen accumulation is associated with increased tissue inhibitor of metalloproteinase (TIMP)1 message. However, the mechanism is unknown. METHODS:hMFBs were isolated by outgrowth from cirrhotic liver ex...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00265-3
更新日期:2002-02-01 00:00:00
abstract:BACKGROUND:Chronic liver failure resulting from hepatitis C virus infection often necessitates orthotopic liver transplantation. Recurrence of hepatitis C virus infection after transplantation is inevitable, and the infection is usually severe. Interferon and ribavirin have both been used to treat hepatitis C virus inf...
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:Periodic endoscopic screening for oesophageal varices is recommended in patients with cirrhosis, but might be limited to a subgroup of patients if a simple non-invasive test was available to select those at risk of bleeding. METHODS:We studied in 165 patients with cirrhosis the relation between the pre...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.04.006
更新日期:2006-08-01 00:00:00
abstract:Background & Aims:Liver enzyme abnormalities are common in patients with coronavirus disease 2019 (COVID-19). Whether or not severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to liver damage per se remains unknown. Herein, we reported the clinical characteristics and liver pathological man...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.05.002
更新日期:2020-10-01 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::In 40 patients with esophageal varices, esophageal variceal pressure was assessed endoscopically using a pneumatic pressure sensor. The effects of vasopressin or nitroglycerin on variceal pressure and endoscopic findings were also assessed in two groups of seven patients. The results were as follows: (1) Variceal pres...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80309-5
更新日期:1994-09-01 00:00:00
abstract:BACKGROUND & AIMS:Visceral adiposity is associated with hepatic steatosis, inflammation, and fibrosis in non-alcoholic fatty liver disease (NAFLD). The visceral adiposity index (VAI), a novel marker of visceral fat distribution and dysfunction, has been correlated with histology in hepatitis C. We assessed the ability ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.03.013
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND/AIM:Steatosis is commonly present in chronic hepatitis C. Our aim was to evaluate host- and disease-specific factors associated with its occurrence. METHODS:Histologic findings in 60 patients were correlated with body mass index, human leukocyte antigens, and other conventional parameters. Comparisons were ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80004-4
更新日期:1998-08-01 00:00:00
abstract:BACKGROUND/AIMS:Portal hypertension is associated with systemic vasodilatation and vascular hyporeactivity, and is reversed by inhibiting nitric oxide biosynthesis. Nitric oxide and calcitonin gene-related peptide are neurotransmitters of non-adrenergic non-cholinergic nerves. The role of nitric oxide and calcitonin ge...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80353-x
更新日期:1998-06-01 00:00:00
abstract:BACKGROUND/AIMS:The objective of this study was to validate, with an independent prospective cohort of patients, our previous data indicating that the proliferating cell nuclear antigen-labeling index (PCNA-LI) reflects the liver functional reserve in human cirrhosis and might have prognostic significance for patient s...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80106-8
更新日期:1999-03-01 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:BACKGROUND/AIMS:Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of chronic liver disease. Brain monoamines have been implicated in the pathogenesis of HE. We examined the relationship between monoamine dysfunction and the degree of portal-systemic shunting (PSS) in rats with varying degrees of PS...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.01.003
更新日期:2004-05-01 00:00:00
abstract:BACKGROUND/AIMS:Interaction between CYP2E1, ethanol metabolites, and enhanced lipid peroxidation is linked to the pathogenesis of alcoholic liver disease. This study was conducted to compare the expression of various cytochrome enzymes and the appearance of aldehyde adducts in humans. METHODS:Acetaldehyde- and lipid p...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80120-8
更新日期:2000-12-01 00:00:00
abstract:BACKGROUND/AIMS:The kinetics of omeprazole and its primary metabolites 5'-hydroxyomeprazole and omeprazole sulfone were studied in healthy volunteers to evaluate omeprazole as a probe drug for the S-mephenytoin hydroxylase (CYP2C19) polymorphism. The plasma metabolic ratio obtained from the concentrations of omeprazole...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:
更新日期:1995-09-01 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::The hepatitis B virus (HBV) is a small enveloped DNA virus, which primarily infects hepatocytes and causes acute and persistent liver disease. Epidemiological studies have provided overwhelming evidence for a causal role of chronic HBV infection in the development of hepatocellular carcinoma, but the molecular mechani...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2009.10.033
更新日期:2010-04-01 00:00:00
abstract:BACKGROUND & AIMS:To follow the local tissue delivery of doxorubicin in HCC explants from patients embolized with drug-eluting beads and to compare it with histologic modifications. METHODS:Six patients with HCC underwent chemoembolization with doxorubicin-eluting beads (caliber 100-300 μm, dose 75-150 mg) followed by...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.03.024
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND/AIMS:The world-wide distribution of hepatitis B virus (HBV) genotypes follows a geographic pattern under the influence of ethnic background. METHODS:Forty eight core genes from four pacific islands were compared with the following findings. RESULTS:First, island-specific variant substitutions were found fo...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.03.025
更新日期:2004-07-01 00:00:00
abstract:BACKGROUND:Serum carbohydrate deficient transferrin is a marker of chronic alcohol consumption; it increases above normal in healthy individuals after a daily alcohol intake of more than 60 g/d for more than 2 weeks. The influence of liver disease itself on carbohydrate deficient transferrin levels has not been suffici...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(95)80037-9
更新日期:1995-12-01 00:00:00
abstract:BACKGROUND & AIMS:Glucagon-like peptide-1 (GLP-1), a gut-derived peptide degraded by dipeptidyl peptidase-4 (DPP4), stimulates insulin secretion in response to nutrients, yet its direct effect on the liver is controversial. We investigated the effects of GLP-1 on hepatic fat and glucose metabolism and elucidated its me...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.09.032
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND/AIMS:Evidence that the geno/subtype of hepatitis C virus (HCV) is predictive of the response to interferon-alpha therapy suggests that typing methods are clinically useful. In the present study, HCV isolates obtained from 74 patients with chronic hepatitis C were used to evaluate three genotyping and two ser...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80108-0
更新日期:1997-05-01 00:00:00
abstract:BACKGROUND & AIMS:FibroTest™ (FT) and Transient Elastography (TE) have been validated as non-invasive markers of METAVIR fibrosis stages from F0 to F4 using biopsy, and as prognostic markers of liver related mortality in patients with chronic hepatitis C. The aim was to extend the validation of FT and TE as markers of ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.11.016
更新日期:2014-04-01 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:In chronic hepatitis C, disease progression and clinical manifestations are heterogenous. To clarify the role and interactions of viral and host factors in inducing liver cell injury, we examined the associations of several virological and metabolic variables with serum alanine aminotransferase levels. ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.01.004
更新日期:2006-04-01 00:00:00
abstract:BACKGROUND/AIMS:An interaction between human schistosomiasis and viral hepatitis B has often been suggested, but never established. The experimental investigation has been hampered by the lack of a suitable model. Only woodchucks are susceptible to both Schistosoma mansoni and a B-like hepatitis virus (WHV) infections....
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)00068-4
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND AND AIMS:Fatty acid translocase CD36 (CD36) is a membrane protein with multiple immuno-metabolic functions. Palmitoylation has been suggested to regulate the distribution and functions of CD36, but little is known about its significance in non-alcoholic steatohepatitis (NASH). METHODS:Human liver tissue sam...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2018.04.006
更新日期:2018-09-01 00:00:00