Abstract:
:Design and endpoints of clinical trials in hepatocellular carcinoma. Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, Sherman M, Schwartz M, Lotze M, Talwalkar J, Gores GJ; for the Panel of Experts in HCC-Design Clinical Trials. The design of clinical trials in hepatocellular carcinoma (HCC) is complex because many patients have concurrent liver disease, which can confound the assessment of clinical benefit. There is an urgent need for high-quality trials in this disease. An expert panel was convened by the American Association for the Study of Liver Diseases to develop guidelines that provide a common framework for designing trials to facilitate comparability of results. According to these guidelines, randomized phase 2 trials with a time-to-event primary endpoint, such as time to progression, are pivotal in clinical research on HCC. Survival remains the main endpoint to measure effectiveness in phase 3 studies, whereas time to recurrence is proposed as an appropriate endpoint in the adjuvant setting. Because progression-free survival and disease-free survival are composite endpoints, they are more vulnerable than others in HCC clinical studies and may not be able to capture clinical benefits. Selection of the target population should be based on the Barcelona Clinic Liver Cancer staging system. New drugs should be tested in patients with well-preserved liver function (Child-Pugh A class). Patients assigned to the control arm should receive standard-of-care therapy, that is, chemoembolization for patients with intermediate-stage disease and sorafenib for patients with advanced-stage disease. Further research is needed to incorporate biomarkers and molecular imaging into clinical research in HCC. These surrogate markers may help to enrich study populations and maximize the cost-benefit ratio of trial execution. Design and conduct of phase 3 trials should be coordinated by centers with appropriate expertise in HCC. [Abstract reproduced by permission of J Natl Cancer Inst 2008;100:698-711.] Link to free abstract at: (http://jnci.oxfordjournals.org/cgi/content/abstract/100/10/698).
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Christensen Edoi
10.1016/j.jhep.2008.07.012subject
Has Abstractpub_date
2008-10-01 00:00:00pages
672-3issue
4eissn
0168-8278issn
1600-0641pii
S0168-8278(08)00484-4journal_volume
49pub_type
评论,杂志文章abstract:BACKGROUND & AIM:Following acetaminophen (APAP) overdose, acute liver injury (ALI) can occur in patients that present too late for N-acetylcysteine treatment, potentially leading to acute liver failure, systemic inflammation, and death. Macrophages influence the progression and resolution of ALI due to their innate imm...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.02.031
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND/AIMS:A variety of data suggest that microbial infections and, in particular, atypical mycobacteria infections, may either initiate and/or be associated with the pathogenesis of primary biliary cirrhosis. METHODS:To address this hypothesis, use was made of polymerase chain reaction techniques and primers spe...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80346-8
更新日期:1999-10-01 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::This study set out to examine the relative effectiveness and tolerability of 12- versus 24-week courses of thrice weekly intramuscular lymphoblastoid interferon in the treatment of hepatitis B 'e' antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection, and to identify pretreatment factors predicting the ou...
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(87)80061-2
更新日期:1987-08-01 00:00:00
abstract:BACKGROUND/AIMS:The endogenous low molecular weight iron chelator, citrate, is considered to be an important contributor to iron transport and the liver the main site of uptake of iron citrate in subjects suffering from diseases of iron overload. Moreover, the citrate-metabolising enzyme, aconitase, is implicated in th...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80156-6
更新日期:1998-10-01 00:00:00
abstract:AIM:In order to study the short-term effect of moderate and severe reduction of liver function by acetaminophen poisoning of different severity on gene expression for liver-specific functions, rats were given 3.75 and 7.5 g per kg body weight acetaminophen intragastrically. The lower dose is associated with low mortali...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(96)80072-9
更新日期:1996-08-01 00:00:00
abstract:BACKGROUND/AIMS:Isolated vessels of portal hypertensive rats exhibit decreased responsiveness to vasoconstrictors. The vasopressin analogue terlipressin is used in the treatment of portal hypertension since it is known to reduce portal pressure, an effect that is thought to arise from splanchnic vasoconstriction via st...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(96)80271-6
更新日期:1996-06-01 00:00:00
abstract:BACKGROUND & AIMS:In patients with primary biliary cholangitis (PBC), the efficacy of budesonide, a synthetic corticosteroid displaying high first-pass metabolism, is unresolved. In a placebo-controlled, double-blind trial, we evaluated the added-value of budesonide in those with PBC and ongoing risk of progressive dis...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.09.011
更新日期:2021-02-01 00:00:00
abstract::Intravascular coagulation is involved in the development of certain types of liver injury, including that induced by dimethylnitrosamine. Nitric oxide inhibits platelet aggregation and adhesion; however, its role in protecting against intravascular coagulation has not been clarified. We therefore investigated the effe...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(95)80068-9
更新日期:1995-11-01 00:00:00
abstract::Hepatitis C virus (HCV) infection is associated with tremendous morbidity and mortality due to liver complications. HCV infection is also associated with many extrahepatic manifestations including cardiovascular diseases, glucose metabolism impairment, cryoglobulinemia vasculitis, B cell non-Hodgkin lymphoma and chron...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2016.06.011
更新日期:2016-10-01 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: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::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 & AIMS:Therapeutic options for patients failing hepatitis C retreatment are limited. EPIC(3) included a prospective trial assessing long-term peginterferon alfa-2b (PegIFNα-2b) maintenance therapy in patients with METAVIR fibrosis scores (MFS) of F2 or F3 who previously failed hepatitis C retreatment. METHO...
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.2012.11.001
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND/AIMS:Inflammation in the liver is a complex interaction between parenchymal and non-parenchymal cells, and therefore can not be studied in vitro in pure cultures of these cells. METHODS:We investigated whether Kupffer cells in the liver slice are still responsive to an inflammatory stimulus of lipopolysacch...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00103-9
更新日期:2001-08-01 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::Familial hypobetalipoproteinemia (FHBL) is an monogenic co-dominant disorder characterized by reduced plasma levels of cholesterol, low density lipoproteins (LDL) and apolipoprotein B (apoB) often associated with non-alcoholic fatty liver disease (NAFLD). It has been suggested that FHBL might predispose to gallstone d...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.03.012
更新日期:2005-07-01 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 interaction between fat-storing cells (FSCs) and Kupffer cells (KCs) in vitro has been studied in an attempt to clarify certain aspects of the pathogenesis of fibrotic process in the liver. FSCs and KCs were isolated from the livers of rats either treated with CCl4 for 6 weeks, or with vitamin A for 6 weeks or fro...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(86)80481-0
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND & AIMS:Hallmarks of non-alcoholic fatty liver disease (NAFLD) are increased triglyceride accumulation within hepatocytes. The prevalence of NAFLD increases steadily with increasing thyrotropin (TSH) levels. However, the underlying mechanisms are largely unknown. Here, we focused on exploring the effect and m...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.06.037
更新日期:2014-12-01 00:00:00
abstract:BACKGROUND & AIMS:High-carbohydrate diets contribute to the development of liver stress and fatty liver disease. While saturated fatty acids are known to induce liver stress, the role of monounsaturated fatty acids (MUFA), synthesized by the stearoyl-CoA desaturase (SCD) family of enzymes, in regulation of liver functi...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2016.03.001
更新日期:2016-07-01 00:00:00
abstract::Thirty-two patients with chronic hepatitis B were randomly assigned to two groups. Sixteen patients received 10 million units of alpha-interferon per square meter of body surface (MU/m2), three times weekly for 4 months. Sixteen patients were treated simultaneously with gamma-interferon at a dose of 2 MU/m2, and 10 MU...
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(05)80212-0
更新日期:1993-03-01 00:00:00
abstract::Hepatitis C virus (HCV) cDNA sequence in the nonstructural region NS3 was amplified from the serum of 66% French non-A, non-B hepatitis patients by the nested polymerase chain reaction. A 407 base-pair sequence was determined from four such cases, which revealed the presence of two different virus genotypes F1 (three ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(91)90019-8
更新日期:1991-01-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatitis B e antigen (HBeAg) seroconversion is an important clinical and virological "landmark" during chronic hepatitis B virus (HBV) infection. Mutant viruses carrying the precore G1896A and/or the basal core promoter (BCP) A1762T/G1764A mutations are associated with HBeAg seroconversion. However, ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.11.012
更新日期:2012-04-01 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::Liver transplantation is performed successfully across major HLA differences between donor and recipient. This may be influenced by the organ specific expression of major histocompatibility complex (MHC) molecules which determine the local immune reactivity and rejection response. The tissue expression of MHC molecule...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/0168-8278(90)90264-r
更新日期:1990-07-01 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:It was recently shown that semi-annual surveillance for hepatocellular carcinoma (HCC) in cirrhotic patients provides a prognostic advantage over the annual program; however, its cost-effectiveness (CE) in the general cirrhotic population still needs to be defined. METHODS:A Markov model was built to...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2011.11.022
更新日期:2012-05-01 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:BACKGROUND/AIMS:Failure to induce apoptosis triggered by members of the death receptor family has been described in hepatocellular carcinoma (HCC) and sensitization of malignant cells to pro-apoptotic molecules such as TRAIL has been proposed as an alternative cancer therapy. Limiting to this approach are the resistanc...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.10.010
更新日期:2007-04-01 00:00:00