Insulin resistance undermines the advantages of IL28B polymorphism in the pegylated interferon alpha-2b and ribavirin treatment of chronic hepatitis C patients with genotype 1.

Abstract:

BACKGROUND & AIMS:Recent studies have suggested that insulin resistance exerts a strong influence on chronic hepatitis C virus (HCV) infection. We analyzed pretreatment factors useful for predicting sustained virological response (SVR), especially interleukin (IL) 28B polymorphism and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). METHODS:This cohort study consisted of 328 chronic hepatitis C patients with HCV genotype 1 who were treated for 48 weeks with pegylated interferon (PegIFN) α-2b and ribavirin (RBV). Genotyping of the polymorphisms in the IL28B gene region (rs8099917) on chromosome 19 was performed on DNA collected from each patient. RESULTS:No significant difference in IL28B genotype distribution was found according to HOMA-IR. Multivariate analysis identified the IL28B TT genotype (OR=5.97, 95% CI 2.15-16.55, p=0.0006) and the baseline HOMA-IR (OR=0.65, 95% CI 0.48-0.87, p=0.0044) as significant, independent pretreatment predictors of SVR. Receiver operating characteristic analyses to determine the optimal threshold values of HOMA-IR for predicting SVR showed that the areas under the curve (AUC) were high for both IL28B TT (AUC=0.774, HOMA-IR cut-off value: 2.45) and IL28B TG/GG genotypes (AUC=0.772, HOMA-IR cut-off value: 1.55). CONCLUSIONS:For HCV genotype 1, both IL28B and baseline HOMA-IR are independent pretreatment predictors of SVR in patients treated with PegIFNα-2b and RBV. Insulin resistance undermines the advantages of IL28B polymorphism to obtain SVR.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Ogawa E,Furusyo N,Murata M,Ikezaki H,Ihara T,Hayashi T,Toyoda K,Taniai H,Okada K,Kainuma M,Hayashi J

doi

10.1016/j.jhep.2012.04.027

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

534-40

issue

3

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(12)00349-2

journal_volume

57

pub_type

杂志文章
  • Extracellular vesicles as biomarkers in liver diseases: A clinician's point of view.

    abstract::Extracellular vesicles are membrane-bound vesicles containing proteins, lipids, RNAs and microRNAs. They can originate from both healthy and stressed cells, and provide a snapshot of the cell of origin in physiological and pathological circumstances. Various processes that may give rise to the release of extracellular...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审

    doi:10.1016/j.jhep.2020.07.014

    authors: Thietart S,Rautou PE

    更新日期:2020-12-01 00:00:00

  • A randomized controlled trial of recombinant interferon alpha-2b in the treatment of Chinese patients with acute post-transfusion hepatitis C.

    abstract::To evaluate the efficacy of recombinant interferon alpha-2b in the treatment of patients with acute post-transfusion hepatitis C, a randomized controlled trial was conducted in 33 acute post-transfusion hepatitis C patients; 16 patients received 3 million units of subcutaneously injected recombinant interferon alpha-2...

    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(94)80246-7

    authors: Hwang SJ,Lee SD,Chan CY,Lu RH,Lo KJ

    更新日期:1994-11-01 00:00:00

  • A specific immune response to purified HA antigen (HAAg) demonstrated by leukocyte migration inhibition in patients recovering from viral hepatitis A.

    abstract::The mechanism responsible for liver cell necrosis in patients with hepatitis A is not known. Since the type of hepatic lesions and the clinical presentation of acute hepatitis B are similar and are probably related to the cell-mediated immune response to a viral antigen located in the liver cell, it is possible that a...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(86)80082-4

    authors: Fasel-Folley J,Overby LR,Frei PC

    更新日期:1986-01-01 00:00:00

  • The Interleukin-1 receptor antagonist is a direct target gene of PPARalpha in liver.

    abstract:BACKGROUND/AIMS:The Peroxisome Proliferator-Activated Receptor (PPAR) alpha belongs to the superfamily of Nuclear Receptors and plays an important role in numerous cellular processes, including lipid metabolism. It is known that PPARalpha also has an anti-inflammatory effect, which is mainly achieved by down-regulating...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2006.11.019

    authors: Stienstra R,Mandard S,Tan NS,Wahli W,Trautwein C,Richardson TA,Lichtenauer-Kaligis E,Kersten S,Müller M

    更新日期:2007-05-01 00:00:00

  • Problems in the management of chronic hepatitis B with interferon: experience in a randomized, multicentre study.

    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

    authors: Realdi G,Fattovich G,Pastore G,Caredda F,Noventa F,Santantonio T,Moroni M,Criscuolo D,Maladorno D,Rugge M

    更新日期:1990-01-01 00:00:00

  • The impact of intestinal microflora on serum bilirubin levels.

    abstract:BACKGROUND/AIMS:Intestinal microflora plays an important role in the pathogenesis of neonatal jaundice by inhibiting enterosystemic circulation of bilirubin. The present study aimed to investigate the influence of intestinal microflora on serum bilirubin levels in hyperbilirubinemic Gunn rats. METHODS:After a baseline...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2004.10.012

    authors: Vítek L,Zelenka J,Zadinová M,Malina J

    更新日期:2005-02-01 00:00:00

  • Hepatic B cell leukemia-3 promotes hepatic steatosis and inflammation through insulin-sensitive metabolic transcription factors.

    abstract:BACKGROUND & AIMS:The pathomechanisms underlying non-alcoholic fatty liver disease (NAFLD) and the involved molecular regulators are incompletely explored. The nuclear factor-kappa B (NF-κB)-cofactor gene B cell leukemia-3 (Bcl-3) plays a critical role in altering the transcriptional capacity of NF-κB - a key inducer o...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2016.06.026

    authors: Gehrke N,Wörns MA,Huber Y,Hess M,Straub BK,Hövelmeyer N,Waisman A,Kim YO,Schuppan D,Galle PR,Schattenberg JM

    更新日期:2016-12-01 00:00:00

  • Clinical significance of worsening portal hypertension during long-term medical treatment in patients with cirrhosis who had been classified as early good-responders on haemodynamic criteria.

    abstract:BACKGROUND & AIMS:It is established that cirrhotic patients who respond to beta-blockers by lowering their hepatic venous pressure gradient (HVPG) to < or =12 mmHg or by > or =20% of the baseline values are protected from bleeding. However, it is not known whether the effect remains unchanged over the treatment period....

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2009.10.014

    authors: Merkel C,Bolognesi M,Berzigotti A,Amodio P,Cavasin L,Casarotto IM,Zoli M,Gatta A

    更新日期:2010-01-01 00:00:00

  • Dicoumarol, an NQO1 inhibitor, blocks cccDNA transcription by promoting degradation of HBx.

    abstract:BACKGROUND & AIMS:Current antiviral therapies help keep HBV under control, but they are not curative, as they are unable to eliminate the intracellular viral replication intermediate termed covalently closed circular DNA (cccDNA). Therefore, there remains an urgent need to develop strategies to cure CHB. Functional sil...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2020.09.019

    authors: Cheng ST,Hu JL,Ren JH,Yu HB,Zhong S,Wai Wong VK,Kwan Law BY,Chen WX,Xu HM,Zhang ZZ,Cai XF,Hu Y,Zhang WL,Long QX,Ren F,Zhou HZ,Huang AL,Chen J

    更新日期:2020-09-25 00:00:00

  • Liver stiffness measurement selects patients with cirrhosis at risk of bearing large oesophageal varices.

    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

    authors: Kazemi F,Kettaneh A,N'kontchou G,Pinto E,Ganne-Carrie N,Trinchet JC,Beaugrand M

    更新日期:2006-08-01 00:00:00

  • Remodelling of calcium signalling during liver regeneration in the rat.

    abstract:BACKGROUND/AIMS:During liver regeneration, a network of cytokines and growth factors interact with hepatocytes, helping to restore the liver mass and functions after partial tissue loss. Agonists that trigger Ca2+ signals in the liver contribute to this process, although little is known about calcium signalling during ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2006.08.014

    authors: Nicou A,Serrière V,Hilly M,Prigent S,Combettes L,Guillon G,Tordjmann T

    更新日期:2007-02-01 00:00:00

  • Quantitation of hepatitis B lamivudine resistant mutants by real-time amplification refractory mutation system PCR.

    abstract:BACKGROUND/AIMS:Lamivudine is an antiviral drug that is used to treat hepatitis B virus (HBV) infection. Long-term therapy does not completely suppress viral replication, and resistant mutants emerge. Resistance is mediated by changes in the tyrosine-methionine-apartate-aspartate (YMDD) motif in the catalytic site of t...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2004.02.009

    authors: Punia P,Cane P,Teo CG,Saunders N

    更新日期:2004-06-01 00:00:00

  • Development of eosinophil peroxidase activity and concomitant alteration of the antioxidant defenses in the liver of mice infected with Schistosoma mansoni.

    abstract:BACKGROUND/AIMS:The tropical parasite Schistosoma mansoni causes granulomatous inflammation following lodging of eggs in portal capillaries. In vitro studies indicated that the host reaction should involve reactive oxygen intermediates; however, it is not known what occurs in vivo at the site of the disease. Moreover, ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(99)80189-5

    authors: Gharib B,Abdallahi OM,Dessein H,De Reggi M

    更新日期:1999-04-01 00:00:00

  • Isolation and characterization of cholic acid 7alpha-dehydroxylating fecal bacteria from cholesterol gallstone patients.

    abstract:BACKGROUND/AIMS:The development of cholesterol gallstones, in some patients, has been associated with increased proportions of deoxycholic acid in the bile acid pool. Deoxycholic acid is a microbial product of cholic acid 7alpha-dehydroxylation in the intestines. The levels and activities of bile acid 7alpha-dehydroxyl...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(00)80183-x

    authors: Wells JE,Berr F,Thomas LA,Dowling RH,Hylemon PB

    更新日期:2000-01-01 00:00:00

  • Virology analyses of HCV isolates from genotype 1-infected patients treated with simeprevir plus peginterferon/ribavirin in Phase IIb/III studies.

    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

    authors: Lenz O,Verbinnen T,Fevery B,Tambuyzer L,Vijgen L,Peeters M,Buelens A,Ceulemans H,Beumont M,Picchio G,De Meyer S

    更新日期:2015-05-01 00:00:00

  • Production of abnormal prothrombin (des-gamma-carboxy prothrombin) by hepatocellular carcinoma. A clinical and experimental study.

    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

    authors: Okuda H,Obata H,Nakanishi T,Furukawa R,Hashimoto E

    更新日期:1987-06-01 00:00:00

  • Hepatocyte-derived extracellular vesicles promote endothelial inflammation and atherogenesis via microRNA-1.

    abstract:BACKGROUND & AIMS:Clinical evidence has indicated a close link between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). However, the underlying mechanism remains to be elucidated. This study aimed to explore a potential role of hepatocyte-derived extracellular vesicles (EVs) in endothelial in...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2019.09.014

    authors: Jiang F,Chen Q,Wang W,Ling Y,Yan Y,Xia P

    更新日期:2020-01-01 00:00:00

  • A long-term study of the interaction between iron and alcohol in an animal model of iron overload.

    abstract:BACKGROUND/AIMS:The hypothesis that chronic alcohol ingestion potentiates iron-associated liver injury was investigated in the 'carbonyl iron-overload rat model'. METHODS:Newborn male and female Wistar-Furth rats (seven per group) were used to investigate iron-alcohol interaction over a 26-week period. Groups 1 and 2 ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/0168-8278(95)80222-3

    authors: Olynyk J,Hall P,Reed W,Williams P,Kerr R,Mackinnon M

    更新日期:1995-06-01 00:00:00

  • Dendritic cell maturation in HCV infection: altered regulation of MHC class I antigen processing-presenting machinery.

    abstract:BACKGROUND & AIMS:Modulation of dendritic cell (DC) function has been theorized as one of the mechanisms used by hepatitis C virus (HCV) to evade the host immune response and cause persistent infection. METHODS:We used a range of cell and molecular biology techniques to study DC subsets from uninfected and HCV-infecte...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2014.04.007

    authors: Leone P,Di Tacchio M,Berardi S,Santantonio T,Fasano M,Ferrone S,Vacca A,Dammacco F,Racanelli V

    更新日期:2014-08-01 00:00:00

  • Applicability of adult-to-adult living donor liver transplantation.

    abstract:BACKGROUND/AIMS:The applicability of adult-to-adult living donor liver transplantation has not been established yet. We report the first data in a European center of the process leading to this procedure from the first moment the patients were informed about it. METHODS:In phase 1 of the process, 121 adult patients en...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2005.02.016

    authors: Rimola A,Llovet JM,Navasa M,Bruix J,Londoño MC,Fuster J,García-Valdecasas JC

    更新日期:2005-07-01 00:00:00

  • Hepatitis C virus and blood transfusion: past and present risks.

    abstract::The risk of HCV transmission by blood and blood products has been greatly reduced since the early 1980's. Selection of non-remunerated donors, donor selection to prevent HIV transmission, initial surrogate testing in some regions, and introduction of anti-HCV testing have all contributed to this. ALT surrogate testing...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审

    doi:10.1016/s0168-8278(99)80384-5

    authors: van der Poel CL

    更新日期:1999-01-01 00:00:00

  • Hepatitis B virus-induced modulation of liver macrophage function promotes hepatocyte infection.

    abstract:BACKGROUND & AIMS:Liver macrophages can be involved in both pathogen clearance and/or pathogenesis. To get further insight on their role during chronic hepatitis B virus (HBV) infections, our aim was to phenotypically and functionally characterize in vivo and ex vivo the interplay between HBV, primary human liver macro...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2019.06.032

    authors: Faure-Dupuy S,Delphin M,Aillot L,Dimier L,Lebossé F,Fresquet J,Parent R,Matter MS,Rivoire M,Bendriss-Vermare N,Salvetti A,Heide D,Flores L,Klumpp K,Lam A,Zoulim F,Heikenwälder M,Durantel D,Lucifora J

    更新日期:2019-12-01 00:00:00

  • Chronic hepatitis in children after liver transplantation: role of hepatitis C virus and hepatitis G virus infections.

    abstract:BACKGROUND/AIMS:Chronic graft hepatitis occurs in 20-30% adults after liver transplantation but the prevalence and causes in children are not known. In adults, hepatitis C virus infection is prevalent prior to transplantation and recurrent infection is a frequent cause of graft dysfunction. The significance of the rece...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(98)80225-0

    authors: Davison SM,Skidmore SJ,Collingham KE,Irving WL,Hubscher SG,Kelly DA

    更新日期:1998-05-01 00:00:00

  • Long-term follow-up of chronic hepatitis C in patients diagnosed at a tertiary-care center.

    abstract:BACKGROUND/AIMS:The natural history of chronic hepatitis C (HCV) is not completely understood. This study was aimed to evaluate the long-term outcome of the disease over a prolonged period of time and to identify factors associated with progression. METHODS:One hundred and sixteen patients with non-cirrhotic chronic n...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(01)00088-5

    authors: Forns X,Ampurdanès S,Sanchez-Tapias JM,Guilera M,Sans M,Sánchez-Fueyo A,Quintó L,Joya P,Bruguera M,Rodés J

    更新日期:2001-08-01 00:00:00

  • Pulmonary contraindications, indications and MELD exceptions for liver transplantation: a contemporary view and look forward.

    abstract::Pulmonary concerns in liver transplant candidates have intraoperative and outcome implications. Evolving MELD exception policies address transplant priority for problems such as hepatopulmonary syndrome, portopulmonary hypertension, and hemorrhagic hereditary telangiectasia. Other pulmonary issues such as refractory h...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审

    doi:10.1016/j.jhep.2013.03.026

    authors: Krowka MJ,Wiesner RH,Heimbach JK

    更新日期:2013-08-01 00:00:00

  • Hedgehog signaling in the liver.

    abstract::Reactivation of Hedgehog (Hh), a morphogenic signaling pathway that controls progenitor cell fate and tissue construction during embryogenesis occurs during many types of liver injury in adult. The net effects of activating the Hedgehog pathway include expansion of liver progenitor populations to promote liver regener...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审

    doi:10.1016/j.jhep.2010.10.003

    authors: Omenetti A,Choi S,Michelotti G,Diehl AM

    更新日期:2011-02-01 00:00:00

  • Resistance of rat hepatocytes against bile acid-induced apoptosis in cholestatic liver injury is due to nuclear factor-kappa B activation.

    abstract:BACKGROUND/AIMS:To examine the extent and mechanisms of apoptosis in cholestatic liver injury and to explore the role of the transcription factor nuclear factor-kappa B in protection against bile acid-induced apoptosis. METHODS:Cholestatic liver injury was induced by bile duct ligation in Wistar rats. Furthermore, pri...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(03)00214-9

    authors: Schoemaker MH,Gommans WM,Conde de la Rosa L,Homan M,Klok P,Trautwein C,van Goor H,Poelstra K,Haisma HJ,Jansen PL,Moshage H

    更新日期:2003-08-01 00:00:00

  • Significance of increased plasma adrenomedullin concentration in patients with cirrhosis.

    abstract:BACKGROUND/AIMS:Adrenomedullin recently discovered in human pheochromocytoma is a potent vasodilatory peptide mainly derived from vascular endothelial and smooth muscle cells. Hyperdynamic circulation, ultimately leading to ascites formation, has been attributed to peripheral vasodilatation in liver cirrhosis. However,...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(98)80235-3

    authors: Kojima H,Tsujimoto T,Uemura M,Takaya A,Okamoto S,Ueda S,Nishio K,Miyamoto S,Kubo A,Minamino N,Kangawa K,Matsuo H,Fukui H

    更新日期:1998-05-01 00:00:00

  • Ascites from cirrhotic patients induces angiogenesis through the phosphoinositide 3-kinase/Akt signaling pathway.

    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

    authors: Morales-Ruiz M,Tugues S,Cejudo-Martín P,Ros J,Melgar-Lesmes P,Fernández-Llama P,Arroyo V,Rodés J,Jiménez W

    更新日期:2005-07-01 00:00:00

  • Evidence that chronic alcohol exposure promotes intestinal oxidative stress, intestinal hyperpermeability and endotoxemia prior to development of alcoholic steatohepatitis in rats.

    abstract:BACKGROUND/AIMS:Not all alcoholics develop liver disease (ALD). Thus, excessive ethanol consumption is necessary, but not sufficient, to induce alcoholic steatohepatitis (ASH) and ALD. Since endotoxemia is present in patients with ALD, it has been proposed that gut-derived, circulating endotoxin is the necessary co-fac...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2008.10.028

    authors: Keshavarzian A,Farhadi A,Forsyth CB,Rangan J,Jakate S,Shaikh M,Banan A,Fields JZ

    更新日期:2009-03-01 00:00:00