Mechanisms of HBV-induced hepatocellular carcinoma.


:Hepatitis B virus (HBV) contributes to hepatocellular carcinoma (HCC) development through direct and indirect mechanisms. HBV DNA integration into the host genome occurs at early steps of clonal tumor expansion and induces both genomic instability and direct insertional mutagenesis of diverse cancer-related genes. Prolonged expression of the viral regulatory protein HBx and/or altered versions of the preS/S envelope proteins dysregulates cell transcription and proliferation control and sensitizes liver cells to carcinogenic factors. Accumulation of preS1 large envelope proteins and/or preS2/S mutant proteins activates the unfold proteins response, that can contribute to hepatocyte transformation. Epigenetic changes targeting the expression of tumor suppressor genes occur early in the development of HCC. A major role is played by the HBV protein, HBx, which is recruited on cellular chromatin and modulates chromatin dynamics at specific gene loci. Compared with tumors associated with other risk factors, HBV-related tumors have a higher rate of chromosomal alterations, p53 inactivation by mutations and overexpression of fetal liver/hepatic progenitor cells genes. The WNT/β-catenin pathway is also often activated but HBV-related tumors display a low rate of activating β-catenin mutations. HBV-related HCCs may arise on non-cirrhotic livers, further supporting the notion that HBV plays a direct role in liver transformation by triggering both common and etiology specific oncogenic pathways in addition to stimulating the host immune response and driving liver chronic necro-inflammation.


J Hepatol


Journal of hepatology


Levrero M,Zucman-Rossi J




Has Abstract


2016-04-01 00:00:00




1 Suppl










  • Taurocholate transport by liver plasma membrane vesicles is not altered in cirrhotic rats.

    abstract::Recently, we have shown that taurocholate transport is impaired in hepatocytes isolated from CCl4 cirrhotic rats. Na+,K+-ATPase activity depends on the lipid composition of the surrounding membrane. Therefore, we performed this study in order to detect differences in plasma membrane composition and membrane functions ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Krähenbühl S,Meier-Abt PJ,Reichen J

    更新日期:1989-07-01 00:00:00

  • Rat liver slices as a tool to study LPS-induced inflammatory response in the liver.

    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


    authors: Olinga P,Merema MT,de Jager MH,Derks F,Melgert BN,Moshage H,Slooff MJ,Meijer DK,Poelstra K,Groothuis GM

    更新日期:2001-08-01 00:00:00

  • Hypolocomotion in rats with chronic liver failure is due to increased glutamate and activation of metabotropic glutamate receptors in substantia nigra.

    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


    authors: Cauli O,Llansola M,Erceg S,Felipo V

    更新日期:2006-11-01 00:00:00

  • Hepatitis C infection and autoimmunity.

    abstract::Since the first tests for antibodies to components of the hepatitis C virus became widely available there has been considerable interest in evidence linking HCV infection with autoimmune liver diseases and other autoimmune conditions. With respect to autoimmune hepatitis, it is now clear that the early tests were quit...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审


    authors: Eddleston AL

    更新日期:1996-01-01 00:00:00

  • Interleukin-1 receptor antagonist plasma concentration is specifically increased by alpha-2A-interferon treatment.

    abstract:BACKGROUND/AIMS:The mechanism of action of recombinant interferon-alpha (rIFN alpha) treatment in chronic hepatitis C is not fully understood, and may include modulation of the immune system as well as a direct antiviral effect. We have therefore evaluated the plasma concentrations of pro- and anti-inflammatory cytokin...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Naveau S,Emilie D,Borotto E,Portier A,Lazizi Y,Giraud V,Grangeot-Keros L,Capron F,Galanaud P,Chaput JC

    更新日期:1997-08-01 00:00:00

  • Identification of naïve HCV-1 patients with chronic hepatitis who may benefit from dual therapy with peg-interferon and ribavirin.

    abstract:BACKGROUND & AIMS:The pool of HCV genotype 1 patients likely to be cured by peg-interferon and ribavirin remains to be quantified. METHODS:In 1045 patients treated with peg-interferon and ribavirin, two therapeutic strategies were confronted: the first one evaluated only baseline variables associated with sustained vi...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Andriulli A,Di Marco V,Margaglione M,Ippolito AM,Fattovich G,Smedile A,Valvano MR,Calvaruso V,Gioffreda D,Milella M,Morisco F,Felder M,Brancaccio G,Fasano M,Gatti P,Tundo P,Barone M,Cozzolongo R,Angelico M,D'Andrea

    更新日期:2014-01-01 00:00:00

  • Interleukins in chronic active hepatitis B. Relationship with viral markers.

    abstract::Interleukin-2, a product of helper T cells, is essentially involved in the regulation of cell-mediated immunity. Two monocyte-derived factors, interleukin-1 and prostaglandin E2, influence interleukin-2 synthesis with opposite actions. To analyse immunoregulatory function in HBsAg-positive chronic active hepatitis, T ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Civeira M,Prieto J,Morte S,Riñon M,Serrano M

    更新日期:1987-08-01 00:00:00

  • Epidemiology of hepatitis C virus infection in an area of Southern Italy.

    abstract:BACKGROUND/AIMS:Hepatitis C virus (HCV) has been recognized as a major cause of liver disease, but little is known about its diffusion at population level. To estimate the prevalence and incidence of HCV infection and to explore potential risk factors at population level, an epidemiologic study was carried out. METHOD...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Osella AR,Misciagna G,Leone A,Di Leo A,Fiore G

    更新日期:1997-07-01 00:00:00

  • Sympathetic nervous activity in cirrhosis. A survey of plasma catecholamine studies.

    abstract::This review summarizes recent progress in the knowledge of catecholamines in cirrhosis. Compensated patients have normal plasma concentration of noradrenaline. Highly elevated plasma noradrenaline concentration in decompensated patients indicates that the sympathetic nervous system is enhanced in this condition. This ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审


    authors: Henriksen JH,Ring-Larsen H,Christensen NJ

    更新日期:1985-01-01 00:00:00

  • Cellular immune response to hepatitis B virus antigens. An overview.

    abstract::It has been suggested that the cellular immune response to HBV antigens is responsible for hepatocellular injury in acute and chronic hepatitis B. However, definitive immunological studies have so far been hampered by the lack of appropriate model systems to study HBV antigen-specific T cells. The availability of high...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审


    authors: Ferrari C,Penna A,DegliAntoni A,Fiaccadori F

    更新日期:1988-08-01 00:00:00

  • Correction of maternal serum bile acid profile during ursodeoxycholic acid therapy in cholestasis of pregnancy.

    abstract:BACKGROUND/AIMS:Intrahepatic cholestasis of pregnancy is characterized by pruritus and increased levels of serum bile acids, and is often associated with premature delivery, fetal distress, and perinatal mortality. The aims of the present study were: (i) to better define the serum bile acid profile in intrahepatic chol...

    journal_title:Journal of hepatology

    pub_type: 临床试验,杂志文章


    authors: Brites D,Rodrigues CM,Oliveira N,Cardoso M,Graça LM

    更新日期:1998-01-01 00:00:00

  • Hepatic and extrahepatic malignancies in autoimmune hepatitis. A long-term follow-up in 473 Swedish patients.

    abstract:BACKGROUND/AIMS:Autoimmune Hepatitis (AIH) is a liver disease which may lead to liver cirrhosis. Cirrhosis is a well-known risk factor for hepatocellular cancer. Lymphoma is a disease, where immune modulating drugs as well as the autoimmune disease itself may contribute to the elevated risk. The aim was to investigate ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Werner M,Almer S,Prytz H,Lindgren S,Wallerstedt S,Björnsson E,Bergquist A,Sandberg-Gertzén H,Hultcrantz R,Sangfelt P,Weiland O,Danielsson A

    更新日期:2009-02-01 00:00:00

  • Ultrarapid hepatitis C virus clearance by daily high-dose interferon in non-responders to standard therapy.

    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 interfe...

    journal_title:Journal of hepatology

    pub_type: 临床试验,杂志文章


    authors: Bekkering FC,Brouwer JT,Leroux-Roels G,Van Vlierberghe H,Elewaut A,Schalm SW

    更新日期:1998-06-01 00:00:00

  • Safety and efficacy of in vitro fertilisation in patients with chronic liver disease and liver transplantation recipients.

    abstract:BACKGROUND:Chronic liver disease and liver transplantation (LT) can delay both timing and ability of women to conceive. With increased awareness and availability of in vitro fertilisation (IVF), the need for accurate counselling is paramount. To date, minimal data exists to inform outcomes of IVF in patients with chron...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Rahim MN,Theocharidou E,Yen Lau KG,Ahmed R,Marattukalam F,Long L,Cannon MD,Heneghan MA

    更新日期:2021-01-15 00:00:00

  • Assessment of hepatitis B virus DNA levels in chronic HBsAg carriers with or without hepatitis delta virus superinfection.

    abstract::In order to document the incidence of hepatitis delta virus (HDV) replication markers and their relationship to HBV replication, 91 HBsAg chronic carriers were studied. Of these, 51 were anti-HD-positive (19 HBeAg-positive and 32 anti-HBe-positive). Liver HDAg was found in 75% of anti-HD-positive patients. Of the 19 p...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Bas C,Bartolomé J,La Banda F,Porres JC,Quiroga JA,Mora I,Carreño V

    更新日期:1988-04-01 00:00:00

  • Transdermal oestrogen therapy protects postmenopausal liver transplant women from osteoporosis. A 2-year follow-up study.

    abstract:BACKGROUND/AIMS:Hormone replacement therapy (HRT) prevents osteoporosis in postmenopausal women by inhibiting bone resorption, but the benefits of oestrogen therapy in liver transplant patients have not been studied. METHODS:The effect of transdermal HRT was studied in 33 postmenopausal liver transplant women. The mai...

    journal_title:Journal of hepatology

    pub_type: 临床试验,杂志文章


    authors: Isoniemi H,Appelberg J,Nilsson CG,Mäkelä P,Risteli J,Höckerstedt K

    更新日期:2001-02-01 00:00:00

  • Dynamic change of cells expressing MMP-2 mRNA and MT1-MMP mRNA in the recovery from liver fibrosis in the rat.

    abstract:BACKGROUND/AIMS:The aim of this study was to investigate whether both matrix metalloproteinase-2 (MMP-2) and membrane type 1 MMP (MT1-MMP) participate in the spontaneous resolution of liver fibrosis. METHODS:Transcription of both genes was examined by reverse transcription-polymerase chain reaction (RT-PCR) and in sit...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Watanabe T,Niioka M,Ishikawa A,Hozawa S,Arai M,Maruyama K,Okada A,Okazaki I

    更新日期:2001-10-01 00:00:00

  • Long term transgene expression by hepatocytes transduced with retroviral vectors requires induction of immune tolerance to the transgene.

    abstract:BACKGROUND/AIMS:Gene therapy for inherited liver diseases requires permanent expression of the therapeutic gene. However, in vivo liver transduction with retroviral vectors triggers an immune elimination of transduced hepatocytes. Here we investigated whether immune response could be prevented by treatment with compoun...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Puppi J,Guillonneau C,Pichard V,Bellodi-Privato M,Cuturi MC,Anegon I,Ferry N

    更新日期:2004-08-01 00:00:00

  • Hematopoietic stem cell transplantation from non-replicative hepatitis B virus carriers is safe.

    abstract:BACKGROUND/AIMS:Hepatitis B virus can cause serious problems in individuals undergoing organ transplantation. The aim of this study was to evaluate the hepatic events among HBs-Ag positive recipients and HBs-Ag negative recipients who received products from hepatitis B virus carriers. METHODS:A total of 151 patients r...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Ustün C,Idilman R,Gürman G,Ozcan M,Akyol G,Akan H,Ilhan O,Beksaç M,Uysal A,Konuk N,Karayalçin S,Poyraz A,Van Thiel D,Koç H

    更新日期:1999-08-01 00:00:00

  • Glucagon increases hepatic efficacy for urea synthesis.

    abstract::The effect of glucagon on the relation between urea synthesis and blood amino acid concentration was studied in seven healthy volunteers. Alanine was given as prime-continuous infusions and, after 1 hr for equilibration, the urea nitrogen synthesis rate was measured in two periods of about 2 hrs as urinary excretion c...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Vilstrup H,Hansen BA,Almdal TP

    更新日期:1990-01-01 00:00:00

  • Targeted impairment of innate antiviral responses in the liver of chronic hepatitis C patients.

    abstract:BACKGROUND & AIMS:Innate sensing of viral infection activates a global defense response including type I interferon (IFN) and IFN-stimulated genes (ISGs) expression. We previously reported that HCV NS3/4A protease, an essential protein in viral polyprotein processing, can abrogate antiviral signaling pathways and effec...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Jouan L,Chatel-Chaix L,Melançon P,Rodrigue-Gervais IG,Raymond VA,Selliah S,Bilodeau M,Grandvaux N,Lamarre D

    更新日期:2012-01-01 00:00:00

  • miR-122 regulates collagen production via targeting hepatic stellate cells and suppressing P4HA1 expression.

    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


    authors: Li J,Ghazwani M,Zhang Y,Lu J,Li J,Fan J,Gandhi CR,Li S

    更新日期:2013-03-01 00:00:00

  • Prevalence and clinical characteristics of TT virus (TTV) in patients with sporadic acute hepatitis of unknown etiology.

    abstract:BACKGROUND/AIMS:Recently, a novel DNA virus was isolated from the serum of a patient with post-transfusion non-A-G hepatitis and named TT virus. The aim of this study was to determine the prevalence and clinical characteristics of TT virus infection in patients with sporadic acute hepatitis of unknown etiology. METHOD...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Parquet MC,Yatsuhashi H,Koga M,Inoue O,Matsumoto T,Hamada R,Igarashi A,Yano M

    更新日期:1999-12-01 00:00:00

  • Controlled HIV viral replication, not liver disease severity associated with low bone mineral density in HIV/HCV co-infection.

    abstract:BACKGROUND & AIMS:To evaluate the prevalence and risk factors for low bone mineral density (BMD) in persons co-infected with HIV and Hepatitis C. METHODS:HIV/HCV co-infected study participants (n=179) were recruited into a prospective cohort and underwent dual-energy X-ray absorptiometry (DXA) within 1 year of a liver...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: El-Maouche D,Mehta SH,Sutcliffe C,Higgins Y,Torbenson MS,Moore RD,Thomas DL,Sulkowski MS,Brown TT

    更新日期:2011-10-01 00:00:00

  • Up-regulated expression of fractalkine and its receptor CX3CR1 during liver injury in humans.

    abstract:BACKGROUND/AIMS:Little is known about the role of fractalkine (CX3CL1) in the liver. The aim of this study was to investigate the expression patterns of fractalkine and its receptor CX3CR1 in normal human liver and in conditions of injury. METHODS:Distribution and expression of fractalkine and its receptor were invest...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Efsen E,Grappone C,DeFranco RM,Milani S,Romanelli RG,Bonacchi A,Caligiuri A,Failli P,Annunziato F,Pagliai G,Pinzani M,Laffi G,Gentilini P,Marra F

    更新日期:2002-07-01 00:00:00

  • Microsteatosis may not interact with macrosteatosis in living donor liver transplantation.

    abstract:BACKGROUND & AIMS:The insignificance of pure microsteatosis (MiS) was reported in living donor liver transplantation (LDLT). However, since steatosis is mostly found in a mixed form of microsteatosis (MiS) and macrosteatosis (MaS), we aimed to determine the importance of MiS mixed with MaS in LDLT. METHODS:Donor match...

    journal_title:Journal of hepatology

    pub_type: 杂志文章


    authors: Han S,Ha SY,Park CK,Joh JW,Kwon CH,Kwon GY,Kim G,Gwak MS,Jeong WK,Ko JS

    更新日期:2015-03-01 00:00:00

  • Short-term effect of recombinant human growth hormone in patients with alcoholic cirrhosis.

    abstract::As growth hormone possesses anabolic properties that are active on protein metabolism, and thus of potential benefit to patients with chronic liver disease, we determined the metabolic effects of recombinant human growth hormone on insulin-like growth factor-I (IGF-I) its specific binding proteins, and liver function....

    journal_title:Journal of hepatology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Møller S,Becker U,Grønbaek M,Juul A,Winkler K,Skakkebaek NE

    更新日期:1994-11-01 00:00:00

  • The new therapeutic frontier--nuclear receptors and the liver.

    abstract::A joint EASL/AASLD Monothematic Conference on 'Nuclear Receptors and Liver Disease' was held from February 27th to March 1st, 2009, in Vienna, Austria, to discuss the latest advances at the forefront of basic and clinical nuclear receptor research and its potential implications for liver diseases. This article reports...

    journal_title:Journal of hepatology



    authors: Karpen SJ,Trauner M

    更新日期:2010-03-01 00:00:00

  • Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial.

    abstract:BACKGROUND/AIMS:Silymarin has protective effects in different experimental conditions, but its efficacy in human liver cirrhosis has not been completely established. Therefore, this study was carried out to determine the effect of silymarin in alcoholics with liver cirrhosis with respect to survival and clinical and la...

    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


    authors: Parés A,Planas R,Torres M,Caballería J,Viver JM,Acero D,Panés J,Rigau J,Santos J,Rodés J

    更新日期:1998-04-01 00:00:00

  • Sustained virologic response of 100% in HCV genotype 1b patients with cirrhosis receiving ombitasvir/paritaprevir/r and dasabuvir for 12weeks.

    abstract:BACKGROUND & AIMS:Patients with chronic hepatitis C virus (HCV) infection and cirrhosis have a higher risk for liver-related complications and have historically been more difficult to cure than patients without cirrhosis. We evaluated the safety and efficacy of ombitasvir/paritaprevir/ritonavir and dasabuvir, without r...

    journal_title:Journal of hepatology

    pub_type: 临床试验,杂志文章


    authors: Feld JJ,Moreno C,Trinh R,Tam E,Bourgeois S,Horsmans Y,Elkhashab M,Bernstein DE,Younes Z,Reindollar RW,Larsen L,Fu B,Howieson K,Polepally AR,Pangerl A,Shulman NS,Poordad F

    更新日期:2016-02-01 00:00:00